Hyperbaric Oxygen Therapy
- “A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities” Miguel A Ortega et al; 2021 Aug 24;57(9):864. doi: 10.3390/medicina57090864
- “Hyperbaric oxygen and radiation therapy: a review” E Fernández et al; 2021 Jun;23(6):1047-1053. doi: 10.1007/s12094-020-02513-5
- “The impact of hyperbaric oxygen therapy on late radiation toxicity and quality of life in breast cancer patients”; Marilot C T Batenburg et al; Breast Cancer Res Treat 2021 Sep;189(2):425-433. doi: 10.1007/s10549-021-06332-2. Epub 2021 Jul 19.
- “Effect of hyperbaric oxygen treatment on skin elasticity in irradiated patients”; Karan Pandey metal;Diving Hyperb Med 2022 Sep 30;52(3):208-212. doi: 10.28920/dhm52.3.208-212
Ozone Therapy
- “Potentiality of oxygen-Ozonetherapy to improve the health of aging people”; Velio Bocci et al; Curr Aging Sci 2010 Dec;3(3):177-87. doi: 10.2174/1874609811003030177
- “Ozone as a bioregulator. Pharmacology and toxicology of Ozonetherapy today”; V Bocci; Biol Regul Homeost Agents 1996 Apr-Sep;10(2-3):31-53.
- “Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study” Bernardino Clavo et al; Evid Based Complement Alternat Med 2004 Dec;1(3):321-325. doi: 10.1093/ecam/neh038. Epub 2004 Oct 16
- “Is it true that Ozone is always toxic? The end of a dogma.” Bocci V. Toxicol Appl Pharmacol. 2006 Nov 1;216(3):493-504. doi: 10.1016/j.taap.2006.06.009. Epub 2006 Jun 27
- “How a calculated oxidative stress can yield multiple therapeutic effects.” Bocci V. Free Radic Res. 2012 Sep;46(9):1068-75. doi: 10.3109/10715762.2012.693609. Epub 2012 May 28
High Dose Vitamin C
1. Bryan Ngo et al, Targeting cancer vulnerabilities with high-dose vitamin C, Nat Rev Cancer 2019 May;19(5):271-282. doi: 10.1038/s41568-019-0135-7.
2. Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, et al. High dose parenteral Ascorbate inhibited pancreatic Cancer growth and metastasis: mechanisms and a phase I/IIa study. Sci Rep. 2017;7(1):17188.
3. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci. 2008;105(32):11105–9.
2. Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, et al. High dose parenteral Ascorbate inhibited pancreatic Cancer growth and metastasis: mechanisms and a phase I/IIa study. Sci Rep. 2017;7(1):17188.
3. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci. 2008;105(32):11105–9.
4. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer Morales KL, Furqan M, et al. O 2 ·− and H 2 O 2 Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017;31(4):487–500.e8.
5. Takahashi H, Mizuno H, Yanagisawa A. High dose intravenous vitamin C improves quality of life in cancer patients. Pers Med Universe. 2012;1(1):49–53.
6. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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;25(6):983–90.
7. 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. 2007;22(1):7.
8. Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z, Crane GM, et al. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017;549(7673):476–81.
9. Bonilla‐Porras AR, Jimenez‐Del‐Rio M, Velez‐Pardo C. Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism. Cancer Cell Int. 2011;11(1):19.
10. Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, et al. Res‐ toration of TET2 Function Blocks Aberrant Self‐Renewal and Leukemia Progression. Cell. 2017;170(6):1079–1095.e20.
11. Iamsawat S, Tian L, Daenthanasanmak A, Wu Y, Nguyen HD, Bastian D, et al. Vitamin C stabilizes CD81 iTregs and enhances their therapeutic potential in controlling murine GVHD and leukemia relapse. Blood Adv. 2019;3(24):4187–201.
12. Mingay M, Chaturvedi A, Bilenky M, Cao Q, Jackson L, Hui T, et al. Vita‐ min C‐induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia. Leukemia. 2018;32(1):11–20.
13. Aguilera O, Muñoz‐Sagastibelza M, Torrejón B, Borrero‐Palacios A, del Puerto‐Nevado L, Martínez‐Useros J, et al. Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget. 2016;7(30):47954–65.
