Miscellaneous Articles

Israel/ Japan  https://www.immunotherapy-clinic-ikiru.com/gcmaf-therapy-case-reports/

(2020) Gurdev Parmar, ND, FABNO. Textbook of Naturopathic Oncology

Dr. Neil McKinney, BSc, ND. Naturopathic Oncology 4: An Encyclopedic Guide for Patients & Physicians  2017.

Lesley Braun, Marc Cohen. “Herbs and Natural Supplements, Volume 2: An Evidence-Based Guide, Volume 2.”

(2008) Mantovani A, Allavena P, Sica A, Balkwill F. “Cancer-related inflammation.” Nature. 2008 Jul 24;454(7203):436-44. doi: 10.1038/nature07205. PMID: 18650914.

(2009) A.R. Amin, O. Kucuk, F.R. Khuri, D.M. Shin.  “Perspectives for cancer prevention with natural compounds.”  J. Clin. Oncol., 27 (2009), pp. 2712-2725

(2010) Henning SM, Zhang Y, Seeram NP, Lee RP, Wang P, Bowerman S, Heber D.  “Antioxidant capacity and phytochemical content of herbs and spices in dry, fresh and blended herb paste form.” Int J Food Sci Nutr. 2011 May;62(3):219-25. doi: 10.3109/09637486.2010.530595. Epub 2010 Dec 1. PMID: 21118053.

(2013) Nousheen Zaidi, et al.  “Lipogenesis and lipolysis: The pathways exploited by the cancer cells to acquire fatty acids.” Progress in Lipid Research. Volume 52, Issue 4, October 2013, Pages 585-589.

(2013) Thornthwaite, J. , Shah, H. , Shah, P. , Peeples, W. and Respess, H.  “The formulation for cancer prevention & therapy.”  Advances in Biological Chemistry, 3, 356-387. doi: 10.4236/abc.2013.33040.

(2014) J.F. Lesgards, N. Baldovini, N. Vidal, S. Pietri.  “Anticancer activities of essential oils constituents and synergy with conventional therapies: a review.”  Phytother. Res., 28 (2014), pp. 1423-1446.

(2014) Saedi, Tayebeh Azam et al. “The effects of herbs and fruits on leukaemia.” Evidence-based complementary and alternative medicine: eCAM vol. 2014 (2014): 494136. doi:10.1155/2014/494136

(2015) Mulpur, Bhageeradh H et al. “Complementary therapy and survival in glioblastoma.” Neuro-oncology practice vol. 2,3 (2015): 122-126. doi:10.1093/nop/npv008

(2015) Greenwell, M, and P K S M Rahman. “Medicinal Plants: Their Use in Anticancer Treatment.” International journal of pharmaceutical sciences and research vol. 6,10 (2015): 4103-4112. doi:10.13040/IJPSR.0975-8232.6(10).4103-12

(2016) Fleischer T, Chang TT, Chiang JH, et al. “Improved Survival With Integration of Chinese Herbal Medicine Therapy in Patients With Acute Myeloid Leukemia: A Nationwide Population-Based Cohort Study.” Integr Cancer Ther. Aug 16 2016.

(2017) James A. McCubrey, etal. “Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs.” Aging 2017. Vol 9, No. 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509453/pdf/aging-09-1477.pdf.

(2017) Vilas Desai and Alok Bhushan.  “Natural Bioactive Compounds: Alternative Approach to the Treatment of Glioblastoma Multiforme.” Hindawi BioMed Research International. Volume 2017, Article ID 9363040, 10 pages.

(2017) Ahsis K. Basu, Takehiko Nohmi. “Chemically-Induced DNA Damage, Mutagenesis, and Cancer.” This is a reprint of articles from the Special Issue published online in the open access journal International Journal of Molecular Sciences (ISSN 1422-0067) from 2017 to 2018 (available at: http:// www.mdpi.com/journal/ijms/special issues/chemical induced mutagenesis)

(2017) Lin SR, Fu YS, Tsai MJ, Cheng H, Weng CF. “Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy.”  Int J Mol Sci. 2017;18(7):1412. Published 2017 Jul 1. doi:10.3390/ijms18071412

(2018) Trogrlić, Ivo et al. “Treatment of glioblastoma with herbal medicines.” World journal of surgical oncology vol. 16,1 28. 13 Feb. 2018, doi:10.1186/s12957-018-1329-2

(2018) Zhang, Qing-Yu et al. “Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects.” Frontiers in pharmacology vol. 9 1253. 6 Nov. 2018, doi:10.3389/fphar.2018.01253

(2019) Rawla P, Sunkara T, Barsouk A. “Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors.” Prz Gastroenterol. 2019;14(2):89-103. doi: 10.5114/pg.2018.81072. Epub 2019 Jan 6. PMID: 31616522; PMCID: PMC6791134.

(2018) Mazumder A, et al.  “Natural scaffolds in anticancer therapy and precision medicine.” Biotechnology Advances. Volume 36, Issue 6, 1 November 2018, Pages 1563-1585

(2020) Sun X, Wang M, Wang M, Yu X, Guo J, Sun T, Li X, Yao L, Dong H, Xu Y. “Metabolic Reprogramming in Triple-Negative Breast Cancer.” Front Oncol. 2020 Mar 31;10:428. doi: 10.3389/fonc.2020.00428. PMID: 32296646; PMCID: PMC7136496.

(2022) Guo Q, Qin H, Liu X, Zhang X, Chen Z, Qin T, Chang L, Zhang W. “The Emerging Roles of Human Gut Microbiota in Gastrointestinal Cancer.” Front Immunol. 2022 Jun 15;13:915047. doi: 10.3389/fimmu.2022.915047. PMID: 35784372; PMCID: PMC9240199.

N-ACETYL-CYSTEINE (NAC)

(2006) Cetinkaya A, Bulbuloglu E, Kurutas EB, Kantarceken B. “N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats.” Med Sci Monit. 2006;12:BR274–BR278.

(2006) Ciralik H, Bulbuloglu E, Cetinkaya A, Kurutas EB, Celik M, Polat A. “Effects of N-acetylcysteine on methotrexate-induced small intestinal damage in rats.” Mt Sinai J Med. 2006;73:1086–1092.

(2007)  Cetinkaya A, Kurutas EB, Bulbuloglu E, Kantarceken B. “The effects of N-acetylcysteine on methotrexate-induced oxidative renal damage in rats.” Nephrol Dial Transplant. 2007;22:284–285.

(2013) Caglar Y, Ozgur H, Matur I, et al. “Ultrastructural evaluation of the effect of N-

acetylcysteine on methotrexate nephrotoxicity in rats.” Histol Histopathol. 2013;28:865–874.

(2014) Afshin Amini, et al. “Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy.”  Journal of Experimental & Clinical Cancer Research. 2014, 33:9. https://doi.org/10.1186/s13046-014-0092-7.

(2014) Sayin V.I., Ibrahim M.X., Larsson E., Nilsson J.A., Lindahl P., Bergo M.O. “Antioxidants Accelerate Lung Cancer Progression in Mice.” Sci. Transl. Med. 2014;6:221ra15. doi: 10.1126/scitranslmed.3007653.

(2016) Amini, Afshin et al. “Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells.” American journal of cancer research vol. 6,2 350-69. 15 Jan. 2016.

(2017) Daniel Monti, et al. “Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.” Seminars in Oncology, 2017; DOI: 10.1053/j.seminoncol.2017.10.001

(2018) Salvatore Grisanti, et al. “Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma.”  Support Care Cancer (2018) 26: 2929. https://doi.org/10.1007/s00520-018-4129-x.

(2019) Deng J, Liu AD, Hou GQ, Zhang X, Ren K, Chen XZ, Li SSC, Wu YS, Cao X. “N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling.” J Exp Clin Cancer Res. 2019;38:2.

(2019) Šalamon, Špela et al. “Medical and Dietary Uses of N-Acetylcysteine.” Antioxidants (Basel, Switzerland) vol. 8,5 111. 28 Apr. 2019, doi:10.3390/antiox8050111

(2020) Pillai K, Mekkawy AH, Akhter J, Badar S, Dong L, Liu AI, Morris DL. “Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.” Am J Transl Res. 2020 Nov 15;12(11):7404-7419. PMID: 33312377; PMCID: PMC7724355.

(2021) Schwalfenberg, Gerry K. “N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks).” Journal of nutrition and metabolism vol. 2021 9949453. 9 Jun. 2021, doi:10.1155/2021/9949453 (Breast Cancer, Prostate Cancer, Lung Cancer, Glioblastoma, and Chronic Lymphocytic Leukemia)

ALPHA LIPOIC ACID

(2002) Jones, et al. “Uptake, Recycling, and Antioxidant Actions of Alpha-lipoic acid in Endothelial Cells.” Free Radic. Biol. Med. 2002; 33 (1): 83-93.

(2002) Gedlicka, et al. “Effective Treatment of Oxaliplatin-Induced Cumulative Poly-Neuropathy with Alpha-Lipoic Acid.”  J. Clin. Oncol. 2002; 20 (5): 3359-3361.

(2003) van de MK, Chen JS, Steliou K, Perrine SP, Faller DV. Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines. J Cell Physiol2003;194:325-40.

(2005) Wenzel, et al.  “Alpha Lipoic Acid Induces Apoptosis in Human Colon Cancer Cells by Increasing Mitochondrial Respiration with a Concomitant O2* Generation.” Apoptosis 2005; 10 (2): 359-368.

(2006) Mantovani G, Macció A, Madeddu C, et al. “A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, Progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress.” Cancer Epidemiol Biomarkers Prev. 2006;15:1030-1034. doi:10.1158/1055-9965.EPI-05-0538

(2006) Moungiaroen, et al.  “Reactive Oxygen Species Mediate Caspase Activation and Apoptosis Induced by Alpha Lipoic Acid in Human Lung Epithelial Cancer Cells Through Bcl-2 Down-regulation.”  J. Pharmacolo. Exp. 2006; 319 (3): 1062-1069.

(2006) Berkson, et al.  “The Long-Term Survival of a Patient with Pancreatic Cancer with Metastases to the Liver After Treatment with the Intravenous Alpha-Lipoic Acid/Low-Dose Naltrexone Protocol.” Integr. Cancer Ther. 2006; 5 (1): 83-89.

(2007) Simbula G, et al. Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells. Apoptosis 2007 Jan;12(1):113-23.

(2008) Shi DY, Liu HL, Stern JS, et al. “Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway”. FEBS Lett. 2008 May 28;582(12):1667-71.

(2008) Park KG, Min AK, Koh EH, et al. “Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate- activated protein kinase (AMPK)-dependent and AMPK-independent pathways.” Hepatology 2008 Nov;48(5):1477-86.

(2008) N.A. Mikirova, et al. “Differential Effect of Alpha-lipoic Acid on Healthy Peripheral Blood Lymphocytes and Leukemic Cells.” Journal of Orthomolecular Medicine Vol. 23, No. 2, 2008 (83-89).

(2009) Berkson BM, Rubin DM, Berkson AJ. “Revisiting the ALA/N (a-Lipoic Acid/Low-Dose Naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases.” Integ Cancer Ther. 2009;8:416-422. doi: 10.1177/1534735409352082.

(2010) Dozio E, et al. “The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells.” Eur J Pharmacol. 2010 Sep 1;641(1):29-34.

(2010) Kisurina-Evgen'eva OP, Onishchenko GE. “Alpha-lipoic acid triggers elimination of cells with abnormal nuclei in human carcinoma epidermoid cell line.” Tsitologiia. 2010;52(3):225-34.

(2010) Srinivasan Krishna, et al. “Differential Effects of Short‐Chain Fatty Acids on Head and Neck Squamous Carcinoma Cells.” The Laryngoscope. Volume 112, Issue 4. April 2002, Pages 645-650 https://cam.cancer.gov/news_and_events/newsletter/2012-spring/feature.htm

(2012) “Alpha-Lipoic Acid Plus Low-Dose Naltrexone Reviewed for Cancer Treatment.”  NIH, Division of Cancer Treatment and Diagnosis. Lymphomas and pancreatic cancers.

https://cam.cancer.gov/news_and_events/newsletter/2012-spring/feature.htm

(2013) Kapoor, Shailendra.  “The Anti-neoplastic Effects of Alpha-Lipoic Acid: Clinical Benefits in System Tumors besides Lung Carcinomas.” Korean Journal of Thoracic Cardiovascular Surgery. 2013; 46:162-163  (melanoma).

(2013) Feng B, Yan XF, Xue JL, Xu L, Wang H. “The protective effects of α-lipoic acid on kidneys in type 2 diabetic Goto-Kakisaki rats via reducing oxidative stress.” Int J Mol Sci. 2013 Mar 26;14(4):6746-56. doi: 10.3390/ijms14046746. PMID: 23531536; PMCID: PMC3645663.

(2013) Hiratsuka, T., et al. "DHL‑TauZnNa, a newly synthesized α-lipoic acid derivative, induces autophagy in human colorectal cancer cells".  Oncology Reports 29.6 (2013): 2140-2146.

(2014) Moon.  “Chemopreventive Effects of Alpha Lipoic Acid on Obesity-Related Cancers.” Ann Nutr Metab 2016;68:137-144. (breast, thyroid, colon, pancreatic and liver).

(2014) Udensi, Udensi K, and Paul B Tchounwou. “Dual effect of oxidative stress on leukemia cancer induction and treatment.” Journal of experimental & clinical cancer research : CR vol. 33 106. 18 Dec. 2014, doi:10.1186/s13046-014-0106-5.

(2014) Guo Y, Jones D, Palmer JL, et al. “Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial.” Support Care Cancer. 2014;22:1223-1231. doi: 10.1007/s00520-013-2075-1.

(2015) Dörsam B, et al. “Lipoic acid induces p53-independent cell death in colorectal cancer cells and potentiates the cytotoxicity of 5-fluorouracil.” Arch Toxicol. 2015 Oct;89(10):1829-46.

(2015) Jeon MJ, Kim WG, Lim S, et al. “Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells.” Mol Cell Endocrinol. 2016;419:113-123. doi: 10.1016/j.mce.2015.10.005

(2015) Kafara P, Icard P, Guillamin M, et al. “Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death.” J Ovarian Res. 2015;8:36-49. doi: 10.1186/s13048-015-0165-z.

(2016) Puchsaka P, Chaotham C, Chanvorachote P. “α-Lipoic acid sensitizes lung cancer cells to chemotherapeutic agents and anoikis via integrin β1/β3 downregulation.” Int J Oncol. 2016;49:1445-1456. doi: 10.3892/ijo.2016.3624

(2016) Lee J, Jung SY, Yang KJ, Kim Y, Lee D, Lee MH, Kim DK. “α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway.” PLoS One. 2019 Dec 26;14(12):e0226769. doi: 10.1371/journal.pone.0226769. PMID: 31877176; PMCID: PMC6932784.

(2016) Alpay M, et al. “Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitro.” Journal of Cancer Research and Therapeutics. 2016;12:2:556-560

(2016) Jeon MJ, Kim WG, Lim S, et al. “Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells.” Mol Cell Endocrinol. 2016;419:113-123. doi: 10.1016/j.mce.2015.10.005

(2017) Kuban-Jankowska A, Gorska-Ponikowska M, Wozniak M. “Lipoic acid decreases the viability of breast cancer cells and activity of PTP1B and SHP2.” Anticancer Res. 2017;37:2893-2898.

(2017) Kismali G, Yurdakok-Dikmem B, Kuzukiran O, et al. “Phthalate induced toxicity in prostate cancer cell lines and effects of alpha lipoic acid.” Bratisl Med J. 2017;118:460-466. doi: 10.4149/BLL_2017_089.

(2017) Desideri I, Francolini G, Becherini C, et al. “Use of an alpha lipoic, methylsulfonylmethane and bromelain dietary supplement (Opera®) for chemotherapy-induced peripheral neuropathy management, a prospective study.” Med Oncol. 2017;34:46. doi: 10.1007/s12032-017-0907-4.

(2017) Yang L, Wen Y, Lv G, et al. “α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation.” Biochem Biophys Res Commun. 2017;494:325-331. doi: 10.1016/j.bbrc.2017.10.030

(2018) Berkson, Burton M, and Francisco Calvo Riera. “The Long-Term Survival of a Patient With Stage IV Renal Cell Carcinoma Following an Integrative Treatment Approach Including the Intravenous α-Lipoic Acid/Low-Dose Naltrexone Protocol.” Integrative cancer therapies vol. 17,3 (2018): 986-993. doi:10.1177/1534735417747984

(2018) Deveci HA, Akyuva Y, Nur G, Nazıroğlu M. “Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line.” Biomed Pharmacother. 2019;111:292-304. doi:10.1016/j.biopha.2018.12.077

(2018) Dinicola S, et al.  “Natural products – alpha-lipoic acid and acetyl-L-carnitine – in the treatment of chemotherapy-induced peripheral neuropathy.” European Review for Medical and Pharmacological Sciences. 2018; 22: 4739-4754.

(2018) Arpag H, Gül M, Aydemir Y, et al. “Protective Effects of Alpha-Lipoic Acid on Methotrexate-Induced Oxidative Lung Injury in Rats.”  J Invest Surg. 2018;31(2):107-113. doi:10.1080/08941939.2017.1296513

(2019) Bahadur S, Sahu AK, Baghel P, Saha S. “Current promising treatment strategy for glioblastoma multiform: A review.” Oncology Reviews. 2019 Jul;13(2):417. DOI: 10.4081/oncol.2019.417.

(2019) Yang Y, Fang E, Luo J, et al. ”The Antioxidant Alpha-Lipoic Acid Inhibits Proliferation and Invasion of Human Gastric Cancer Cells via Suppression of STAT3-Mediated MUC4 Gene Expression.” Oxidative Medicine and Cellular Longevity. 2019 ;2019:3643715. DOI: 10.1155/2019/3643715. PMID: 31915505; PMCID: PMC6930776. Conclusion: ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.

(2019) Neitzel C, Seiwert N, Göder A, Diehl E, Weber C, Nagel G, Stroh S, Rasenberger B, Christmann M, Fahrer J. “Lipoic Acid Synergizes with Antineoplastic Drugs in Colorectal Cancer by Targeting p53 for Proteasomal Degradation.” Cells. 2019 Jul 30;8(8):794. doi: 10.3390/cells8080794. PMID: 31366086; PMCID: PMC6721634.

(2020) Pibiri, M., Sulas, P., Camboni, T. et al. “α-Lipoic acid induces Endoplasmic Reticulum stress-mediated apoptosis in hepatoma cells.” Sci Rep 10, 7139 (2020). https://doi.org/10.1038/s41598-020-64004-5. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells

(2020) Jaytirmay Tripathy, etal. “α-Lipoic acid inhibits the migration and invasion of breast cancer cells through inhibition of TGFβ signaling.” Life Sciences, Vol 27, pp 15-22, 15 Aug 2018.

(2020) Farhat, D., Léon, S., Ghayad, S.E. et al. “Lipoic acid decreases breast cancer cell proliferation by inhibiting IGF-1R via furin downregulation.” Br J Cancer 122, 885–894 (2020). https://doi.org/10.1038/s41416-020-0729-6

(2020) Neitzel C, Demuth P, Wittmann S, Fahrer J. “Targeting Altered Energy Metabolism in Colorectal Cancer: Oncogenic Reprogramming, the Central Role of the TCA Cycle and Therapeutic Opportunities.” Cancers (Basel). 2020 Jun 29;12(7):1731. doi: 10.3390/cancers12071731. PMID: 32610612; PMCID: PMC7408264. (alpha-lipoic acid)

(2021) Hanan Ibrahim Elkerdasy. “Histological and Immunohistochemical Study, on the Effect of Cyclophospahmide in Testis of Adult Albino Rats and the possible protective role of Vitamin E and Alpha Lipoic Acid.”  Egyptian Journal of Histology, 2021, doi: 10.21608/ejh.2021.71326.1458

Alpha lipoic acid comparatively preserved the normal histological structure of testis and normal spermatogenesis than vitamin E. However, administration of vitamin E and alpha lipoic acid together was almost totally prevented the damaging effect of cyclophosphamide.

(2023) Celik, A., Bakar-Ates, F. “Alpha-lipoic acid induced apoptosis of PC3 prostate cancer cells through an alteration on mitochondrial membrane depolarization and MMP-9 mRNA expression.” Med Oncol 40, 244 (2023). https://doi.org/10.1007/s12032-023-02113-7

ANTIBIOTICS

(2020) Gao Y, Shang Q, Li W, Guo W, Stojadinovic A, Mannion C, Man YG, Chen T. “Antibiotics for cancer treatment: A double-edged sword.” J Cancer. 2020 Jun 28;11(17):5135-5149. doi: 10.7150/jca.47470. PMID: 32742461; PMCID: PMC7378927.

(2020) Lurienne L, Cervesi J, Duhalde L, de Gunzburg J, Andremont A, Zalcman G, Buffet R, Bandinelli PA. “NSCLC Immunotherapy Efficacy and Antibiotic Use: A Systematic Review and Meta-Analysis.”  J Thorac Oncol. 2020 Jul;15(7):1147-1159. doi: 10.1016/j.jtho.2020.03.002. Epub 2020 Mar 12. PMID: 32173463.

(2021) Patel P, Poudel A, Kafle S, Thapa Magar M, Cancarevic I. “Influence of Microbiome and Antibiotics on the Efficacy of Immune Checkpoint Inhibitors.” Cureus. 2021 Aug 2;13(8):e16829. doi: 10.7759/cureus.16829. PMID: 34522484; PMCID: PMC8425062.

ARTESUNATE/ARTEMISININ

(2004) Singh NP, Lai HC. “Artemisinin induces apoptosis in human cancer cells.” Anticancer Res. 2004 Jul-Aug;24(4):2277-80. PMID: 15330172.

(2005) Singh NP, Lai HC. “Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells.” Anticancer Res. 2005 Nov-Dec;25(6B):4325-31. PMID: 16309236.

(2008) Sundar SN, Marconett CN, Doan VB, Willoughby JA Sr, Firestone GL. “Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells.” Carcinogenesis. 2008 Dec;29(12):2252-8. doi: 10.1093/carcin/bgn214. Epub 2008 Sep 10. PMID: 18784357; PMCID: PMC2639250.

(2009) Willoughby JA Sr, Sundar SN, Cheung M, Tin AS, Modiano J, Firestone GL. “Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression.” J Biol Chem. 2009 Jan 23;284(4):2203-13. doi: 10.1074/jbc.M804491200. Epub 2008 Nov 17. PMID: 19017637; PMCID: PMC2629082.

(2010) Wang Lijuan, Yang Yucong, Gou Wenli.  “Effect of artesunate on human endometrial carcinoma HEC-1B cells.” Journal of Medical Colleges of PLA. Vol 25, Issue 3, June 2010, Pages 142-151.

(2013) Jiang We, et al. “The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo.” Asian Pac J Cancer Prev, 14 (8), 4615-4619.

(2014) Li P, Yang S, Dou M, Chen Y, Zhang J, Zhao X. “Synergic effects of artemisinin and resveratrol in cancer cells.” J Cancer Res Clin Oncol. 2014 Dec;140(12):2065-75. doi: 10.1007/s00432-014-1771-7. Epub 2014 Jul 22. PMID: 25048878.

(2014) Wickerath M, Singh NP. “Additive cytotoxic effects of dihydroartemisinin and sodium salicylate on cancer cells. Anticancer Res.” 2014 Jul;34(7):3399-401. PMID: 24982346.

(2014) Odaka, et al. “Dihydroartemisinin inhibits the mammalian target of rapamycin-mediated signaling pathways in tumor cells.” Carcinogenesis. 2014 Jan;35(1):192-200. doi: 10.1093/carcin/bgt277. Rhabdomyosarcoma.

(2014) Tran KQ, Tin AS, Firestone GL. “Artemisinin triggers a G1 cell cycle arrest of human Ishikawa endometrial cancer cells and inhibits cyclin-dependent kinase-4 promoter activity and expression by disrupting nuclear factor-κB transcriptional signaling.” Anticancer Drugs. 2014 Mar;25(3):270-81. doi: 10.1097/CAD.0000000000000054. PMID: 24296733; PMCID: PMC4172338.

(2015) Hargraves, et al. “Phytochemical regulation of the tumor suppressive microRNA, miR-34a, by p53-dependent and independent responses in human breast cancer cells.” Mol Carcinog. 2016 May;55(5):486-98. doi: 10.1002/mc.22296. Epub 2015 Mar 19. Artemisinin.

(2015) . Zhang ZS, et al. “Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy.” Oncol Lett 2015;10:379-83

(2016) Drenberg, Christina D et al. “Evaluation of artemisinins for the treatment of acute myeloid leukemia.” Cancer chemotherapy and pharmacology vol. 77,6 (2016): 1231-43. doi:10.1007/s00280-016-3038-2

(2017) Slezakova, et al.  “Anticancer Activity of Artemisinin and its Derivatives.” Anticancer Research November 2017 vol. 37 no. 11 5995-6003.

(2017) Kumar B. et al.  “Antileukemic activity and cellular effects of the antimalarial agent artesunate in acute myeloid leukemia.” Leuk Res. 2017 May. DOI: 10.1016/j.leukres.2017.05.007.

(2017) Thomas Efferth.  “Cancer combination therapies with artemisinin-type drugs.”  Biochemical Pharmacology, Volume 139, 2017, Pages 56-70, ISSN 0006-2952, https://doi.org/10.1016/j.bcp.2017.03.019.

(2018) Dou, et al. “Cytotoxic effect of Artesunate on myeloid leukemia cell lines through up-regulating miR-29c expression.” Translational Cancer Research. Vol 7, No 6 (December 2018)

(2018) Våtsveen TK, Myhre MR, Steen CB, Wälchli S, Lingjærde OC, Bai B, Dillard P, Theodossiou TA, Holien T, Sundan A, Inderberg EM, Smeland EB, Myklebust JH, Oksvold MP. “Artesunate shows potent anti-tumor activity in B-cell lymphoma.” J Hematol Oncol. 2018 Feb 20;11(1):23. doi: 10.1186/s13045-018-0561-0. PMID: 29458389; PMCID: PMC5819282.

(2019) Lam, et al. “Artemisinin and its derivatives: A potential treatment for leukemia.” (AML) Anti-Cancer Drugs 2019 Jan;30(1):1-18:1-18.

(2019) Li Z, Ding X, Wu H, Liu C. “Artemisinin inhibits angiogenesis by regulating p38 MAPK/CREB/TSP-1 signaling pathway in osteosarcoma.” J Cell Biochem. 2019 Feb 11. doi: 10.1002/jcb.28424. Epub ahead of print. PMID: 30746754.

(2020) Chen GQ, Benthani FA, Wu J, Liang D, Bian ZX, Jiang X. “Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis.” Cell Death Differ. 2020 Jan;27(1):242-254. doi: 10.1038/s41418-019-0352-3. Epub 2019 May 21. PMID: 31114026; PMCID: PMC7205875.

(2020) Augustin Y, Staines HM, Krishna S. “Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing.” Pharmacol Ther. 2020 Dec;216:107706. doi: 10.1016/j.pharmthera.2020.107706. Epub 2020 Oct 16. PMID: 33075360; PMCID: PMC7564301.

(2021) Otto-Ślusarczyk D, Mielczarek-Puta M, Graboń W. “The Real Cytotoxic Effect of Artemisinins on Colon Cancer Cells in a Physiological Cell Culture Setting. How Composition of the Culture Medium Biases Experimental Findings.” Pharmaceuticals (Basel). 2021 Sep 26;14(10):976. doi: 10.3390/ph14100976. PMID: 34681200; PMCID: PMC8540140.

(2022) Hu Y, Guo N, Yang T, Yan J, Wang W, Li X. “The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer.” Oxid Med Cell Longev. 2022 Jan 4;2022:1458143. doi: 10.1155/2022/1458143. PMID: 35028002; PMCID: PMC8752222.

ASTAXANTHIN

(2015) Zhang, Li, and Handong Wang. “Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin.” Marine drugs vol. 13,7 4310-30. 14 Jul. 2015, doi:10.3390/md13074310

(2016) Kai-Sheng Liao, et al. “Astaxanthin enhances pemetrexed-induced cytotoxicity by downregulation of thymidylate synthase expression in human lung cancer cells.” Regulatory Toxicology and Pahramcology. November 2016. 81.  DOI:10.1016/j.yrtph.2016.09.031.

(2019) Kim, HY., Kim, YM. & Hong, S.  “Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a.” Sci Rep 9, 9457 (2019). https://doi.org/10.1038/s41598-019-45924-3

(2019) Maryam Hormozi, Shadi Ghoreishi & Parasto Baharvand. “Astaxanthin induces apoptosis and increases activity of antioxidant enzymes in LS-180 cells.” Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 891-895, DOI: 10.1080/21691401.2019.1580286

(2020) Immacolata Faraone, et al. “Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: A systematic review.” Pharmacological Research.  Vol 155, May 2020, 104689.

(2020) Jeong, Seong Mun, and Yeon-Jeong Kim. “Astaxanthin Treatment Induces Maturation and Functional Change of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice.” Antioxidants (Basel, Switzerland) vol. 9,4 350. 23 Apr. 2020, doi:10.3390/antiox9040350

(2020) Mancuso, Foglio, Olalla Saad. “Artemisinin-type drugs for the treatment of hematological malignancies.” Cancer Chemother Pharmacology. 2021 Jan;87(1):1-22. doi: 10.1007/s00280-020-04170-5.

(2023) Erzurumlu Y, Catakli D, Dogan HK. “Potent carotenoid astaxanthin expands the anti-cancer activity of cisplatin in human prostate cancer cells.” J Nat Med. 2023 Jun;77(3):572-583. doi: 10.1007/s11418-023-01701-1. Epub 2023 May 2. PMID: 37130999.

ASTRAGALUS
(2006) McCulloch M, See C, Shu XJ, et al. “Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.” J Clin Oncol. 2006 Jan 20;24(3):419-30.

(2012) Auyeung KK, Woo PK, Law PC, Ko JK. “Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells.”  JEthnopharmacol. 2012;141(2):635-41.

(2012) Guo L, Bai SP, Zhao L, Wang XH. “Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival.”  Med Oncol. 2012;29(3):1656-62.

(2012) Law PC, Auyeung KK, Chan LY, et al. “Astragalus saponins downregulate vascular endothelial growth factor under cobalt chloride-stimulated hypoxia in colon cancer cells.” BMC Complement Altern Med. 2012;12:160.

(2012) Huang, et al.  “Astragalus membranaceus lectin (AML) induces caspase-dependent apoptosis in human leukemia cells (CML).” Cell Prolif. 2012 Feb;45(1):15-21.

(2014) Auyeung KK, Law PC, Ko JK. “Combined therapeutic effects of vinblastine and Astragalus saponins in human colon cancer cells and tumor xenograft via inhibition of tumor growth and proangiogenic factors.” Nutr Cancer. 2014;66(4):662-674.

(2014) Wang Y, Auyeung KK, Zhang X, et al. “Astragalus saponins modulates colon cancer development by regulating calpain-mediated glucose-regulated protein expression.” BMC Complement Altern Med. 2014;14:401.

(2016) Wang, S F et al. “Astragalus-containing Traditional Chinese Medicine, with and without prescription based on syndrome differentiation, combined with chemotherapy for advanced non-small-cell lung cancer: a systemic review and meta-analysis.” Current oncology (Toronto, Ont.) vol. 23,3 (2016): e188-95.

(2016) Huang WH, Liao WR, Sun RX. “Astragalus polysaccharide induces the apoptosis of human hepatocellular carcinoma cells by decreasing the expression of Notch1.” Int J Mol Med. Aug 2016;38(2):551-557.

(2016) Auyeung KK, Han QB, Ko JK. “Astragalus membranaceus: A Review of its Protection Against Inflammation and Gastrointestinal Cancers.” Am J Chin Med. 2016;44(1):1-22.

(2016) Tseng A, Yang CH, Chen CH, et al. “An in vivo molecular response analysis of colorectal cancer treated with Astragalus membranaceus extract.” Oncol Rep. Feb 2016;35(2):659-668.

(2018) Zhang J, Liu L, Wang J, Ren B, Zhang L, Li W. “Formononetin, an isoflavone from Astragalus membranaceus inhibits proliferation and metastasis of ovarian cancer cells.”  J Ethnopharmacol. 2018 Jul 15;221:91-99.

(2019) Huang W-C, Kuo K-T, Bamodu OA, Lin Y-K, Wang C-H, Lee K-Y, Wang L-S, Yeh C-T, Tsai J-T. “Astragalus polysaccharide (PG2) Ameliorates Cancer Symptom Clusters, as well as Improves Quality of Life in Patients with Metastatic Disease, through Modulation of the Inflammatory Cascade.” Cancers. 2019; 11(8):1054. https://doi.org/10.3390/cancers11081054

(2020) Yanling Guo, Zhenxing Zhang, Zhaoxia Wang, Guoqi Liu, Yingying Liu, Huijie Wang; “Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway.” Biosci Rep 27 March 2020; 40 (3): BSR20193396.

(2023) Shen M, Wang YJ, Liu ZH, Chen YW, Liang QK, Li Y, Ming HX. “Inhibitory Effect of Astragalus Polysaccharide on Premetastatic Niche of Lung Cancer through the S1PR1-STAT3 Signaling Pathway.” Evid Based Complement Alternat Med. 2023 Jan 20;2023:4010797. doi: 10.1155/2023/4010797. PMID: 36714534; PMCID: PMC9883101

BERBERINE

(2006) Mantena SK, Sharma SD, Katiyar SK. “Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP.” Carcinogenesis 27: 2018–2027.

(2007) Yu, et al.  “Berberine inhibits WEHI-3 leukemia cells in vivo.” In vivo (Athens, Greece) 21(2):407-12 · March 2007

(2008) LI, et al.  “Berberine inhibits SDF-1-induced AML cells and leukemic stem cells migration via regulation of SDF-1 level in bone marrow stromal cells.” Biomed Pharmacother. 2008 Nov;62(9):573-8. doi: 10.1016/j.biopha.2008.08.003. Epub 2008 Sep 4.

(2010) Li GH, et al.  “Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.” Medical Oncology. 2010 Sep;27(3):919-25. doi: 10.1007/s12032-009-9307-8. Epub 2009 Sep 16.

(2012) Goto H, Kariya R, Shimamoto M, Kudo E, Taura M, Katano H, Okada S. “Antitumor effect of berberine against primary effusion lymphoma via inhibition of NF-κB pathway.” Cancer Sci. 2012 Apr;103(4):775-81. doi: 10.1111/j.1349-7006.2012.02212.x. Epub 2012 Feb 21. PMID: 22320346; PMCID: PMC7659260.

(2012) Park KS, Kim JB, Bae J, Park SY, Jee HG, Lee KE, Youn YK. “Berberine inhibited the growth of thyroid cancer cell lines 8505C and TPC1.” Yonsei Med J. 2012 Mar;53(2):346-51. doi: 10.3349/ymj.2012.53.2.346. PMID: 22318822; PMCID: PMC3282951.

(2014) Parham Jabbarzadeh Kaboli, et al. “Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer.” European Journal of Pharmacology 740:584-595 · June 2014. DOI: 10.1016/j.ejphar.2014.06.025.

(2014) Luis Miguel Guamán Ortiz, Micol Tillhon, Michael Parks, et al. “Multiple Effects of Berberine Derivatives on Colon Cancer Cells.” BioMed Research International, vol. 2014, Article ID 924585, 12 pages, 2014. https://doi.org/10.1155/2014/924585.

(2014) Zhu, Yu et al. “Berberine induces apoptosis and DNA damage in MG‑63 human osteosarcoma cells.” Molecular medicine reports vol. 10,4 (2014): 1734-8.

(2014), Zhang, et al. “Berberine inhibits the expression of hypoxia induction factor-1alpha and increases the radiosensitivity of prostate cancer.” Diagn Pathol (2014) 9: 98. https://doi.org/10.1186/1746-1596-9-98

(2015) Pandey A.  “Berberine and Curcumin Target Survivin and STAT3 in Gastric Cancer Cells and Synergize Actions of Standard Chemotherapeutic 5-Fluorouracil.”  Nutrition and Cancer. 2015;67(8):1293-304. doi: 10.1080/01635581.2015.1085581. Epub 2015 Oct 22.

(2015) Liu, et al. “Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE₂ Mediated JAK2/STAT3 Signaling Pathway.” PLoS One. 2015; 10(5): e0123478.

(2015) Zhu T, Li LL, Xiao GF, Luo QZ, Liu QZ, Yao KT, et al. “Berberine increases doxorubicin sensitivity by suppressing STAT3 in lung cancer.” Am J Chin Med 2015; 43:1487-1502.

(2015) Lu W, Du S, Wang J. “Berberine inhibits the proliferation of prostate cancer cells and induces G₀/G₁ or G₂/M phase arrest at different concentrations.” Mol Med Rep. 2015 May;11(5):3920-4. doi: 10.3892/mmr.2014.3139. Epub 2014 Dec 30. PMID: 25572870.

(2016) Wang, Jiwei et al. “Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway.” Oncotarget vol. 7,41 (2016): 66944-66958.

(2016) Jin, Hao et al. “Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis.” Oncology reports vol. 37,2 (2017): 729-736. doi:10.3892/or.2016.5327.

(2016) Wen C, Wu L, Fu L, Zhang X, Zhou H. “Berberine enhances the anti‑tumor activity of tamoxifen in drug‑sensitive MCF‑7 and drug‑resistant MCF‑7/TAM cells.” Mol Med Rep. 2016 Sep;14(3):2250-6. doi: 10.3892/mmr.2016.5490. Epub 2016 Jul 8. PMID: 27432642. B‑cell CLL/ lymphoma.

(2017) Pan, Yue et al. “Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer.” Journal of Cancer. vol. 8,9 1679-1689. 5 Jun. 2017, doi:10.7150/jca.19106.

(2017) Mohammadi S, Seyedhoseini FS, Asadi J, et al. “Effects of berberine on the secretion of cytokines and expression of genes involved in cell cycle regulation in THP-1 monocytic cell line.” (AML) Iran J Basic Med Sci. 2017;20:530–537.