14. Brandt KE, Falls KC, Schoenfeld JD, Rodman SN, Gu Z, Zhan F, et al. Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells. Redox Biol. 2018;14(July 2017):82–7
15. Cenigaonandia‐Campillo A, Serna‐Blasco R, Gómez‐Ocabo L, Solanes‐ Casado S, Baños‐Herraiz N, Del Puerto‐ Nevado L, et al. Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic KRAS mutant colon cancer. Theranostics. 2021;11(8):3595–606.
16. Mamede AC, Pires AS, Abrantes AM, Tavares SD, Gonçalves AC, Casalta‐ Lopes JE, et al. Cytotoxicity of ascorbic acid in a human colorectal adenocarcinoma cell line (WiDr): in vitro and in vivo studies. Nutr Cancer. 2012;64(7):1049–57.
17. Nakanishi K, Hiramoto K, Ooi K. High‐dose vitamin C exerts its anti‐ cancer effects in a Xenograft model of Colon Cancer by suppressing angiogenesis. Biol Pharm Bull. 2021;44(6):884–7.
18. Pires AS, Marques CR, Encarnação JC, Abrantes AM, Mamede AC, Laranjo M, et al. Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile. Eur J Cell Biol. 2016;95(6–7):208–18.
19. Wang G, Yin T, Wang Y. In vitro and in vivo assessment of high‐dose vitamin C against murine tumors. Exp Ther Med. 2016;12(5):3058–62.
20. Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by target‐ ing GAPDH. Science (80‐ ). 2015;350(6266):1391–6.
21. Nakanishi K, Hiramoto K, Sato EF, Ooi K. High‐dose vitamin C adminis‐ tration inhibits the invasion and proliferation of melanoma cells in mice ovary. Biol Pharm Bull. 2021;44(1):75–81.
22. Chen XY, Chen Y, Qu CJ, Pan ZH, Qin Y, Zhang X, et al. Vitamin C induces human melanoma A375 cell apoptosis via Bax‐ and Bcl‐2‐mediated mitochondrial pathways. Oncol Lett. 2019;18(4):3880–6.
23. Kang JS, Cho D, Kim Y‐I, Hahm E, Yang Y, Kim D, et al. L‐ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase‐8?Independent pathway. Cancer Immunol Immunother. 2003;52(11):693–8.
24. Mustafi S, Sant DW, Liu Z‐J, Wang G. Ascorbate induces apoptosis in melanoma cells by suppressing Clusterin expression. Sci Rep. 2017;7(1):3671.
25. Serrano OK, Parrow NL, Violet P‐C, Yang J, Zornjak J, Basseville A, et al. Antitumor effect of pharmacologic ascorbate in the B16 murine mela‐ noma model. Free Radic Biol Med. 2015;87:193–203.
26. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang S, et al. Mechanisms of Ascorbate‐induced cytotoxicity in pancreatic Cancer. Clin Cancer Res. 2010;16(2):509–20.
27. Pollard HB, Levine MA, Eidelman O, Pollard M. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone‐ refractory prostate cancer. In Vivo. 2010;24(3):249–55.
28. Li Z, He P, Luo G, Shi X, Yuan G, Zhang B, et al. Increased Tumoral micro‐ environmental pH improves cytotoxic effect of pharmacologic ascorbic acid in castration‐resistant prostate Cancer cells. Front Pharmacol. 2020;11:570939.
29. Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, et al. Pharmacologi‐ cal ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anti‐Cancer Drugs. 2012;23(4):437–44.
6. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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;25(6):983–90.
7. 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. 2007;22(1):7.
8. Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z, Crane GM, et al. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017;549(7673):476–81.
9. Bonilla‐Porras AR, Jimenez‐Del‐Rio M, Velez‐Pardo C. Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism. Cancer Cell Int. 2011;11(1):19.
10. Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, et al. Res‐ toration of TET2 Function Blocks Aberrant Self‐Renewal and Leukemia Progression. Cell. 2017;170(6):1079–1095.e20.
11. Iamsawat S, Tian L, Daenthanasanmak A, Wu Y, Nguyen HD, Bastian D, et al. Vitamin C stabilizes CD81 iTregs and enhances their therapeutic potential in controlling murine GVHD and leukemia relapse. Blood Adv. 2019;3(24):4187–201.
12. Mingay M, Chaturvedi A, Bilenky M, Cao Q, Jackson L, Hui T, et al. Vita‐ min C‐induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia. Leukemia. 2018;32(1):11–20.