(2017) Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H, Goudarzi M. “Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats.” Biomed Pharmacother. 2018;97:233-239. doi:10.1016/j.biopha.2017.10.113

(2017) Liang Li, Xingchun Wang, Rampersad Sharvan, Jingyang Gao, Shen Qu.  “Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways.” Biomedicine & Pharmacotherapy, Volume 95, 2017, Pages 1225-1231, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2017.09.010.

(2018) Jin, Hao et al. “Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis.” Oncology reports vol. 37,2 (2016): 729-736.

(2018) Wang Y, Zhang S. “Berberine suppresses growth and metastasis of endometrial cancer cells via miR-101/COX-2.”  Biomed Pharmacother. 2018 Jul;103:1287-1293. doi: 10.1016/j.biopha.2018.04.161. Epub 2018 May 7. PMID: 29864910.

(2018) Li, J., Yang, L., Shen, R. et al. “Self-nanoemulsifying system improves oral absorption and enhances anti-acute myeloid leukemia activity of berberine.”  J Nanobiotechnol 16, 76 (2018) doi:10.1186/s12951-018-0402-x

(2019) Shinji, et al. “Berberine and palmatine inhibit the growth of human rhabdomyosarcoma cells.” Biosci Biotechnol Biochem. 2019 Aug 29:1-13. doi: 10.1080/09168451.2019.1659714.

(2019) Dai, et al. “Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis.” Medical Science Monitor. 2019 Jan 25;25:730-738. doi: 10.12659/MSM.912082.

(2019) Wang Y, Liu Y, Du X, Ma H, Yao J. “The Anti-Cancer Mechanisms of Berberine: A Review.” Cancer Manag Res. 2020;12:695-702  https://doi.org/10.2147/CMAR.S242329

(2020) Chaohe Zhang, et al. “Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review.” Front. Pharmacol., 15 January 2020 | https://doi.org/10.3389/fphar.2019.01461.  (Thyroid)

(2021) Ren S, Cai Y, Hu S, Liu J, Zhao Y, Ding M, Chen X, Zhan L, Zhou X, Wang X. “Berberine exerts anti-tumor activity in diffuse large B-cell lymphoma by modulating c-myc/CD47 axis.” Biochem Pharmacol. 2021 Jun;188:114576. doi: 10.1016/j.bcp.2021.114576. Epub 2021 Apr 28. PMID: 33930347.

(2021) Rauf A, Abu-Izneid T, Khalil AA, Imran M, Shah ZA, Emran TB, Mitra S, Khan Z, Alhumaydhi FA, Aljohani ASM, Khan I, Rahman MM, Jeandet P, Gondal TA. ”Berberine as a Potential Anticancer Agent: A Comprehensive Review.” Molecules. 2021 Dec 4;26(23):7368. doi: 10.3390/molecules26237368. PMID: 34885950; PMCID: PMC8658774.

(2023) Tarawneh N, Hamadneh L, Abu-Irmaileh B, Shraideh Z, Bustanji Y, Abdalla S. “Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions.” Molecules. 2023; 28(9):3823. https://doi.org/10.3390/molecules28093823

BICARBONATE

(2009) Robey, et al. “Bicarbonate increases tumor pH and inhibits spontaneous metastases.” Cancer Res. 2009 Mar 15;69(6):2260-8. doi: 10.1158/0008-5472.CAN-07-5575. Epub 2009 Mar 10.

(2022) Eunus S. Ali etal. “The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo neulceotide synthesis.” Molecular Cell (2022). DOI: 10.1016/j.molcel.2022.06.008

(2022) Qiang, L., Dougan, S.K. “Bicarbonate transport as a vulnerability in pancreatic cancer.” Nat Cancer 3, 1449–1451 (2022). https://doi.org/10.1038/s43018-022-00492-w

BLACK CUMIN/ BLACK SEED OIL/ NIGELLA SATIVA

(2007) Mbarek L, et al.  “Anti-tumor effect of blackseed (Nigella sativa L) extracts.” Brazilian Journal of Medical and Biological Research (2007) 40: 839-847 ISSN 0100-879X

(2011) Khan, Md Asaduzzaman et al. “Anticancer activities of Nigella sativa (black cumin).” African journal of traditional, complementary, and alternative medicines.” AJTCAM vol. 8,5 Suppl (2011): 226-32. doi:10.4314/ajtcam.v8i5S.10

(2014) Arshad H. Rahmani, et al.  “Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways.” Evidence-Based Complementary and Alternative Medicine. Volume 2014 |Article ID 724658 | https://doi.org/10.1155/2014/724658

(2016) Amin F.Majdalawieh and Muneera W.Fayyad.  “Recent advances on the anti-cancer properties of Nigella sativa, a widely used food additive.” Journal of Ayurveda and Integrative Medicine. Volume 7, Issue 3, July–September 2016, Pages 173-180

(2019) Ebrahim M. Yimer, et al.  “Nigella sativa L. (Black Cumin): A Promising Natural Remedy for Wide Range of Illnesses.” Evidence-Based Complementary and Alternative Medicine. Volume 2019 |Article ID 1528635 | https://doi.org/10.1155/2019/1528635

BOSWELLIA

(1999) Jing, Y., S. Nakajo, L. Xia, K. Nakaya, Q. Fang, S. Waxman and R. Han, 1999. “Boswellic acid acetate induces differentiation and apoptosis in leukemia cell lines.” Leukemia Res., 23: 43-50.

(1999) Glaser T, Winter S, Groscurth P et al.  “Boswellic acids and malignant glioma: Induction of apoptosis but no modulation of drug sensitivity.” Br J Cancer. 80:756-765, 1999.

(1999) Hoernlein, R.F., T. Orlikowsky, C. Zehrer, D. Niethammer and E.R. Sailer et al., 1999. “Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells and inhibits topoisomerase I.” J. Pharmacol. Exp. Ther., 288: 613-619.

(2000) Huang MT, Badmaev V, Ding Y, Liu Y, Xie JG, Ho CT. “Anti-tumor and anti-carcinogenic activities of triterpenoid, β-boswellic acid.” Biofactors. 2000;13:225-230.

(2000) Winking M, Sarikaya S, Rahmanian A, Jodicke A, Boker DK. “Boswellic acids inhibit glioma growth: a new treatment option?” J Neurooncol. 2000;46:97-103.

(2002) Hostanska K, Daum G, Saller R. “Cytostatic and apoptosisinducing activity of boswellic acids toward malignant cell lines in vitro.” Anticancer Res. 2002;22:2853-2862.

(2005) Syrovets, T.; Gschwend, J.E.; Buchele, B.; Laumonnier, Y.; Zugmaier, W.; Genze, F.; Simmet, T. “Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo.”  J. Biol. Chem. 2005, 280, 6170–6180.

(2005) Xia L, Chen D, Han R, Fang Q, Waxman S, Jing Y. “Boswellic acid acetate induces apoptosis through caspase-mediated pathways in myeloid leukemia cells.” Mol Cancer Ther. 2005;4(3):381-388. doi:10.1158/1535-7163.MCT-03-0266.

(2006) Liu, J.J., B. Huang and S.C. Hooi, 2006. “Acetyl-keto-β-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells.” Br. J. Pharmacol., 148: 1099-1107.

(2007) Bhushan, S., A. Kumar, F. Malik, S.S. Andotra and V.K. Sethi et al., 2007. “A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells.” Apoptosis, 12: 1911-1926.

(2008) Lu, M.; Xia, L.; Hua, H.; Jing, Y. “Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells.” Cancer Res. 2008, 68, 1180–1186.

(2008) Yuan, H.Q.; Kong, F.; Wang, X.L.; Young, C.Y.; Hu, X.Y.; Lou, H.X. “Inhibitory effect of acetyl-11-ketobeta-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells.” Biochem. Pharmacol. 2008, 75, 2112–2121.

(2008) Kim HR, Kim, MS, Kwon DY, et al. “Boswellia serrata-induced apoptosis in related with ER stress and calcium release.”  Genes Nutr.  2:371-374, 2008.

(2009) Bhushan S, Malik F, Kumar A, et al. “Activation of p53/p21/PUMA alliance and disruption of PI-3/Akt multimodal targeting of apoptotic signaling cascades in cervical cancer cells by pentacyclic triterpenediol from Boswellia serrata.”  Mol Carcinog. 48:1093-1108, 2009.

(2009) Liu, J.J. and R.D. Duan, 2009. “LY294002 enhances boswellic acid-induced apoptosis in colon cancer cells.” Anticancer Res., 29: 2987-2991.

(2009) Frank MB, Yang Q, Osban J, et al. “Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity”. BMC Complement Altern Med. 2009;9:6.

(2009) Pang, X.; Yi, Z.; Zhang, X.; Sung, B.; Qu, W.; Lian, X.; Aggarwal, B.B.; Liu, M. “Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.” Cancer Res. 2009, 69, 5893–5900.

(2010) Qurishi, Y., A. Hamid, M.A. Zargar, S.K. Singh and A.K. Saxena, 2010. “Potential role of natural molecules in health and disease: Importance of boswellic acid.” J. Med. Plants Res., 4: 2778-2785.

(2011) Suhail MM, Wu W, Cao A, et al. “Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells.” BMC Complement Altern Med. 2011;11:129.

(2011) Park, B., B. Sung, V.R. Yadav, S.G. Cho, M. Liu and B.B. Aggarwal, 2011. “Acetyl-11-keto-β-boswellic acid suppresses invasion of pancreatic cancer cells through the downregulation of CXCR4 chemokine receptor expression.” Int. J. Cancer, 129: 23-33.

(2011) Eichhorn, Tolga et al. “Molecular Determinants of the Response of Tumor Cells to Boswellic Acids.” Pharmaceuticals vol. 4,8 1171–1182. 19 Aug. 2011, doi:10.3390/ph4081171

(2011) Kirste S, Treier M, Wehrle SJ, et al. “Boswellia extract acts on cerebral edema in patients irradiated for brain tumors: A prospective, randomized, placebo-controlled, double-blind pilot trial.”  Cancer. 117:3788-3795, 2011.

(2012) Paul, M., 2012. “Chemotaxonomic investigation on resins of the frankincense species Boswellia papyrifera, Boswellia serrata, Boswellia sacra respectively, Boswellia carterii.” Ph.D. Thesis, Saarland University, Saarbrucken, Saarland, Germany.

(2012) Ni X, Suhail MM, Yang Q, et al. “Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft murine model.” BMC Complement Altern Med. 2012;12:253.

(2013) Fung KM, Suhail MM, McClendon B, Woolley CL, Young DG, Lin HK. “Management of basal cell carcinoma of the skin using frankincense (Boswellia sacra) essential oil: a case report.” OA Altern Med. 2013;1:14.

(2013) Qurishi Y, Hamid A, Sharma PR, et al. “NF-ƙB down-regulation and PARP cleavage by novel 3-α-butyryloxy-β-boswellic acid results in cancer cell specific apoptosis and in vivo tumor regression.”  Anticancer Agents Med Chem.  13:777-790, 2013.

(2014) Dozmorov MG, Yang Q, Wu W, et al. “Differential effects of selective frankincense (Ru Xiang) essential oil versus nonselective sandalwood (Tan Xiang) essential oil on cultured bladder cancer cells: a microarray and bioinformatics study.” Chin Med. 2014;9:18.

(2014) Neeta and Harish Dureja, “Role of Boswellic Acids in Cancer Treatment.” Journal of Medical Sciences, 2014:14: 261-269.

(2014) Wang r, Wany Y, Gao Z, et al. “The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC(Min/+) mice.” Drug Discov Ther. 8:25-32, 2014.

(2015) Togni S, Maramaldi G, Bonetta A, Giacomelli L, Di Pierro F. “Clinical evaluation of safety and efficacy of Boswellia based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma: a randomized placebo controlled trial.” Eur Rev Med Pharmacol Sci. 2015;19: 1338-1344.

(2015) Pasta V, Gullo G, Giuliani A, et al. “An association of Boswellia, betaine and myo-inositol (EUmastos) in the treatment of mammographic breast density: A randomized, double-blind study.”  Eur Rev med Pharmacol Sci. 19:4419-4426, 2015.

(2016) Hamidpour R, Hamidpour S, Hamidpour M et al. “Frankincense (Boswellia Species): The Novel Phytotherapy for Drug Targeting in Cancer.” Arch Cancer Res. 2016, 4:1.

(2017) Ranjbarnejad T, Saidijam M, Moradkhani S, et al. “Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human cells.” Prostaglandins Other Lipid Mediat. 131:1-8, 2017.

(2018) Huang, M.; Li, A.; Zhao, F.; Xie, X.; Li, K.; Jing, Y.; Liu, D.; Zhao, L. “Design, synthesis and biological evaluation of ring A modified 11-keto-boswellic acid derivatives as Pin1 inhibitors with remarkable anti-prostate cancer activity.” Bioorganic Med. Chem. Lett. 2018, 28, 3187–3193.

(2018) Conti S, Vexler A, Edry-Botzer L, et al. “Combined acetyl-11-ketoboswellic acid and radiation treatment inhibited glioblastoma tumor cells.” PLoS One 13:e0198627, 2018.

(2019) Liu, YQ, et al. “Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties.”  Acta Pharmacol Sin. 2019 May;40(5):689-698. doi: 10.1038/s41401-018-0157-9. Epub 2018 Aug 31. (colon cancer, malignant glioma, prostate cancer, and leukemia)

BROMELAIN

(2008) Onken JE, Greer PK, Calingaert B, et al. “Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro.” Clin Immunol. 2008;126:345-52.

(2010) Katya Chobotova, et al. “Bromelain's activity and potential as an anti-cancer agent: Current evidence and perspectives.” Cancer Lett. 2010 Apr 28;290(2):148-56. doi: 10.1016/j.canlet.2009.08.001.

(2013) Barbara Romano, et al.  “The chemopreventive action of bromelain, from pineapple stem (Ananas comosusL.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects.” Molecular Nutrition & Food Research. Oct 1, 2013. https://doi.org/10.1002/mnfr.201300345

(2014) Pillai K, Ehteda A, Akhter J, Chua TC, Morris DL.  “Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells.” Anticancer Drugs. 2014 Feb;25(2):150-60. doi: 10.1097/CAD.0000000000000039. PMID: 24366282.

(2015) Afshin Amini. “Effects of bromelain and N-acetylcysteine on mucinexpressing human gastrointestinal carcinoma cells and their peritoneal spread: towards development of novel locoregional approaches to peritoneal surface malignancies and pathological mucin synthesis.” Thesis for Doctor of Philosophy. St George & Sutherland Clinical School Faculty of Medicine University of New South Wales. Sydney, NSW, Australia, May 2015.

(2016) Amini, Afshin et al. “Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells.” American journal of cancer research vol. 6,2 350-69. 15 Jan. 2016

(2018) Park, Sujeong et al. “Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis.” Animal cells and systems vol. 22,5 334-340. 30 Aug. 2018, doi:10.1080/19768354.2018.1512521

(2019) Tung-Cheng Chang, et al. “Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy.” PLoS One. 2019; 14(1): e0210274

(2019) Nurul Elyani Mohamad, et al. “Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo.” Integrative Cancer Therapies. November 21, 2019. https://journals.sagepub.com/doi/full/10.1177/1534735419880258#_i20

(2020) Pillai K, Mekkawy AH, Akhter J, Badar S, Dong L, Liu AI, Morris DL. ”Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.” Am J Transl Res. 2020 Nov 15;12(11):7404-7419. PMID: 33312377; PMCID: PMC7724355.

BUTYRATE/ BUTYRIC ACID- may cause false elevation in CEA

(2004) Louis M, Rosato RR, Brault L, Osbild S, Battaglia E, Yang XH, Grant S, Bagrel D. “The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress.” Int J Oncol. 2004 Dec;25(6):1701-11. PMID: 15547708.

(2005) Singh NP, Lai HC. “Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells.” Anticancer Res. 2005 Nov-Dec;25(6B):4325-31. PMID: 16309236.

(2008) Hamer HM, et al. “Review article: The role of butyrate on colonic function.” Aliment Pharmacol. Ther. 2008;27:104–119. doi: 10.1111/j.1365-2036.2007.03562.x.

(2009) Valerie Chopin, et al. “Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells.” British Journal of Pharmacology. First published: 29 January 2009

https://doi.org/10.1038/sj.bjp.0704456

(2017) Salimi V, Shahsavari Z, Safizadeh B, Hosseini A, Khademian N, Tavakoli-Yaraki M. “Sodium butyrate promotes apoptosis in breast cancer cells through reactive oxygen species (ROS) formation and mitochondrial impairment.” Lipids Health Dis. 2017 Nov 2;16(1):208. doi: 10.1186/s12944-017-0593-4. PMID: 29096636; PMCID: PMC5669027.

(2018) Jiezhong Chen, Luis Vitetta. “Inflammation-Modulating Effect of Butyrate in the Prevention of Colon Cancer by Dietary Fiber.” Clinical Colorectal Cancer, Volume 17, Issue 3, 2018, Pages e541-e544.

ISSN 1533-0028, https://doi.org/10.1016/j.clcc.2018.05.001. “Butyrate has been well demonstrated to be effective in the prevention of colon cancer.”

(2018) Li Q, Cao L, Tian Y, Zhang P, Ding C, Lu W, Jia C, Shao C, Liu W, Wang D, Ye H, Hao H. “Butyrate Suppresses the Proliferation of Colorectal Cancer Cells via Targeting Pyruvate Kinase M2 and Metabolic Reprogramming.” Mol Cell Proteomics. 2018 Aug;17(8):1531-1545. doi: 10.1074/mcp.RA118.000752. Epub 2018 May 8. PMID: 29739823; PMCID: PMC6072541.

(https://www.sciencedirect.com/science/article/pii/S1533002818301397)

(2018) Xu Z, Tao J, Chen P, Chen L, Sharma S, Wang G, Dong Q. “Sodium Butyrate Inhibits Colorectal Cancer Cell Migration by Downregulating Bmi-1 Through Enhanced miR-200c Expression.” Mol Nutr Food Res. 2018 Mar;62(6):e1700844. doi: 10.1002/mnfr.201700844. Epub 2018 Feb 27. PMID: 29418071.

(2020) Wang W, Fang D, Zhang H, Xue J, Wangchuk D, Du J, Jiang L. “Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1.” Onco Targets Ther. 2020 May 27;13:4691-4704. doi: 10.2147/OTT.S235575. PMID: 32547098; PMCID: PMC7263851.

(2020) Semaan J, El-Hakim S, Ibrahim JN, Safi R, Elnar AA, El Boustany C. “Comparative effect of sodium butyrate and sodium propionate on proliferation, cell cycle and apoptosis in human breast cancer cells MCF-7.” Breast Cancer. 2020 Jul;27(4):696-705. doi: 10.1007/s12282-020-01063-6. Epub 2020 Feb 24. PMID: 32095987.

(2021) Hajjar R, Richard CS, Santos MM. “The role of butyrate in surgical and oncological outcomes in colorectal cancer.” Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1;320(4):G601-G608. doi: 10.1152/ajpgi.00316.2020. Epub 2021 Jan 6. PMID: 33404375; PMCID: PMC8238168.

(2021) Xi Y, Jing Z, Wei W, Chun Z, Quan Q, Qing Z, Jiamin X, Shuwen H. “Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network.” BMC Cancer. 2021 Feb 6;21(1):127. doi: 10.1186/s12885-021-07845-1. PMID: 33549042; PMCID: PMC7866666.

(2021) Li M, McGhee EM, Shinno L, Lee K, Lin YL. “Exposure to Microbial Metabolite Butyrate Prolongs the Survival Time and Changes the Growth Pattern of Human Papillomavirus 16 E6/E7-Immortalized Keratinocytes in Vivo.” Am J Pathol. 2021 Oct;191(10):1822-1836. doi: 10.1016/j.ajpath.2021.06.005. Epub 2021 Jun 29. PMID: 34214507; PMCID: PMC8579241.

(2022) Park B, Kim JY, Riffey OF, Dowker-Key P, Bruckbauer A, McLoughlin J, Bettaieb A, Donohoe DR. “Pyruvate kinase M1 regulates butyrate metabolism in cancerous colonocytes.” Sci Rep. 2022 May 24;12(1):8771. doi: 10.1038/s41598-022-12827-9. PMID: 35610475; PMCID: PMC9130307.

CAM MEDICINE

(2011) Michael McCulloch, Michael Broffman, Mark van der Laan, Alan Hubbard, Lawrence Kushi, Alan Kramer, Jin Gao and John M. Colford, Jr.  “Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods Lung Cancer Survival With Herbal Medicine and Vitamins in a Whole-Systems Approach : Ten-Year”.  Integrative Cancer Therapies.  2011 10: 260 originally published online 8 August 2011.

L-CARNITINE

(2018) Dinicola S, et al.  “Natural products – alpha-lipoic acid and acetyl-L-carnitine – in the treatment of chemotherapy-induced peripheral neuropathy.” European Review for Medical and Pharmacological Sciences. 2018; 22: 4739-4754.

COQ10

(1994) Lockwood, et al. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10.” Biochem Biophys Res Commun. 1994 Mar 30;199(3):1504-8. “PMID:7908519 DOI:10.1006/bbrc.1994.1401

(2005) Malik, et al. “Coenzyme Q10 inhibits proliferation of breast cancer cells while stabilizing growth in primary cells in vitro.”  Cancer Res May 1 2005 (65) (9 Supplement) 1384-1385;

(2009) Hertz, et al. “Improved Survival in Patients with Endstage Cancer Treated with Coenzyme Q10 and Other Antioxidants: a Pilot Study.” The Journal of International Medical Research. 2009; 37: 1961 – 1971

(2014) Mathews, et al.  “The effects of coenzyme Q10 on women with breast cancer: a systematic review protocol.” JBI Database of Systematic Reviews & Implementation Reports 2014;12(8) 127 – 144.

(2015) Asuka Yasueda, et al. “Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review.” Integrative Cancer Therapies. Oct 26, 2015.

(2016) Iwase, S, et al. “Efficacy and safety of an amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: a multi-institutional, randomized, exploratory trial (JORTC-CAM01).” Support Care Cancer. 2016 Feb;24(2):637-646. doi: 10.1007/s00520-015-2824-4. Epub 2015 Jun 24.

(2017) Tafazoli, A. “Coenzyme Q10 in breast cancer care.” Future Oncol. 2017 May;13(11):1035-1041. doi: 10.2217/fon-2016-0547.

(2017) Jang, et al. “Effect of coenzyme Q10 via nitric oxide production and growth arrest of human colon cancer HCT116 cells.” J. Prev. Vet. Med 2017; 41(2): 59-65.

(2018) Coenzyme Q10 PDQ. https://www.ncbi.nlm.nih.gov/books/NBK65890/

(2019) Aksoy, et al.  “An investigation of oxidative stress and coenzyme Q10 levels in patients with head and neck squamous cell carcinomas.” Eur Arch Otorhinolaryngol. 2019 Apr;276(4):1197-1204. doi: 10.1007/s00405-019-05328-5. Epub 2019 Feb 7.

(2019) Irem Kaymak, et al.  “Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress.” https://cancerres.aacrjournals.org/content/canres/early/2019/12/19/0008-5472.CAN-19-0650.full.pdf

(2020) PR Palan, et al.  “Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer.” Europena Journal of Cancer Protection 12(40): 321-6.

(2021) Mantle, David et al. “Coenzyme Q10 and Immune Function: An Overview.” Antioxidants (Basel, Switzerland) vol. 10,5 759. 11 May. 2021, doi:10.3390/antiox10050759

CURCUMIN

(1999) Han SS, Chung ST, Robertson DA, Ranjan D, Bondada S. “Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53.” Clin Immunol. 1999 Nov;93(2):152-61. doi: 10.1006/clim.1999.4769. PMID: 10527691.

(2004) Myung-Ju Ahn, et al. “Mechanisms of proapoptotic properties of curcumin in chronic and acute myeloid leukemia.” AACR. April 2004: Vol 64:7

(2009) Ravindran, Jayaraj et al. “Curcumin and cancer cells: how many ways can curry kill tumor cells selectively?” AAPS journal vol. 11,3 (2009): 495-510.

(2011) Wang Y., Rishi A.K., Wu W., Polin L., Sharma S., Levi E., Albelda S., Pass H.I., Wali A. “Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.” Mol. Cell. Biochem. 2011;357:83–94. doi: 10.1007/s11010-011-0878-2

(2013) Yu, Jianhua et al. “Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia.” PloS one vol. 8,2 (2013): e55934. doi:10.1371/journal.pone.0055934

(2014) Troselj KG.  “Curcumin in combined cancer therapy.” Current Pharmaceutical Design. 2014;20(42):6682-96.

(2014) Miller J.M., Thompson J.K., MacPherson M.B., Beuschel S.L., Westbom C.M., Sayan M., Shukla A. “Curcumin: A double hit on malignant mesothelioma.” Cancer Prev. Res. 2014;7:330–340. doi: 10.1158/1940-6207.CAPR-13-0259.

(2015) Zeng, Yingjian et al. “Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells.” Oncology reports vol. 36,3 (2016): 1233-42.

(2015) Mayol L., Serri C., Menale C., Crispi S., Piccolo M.T., Mita L., Giarra S., Forte M., Saija A., Biondi M., et al.  “Curcumin loaded PLGA-poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells.”  Eur. J. Pharm. Biopharm. 2015;93:37–45. doi: 10.1016/j.ejpb.2015.03.005.

(2015)- Ramasamy TS, Ayob AZ, Myint HH, Thiagarajah S, Amini F. “Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy.” Cancer Cell Int. 2015;15:96. doi: 10.1186/s12935-015-0241-x.

(2015) Chen QH. “Curcumin-based anti-prostate cancer agents.” Anticancer Agents Med Chem. 2015;15(2):138-56. doi: 10.2174/1871520615666150116102442. PMID: 25594891.

(2016) James MI, Iwuji C, Irving G, Karmokar A, Higgins JA, Griffin-Teal N, Thomas A, Greaves P, Cai H, Patel SR, Morgan B, Dennison A, Metcalfe M, et al. “Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy.” Cancer Lett. 2015;364:135–41. doi: 10.1016/j.canlet.2015.05.005.

(2016) Kantara C, O’Connell M, Sarkar S, Moya S, Ullrich R, Singh P. “Curcumin promotes autophagic survival of a subset of colon cancer stem cells, which are ablated by DCLK1-siRNA.” Cancer Res. 2014;74:2487–98. doi: 10.1158/0008-5472.CAN-13-3536.

(2016)  Huang YT, Lin YW, Chiu HM, Chiang BH. “Curcumin induces apoptosis of colorectal cancer stem cells by coupling with CD44 marker.”  J Agric Food Chem. 2016;64:2247–53. doi: 10.1021/acs.jafc.5b05649.

(2016) Yi Deng, et al. “Molecular Mechanisms of Anti-metastatic Activity of Curcumin.” Anticancer Research. 36: 5639-5648 (2016) doi:10.21873/anticanres.11147.

(2016) James MI, Iwuji C, Irving G, Karmokar A, Higgins JA, Griffin-Teal N, Thomas A, Greaves P, Cai H, Patel SR, Morgan B, Dennison A, Metcalfe M, et al. “Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy.” Cancer Lett. 2015;364:135–41. doi: 10.1016/j.canlet.2015.05.005.

(2016) Gardane, et al. “Curcumin sensitizes quiescent leukemic cells to antimitotic drug 5-fluorouracil by inducing proliferative responses in them.” J Cancer Metastasis Treat 2016;2:245-52.

(2016) He M., Wang D., Zou D., Wang C., Lopes-Bastos B., Jiang W.G., Chester J., Zhou Q., Cai J. “Re-purposing of curcumin as an anti-metastatic agent for the treatment of epithelial ovarian cancer: In vitro model using cancer stem cell enriched ovarian cancer spheroids.” Oncotarget. 2016;7:86374–86387. doi: 10.18632/oncotarget.13413.

(2016) Schmidt KT, Figg WD. “The potential role of curcumin in prostate cancer: the importance of optimizing pharmacokinetics in clinical studies.” Transl Cancer Res. 2016 Nov;5(Suppl 6):S1107-S1110. doi: 10.21037/tcr.2016.11.04. PMID: 30613476; PMCID: PMC6320229.

(2017) Animesh Kumar, et al.  “Enhanced apoptosis, survivin down-regulation and assisted immunochemotherapy by curcumin loaded amphiphilic mixed micelles for subjugating endometrial cancer.” Nanomedicine: Nanotechnology, Biology and Medicine. Volume 13, Issue 6, August 2017, Pages 1953-1963.

(2017) Zaidi, Abbas et al. “Long-term stabilisation of myeloma with curcumin.” BMJ case reports vol. 2017 bcr2016218148. 16 Apr. 2017, doi:10.1136/bcr-2016-218148

(2017) Masuelli L., Benvenuto M., Di Stefano E., Mattera R., Fantini M., De Feudis G., De Smaele E., Tresioldi I., Giganti M.G., Modesti A., et al. “Curcumin blocks autophagy and activates apoptosis of malignant mesothelioma cell lines and increases the survival of mice intraperitoneally transplanted with a malignant mesothelioma cell line.” Oncotarget. 2017;8:34405–34422. doi: 10.18632/oncotarget.14907.

(2018) Sourav Banerjee, et al.  “Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2.” Proceedings of the National Academy of Sciences, 2018; 201806797 DOI: 10.1073/pnas.1806797115. Anti-cancer therapy.

(2018) Li, et al. “Evaluation of curcumin, a natural product in turmeric, on Burkitt lymphoma and acute myeloid leukemia cancer stem cell markers.” Future Oncol. 2018 Oct;14(23):2353-2360.

(2018) Zhang C., Hao Y., Wu L., Dong X., Jiang N., Cong B., Liu J., Zhang W., Tang D., De Perrot M., et al. “Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma.” Int. J. Oncol. 2018;53:2531–2541. doi: 10.3892/ijo.2018.4569

(2018) Melekoglu R, Ciftci O, Eraslan S, Cetin A, Basak N. “Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model.” J Ovarian Res. 2018 Apr 26;11(1):33. doi: 10.1186/s13048-018-0409-9. PMID: 29699594; PMCID: PMC5918567.

(2019) Howells LM, Iwuji CO, Irving GR, Barber S, Walter H, Sidat Z, et al. “Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial.” J Nutr. 2019;149(7):1133–9.

(2019) “Curcumin improves FOLFOX chemotherapy response in Colorectal Cancer patients.” Nov 4, 2019. https://addon.life/2019/11/04/curcumin-folfox-colorectal/

(2019) Di Meo F., Filosa S., Madonna M., Giello G., Di Pardo A., Maglione V., Baldi A., Crispi S.  “Curcumin C3 complex^®/Bioperine^® has antineoplastic activity in mesothelioma: An in vitro and in vivo analysis.” J. Exp. Clin. Cancer Res. 2019;38:360. doi: 10.1186/s13046-019-1368-8.

(2019) El Khoury, Diala et al. “Curcumin and endometrial carcinoma: an old spice as a novel agent.” International journal of women's health vol. 11 249-256. 16 Apr. 2019, doi:10.2147/IJWH.S194262

(2020) Akomolafe SF, Olasehinde TA, Oyeleye SI, Aluko TB, Adewale OO, Ijomone OM. “Curcumin Administration Mitigates Cyclophosphamide-Induced Oxidative Damage and Restores Alteration of Enzymes Associated with Cognitive Function in Rats' Brain.” Neurotox Res. 2020 Jun;38(1):199-210. doi: 10.1007/s12640-020-00205-0. Epub 2020 May 14. PMID: 32405958.

(2020) Mansouri, K., Rasoulpoor, S., Daneshkhah, A. et al. “Clinical effects of curcumin in enhancing cancer therapy: A systematic review. “BMC Cancer 20, 791 (2020). https://doi.org/10.1186/s12885-020-07256-8  FOLFOX

(2020) Baldi, Alfonso et al. “Curcumin as an Anticancer Agent in Malignant Mesothelioma: A Review.” International journal of molecular sciences vol. 21,5 1839. 7 Mar. 2020, doi:10.3390/ijms21051839.

(2020) Jahanbakhshi, F., Maleki Dana, P., Badehnoosh, B. et al. “Curcumin anti‐tumor effects on endometrial cancer with focus on its molecular targets.” Cancer Cell Int 21, 120 (2021). https://doi.org/10.1186/s12935-021-01832-z

(2020) Pourhanifeh, M.H., Darvish, M., Tabatabaeian, J. et al. “Therapeutic role of curcumin and its novel formulations in gynecological cancers.”  J Ovarian Res 13, 130 (2020). https://doi.org/10.1186/s13048-020-00731-7

(2020) Chen L, Zhan CZ, Wang T, You H, Yao R. “Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis.” Yonsei Med J. 2020 Jan;61(1):20-29. doi: 10.3349/ymj.2020.61.1.20. PMID: 31887796; PMCID: PMC6938780.

(2020) Termini D, Den Hartogh DJ, Jaglanian A, Tsiani E. “Curcumin against Prostate Cancer: Current Evidence.” Biomolecules. 2020 Nov 10;10(11):1536. doi: 10.3390/biom10111536. PMID: 33182828; PMCID: PMC7696488.

(2021) Zoi V, Galani V, Lianos GD, Voulgaris S, Kyritsis AP, Alexiou GA. “The Role of Curcumin in Cancer Treatment.” Biomedicines. 2021 Aug 26;9(9):1086. doi: 10.3390/biomedicines9091086. PMID: 34572272; PMCID: PMC8464730.

(2021) Zhang, Yu et al. “Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway.” Frontiers in oncology vol. 11 656045. 11 Aug. 2021, doi:10.3389/fonc.2021.656045

(2022) Wang G, Duan P, Wei Z, Liu F. “Curcumin sensitizes carboplatin treatment in triple negative breast cancer through reactive oxygen species induced DNA repair pathway.” Mol Biol Rep. 2022 Apr;49(4):3259-3270. doi: 10.1007/s11033-022-07162-1. Epub 2022 Jan 25. PMID: 35076853.

(2022) Farghadani R, Naidu R. “Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer.” Int J Mol Sci. 2022 Feb 15;23(4):2144. doi: 10.3390/ijms23042144. PMID: 35216255; PMCID: PMC8878285.

ENZYMES

(2014) Herszényi, László et al. “Impact of proteolytic enzymes in colorectal cancer development and progression.” World journal of gastroenterology vol. 20,37 (2014): 13246-57. doi:10.3748/wjg.v20.i37.13246

(2018) Kirstine Lavrsen, Sally Dabelsteen, Sergey Y. Vakhrushev, Asha M. R. Levann, Amalie Dahl Haue, August Dylander, Ulla Mandel, Lars Hansen, Morten Frödin, Eric P. Bennett, Hans H. Wandall.  “De novoexpression of human polypeptideN-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium.” Journal of Biological Chemistry, 2018; 293 (4): 1298 DOI: 10.1074/jbc.M117.812826

EXERCISE

(2018) Agarwal RP, Maroko-Afek A. “Yoga into cancer care: A review of the evidence-based research.” Int J Yoga 2018;11:3-29.

(2021) Cannioto RA, et.al.  “Physical Activity Before, During, and After Chemotherapy for High-Risk Breast Cancer: Relationships With Survival.” JNCI J Natl Cancer Inst (2021) 113(1): djaa046 doi: 10.1093/jnci/djaa046

(2022) Zheng A, Zhang L, Yang J, Yin X, Zhang T, Wu X and Ma X. “Physical activity prevents tumor metastasis through modulation of immune function.” (2022). Front. Pharmacol. 13:1034129. doi: 10.3389/fphar.2022.1034129

FATS/LIPIDS

(2017) Pabst, Thomas et al. “The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features.” BBA clinical vol. 7 105-114. 8 Mar. 2017, doi:10.1016/j.bbacli.2017.03.002

FEBENDAZOLE/MEBENDAZOLE

(2008) Gao, Ping et al. “Unexpected antitumorigenic effect of fenbendazole when combined with supplementary vitamins.” Journal of the American Association for Laboratory Animal Science : JAALAS vol. 47,6 (2008): 37-40.

(2014) Pantziarka Pan, at al. “Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent” ecancer 8 443

(2018) Dogra, Nilambra et al. “Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways.” Scientific reports vol. 8,1 11926. 9 Aug. 2018, doi:10.1038/s41598-018-30158-6

(2019) Guerini, et al. “Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature.” Cancers 2019, 11(9), 1284; https://doi.org/10.3390/cancers11091284

(2019) Rushworth, L.K., Hewit, K., Munnings-Tomes, S. et al. “Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment.” Br J Cancer (2019). https://doi.org/10.1038/s41416-019-0681-5

FLAVONOIDS

(2007) J. J. Raffoul, F. H. Sarkar, and G. G. Hillman. “Radiosensitization of prostate cancer by soy isoflavones.” Current Cancer Drug Targets, vol. 7, no. 8, pp. 759–765, 2007.

(2010) I. U. Ahmad, J. D. Forman, F. H. Sarkar et al. “Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer.” Nutrition and Cancer, vol. 62, no. 7, pp. 996–1000, 2010.

(2011) G. G. Hillman and V. Singh-Gupta. “Soy isoflavones sensitize cancer cells to radiotherapy.” Free Radical Biology & Medicine, vol. 51, no. 2, pp. 289–298, 2011.

(2011) V. Singh-Gupta, M. C. Joiner, L. Runyan et al. “Soy isoflavones augment radiation effect by inhibiting APE1/ref-1 DNA repair activity in non-small cell lung cancer.” Journal of Thoracic Oncology, vol. 6, no. 4, pp. 688–698, 2011.

FLAXSEEDS

(1998) Lin Yan, et al.  “Dietary flaxseed supplementation and experimental metastasis of melanoma cells in mice.” Cancer Letters. Volume 124, Issue 2, 27 February 1998, Pages 181-186

(2005) Dwivedi C, Natarajan K, Matthees DP.  “Chemopreventive effects of dietary flaxseed oil on colon tumor development.” Nutr Cancer. 2005;51(1):52-8.

(2015) Han, J, et al.  “Flax seed oil inhibits metastatic melanoma and reduces lung tumor formation in mice.” Journal BUON. 2015 Nov-Dec;20(6):1546-52.

(2017) Kim, Dong Joon et al. “Herbacetin suppresses cutaneous squamous cell carcinoma and melanoma cell growth by targeting AKT and ODC.” Carcinogenesis vol. 38,11 (2017): 1136-1146.