13. Aguilera O, Muñoz‐Sagastibelza M, Torrejón B, Borrero‐Palacios A, del Puerto‐Nevado L, Martínez‐Useros J, et al. Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget. 2016;7(30):47954–65.
14. Brandt KE, Falls KC, Schoenfeld JD, Rodman SN, Gu Z, Zhan F, et al. Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells. Redox Biol. 2018;14(July 2017):82–7
15. Cenigaonandia‐Campillo A, Serna‐Blasco R, Gómez‐Ocabo L, Solanes‐ Casado S, Baños‐Herraiz N, Del Puerto‐ Nevado L, et al. Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic KRAS mutant colon cancer. Theranostics. 2021;11(8):3595–606.
16. Mamede AC, Pires AS, Abrantes AM, Tavares SD, Gonçalves AC, Casalta‐ Lopes JE, et al. Cytotoxicity of ascorbic acid in a human colorectal adenocarcinoma cell line (WiDr): in vitro and in vivo studies. Nutr Cancer. 2012;64(7):1049–57.
17. Nakanishi K, Hiramoto K, Ooi K. High‐dose vitamin C exerts its anti‐ cancer effects in a Xenograft model of Colon Cancer by suppressing angiogenesis. Biol Pharm Bull. 2021;44(6):884–7.
18. Pires AS, Marques CR, Encarnação JC, Abrantes AM, Mamede AC, Laranjo M, et al. Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile. Eur J Cell Biol. 2016;95(6–7):208–18.
19. Wang G, Yin T, Wang Y. In vitro and in vivo assessment of high‐dose vitamin C against murine tumors. Exp Ther Med. 2016;12(5):3058–62.
20. Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by target‐ ing GAPDH. Science (80‐ ). 2015;350(6266):1391–6.
21. Nakanishi K, Hiramoto K, Sato EF, Ooi K. High‐dose vitamin C adminis‐ tration inhibits the invasion and proliferation of melanoma cells in mice ovary. Biol Pharm Bull. 2021;44(1):75–81.
22. Chen XY, Chen Y, Qu CJ, Pan ZH, Qin Y, Zhang X, et al. Vitamin C induces human melanoma A375 cell apoptosis via Bax‐ and Bcl‐2‐mediated mitochondrial pathways. Oncol Lett. 2019;18(4):3880–6.
23. Kang JS, Cho D, Kim Y‐I, Hahm E, Yang Y, Kim D, et al. L‐ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase‐8?Independent pathway. Cancer Immunol Immunother. 2003;52(11):693–8.
24. Mustafi S, Sant DW, Liu Z‐J, Wang G. Ascorbate induces apoptosis in melanoma cells by suppressing Clusterin expression. Sci Rep. 2017;7(1):3671.
25. Serrano OK, Parrow NL, Violet P‐C, Yang J, Zornjak J, Basseville A, et al. Antitumor effect of pharmacologic ascorbate in the B16 murine mela‐ noma model. Free Radic Biol Med. 2015;87:193–203.
26. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang S, et al. Mechanisms of Ascorbate‐induced cytotoxicity in pancreatic Cancer. Clin Cancer Res. 2010;16(2):509–20.
27. Pollard HB, Levine MA, Eidelman O, Pollard M. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone‐ refractory prostate cancer. In Vivo. 2010;24(3):249–55.
28. Li Z, He P, Luo G, Shi X, Yuan G, Zhang B, et al. Increased Tumoral micro‐ environmental pH improves cytotoxic effect of pharmacologic ascorbic acid in castration‐resistant prostate Cancer cells. Front Pharmacol. 2020;11:570939.
29. Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, et al. Pharmacologi‐ cal ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anti‐Cancer Drugs. 2012;23(4):437–44.
30. Ramezankhani B, Taha MF, Javeri A. Vitamin C counteracts miR‐302/367‐in‐ duced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity. J Cell Physiol. 2019;234(3):2672–82.
31. Xu Y, Guo X, Wang G, Zhou C. Vitamin C inhibits metastasis of peritoneal tumors by preventing spheroid formation in ID8 murine epithelial peritoneal Cancer model. Front Pharmacol. 2020;11:645.
32. Gregoraszczuk EL, Zajda K, Tekla J, Respekta N, Zdybał P, Such A. Vitamin C supplementation had no side effect in non‐cancer, but had antican‐ cer properties in ovarian cancer cells. Int J Vitam Nutr Res. 2020;3:1–11.