(2018) Calado, Ana et al. “The Effect of Flaxseed in Breast Cancer: A Literature Review.” Frontiers in nutrition vol. 5 4. 7 Feb. 2018, doi:10.3389/fnut.2018.00004

(2018) Shahira M. Ezzat, et al. “Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars.” Nature Scientific Reports. January 11, 2018.  https://www.nature.com/articles/s41598-017-18944-0 .pdf

FOLATE

(2018) Michelle Claire Rudd, Prof Robert Lea, Dr Jane Alder; University of Central Lancashire. “Folate: Friend or Foe? An Investigation Into the Opposing Roles of Folate in Glioma.”  Neuro-oncology.  Jan 2018.

(2018) Pieroth, Renee et al. “Folate and Its Impact on Cancer Risk.” Current nutrition reports vol. 7,3 (2018): 70-84.

FUCOIDAN (Brown Seaweed)

Website product comparison- https://mosteffectivefucoidan.com/home-page/#:~:text=1%20Life%20Extension%20Fucoidan.%20This%20brand%20contains%2088.5,Products.%20...%209%20Ocean%E2%80%99s%20Bounty.%20...%2010%20Brolico

(2006) Moreau, D., et al. “An extract from the brown alga bifurcaria bifurcata induces irreversible arrest of cell proliferation in a non-small-cell bronchopulmonary carcinoma line.”  J. Appl. Phycol. 2006, 18, 87–93.

(2010) Kim, E.J., et al.  “Fucoidan present in brown algae induces apoptosis of human colon cancer cells.”  BMC Gastroenterol. 2010, 10, 96, doi:10.1186/1471-230X-10-96.

(2011) Boo, H.J., et al. “Fucoidan from undaria pinnatifida induces apoptosis in a549 human lung carcinoma cells.”  Phytother. Res. 2011, 25, 1082–1086.

(2011) Ikeguchi, M., et al.  “Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer.” Oncol. Lett. 2011, 2, 319–322. 62.

(2012) Azuma K, Ishihara T, Nakamoto H, Amaha T, Osaki T, Tsuka T, Imagawa T, Minami S, Takashima O, Ifuku S, et al. “Effects of oral administration of fucoidan extracted from Cladosiphon okamuranus on tumor growth and survival time in a tumor-bearing mouse model.” Mar Drugs. 2012;10(10):2337–48.

(2012) Lv, Y., et al. “Comparison of the effects of marchantin c and fucoidan on sflt-1 and angiogenesis in glioma microenvironment.”  J. Pharm. Pharmacol. 2012, 64, 604–609.

(2013) Kimura, Ryuichiro et al. “Cytotoxic effects of fucoidan nanoparticles against osteosarcoma.” Marine drugs vol. 11,11 4267-78. 30 Oct. 2013, doi:10.3390/md11114267.

(2013) Boo, H.J, et al. “The anticancer effect of fucoidan in pc-3 prostate cancer cells.” Mar. Drugs 2013, 11, 2982–2999.

(2013) Banafa, A.M., et al. “Fucoidan induces g1 phase arrest and apoptosis through caspases-dependent pathway and ros induction in human breast cancer mcf-7 cells.”  J. Huazhong Univ. Sci. Technol. Med. Sci. 2013, 33, 717–724.

(2013) Hsu HY, Lin TY, Hwang PA, Tseng LM, Chen RH, Tsao SM, Hsu J. “Fucoidan induces changes in the epithelial to mesenchymal transition and decreases metastasis by enhancing ubiquitin-dependent TGFbeta receptor degradation in breast cancer.” Carcinogenesis. 2013;34(4):874–84.

(2015) Atashrazm, Farzaneh et al. “Fucoidan and cancer: a multifunctional molecule with anti-tumor potential.” Marine drugs vol. 13,4 2327-46. 14 Apr. 2015, doi:10.3390/md13042327.

(2015) Kalimuthu, S.; Kim, S. “Fucoidan, a sulfated polysaccharides from brown algae as therapeutic target for cancer.” In Handbook of Anticancer Drugs from Marine Origin; Kim, S., Ed.; Springer International Publishing: Cham, Switzerland, 2015; p. 147.

(2015) Wei, et al. “Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species.” Mol Med Rep. 2015 Nov;12(5):6649-55.

(2015) Yang G, Zhang Q, Kong Y, Xie B, Gao M, Tao Y, Xu H, Zhan F, Dai B, Shi J, et al. “Antitumor activity of fucoidan against diffuse large B cell lymphoma in vitro and in vivo.” Acta Biochim Biophys Sin. 2015;47(11):925–31.

(2016) Atashrazm, et al.  “Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo.” J Cell Physiol. 2016 Mar;231(3):688-97.

(2016) Liu, et al.  “Fucoidan inhibits angiogenesis induced by multiple myeloma cells.” Spandidos Pub, Oncology Reports. October 2016. Volume 36 Issue 4 (1963-1972).

(2016) Choo GS, Lee HN, Shin SA, Kim HJ, Jung JY.  “Anticancer effect of fucoidan on DU-145 prostate cancer cells through inhibition of PI3K/Akt and MAPK pathway expression.” Mar Drugs. 2016;14(7):126.

(2016) Cho Y, Cho EJ, Lee JH, Yu SJ, Kim YJ, Kim CY, Yoon JH. “Fucoidan-induced ID-1 suppression inhibits the in vitro and in vivo invasion of hepatocellular carcinoma cells.” Biomed Pharmacother. 2016;83:607–16.

(2017) Tsai HL, Tai CJ, Huang CW, Chang FR, Wang JY. “Efficacy of low-molecular-weight fucoidan as a supplemental therapy in metastatic colorectal cancer patients: a double-blind randomized controlled trial. Mar Drugs.” 2017;15(4):122.

(2018) Kim IH, Nam TJ. “Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells.” Oncol Rep. 2018;39(3):1516–22.

(2019) Hsu, Hsien-Yeh, and Pai-An Hwang. “Clinical applications of fucoidan in translational medicine for adjuvant cancer therapy.” Clinical and translational medicine vol. 8,1 15. 1 May. 2019, doi:10.1186/s40169-019-0234-9

(2019) Bobiński M, Okła K, Bednarek W, Wawruszak A, Dmoszyńska-Graniczka M, Garcia-Sanz P, Wertel I, Kotarski J. “The effect of fucoidan, a potential new, natural, anti-neoplastic agent on uterine sarcomas and carcinosarcoma cell lines: ENITEC collaborative study.” Archivum Immunologiae et Therapiae Experimentalis. 2019;67(2):125–31.

(2020) Duan Y, Li J, Jing X, Ding X, Yu Y, Zhao Q. “Fucoidan induces apoptosis and inhibits proliferation of hepatocellular carcinoma via the p38 MAPK/ERK and PI3K/Akt signal pathways.” Cancer Manag Res. 2020;12:1713–23.

(2023) Turrini E, Maffei F, Fimognari C. “Ten Years of Research on Fucoidan and Cancer: Focus on Its Antiangiogenic and Antimetastatic Effects.” Mar Drugs. 2023 May 18;21(5):307. doi: 10.3390/md21050307. PMID: 37233501; PMCID: PMC10223425.

GLUCOSE

Rath,Linda. “Cancer and Sugar: Is There a Link?” https://www.webmd.com/cancer/features/cancer-sugar-link#1

Heather Christofk, PhD, co-leader of the UCLA Metabolomics Center. “Most Cancers Use Glucose.” https://medschool.ucla.edu/metabolism/cancer-glucose-metabolism

(2015) Granja, et al. “Glucose Addiction in Cancer Therapy: Advances and Drawbacks.”

Curr Drug Metab. 2015;16(3):221-42.

(2016) Yu, et al.  “The sweet trap in tumors: aerobic glycolysis and potential targets for therapy.” Oncotarget. 2016 Jun 21;7(25):38908-38926. doi: 10.18632/oncotarget.7676.

(2017) Santye, Lauren. “Squamous Cell Carcinoma Significantly More Dependent on Sugar Than Other Cancer Types.” https://www.pharmacytimes.com/news/squamous-cell-carcinoma-significantly-more-dependent-on-sugar-than-other-cancer-types. May 31,2017.

(2018) “A Breakthrough in the Connection Between Sugar and Lung Cancer.” American Lung Association. https://www.lung.org/about-us/blog/2018/02/sugar-and-lung-cancer.html.  February 12, 2018.

(2018) Bise, et al, “Glucose Metabolism in Cancer.” Adv Exp Med Biol. 2018;1063:3-12. doi: 10.1007/978-3-319-77736-8_1.

(2019) Arthur Dyer, et al.  “Antagonism of Glycolysis and Reductive Carboxylation of Glutamine Potentiates Activity of Oncolytic Adenoviruses in Cancer Cells.” Cancer Res January 15 2019 (79) (2) 331-345; DOI: 10.1158/0008-5472.CAN-18-1326 Published January 2019

GLUTAMINE- avoid with Sarcoma

(2015) Krzysztof Piotr Michalak,1,2 Agnieszka MaTkowska-Kwdziora,3 BogusBaw Sobolewski,4 and Piotr Wofniak. “Key Roles of Glutamine Pathways in Reprogramming the Cancer Metabolism.” Oxidative Medicine and Cellular Longevity Volume 2015, Article ID 964321, 14 pages

(2016) Bajpai, R et al. “Targeting glutamine metabolism in multiple myeloma enhances BIM binding to BCL-2 eliciting synthetic lethality to venetoclax.” Oncogene vol. 35,30 (2016): 3955-64. doi:10.1038/onc.2015.464

(2016) Bolzoni, et al.  “Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: A new attractive target.” Blood 128(5) · June 2016

(2018) Choi, Yeon-Kyung, and Keun-Gyu Park. “Targeting Glutamine Metabolism for Cancer Treatment.” Biomolecules & therapeutics vol. 26,1 (2018): 19-28. doi:10.4062/biomolther.2017.178

(2019) Jiang, Jie et al. “Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?.” Cancers vol. 11,6 804. 11 Jun. 2019, doi:10.3390/cancers11060804

(2019) Grinde, M.T., Hilmarsdottir, B., Tunset, H.M. et al. “Glutamine to proline conversion is associated with response to glutaminase inhibition in breast cancer.” Breast Cancer Res 21, 61 (2019) doi:10.1186/s13058-019-1141-0

(2020) Lee P, Malik D, Perkons N, Huangyang P, Khare S, Rhoades S, Gong YY, Burrows M, Finan JM, Nissim I, Gade TPF, Weljie AM, Simon MC. “Targeting glutamine metabolism slows soft tissue sarcoma growth.” Nat Commun. 2020 Jan 24;11(1):498. doi: 10.1038/s41467-020-14374-1. PMID: 31980651; PMCID: PMC6981153.

GLUTATHIONE

(1986) Midander J, Deschavanne PJ, Debieu D, Malaise EP, Revesz L. “Reduced repair of potentially lethal radiation damage in glutathione synthetase-deficient human fibroblasts after X-irradiation.” Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Mar;49(3):403-13. PMID: 3485589.

(1995) Cascinu S, Cordella L, Del Ferro E, Fronzoni M, Catalano G. “Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.” J Clin Oncol. 1995 Jan;13(1):26-32. PubMed PMID: 7799029.

(1997) Smyth JF, et al. “Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomized trial.” Ann Oncol. 1997 Jun;8(6):569-73. PubMed PMID: 9261526.

(2002) Cascinu S, et al. “Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.” J Clin Oncol. 2002 Aug 15;20(16):3478-83. PubMed PMID: 12177109.

(2003) Bakan, Nuri et al. “Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia.” Clinica chimica acta; international journal of clinical chemistry vol. 338,1-2 (2003): 143-9. doi:10.1016/j.cccn.2003.08.013

(2007) Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. “The central role of glutathione in the pathophysiology of human diseases.” Arch Physiol Biochem. 2007 Oct-Dec;113(4-5):234-58. Review. PubMed PMID: 18158646.

(2007) King-TehLee, et al. “Glutathione status in the blood and tissues of patients with virus-originated hepatocellular carcinoma.” Clinical Biochemstry. Volume 40, Issue 15, October 2007, Pages 1157-1162.

(2008) Sreeja L, Syamala V, Hariharan S, Syamala VS, Raveendran PB, Sivanandan CD, Madhavan J, Ankathil R. “Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients.” J Exp Ther Oncol. 2008;7(1):73-85. PubMed PMID: 18472644.

(2009) Pujari G, Berni A, Palitti F, Chatterjee A. “Influence of glutathione levels on radiation-induced chromosomal DNA damage and repair in human peripheral lymphocytes.” Mutat Res. 2009 JunJul;677(1-2):109-10. PMID: 19386243

(2009) Milla P, et al. “Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity.” Anticancer Drugs. 2009 Jun;20(5):396-402. PubMed PMID: 19287306.

(2010) Kilburn L, et al.  “Glutathione S-transferase polymorphisms are associated with survival in anaplastic glioma patients.” Cancer. 2010 Feb 24. [Epub ahead of print] PubMed PMID: 20187096.

(2011) Angel L. Ortega, at al. “Glutathione in Cancer Cell Death.”  Cancers 2011, 3, 1285-1310; doi:10.3390/cancers3011285.

(2013) Nicola Traverso, et al., “Role of Glutathione in Cancer Progression and Chemoresistance (AML).” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 972913, 10 pages, 2013. doi:10.1155/2013/972913.

(2014) Mitchell, Gaynor.  “Complete Remission of Widely Metastatic Melanoma: A Case Report.” Cancer Strategies Journal.  Spring 2014.

(2017) Zhou, et al. “Detection of Glutathione in Oral Squamous Cell Carcinoma Cells With a Fluorescent Probe During the Course of Oxidative Stress and Apoptosis.” J Oral Maxillofac Surg. 2017 Jan;75(1):223.e1-223.e10. doi: 10.1016/j.joms.2016.08.010. Epub 2016 Aug 24.

(2018) Bansal, Ankita and Simon, Celeste.  “Glutathione metabolism in cancer progression and treatment resistance.”  J Cell Biol (2018) 217 (7): 2291–2298.

(2020) Luke Kennedy, et al. “Role of Glutathione in Cancer: From Mechanisms to Therapies.” Biomolecules. 2020, 10, 1429; doi:10.3390/biom10101429

(2021) Kochman J, Jakubczyk K, Bargiel P, Janda-Milczarek K. “The Influence of Oxidative Stress on Thyroid Diseases.” Antioxidants (Basel). 2021 Sep 10;10(9):1442. doi: 10.3390/antiox10091442. PMID: 34573074; PMCID: PMC8465820.

(2022) Sekhar KR, Hanna DN, Cyr S, Baechle JJ, Kuravi S, Balusu R, Rathmell K, Baregamian N. “Glutathione peroxidase 4 inhibition induces ferroptosis and mTOR pathway suppression in thyroid cancer.” Sci Rep. 2022 Nov 12;12(1):19396. doi: 10.1038/s41598-022-23906-2. PMID: 36371529; PMCID: PMC9653479.

(2022) Criscuolo D, Avolio R, Parri M, Romano S, Chiarugi P, Matassa DS, Esposito F. “Decreased Levels of GSH Are Associated with Platinum Resistance in High-Grade Serous Ovarian Cancer.” Antioxidants. 2022; 11(8):1544. https://doi.org/10.3390/antiox11081544

(2023) Marini HR, Facchini BA, di Francia R, Freni J, Puzzolo D, Montella L, Facchini G, Ottaiano A, Berretta M, Minutoli L.  “Glutathione: Lights and Shadows in Cancer Patients.”  Biomedicines. 2023 Aug 8;11(8):2226. doi: 10.3390/biomedicines11082226. PMID: 37626722; PMCID: PMC10452337.

GRAPESEED EXTRACT

(2008) American Association for Cancer Research. "Grape-seed Extract Kills Laboratory Leukemia Cells, Proving Value Of Natural Compounds." ScienceDaily. ScienceDaily, 1 January 2009. <www.sciencedaily.com/releases/2008/12/081231005257.htm>.

GREEN TEA EXTRACT/ EGCG

(2002) Sartippour, Shao, Heber, et al. “Green Tea Inhibits VEGF Induction in Human Breast Cancer Cells.”  J. Nutr. 2002; 132: 2307-2311.

(2002) Hsu SD, Singh BB, Lewis JB, Borke JL, Dickinson DP, Drake L, Caughman GB, Schuster GS. “Chemoprevention of oral cancer by green tea.” Gen Dent. 2002 Mar-Apr;50(2):140-6. PMID: 12004708.

(2004) Kay. “Green Tea Component Destroys Leukemia Cells.”  Blood Mar.2, 2004 On-line edition.

(2004) Yokoyama, Noguchi, Nakao, et al. “The Tea Polyphenol, (-)-Epigallocatechin Gallate Effects on Growth, Apoptosis, and Telomerase Activity in Cervical Cell Lines.” Gynecol. Oncol. 2004; 92 (1): 197-204.

(2004) Mittal, Pate, Wylie, et al.  “EGCG Down-Regulates Telomerase in Human Breast Carcinoma MCF-7 Cells, Leading to Suppression of Cell Viability and Induction of Apoptosis.” Int. J. Oncol. 2004; 24 (3): 703-710.

(2004) Pezzato, Sartor, Dell’Aica, et al. “Prostate Carcinoma and Green Tea: PSA-Triggered Basement Membrane Degradation and MMP-2 Activation are Inhibited by (-) Epigallocatechin-3-Gallate.”  Int. J. Cancer 2004; 112 (5): 787-792.

 

(2005) Shimizu, Deguchi , Joe, et al. “EGCG Inhibits Activation of HER3 and Expression of Cyclooxygenase-2 in Human Colon Cancer Cells.”  J. Exp. Ther. Oncol. 2005; 5 (1): 69-78.

(2006) Shanafelt, Lee, Call, et al. “Clinical Effects of Oral Green Tea Extracts in Four Patients with Low Grade B-Cell Malignancies.”  Leuk. Res. 2006; 30: 707-712.

(2006) Tait D. Shanafelt, Yean K. Lee, Susan M. Geyer, Deanna Grote, Mary Stenson, Steven Zincke, Stephen M. Ansell, Thomas E. Witzig, Neil E. Kay; “The Green Tea Extract Epigallocatechin Induces In Vitro Cell Death in Primary Human Lymphoma Cells through an ROS Dependent Mechanism.” Blood 2006; 108 (11): 234. doi: https://doi.org/10.1182/blood.V108.11.234.234

(2008) Ergruder, Namusui, Sozener, et al. “Effects of Aqueous Green Tea Extract on Activities of DNA Turn-over Enzymes in Cancerous and Non-Cancerous Human Gastric and Colon Tissues.”  Altern. Ther. Health Med.  2008; 14 (3): 30-33. 

(2008) Shankar, Ganapathy, Hingorani & Srivastava. “EGCG Inhibits Growth, Invasion, Angiogenesis and Metastasis of Pancreatic Cancer.”  Front. Biosci. 2008; 13: 440-452.

(2009) Angelo, Laura S, and Razelle Kurzrock. “Turmeric and green tea: a recipe for the treatment of B-chronic lymphocytic leukemia.” Clinical cancer research : an official journal of the American Association for Cancer Research vol. 15,4 (2009): 1123-5. doi:10.1158/1078-0432.CCR-08-2791.

(2009) Park, Lee, Hwang, et al. “Green Tea Catechin Controls Apoptosis in Colon Cancer Cells by Attenuation of H2O2-Stimulated COX-2 Expression via the AMPK Signaling Pathway at Low-Dose H2O2.” Ann. N.Y. Acad. Sci. 2009; 1171: 538-544.  [re: NAC blocks EGCG effects].

(2010) Shanafelt, Call, Zent, et al. “Phase II Trial of Daily, Oral Green Tea Extract in Patients with Asymptomatic, Rai Stage 0-II Chronic Lymphocytic Leukemia (CLL).”  J. Clin. Oncol. 2010; 28 (Suppl.): S7. Abstract 6522 ASCO 2010.

(2013) Satoh, Motohiko et al. “EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy.” Cancer cell international vol. 13,1 19. 23 Feb. 2013, doi:10.1186/1475-2867-13-19

(2014) Renno, Waleed M et al. “(-)-Epigallocatechin-3-gallate modulates spinal cord neuronal degeneration by enhancing growth-associated protein 43, B-cell lymphoma 2, and decreasing B-cell lymphoma 2-associated x protein expression after sciatic nerve crush injury.” Journal of neurotrauma vol. 32,3 (2015): 170-84. doi:10.1089/neu.2014.3491

(2015) Penn State University. (2015, January 28). “Green tea ingredient may target protein to kill oral cancer cells.” Retrieved from https://news.psu.edu/story/342487/2015/01/28/research/green-tea-ingredient-may-target-protein-kill-oral-cancer-cells

(2015) Jaques Raphael, et al.  “Spontaneous regression of malignant pleural mesothelioma: A case report.” Cancer Treatment Communications.  Vol3, 2015, Pages 24-27

(2015) Wang, J., Xie, Y., Feng, Y., Zhang, L., Huang, X., Shen, X., Luo, X."(-)-Epigallocatechingallate induces apoptosis in B lymphoma cells via caspase-dependent pathway and Bcl-2 family protein modulation.” International Journal of Oncology 46.4 (2015): 1507-1515.

(2017) Y. Zhang, S.-X. Wang, J.-W. Ma et al. “EGCG inhibits properties of glioma stem-like cells and synergizes with temozolomide through downregulation of P-glycoprotein inhibition.” Journal of Neuro-Oncology, vol. 121, no. 1, pp. 41–52, 2015.

(2018) Ugai T, Matsuo K, Sawada N, et al. “Coffee and green tea consumption and subsequent risk of acute myeloid leukemia and myelodysplastic syndromes in Japan.” Int J Cancer. 2018;142(6):1130-1138. doi:10.1002/ijc.31135

(2018) Borutinskaitė V, Virkšaitė A, Gudelytė G, Navakauskienė R. “Green tea polyphenol EGCG causes anti-cancerous epigenetic modulations in acute promyelocytic leukemia cells.” Leuk Lymphoma. 2018 Feb;59(2):469-478. doi: 10.1080/10428194.2017.1339881. Epub 2017 Jun 22. PMID: 28641467.

(2018) Bange, Erin et al. “Evidence for and Against Green Tea and Turmeric in the Management of Chronic Lymphocytic Leukemia.” Clinical lymphoma, myeloma & leukemia vol. 18,10 (2018): e421-e426. doi:10.1016/j.clml.2018.06.021

(2019) Roomi MW, et al. “A novel nutrient mixture induces apoptosis in human mesothelioma cells (MTSO-211H0 via activation of capsases).” Glob J Cancer Ther 5(1):007-011. DOI: 10.17352/2581-5407.000024 (Vit C, green tea, lysine, proline)

(2019) Miyata Y, Shida Y, Hakariya T, Sakai H. “Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer.” Molecules. 2019 Jan 7;24(1):193. doi: 10.3390/molecules24010193. PMID: 30621039; PMCID: PMC6337309.

(2020) Filippini T, Malavolti M, Borrelli F, Izzo AA, Fairweather-Tait SJ, Horneber M, Vinceti M. “Green tea (Camellia sinensis) for the prevention of cancer.” Cochrane Database Syst Rev. 2020 Mar 2;3(3):CD005004. doi: 10.1002/14651858.CD005004.pub3.PMID: 32118296

(2020) Almatroodi SA, Almatroudi A, Khan AA, Alhumaydhi FA, Alsahli MA, Rahmani AH. “Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer.” Molecules. 2020;25(14):3146. Published 2020 Jul 9. doi:10.3390/molecules25143146

(2020) Man, G.C.W., Wang, J., Song, Y. et al. “Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer.” BMC Cancer 20, 964 (2020). https://doi.org/10.1186/s12885-020-07455-3

(2021) Elham Sharifi-Zahabi, Fatemeh Hajizadeh-Sharafabad, Hadi Abdollahzad, Afsaneh Dehnad, Farzad Shidfar. “The effect of green tea on prostate specific antigen (PSA): A systematic review and meta-analysis of randomized controlled trials.” Complementary Therapies in Medicine, Volume 57, 2021, 102659, ISSN 0965-2299, https://doi.org/10.1016/j.ctim.2020.102659.

HERBAL TREATMENTS

(2019) Yue-qun Chen, Hua-li Fei, Hong-li Zhu. “Bu Shen Yang Xue Prescription has treating effect on Endometrial Cancer through FSH/PI3K/AKT/Gankyrin/HIF-α/cyclinD 1 pathway in Ishikawa Cells.” Evidence-Based Complimentary and Alternative Medicine, vol. 2018, Article ID 8412984, 10 pages, 2018. https://doi.org/10.1155/2018/8412984

(2020) Yoon, Sung Soo et al. “Prolonged Progression-Free Survival in a Patient With Malignant Pleural Mesothelioma Following Korean Herbal Medicine Treatment Alone: A Case Report.” Integrative cancer therapies vol. 19 (2020): 1534735420908345. doi:10.1177/1534735420908345 (Astragalus membranaceus 24g/d, Atractylodes macrocephala Koidzumi 12 g/d, Poria cocos Wolf 12 g/d, Pinellia ternata Breitenbach 12 g/d, Citrus unshiu Markovich 12 g/d, Agastache rugosa O. Kuntze 4 g/d, Alisma orientale Juzepczuk 12 g/d, Plantago asiatica Linné 8 g/d, Spatholobus suberectus Dunn 8 g/d, Zizyphus jujuba Miller var. inermis Rehder 12 g/d, Glycine max Merrill 8 g/d, Crataegus pinnatifida Bunge 6 g/d, Hordeum vulgare Linné var. hexastichon Aschers 6 g/d, Prunus mume Siebold et Zuccarini 6 g/d, and Glycyrrhiza uralensis) Fischer 6g/d.

HIPEC (Hyperthermic intraperitoneal chemotherapy)

New Enhanced Recovery Pathway After HIPEC Improves Outcomes

(2014) Glockzin, G., Gerken, M., Lang, S.A. et al. “Oxaliplatin-based versus irinotecan-based hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis from appendiceal and colorectal cancer: a retrospective analysis.” BMC Cancer 14, 807 (2014). https://doi.org/10.1186/1471-2407-14-807

(2020) Leimkühler M, Hentzen JEKR, Hemmer PHJ, Been LB, van Ginkel RJ, Kruijff S, van Leeuwen BL, de Bock GH. “Systematic Review of Factors Affecting Quality of Life After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.” Ann Surg Oncol. 2020 Oct;27(10):3973-3983. doi: 10.1245/s10434-020-08379-9. Epub 2020 Apr 26. PMID: 32335752; PMCID: PMC7471142.

(2020) Fiorentini G, Sarti D, Patriti A, Eugeni E, Guerra F, Masedu F, Mackay AR, Guadagni S. “Immune response activation following hyperthermic intraperitoneal chemotherapy for peritoneal metastases: A pilot study.” World J Clin Oncol. 2020 Jun 24;11(6):397-404. doi: 10.5306/wjco.v11.i6.397. PMID: 32874953; PMCID: PMC7450817.

(2021) Samuel Klempner and David Ryan.  “HIPEC for colorectal peritoneal metastases.”  The Lancet Oncology. January 18, 2021. DOI: https://doi.org/10.1016/S1470-2045(20)30693-8

(2021) Fan, B., Bu, Z., Zhang, J. et al. “Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery.” BMC Cancer 21, 216 (2021). https://doi.org/10.1186/s12885-021-07925-2

(2021) Simkens GA, Wintjens AGWE, Rovers KP, Nienhuijs SW, de Hingh IH. “Effective Strategies to Predict Survival of Colorectal Peritoneal Metastases Patients Eligible for Cytoreductive Surgery and HIPEC.” Cancer Manag Res. 2021;13:5239-5249. https://doi.org/10.2147/CMAR.S277912

(2022) Cashin P, Sugarbaker PH. “Hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases: lessons learned from PRODIGE 7.” J Gastrointest Oncol. 2021 Apr;12(Suppl 1):S120-S128. doi: 10.21037/jgo-2020-05. PMID: 33968432; PMCID: PMC8100699.

(2022) Wu, Y., Zheng, X., Sun, C. et al. “Hyperthermic intraperitoneal chemotherapy for patients with gastric cancer based on laboratory tests is safe: a single Chinese center analysis.” BMC Surg 22, 342 (2022). https://doi.org/10.1186/s12893-022-01795-6

(2023) Willemien van Driel, et al. “Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.” N Engl J Med 2018; 378:230-240. January 18, 2023. DOI: 10.1056/NEJMoa1708618

(2023) Ylikauma, L.A., Tuovila, M.J., Ohtonen, P.P. et al. “Reliability of bioreactance and pulse power analysis in measuring cardiac index during cytoreductive abdominal surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).” BMC Anesthesiol 23, 38 (2023). https://doi.org/10.1186/s12871-023-01988-3

(2023) Yang, R., Zhao, X., Fu, YB. et al. “Etiological analysis of infection after CRS + HIPEC in patients with PMP.” BMC Cancer 23, 903 (2023). https://doi.org/10.1186/s12885-023-11404-1

(2023) Kepenekian, V., Sgarbura, O., Marchal, F. et al. “Peritoneal Mesothelioma: Systematic Review of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Protocol Outcomes.” Indian J Surg Oncol 14 (Suppl 1), 39–59 (2023). https://doi.org/10.1007/s13193-023-01728-6

HORMONE REPLACEMENT THERAPY (HRT)

(2015) “Bio-identical hormones replacement therapy and the quality of life for breast cancer patients.” Journal of Clinical Oncology 33, no. 28_suppl (October 01, 2015) 87-87.

HYPERBARIC OXYGEN THERAPY (HBOT)

(1966) Van den Brenak, et al. “RESULTS FROM TOURNIQUET ANOXIA AND HYPERBARIC OXYGEN TECHNIQUES COMBINED WITH MEGAVOLTAGE TREATMENT OF SARCOMAS Of bone and soft tissue.” From the Radiobiological and Hyperbaric Oxygen Research Units, Cancer Institute Board, Melbourne, Australia. March 1966, Pgs 760-766.

(1972) Dische S, Senanayake F. “Radiotherapy using hyperbaric oxygen in the palliation of carcinoma of colon and rectum.” Clin Radiol. 1972;23:512–518. doi: 10.1016/S0009-9260(72)80032-1

(1998) Kalns J, Krock L, Piepmeier E., Jr. “The effect of hyperbaric oxygen on growth and chemosensitivity of metastatic prostate cancer.” Anticancer Res. 1998;18:363–367.

(2002) Harris AL. “Hypoxia—a key regulatory factor in tumor growth.” Nat Rev Cancer. 2002;2:38–47. doi: 10.1038/nrc704

(2003) Perte, et al.  “Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model.”  The Journal of Thoracic and Cardiovascular Surgery. Volume 125, Issue 1, January 2003, Pages 85-95

(2003) Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D. “Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies.” Cancer Treat Rev. 2003;29:297–307. doi: 10.1016/S0305-7372(03)00003-3

(2005) Hjelde A, Gederaas OA, Krokan HE, Brubakk AO. “Lack of effect of hyperoxia on photodynamic therapy and lipid peroxidation in three different cancer cell lines.” Med Sci Monit. 2005;11:BR351–BR356.

(2007) Raa A, Stansberg C, Steen VM, Bjerkvig R, Reed RK, Stuhr LE. “Hyperoxia retards growth and induces apoptosis and loss of glands and blood vessels in DMBA-induced rat mammary tumors.” BMC Cancer. 2007;7:23. doi: 10.1186/1471-2407-7-23.

(2007) Stuhr LE, Raa A, Oyan AM, Kalland KH, Sakariassen PO, Petersen K, Bjerkvig R, Reed RK. “Hyperoxia retards growth and induces apoptosis, changes in vascular density and gene expression in transplanted gliomas in nude rats.” J Neurooncol. 2007;85:191–202. doi: 10.1007/s11060-007-9407-2.

(2007) Tonomura N, Granowitz EV. “Hyperbaric oxygen: a potential new therapy for leukemia?” Leuk Res. 2007;31:745–746. doi: 10.1016/j.leukres.2006.11.020

(2009) Tie Fu Liu, Jiaozhong Cai, Denise M. Gibo and Waldemar Debinski.  “Reoxygenation of Hypoxic Glioblastoma Multiforme Cells Potentiates the Killing Effect of an Interleukin-13-Based Cytotoxin.” Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-08-2151 Published January 2009.

(2009) Moen I, Tronstad KJ, Kolmannskog O, Salvesen GS, Reed RK, Stuhr LE. “Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma.” BMC Cancer. 2009;9:446. doi: 10.1186/1471-2407-9-446

(2009) Kawasoe Y, Yokouchi M, Ueno Y, Iwaya H, Yoshida H, Komiya S. “Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of osteosarcoma.” Oncol Rep. 2009;22:1045–1050

(2009) Suzuki Y, Tanaka K, Negishi D, Shimizu M, Yoshida Y, Hashimoto T, Yamazaki H. “Pharmacokinetic investigation of increased efficacy against malignant gliomas of carboplatin combined with hyperbaric oxygenation.” Neurol Med Chir (Tokyo) 2009;49:193–197. doi: 10.2176/nmc.49.193.

(2009) Ohguri T, Imada H, Narisada H, Yahara K, Morioka T, Nakano K, Miyaguni Y, Korogi Y. “Systemic chemotherapy using paclitaxel and carboplatin plus regional hyperthermia and hyperbaric oxygen treatment for non-small cell lung cancer with multiple pulmonary metastases: preliminary results.” Int J Hyperthermia. 2009;25:160–167. doi: 10.1080/02656730802610357.

(2010) Selvendiran K, Kuppusamy ML, Ahmed S, Bratasz A, Meenakshisundaram G, Rivera BK, Khan M, Kuppusamy P. “Oxygenation inhibits ovarian tumor growth by downregulating STAT3 and cyclin-D1 expressions.” Cancer Biol Ther. 2010;10:386–390. doi: 10.4161/cbt.10.4.12448

(2012) Moen, Ingrid, and Linda E B Stuhr. “Hyperbaric oxygen therapy and cancer--a review.” Targeted oncology vol. 7,4 (2012): 233-42. doi:10.1007/s11523-012-0233-x

(2013) Ogawa K, et al.  “Old but new methods in radiation oncology: hyperbaric oxygen therapy.” Int J Clin Oncol. 2013 Jun;18(3):364-70. doi: 10.1007/s10147-013-0537-6. Epub 2013 Mar 5.  https://www.ncbi.nlm.nih.gov/pubmed/23463521

(2014) Peng, Hai-Shan, et al. “Synergistic inhibitory effect of hyperbaric oxygen combined with sorafenib on hepatoma cells.”  PloS one vol. 9,6 e100814. 23 Jun. 2014, doi:10.1371/journal.pone.0100814.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067386/

(2015) Bennett MH, Feldmeier J, Hampson NB, Smee R, Milross C. “Hyperbaric oxygen therapy for late radiation tissue injury.”  Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No.: CD005005. DOI: 10.1002/14651858.CD005005.pub4

(2016) Stępień, Katarzyna et al. “Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours.” Medical oncology (Northwood, London, England) vol. 33,9 (2016): 101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971045/

(2016) Yahara, Katsuya et al. “Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma.” Journal of radiation research vol. 58,3 (2016): 351-356.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440883/

(2017) Singh, et al. “Hyperbaric Oxygen Therapy for Radiation-Related CNS Necrosis in Children with Brain Tumors: A Single Institution Experience.” International Journal of Radiation Oncology  Biology  Physics, 3360.

(2018) Huang, Lei et al. “Hyperbaric oxygen therapy as adjunctive strategy in treatment of glioblastoma multiforme.” Medical gas research vol. 8,1 24-28. 18 Apr. 2018, doi:10.4103/2045-9912.229600https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937300/

(2018) “NCI Awards Omar Aljitawi, M.D., $1M to Study Hyperbaric Oxygen Therapy for Cancer.” University of Rochester. Multiple Myeloma. https://www.urmc.rochester.edu/news/story/5334/nci-awards-omar-aljitawi-m.d.-1m-to-study-hyperbaric-oxygen-therapy-for-cancer.aspx

(2018) Bennett MH, Feldmeier J, Smee R, Milross C. “Hyperbaric oxygenation for tumour sensitisation to radiotherapy.” Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No.: CD005007. DOI: 10.1002/14651858.CD005007.pub4

(2019) Lu QZ, Li X, Ouyang J, Li JQ, Chen G. “Further application of hyperbaric oxygen in prostate cancer.” Med Gas Res. 2019 Jan 9;8(4):167-171. doi: 10.4103/2045-9912.248268. PMID: 30713670; PMCID: PMC6352573.

(2021) Li YC, Chen CH, Chang CL, Chiang JY, Chu CH, Chen HH, Yip HK. “Melatonin and hyperbaric oxygen therapies suppress colorectal carcinogenesis through pleiotropic effects and multifaceted mechanisms.” Int J Biol Sci. 2021 Aug 27;17(14):3728-3744. doi: 10.7150/ijbs.62280. PMID: 34671196; PMCID: PMC8495382.

(2021) Chen, SY., Tsuneyama, K., Yen, MH. et al. “Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer.” Sci Rep 11, 12033 (2021). https://doi.org/10.1038/s41598-021-91454-2

(2021) Alpuim Costa D, Amaro CE, Nunes A, Cardoso JS, Daniel PM, Rosa I, Branco JV. “Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis: Useless or useful? - A literature review.” World J Gastroenterol. 2021 Jul 21;27(27):4413-4428. doi: 10.3748/wjg.v27.i27.4413. PMID: 34366613; PMCID: PMC8316904.

(2022) Geldof, N.I., van Hulst, R.A., Ridderikhof, M.L. et al. “Hyperbaric oxygen treatment for late radiation-induced tissue toxicity in treated gynaecological cancer patients: a systematic review.” Radiat Oncol 17, 164 (2022). https://doi.org/10.1186/s13014-022-02067-6

(2023) Baude J, Cooper JS. “Hyperbaric Contraindicated Chemotherapeutic Agents.” [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560873/

(2023) Cooper JS, Hanley ME. “Hyperbaric Treatment of Radiation Proctitis.” [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537343/

HYPERTHERMIA

Hyperthermia Cancer Institute- Santa Monica, CA.  (888)580-5900.

Texas Oncology- multiple locations.

UCSF Health- Dr. I-Chow (Joe) Hsu, Dr Sue Yom. San Francisco. (415) 353-7175.

Integrated Health Clinic- Fort Langley, British Columbia, Sarah Soles, MSc, ND. (604) 888-8325

Hufeland Klinik- Bad Mergentheim, Germany.

Medical Center Germany- Frankfurt.  Holistic Care.

Sanoviv Medical Institute- Baja California, Mexico

The Grace Gawler Institute- Australia, New Zealand

(2002) Ohno S, et al.  “Hyperthermia for rectal cancer.” Surgery. 2002 Jan;131(1 Suppl):S121-7.

(2003) P. R. Wachsberger, R. Burd, A. Bhala, S. B. Bobyock, M. L. Wahl, C. S. Owen, S. B. Rifat & D. B. Leeper.  “Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia.” International Journal of Hyperthermia, 19:5, 507-519, DOI: 10.1080/0265673031000078697

(2004) Hildebrandt B, et al. “Treatment of locally recurrent rectal cancer with special focus on regional pelvic hyperthermia.” Onkologie. 2004 Oct;27(5):506-11.

(2009) Skitzki JJ, Repasky EA, Evans SS. “Hyperthermia as an immunotherapy strategy for cancer.” Curr Opin Investig Drugs. 2009 Jun;10(6):550-8. PMID: 19513944; PMCID: PMC2828267.

(2012) Lin CY, et al. “Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug.” Int J Nanomedicine. 2012;7:2143-52. doi: 10.2147/IJN.S29514. Epub 2012 Apr 24.

(2012) Lee, Doo Yun, et al.  “Complete Remission of SCLC with Chemotherapy and Oncothermia (Case Report)”. Oncothermia Journal 5:43-51 (2012)

(2013) Gao, et al.  “Water bath hyperthermia reduces stemness of colon cancer cells.” Clinical Biochemistry. Volume 46, Issues 16–17, November 2013, Pages 1747-1750

(2014) Gianfranco Baronzio, et al. “A brief overview of hyperthermia in cancer treatment.” J Integr Oncol 2014, 3:1.

(2014) Wu, Sheng-Kai et al. “Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.” International journal of nanomedicine vol. 9 4485-94. 19 Sep. 2014, doi:10.2147/IJN.S68347

(2014) Lee H, Park HJ, Park CS, Oh ET, Choi BH, Williams B, Lee CK, Song CW. “Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.” PLoS One. 2014 Feb 5;9(2):e87979. doi: 10.1371/journal.pone.0087979. PMID: 24505341; PMCID: PMC3914884.

(2015) Aryal M, et al. “Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model.” Phys Med Biol. 2015 Mar 21;60(6):2511-27. doi: 10.1088/0031-9155/60/6/2511. Epub 2015 Mar 6.

(2015) PLOS ONE Staff. “Correction: First clinical experience of intra-operative high intensity focused ultrasound in patients with colorectal liver metastases: a phase I-IIa study.” PLoS One. 2015 Mar 30;10(3):e0123751. doi: 10.1371/journal.pone.0123751. eCollection 2015.

(2015)Takayuki Ohguri, Naoki Kunugita, Katsuya Yahara, Hajime Imada, Hidehiko Uemura, Nadayoshi Shinya, Gotou Youjirou, Chijiwa Takashi, Ryuji Okazaki, Akira Ootsuyama & Yukunori Korogi. “Efficacy of hyperbaric oxygen therapy combined with mild hyperthermia for improving the anti-tumour effects of carboplatin.” International Journal of Hyperthermia, 31:6, 643-648, DOI: 10.3109/02656736.2015.1055832

(2015) Oei AL, Vriend LE, Crezee J, Franken NA, Krawczyk PM. ”Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all.” Radiat Oncol. 2015 Aug 7;10:165. doi: 10.1186/s13014-015-0462-0. PMID: 26245485; PMCID: PMC4554295.

(2016) Chu W, Staruch RM, Pichardo S, Tillander M, Köhler MO, Huang Y, Ylihautala M, McGuffin M, Czarnota G, Hynynen K. “Magnetic Resonance-Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation.” Int J Radiat Oncol Biol Phys. 2016 Jul 15;95(4):1259-67. doi: 10.1016/j.ijrobp.2016.03.019. Epub 2016 Mar 24.

(2016) VanOsdol J, Ektate K, Ramasamy S, Maple D, Collins W, Malayer J, Ranjan A. “Sequential HIFU heating and nanobubble encapsulation provide efficient drug penetration from stealth and temperature sensitive liposomes in colon cancer.” J Control Release. 2017 Feb 10;247:55-63. doi: 10.1016/j.jconrel.2016.12.033. Epub 2016 Dec 30.

(2017) Wu sk, et al. “Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer.” Ultrason Sonochem. 2017 May;36:198-205. doi: 10.1016/j.ultsonch.2016.11.033. Epub 2016 Nov 28.

(2017) Fahimeh Faghihi Moghadam, et al. “A BRIEF REVIEW OF HYPERTHERMIA AS A NEOADJUVANT THERAPY METHOD RELATED TO CANCER TREATMENT”.  Journal of Cellular Immunotherapy 3 (2017) 2-30. Department of Medical Physics, Faculty of Medical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran; Department of Radiology, Faculty of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;  Institute for Hyperthermia Research, Partner of the Marien Hospital Herne, Hospital of the Ruhr-University, Bochum, Germany

(2017) VanOsdol J, Ektate K, Ramasamy S, Maples D, Collins W, Malayer J, Ranjan A. “Sequential HIFU heating and nanobubble encapsulation provide efficient drug penetration from stealth and temperature sensitive liposomes in colon cancer.” J Control Release. 2017 Feb 10;247:55-63. doi: 10.1016/j.jconrel.2016.12.033. Epub 2016 Dec 30.

(2017) Boissenot T, Bordat A, Larrat B, Varna M, Chacun H, Paci A, Poinsignon V, Fattal E, Tsapis N. “Ultrasound-induced mild hyperthermia improves the anticancer efficacy of both Taxol® and paclitaxel-loaded nanocapsules.” J Control Release. 2017 Oct 28;264:219-227. doi: 10.1016/j.jconrel.2017.08.041. Epub 2017 Sep 1.

(2017) Yagawa Y, et al. “Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery.” J Cancer Metastasis Treat 2017;3:218-230

(2017) Maeda M, Muragaki Y, Okamoto J, Yoshizawa S, Abe N, Nakamoto H, Ishii H, Kawabata K, Umemura S, Nishiyama N, Kataoka K, Iseki H. “Sonodynamic Therapy Based on Combined Use of Low Dose Administration of Epirubicin-Incorporating Drug Delivery System and Focused Ultrasound.” Ultrasound Med Biol. 2017 Oct;43(10):2295-2301. doi: 10.1016/j.ultrasmedbio.2017.06.003. Epub 2017 Jul 10.

(2017) A. L. Oei, L. E. M. Vriend, P. M. Krawczyk, M. R. Horsman, N. A. P. Franken & J. Crezee. “Targeting therapy-resistant cancer stem cells by hyperthermia.”  International Journal of Hyperthermia, 33:4, 419-427, DOI: 10.1080/02656736.2017.1279757

(2017) Huang H, Yu K, Mohammadi A, Karanthanasis E, Godley A, Yu JS. “It's Getting Hot in Here: Targeting Cancer Stem-like Cells with Hyperthermia.” J Stem Cell Transplant Biol. 2017;2(2):113. Epub 2017 Dec 29. PMID: 30542674; PMCID: PMC6287629.

(2018) Ektate K, Munteanu MC, Ashar H, Malayer J, Ranjan A. “Chemo-immunotherapy of colon cancer with focused ultrasound and Salmonella-laden temperature sensitive liposomes (thermobots).” Sci Rep. 2018 Aug 30;8(1):13062. doi: 10.1038/s41598-018-30106-4.

(2018) Byun YH, et al. “Local recurrence of brain metastasis reduced by intra-operative hyperthermia treatment.” Int J Hyperthermia. 2019 Jan 1;35(1):168-175. doi: 10.1080/02656736.2018.1488004. Epub 2018 Oct 8.

(2018) Vancsik T, et a;. “Modulated electro-hyperthermia induced loco-regional and systemic tumor destruction in colorectal cancer allografts.”  J Cancer 2018; 9(1):41-53. Doi:10.7150/jca.21520

(2019) Chiang CF, et al. “Pulsed-wave Ultrasound Hyperthermia Enhanced Nanodrug Delivery Combined with Chloroquine Exerts Effective Antitumor Response and Postpones Recurrence.” Sci Rep. 2019 Aug 28;9(1):12448. doi: 10.1038/s41598-019-47345-8.

(2019) Liu, Zichuan. “Clinical effects of high frequency hyperthermia-assisted irinotecan chemotherapy on patients with middle and advanced colorectal cancer and its safety assessment.” Oncology letters vol. 17,1 (2019): 215-220. doi:10.3892/ol.2018.9574.

(2019) Mantso T, et al. “Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma.” ANTICANCER RESEARCH 39: 2307-2315 (2019) doi:10.21873/anticanres.13347

(2019) Li M, Wan G, Yu H, Xiong W. “High-intensity focused ultrasound inhibits invasion and metastasis of colon cancer cells by enhancing microRNA-124-mediated suppression of STAT3.” FEBS Open Bio. 2019 Jun;9(6):1128-1136. doi: 10.1002/2211-5463.12642. Epub 2019 May 4.

(2019) Ma B, Liu X, Yu Z. “The effect of high intensity focused ultrasound on the treatment of liver cancer and patients' immunity.” Cancer Biomark. 2019;24(1):85-90. doi: 10.3233/CBM-181822.

(2020) Ou J, Zhu X, Chen P, Du Y, Lu Y, Peng X, Bao S, Wang J, Zhang X, Zhang T, Pang CLK. “A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer.”  J Adv Res. 2020 Mar 17;24:175-182. doi: 10.1016/j.jare.2020.03.004. PMID: 32368355; PMCID: PMC7190757.

(2020) Kuo IM, Lee JJ, Wang YS, Chiang HC, Huang CC, Hsieh PJ, Han W, Ke CH, Liao ATC, Lin CS. “Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia.” BMC Cancer. 2020 Jun 29;20(1):603. doi: 10.1186/s12885-020-07072-0. PMID: 32600429; PMCID: PMC7324975.

(2021) Kozłowski HM, Pawlikowska M, Sobocińska J, Jędrzejewski T, Dzialuk A, Wrotek S. “Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (Viscum album L.) Extract.” Pharmaceuticals (Basel). 2021 Jun 8;14(6):551. doi: 10.3390/ph14060551. PMID: 34201348; PMCID: PMC8229697.

(2021) Quintana M, Saavedra E, Del Rosario H, González I, Hernández I, Estévez F, Quintana J. “Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells.” Int J Mol Sci. 2021 May 6;22(9):4948. doi: 10.3390/ijms22094948. PMID: 34066632; PMCID: PMC8125413.

(2022) Yi GY, Kim MJ, Kim HI, Park J, Baek SH. “Hyperthermia Treatment as a Promising Anti-Cancer Strategy: Therapeutic Targets, Perspective Mechanisms and Synergistic Combinations in Experimental Approaches.” Antioxidants (Basel). 2022 Mar 24;11(4):625. doi: 10.3390/antiox11040625. PMID: 35453310; PMCID: PMC9030926.

ICD- 10 codes: DDY58ZZ Hyperthermia of colon, DDY78ZZ Hyperthermia of rectum

INDOLE-3-CARBINOL

(1999) Cover, Hsieh, Cram, et al. “Indole-3-Carbinol and Tamoxifen Cooperate to Arrest the Cell Cycle of MCF-7 Human Breast Cancer Cells.”  Cancer Res. 1999; 59 (6):1244-1251.

(2001) Chinni, Li, Upadhyay, et al.  “Indole-3-Carbinol (I3C) Induced Cell Growth Inhibition, G1 Cell Cycle Arrest and Apoptosis in Prostate Cancer Cells.”  Oncogene 2001.

(2003) Zhang, Hsu, Kinseth, et al.  “Indole-3-Carbinol Induces a G1 Cell Cycle Arrest and Inhibits Prostate-Specific Antigen Production in Human LNCaP Prostate Carcinoma Cells.” Cancer 2003; 98 (11): 2511-2520.

 

(2004) Sarkar. “Indole-3-Carbinol and Prostate Cancer.”  J. Nutr. 2004; 134 (12 Suppl): 3493S-3498S.

(2005) Takada, Yasunari et al. “Indole-3-carbinol suppresses NF-kappaB and IkappaBalpha kinase activation, causing inhibition of expression of NF-kappaB-regulated antiapoptotic and metastatic gene products and enhancement of apoptosis in myeloid and leukemia cells.” Blood vol. 106,2 (2005): 641-9. doi:10.1182/blood-2004-12-4589

(2005) Hsu, Zhang, Dev, et al. “Indole-3-Carbinol Inhibition of Androgen Receptor Expression and Down-regulation of Androgen Responsiveness in Human Prostate Cancer Cells.”  Carcinogenesis 2005.

(2005) Garikpaty, et al.  “Anti-Carcinogenic and Anti-Metastatic Properties of Indole-3-Carbinol in Prostate Cancer.”  Oncol. Rep.  2005; 13 (1): 89-93.

(2005) Li, Chinni & Sarkhar. “ Selective Growth Regulatory and Pro-apoptotic Effects of DIM is Mediated by AKT and NF-kappaB Pathways in Prostate Cancer Cells.”  Front. Biosci. 2005; 10: 236-243.

(2006) Kim, Jeong, Moon, et al.  “Indole-3-Carbinol Enhances Ultraviolet-B-induced Apoptosis by Sensitizing Human Melanoma Cells.” Cell. Mol. Life Sci. 2006; 63 (22): 2661-2668.

(2010) Nguyen, et al. “1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol derivative with significantly enhanced potency of anti-proliferative and anti-estrogenic properties in human breast cancer cells.” Chemico-biological interactions 186(3):255-66 · August 2010.

(2013) Bai LY, Weng JR, Chiu CF, et al. “OSU-A9, an indole-3-carbinol derivative, induces cytotoxicity in acute myeloid leukemia through reactive oxygen species-mediated apoptosis.” Biochem Pharmacol. 2013;86:1430–1440.

(2014), Tin, et al.  “Essential role of the cancer stem/progenitor cell marker nucleostemin for indole-3-carbinol anti-proliferative responsiveness in human breast cancer cells.” BMC Biology volume 12, Article number: 72 (2014).

(2014) Tavasoli B, Ebrahimi S, Manafi R, et al.  “Indole-3-carbinol induces G1 cell cycle arrest in pre-B acute lymphoblastic leukemia cell line.”  J Arak Univ Med Sci. 2014;17:30–40.

(2016) Perez-Chacon G, Martinez-Laperche C, Rebolleda N, et al. “Indole-3-carbinol synergizes with and restores fludarabine sensitivity in chronic lymphocytic leukemia cells irrespective of p53 activity and treatment resistances.” Clin Cancer Res. 2016;22:134–145.

(2017) Mohammadi, et al. “Indole-3-carbinol induces G1 cell cycle arrest and apoptosis through aryl hydrocarbon receptor in THP-1 monocytic cell line.” (AML) Journal of Receptors and Signal Transduction.  Volume 37, 2017 - Issue 5.

(2017) Safa M, et al. “Indole-3-carbinol induces apoptosis of chronic myelogenous leukemia cells through suppression of STAT5 and Akt signaling pathways.” Tumor Biology 39(6):101042831770576. June 2017.

(2019) Wu Y, Li RW, Huang H, Fletcher A, Yu L, Pham Q, Yu L, He Q, Wang TTY. “Inhibition of Tumor Growth by Dietary Indole-3-Carbinol in a Prostate Cancer Xenograft Model May Be Associated with Disrupted Gut Microbial Interactions.” Nutrients. 2019 Feb 22;11(2):467. doi: 10.3390/nu11020467. PMID: 30813350; PMCID: PMC6413210.

IRON

(2015) Heinz Ludwig H, Evstatiev R, Kornek G, Aapro M, Bauernhofer T, Buxhofer-Ausch V, Fridrik M, Geissler D, Geissler K, Gisslinger H, Koller E, Kopetzky G, Lang A, Rumpold H, Steurer M, Kamali H, Link H. “Iron metabolism and iron supplementation in cancer patients.” Wien Klin Wochenschr. 2015 Dec;127(23-24):907-19. doi: 10.1007/s00508-015-0842-3. Epub 2015 Sep 15. Erratum in: Wien Klin Wochenschr. 2015 Dec;127(23-24):920-1. PMID: 26373748; PMCID: PMC4679104.

(2017) Wilson, M J et al. “The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment.” International journal of colorectal disease vol. 32,11 (2017): 1617-1624. doi:10.1007/s00384-017-2898-1.

IVERMECTIN- take at least 5 hours away from quercetin

(2022 last update) The Magic of Ivermectin in Oncology. https://www.cancertreatmentsresearch.com/ivermectin-in-oncology/

(2021) Zhou, Shican et al. “Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth.” Frontiers in pharmacology vol. 12 717529. 13 Aug. 2021, doi:10.3389/fphar.2021.717529

(2021) Tang M, Hu X, Wang Y, Yao X, Zhang W, Yu C, Cheng F, Li J, Fang Q. “Ivermectin, a potential anticancer drug derived from an antiparasitic drug.”  Pharmacol Res. 2021 Jan;163:105207. doi: 10.1016/j.phrs.2020.105207. Epub 2020 Sep 21. PMID: 32971268; PMCID: PMC7505114.

(2021) Dobrin Draganov, et al. “Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer.” Npj Breast Cancer. 7, Article number: 22 (2021). Nature.

(2020) Li N, Zhan X. “Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes.” EPMA J. 2020 May 28;11(2):289-309. doi: 10.1007/s13167-020-00209-y. PMID: 32549918; PMCID: PMC7272521.

(2023) Jawad MJ, Richardson A. “Ivermectin Augments the Anti-Cancer Activity of Pitavastatin in Ovarian Cancer Cells.” Diseases. 2023 Mar 14;11(1):49. doi: 10.3390/diseases11010049. PMID: 36975598; PMCID: PMC10047003.

LIGHT THERAPY

(2008) Ishibashi J, Yamashita K, Ishikawa T, Hosokawa H, Sumida K, Nagayama M, Kitamura S. “The effects inhibiting the proliferation of cancer cells by far-infrared radiation (FIR) are controlled by the basal expression level of heat shock protein (HSP) 70A.” Med Oncol. 2008;25(2):229-37. doi: 10.1007/s12032-007-9020-4. Epub 2007 Oct 30. PMID: 17968683; PMCID: PMC2386844.

(2011) NIH Research Matters “Targeted Light Therapy Destroys Cancer Cells.” Dec 5, 2011.

https://www.nih.gov/news-events/nih-research-matters/targeted-light-therapy-destroys-cancer-cells

(2013) Jane Feinmann. “A revolutionary laser treatment could kill off breast cancer in 15 minutes - and with no need for a mastectomy. No wonder doctors are excited.” Daily Mail. https://www.dailymail.co.uk/health/article-2439464/Photodynamic-laser-treatment-kill-breast-cancer-15-minutes.html

(2014) Jim Fessenden. “Tuning light to kill deep cancer tumors.”  UMass Chan Medical School. October 15, 2014. https://www.umassmed.edu/news/news-archives/2014/10/tuning-light-to-kill-deep-cancer-tumors/

(2014) Photoimmune Discoveries. “Light-based therapy for pancreatic cancer.” Science Daily. March 31, 2014. http://photoimmune.org/light-based-therapy-pancreatic-cancer/

(2015) Evans SS, Repasky EA, Fisher DT. “Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol.” 2015 Jun;15(6):335-49. doi: 10.1038/nri3843. Epub 2015 May 15. PMID: 25976513; PMCID: PMC4786079.

(2016) Zecha JA, Raber-Durlacher JE, Nair RG, Epstein JB, Elad S, Hamblin MR, Barasch A, Migliorati CA, Milstein DM, Genot MT, Lansaat L, van der Brink R, Arnabat-Dominguez J, van der Molen L, Jacobi I, van Diessen J, de Lange J, Smeele LE, Schubert MM, Bensadoun RJ. “Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols.” Support Care Cancer. 2016 Jun;24(6):2793-805. doi: 10.1007/s00520-016-3153-y. Epub 2016 Mar 17. PMID: 26984249; PMCID: PMC4846551.

(2016) University College London. “Light therapy effectively treats early prostate cancer.” Dec 19, 2016. https://www.sciencedaily.com/releases/2016/12/161219202008.htm

(2016) Abdel-Rahmène Azzouzi, Sébastien Vincendeau, Eric Barret, Antony Cicco, François Kleinclauss, Henk G van der Poel, Christian G Stief, Jens Rassweiler, Georg Salomon, Eduardo Solsona, Antonio Alcaraz, Teuvo T Tammela, Derek J Rosario, Francisco Gomez-Veiga, Göran Ahlgren, Fawzi Benzaghou, Bertrand Gaillac, Billy Amzal, Frans M J Debruyne, Gaëlle Fromont, Christian Gratzke, Mark Emberton. “Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.” The Lancet Oncology, 2016; DOI: 10.1016/S1470-2045(16)30661-1

(2017) Tibi Puiu. “New treatment kills cancer cells with near infrared light.” ZME Science pulled from Alternative Medicine, Health & Medicine, Research. https://www.zmescience.com/research/new-treatment-kills-cancer-cells-with-near-infrared-light/

(2017) Djavid GE, Bigdeli B, Goliaei B, Nikoofar A, Hamblin MR. “Photobiomodulation leads to enhanced radiosensitivity through induction of apoptosis and autophagy in human cervical cancer cells.” J Biophotonics. 2017 Dec;10(12):1732-1742. doi: 10.1002/jbio.201700004. Epub 2017 May 2. PMID: 28464474; PMCID: PMC5668202. (685 nm).

(2017) Baxter GD, Liu L, Petrich S, Gisselman AS, Chapple C, Anders JJ, Tumilty S. “Low level laser therapy (Photobiomodulation therapy) for breast cancer-related lymphedema: a systematic review.” BMC Cancer. 2017 Dec 7;17(1):833. doi: 10.1186/s12885-017-3852-x. PMID: 29216916; PMCID: PMC5719569.

(2017) Tsai SR, Hamblin MR. “Biological effects and medical applications of infrared radiation.” J Photochem Photobiol B. 2017 May;170:197-207. doi: 10.1016/j.jphotobiol.2017.04.014. Epub 2017 Apr 13. PMID: 28441605; PMCID: PMC5505738.

(2018) University of Cincinnati  Academic Health Center. “Researcher fighting breast cancer with light therapy.” October 17, 2018. https://medicalxpress.com/news/2018-10-breast-cancer-therapy.html

(2018) Bensadoun RJ. “Photobiomodulation or low-level laser therapy in the management of cancer therapy-induced mucositis, dermatitis and lymphedema.” Curr Opin Oncol. 2018 Jul;30(4):226-232. doi: 10.1097/CCO.0000000000000452. PMID: 29794809.

(2019) Yehuda Zadik, Praveen R. Arany, Eduardo Rodrigues Fregnani, Paolo Bossi, Héliton Spindola Antunes, René-Jean Bensadoun, Luiz Alcino Gueiros, Alessandra Majorana, Raj G. Nair, Vinisha Ranna, Wim J. E. Tissing, Anusha Vaddi, Rachel Lubart, Cesar Augusto Migliorati, Rajesh V. Lalla, Karis Kin Fong Cheng, Sharon Elad. “Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines.” Supportive Care in Cancer, 2019; DOI: 10.1007/s00520-019-04890-2

(2020) Yang KL, Khoo BY, Ong MT, Yoong ICK, Sreeramanan S. “In vitro anti-breast cancer studies of LED red light therapy through autophagy.” Breast Cancer. 2021 Jan;28(1):60-66. doi: 10.1007/s12282-020-01128-6. Epub 2020 Jul 11. PMID: 32654094. (LED 660 nm)

(2021) NIH. “Photodynamic Therapy to Treat Cancer.” June 21, 2021.  https://www.cancer.gov/about-cancer/treatment/types/photodynamic-therapy

(2021) American Cancer Society. “Getting photodynamic Therapy.” November 19,2021. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation/photodynamic-therapy.html

(2021) Cory Tays. “UI researchers examine potential for light, photosensitizing agents to treat soft tissue sarcoma.” University of Iowa Technology Institute. March 23, 2021. https://iti.uiowa.edu/articles/2021/03/ui-researchers-examine-potential-light-photosensitizing-agents-treat-soft-tissue

(2022) Mayo Clinic. “Photodynamic Therapy.” March 5, 2022. https://www.mayoclinic.org/tests-procedures/photodynamic-therapy/about/pac-20385027

(2022) Martella E, Dozza B, Ferroni C, Obeyok CO, Guerrini A, Tedesco D, Manet I, Sotgiu G, Columbaro M, Ballestri M, Martini L, Fini M, Lucarelli E, Varchi G, Duchi S. “Two Beats One: Osteosarcoma Therapy with Light-Activated and Chemo-Releasing Keratin Nanoformulation in a Preclinical Mouse Model.” Pharmaceutics. 2022 Mar 19;14(3):677. doi: 10.3390/pharmaceutics14030677. PMID: 35336051; PMCID: PMC8950553.

(2022) Tabosa ATL, Souza MG, de Jesus SF, Rocha DF, Queiroz LDRP, Santos EM, Guimarães VHD, Andrade LAA, Santos SH, de Paula AMB, de Souza PEN, Farias LC, Guimarães ALS. “Effect of low-level light therapy before radiotherapy in oral squamous cell carcinoma: An in vitro study.” Lasers Med Sci. 2022 Aug 24. doi: 10.1007/s10103-022-03632-x. Epub ahead of print. PMID: 36001245.

LOW DOSE NALTREXONE

See Alpha-lipoic section for further combination treatment.

(2007) Berkson, B, et al.  “Reversal of Signs and Symptoms of a B-Cell Lymphoma in a Patient Using Only Low-Dose Naltrexone.” INTEGRATIVE CANCER THERAPIES 6(3); 2007 pp. 293-296

(2011) “Low-dose naltrexone (LDN): Tricking the body to heal itself.” Science Daily. September 2, 2011. https://www.sciencedaily.com/releases/2011/09/110902133047.htm

(2018) Miskoff, Jeffrey A, and Moiuz Chaudhri. “Low Dose Naltrexone and Lung Cancer: A Case Report and Discussion.” Cureus vol. 10,7 e2924. 5 Jul. 2018, doi:10.7759/cureus.2924

(2018) Li Z, You Y, Griffin N, Feng J, Shan F. “Low-dose naltrexone (LDN): a promising treatment in immune-related diseases and cancer therapy.” Int Immunopharmacol. 2018 Aug;61:178-184.

LYCOPENE

(2001) Nahum, A., Hirsch, K., Danilenko, M. et al. “Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27^Kip1 in the cyclin E–cdk2 complexes.” Oncogene 20, 3428–3436 (2001). https://doi.org/10.1038/sj.onc.1204452

(2007) Keren Hirsch, et al.” Lycopene and other carotenoids inhibit estrogenic activity of 17-estradiol and genistein in cancer cells.” Breast Cancer Research and Treatment. September 2007: 104(2):221-30.

(2008) van Breemen, Richard B, and Natasa Pajkovic. “Multitargeted therapy of cancer by lycopene.” Cancer letters vol. 269,2 (2008): 339-51. doi:10.1016/j.canlet.2008.05.016

(2011) Chih-Min Yang. “Lycopene inhibits the proliferation of androgen-dependent human prostate tumor cells through activation of PPARγ-LXRα-ABCA1 pathway.” The Journal of Nutritional Biochemistry. February 2011: 23(1):8-17.

(2017) Nina Pauline Holzapfel. “Investigation of the Potential Anticancer Effects of Lycopene in Tissue Engineered in Vitro and in Vivo Models.” Doctoral research project. Queensland University of Technology, School of Biomedical Sciences, Faculty of Health. 2016/2017. https://eprints.qut.edu.au/107571/1/Nina%20Pauline_Holzapfel_Thesis.pdf

(2019) Jiang LN, et al. “Lycopene exerts anti-inflammatory effect to inhibit prostate cancer progression.” Asian J Androl 2019;21: 80-5

MANUKA HONEY

(2020) Simona Martinotti, et al. “Manuka Honey Induces Apoptosis of Epithelial Cancer Cells through Aquaporin-3 and Calcium Signaling.” Life 2020, 10(11), 256; https://doi.org/10.3390/life10110256

MELATONIN

(2006) Büyükavci M, et al. “Melatonin cytotoxicity in human leukemia cells: relation with its pro-oxidant effect.” Fundam Clin Pharmacol. 2006 Feb;20(1):73-9.

(2008) Viswanathan, Akila N, and Eva S Schernhammer. “Circulating melatonin and the risk of breast and endometrial cancer in women.” Cancer letters vol. 281,1 (2009): 1-7. doi:10.1016/j.canlet.2008.11.002

(2011) Büyükavci M, et al.  “Effect of melatonin on the cytotoxicity of chemotherapeutic drugs in human leukemia cells.” In Vivo. 2011 May-Jun;25(3):405-9.

(2013) Martin V, et al. “Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells.” Br J Cancer 2013;108:2005-12

(2014) Mihandoost E, Shirazi A, Mahdavi SR, Aliasgharzadeh A. “Can melatonin help us in radiation oncology treatments?” Biomed Res Int. 2014;2014:578137. doi:10.1155/2014/578137.

(2017) Najafi, M et al. “The melatonin immunomodulatory actions in radiotherapy.”  Biophysical reviews vol. 9,2 (2017): 139-148. doi:10.1007/s12551-017-0256-8.

(2017) Li, Ya et al. “Melatonin for the prevention and treatment of cancer.” Oncotarget vol. 8,24 (2017): 39896-39921. doi:10.18632/oncotarget.16379.

(2018) Favero, et al.  “Promising Antineoplastic Actions of Melatonin.” Front. Pharmacol., 16 October 2018.

(2018) Farhood, et al. “Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization.”  Clin Transl Oncol. 2019 Mar;21(3):268-279. doi: 10.1007/s12094-018-1934-0.

(2019) y. Wang, Y. Wo, T. Lu, W. Jiao.  “P2.14-31 Melatonin inhibits proliferation and invasion through downregulation CircRNA NID1 in non-small cell lung cancer cells.” Journal of Thoracic Oncology.  Vol 14, Issue 10, Supplement, S841, October 1, 2019.

(2020) Chunjie Gu, et al. “Melatonin alleviates progression of uterine endometrial cancer by suppressing estrogen/ubiquitin C/SDHB-mediated succinate accumulation.” Cancer Letters.  Vol 476, 28 April 2020, Pages 34-47.

(2021) Gurunathan S, Qasim M, Kang MH, Kim JH. “Role and Therapeutic Potential of Melatonin in Various Type of Cancers.” Onco Targets Ther. 2021;14:2019-2052
https://doi.org/10.2147/OTT.S298512 (lung, breast, prostate, colorectal, skin, liver, cervical, and ovarian cancers)

(2021) Saeed Mehrzadi, et al. “An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress.”  Cancer Cell International.  21, Article number: 188 (2021)

(2021) Shen, D., Ju, L., Zhou, F. et al. “The inhibitory effect of melatonin on human prostate cancer.” Cell Commun Signal 19, 34 (2021). https://doi.org/10.1186/s12964-021-00723-0

(2021) Wang SW, Tai HC, Tang CH, Lin LW, Lin TH, Chang AC, Chen PC, Chen YH, Wang PC, Lai YW, Chen SS. “Melatonin impedes prostate cancer metastasis by suppressing MMP-13 expression.” J Cell Physiol. 2021 May;236(5):3979-3990. doi: 10.1002/jcp.30150. Epub 2020 Nov 29. PMID: 33251599.

METHYLSULFONYLMETHANE (MSM)

(2010) Caron, Joan McIntyre et al. “Methyl sulfone induces loss of metastatic properties and reemergence of normal phenotypes in a metastatic cloudman S-91 (M3) murine melanoma cell line.” PloS one vol. 5,8 e11788. 4 Aug. 2010, doi:10.1371/journal.pone.0011788

(2012) Jafari N, et al.  “Cytotoxicity of methylsulfonylmethane on gastrointestinal (AGS, HepG2, and KEYSE-30) cancer cell lines.”  J Gastrointestinal Cancer. 2012 Sep;43(3):420-5. doi: 10.1007/s12029-011-9291-z.

(2012) Lim, Eun Joung et al. “Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.” PloS one vol. 7,4 (2012): e33361.

(2014) Joung YH, et al.  “Combination of AG490, a Jak2 inhibitor, and methylsulfonylmethane synergistically suppresses bladder tumor growth via the Jak2/STAT3 pathway.”   Int J Oncol. 2014 Mar;44(3):883-95. doi: 10.3892/ijo.2014.2250. Epub 2014 Jan 8.

(2014) Kim JH, et al.  “Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis.”  World J Hepatol. 2014 Feb 27;6(2):98-106. doi: 10.4254/wjh.v6.i2.98.

(2015) SPN, et al. “The combination of methylsulfonylmethane and tamoxifen inhibits the Jak2/STAT5b pathway and synergistically inhibits tumor growth and metastasis in ER-positive breast cancer xenografts.”  BMC Cancer. 2015 Jun 19;15:474. doi: 10.1186/s12885-015-1445-0.

(2016) Kang DY, etal.  “Methylsulfonylmethane inhibits HER2 expression through STAT5b in breast cancer cells.”  Int J Oncol. 2016 Feb;48(2):836-42. doi: 10.3892/ijo.2015.3277. Epub 2015 Dec 7.

(2016) Karahay AZ, et al.  “Methylsulfonylmethane Induces p53 Independent Apoptosis in HCT-116 Colon Cancer Cells.”  Int J Mol Sci. 2016 Jul 15;17(7). pii: E1123. doi: 10.3390/ijms17071123.

(2021) Kowalska, K., Habrowska-Górczyńska, D.E., Kurczewska, D. et al. “Methylsulfonylmethane sensitizes endometrial cancer cells to doxorubicin.” Cell Biol Toxicol 37, 261–275 (2021). https://doi.org/10.1007/s10565-020-09542-4

MISTLETOE (Helixor, Iscador)

May interact with warfarin in combination with pancreatic cancer and chemotherapy leading to anemic syndrome.

Side effects: injection site fever, fatigue, chills, nausea, flu-like sx, leukocytosis. Other less common such as diarrhea, n/v, pruritus, etc. Monitor ALT/AST.

Contraindications: avoid with pregnancy

(2009) Ostermann, Thomas et al. “Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review.” BMC cancer vol. 9 451. 18 Dec. 2009, doi:10.1186/1471-2407-9-451

(2014) Marvibaigi, M., Supriyanto, E., Amini, N., Abdul Majid, F. A., & Jaganathan, S. K. (2014). Preclinical and Clinical Effects of Mistletoe against Breast Cancer. BioMed Research International, 2014, 1–15. https://doi.org/10.1155/2014/785479

(2018) Pelzer F, Troger W.  “Complementary Treatment with Mistletoe Extracts During Chemotherapy: Safety, Neutropenia, Fever, and Quality of Life Assessed in a Randomized Study.” J Altern Complement Med. 2018 Sep 1; 24(9-10): 954–961.

(2019) Oei, S. L., Thronicke, A., & Schad, F. “Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies.” Evidence-Based Complementary and Alternative Medicine, 2019, 1–6. https://doi.org/10.1155/2019/5893017

(2020) Loef M, Walach H. “Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis.” BMC Complement Med Ther. 2020 Jul 20;20(1):227. doi: 10.1186/s12906-020-03013-3. PMID: 32690087; PMCID: PMC7370416.

(2020) Ostermann, T., Appelbaum, S., Poier, D., Boehm, K., Raak, C., & Büssing, A. “A Systematic Review and Meta-Analysis on the Survival of Cancer Patients Treated with a Fermented Viscum album L. Extract (Iscador): An Update of Findings.” Complementary Medicine Research, 27(4), 260–271. https://doi.org/10.1159/000505202

(2021) Baek JH, Jeon Y, Han KW, Jung DH, Kim KO. “Effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer: a cohort study.” World J Surg Oncol. 2021 Jun 15;19(1):178. doi: 10.1186/s12957-021-02293-4. PMID: 34130688; PMCID: PMC8207698.

(2022) Shatat, M. A., Gauthier, B., Yoon, S., Yuan, E., Yang, P., Goutham Narla, Afshin Dowlati, & Lee, R. T. “Mistletoe lectin inhibits growth of Myc‐amplified small‐cell lung cancer.” 12(7), 8378–8387. https://doi.org/10.1002/cam4.5558

(2023) Paller, Channing, et al.  “Phase I Trial of Intravenous Mistletoe Extract in Advanced Cancer.” Cancer Research Communications (2023) 3 (2): 338–346. Viscum album, Helixor M, IV mistletoe 600mg 3x week. Four dose levels of mistletoe were evaluated: 150, 300, 600, and 900 mg. At each dose level, patients received a lead dose of 50 mg on week 1 day 1 and the assigned dose level thereafter. Patients were observed for dose-limiting toxicities (DLT) for 28 days after the first dose.

(2023) Juengel, E., Rutz, J., Meiborg, M., Markowitsch, S. D., Maxeiner, S., Grein, T., Thomas, A., Chun, F. K.-H. ., Haferkamp, A., Tsaur, I., Vakhrusheva, O., & Blaheta, R. A. “Mistletoe Extracts from Different Host Trees Disparately Inhibit Bladder Cancer Cell Growth and Proliferation.” Cancers, 15(19), 4849. https://doi.org/10.3390/cancers15194849

(2023) Davis, D., Seely, D., Morash, C., Armstrong, J., Meng, M., Lowe, P., Kogan, M., Morash, C., Armstrong, C., John's Health, S., Jackson, Wyoming, U., & Kogan. (n.d.). “Complete Remission of BCG-Refractory High-grade Bladder CIS with Pharmacologic Ascorbate and Mistletoe.” http://www.alternative-therapies.com/oa/pdf/7382.pdf

MODIFIED CITRUS PECTIN

(2001) Honjo Y, Nangia-Makker P, Inohara H, Raz A. “Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells.” Clin Cancer Res. 2001 Mar;7(3):661-8.