33. Lv H, Wang C, Fang T, Li T, Lv G, Han Q, et al. Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT‐2. npj Precis Oncol. 2018;2(1):1.
34. Alyoussef A, Al‐Gayyar MMH. Cytotoxic and partial hepatoprotective activity of sodium ascorbate against hepatocellular carcinoma through inhibition of sulfatase‐2 in vivo and in vitro. Biomed Pharmacother. 2018;103:362–72.
35. Volta V, Ranzato E, Martinotti S, Gallo S, Russo MV, Mutti L, et al. Preclini‐ cal Demonstration of Synergistic Active Nutrients/Drug (AND) Com‐ bination as a Potential Treatment for Malignant Pleural Mesothelioma. McCormick DL, editor. PLoS One. 2013;8(3):e58051.
36. Ranzato E, Biffo S, Burlando B. Selective Ascorbate toxicity in malignant mesothelioma. Am J Respir Cell Mol Biol. 2011;44(1):108–17.
37. Su X, Shen Z, Yang Q, Sui F, Pu J, Ma J, et al. Vitamin C kills thyroid cancer cells through ROS‐dependent inhibition
of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics. 2019;9(15):4461–73.
38. Tronci L, Serreli G, Piras C, Frau DV, Dettori T, Deiana M, et al. Vitamin C cytotoxicity and its effects in redox homeostasis and energetic metabolism in papillary thyroid carcinoma cell lines. Antioxidants. 2021;10(5):809.
39. Zhou J, Chen C, Chen X, Fei Y, Jiang L, Wang G. Vitamin C promotes apoptosis and cell cycle arrest in Oral squamous cell carcinoma. Front Oncol. 2020;10:976.
40. Deubzer B, Mayer F, Kuçi Z, Niewisch M, Merkel G, Handgretinger R,et al. H2O2‐mediated cytotoxicity of
pharmacologic Ascorbate concen‐ trations to neuroblastoma cells: potential role of lactate and ferritin. Cell Physiol
Biochem. 2010;25(6):767–74.
41. Castro M,Carson G, McConnell M, Herst P. High dose Ascorbate causes both Genotoxic and metabolic stress in Glioma cells. Antioxidants. 2017;6(3):58.
42. Gokturk D, Kelebek H, Ceylan S, Yilmaz DM. The effect of ascorbic acid over the Etoposide‐ and Temozolomide‐ mediated cytotoxic‐ ity in Glioblastoma cell culture: a molecular study. Turk Neurosurg. 2018;28(1):13–8.
43. Campbell EJ, Dachs GU. Current limitations of murine models in oncol‐ ogy for Ascorbate research. Front Oncol. 2014;4:282.
44. Campbell EJ, Vissers MCM, Wohlrab C, Hicks KO, Strother RM, BOzonet SM, et al. Pharmacokinetic and anti‐ cancer properties of high dose ascorbate in solid tumours of ascorbate‐dependent mice. Free Radic Biol Med. 2016;99:451–62.
45. Chen P, Stone J, Sullivan G, Drisko JA, Chen Q. Anti‐cancer effect of pharmacologic ascorbate and its interaction with supplementary par‐ enteral glutathione in preclinical cancer models. Free Radic Biol Med. 2011;51(3):681–7.
46. Taper HS, Jamison JM, Gilloteaux J, Summers JL, Calderon PB. Inhibition of the development of metastases by dietary vitamin C:K 3 combination. Life Sci. 2004;75(8):955–67.
47. Alessandro Magrì et al: High-dose vitamin C enhances cancer immunotherapy: Sci Transl Med 2020 Feb 26;12(532):eaay8707. doi: 10.1126/scitranslmed.aay8707.
48. Franziska Böttger et al. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer: J Exp Cain Cancer Res 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y.
49. Manuela Giansanti et al: High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients Cancers (Basel) 2021 Mar 20;13(6):1428. doi: 10.3390/cancers13061428.
References for IVC monotherapy in palliative care and quality of life (EOL)
1. Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, et al. High dose parenteral Ascorbate inhibited pancreatic Cancer growth and metasta‐ sis: mechanisms and a phase I/IIa study. Sci Rep. 2017;7(1):17188.