(2007) Azemar M, Hildenbrand B, Haering B, Manfred E. Heim, ME, Unger, C. “Clinical benefit in patients with advanced solid tumors treated with modified citrus pectin: a prospective pilot study.” Clinical Medicine: Oncology 2007:1 73-80.

(2009) Glinsky, Vladislav V, and Avraham Raz. “Modified citrus pectin anti-metastatic properties: one bullet, multiple targets.” Carbohydrate research vol. 344,14 (2009): 1788-91. doi:10.1016/j.carres.2008.08.038

(2010) Yan, J, and Katz, AE. “PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells.” Integr Cancer Ther 2010;9:197-203.

(2011) Ramachandran, Cheppail et al. “Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin.” BMC complementary and alternative medicine vol. 11 59. 4 Aug. 2011, doi:10.1186/1472-6882-11-59

(2013) Leclere Lionel, Van Cutsem Pierre, Michiels Carine. “Anti-cancer activities of pH- or heat-modified pectin.”  Frontiers in Pharmacology. 4:128, 2013. URL=https://www.frontiersin.org/article/10.3389/fphar.2013.00128

(2018) Contj S, et al. “Modified Citrus Pectin as a Potential Sensitizer for Radiotherapy in Prostate Cancer.”  Integrative Cancer Therapies. Volume: 17 issue: 4, page(s): 1225-1234

(2019) Eliaz, Isaac, and Avraham Raz. “Pleiotropic Effects of Modified Citrus Pectin.” Nutrients vol. 11,11 2619. 1 Nov. 2019, doi:10.3390/nu11112619

MUSHROOMS

(2006) Muller, et al. “Ganoderma lucidum causes apoptosis in leukemia, lymphoma and multiple myeloma cells.” (Reishi) Leuk Res. 2006 Jul;30(7):841-8. Epub 2006 Jan 19. (Reishi)

(2007) Cheuk W, Chan JK, Nuovo G, Chan MK, Fok M. “Regression of gastric large B-Cell lymphoma accompanied by a florid lymphoma-like T-cell reaction: immunomodulatory effect of Ganoderma lucidum (Lingzhi)?” Int J Surg Pathol. 2007 Apr;15(2):180-6. doi: 10.1177/1066896906295890. PMID: 17478779.

(2011) Hetland, Geir et al. “The Mushroom Agaricus blazei Murill Elicits Medicinal Effects on Tumor, Infection, Allergy, and Inflammation through Its Modulation of Innate Immunity and Amelioration of Th1/Th2 Imbalance and Inflammation.” Advances in pharmacological sciences vol. 2011 (2011): 157015. doi:10.1155/2011/157015. (Brazilian rain forest)

(2011) Calviño E, Pajuelo L, Casas JA, Manjón JL, Tejedor MC, Herráez A, Alonso MD, Diez JC. “Cytotoxic action of Ganoderma lucidum on interleukin-3 dependent lymphoma DA-1 cells: involvement of apoptosis proteins.” Phytother Res. 2011 Jan;25(1):25-32. doi: 10.1002/ptr.3202. PMID: 20568239.

(2014) Patel, Seema, and Arun Goyal. “Recent developments in mushrooms as anti-cancer therapeutics: a review.” 3 Biotech vol. 2,1 (2012): 1-15. doi:10.1007/s13205-011-0036-2.

(2017) Tangen, et al. “Cytotoxic Effect on Human Myeloma Cells and Leukemic Cells by the Agaricus blazei Murill Based Mushroom Extract, Andosan.” BioMed Research International
Volume 2017, Article ID 2059825, 7 pages.

(2017) Figueiredo, L., & Régis, W. C. B. “Medicinal mushrooms in adjuvant cancer therapies: an approach to anticancer effects and presumed mechanisms of action.” Nutrire, 42(1). https://doi.org/10.1186/s41110-017-0050-1

(2017) Joseph, T. P., Chanda, W., Padhiar, A. A., Batool, S., LiQun, S., Zhong, M., & Huang, M. “A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.” Integrative Cancer Therapies, 17(2), 200–209. https://doi.org/10.1177/1534(2018) Blagodatski, A., Yatsunskaya, M., Mikhailova, V., Tiasto, V., Kagansky, A., & Katanaev, V. L. “Medicinal mushrooms as an attractive new source of natural compounds for future cancer therapy.” Oncotarget, 9(49). https://doi.org/10.18632/oncotarget.25660

(2020) Jeitler, M., Michalsen, A., Frings, D., Hübner, M., Fischer, M., Koppold-Liebscher, D. A., Murthy, V., & Kessler, C. S. “Significance of medicinal mushrooms in integrative oncology: A narrative review.” Frontiers. https://www.frontiersin.org/articles/10.3389/fphar.2020.580656/full

(2020) Jędrzejewski T et al.  “Protein-Bound Polysaccharides from Coriolus Versicolor Fungus Disrupt the Crosstalk Between Breast Cancer Cells and Macrophages through Inhibition of Angiogenic Cytokines Production and Shifting Tumour-Associated Macrophages from the M2 to M1 Subtype.” Cell Physiol Biochem. 2020 Jun 20;54(4):615-628. doi: 10.33594/000000244

(2021) Yue, G. G.-L., Lau, C. B.-S., & Leung, P.-C. “Medicinal Plants and Mushrooms with Immunomodulatory and Anticancer Properties—A Review on Hong Kong’s Experience.” Molecules, 26(8), 2173. https://doi.org/10.3390/molecules26082173

 

(2021) Nowakowski, P., Markiewicz-Żukowska, R., Bielecka, J., Mielcarek, K., Grabia, M., & Socha, K. “Treasures from the forest: Evaluation of mushroom extracts as anti-cancer agents.” Biomedicine & Pharmacotherapy, 143, 112106. https://doi.org/10.1016/j.biopha.2021.112106

735417736861

(2022) Pilkington K, Wieland LS, Teng L, Jin XY, Storey D, Liu JP.  “Coriolus (Trametes) versicolor mushroom to reduce adverse effects from chemotherapy or radiotherapy in people with colorectal cancer.” Cochrane Database Syst Rev. 2022 Nov 29;11(11):CD012053. doi: 10.1002/14651858.CD012053.pub2. PMID: 36445793; PMCID: PMC9707730.

(2022) Panda SK, Sahoo G, Swain SS, Luyten W. “Anticancer Activities of Mushrooms: A Neglected Source for Drug Discovery.” Pharmaceuticals (Basel). 2022 Jan 31;15(2):176. doi: 10.3390/ph15020176. PMID: 35215289; PMCID: PMC8876642.

(2022) Park, H.-J. “Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.” International Journal of Molecular Sciences, 23(18), 10502. https://doi.org/10.3390/ijms231810502

(2023) Narayanan, S., de Mores, A. R., Cohen, L., Anwar, M. M., Lazar, F., Hicklen, R., Lopez, G., Yang, P., & Bruera, E. “Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies.” Current Oncology Reports. https://doi.org/10.1007/s11912-023-01408-2

(2023) Dan A, Swain R, Belonce S, Jacobs RJ. “Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review.” Cureus. 2023 Apr 14;15(4):e37574. doi: 10.7759/cureus.37574. PMID: 37193480; PMCID: PMC10183216.

NICLOSAMIDE ETHANOLAMINE

 

NITRIC OXIDE

(2015) Sudjit Luanpitpong and Pithi Chanvorachote.  “Nitric Oxide and Aggressive Behavior of Lung Cancer Cells “. Anticancer Research. September 2015 vol. 35no. 9 4585-4592

(2016) Vahora, Huzefa et al. “The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention” Journal of cancer prevention vol. 21,1 (2016): 1-12.

OLIVE LEAF (Oleuropein)

(2015) Carla Marchetti, et al.  “Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells.” Evid Based Complement Alternat Med. 2015;2015:908493. doi: 10.1155/2015/908493. Epub 2015 Nov 26.

OREGANO

(2009) Savini I, Arnone R, Catani MV, Avigliano L. “Origanum vulgare induces apoptosis in human colon cancer caco2 cells.” Nutr Cancer. 24 Volume 3, Number 3 • May 2014 • www.gahmj.com GLOBAL ADVANCES IN HEALTH AND MEDICINE Original Research 2009;61(3):381-9

(2015) H.S. Elshafie, M.F. Armentano, M. Carmosino, S.A. Bufo, V. De Feo, I. Camele.  “Cytotoxic activity of Origanum vulgare L. on hepatocellular carcinoma cell line HepG2 and evaluation of its biological activity.”  Molecules, 22 (9) (2015), p. E1435

(2017) K.R. Begnini, et al.  “Composition and antiproliferative effect of essential oil of Origanum vulgare against tumor cell lines.” J. Med. Food., 17(10)(2017), pp. 1-5

(2018) Sri Renukadevi Balusamy, Haribalan Perumalsamy, Md. Amdad Huq, Balamuralikrishnan Balasubramanian.  “Anti-proliferative activity of Origanum vulgare inhibited lipogenesis and induced mitochondrial mediated apoptosis in human stomach cancer cell lines.”  Biomedicine & Pharmacotherapy, Volume 108, 2018, Pages 1835-1844.

OZONE THERAPY

(1980) Sweet F, Kao MS, Lee SC, Hagar WL, Sweet WE. “Ozone selectively inhibits growth of human cancer cells.” Science. 1980 Aug 22;209(4459):931-3. doi: 10.1126/science.7403859. PMID: 7403859.

(2004) Clavo B, Ruiz A, Lloret M, López L, Suárez G, Macías D, Rodríguez V, Hernández MA, Martín-Oliva R, Quintero S, Cuyás JM, Robaina F.  “Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study.” Evid Based Complement Alternat Med. 2004 Dec;1(3):321-325. doi: 10.1093/ecam/neh038. Epub 2004 Oct 16. PMID: 15841266; PMCID: PMC538509.

(2005) Bocci V, Larini A, Micheli V. “Restoration of normoxia by ozone therapy may control neoplastic growth: a review and a working hypothesis.”  J Altern Complement Med. 2005 Apr;11(2):257-65. doi: 10.1089/acm.2005.11.257. PMID: 15865491.

(2015) Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. “Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model.” Altern Ther Health Med. 2015 Mar-Apr;21(2):24-9. PMID: 25830277.

(2017) Luongo, et al. “Review: Possible Therapeutic Effects of Ozone Mixture on Hypoxia in Tumor Development.” Anticancer Research, February 2017 37 (2) 425-435.

(2017) Hussain S, Sharma DB, Solanki FS, Pathak A, Sharma D. “Intraprostatic ozone therapy: A minimally invasive approach in benign prostatic hyperplasia.” Urol Ann. 2017 Jan-Mar;9(1):37-40. doi: 10.4103/0974-7796.198843. PMID: 28216927; PMCID: PMC5308035.

(2018) Dogan R, Hafız AM, Kiziltan HS, Yenigun A, Buyukpinarbaslili N, Eris AH, Ozturan O. “Effectiveness of radiotherapy+ozone on tumoral tissue and survival in tongue cancer rat model.” Auris Nasus Larynx. 2018 Feb;45(1):128-134. doi: 10.1016/j.anl.2017.03.017. Epub 2017 Apr 6. PMID: 28390748.

(2018) Clavo, Bernardino et al. “Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?” Evidence-based complementary and alternative medicine : eCAM vol. 2018 7931849. 9 Sep. 2018, doi:10.1155/2018/7931849

(2019) Bernardino Clavo, et al. “Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects.” Antioxidants 2019, 8, 588; doi:10.3390/antiox8120588

(2020) Rodionova, O. G., Gusareva, M. А., Voshedskiy, V. I., Vasilyeva, E. O., Sheiko, E. A., Solntseva, A. A., Sakun, P. G., Власов, С. Г., Museyko, K. N., Pustovalova, A. V., Chalabova, T. G., & Kit, O. I. “Ozone therapy as accompanying treatment for chemoradiotherapy in patients with locally advanced cervical cancer.” Journal of Clinical Oncology, 38(15_suppl), e18030–e18030. https://doi.org/10.1200/jco.2020.38.15_suppl.e18030

(2021) Rodionova, O. G., Gusareva, M. А., Sheiko, E. A., Voshedskiy, V. I., Sakun, P. G., Vasilieva, E. О., Karnaukhova, E. A., Solntseva, A. A., Кошелева, Н. Г., Krokhmal, Y. N., Pustovalova, A. V., Chalabova, T. G., Dontsov, V. A., Kabanov, S. N., & Власов, С. Г. “Combination ozone therapy as an effective method of radiomodification in chemoradiation treatment of patients with cervical cancer.” Journal of Clinical Oncology, 39(15_suppl), e17515–e17515. https://doi.org/10.1200/jco.2021.39.15_suppl.e17515

(2021) Viebahn-Haensler, R., & León Fernández, O. S. “Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases.” International Journal of Molecular Sciences, 22(15), 7890. https://doi.org/10.3390/ijms22157890

(2021) Baeza-Noci J, Pinto-Bonilla R. “Systemic Review: Ozone: A Potential New Chemotherapy.” Int J Mol Sci. 2021 Oct 30;22(21):11796. doi: 10.3390/ijms222111796. PMID: 34769225; PMCID: PMC8584016.

PEDIATRICS

(2021) Stub, T., Quandt, S.A., Kristoffersen, A.E. et al. “Communication and information needs about complementary and alternative medicine: a qualitative study of parents of children with cancer.” BMC Complement Med Ther 21, 85 (2021). https://doi.org/10.1186/s12906-021-03253-x

PEPTIDES

(2015) Xiao, Yu-Feng, et al. “Peptide-based Treatment: A Promisinf

(2021) Li CM, Haratipour P, Lingeman RG, Perry JJP, Gu L, Hickey RJ, Malkas LH. “Novel Peptide Therapeutic Approaches for Cancer Treatment.” Cells. 2021 Oct 27;10(11):2908. doi: 10.3390/cells10112908. PMID: 34831131; PMCID: PMC8616177.

(2022) Karami Fath, M., Babakhaniyan, K., Zokaei, M. et al. “Anti-cancer peptide-based therapeutic strategies in solid tumors.” Cell Mol Biol Lett 27, 33 (2022). https://doi.org/10.1186/s11658-022-00332-w

(2023) Vadevoo, S.M.P., Gurung, S., Lee, HS. et al. “Peptides as multifunctional players in cancer therapy.” Exp Mol Med (2023). https://doi.org/10.1038/s12276-023-01016-x

QIGONG/ TAI CHI

(2017) Klein, Penelope. “Qigong in Cancer Care: Theory, Evidence-Base, and Practice.” Medicines (Basel, Switzerland) vol. 4,1 2. 12 Jan. 2017, doi:10.3390/medicines4010002

QUERCETIN - take at least 5 hours away from Ivermectin

(2011) Wang K, et al. “Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling”. Autophagy. 2011;7(9):966–978. doi: 10.4161/auto.7.9.15863.

(2011) Gibellini, L., Pinti, M., Nasi, M., Montagna, J. P., De Biasi, S., Roat, E., Bertoncelli, L., Cooper, E. L., & Cossarizza, A. “Quercetin and Cancer Chemoprevention.” Evidence-Based Complementary and Alternative Medicine, 2011, 1–15. https://doi.org/10.1093/ecam/neq053

(2012) Jacquemin, Guillaume et al. “Quercetin-mediated Mcl-1 and survivin downregulation restores TRAIL-induced apoptosis in non-Hodgkin's lymphoma B cells.” Haematologica vol. 97,1 (2012): 38-46. doi:10.3324/haematol.2011.046466

(2013) Dneg, et al. “Effects of quercetin on the proliferation of breast cancer cells and expression of survivin in vitro.” EXPERIMENTAL AND THERAPEUTIC MEDICINE  6:  1155-1158,  2013.

(2014) Li, X., Wang, X., Zhang, M. et al. “Quercetin Potentiates the Antitumor Activity of Rituximab in Diffuse Large B-Cell Lymphoma by Inhibiting STAT3 Pathway.” Cell Biochem Biophys 70, 1357–1362 (2014). https://doi.org/10.1007/s12013-014-0064-8

(2014) Maso V, et al. “Multitarget effects of quercetin in leukemia.” Cancer Prev Res (Phila) 2014;7(12):1240–1250. doi: 10.1158/1940-6207.CAPR-13-0383

(2017) Granato, Marisa, et al. “Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways.” J Nutr Biochem. 2017 Mar;41:124-136. doi: 10.1016/j.jnutbio.2016.12.011.

(2017) Zhou, Jin et al. “Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo.” PloS one vol. 12,3 e0172838. 6 Mar. 2017, doi:10.1371/journal.pone.0172838 (quercetin can significantly inhibit the growth and proliferation of several types of cancer, including breast, liver, nasopharyngeal, colorectal, gastric, endometrial cancers, and leukemia).

(2017) Russo, M., Milito, A., Spagnuolo, C., Carbone, V., Rosén, A., Minasi, P., Lauria, F., & Russo, G. L. “CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia.” Oncotarget, 8(26), 42571–42587. https://doi.org/10.18632/oncotarget.17246

(2018) Wang, Rong et al. “Quercetin Inhibits Breast Cancer Stem Cells via Downregulation of Aldehyde Dehydrogenase 1A1 (ALDH1A1), Chemokine Receptor Type 4 (CXCR4), Mucin 1 (MUC1), and Epithelial Cell Adhesion Molecule (EpCAM).” Medical science monitor : international medical journal of experimental and clinical research vol. 24 412-420. 21 Jan. 2018, doi:10.12659/msm.908022.

(2018) Nezami MA, et al. “Proof of concept in a case study of glioblastoma multiforme successfully treated with IV Quercetin in combination with leading edge gamma knife and standard treatments.”  J Cancer Ther 2018;9:522-8.

(2018) Alvarez, Marisa Claudia et al. “The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes.” Clinical epigenetics vol. 10,1 139. 8 Nov. 2018, doi:10.1186/s13148-018-0563-3

(2018) Calgarotto, A.K., Maso, V., Junior, G.C.F. et al.  “Antitumor activities of Quercetin and Green Tea in xenografts of human leukemia HL60 cells.” Sci Rep 8, 3459 (2018). https://doi.org/10.1038/s41598-018-21516-5

(2018) Ward AB, Mir H, Kapur N, Gales DN, Carriere PP, Singh S. “Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways.” World J Surg Oncol. 2018 Jun 14;16(1):108. doi: 10.1186/s12957-018-1400-z. PMID: 29898731; PMCID: PMC6001031.

(2019) Naimi A, Entezari A, Hagh MF, Hassanzadeh A, Saraei R, Solali S. “Quercetin sensitizes human myeloid leukemia KG-1 cells against TRAIL-induced apoptosis.” J Cell Physiol. 2019;234(8):13233-13241. doi:10.1002/jcp.27995

(2019) Reyes-Farias, M., & Carrasco-Pozo, C. “The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism.” International Journal of Molecular Sciences, 20(13), 3177. https://doi.org/10.3390/ijms20133177

(2019) Shafabakhsh, R., & Asemi, Z. “Quercetin: a natural compound for ovarian cancer treatment.” Journal of Ovarian Research, 12(1). https://doi.org/10.1186/s13048-019-0530-4

 

(2019) Tang, S.-M., Deng, X.-T., Zhou, J., Li, Q.-P., Ge, X.-X., & Miao, L. “Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.” Biomedicine & Pharmacotherapy. https://www.sciencedirect.com/science/article/pii/S0753332219352266?via%3Dihub

(2020) Vafadar, A., Shabaninejad, Z., Movahedpour, A. et al. “Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells.” Cell Biosci 10, 32 (2020). https://doi.org/10.1186/s13578-020-00397-0

(2020) Ezzati, M., Yousefi, B., Velaei, K., & Safa, A. “A review on anti-cancer properties of Quercetin in breast cancer.” Life Sciences, 248, 117463. https://doi.org/10.1016/j.lfs.2020.117463

(2020) “Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.” Biomedicine & Pharmacotherapy, 121, 109604. https://doi.org/10.1016/j.biopha.2019.109604

(2021) Ghafouri-Fard S, Shabestari FA, Vaezi S, Abak A, Shoorei H, Karimi A, Taheri M, Basiri A. “Emerging impact of quercetin in the treatment of prostate cancer.” Biomed Pharmacother. 2021 Jun;138:111548. doi: 10.1016/j.biopha.2021.111548. Epub 2021 Apr 1. PMID: 34311541.

RESVERATROL

(2002) Shih A, Davis FB, Lin HY, Davis PJ. “Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism.” J Clin Endocrinol Metab. 2002 Mar;87(3):1223-32. doi: 10.1210/jcem.87.3.8345. PMID: 11889192.

(2004) Simone Fulda and Klaus-Michael Debati. “Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent resveratrol.” Oncogene (2004) 23, 6702–6711.

(2004) Jazirehi, Ali R, and Benjamin Bonavida. “Resveratrol modifies the expression of apoptotic regulatory proteins and sensitizes non-Hodgkin's lymphoma and multiple myeloma cell lines to paclitaxel-induced apoptosis.” Molecular cancer therapeutics vol. 3,1 (2004): 71-84.

(2006) Sexton, Emilie et al. “Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells.” Molecular cancer vol. 5 45. 17 Oct. 2006, doi:10.1186/1476-4598-5-45

(2006) Faber AC, Chiles TC. “Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling.” Int J Oncol. 2006 Dec;29(6):1561-6. PMID: 17088997.

(2007) C. Gill, S. E. Walsh, C. Morrissey, J. M. Fitzpatrick, and R. W. G. Watson. “Resveratrol sensitizes androgen independent prostate cancer cells to death-receptor mediated apoptosis through multiple mechanisms.” The Prostate, vol. 67, no. 15, pp. 1641– 1653, 2007.

(2009) Nguyen, et al. “Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer.” Cancer Management and Research 2009:1 25–37.

(2010) K. R. Patel, V. A. Brown, D. J. L. Jones et al. “Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients.” Cancer Research, vol. 70, no. 19, pp. 7392–7399, 2010.

(2011) ] J. Ryu, B. M. Ku, Y. K. Lee et al. “Resveratrol reduces tnf-alphainduced u373mg human glioma cell invasion through regulating nf-kappab activation and upa/upar expression.” Anticancer Research, vol. 31, pp. 4223–4230, 2011.

(2011) Duntas LH. “Resveratrol and its impact on aging and thyroid function.” J Endocrinol Invest. 2011 Nov;34(10):788-92. doi: 10.3275/7926. Epub 2011 Sep 23. PMID: 21946130.

(2012) Meher U. Nessa, et al. “Combinations of Resveratrol, Cisplatin and Oxaliplatin Applied to Human Ovarian Cancer Cells.” Anticancer Research. 32: 53-60 (2012)

(2012) (2012) Vetvicka V, Vetvickova J. “Combination of glucan, resveratrol and vitamin C demonstrates strong anti-tumor potential.” Anticancer Res. 2012;32:81–87.

(2012) Lee, K.A.; Lee, Y.J.; Ban, J.O.; Lee, Y.J.; Lee, S.H.; Cho, M.K.; Nam, H.S.; Hong, J.T.; Shim, J.H.  “The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1.”  Int. J. Mol. Med. 2012, 30, 21–27.

(2014) Chottanapund S, et al.  “Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts.”  Toxicol In Vitro. 2014 Oct;28(7):1215-21. doi: 10.1016/j.tiv.2014.05.015. Epub 2014 Jun 12.

(2014) Carter, L.G.; D’Orazio, J.A.; Pearson, K.J. “Resveratrol and cancer: Focus on in vivo evidence.” Endocr. Relat. Cancer 2014, 21, R209–R225.

(2015) Shi, Q.; Geldenhuys, W.; Sutariya, V.; Bishayee, A.; Patel, I.; Bhatia, D.  “CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells.” Genes Cancer 2015, 6, 220–230.

(2016) Zhong, L-X et al. “Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells.” Cell death discovery vol. 2 15071. 25 Jan. 2016, doi:10.1038/cddiscovery.2015.71

(2016) Shindikar, A., Singh, A., Nobre, M., & Kirolikar, S. “Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer.” Journal of Oncology, 2016, e9750785. https://doi.org/10.1155/2016/9750785

(2016) Mondal, A.; Bennett, L.L. “Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage.” Biomed. Pharmacother. 2016, 84, 1906–1914.

(2016) Lee, Y.J.; Lee, G.J.; Yi, S.S.; Heo, S.H.; Park, C.R.; Nam, H.S.; Cho, M.K.; Lee, S.H. “Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells.”  Food Chem. Toxicol. 2016, 97, 96–107.

(2017) Andreani, et al. “Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor.” AGING 2017, Vol 9.

(2017) C. Cilibrasi, G. Riva, G. Romano et al. “Resveratrol impairs glioma stem cells proliferation and motility by modulating the wnt signaling pathway.” PLoS ONE, vol. 12, no. 1, Article ID e0169854, 2017.

(2017) Sui X, Zhang C, Zhou J, Cao S, Xu C, Tang F, Zhi X, Chen B, Wang S, Yin L. “Resveratrol inhibits Extranodal NK/T cell lymphoma through activation of DNA damage response pathway.” J Exp Clin Cancer Res. 2017 Sep 26;36(1):133. doi: 10.1186/s13046-017-0601-6. PMID: 28950914; PMCID: PMC5615630.

(2018) Liu Y, et al. “Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway.” J Cell Biochem. 2018 Jul;119(7):6162-6172. doi: 10.1002/jcb.26822. Epub 2018 Apr 16.

(2018) Stefan Poschner, et al.  “Resveratrol Inhibits Key Steps of Steroid Metabolism in a Human Estrogen-Receptor Positive Breast Cancer Model: Impact on Cellular Proliferation.” Frontiers in Pharmacology. 10 July 2018. https://doi.org/10.3389/fphar.2018.00742

(2018) Varghese, E., Samuel, S., Abotaleb, M., Cheema, S., Mamtani, R., & Büsselberg, D. “The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers.” Cancers, 10(10), 346. https://doi.org/10.3390/cancers10100346

(2020) XY Kong, et al.  “Resveratrol inhibits invasion and migration of endometrial cancer by reversing MTA1-ZEB2-induced epithelial-mesenchymal transition.”  Gynecologic Oncology. LBA 3-sunrise session.  Vol 159, Supplement 1, 38, October 1, 2020.

(2020) Xiaodong Sun, et al. “Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3 TYR705 phosphorylation.” Wiley Online Library. 10 October 2020.

(2021) Liang ZJ, Wan Y, Zhu DD, Wang MX, Jiang HM, Huang DL, Luo LF, Chen MJ, Yang WP, Li HM, Wei CY. “Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression.” Front Oncol. 2021 Feb 25;11:569295. doi: 10.3389/fonc.2021.569295. PMID: 33747905; PMCID: PMC7970754.

(2022) Zaffaroni N, Beretta GL. “Resveratrol and Prostate Cancer: The Power of Phytochemicals.” Curr Med Chem. 2021;28(24):4845-4862. doi: 10.2174/0929867328666201228124038. PMID: 33371831.

(2023) Sakamoto T, Tanimoto K, Eguchi H, Sasaki S, Tsuboi K, Hayashi SI, Ichihara S. “Resveratrol exhibits diverse anti-cancer activities through epigenetic regulation of E-cadherin and p21 in triple-negative breast cancer cells.” Breast Cancer. 2023 May 11. doi: 10.1007/s12282-023-01465-2. Epub ahead of print. PMID: 37166625.

SELENIUM

(2010) Muecke, et al.  “Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology.” Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):828-35. doi: 10.1016/j.ijrobp.2009.08.013. Epub 2010 Feb 3.

(2010) Buntzel, J, Riesenbeck, D, Glatzel, M.  “Limited effects of selenium substitution in the prevention of radiation-associated toxicities: results of a randomized study in head and neck cancer patients.” Anticancer Res. 2010;30:1829-1832

(2013) Muecke, R, Micke, O, Schomburg, L. “Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology: a subgroup analysis of a multicenter, phase III trial.”  Radiat Oncol. 2013;8:72

(2016) Cai, Xianlei et al. “Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression.” Scientific reports vol. 6 19213. 20 Jan. 2016, doi:10.1038/srep19213.

SLEEP ISSUES

(2019) Sulli G, Lam MTY, Panda S. “Interplay between Circadian Clock and Cancer: New Frontiers for Cancer Treatment.” Trends Cancer. 2019 Aug;5(8):475-494. doi: 10.1016/j.trecan.2019.07.002. Epub 2019 Aug 3. PMID: 31421905; PMCID: PMC7120250.

(2019) Ayesha A. Shafi and Karne Knudsen. “Cancer and the Circadian Clock.” Cancer Res (2019) 79 (15): 3806–3814. https://doi.org/10.1158/0008-5472.CAN-19-0566

(2020) Sadiq Z, Varghese E, Büsselberg D. “Cisplatin's dual-effect on the circadian clock triggers proliferation and apoptosis.” Neurobiol Sleep Circadian Rhythms. 2020 Jul 30;9:100054. doi: 10.1016/j.nbscr.2020.100054. PMID: 33364523; PMCID: PMC7752721.

(2021) Lee, Y. “Roles of circadian clocks in cancer pathogenesis and treatment.” Exp Mol Med 53, 1529–1538 (2021). https://doi.org/10.1038/s12276-021-00681-0

(2021) Battaglin, F., Chan, P., Pan, Y. et al. “Clocking cancer: the circadian clock as a target in cancer therapy.” Oncogene 40, 3187–3200 (2021). https://doi.org/10.1038/s41388-021-01778-6

(2022) Amidi A, Wu LM. “Circadian disruption and cancer- and treatment-related symptoms.” Front Oncol. 2022 Oct 28;12:1009064. doi: 10.3389/fonc.2022.1009064. PMID: 36387255; PMCID: PMC9650229.

SPIROLINA

(2011) Bhattacharyya, S., & Mehta, P. “The hepatoprotective potential of spirulina and vitamin C supplementation in cisplatin toxicity.” Food & Function, 3(2), 164-169. doi: 10.1039/c1fo10172b  (Mesothelioma)

(2013) Zhang BC, Zhang XW.  “Separation and nanoencapsulation of antitumor polypeptide from Spirulina platensis.” Biotechnol Prog 29:1230–1238

(2014) Koníčková R, Vaňková K, Vaníková J, Váňová K, Muchová L, Subhanová I, Zadinová M, Zelenka J, Dvořák A, Kolář M, Strnad H, Rimpelová S, Ruml T, J Wong R, Vítek L. “Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds.” Ann Hepatol. 2014 Mar-Apr;13(2):273-83. PMID: 24552870.

(2016) Wang Z, Zhang X.  “Inhibitory effects of small molecular peptides from Spirulina (Arthrospira) platensis on cancer cell growth.”  Food Funct 7:781–788.

(2022) Fais G, Manca A, Bolognesi F, Borselli M, Concas A, Busutti M, Broggi G, Sanna P, Castillo-Aleman YM, Rivero-Jiménez RA, Bencomo-Hernandez AA, Ventura-Carmenate Y, Altea M, Pantaleo A, Gabrielli G, Biglioli F, Cao G, Giannaccare G. “Wide Range Applications of Spirulina: From Earth to Space Missions.” Mar Drugs. 2022 Apr 28;20(5):299. doi: 10.3390/md20050299. PMID: 35621951; PMCID: PMC9143897. Breast, liver, lung cancers.

SULFORPHANE

(2012) Abbaoui, Besma et al. “Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion.” Molecular nutrition & food research vol. 56,11 (2012): 1675-87.

(2014) Bergantin, Elisa et al. “Sulforaphane induces apoptosis in rhabdomyosarcoma and restores TRAIL-sensitivity in the aggressive alveolar subtype leading to tumor elimination in mice.” Cancer biology & therapy vol. 15,9 (2014): 1219-25.

(2014) Jo, G. H., et al. "Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: The involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway.” International Journal of Oncology 45.4 (2014): 1497-1506.

(2017) Leone, Andrew et al. “Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach.” Oncotarget vol. 8,21 (2017): 35412-35424.

(2018) Lei Huang, et al. “Sulforaphane inhibits human bladder cancer cell invasion by reversing epithelial-to-mesenchymal transition via directly targeting microRNA-200c/ZEB1 axis.”  Journal of Functional Foods. Volume 41, February 2018, Pages 118-126.

(2018) Sato S, et al. “Sulforaphane Inhibits Liver Cancer Cell Growth and Angiogenesis.” iMed Pub Journals. 2018. Vol 6. No 4:23. DOI: 10.21767/2254-6081.100189

(2020) Kamal MM, Akter S, Lin CN, Nazzal S. “Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems.”  Arch Pharm Res. 2020 Apr;43(4):371-384. doi: 10.1007/s12272-020-01225-2. Epub 2020 Mar 10. PMID: 32152852.

(2021) Kaiser AE, Baniasadi M, Giansiracusa D, Giansiracusa M, Garcia M, Fryda Z, Wong TL, Bishayee A. “Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential.” Cancers (Basel). 2021 Sep 25;13(19):4796. doi: 10.3390/cancers13194796. PMID: 34638282; PMCID: PMC8508555.

(2022) Zhang, Y., Lu, Q., Li, N. et al. “Sulforaphane suppresses metastasis of triple-negative breast cancer cells by targeting the RAF/MEK/ERK pathway.” npj Breast Cancer 8, 40 (2022). https://doi.org/10.1038/s41523-022-00402-4

(2023) Ali, Muhammad Asif, etal. “Anticancer properties of sulforaphane: current insights at the molecular level.” Front. Oncol., June 2023. Sec. Pharmacology of anti-cancer drugs. Volume 13-2023. https://doi.org/10.3389/fonc.2023.1168321.

VITAMIN B12

(2013) Yang, Tsung-Ying et al. “Effect of folic acid and vitamin B12 on pemetrexed antifolate chemotherapy in nutrient lung cancer cells.” BioMed research international vol. 2013 (2013): 389046. doi:10.1155/2013/389046

(2014) Takagi, Yusuke et al. “A prospective study of shortened vitamin supplementation prior to cisplatin-pemetrexed therapy for non-small cell lung cancer.” The oncologist vol. 19,11 (2014): 1194-9. doi:10.1634/theoncologist.2014-0221 (B12 and folate)

(2018) Fanidi A, Et al. “Is high vitamin B12 status a cause of lung cancer?” Int J Cancer. 2018 Nov 29. doi: 10.1002/ijc.32033

(2019) Navneet Singh, et al. “Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first‐line treatment of patients with nonsquamous non–small cell lung cancer using pemetrexed‐based chemotherapy: The PEMVITASTART randomized trial.” Cancer July 1, 2019. Vol 125:13, P 2203-2212.

VITAMIN C (ASCORBIC ACID)

Linus Pauling Institute.  Oregon State University.

https://www.cancer.gov/about-cancer/treatment/cam/hp/vitamin-c-pdq#_16

https://www.medicalnewstoday.com/articles/319017.php#1

https://now.uiowa.edu/2017/01/why-high-dose-vitamin-c-kills-cancer-cells#.WJo_O1qD2kY.twitter

https://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30062-4

https://www.cancer.gov/research/key-initiatives/ras/ras-central/blog/2020/yun-cantley-vitamin-c?trk=public_post_comment-text

https://www.medicalnewstoday.com/articles/vitamin-c-and-fasting-mimicking-diet-can-shrink-tumors

University of Kansas Medical Center Integrative Medicine.  Clinical Trials high dose vitamin C.

University of Wisconsin, School of Medicine and Public Health.  High-Dose Vitamin C (PDQ®): Integrative, alternative, and complementary therapies - Health Professional Information [NCI]

(1975) Cameron E, et al. “The orthomolecular treatment of cancer. III. Reticulum cell sarcoma: double complete regression induced by high-dose ascorbic acid therapy.” Chemico-biological Interactions. 1975 Nov;11(5):387-93.

(1978) Cameron E, Pauling L. “Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer.” Proceedings of the National academy of Science of the USA. 1978 Sep;75(9):4538-42.

(1990) Mehta JB, Singhal SB, Mehta BC. “Ascorbic-acid-induced haemolysis in G-6-PD deficiency.” Lancet. Oct 13 1990;336(8720):944.

(1991) G. Block.  “Vitamin C and cancer prevention: the epidemiologic evidence.” American Journal of Clinical Nutrition, 1991, Jan.;53(1 Suppl):270S-82S

(1991) G. Block. “Epidemiologic evidence regarding vitamin C and cancer.” American Journal of Clinical Nutrition, 1991 Dec.;54(6 Suppl):1310S

(1993) Rees DC, Kelsey H, Richards JD. “Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency.” BMJ. Mar 27 1993;306(6881):841-842.

(1996) Kurbacher, et al. “Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro.” Cancer letters. 103. 183-9. 10.1016/0304-3835(96)04212-7.

(1998) Antunes LM, Takahashi CS. “Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells.” Mutat Res. 1998 Nov 9;419(1-3):137-43. doi: 10.1016/s1383-5718(98)00134-x. PMID: 9804927.

(1998) K.A. Head.  “Ascorbic acid in the prevention and treatment of cancer”. Alternative Medicine Review, 1998, June;3(3):174-86

(2000) Andrew G, Bowie2 , O’Neill LAJ. “Vitamin C Inhibits NF-kB Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase.” The J Immunol. 2000, 165: 7180-7188.

(2001) Casciari JJ, Riordan NH. “Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fiber in vitro tumors.” Br J Cancer. 2001, 84: 1544-1550. 10.1054/bjoc.2001.1814.

(2001) Khaw KT, et al.  “Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition.”  Lancet. 2001 Mar 3;357(9257):657-63.

(2002) Bowie AG, Carcamo JM, Pedraza A, Borquez-Qjeda O, Golde DW. “Vitamin C suppresses TNFa-induced NFkB activation by inhibiting IkαB phosphorilation.” Biochemistry. 2002, 41: 12995-13002. 10.1021/bi0263210.

(2004) Padayatty SJ, Sun H, Wang Y, et al. “Vitamin C pharmacokinetics: implications for oral and intravenous use.” Ann Intern Med 140 (7): 533-7, 2004.

(2004) Park, et al. “L-ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide-mediated mechanisms.” The International Journal of Biochemisby & Cell Biology 36 (2004) 2180-2195.

(2004) Park, et al. “L-Ascorbic Acid Represses Constitutive Activation of NF-KB and COX-2 Expression in Human Acute Myeloid Leukemia, HL-60.” Journal of Cellular Biochemistry, 2004, 93(2):257-270.

(2005) Levine M, Espey MG, Chen Q.  “Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment.”  Free Radic Biol Med. 2009 Jul 1;47(1):27-9. doi: 10.1016/j.freeradbiomed.2009.04.001. Epub 2009 Apr 8.

(2005) Chen Q, Espey MG, Krishna MC. “Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.” Proc Natl Acad Sci U S A. 2005, 102: 13604-13609. 10.1073/pnas.0506390102.

(2005) Pathak AK, Bhutani M, Guleria R, et al. “Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non-small cell lung cancer.” J Am Coll Nutr. Feb 2005;24(1):16-21.

(2006) Sebastian J Paddayatty, Hugh D Riordan, Stephen M Hewitt, Arie Katz, L John Hoffer, Mark Levine. “Intravenously Administered Vitamin C as Cancer Therapy: Three Cases.”  CMAJ: March 28, 2006: 174(7) 937 (B-cell lymphoma, renal cell carcinoma, bladder cancer)

(2006) H Kawada et al. “Phase I Clinical Trial of Intravenous L-ascorbic Acid Following Salvage Chemotherapy for Relapsed B-cell non-Hodgkin’s Lymphoma’. Tokai Journal of Experimental and Clinical Medicine, 2014, Sep 20;39(3):111-5; S.J. Padayatty et al., ‘Intravenously administered vitamin C as cancer therapy: three cases’, Canadian Medical Association Journal, 2006, Mar. 28;174(7):937-42

(2007) Yeom CH, Jung GC, Song KJ. “Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration.” J Korean Med Sci 22 (1): 7-11, 2007.

(2007) Duconge J, Miranda-Massari JR, González MJ, Taylor PR, Riordan HD, Riordan NH, Casciari JJ, Alliston K.  “Vitamin C pharmacokinetics after continuous infusion in a patient with prostate cancer.” Ann Pharmacother. 2007, 41 (6): 1082-1083. 10.1345/aph.1H654.

(2008) Duconge J, Miranda-Massari JR, Gonzalez MJ, Jackson JA, Warnock W, Riordan NH. “Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate.” P R Health Sci J. 2008 Mar;27(1):7-19.

(2008) Mikirova NA, Ichim TE, Riordan NH. “Anti-angiogenic effect of high doses of ascorbic acid.” J Transl Med. 2008 Sep 12;6:50. doi: 10.1186/1479-5876-6-50.

(2008) Cameron E, Pauling L. “Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer.” Proc. Natl. Acad. Sci. USA. 1976, 73: 3685-3689. 10.1073/pnas.73.10.3685.corbate. P R Health Sci J. 2008, 27 (1): 7-19. Review

(2008) Hofer, et al. “Phase I clinical trial of i.v. ascorbic acid in advanced malignancy.” Annals of Oncology. 2008 Nov;19(11):1969-74. doi: 10.1093/annonc/mdn377. Epub 2008 Jun 9.

(2009) Levine M, Espey MG, Chen Q. “Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment.” Free Radic Biol Med. 2009 Jul 1;47(1):27-9. doi: 10.1016/j.freeradbiomed.2009.04.001. Epub 2009 Apr 8.

(2011) Pathi SS, Lei P, Sreevalsan S, Chadalapaka G, Jutooru I, Safe S. “Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells.” Nutr Cancer. 2011;63(7):1133-42. doi: 10.1080/01635581.2011.605984. Epub 2011 Sep 15. PMID: 21919647; PMCID: PMC3359146.  This study demonstrates for the first time that the anticancer activities of ascorbic acid are due, in part, to ROS-dependent repression of Sp transcription factors.

(2011) C Vollbracht et al. “Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany.”  In Vivo, 2011, Nov-Dec;25(6):983-90

(2012) Monti DA, Mitchell E, Bazzan AJ, et al. “Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.” PLoS One 7 (1): e29794, 2012.

(2009) Ohno, et al.  “High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced Cancer.” Anticancer Research March 2009 vol. 29 no. 3 809-815.

(2010) Li W, Wu JX, Tu YY. “Synergistic effects of tea polyphenols and ascorbic acid on human lung adenocarcinoma SPC-A-1 cells.” J Zhejiang Univ Sci B. 2010;11:458–464.

(2010) Takemura Y, Satoh M, Satoh K, Hamada H, Sekido Y, Kubota S. “High dose of ascorbic acid induces cell death in mesothelioma cells.”  Biochem Biophys Res Commun. 2010 Apr 2;394(2):249-53. doi: 10.1016/j.bbrc.2010.02.012. Epub 2010 Feb 19. PMID: 20171954.

(2010) Elia Ranzato, et al.  “Selective ascorbate toxicity in malignant mesothelioma a redox trojan mechanism.” American Journal of Respiratory Cell and Molecular Biology. Vol 44. Pp 108-117, 2011.

(2010) Muralikrishnan G, Amanullah S, Basha MI, Boopalan S, Vijayakumar S, Shakeel F. “Effect of vitamin C on lipidperoxidation and antioxidant status in tamoxifen-treated breast cancer patients.” Chemotherapy. 2010;56(4):298-302. doi: 10.1159/000320030. Epub 2010 Aug 13. PMID: 20714147.

(2011) Vollbracht C, Schneider B, Leendert V, et al. “Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany.” In Vivo 25 (6): 983-90, 2011 Nov-Dec.

(2011) Nakano, et al. “Delayed treatment with vitamin C and N-acetyl-L-cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib.” Int J Hematol. 2011 Jun;93(6):727-735. doi: 10.1007/s12185-011-0850-7. Epub 2011 Apr 28.

(2011) K. Hosokawa et al. “Ascorbic acid enhances radiation-induced apoptosis in an HL60 human leukemia cell line”. .J Radiat Res. 2011;52(2):229-37

(2012) Klingelhoeffer C, Kammerer U, Koospal M, et al. “Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress.” BMC Complement Altern Med. 2012;12:61.

(2012) Monit, et al. “Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.” PLoS One. 2012;7(1):e29794. doi: 10.1371/journal.pone.0029794. Epub 2012 Jan 17.

(2012) Mikirova, Nina et al. “Effect of high-dose intravenous vitamin C on inflammation in cancer patients.” Journal of translational medicine vol. 10 189. 11 Sep. 2012, doi:10.1186/1479-5876-10-189

(2012) Chen P, et al. “Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy.” Anticancer Drugs. 2012 Apr;23(4):437-44.

(2012) Vetvicka V, Vetvickova J. “Combination of glucan, resveratrol and vitamin C demonstrates strong anti-tumor potential.” Anticancer Res. 2012;32:81–87.

(2012) Moens B, Decanine D, Menezes SM, Khouri R, Silva-Santos G, et al.  “Ascorbic Acid Has Superior Ex Vivo Antiproliferative, Cell Death-Inducing and Immunomodulatory Effects over IFN-a in HTLV-1-Associated Myelopathy.” PLoS Negl Trop Dis 6(7): e1729. doi:10.1371/journal.pntd.0001729

(2013) Riordan Clinic Research Institute. “The Riordan IVC Protocol for Adjunctive Cancer Care Intravenous Ascorbate as a Chemotherapeutic and Biological Response Modifying Agent.”  February 2013.

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(2013) Stephenson CM, Levin RD, Spector T, Lis CG. “Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer.” Cancer Chemother Pharmacol. 2013;72(1):139-146.

(2013) Welsh JL, Wagner BA, van't Erve TJ, et al. “Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.” Cancer Chemother Pharmacol 71 (3): 765-75, 2013.

(2013) Lam, Tram Kim et al. “Prediagnostic plasma vitamin C and risk of gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population.” American journal of clinical nutrition vol. 98,5 (2013): 1289-97.

(2013) Viviana Ulloa, etal. “Human choroid plexus papilloma cells efficiently transport glucose and vitamin C.” Journal of Neurochemistry. 127: 403-414, 2013.

(2013) Alexander B, Fishman AI, Eshghi M, Choudhury M, Konno S. “Induction of cell death in renal cell carcinoma with combination of D-fraction and vitamin C.” Integr Cancer Ther. 2013;12:442–448.

(2013) C.M. Stephensen et al. “Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer.” Cancer Chemotherapy Pharmacology, 2013, Jul;72(1):139-46

(2013) Putchala MC, Ramani P, Sherlin HJ, Premkumar P, Natesan A.  “Ascorbic acid and its pro-oxidant activity as a therapy for tumours of oral cavity -- a systematic review.”  Arch Oral Biol. 2013 Jun;58(6):563-74. doi: 10.1016/j.archoralbio.2013.01.016. Epub 2013 Mar 8. PMID: 23477602.

(2014) Ma Y, Chapman J, Levine M, et al. “High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.” Sci Transl Med 6 (222): 222ra18, 2014.

(2014) Riordan H, Riordan N, et al. “The Riordan intravenous vitamin C (IVC) protocol for adjunctive cancer care: IVC as a chemotherapeutic and biological response modifying agent.” In: “The orthomolecular treatment of chronic disease”, edited by AW Saul, Basic Health Publications, Inc. 2014, 750-766.

(2014) Carr, Anitra C et al. “The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life.” Frontiers in oncology vol. 4 283. 16 Oct. 2014, doi:10.3389/fonc.2014.00283

(2014) Fritz, H., Flower, G., Weeks, L., Cooley, K., Callachan, M., McGowan, J. Seely, D. “Intravenous Vitamin C and Cancer: A Systematic Review.” Integrative Cancer Therapies, 13(4), 280–300.

(2014) H.S. Kiziltan.  “Ascorbic-acid Treatment for Progressive Bone Metastases After Radiotherapy: A Pilot Study.”  Alternative Therapies in Health and Medicine, 2014, Oct;20 Suppl 2:16-20.

(2014) Chakraborthy A, Ramani P, Sherlin HJ, Premkumar P, Natesan A.  “Antioxidant and pro-oxidant activity of Vitamin C in oral environment.” Indian J Dent Res. 2014 Jul-Aug;25(4):499-504. doi: 10.4103/0970-9290.142547. PMID: 25307916.

(2015) Jocelyn Kaisar.  “Vitamin C kills tumor cells with hard-to-treat mutation.” Science.  November 5, 2015. doi:10.1126/science.aad7397

(2015) Michael J. Gonzalez NMD, DSc, PhD, FANMA, FACN, Jorge R. Miranda-Massari PharmD, Jorge Duconge PhD,  Miguel J. Berdiel MD.  Increasing the Effectiveness of Intravenous Vitamin C as an Anticancer Agent.  Journal of Orthomolecular Medicine Volume 32, Number 1, 2017

(2015) Hoffer, L John et al. “High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.” PloS one vol. 10,4 e0120228. 7 Apr. 2015, doi:10.1371/journal.pone.0120228

(2015) Yun, J. “Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.” Science 2015, 350, 1391–1396.

(2015) J. Du et al. “Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer”. Cancer Research, 2015, Aug 15;75(16):3314-26. doi: 10.1158/0008-5472.CAN-14-1707. Epub 2015, Jun 16

(2015) M.S. Seo et al. “High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma.” Yonsei Medical Journal, 2015, Sep;56(5):1449-52. doi: 10.3349/ymj.2015.56.5.1449

(2015) Raymond, Y. C. F., Glenda, C. S. L., & Meng, L. K. (2015). “Effects of High Doses of Vitamin C on Cancer Patients in Singapore.” Integrative Cancer Therapies, 15(2), 197–204. https://doi.org/10.1177/1534735415622010

(2016) Nina Mikirova, Neil Riordan, Joseph Casciari.  “Modulation of Cytokines in Cancer Patients by Intravenous Ascorbate Therapy.” Medical Science Monitor. 2016; 22:14-25

(2016) Rosário PW, Batista KC, Calsolari MR. “Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants).”  Arch Endocrinol Metab. 2016 Aug;60(4):328-32. doi: 10.1590/2359-3997000000128. Epub 2016 Feb 23. PMID: 26910631.

(2016) Lauren Rouleau, Anil Noronha Antony, Sara Bisetto, Andrew Newberg, Cataldo Doria, Mark Levine, Daniel A. Monti, and Jan B. Hoek  “Synergistic effects of ascorbate and sorafenib in hepatocellular carcinoma: New insights into ascorbate cytotoxicity.” Free Radic Biol Med . 2016 June ; 95: 308–322. doi:10.1016/j.freeradbiomed.2016.03.031.

(2016) Y.C Raymond et al. “Effects of High Doses of Vitamin C on Cancer Patients in Singapore: Nine Cases.” Integral Cancer Therapy, 2016, Jun;15(2):197-204. doi: 10.1177/1534735415622010. Epub 2015 Dec 17.

(2016) N. Mikirova et al. “High-Dose Intravenous Vitamin C Treatment of a Child with Neurofibromatosis Type 1 and Optic Pathway Glioma: A Case Report.”  https://www.ncbi.nlm.nih.gov/pubmed/27773919, American Journal of Case Reports. 2016, Oct 24;17:774-781.

(2016) G.V Frajese et al. “Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro.” Oncology Letters, 2016, Jun;11(6):4224-4234. Epub 2016, Apr 27

(2017) University of Iowa Health Care. “Why High Dose Vitamin C Kills Cancer Cells.”  Science Daily.  January 9, 2017. file:///C:/Users/krisr06/Documents/Clinic%20Business/IV.IMJ%20Therapy/Why%20high-dose%20vitamin%20C%20kills%20cancer%20cells_%20Science%20Daily%202017.html

(2017) Schoenfeld, Joshua D. et al. “O₂^⋅− and H₂O₂-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate.”  Cancer Cell, Volume 31 , Issue 4 , 487 - 500.e8

(2017) Jennifer Brown. “High-dose vitamin C proves safe and well-tolerated in brain and lung cancer trials.”  Study identifies flaws in cancer cell metabolism that make high-dose vitamin C toxic to tumor cells.  University of Iowa.

(2017) “High doses of vitamin C to improve cancer treatment passes human safety trial.”  Science Daily, Cell Press. March 30, 2017.

(2017) Xia, Jiliang et al.  “Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid.” EBioMedicine, Volume 18 , 41 – 49.

(2017) Brickner, et al.  “Abstract CT061: Novel safety of high dose ascorbic acid and induction chemotherapy for high risk pancreatic cancer.” AACR Publications. 10.1158/1538-7445.AM2017-CT061 Published July 2017

(2017) Cimmino, Luisa, et al. “Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression.” Cell. Volume 170, Issue 6, P1079-1095.E20, September 07, 2017. (High dose Vitamin C.

(2017) Gonzalez, et al. “High Dose IV Vitamin C and Metastatic Breast Cancer: A Case Report.” J Orthmol Med. 32(6)

(2017) Polireddy, et al. “High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study.” Sci Rep. 2017 Dec 7;7(1):17188. doi: 10.1038/s41598-017-17568-8.

(2017) Agathocleous, et al. “Ascorbate regulates haematopoietic stem cell function and leukaemogenesis.” Nature. 2017 Sep 28;549(7673):476-481. doi: 10.1038/nature23876. Epub 2017 Aug 21.

(2017) Violet, et al. “Pharmacologic Ascorbate in Myeloma Treatment: Doses Matter.” EBioMedicine 2017, 18, 9–10

(2017) Shenoy, et al. “Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells.”  Blood Cancer J. 2017, 7, e587.

(2017) Roa, Francisco J et al. “Therapeutic Use of Vitamin C in Cancer: Physiological Considerations.” Frontiers in pharmacology vol. 11 211. 3 Mar. 2020, doi:10.3389/fphar.2020.00211

(2017) Mastrangelo D, Massai L, Fioritoni G, et al. “High Doses of Vitamin C and Leukaemia: In Vitro Update.” Advanced Leuk Res Treat. 1(1):5-19, 2017.

(2017) Clinical Trial Phase 3. “IV ascorbic acid in advanced gastric cancer.”  https://clinicaltrials.gov/ct2/show/NCT03015675.

(2017) University of Iowa Health Care. “Why high-dose vitamin C kills cancer cells: Low levels of catalase enzyme make cancer cells vulnerable to high-dose vitamin C.”  Science Daily.  January 9, 2017. https://www.sciencedaily.com/releases/2017/01/170109134014.htm.

(2017) University of Iowa Health Care. “High-dose vitamin C proves safe and well-tolerated in brain and lung cancer trials.” March 30, 2017. https://now.uiowa.edu/2017/03/high-dose-vitamin-c-proves-safe-and-well-tolerated-brain-and-lung-cancer-trials

(2017) Schoenfeld et al.  “O2 ,– and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate.” Cancer Cell 31, 487–500 April 10, 2017

(2017) Magdelana Kegel.  “High-dose vitamin C may be effective against lymphoma, other blood cancers, say researchers.”  Lymphoma News Today. August 21, 2017 https://lymphomanewstoday.com/2017/08/21/high-dose-vitamin-c-seen-to-fight-lymphoma-other-blood-cancers/

(2017) Hosokawa Y et al. “Ascorbic acid does not reduce the anticancer effect of radiotherapy.” Biomed Rep., 2017, Jan;6(1):103-107

(2018) Michael Greger. “The vitamin C study that started it all.” Nutritionfacts.org. https://nutritionfacts.org/2018/06/14/the-vitamin-c-cancer-study-that-started-it-all/.  Non-Hodgkins Lymphoma.

(2018) Jeanne A. Drisko, Oscar K. Serrano, Lisa R. Spruce, Qi Chen and Mark Levine.  Treatment of pancreatic cancer with intravenous vitamin C: a case report.  Anti-Cancer Drugs 2018, 29:373–379

(2018) Klimant, E., Wright, H., Rubin, D., Seely, D., & Markman, M. (2018). Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Current Oncology, 25(2), 139–148. http://doi.org/10.3747/co.25.3790

(2018) Sant DW, Mustafi S, Gustafson CB, Chen J, Slingerland JM, Wang G. Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression. Scientific Reports. 2018;8:5306. doi:10.1038/s41598-018-23714-7.

(2018) El Halabi, Ibrahim et al. “Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications” International journal of molecular sciences vol. 19,9 2752. 13 Sep. 2018, doi:10.3390/ijms19092752

(2018) Baillie, Nicola et al. “The Use of Intravenous Vitamin C as a Supportive Therapy for a Patient with Glioblastoma Multiforme.” Antioxidants (Basel, Switzerland) vol. 7,9 115. 30 Aug. 2018, doi:10.3390/antiox7090115

(2018) Yuen Chuen Fong Raymond, et al.  “High-Dose Vitamin C Helps Prevent Recurrence of Stage IV Ovarian Cancer: A Case Report.” International Society for Orthomolecular Medicine. Vol. 33, No. 4.

(2018) Foster, et al. “Intravenous Vitamin C Administration Improved Blood Cell Counts and Health-Related Quality of Life of Patient with History of Relapsed Acute Myeloid Leukaemia.” Antioxidants 2018, 7, 92; doi:10.3390/antiox7070092.

(2018) Carr, Cook.  “Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge.” Front. Physiol., 23 August 2018 | https://doi.org/10.3389/fphys.2018.01182

(2018) Cimmino, L., Neel, B., & Aifantis, I. “Vitamin C in STEM cell reprogramming and cancer - cell press.” Trends in Cell Biology. https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(18)30064-3

(2018) Lv, H., Wang, C., Fang, T. et al.  “Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2.” npj Precision Onc 2, 1 (2018) doi:10.1038/s41698-017-0044-8

(2018) Schoenfeld, Joshua D et al. “Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue.” Seminars in radiation oncology vol. 29,1 (2019): 25-32. doi:10.1016/j.semradonc.2018.10.006

(2018) Mingay, M. et al. “Vitamin C-induced epigenomic remodeling in IDH1 mutant acute myeloid leukaemia.” Leukemia 32, 11–20 (2018).

(2018) Pires, Ana S et al. “Ascorbic Acid Chemosensitizes Colorectal Cancer Cells and Synergistically Inhibits Tumor Growth.” Frontiers in physiology vol. 9 911. 23 Jul. 2018, doi:10.3389/fphys.2018.00911

(2019) Blaszczak, Wiktoria et al. “Vitamin C as a Modulator of the Response to Cancer Therapy.” Molecules (Basel, Switzerland) vol. 24,3 453. 28 Jan. 2019, doi:10.3390/molecules24030453

(2019) Gonzalez, et al. “Increasing the Effectiveness of Intravenous Vitamin C as an Anticancer Agent.” International Society for Orthomolecular Medicine. Volume 34, Number 2, 2019.

(2019) Lee, et al. “Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells.” Anticancer Res. 2019 Feb;39(2):751-758. doi: 10.21873/anticanres.13172.

(2019) Gonzalez, et al. “High dose IV Vitamin C and Breast Cancer: A case report.” International Society for Orthomolecular Medicine. 32(6). 2019.https://isom.ca/article/high-dose-iv-vitamin-c-metastatic-breast-cancer-case-report/

(2019) Pena E, et al. “Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer.” Free Radic Biol Med. 2019 May 1;135:283-292. doi: 10.1016/j.freeradbiomed.2019.03.015. Epub 2019 Mar 19.

(2019) Pawlowska, Elzbieta et al. “Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.” Oxidative medicine and cellular longevity vol. 2019 7286737. 24 Dec. 2019, doi:10.1155/2019/7286737

(2019) van Gorkom, Gwendolyn N Y et al. “The Effect of Vitamin C (Ascorbic Acid) in the Treatment of Patients with Cancer: A Systematic Review.” Nutrients vol. 11,5 977. 28 Apr. 2019, doi:10.3390/nu11050977

(2019) Das, A.B., Kakadia, P.M., Wojcik, D. et al. “Clinical remission following ascorbate treatment in a case of acute myeloid leukemia with mutations in TET2 and WT1.” Blood Cancer J. 9, 82 (2019). https://doi.org/10.1038/s41408-019-0242-4

(2019) Behnaz Abiri, Mohammadreza Vafa.  “Vitamin C and Cancer: The Role of Vitamin C in Disease Progression and Quality of Life in Cancer Patients.”  Nutrition and Cancer 25, 1-11.
Online publication date: 21-Jul-2020.

(2019) Roomi MW, et al. “A novel nutrient mixture induces apoptosis in human mesothelioma cells (MTSO-211H0 via activation of capsases).” Glob J Cancer Ther 5(1):007-011. DOI: 10.17352/2581-5407.000024 (Vit C, green tea, lysine, proline)

(2019) Ngo B, Van Riper JM, Cantley LC, Yun J. “Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer.” 2019 May;19(5):271-282. doi: 10.1038/s41568-019-0135-7. PMID: 30967651; PMCID: PMC6526932.

(2019) Su X, Shen Z, Yang Q, Sui F, Pu J, Ma J, Ma S, Yao D, Ji M, Hou P. “Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms.” Theranostics. 2019 Jun 9;9(15):4461-4473. doi: 10.7150/thno.35219. PMID: 31285773; PMCID: PMC6599666.

(2019) Gillberg L, Ørskov AD, Nasif A, Ohtani H, Madaj Z, Hansen JW, Rapin N, Mogensen JB, Liu M, Dufva IH, Lykkesfeldt J, Hajkova P, Jones PA, Grønbæk K. “Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes.” Clin Epigenetics. 2019 Oct 17;11(1):143. doi: 10.1186/s13148-019-0739-5. PMID: 31623675; PMCID: PMC6798470.

(2020) Roa, Francisco J et al. “Therapeutic Use of Vitamin C in Cancer: Physiological Considerations.” Frontiers in pharmacology vol. 11 211. 3 Mar. 2020, doi:10.3389/fphar.2020.00211

(2020) Choi YK, Kang JI, Han S, et al. “L-Ascorbic Acid Inhibits Breast Cancer Growth by Inducing IRE/JNK/CHOP-Related Endoplasmic Reticulum Stress-Mediated p62/SQSTM1 Accumulation in the Nucleus.” Nutrients. 2020;12(5):1351. Published 2020 May 8. doi:10.3390/nu12051351

(2020) Codini, M. “Why Vitamin C Could Be an Excellent Complementary Remedy to Conventional Therapies for Breast Cancer.” International Journal of Molecular Sciences, 21(21), E8397. https://doi.org/10.3390/ijms21218397

(2020) Behnaz Abiri, Mohammadreza Vafa. “Vitamin C and Cancer: The Role of Vitamin C in Disease Progression and Quality of Life in Cancer Patients.”  Nutrition and Cancer 25, 1-11. Online publication date: 21-Jul-2020.

(2020) Anderson, Paul. “Intravenous Ascorbate and oncological agents.”

(2020) Magrì, A., Germano, G., Lorenzato, A., Lamba, S., Chilà, R., Montone, M., Amodio, V., Ceruti, T., Sassi, F., Arena, S., Abrignani, S., D’Incalci, M., Zucchetti, M., Nicolantonio, F. D., & Bardelli, A.  “High-dose vitamin C enhances cancer immunotherapy.” Science Translational Medicine, 12(532). https://doi.org/10.1126/scitranslmed.aay8707

(2020) Park, Hyunwoo et al. “The Effect of High Dose Intravenous Vitamin C During Radiotherapy on Breast Cancer Patients' Neutrophil-Lymphocyte Ratio.” Journal of alternative and complementary medicine (New York, N.Y.) vol. 26,11 (2020): 1039-1046. doi:10.1089/acm.2020.0138

(2020) Luchtel RA, Bhagat T, Pradhan K, Jacobs WR Jr, Levine M, Verma A, Shenoy N. “High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model.” Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1666-1677. doi: 10.1073/pnas.1908158117. Epub 2020 Jan 7. PMID: 31911474; PMCID: PMC6983418.

(2020) Kaźmierczak-Barańska J, Boguszewska K, Adamus-Grabicka A, Karwowski BT. “Two Faces of Vitamin C-Antioxidative and Pro-Oxidative Agent.” Nutrients. 2020 May 21;12(5):1501. doi: 10.3390/nu12051501. PMID: 32455696; PMCID: PMC7285147. Addresses radiation treatments.

(2020) Ou, J., Zhu, X., Zhang, H., Du, Y., Chen, P., Wang, J., Peng, X., Bao, S., Zhang, X., Zhang, T., & Clifford. “A Retrospective Study of Gemcitabine and Carboplatin With or Without Intravenous Vitamin C on Patients With Advanced Triple-Negative Breast Cancer. Integrative Cancer Therapies.” 19, 153473541989559-153473541989559. https://doi.org/10.1177/1534735419895591

(2020) Antonio Viana do Nascimento Filho,et al. “Vitamin C Protects Against Doxorubicin-Induced Muscle Oxidative Stress.” The FASEB Journal. 13 May 2022, Vol 36, Issue S1.

https://doi.org/10.1096/fasebj.2022.36.S1.R5111. Vitamin C protects against doxorubicin-induced skeletal muscle atrophy and oxidative stress, suggesting a potential approach to management cardio functional disorder in patients under doxorubicin treatment.

(2021) Abiri B, Vafa M. “Vitamin C and Cancer: The Role of Vitamin C in Disease Progression and Quality of Life in Cancer Patients.” Nutr Cancer. 2021;73(8):1282-1292. doi: 10.1080/01635581.2020.1795692. Epub 2020 Jul 21. PMID: 32691657.

(2021) Böttger F, Vallés-Martí A, Cahn L, Jimenez CR. “High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.” J Exp Clin Cancer Res. 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y. PMID: 34717701; PMCID: PMC8557029.

(2021) Böttger, Franziska et al. “High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.” Journal of experimental & clinical cancer research : CR vol. 40,1 343. 30 Oct. 2021, doi:10.1186/s13046-021-02134-y

(2021) HAMAGUCHI, R., NARUI, R., MORIKAWA, H., & WADA, H. “Improved Chemotherapy Outcomes of Patients With Small-cell Lung Cancer Treated With Combined Alkalization Therapy and Intravenous Vitamin C.” Cancer Diagnosis & Prognosis, 1(3), 157–163. https://doi.org/10.21873/cdp.10021

(2022) Mohseni S, Tabatabaei-Malazy O, Ejtahed HS, Qorbani M, Azadbakht L, Khashayar P, Larijani B. “Effect of vitamins C and E on cancer survival; a systematic review.” Daru. 2022 Sep 22. doi: 10.1007/s40199-022-00451-x. Epub ahead of print. PMID: 36136247.

(2022) Mussa, A., Mohd Idris, R. A., Ahmed, N., Ahmad, S., Murtadha, A. H., Tengku Din, T. A. D. A. A., Yean, C. Y., Wan Abdul Rahman, W. F., Mat Lazim, N., Uskoković, V., Hajissa, K., Mokhtar, N. F., Mohamud, R., & Hassan, R. “High-Dose Vitamin C for Cancer Therapy.” Pharmaceuticals, 15(6), 711. https://doi.org/10.3390/ph15060711

(2022) Chen, Zeyu, etal. “Vitamin Intake and Cancers: An Umbrella Review.” Front. Nutr., 20 January 2022.  Sec. Nutritional Epidemiology. Volume 8-2021. https://doi.org/10.3389/fnut.2021.812394

(2022) Khazaei S, Nilsson L, Adrian G, Tryggvadottir H, Konradsson E, Borgquist S, Isaksson K, Ceberg C, Jernström H.  “Impact of combining vitamin C with radiation therapy in human breast cancer: does it matter?” Oncotarget. 2022 Feb 22;13:439-453. doi: 10.18632/oncotarget.28204. PMID: 35222809; PMCID: PMC8863110.

(2023) Fan D, Liu X, Shen Z, Wu P, Zhong L, Lin F. “Cell signaling pathways based on vitamin C and their application in cancer therapy.” Biomed Pharmacother. 2023 Jun;162:114695. doi: 10.1016/j.biopha.2023.114695. Epub 2023 Apr 13. PMID: 37058822. Addresses radiation therapy.

Vitamin C and Infection

(2007) Hemilä H, Louhiala P. “Vitamin C may affect lung infections.” J R Soc Med. 2007 Nov;100(11):495-8. doi: 10.1177/014107680710001109. PMID: 18048704; PMCID: PMC2099400.

(2012) Kallio J, Jaakkola M, Mäki M, Kilpeläinen P, Virtanen V. “Vitamin C inhibits staphylococcus aureus growth and enhances the inhibitory effect of quercetin on growth of Escherichia coli in vitro.” Planta Med. 2012 Nov;78(17):1824-30. doi: 10.1055/s-0032-1315388. Epub 2012 Oct 11. PMID: 23059632.

(2017) Hemilä H. “Vitamin C and Infections.” Nutrients. 2017 Mar 29;9(4):339. doi: 10.3390/nu9040339. PMID: 28353648; PMCID: PMC5409678.

(2019) Ngo B, Van Riper JM, Cantley LC, Yun J. “Targeting cancer vulnerabilities with high-dose vitamin C.” Nat Rev Cancer. 2019 May;19(5):271-282. doi: 10.1038/s41568-019-0135-7. PMID: 30967651; PMCID: PMC6526932.

(2020) Magrì A, Germano G, Lorenzato A, Lamba S, Chilà R, Montone M, Amodio V, Ceruti T, Sassi F, Arena S, Abrignani S, D'Incalci M, Zucchetti M, Di Nicolantonio F, Bardelli A. “High-dose vitamin C enhances cancer immunotherapy.” Sci Transl Med. 2020 Feb 26;12(532):eaay8707. doi: 10.1126/scitranslmed.aay8707. PMID: 32102933.

(2021) Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. “High-Dose Vitamin C in Advanced-Stage Cancer Patients.” Nutrients. 2021 Feb 26;13(3):735. doi: 10.3390/nu13030735. PMID: 33652579; PMCID: PMC7996511.

(2021) Böttger F, Vallés-Martí A, Cahn L, Jimenez CR. “High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.” J Exp Clin Cancer Res. 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y. PMID: 34717701; PMCID: PMC8557029.

(2021) Giansanti M, Karimi T, Faraoni I, Graziani G. “High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients.” Cancers (Basel). 2021 Mar 20;13(6):1428. doi: 10.3390/cancers13061428. PMID: 33804775; PMCID: PMC8003833.

 

VITAMIN D

(2004) Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004; 79:362-71.

(2006) Garland, C. F., Garland, F. C., Gorham, E. D., Lipkin, M., Newmark, H., Mohr, S. B., & Holick, M. F. “The Role of Vitamin D in Cancer Prevention.” American Journal of Public Health, 96(2), 252–261. http://doi.org/10.2105/AJPH.2004.045260

(2007) Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst. 2007; 99:1120-9.

(2007) Garland CF, Gorham ED, Mohr SB, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007; 103:708-11.

(2007) Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007; 32:210-6.

(2008) Joyce Maalouf, Mona Nabulsi, Reinhold Vieth, Samantha Kimball, Rola El-Rassi, Ziyad Mahfoud, and Ghada El-Hajj Fuleihan. Short term and long term safety of weekly high dose vitamin D₃ supplementation in school children. J. Clin. Endocrinol. Metab., Published April 29, 2008 DOI: 10.1210/jc.2007-2530

(2009) Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009; 19:468-83.

(2009) Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk.  Aliment Pharmacol Ther. 2009; 30:113-25.

(2011) Takako Araki, Michael F. Holick, Bianca D. Alfonso, Esti Charlap, Carla M. Romero, Dahlia Rizk, Lisa G. Newman; Vitamin D Intoxication with Severe Hypercalcemia due to Manufacturing and Labeling Errors of Two Dietary Supplements Made in the United States, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 12, 1 December 2011, Pages 3603–3608, https://doi.org/10.1210/jc.2011-1443

(2013) Frangou C, et al. “25(OH) Vitamin D₃ Affects Acute Myeloid Leukemia Cell Proliferation.” Blood (2013) 122 (21): 5026.

(2015) Sharon Theimer.  “Vitamin D Toxicity Rare in People Who Take Supplements.” Mayo. https://newsnetwork.mayoclinic.org/discussion/vitamin-d-toxicity-rare-in-people-who-take-supplements-mayo-clinic-study-finds/ Clinic Study Finds

(2015) Park S, Lee DH, Jeon JY, Ryu J, Kim S, Kim JY, Park HS, Kim SI, Park BW. “Serum 25-hydroxyvitamin D deficiency and increased risk of breast cancer among Korean women: a case-control study.” Breast Cancer Res Treat. 2015 Jul;152(1):147-154.

(2016) Alison M. Mondul, Stephanie J. Weinstein, Kristin A. Moy, Satu Mannisto and Demetrius Albanes. Circulating 25-hydroxyvitamin D and prostate cancer survival. Cancer Epidemiol Biomarkers Prev January 25 2016 DOI: 10.1158/1055-9965.EPI-15-0991

(2016) Kubeczko, Marcin et al. “Efficacy and safety of vitamin D supplementation in patients with chronic lymphocytic leukemia.” Postepy higieny i medycyny doswiadczalnej (Online) vol. 70,0 534-41. 21 May. 2016, doi:10.5604/17322693.1202482

(2017) Kulling, Paige M et al. “Vitamin D in hematological disorders and malignancies.” European journal of haematology vol. 98,3 (2017): 187-197. doi:10.1111/ejh.12818 (Lymphoma, leukemia)

(2017) Editorial. “Low vitamin D levels as a risk factor for cancer.” BMJ 2017;359:j4952

(2017) Pandolfi, F., Franza, L., Mandolini, C., & Conti, P. “Immune Modulation by Vitamin D: Special Emphasis on Its Role in Prevention and Treatment of Cancer.” Clinical Therapeutics, 39(5), 884–893. https://doi.org/10.1016/j.clinthera.2017.03.012

(2017) Anand, A., Singh, S., Sonkar, A. A., Husain, N., Singh, K. R., Singh, S., & Kushwaha, J. K. “Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in Advanced cancer treatment.” Contemporary Oncology/Współczesna Onkologia. https://www.termedia.pl/Expression-of-vitamin-D-receptor-and-vitamin-D-status-in-patients-with-oral-neoplasms-and-effect-of-vitamin-D-supplementation-on-quality-of-life-in-advanced-cancer-treatment,3,30175,0,1.html

(2017) Seyedalipour, Fatere et al. “High Prevalence of Vitamin D Deficiency in Newly Diagnosed Acute Myeloid Leukemia Patients and Its Adverse Outcome.” International journal of hematology-oncology and stem cell research vol. 11,3 (2017): 209-216.

(2018) Trump, D., & Aragon-Ching, J. “Vitamin D in prostate cancer.” Asian Journal of Andrology, 20(3), 244. https://doi.org/10.4103/aja.aja_14_18

(2018) Budhathoki Sanjeev, Hidaka Akihisa, Yamaji Taiki, Sawada Norie, Tanaka-Mizuno Sachiko, KuchibaAya et al. “Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort”. BMJ 2018;360 :k671

(2018) William B Grant. A Review of the Evidence Supporting the Vitamin D-Cancer Prevention Hypothesis in 2017.” Anticancer Research 38: 1121-1136 (2018)

(2018) Wilhelm CA, et al. “Effect of Vitamin D on Paclitaxel Efficacy in Triple-negative

Breast Cancer Cell Lines.” Anticancer Res. 2018 Sep;38(9):5043-5048. doi: 10.21873/anticanres.12823.

(2018) Song ZY, Yao Q, Zhuo Z, Ma Z, Chen G. “Circulating vitamin D level and mortality in prostate cancer patients: a dose-response meta-analysis.” Endocr Connect. 2018 Dec 1;7(12):R294-R303. doi: 10.1530/EC-18-0283. PMID: 30352424; PMCID: PMC6240137.

(2019) Song, Dingli et al. “Vitamin D intake, blood vitamin D levels, and the risk of breast cancer: a dose-response meta-analysis of observational studies.” Aging vol. 11,24 (2019): 12708-12732. doi:10.18632/aging.102597

(2019) Wu, X., Hu, W., Lu, L., Zhao, Y., Zhou, Y., Xiao, Z., Zhang, L., Zhang, H., Li, X., Li, W., Wang, S., Cho, C. H., Shen, J., & Li, M. “Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment.” Acta Pharmaceutica Sinica B, 9(2), 203–219. https://doi.org/10.1016/j.apsb.2018.09.002

 

(2019) SKRAJNOWSKA, D., & BOBROWSKA-KORCZAK, B. Potential Molecular “Mechanisms of the Anti-cancer Activity of Vitamin D.” Anticancer Research, 39(7), 3353–3363. https://doi.org/10.21873/anticanres.13478

(2020) Iacopo Gesmundo, et al.  “Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells.” Front. Endocrinol., 08 October 2020

(2020) Blasiak J, et al. “Vitamin D in Triple-Negative and BRCA1-Deficient Breast

Cancer-Implications for Pathogenesis and Therapy.”  Int J Mol Sci. 2020 May

23;21(10):3670. doi: 10.3390/ijms21103670.

(2020) Qin B, et al. “Intake of vitamin D and calcium, sun exposure, and risk of breast

cancer subtypes among black women.”  Am J Clin Nutr. 2020 Feb 1;111(2):396-405. doi: 10.1093/ajcn/nqz302. PMID: 31826233 Free PMC article.

(2021) Varghese, J. E., Balasubramanian, B., Velayuthaprabhu, S., Thirunavukkarasu, V., Rengarajan, R. L., Murugesh, E., Manikandan, P., Arun, M., & Anand, A. V. “Therapeutic effects of vitamin D and cancer: An overview.” Food Frontiers, 2(4), 417–425. https://doi.org/10.1002/fft2.97

 

(2021) Songyang, Y., Song, T., Shi, Z., Li, W., Yang, S., & Li, D. “Effect of vitamin D on malignant behavior of non-small cell lung cancer cells.” Gene, 768, 145309. https://doi.org/10.1016/j.gene.2020.145309

 

(2022) Vanhevel, J., Verlinden, L., Doms, S., Wildiers, H., & Verstuyf, A. “The role of vitamin D in breast cancer risk and progression.” Endocrine-Related Cancer, 29(2), R33–R55. https://doi.org/10.1530/erc-21-0182

(2022) Kanaan, Y., Copeland, R.L. “The link between vitamin D and prostate cancer.” Nat Rev Cancer 22, 435 (2022). https://doi.org/10.1038/s41568-022-00493-y

ZINC

(2013) Consolo, L., Melnikov, P., Cônsolo, F. et al. “Zinc supplementation in children and adolescents with acute leukemia.” Eur J Clin Nutr 67, 1056–1059 (2013). https://doi.org/10.1038/ejcn.2013.146

(2016) Pradhan R, et al.  “Protection against Methotrexate Induced Hepato-Renal Toxicity in Rats by Zinc and its Combination with Vitamin C and Vitamin E.” Med Safe Glo Heal 2016, 5:2 Research Article Open Access Med Safe Glo Heal, an open access journal Volume 5 • Issue 2 • 1000127

(2018) Mehrzad, Valiollah et al. “Determination Relation of the Zinc Serum Level in Acute Leukemia Adult Patients with Mucositis and Neutropenic Prevalence before and after Treatment in Isfahan' Seyed-Al-Shohada Hospital, 2012-2013.” Advanced biomedical research vol. 7 31. 16 Feb. 2018, doi:10.4103/abr.abr_7_15

(2019) Valadbeigi S, et al. “ASSESSMENT OF TRACE ELEMENTS IN SERUM OF ACUTE LYMPHOBLASTIC AND MYELOID LEUKEMIA PATIENTS.” Exp Oncol 2019 41, 1, 69–71

(2020) To PK, Do MH, Cho JH, Jung C. “Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics.” Int J Mol Sci. 2020 Apr 23;21(8):2991. doi: 10.3390/ijms21082991. PMID: 32340289; PMCID: PMC7216164.

(2021) Hoppe, C et al. “Zinc as a complementary treatment for cancer patients: a systematic review.” Clinical and experimental medicine vol. 21,2 (2021): 297-313. doi:10.1007/s10238-020-00677-6

(2022) Zhang Y, Song M, Mucci LA, Giovannucci EL. “Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study.” Eur J Epidemiol. 2022 Dec;37(12):1251-1260. doi: 10.1007/s10654-022-00922-0. Epub 2022 Nov 3. PMID: 36326979; PMCID: PMC9630799.

 

CHEMOTHERAPY and IMMUNOTHERAPY AGENTS

Drug-induced nutrient depletions: what pharmacists need to know. U.S. Pharmacist. December 17, 2019. https://www.uspharmacist.com/article/druginduced-nutrient-depletions-what-pharmacists-need-to-know/preview/uspeditorial?utm_source=TrendMD&utm_medium=cpc&utm_campaign=US_Pharmacist_TrendMD_1&origin=e0460f6eeaa658e9d31d5af2a34293e0

Riordan Clinic - IVC Protocol- https://riordanclinic.org/research-study/vitamin-c-research-ivc-protocol/

LOW DOSE (Metronomic Therapy) vs HIGH DOSE CHEMOTHERAPY

(2016) Chan et al. “Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells.” J. Exp. Med, November 2016 DOI: 10.1084/jem.20151665

(2016) “Study shows low-dose chemo keeps cancer under control.” February 24, 2016. https://medicalxpress.com/news/2016-02-low-dose-chemo-cancer.html

(2017) Xie, Xianhe et al. “Efficacy and Toxicity of Low-Dose versus Conventional-Dose Chemotherapy for Malignant Tumors: a Meta-Analysis of 6 Randomized Controlled Trials.” Asian Pacific journal of cancer prevention : APJCP vol. 18,2 479-484. 1 Feb. 2017, doi:10.22034/APJCP.2017.18.2.479

(2017) Bishnoi, R., Shah, C., Bejjanki, H. et al. “An alternative approach with a low dose and prolonged chemotherapy for palliative treatment of locally advanced, metastatic or recurrent squamous cell head and neck cancer.”  Appl Cancer Res 37, 43 (2017). https://doi.org/10.1186/s41241-017-0049-1

(2017) Cary Goldberg.  “When Cancer Can't Be Cured, Low-Dose Chemo Aims To Keep It In Check.” https://www.wbur.org/commonhealth/2017/05/19/low-dose-chemo-cancer-treatment

(2019) Nicholas C Rohs, MD. “Lower-dose chemotherapy benefits older, frail patients with advanced gastroesophageal cancer.” HemOnc Today. May 16, 2019.

(2023) Patil VM, Noronha V, Menon N, Rai R, Bhattacharjee A, Singh A, Nawale K, Jogdhankar S, Tambe R, Dhumal S, Sawant R, Alone M, Karla D, Peelay Z, Pathak S, Balaji A, Kumar S, Purandare N, Agarwal A, Puranik A, Mahajan A, Janu A, Kumar Singh G, Mittal N, Yadav S, Banavali S, Prabhash K. “Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study.” J Clin Oncol. 2023 Jan 10;41(2):222-232. doi: 10.1200/JCO.22.01015. Epub 2022 Oct 20. PMID: 36265101.

NATURAL TREATMENTS AND CHEMO/RADIATION/ IMMUNOTHERAPY

(2011) Vollbracht C, Schneider B, Leendert V, et al. “Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany.” In Vivo 25 (6): 983-90, 2011 Nov-Dec.

(2014) Ma Y, Chapman J, Levine M, et al. “High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.” Sci Transl Med 6 (222): 222ra18, 2014.

(2018) Nauman, Gina et al. “Systematic Review of Intravenous Ascorbate in Cancer Clinical Trials.” Antioxidants (Basel, Switzerland) vol. 7,7 89. 12 Jul. 2018, doi:10.3390/antiox7070089

(2018) Anitra Carr and John Cook. “Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge.” Front. Physiol., 23 August 2018 | https://doi.org/10.3389/fphys.2018.01182.  Human trials have shown no adverse effects from combining IVC with a number of different chemotherapeutic agents (e.g., carboplatin, paclitaxel, decitabine, cytarabine, aclarubicin, gemcitabine, erlotinib, and temozolomide.

(2018) Ong C.P. “High Dose Vitamin C and Low Dose Chemo Treatment Background Information”. J Cancer Sci. 2018;5(1): 4. Research has shown that intravenous high dose vitamin C in cancer therapy cannot be dismissed but that it warrants further investigation. Recent studies have made more inroads into the understanding of the role of vitamin C, bolstering more the use of the therapy by practitioners in complementary and alternative medicine. The efficaciousness of a new high dose vitamin C and low-dose chemo therapy (HiCLoChemo) reported here indicates a quantum leap in cancer treatment, which borders on the miraculous. The results of the preliminary trial on 20 patients suffering from end stage metastatic cancers, including those of the liver, lung, breast, pancreas, uterus, brain glioma, and prostate, show a remission of cancer, some complete, as confirmed by the PET/ CT images before and after the treatment protocol. The components of the treatment are not new and their variational combinations have also been used before. The key difference lies in the application of the HiCLoChemo protocol, where the vitamin C infused first, facilitates the delivery of the chemo drugs at the microenvironment of the tumor. The paper discusses the vital role of vitamin C and factors that lead to the inducement of the immune system being recruited to join in the cancer battle. The aim is to enlist cancer researchers, oncologists and cancer treatment centers to undertake clinical trials of the HiCLoChemo protocol. With confirmation of the findings, the treatment will represent a game-changer as it offers a treatment for terminal cancers that promises cancer remission at affordable cost, which is sorely needed.

ABEMACICLIB (Verzenio)

Approved for use in US 2017. Oral medication. For hormone (+), HER2 (-). Mainly metabolized by liver enzyme CYP3A4, ketoconazole will increase its blood plasma concentration. Half-life 18.3 hours, excreted primarily through feces and 5% through urine. Highest blood concentration reached after 8hrs. Bioavailability 45%. Inhibits cyclin-dependent kinase (CDK4) and cyclin-dependent kinase 6 (CDK6) stopping cell cycle at G1.

Side Effects: anemia (low RBC & WBC), decreased appetite, diarrhea, fatigue, headache, nausea, vomiting.

Interactions: ketoconazole

Conditions treated: advanced or metastatic breast cancer.

ARSENIC TRIOXIDE (Trisenox)

Approved for use in the US in 2000. IV infusion. Usually given along with tretinoin. Avoid during pregnancy. Important to monitor Thiamine (Vitamin B1) to prevent risk of brain disease.

Side Effects: Chills, cough, dry mouth, eye pain, irregular heartbeat, loss of appetite, nausea, seizures, trouble breathing, numbness of hands, feet, and lips, decreased urine output, muscle pain, and vomiting.

Interactions: with Bepridil, Cisapride, Dronedarone, Foscarnet, Levoketoconazole, Lidoflazine, Mesoridazine, Pimozide, Piperaquine, Saquinavir, Sparfloxacin, Terfenadine, Thioridazine, Ziprasidone. No known negative interactions with supplements.

Conditions Treated: newly diagnosed low-risk acute promyelocytic leukemia (APL), or those who have not responded well to other medication. May be used to treat other kinds of cancer.

(2020) Wei Tian, et al.  “Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic Trioxide via Promoting Reactive Oxygen Species-Dependent Apoptosis and Pyroptosis.” Front. Pharmacol., 21 February 2020

AZACITIDINE

Approved for use in the US in 2004. IV infusion or IM. Avoid during pregnancy. With AML might take as an oral tablet.

Side Effects: Low WBC and platelets, black tarry stool, bladder pain, bleeding gums, body aches, chills, difficulty breathing and swallowing, blood in urine, swelling of the face, arms, hands, and legs, fever.

Interactions: Cedazuridine and Methotrexate. No known negative interactions with any supplements.

Conditions Treated: French-American-British (FAB) myelodysplastic syndrome (bone marrow problem) subtypes, including refractory anemia or chronic leukemia, juvenile myelomonocytic leukemia (JMML).

(2019) Gillberg, L., Ørskov, A.D., Nasif, A. et al. “Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes.” Clin Epigenet 11, 143 (2019). https://doi.org/10.1186/s13148-019-0739-5

BENDAMUSTINE (Bendeka, Treanda)

Approved for use in the US in 2008. IV infusion. Interferes with the function of RNA and DNA.  Originated from nitrogen mustard.  Metabolized in the liver by cytochrome p450.  Eliminated through the kidneys.  Alkylating agent. Given 2 consecutive days every 21 to 28 days. Often given with Rituximab. Half-life 40 min, metabolite 3 (M3) 3hours, metabolite 4 (M4) 30min.

Side Effects: anemia, low WBC, fever, constipation, cough, nausea, diarrhea, loss of appetite, skin and mouth rash, vomiting, weight loss.

Interactions: with alcohol, caffeine, tobacco

Conditions treated: CLL, follicular lymphoma, indolent B-cell non-Hodgkin Lymphoma, small lymphocytic lymphoma, multiple myeloma, mantle cell lymphoma (MCL).

BEVACIZUMAB CARBOPLATIN (Avastin)  (Avoid green tea)

Approved in US in 2004. Usually delivered IV every 14 days. Monoclonal antibody.

Side Effects: hypertension, fatigue, diarrhea & abdominal pain, nose bleeds proteinuria, hemorrhage

Hypertension: Crataegus, hibiscus

Conditions treated: cervical cancer, colorectal cancer, glioblastoma, hepatocellular carcinoma, non-squamous non-small cell lung cancer, ovarian/fallopian tubes/primary peritoneal cancer, renal cell carcinoma.

(2014) Gao JZ, DU JL, Wang YL, Li J, Wei LX, Guo MZ. “Synergistic effects of curcumin and bevacizumab on cell signaling pathways in hepatocellular carcinoma.” Oncol Lett. 2015 Jan;9(1):295-299. doi: 10.3892/ol.2014.2694. Epub 2014 Nov 10. PMID: 25435978; PMCID: PMC4246621.

(2022) Wang G, Duan P, Wei Z, Liu F. “Curcumin sensitizes carboplatin treatment in triple negative breast cancer through reactive oxygen species induced DNA repair pathway.” Mol Biol Rep. 2022 Apr;49(4):3259-3270. doi: 10.1007/s11033-022-07162-1. Epub 2022 Jan 25. PMID: 35076853.

BLEOMYCIN (Blenoxane)- Must wait 3 days post tx for HBOT.

Approved for use in U.S. in 1973. Delivered via IV, IM, subQ. Acts by causing DNA strand breaks. Drinks lots of fluids. Typically used along with other medications. Chest X-rays are typically done every month. Half-life 2 hours. Excretion renal. May chelate metals, especially iron to produce SOD and hydroxide free radicals. Found by Japanese scientists while screening culture filtrates of Streptomyces verticillus. Lifetime cumulative dose 400 units.

Side Effects: alopecia, chills, fever, inflammation of the lungs, rash, Raynaud’s phenomenon, weight loss, vomiting.

Interactions: with Adriamycin (doxorubicin), Cytoxan (cyclophosphamide), etopophos (etoposide)

Conditions treated: cervical cancer, Hodgkin’s and non-Hodgkin’s lymphomas, ovarian cancer, testicular cancer.

BORTEZOMIB (VELCADE) (Avoid St. John’s wort, quercetin, green tea extract)

Approved for use in U.S. in 2003. Proteasome Enzyme Inhibitor. Drinks lots of fluids.

Side Effects: anemia (decreases RBC & WBC production), bleeding gums, blood in urine, tingling feelings, chest pain, fever, pale skin, painful urination, peripheral neuropathy, difficulty breathing, swollen glands, shingles, blurred vision, black tarry stool, body aches

Interactions: with rifamycin, carbamazepine, phenytoin.

Conditions treated: multiple myeloma and mantle cell lymphoma.

(2011) Nakano, et al. “Delayed treatment with vitamin C and N-acetyl-L-cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib.” Int J Hematol. 2011 Jun;93(6):727-735. doi: 10.1007/s12185-011-0850-7. Epub 2011 Apr 28.

(2020) Takács, A., Lajkó, E., Láng, O. et al. “Alpha-lipoic acid alters the antitumor effect of bortezomib in melanoma cells in vitro.” Sci Rep 10, 14287 (2020). https://doi.org/10.1038/s41598-020-71138-z

CAPECITABINE (Xeloda, F-FU)

Approved for medical use in 1998. Converts to 5-fluoropyrimidnies (5-FU). In the class fluoropyrimidines.  Monitor folate levels but do not over treat. Avoid during pregnancy.

Side Effects: abdominal pain, diarrhea, edema, fatigue, hair loss, low RBC & WBC count, nausea, rashes, vomiting, weakness.

Interactions: calcium folinate, phenytoin (Dilantin), sorivudine, warfarin and coumadin-derivative anticoagulants.

Conditions treated: breast, colorectal, and gastric cancer.

(2015) Hoffer, L John et al. “High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.” PloS one vol. 10,4 e0120228. 7 Apr. 2015, doi:10.1371/journal.pone.0120228

(2015) Mohamed SA. El-Gerbed. “Hepatoprotective effect of vitamin C on capecitabine-induced liver injury in rats.” Egypt J Exp Bio. 2015:11(1): 61-69

(2020) Aysen Altiner. “Immunosuppressive Effects of Capecitabine Chemotherapy and Protective Effects of Vitamin C.” International Journal of Academic Medicine and Pharmacy Volume: 2 Issue: 2(Volume: 2 Issue: 2):158-164

CARBOPLATIN (Paraplatin)

Approved for use in the USA in 1989. Analog of cisplatin, with less side effects. IV infusion. Avoid during pregnancy. May impact sperm health. Interferes with DNA replication. Half-life 30 hours. Excreted through the urine. Monitor kidney function.

Side Effects: anemia (low RBC and WBC counts), bleeding gums, bruising, electrolyte imbalance, nausea, numbness or tingling in fingers and toes, unusual tiredness/weakness, vomiting.

Interactions: with adenovirus, amphotericin B deoxycholate, bacitracin, cidofovir, influenza virus vaccine, palifermin, tofacitinib.

Mild interactions: with vitamin A and E

Conditions treated: brain cancer, head/neck cancer, lung cancer, neuroblastoma, NSCLC, ovarian cancer, testicular cancer, triple negative breast cancer.

(2014) Yan Ma, et al. “Pharmacological use of ascorbate acid (Vitamin C) enhanced chemosensitivity of ovarian cancer in preclinical models and reduced chemotherapy-associated toxicity in patients.” Science Translational Medicine 05 Feb 2014: 222RA18

(2015) Hoffer, L John et al. “High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.” PloS one vol. 10,4 e0120228. 7 Apr. 2015, doi:10.1371/journal.pone.0120228

(2018) Carr, Anitra C, and John Cook. “Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge.” Frontiers in physiology vol. 9 1182. 23 Aug. 2018, doi:10.3389/fphys.2018.01182 (gemcitabine, paclitaxel, carboplatin, melphalan, carfilzomib, bortezomib, cisplatin, and temozolomide)

(2018) Klimant, E. et al. “Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach.” Current Oncology, [S.l.], v. 25, n. 2, p. 139-148, apr. 2018. ISSN 1718-7729. Available at: <https://current-oncology.com/index.php/oncology/article/view/3790/2712>. Date accessed: 06 feb. 2020. doi:http://dx.doi.org/10.3747/co.25.3790.

CETUXIMAB (Erbitux)

Approved for medical use in 2004. IV infusion.  Epidermal growth factor receptor (EGFR) inhibitor. Monoclonal antibody. Magnesium wasting, leading to hypomagnesemia. Monitor electrolyte balance.

Side Effects: acne-like rash, body pain, edema, deep grooves in skin, dry skin, fever, nausea/vomiting, painful urination, rapid weight gain, tightness in chest, tingling in hands/feet, runny nose, unusual bleeding and bruising.

Interactions: Aminolevulinic acid (Levulan), thalidomide, plus 19 other moderate drug interactions.

Conditions treated: advanced colorectal cancer with wild-type KRAS, squamous cell carcinoma of the head and neck.

CISPLATIN (Avoid NAC, must wait 3 days post tx for HBOT.)

Approved for medical use in 1978. IV infusion. Half-life 1.5-3.6 hours.  Avoid photosensitive medications and supplements for 24 hours, up to 2 weeks, to reduce risk of sunburn. Avoid in pregnancy. Binds to DNA to inhibit replication. May cause hypomagnesemia, hypokalemia, hypocalcemia. Kidney toxic. May cause nerve damage, hearing loss, and hemolytic anemia. Interferes with DNA replication.

Side Effects: anemia (reduces both RBC & WBC counts), hearing issues, kidney damage, nausea/vomiting, numbness.

Interactions: Abraxane, Adriamycin (doxorubicin), Alimta, Cytoxan, Decadron (dexamethasone), Neulasta, Neupogen, taxol (paclitaxel), Taxotrene (docetaxel).

Conditions treated: brain cancer, bladder cancer, cervical cancer, esophageal cancer, head & neck cancer, lung cancer, mesothelioma, neuroblastoma, ovarian cancer, sarcomas, testicular cancer.

(1997) Smyth JF, et al. “Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomized trial.” Ann Oncol. 1997 Jun;8(6):569-73. PubMed PMID: 9261526.

(2009) Kyung Pyo Kang, Duk Hoon Kim, Yu Jin Jung, Ae Sin Lee, Sik Lee, Sang Yong Lee, Kyu Yun Jang, Mi Jeong Sung, Sung Kwang Park, Won Kim. “Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation.”  Nephrology Dialysis Transplantation, Volume 24, Issue 10, October 2009, Pages 3012-3020,  https://doi.org/10.1093/ndt/gfp242

(2011) Bhattacharyya, S., & Mehta, P. “The hepatoprotective potential of spirulina and vitamin C supplementation in cisplatin toxicity.” Food & Function, 3(2), 164-169. doi: 10.1039/c1fo10172b

(2012) Meher U. Nessa, et al. “Combinations of Resveratrol, Cisplatin and Oxaliplatin Applied to Human Ovarian Cancer Cells.” Anticancer Research. 32: 53-60 (2012)

(2013) Pillai K, Akhter J, Chua TC, Morris DL.  “Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma.” Cancer Invest. 2013 May;31(4):241-50. doi: 10.3109/07357907.2013.784777. Epub 2013 Apr 9. PMID: 23570457.

(2014) Pillai K, Ehteda A, Akhter J, Chua TC, Morris DL.  “Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells.” Anticancer Drugs. 2014 Feb;25(2):150-60. doi: 10.1097/CAD.0000000000000039. PMID: 24366282.

(2015) Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, Zakaria Z, Yahaya BH. “Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines.” Oncol Rep. 2016 Jan;35(1):13-25. doi: 10.3892/or.2015.4371. Epub 2015 Nov 2. PMID: 26531053; PMCID: PMC4699625.

(2016) Lee, Y.J.; Lee, G.J.; Yi, S.S.; Heo, S.H.; Park, C.R.; Nam, H.S.; Cho, M.K.; Lee, S.H. “Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells.”  Food Chem. Toxicol. 2016, 97, 96–107.

(2019) Lee J, Jung SY, Yang KJ, Kim Y, Lee D, Lee MH, Kim DK. “α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway.” PLoS One. 2019 Dec 26;14(12):e0226769. doi: 10.1371/journal.pone.0226769. PMID: 31877176; PMCID: PMC6932784.

(2019) Nurul Elyani Mohamad, et al. “Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo.” Integrative Cancer Therapies. November 21, 2019. https://journals.sagepub.com/doi/full/10.1177/1534735419880258#_i20

(2019) Tan BL, Norhaizan ME. “Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer.” Molecules. 2019 Jul 10;24(14):2527. doi: 10.3390/molecules24142527. PMID: 31295906; PMCID: PMC6680685.

(2020) Pillai K, Mekkawy AH, Akhter J, Badar S, Dong L, Liu AI, Morris DL. ”Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.” Am J Transl Res. 2020 Nov 15;12(11):7404-7419. PMID: 33312377; PMCID: PMC7724355.

(2021) Hussain Y, Islam L, Khan H, Filosa R, Aschner M, Javed S. “Curcumin-cisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects.” Phytother Res. 2021 Dec;35(12):6514-6529. doi: 10.1002/ptr.7225. Epub 2021 Aug 4. PMID: 34347326.

(2022) Criscuolo D, Avolio R, Parri M, Romano S, Chiarugi P, Matassa DS, Esposito F. “Decreased Levels of GSH Are Associated with Platinum Resistance in High-Grade Serous Ovarian Cancer.” Antioxidants. 2022; 11(8):1544. https://doi.org/10.3390/antiox11081544

(2022) Karami P, Othman G, Housein Z, Salihi A, Hosseinpour Feizi MA, Azeez HJ, Babaei E. “Nanoformulation of Polyphenol Curcumin Enhances Cisplatin-Induced Apoptosis in Drug-Resistant MDA-MB-231 Breast Cancer Cells.” Molecules. 2022 May 3;27(9):2917. doi: 10.3390/molecules27092917. PMID: 35566271; PMCID: PMC9104165.

(2023) Erzurumlu Y, Catakli D, Dogan HK. “Potent carotenoid astaxanthin expands the anti-cancer activity of cisplatin in human prostate cancer cells.” J Nat Med. 2023 Jun;77(3):572-583. doi: 10.1007/s11418-023-01701-1. Epub 2023 May 2. PMID: 37130999.

CYCLOPHOSPHAMIDE (Cytoxan) Avoid or take away from St. John’s wort, turmeric, curcumin, chloroquine, metformin

Approved for use in the US in 1959.  Commonly used as an oral medication via tablet/capsule (do not chew or crush up). May be delivered IV. Must increase hydration to avoid kidney and bladder side effects. Half-life 3-12 hours.

Side Effects: nausea, vomiting, loss of appetite, abdominal pain, diarrhea, darkening of skin/nails.  Temporary hair loss. Decreases bone marrow function results in low WBC, RBC and platelets.

Interactions: allopurinol, chloroquine, digoxin, phenobarbital, phenothiazines, primidone, St. John’s wort, turmeric (curcumin), voclosporin.

Conditions treated: autoimmune disease, breast cancer, leukemia, lymphoma, multiple myeloma, neuroblastoma, ovarian cancer, sarcoma, small cell lung cancer.

(2006) Mythili Y, Sudharsan PT, Sudhahar V, Varalakshmi P. “Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced hyperlipidemic cardiomyopathy.” Eur J Pharmacol. 2006 Aug 14;543(1-3):92-6. doi: 10.1016/j.ejphar.2006.06.007. Epub 2006 Jun 9. PMID: 16814280.

(2010) Prasad, Surya, etal. “Cyclophosphamide and ascorbic acid-mediated ultrastructural and biochemical changes in Dalton's lymphoma cells in vivo.” European Journal of Pharmacology. Volume 645, Issues 1–3, 25 October 2010, Pages 47-54

(2016) Alencar, Marcus,etal. “Ascorbic acid modulates doxorubicin and cyclophosphamide-induced cytogenetic damages in Sarcoma 180 cells.”  International archives of medicine. August 2016. DOI: 10.3823/2052

(2018) Melekoglu R, Ciftci O, Eraslan S, Cetin A, Basak N. “Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model.” J Ovarian Res. 2018 Apr 26;11(1):33. doi: 10.1186/s13048-018-0409-9. PMID: 29699594; PMCID: PMC5918567.

(2020) Akomolafe SF, Olasehinde TA, Oyeleye SI, Aluko TB, Adewale OO, Ijomone OM. “Curcumin Administration Mitigates Cyclophosphamide-Induced Oxidative Damage and Restores Alteration of Enzymes Associated with Cognitive Function in Rats' Brain.” Neurotox Res. 2020 Jun;38(1):199-210. doi: 10.1007/s12640-020-00205-0. Epub 2020 May 14. PMID: 32405958.

CYTARABINE

Approved for medical use in 1969. IV infusion. Half-life biphasic 10min, 1-3 hours. Excreted through kidneys.

Side effects: bone marrow suppression, vomiting, diarrhea, liver problems, rash, ulcer formation in the mouth, and bleeding.

Interactions: Measles, Mumps, Rotavirus, Rubella, Varicella, and Zoster vaccines.

Conditions treated: Acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin’s lymphoma.

(2017) Huihui Zhao, et al. “The Synergy of Vitamin C with Decitabine Activates TET2 in Leukemic Cells and Significantly Improves Overall Survival in Elderly Patients with Acute Myeloid Leukemia.” Blood (2017) 130 (Supplement 1): 1339. https://doi.org/10.1182/blood.V130.Suppl_1.1339.1339

(2018) Dinicola S, et al.  “Natural products – alpha-lipoic acid and acetyl-L-carnitine – in the treatment of chemotherapy-induced peripheral neuropathy.” European Review for Medical and Pharmacological Sciences. 2018; 22: 4739-4754.

(2019) Das, A.B., Kakadia, P.M., Wojcik, D. et al. “Clinical remission following ascorbate treatment in a case of acute myeloid leukemia with mutations in TET2 and WT1.” Blood Cancer J. 9, 82 (2019). https://doi.org/10.1038/s41408-019-0242-4

(2020) Muluken Altaye Ayza, et al.  “The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity.” Oxidative Medicine and Cellular Longevity. https://www.hindawi.com/journals/omcl/2020/4965171/

DENOSUMAB

Approved in 2010

Side Effects: bone pain, fractures,

Infection tx: usnea, Andrographis, ligusticum

Conditions treated: mets to bone and prostate, multiple myeloma

Osteonecrosis tx: Ca, MG, D3, MK4

 

DOXORUBICIN (Adriamycin, Doxil, Rubex, Caelyx) Avoid Curcumin 24 hrs each side. Avoid metformin. Must wait 3 days post tx for HBOT.

Approved in 1974. IV infusion.  Urine may have a red color for a few days after IV. Derived from Streptomyces peucetius.  Halts DNA replication.

Side effects: anemia, low WBC, hair loss, N/V, skin and mouth inflammation.

Conditions treated: breast, bladder, Kaposi’s sarcoma, lymphoma, ovarian (after failing platinum chemotherapy), ALL cancers.

(1996) Kurbacher, et al. “Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro.” Cancer letters. 103. 183-9. 10.1016/0304-3835(96)04212-7.

(1998) Antunes LM, Takahashi CS. “Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells.” Mutat Res. 1998 Nov 9;419(1-3):137-43. doi: 10.1016/s1383-5718(98)00134-x. PMID: 9804927.

(2014) Guerriero, Eliana, et al. “Vitamin C Effect on Mitoxantrone-Induced Cytotoxicity in Human Breast Cancer Cell Lines.” PLoS ONE 9(12): e115287. doi:10.1371/journal.pone. 0115287

(2014) Michaud, Christie, Byron Murray.  “Reduction in Toxicity of Doxorubicin by ᾀ-Tocopherol Succinate (Vitamin E) ad Ascorbic Acid (vitamin C) in Human Adenbocarcinoma cells.” Journal of Undergraduate Cells.  Jan 30, 2014.

(2016) Alencar, Marcus,etal. “Ascorbic acid modulates doxorubicin and cyclophosphamide-induced cytogenetic damages in Sarcoma 180 cells.”  International archives of medicine. August 2016. DOI: 10.3823/2052

(2017) Akolkar, et al. “Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.” Am J Physiol Heart Circ Physiol. 2017 Oct 1;313(4):H795-H809.

(2017) Bober, P., Alexovic, M., Talian, I. et al. “Proteomic analysis of the vitamin C effect on the doxorubicin cytotoxicity in the MCF-7 breast cancer cell line.”  J Cancer Res Clin Oncol 143, 35–42 (2017).

(2017) Gauri Akolkar, et al. “Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases.” Am J Physiol Cell Physiol 312: C418–C427, 2017.

(2018) Yi, et al. “Glutathione-triggered dual release of doxorubicin and camptothecin for highly efficient synergistic anticancer therapy.” Colloids Surf B Biointerfaces. 2018 Sep 1;169:273-279. doi: 10.1016/j.colsurfb.2018.05.025. Epub 2018 May 17.

(2018) Zhen Lui, et al. “Switching off the interactions between graphene oxide and doxorubicin using vitamin C: combining simplicity and efficiency in drug delivery.” Journal of Materials Chemistry B. Issue 8, 2018. “As a result, improvement of DOX delivery from the GO surface can be achieved using vitamin C.”

(2018) Yahuafai J, Asai T, Oku N, Siripong P. “Anticancer Efficacy of the Combination of Berberine and PEGylated Liposomal Doxorubicin in Meth A Sarcoma-Bearing Mice.” Biol Pharm Bull. 2018;41(7):1103-1106. doi: 10.1248/bpb.b17-00989. PMID: 29962406.

(2019) Shen, et al.  “Is the combinational administration of doxorubicin and glutathione a reasonable proposal?” Acta Pharmacologica Sinica volume 40, pages699–709 (2019).  Avoid glutathione supplements with doxo).

(2019) Kunter, L, et al. “The effect of neopterin alone or in combination with doxorubicin, cisplatin and Vitamin C on the viability of different hepatocellular carcinoma cell lines.” Eurasian Journal of Biological and Chemical Sciences 2 (2019): 115-119. “We found that the addition of cisplatin to the combination of neopterin and vitamin C, causes a greater decrease in cell viability of SNU-449 cells compared to the dual therapy with neopterin and vitamin C, while the addition of doxorubicin to the same dual therapy, leads to a decrease in the effectivity of it.”

(2020) Zhengzhong Wu,et al. “Exogenous Vitamin C-Triggered Surface Charge Conversion of pH/Reduction-Responsive Micelles for the Enhanced Tumor-Specific Activity of Loaded Doxorubicin.”  Molecular Pharmaceutics 2020 17 (3), 954-964

(2020) Antonio Viana do Nascimento Filho,et al. “Vitamin C Protects Against Doxorubicin-Induced Muscle Oxidative Stress.” The FASEB Journal. 13 May 2022, Vol 36, Issue S1.

https://doi.org/10.1096/fasebj.2022.36.S1.R5111. Vitamin C protects against doxorubicin-induced skeletal muscle atrophy and oxidative stress, suggesting a potential approach to management cardio functional disorder in patients under doxorubicin treatment.

(2021) Kowalska, K., Habrowska-Górczyńska, D.E., Kurczewska, D. et al. “Methylsulfonylmethane sensitizes endometrial cancer cells to doxorubicin.” Cell Biol Toxicol 37, 261–275 (2021). https://doi.org/10.1007/s10565-020-09542-4

(2021) Böttger F, Vallés-Martí A, Cahn L, Jimenez CR. “High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.” J Exp Clin Cancer Res. 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y. PMID: 34717701; PMCID: PMC8557029. Combining topoisomerase II inhibitor doxorubicin with medium dose (200 μM) VitC lead to a down-regulation of ribosomal, transcriptional and translational, as well and anti-oxidant (eg. SOD1) proteins.

DABRAFENIB

Approved 2013. Pediatrics in 2023. Half-life is 8 hours. Taken Orally, as a capsule or as a tablet dissolved in water.

Side Effects: >10%: Alopecia, Constipation, Diarrhea, Nausea, Vomiting, Fatigue, Myelosuppression, Cough, Headache, increased LFT’s. 5-10%: Hypertension, Hyperglycemia

Interactions: Bepridil, Cisapride, Dronedarone, Fluconazole, Ketoconazole, Levoketoconazole, Mavacamten, Mesoridazine, Pimozide, Piperaquine, Posaconazole, Saquinavir, Sparfloxacin, Terfenadine, Thioridazine, Ziprasidone.

Conditions treatments: melanoma

 

DABRAFENIB + TRAMETINIB

2014 combo approved to overcome resistance to dabrafenib. Both are an oral pill.

Dabrafenib (Tafinlar)- inhibits B-raf to inhibit cell growth. Approved 2013.

Trametinib (Mekinist)- inhibits MEK-1 and MEK-2. Approved in 2013.

Side effects: headache, n/v, fever, fatigue, joint pain, hair loss, peripheral edema, thickening of skin

Conditions treated: melanoma, NSCLC, anaplastic thyroid cancer, other metastatic unresectable solid tumors.

 

EXEMESTANE (Aromasin)

Approved for use in 1999. Oral medication. Half-life 24 hours. It is a steroidal aromatase inhibitor. Duration of action 4-5 days. Eliminated via urine and feces. Contraindicated in premenopausal women. Metabolized in the liver via CYP3A4.

Side Effects: acne, fatigue, headaches, hot flashes, insomnia, joint pain, nausea, weight gain.

Interactions: Carbamazepine, Rifampicin, St. John’s Wart

Conditions Treated: Postmenopausal woman with estrogen receptor positive early or advanced breast cancer. Often used after a woman has been on tamoxifen for 3 years.

5-FLUOROURACIL, 5-FU (Not compatible with NAC, may cause an elevation in CEA)

Patented in 1956, medical use 1962.  IV infusion. Believed to halt replication of DNA.

Side Effects: anemia, appetite loss, diarrhea, hair loss, inflammation of mouth and skin, n/v.

Interactions: warfarin, allopurinol, NAC

Conditions treated: anal, breast, cervical, colorectal, esophageal, gastric, pancreatic, skin. AS a cream used for actinic keratosis, basal cell carcinoma, skin warts.

(2019) Tan BL, Norhaizan ME. “Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer.” Molecules. 2019 Jul 10;24(14):2527. doi: 10.3390/molecules24142527. PMID: 31295906; PMCID: PMC6680685.

FOLFOX (folinic acid, fluorouracil, oxaliplatin)

IV infusion. Fluorouracil infused over 46 hours by a small portable pump.  Often 12 cycles, given every two weeks. May affect ability to be or get someone pregnant.

Side effects: amenorrhea, anemia, cold sensitivity, diarrhea, low WBC count, fatigue, neuropathy, nausea, stomitis.

Interactions: Adenovirus types 4 and 7, influenza virus vaccine, palifermin, BCG vaccine, germanium.

Conditions treated: colorectal cancer, mucinous ovarian cancer.

(2014) Menghua Chen, Brian H May, Iris W Zhou, Charlie C L Xue, Anthony L Zhang. “FOLFOX 4 combined with herbal medicine for advanced colorectal cancer: a systematic review.” Phytother Res 2014 Jul;28(7):976-91. doi: 10.1002/ptr.5092. Epub 2013 Dec 17.  The most frequently used herbs were Astragalus membranaceus, Panax ginseng, Atractylodes macrocephala, Poria cocos, Coix lachryma-jobi and Sophora flavescens. In experimental studies, each of these herbs has shown actions that could have contributed to improved tumor response.

(2016) James MI, Iwuji C, Irving G, Karmokar A, Higgins JA, Griffin-Teal N, Thomas A, Greaves P, Cai H, Patel SR, Morgan B, Dennison A, Metcalfe M, et al. “Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy.” Cancer Lett. 2015;364:135–41. doi: 10.1016/j.canlet.2015.05.005.

(2018) William J Mullally, Awis Naeem, Colum Dennehy, Caitriona Goggin, Jack Patrick Gleeson, John Patrick Greene, Mohammed Adam Ibrahim Dawod, Seamus O'Reilly, Deirdre O'Mahony, Derek Gerard Power, and Richard Martin Bambury. “Safety and tolerability of adjuvant FOLFOX vs. CAPOX in colon cancer: A real-world experience.” Journal of Clinical Oncology 2018 36:15

(2019) Wang, F., He, M., Wang, Z. et al. “Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer.” BMC Cancer 19, 460 (2019). https://doi.org/10.1186/s12885-019-5696-z

(2019) Howells LM, Iwuji CO, Irving GR, Barber S, Walter H, Sidat Z, et al. “Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial.” J Nutr. 2019;149(7):1133–9.

(2019) “Curcumin improves FOLFOX chemotherapy response in Colorectal Cancer patients.” Nov 4, 2019. https://addon.life/2019/11/04/curcumin-folfox-colorectal/

(2019) Dan Zhang, et al. “Network Meta-Analysis of Chinese Herbal Injections Plus the FOLFOX Regimen for the Treatment of Colorectal Cancer in China.” Integrative Cancer Therapies 1–18 © The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1534735419827098 journals.sagepub.com/home/ict

(2020) Mansouri, K., Rasoulpoor, S., Daneshkhah, A. et al. “Clinical effects of curcumin in enhancing cancer therapy: A systematic review. “BMC Cancer 20, 791 (2020). https://doi.org/10.1186/s12885-020-07256-8  FOLFOX

GEMCITIBINE (Gemzar)- no known adverse reaction with Vit C

Patented in 1983, approved for medical use in 1995. IV infusion. Acts as a faulty base pair in DNA leading to irreparable damage halting inhibition of DNA synthesis. A synthetic pyrimidine nucleoside.

Side effects: anemia, low WBC, n/v, hair loss, fever, rash, neuropathy, SOB, low libido, amenorrhea.

Interactions: adenovirus types 4 and 7 live, Cedazuridine, influenza virus vaccine quadrivalent, Palifermin, tofacitinib

Conditions treated: biliary tract, bladder, breast, cholangiocarcinoma, NSCLC, ovarian, pancreatic, testicular cancer.

(2012) Monti DA, et al. “Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.” PLoS One. 2012;7(1):e29794. doi: 10.1371/journal.pone.0029794. Epub 2012 Jan 17.

(2013) Welsh JL, Wagner BA, van't Erve TJ, et al. “Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.” Cancer Chemother Pharmacol 71 (3): 765-75, 2013.

(2016) Monti, et al.  “Intravenous vitamin C in combination with gemcitabine and erlotinib in subjects with metastatic pancreatic cancer.” DOI: 10.1200/jco.2011.29.15_suppl.e14547. Journal of Clinical Oncology 2. Published online September 22, 2016.9, no. 15_suppl

(2017) Polireddy, et al. “High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study.” Sci Rep. 2017 Dec 7;7(1):17188. doi: 10.C1038/s41598-017-17568-8.

(2020) Pillai K, Mekkawy AH, Akhter J, Badar S, Dong L, Liu AI, Morris DL. ”Enhancing the potency of chemotherapeutic agents by combination with bromelain and N-acetylcysteine - an in vitro study with pancreatic and hepatic cancer cells.” Am J Transl Res. 2020 Nov 15;12(11):7404-7419. PMID: 33312377; PMCID: PMC7724355.

HERCEPTIN (Trastuzumab, monoclonal Ab)  avoid alcohol, beef, Reishi, soy

Approved for medical use in 1998. Most often IV infusion. May be given subQ. HER2 receptor blocker, often used with Perjeta. Monoclonal antibody. Often used up to one year.

Side Effects: fever, headache, cough, n/v, rash, sleep disruption.

Interactions: cyclosporine, Daclizumab, eculizumab, etanercept, fingolimod, glatiramer, golimumab, guselkumab, infliximab, ixekizumab, leflunomide, mycophenolate.

Conditions treated: HER2-positive breast, gastric cancer.

 

HYDROXYUREA- no known adverse reaction with Vit C

Approved for medical use in 1998. Taken Orally, as a capsule or as a tablet with a glass of water. Half-life is 2-4 hours. May increase risk of developing skin cancer, avoid exposure to sunlight, use sunscreen.

Side Effects: black tarry stool, bleeding and bruising, blood in urine, chills, fever, lower back/side pain, painful urination, pale skin, sore throat, tiredness/weakness.

Interactions: any “live” vaccine, amphotericin B., Azathioprine, Baricitinib, bacillus Calmette-Guerin (BCG), cladribine, Clozapine, colchicine

Conditions treated: chronic myeloid leukemia (CML). Ovarian cancer. It may also be given together with radiation treatment for head and neck cancer.

IPILIMUMAB

Approved In 2011. A type of immunotherapy. IV Infusion. Half-life is 14.7 days.

Side effects: decreased appetite, diarrhea, difficulty sleeping, headache, itching, nausea, tiredness, weight loss.

Interactions: Leflunomide, vemurafenib, corticosteroids, and anticoagulants

Conditions treated: late-stage melanoma.

IMATINIB

Approved 2001. Half-life is about 18 hours. Taken orally as a tablet. Can be dissolved. Taken with water and a meal to prevent stomach irritation. Avoid grapefruit juice.

Side Effects: >10%: neutropenia, thrombocytopenia, fatigue, rash, diarrhea, nausea, vomiting, arthralgia, muscle cramps, cough.  5-10%: nasopharyngitis, dyspnea, hypokalemia, constipation.

Interactions: acetaminophen (Tylenol), warfarin (Coumadin), several cholesterol medications, certain antibiotics, St. John’s wortEliglustat, Flibanserin, Lomitapide, Measles virus live vaccine, Mumps virus live vaccine, Rotavirus live vaccine, Rubella virus live vaccine, Varicella virus live vaccine, Zoster live vaccine.

Conditions treated: Aggressive systemic mastocytosis (ASM), Chronic eosinophilic leukemia (CEL), Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), Gastrointestinal stromal tumors (GIST)

Side effect treatments:

• Leukopenia, neutropenia: Astragalus membranaceous, Coriolus versicolor
• Adequate protein intake
• Fatigue: Vitamin D, Vitamin B12, Iron status, Magnesium/Potassium electrolyte level/balance
• Muscle cramps/myalgia: check electrolytes and hydration status

IRINOTECAN- avoid curcumin 48 hours before/after

Approved 1996. Half-life 6-12 hours. IV infusion.

Side effects: Anxiety, changes in skin color, dark urine, dizziness, blurred vision, cold hands/feet, chest pain/discomfort, itching, loss of appetite, neuropathy, headache, swelling of legs and stomach.

Interactions: Atazanavir, Itraconazole, Ketoconazole, Measles Virus Vaccine, Live, Mumps Virus Vaccine, Live, Rotavirus Vaccine, Live, Rubella Virus Vaccine, Live, Varicella Virus Vaccine, Live, Zoster Vaccine, Live

Conditions treated: Metastatic cancer of the colon or rectum.

(2019) Tan BL, Norhaizan ME. “Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer.” Molecules. 2019 Jul 10;24(14):2527. doi: 10.3390/molecules24142527. PMID: 31295906; PMCID: PMC6680685.

METHOTREXATE

Approved 1996. Half-life 3-10 hours. Administered as a shot under your skin or into your vein.

Side effects: black tarry stool, bleeding gums, bleeding/bruising, diarrhea, blood in the urine, itching, joint pain nausea/vomiting, sores in mouth, stomach pain, trouble breathing.

Interactions: Zorprin, Excedrin (aspirin), Prolensa, Bromday (bromfenac), Lodine (etodolac), Nalfon (fenoprofen), Advil, Motrin (ibuprofen), Aleve, Naprosyn (naproxen), Doan's (magnesium salicylate), Salsalate.

Conditions treated: liver cancer, metastatic cancer of the colon or rectum, triple negative breast cancer.

(2014) Yiang, Giou-Teng et al. “Vitamin C enhances anticancer activity in methotrexate‑treated Hep3B hepatocellular carcinoma cells.” Oncology reports vol. 32,3 (2014): 1057-63. doi:10.3892/or.2014.3289

(2016) Pradhan R, et al.  “Protection against Methotrexate Induced Hepato-Renal Toxicity in Rats by Zinc and its Combination with Vitamin C and Vitamin E.” Med Safe Glo Heal 2016, 5:2 Research Article Open Access Med Safe Glo Heal, an open access journal Volume 5 • Issue 2 • 1000127

(2017) Wu CW, Liu HC, Yu YL, Hung YT, Wei CW, Yiang GT. “Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways.” Oncol Rep. 2017;37(4):2177-2184. doi:10.3892/or.2017.5439

(2017) Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H, Goudarzi M. “Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats.” Biomed Pharmacother. 2018;97:233-239. doi:10.1016/j.biopha.2017.10.113

NIVOLUMAB

Approved 2014. Half-life is 26 days. IV infusion.

Side effects: back pain, blistering of the skin, change/loss of taste, depressed mood, dizziness, fainting, hair loss, headache, itching, joint/muscle pain, loss of appetite, nausea, redness of the skin, weight gain.

Interactions: axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, dexamethasone, etrasimod, idecabtagene vicleucel, ifosfamide, lisocabtagene maraleucel, lomustine, mechlorethamine, melphalan, palifermin, procarbazine, Selinexor, thalidomide, tisagenlecleucel      Conditions treated: Classic Hodgkin lymphoma, colorectal cancer, esophageal cancer, gastric cancer, melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, Urothelial carcinoma

(2019) Cusato, Jessica et al. “Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab.” Cancers vol. 11,1 125. 21 Jan. 2019, doi:10.3390/cancers11010125

OLAPARIB

Approved 2014. Half-life is 12 hours. Taken orally, as a tablet swallowed whole. Avoid consuming grapefruits and Seville oranges while taking this medication (can increase side effects).

Side effects: > 20%: Anemia, Nausea, Vomiting, Fatigue. 10-20%: Diarrhea, Stomatitis, Decreased appetite, Headache, Dysgeusia. Data from RCTs demonstrate median increase in creatinine up to 23% from baseline.

Interactions: clarithromycin, erythromycin, phenytoin, carbamazepine, ketoconazole, itraconazole, ritonavir, cobicistat, cisplatin, docetaxel, amiodarone, diltiazim

Conditions treated: breast cancer, ovarian cancer, pancreatic cancer, prostate cancer.

OMACETAXINE

Approved in 2012. Half-life is 7 hours. Administered as a shot under your skin. Do not take if pregnant. Men should not. Father a child during treatment and up to 3 months after. Monitor CBC panel for myelosuppression and glucose levels.

Side effects: back/side pain, black tarry stool, bleeding gums, bloating of body parts, blood in urine, bloody nose, chills, fever, neuropathy, painful urination, sore throat, sores in mouth, weight gain.

Interactions: Antiplatelet drugs, aspirin, NSAID’s

Conditions treated: chronic or accelerated phase chronic myeloid leukemia (CML)

(2021) Zhang, Yu et al. “Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway.” Frontiers in oncology vol. 11 656045. 11 Aug. 2021, doi:10.3389/fonc.2021.656045

OXALIPLATIN

Approved in IV infusion. Half-life is 16 hours. Avoid pregnancy.

Side effects: abdominal pain, anemia, constipation, fatigue, fever, diarrhea, nausea, neuropathy, sensitivity to cold, vomiting.

Interactions: adenovirus types 4 and 7 live, oral, BCG vaccine live, Dronedarone, influenza virus vaccine quadrivalent, intranasal, measles and mumps vaccine, pimozide, rotavirus oral live vaccine, rubella vaccine, smallpox (vaccinia) live vaccine, thioridazine, typhoid polysaccharide vaccine, typhoid live vaccine, varicella virus live vaccine, yellow fever vaccine, zoster live vaccine

Conditions treated: colorectal cancer, ovarian cancer, cholangiocarcinoma, pancreatic adenocarcinoma.

(1986) Midander J, Deschavanne PJ, Debieu D, Malaise EP, Revesz L. “Reduced repair of potentially lethal radiation damage in glutathione synthetase-deficient human fibroblasts after X-irradiation.” Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Mar;49(3):403-13. PMID: 3485589

(2002) Gedlicka, et al. “Effective Treatment of Oxaliplatin-Induced Cumulative Poly-Neuropathy with Alpha-Lipoic Acid.”  J. Clin. Oncol. 2002; 20 (5): 3359-3361.

(2002) Cascinu S, et al. “Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.” J Clin Oncol. 2002 Aug 15;20(16):3478-83. PubMed PMID: 12177109.

(2009) Milla P, et al. “Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity.” Anticancer Drugs. 2009 Jun;20(5):396-402. PubMed PMID: 19287306.

(2009) Pujari G, Berni A, Palitti F, Chatterjee A. “Influence of glutathione levels on radiation-induced chromosomal DNA damage and repair in human peripheral lymphocytes.” Mutat Res. 2009 JunJul;677(1-2):109-10. PMID: 19386243

(2012) Meher U. Nessa, et al. “Combinations of Resveratrol, Cisplatin and Oxaliplatin Applied to Human Ovarian Cancer Cells.” Anticancer Research. 32: 53-60 (2012)

(2020) Lu Y, Wu S, Xiang B, Li L, Lin Y. “Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway.” Drug Des Devel Ther. 2020 Jan 9;14:73-85. doi: 10.2147/DDDT.S224318. PMID: 32021093; PMCID: PMC6956999.

PACLITAXEL/ DOXORUBICIN (Pacific Yew)

Approved in 1993. Half-life is 27 hours. IV Infusion.

Foods to limit with Taxol- acai, caffeine, Green tea, grapefruit, (lemon, lime, orange peel based foods), pineapple, sage, excess salt, shellfish, Soy products, Yerba Mate.

Side effects: Neutropenia, alopecia, anemia, diarrhea, joint pain, nausea, neuropathy

Interactions: adenovirus, Apalutamide, deferiprone, eluxadoline, erdafitinib, etrasimod, fexinidazole, idarubicin, idelalisib eniolisib, Lopinavir, mifepristone, nefazodone, pacritinib, palifermin, quinidine

Conditions treated: Ovarian cancer, breast cancer, non-small cell lung cancer (NSCLC), pancreatic cancer.

(1996) Kurbacher, et al. “Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro.” Cancer letters. 103. 183-9. 10.1016/0304-3835(96)04212-7.

(2004) Jazirehi, Ali R, and Benjamin Bonavida. “Resveratrol modifies the expression of apoptotic regulatory proteins and sensitizes non-Hodgkin's lymphoma and multiple myeloma cell lines to paclitaxel-induced apoptosis.” Molecular cancer therapeutics vol. 3,1 (2004): 71-84.

(2014) Ma Y, Chapman J, Levine M, et al. “High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.” Sci Transl Med 6 (222): 222ra18, 2014.

(2018) Anitra Carr and John Cook. “Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge.” Frontiers in physiology.  August 23, 2018. https://www.frontiersin.org/articles/10.3389/fphys.2018.01182/full

(2019) Tan BL, Norhaizan ME. “Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer.” Molecules. 2019 Jul 10;24(14):2527. doi: 10.3390/molecules24142527. PMID: 31295906; PMCID: PMC6680685.

(2020 Lee WH, Loo CY, Traini D, Young PM. “Development and Evaluation of Paclitaxel and Curcumin Dry Powder for Inhalation Lung Cancer Treatment.” Pharmaceutics. 2020 Dec 22;13(1):9. doi: 10.3390/pharmaceutics13010009. PMID: 33375181; PMCID: PMC7822152.

(2020) Saghatelyan T, Tananyan A, Janoyan N, Tadevosyan A, Petrosyan H, Hovhannisyan A, Hayrapetyan L, Arustamyan M, Arnhold J, Rotmann AR, Hovhannisyan A, Panossian A. “Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial.” Phytomedicine. 2020 Apr 18;70:153218. doi: 10.1016/j.phymed.2020.153218. Epub ahead of print. PMID: 32335356.

Paclitaxel overview- https://www.medicines.org.uk/emc/product/3891/smpc

PALBOCICLIB

Approved 2016. Half-life is 29 hours. Avoid grapefruit and St John/s Wort. Avoid pregnancy.

Side effects: alopecia, decreased WBC, neutrophils, and platelets, diarrhea, fatigue, infections, nausea.

Interactions: Apalutamide, atazanavir, carbamazepine, ceritinib, chloramphenicol, clarithromycin, cobicistat, conivaptan, dabrafenib, darunavir, dexamethasone

Conditions treated: breast cancer.

PEMBROLIZUMAB (Keytruda)

Approved 2014. IV infusion. Indicated when MSI-H (metastatic micro satellite instability-high) or dMRR (mismatch repair deficient) are present.

Side effects: adrenal fatigue, colitis, cough, decreased appetite, fatigue, fever, hepatitis, hypo or hyperthyroidism, fatigue, joint pain, muscle pain, pneumonitis, pruritis, rash, vitiligo.

Conditions treated: bladder cancer, breast cancer, cervical cancer, colorectal, endometrial, esophageal, head and neck, lung cancer, melanoma, Hodgkin’s lymphoma, urothelial, RCC, triple negative breast cancer.

Side effects treatments:

• Skin: consistent and frequent moisturizer application—Cocos nucifera, Shea Butter; Cocoa Butter
• Colitis: Althea off, Ulmus rubra, Curcumin, Dietary Changes, high fiber foods
• Fatigue: Intravenous therapies, Panax ginseng
• Myalgia: Magnesium, PEA
• Arthralgia: Hyaluronic acid, NEM, Boswellia
• Pneumonitis: Hedera helix

PEMETREXED (Alimata)

Approved in 2004. Half-life is 3.5 hours. IV Infusion. Avoid Pregnancy. Take B12 during treatment.

Side effects: anemia, anorexia, constipation, diarrhea, fatigue, nausea, neutropenia, rash, vomiting.

Interactions: aspirin, bacitracin, celecoxib, deferiprone, diclofenac, etodolac, ibuprofen, indomethacin, ketoprofen, meloxicam, naproxen, oxaprozin, palifermin, salsalate, sulindac, tolmetin

Conditions treated: Non-squamous Non-Small Cell Lung Carcinoma

(2016) Kai-Sheng Liao, et al. “Astaxanthin enhances pemetrexed-induced cytotoxicity by downregulation of thymidylate synthase expression in human lung cancer cells.” Regulatory Toxicology and Pahramcology. November 2016. 81.  DOI:10.1016/j.yrtph.2016.09.031.

PERJETA (Pertuzumab)

Approved in 2017. IV Infusion. Half-life is 18 days. Avoid Pregnancy. HER2 receptor blocker, often used with Herceptin.

Side effects: Alopecia, diarrhea, nausea, fatigue, rash, neuropathy, decreased appetite, vomiting, naild disorder, anemia, headache, mucosal inflammation, dry skin, Hypertension

Interactions: efgartigimod, idelalisib, rozanolixizumab

Conditions treated: breast cancer, gastric cancer.

RITUXIMAB (Rituxan)

Approved 1997 for use in U.S. IV infusion.  Monoclonal antibody.   Working against CD20 on the surface of B cells. It binds to the protein and triggers cell death. Half-life is 30-400 hours depending on dose and length of treatment.

Side Effects: >10%: leukopenia, neutropenia, thrombocytopenia, headache, chills, fever, nausea, pruritus, fatigue; 5-10%: cough, rhinitis, dizziness, myalgia, arthralgia, hyperglycemia.  Often occurs within 2 hours of treatment.

Interactions: Probiotics (Bifidobacterium infantis and Lactobacillus acidophilus)

Conditions treated: chronic lymphocytic leukemia, diffuse Large B-cell lymphoma, EBV, follicular lymphoma, myasthenia gravis, non-Hodgkin lymphoma, pemphigus vulgaris, rheumatoid arthritis

Treatments for side effects:

• Headache: Adequate hydration, CoQ10, Magnesium
• Fatigue: Panax ginseng, P. quinquefolia, Adequate protein intake, IVC
• Leukopenia, neutropenia: IVC, Vitamin D, Astragalus membranaceous, Adequate protein intake, Coriolus versicolor Grifola frondose.
• Considerations: hypo/hyperglycemia, hypomagnesemia, hypokalemia, CRP (and its association with neutropenia).

SORAFENIB

Approved 2005. Taken Orally. Half-life is 25-48 hours.

Side effects: abdominal pain, anemia anorexia, diarrhea, fatigue, nausea, rash, weight loss.

Interactions: dronedarone, Lefamulin, pimozide, saquinavir, thioridazine, ziprasidone

Conditions treated: Renal Cell Carcinoma, hepatocellular carcinoma, thyroid cancer.

(2016) Yassem M Saleh and Waleed Hammam. “Efficacy and Safety of Sorafenib in Patients with Advanced Hepatocellular Cancer.”  Journal of Cancer and Tumor International. 3(1): 1-7, 2016. doi: 10.9734/JCTI/2016/22142

(2016) Potenza N, Mosca N, Zappavigna S, Castiello F, Panella M, Ferri C, Vanacore D, Giordano A, Stiuso P, Caraglia M, Russo A. “MicroRNA-125a-5p is a downstream effector of sorafenib in its antiproliferative activity toward human hepatocellular carcinoma cells.” J Cell Physiol. 2016 Dec 16. doi: 10.1002/jcp.25744.

(2016) Mondal, A.; Bennett, L.L. “Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage.” Biomed. Pharmacother. 2016, 84, 1906–1914.

(2016) Lauren Rouleau, Anil Noronha Antony, Sara Bisetto, Andrew Newberg, Cataldo Doria, Mark Levine, Daniel A. Monti, and Jan B. Hoek  “Synergistic effects of ascorbate and sorafenib in hepatocellular carcinoma: New insights into ascorbate cytotoxicity.” Free Radic Biol Med . 2016 June ; 95: 308–322. doi:10.1016/j.freeradbiomed.2016.03.031.

(2017) Yan-jing Zhu & Bo Zheng. “New knowledge of the mechanisms of sorafenib resistance in liver cancer.” Acta Pharmacologica Sinica.  (2017) 38, 614-622.  Dio: 10.1038/aps.2017.5

TAMOXIFEN- avoid Curcumin

Approved 1997. Taken orally. Half-life 7-14 hours. Avoid pregnancy.

Side Effects: amenorrhea, hot flashes, menstrual changes, vaginal discharge.

Interactions: afatinib, anastrozole, apalutamide, atazanavir, bosutinib, ceritinib, cobicistat, conivaptan, dacomitinib, darunavir, edoxaban, enzalutamide, etrasimod, fexinidazole, fosamprenavir, idelalisib, iloperidone, indinavir, ivosidenib, letrozole.

Conditions treated: breast cancer.

(2010) Muralikrishnan G, Amanullah S, Basha MI, Boopalan S, Vijayakumar S, Shakeel F. “Effect of vitamin C on lipidperoxidation and antioxidant status in tamoxifen-treated breast cancer patients.” Chemotherapy. 2010;56(4):298-302. doi: 10.1159/000320030. Epub 2010 Aug 13. PMID: 20714147. The results compared vitamin C-treated breast cancer patients with normal individuals and showed that co-administration of vitamin C is more beneficial in breast cancer patients treated with tamoxifen.

(2014) Subramani, et al. “Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen.” Journal of Cellular and Molecular Medicine. 2014 Feb;18(2):305-13. doi: 10.1111/jcmm.12188. Epub 2013 Nov 25.

TAXOTERE (Docetaxel) avoid grapefruit it increases blood levels of the medication.

Approved 2004. IV Infusion. Half-life 11 hours. Avoid pregnancy.

Side Effects: alopecia, anemia, fatigue, leukopenia, neutropenia, weakness.

Interactions: adenovirus types 4 and 7 live, Apalutamide, ceritinib, chloramphenicol, deferiprone, enzalutamide, erdafitinib, etrasimod, fexinidazole, idelalisib, influenza virus vaccine

Conditions treated: breast cancer, gastric cancer, head/neck cancer, prostate cancer, non-small cell lung cancer.

(2023) Paller, Channing Judith, etal. “Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.” Meeting Abstract 2023 ASCO Annual Metting I. Genitourinary cancer- prostate, testicular, and penile. Trial did not show benefit with Vit C.  Needs further review.

TEMOZOLOMIDE

Approved 2005. IV infusion. Half-life 1.8 hours. Avoid pregnancy.

Side effects: alopecia, constipation, convulsions, headache, fatigue, lymphopenia, nausea, vomiting.

Interactions: adenovirus types 4 and 7 live, axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, deferiprone, etrasimod, idecabtagene vicleucel, influenza virus vaccine quadrivalent, adjuvanted, influenza virus vaccine trivalent, adjuvanted, lisocabtagene maraleucel, palifermin, ropeginterferon alfa, tisagenlecleucel, tofacitinib

Conditions treated: brain cancer.

(2012) Yuan Y, et al. “Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSCmtor signaling pathway.” CNS Neurosci Ther 2012;00:1-11.

(2012) Shih CM, et al. “Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy.” Free Radical Biol Med 2012;52:377-91.

(2015) Filho AZ, et al. “Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas.” Cancer Lett 2015;358:220-31.

(2015) Zhang ZS, et al. “Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy.” Oncol Lett 2015;10:379-83

(2016) Bak DH. “Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy.” Exp Ther Med 2016;11:2153-62

(2018) McConnell, Diane D et al. “Do Anti-Oxidants Vitamin D_3, Melatonin, and Alpha-Lipoic Acid Have Synergistic Effects with Temozolomide on Cultured Glioblastoma Cells?.” Medicines (Basel, Switzerland) vol. 5,2 58. 20 Jun. 2018, doi:10.3390/medicines5020058

TRAMETINIB

Approved in 2013. Taken orally as a solution, on an empty stomach. Half-life is 3.9-4.8 days.

Side Effects: alopecia, anemia, diarrhea, headache, hyperglycemia, increase in AST, leukopenia, rashes.

Interactions: Etrasimod, palifermin, cholera vaccine, dengue vaccine, desmopressin, dichlorphenamide, ponesimod, siponimod

Conditions treated: Melanoma, non-small lung cancer, thyroid cancer.

TRASTUZUMAB

Approved 1998. IV Infusion. Half-life is 28 days. Avoid pregnancy.

Side Effects: abdominal pain, anorexia, back pain, chills, cough, diarrhea, dizziness, fatigue, fever, headache, infections, insomnia, nausea, rash, vomiting, weakness.

Interactions: axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, daunorubicin, doxorubicin, doxorubicin liposomal, epirubicin, etrasimod, idarubicin, idecabtagene vicleucel, lisocabtagene maraleucel, ropeginterferon alfa 2b, tisagenlecleucel.

Conditions treated: breast cancer, gastric cancer, pancreatic cancer. 

VINBLASTINE / VINCRISTINE (Madagascar Periwinkle)

Approved in 1965. IV Infusion. Half-life is 24.8 hours. Do not breast feed during treatment.

Side Effects: alopecia, anemia, constipation, diarrhea, leukopenia, nausea, neuropathy, vomiting.

Interactions: Apalutamide, berotralstat, chloramphenicol, dabigatran, deferiprone, edoxaban, enzalutamide, erdafitinib, etrasimod, fexinidazole, idelalisib, ivosidenib, Lasmiditan, letermovir, lonafarnib, lopinavir, nefazodone, nintedanib, Palifermin, pomalidomide, Posaconazole, quinidine

Conditions treated: bladder cancer, Hodgkin’s disease, melanoma, non-small cell lung cancer, ovarian cancer, prostate cancer testicular cancer.

ZOLEDRONIC ACID (Zoledronate, Zometa)

Approved for use in the U.S. in 2001.  Administered by IV.  It’s a bisphosphonate. Blocks osteoclast cells to decrease breakdown of bone.  Avoid with kidney disease. Half-life 146 hours.

Side Effects: anemia, diarrhea, edema, fatigue, fever, hypertension, joint pain.

Interactions: gentamicin, NSAIDs (ibuprofen), tacrolimus, tobramycin

Conditions treated: bone breakdown d/t cancer, high blood calcium d/t cancer, Duchenne muscular dystrophy, osteoporosis, Paget’s disease of the bone.

IMMUNOTHERAPY Miscellaneous Information

Biologic sources

• Chimeric human-mouse drugs---end in- ximab; rituximab
• Humanized mouse drugs---end in -zumab; bevacizumab
• Fully human drugs---end in –mumab; ipilimumab

Target of the drug

• Tu---tumor
• Ci---circulatory system
• Li---immune system
• Intracellular
  • Tyrosine kinase inhibition--- -tinib; imatinib
  • Proteasome inhibition---- -zomib; bortezomib
  • Cyclin-dependent kinase inhibition--- -ciclib; seliciclib

Clinical Trials with Vitamin C and Standard of Care oncology

Pazopanib Hydrochloride with or without Ascorbic Acid in Treating Patients with Kidney Cancer That Is Metastatic or Cannot Be Removed by Surgery

(2018) Anitra Carr and John Cook. “Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge.” Front. Physiol., 23 August 2018

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TRADITIONAL ONCOLOGY TEST MARKERS (elevations)

CA 15-3 (<30 U/ml) - Healthy cells in the breast release a protein called CA 15-3. When a person has breast cancer, cancerous cells or tumors in the breast can release higher levels of CA 15-3 into the bloodstream.

• Most often used to assess treatment results, assess for advanced cancer, or check for recurrence. Not very useful for early stage or localized cancer.
• Common cancers: breast, lung, ovary, prostate.
• Non-cancerous: benign breast or ovarian disease, endometriosis, hepatitis, lactation, PID, pregnancy.

CA 27-29 (<40 U/ml)- not a screening test, used to assess treatment, recurrence, metastases.

• Common cancers: breast, colorectal, kidney, liver, lung, ovarian, pancreas, stomach, uterus.
• Non-cancerous: breast disease, first trimester of pregnancy, kidney or liver disease, lactation, ovarian cysts.

CA 19-9 (glycoprotein, <38 U/ml)- Research shows CA 19-9 levels can be significantly lower in benign than in malignant conditions.  Elevated CA 19-9 may be found in patients with benign as well as malignant disease. Therefore, it is important (1) that elevated levels of CA 19-9 are interpreted in the light of the clinical presentation of the patient and (2) to be aware of the benign conditions that can be associated with increased levels of this marker. Significantly elevated CA19-9 levels are not proof of pancreatobiliary malignancy. CA19-9 is not an ideal tumor marker and that the results of CA19-9 tests should therefore be interpreted with some caution.

• Common cancers causing elevation: pancreatic, colorectal, gallbladder, lung, ovarian.
• Non-cancerous conditions that can cause high CA 19-9 levels include: biliary infection (cholangitis), benign ovarian tumor, blockage of the bile duct (jaundice), Cystic fibrosis, gallstones, Liver disease, Pancreatitis (swelling of the pancreas). During radiation therapy, CA 19-9 levels might be raised as dying cancer cells release CA 19-9. For this reason, the test is not usually done while the patient receives radiation treatment.
• In a 2017 case report, doctors wrote that using this tumor marker to predict ovarian cancer should be avoided because it can lead to anxiety without providing a clear diagnosis.
• Preoperative CA19.9 levels cannot be used to predict whether a suspected ovarian mucinous tumour is benign, borderline or malignant. Markedly elevated serum levels (>1000 U/ml) may be found in benign mucinous neoplasms as well as in borderline and malignant tumours.
• Akdoğan M, Saşmaz N, Kayhan B, Biyikoğlu I, Dişibeyaz S, Sahin B. “Extraordinarily elevated CA19-9 in benign conditions: a case report and review of the literature.” 2001 Sep-Oct;87(5):337-9. doi: 10.1177/030089160108700513. PMID: 11765186.
• Kim, S., Park, B.K., Seo, J.H. et al.“Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases.” Sci Rep 10, 8820 (2020). https://doi.org/10.1038/s41598-020-65720-8
• Pavai S, Yap SF. “The clinical significance of elevated levels of serum CA 19-9.” Med J Malaysia. 2003 Dec;58(5):667-72. PMID: 15190651.

CA125 (Mucin-16, glycoprotein)- According to the Ovarian Cancer Research Alliance, over 80 percent of women with advanced ovarian cancer and 50 percent of those with earlier stage ovarian cancer have elevated amounts of CA-125 in their blood. In adult tissue, CA-125 is primarily expressed in mesothelial cells lining the peritoneum, fallopian tube, endometrium and pleura. The CA-125 level can be increased by various mechanisms, for instance, by increased production owing to greater cell turnover in cancer cells or increased production due to irritation or inflammation of tissue producing CA-125. Furthermore, stretch of the peritoneum and decreased clearance by the liver can cause a rise of CA-125.

• Associated cancers: endometrial, epithelial ovarian, fallopian tube, primary peritoneal. Breast, colon, gallbladder, hematological malignancy, liver, lung, pancreas.
• Benign gynecological conditions: adenomyosis, benign ovarian neoplasms, dermoid cyst, endometriosis, fibroids, functional ovarian cysts, Meig’s syndrome, menstruation, ovarian hyperstimulation, PID, pregnancy, uterine leiomyomas.
• Other benign conditions: ascites, appendicular abscess, cirrhosis and other liver disease, colitis, cystic fibrosis, diverticulitis, heart failure, myocardial infarction, myocardiopathy, pancreatitis, pericardial disease, pleural effusion, pneumonia, pulmonary embolism, recent surgery, renal insufficiency, sarcoidosis, SLE, tuberculosis peritonitis, UTI.
• The sensitivity of CA-125 is lower in premenopausal women.
• Tolman CJ, Vaid T, Schreuder HW. “Extremely elevated CA-125 in benign ovarian disease due to stretch of the peritoneum.” BMJ Case Rep. 2012 Nov 27;2012:bcr2012006664. doi: 10.1136/bcr-2012-006664. PMID: 23188839; PMCID: PMC4543764.
• Buamah P. “Benign conditions associated with raised serum CA-125 concentration.” J Surg Oncol. 2000 Dec;75(4):264-5. doi: 10.1002/1096-9098(200012)75:4<264::aid-jso7>3.0.co;2-q. PMID: 11135268.
• Sevinc A, Adli M, Kalender ME, Camci C. “Benign causes of increased serum CA-125 concentration.” Lancet Oncol. 2007 Dec;8(12):1054-1055. doi: 10.1016/S1470-2045(07)70357-1. PMID: 18054877.
• UpToDate https://www.uptodate.com/contents/image?imageKey=OBGYN%2F81621#!

CEA (Carcinoembryonic Antigen, 0-3 ng/ml)

• Cancers causing elevation: breast, colorectal, esophageal, gastric, large-cell lung, leukemia, neuroblastoma, ovarian, pancreatic, prostate, thyroid
• Non-cancerous factors, health circumstances, supplements or medications than can raise CEA in a blood test: Tobacco use (#1), chemotherapy, cirrhosis, Crohn’s disease, diverticulitis, hepatitis, hypothyroidism, kidney failure, pancreatitis, peptic ulcer, pregnancy, pulmonary emphysema, rectal polyps, ulcerative colitis, X-ray, tissue injury; medications- anticoagulants (heparin), antineoplastics (fluorouracil), staurosporine; supplements- Na butyrate.

HE4 (0-150 pmol/L)- Human epididymis protein 4 (HE4) is another tumor marker. It’s often overexpressed in epithelial ovarian cancer cells, which are cells in the outer layer of the ovary.

Mucinous Tumors

Babaier A, Ghatage P. “Mucinous Cancer of the Ovary: Overview and Current Status. Diagnostics (Basel).” 2020 Jan 19;10(1):52. doi: 10.3390/diagnostics10010052. PMID: 31963927; PMCID: PMC7168201.

 

Pain relief Options

Opioids

Long-acting opioids are called extended release (ER), long-acting (LA), controlled release (CR), and sustained release (SR). This means they release a little bit of the medication over a longer period. They are often taken once or twice a day to treat chronic pain.

Immediate release (IR) opioids are short-acting forms and release their medicine quickly over a shorter period of time. These opioids are used to treat breakthrough pain. They might be taken several times a day depending on pain level.

• Tramadol (Ultram)
• Hydromorphone (Dilaudid)
• Methadone (Dolophine, Methadose)
• Morphine (Apokyn, Avinza, Kadian, MS-Contin, and others)
• Oxycodone (OxyContin, OxyIR, Roxicodone)- may be added to aspirin, acetaminophen, or ibuprofen. Percodan has aspirin, Percocet has acetaminophen, Combunox has aspirin.
• Hydrocodone may be added to acetaminophen or ibuprofen. Vicodin and Norco have acetaminophen, Vicoprofen has ibuprofen.
• Oxymorphone (Opana)
• Fentanyl (Actiq, Duragesic, Fentora, Lazanda, Subsys, and others)
• Tapentadol (Nucynta)

Steroids

Help relieve bone pain and inflammation.

• Dexamethasone (Decadron)- corticosteroid. Long term use can result in bone loss. Can increase the antiemetic effect of ondansetron. Amy also treat hematological malignancies in combination with other chemotherapeutic drugs.
• Prednisone

NSAIDS

Over the Counter

• Acetaminophen (Tylenol)
• Aspirin
• Ibuprofen

Prescription

• Celecoxib (Celebrix)
• Diclofenac (Voltaren, Cambia)
• Indomethacin (Indocin)
• Ketorolac
• Meloxicam (Mobic)
• Nabumetone
• Naproxen
• Oxaprozin (Daypro)
• Piroxicam (Feldene)
• Sulindac

Antidepressants- treats tingling or burning pain from damaged nerves

• Amitriptyline (Elavil)
• Bupropion (Wellbutrin, Zyban)
• Imipramine (Tofranil)
• Nortriptyline (Pamelor)
• Desipramine
• Doxepin (Silenor)
• Duloxetine (Cymbalta)
• Venlafaxine (Effexor)

Antihistamines- help reduce nausea and itching

• Hydroxyzine (Atarax, Vistaril)
• Diphenhydramine (Benadryl)

Anti-anxiety Drugs- treat muscle spasms, lessen anxiety

• Diazepam (Valium)
• Lorazepam (Ativan)

Anti-convulsants- treats nerve pain that is tingling or burning

• Carbamazepine (Tegretol)
• Clonazepam (Klonopin)
• Gabapentin (Neurontin)
• Pregabalin (Lyrica)

Stimulants and amphetamines- increase the pain-relieving action of opioids and reduce drowsiness caused by opioids

• Caffeine
• Methylphenidate (Ritalin)