2. Takahashi H, Mizuno H, Yanagisawa A. High‐dose intravenous vitamin C improves quality of life in cancer patients. Pers Med Universe. 2012;1(1):49–53.
3. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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;25(6):983–90.
4. 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. 2007;22(1):7.
31. Xu Y, Guo X, Wang G, Zhou C. Vitamin C inhibits metastasis of peritoneal tumors by preventing spheroid formation in ID8 murine epithelial peritoneal Cancer model. Front Pharmacol. 2020;11:645.
32. Gregoraszczuk EL, Zajda K, Tekla J, Respekta N, Zdybał P, Such A. Vitamin C supplementation had no side effect in non‐cancer, but had antican‐ cer properties in ovarian cancer cells. Int J Vitam Nutr Res. 2020;3:1–11.
33. Lv H, Wang C, Fang T, Li T, Lv G, Han Q, et al. Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT‐2. npj Precis Oncol. 2018;2(1):1.
34. Alyoussef A, Al‐Gayyar MMH. Cytotoxic and partial hepatoprotective activity of sodium ascorbate against hepatocellular carcinoma through inhibition of sulfatase‐2 in vivo and in vitro. Biomed Pharmacother. 2018;103:362–72.
35. Volta V, Ranzato E, Martinotti S, Gallo S, Russo MV, Mutti L, et al. Preclini‐ cal Demonstration of Synergistic Active Nutrients/Drug (AND) Com‐ bination as a Potential Treatment for Malignant Pleural Mesothelioma. McCormick DL, editor. PLoS One. 2013;8(3):e58051.
36. Ranzato E, Biffo S, Burlando B. Selective Ascorbate toxicity in malignant mesothelioma. Am J Respir Cell Mol Biol. 2011;44(1):108–17.
37. Su X, Shen Z, Yang Q, Sui F, Pu J, Ma J, et al. Vitamin C kills thyroid cancer cells through ROS‐dependent inhibition
of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics. 2019;9(15):4461–73.
38. Tronci L, Serreli G, Piras C, Frau DV, Dettori T, Deiana M, et al. Vitamin C cytotoxicity and its effects in redox homeostasis and energetic metabolism in papillary thyroid carcinoma cell lines. Antioxidants. 2021;10(5):809.
39. Zhou J, Chen C, Chen X, Fei Y, Jiang L, Wang G. Vitamin C promotes apoptosis and cell cycle arrest in Oral squamous cell carcinoma. Front Oncol. 2020;10:976.
40. Deubzer B, Mayer F, Kuçi Z, Niewisch M, Merkel G, Handgretinger R,et al. H2O2‐mediated cytotoxicity of
pharmacologic Ascorbate concen‐ trations to neuroblastoma cells: potential role of lactate and ferritin. Cell Physiol
Biochem. 2010;25(6):767–74.
41. Castro M,Carson G, McConnell M, Herst P. High dose Ascorbate causes both Genotoxic and metabolic stress in Glioma cells. Antioxidants. 2017;6(3):58.
42. Gokturk D, Kelebek H, Ceylan S, Yilmaz DM. The effect of ascorbic acid over the Etoposide‐ and Temozolomide‐ mediated cytotoxic‐ ity in Glioblastoma cell culture: a molecular study. Turk Neurosurg. 2018;28(1):13–8.
43. Campbell EJ, Dachs GU. Current limitations of murine models in oncol‐ ogy for Ascorbate research. Front Oncol. 2014;4:282.
44. Campbell EJ, Vissers MCM, Wohlrab C, Hicks KO, Strother RM, BOzonet SM, et al. Pharmacokinetic and anti‐ cancer properties of high dose ascorbate in solid tumours of ascorbate‐dependent mice. Free Radic Biol Med. 2016;99:451–62.
45. Chen P, Stone J, Sullivan G, Drisko JA, Chen Q. Anti‐cancer effect of pharmacologic ascorbate and its interaction with supplementary par‐ enteral glutathione in preclinical cancer models. Free Radic Biol Med. 2011;51(3):681–7.
46. Taper HS, Jamison JM, Gilloteaux J, Summers JL, Calderon PB. Inhibition of the development of metastases by dietary vitamin C:K 3 combination. Life Sci. 2004;75(8):955–67.
47. Alessandro Magrì et al: High-dose vitamin C enhances cancer immunotherapy: Sci Transl Med 2020 Feb 26;12(532):eaay8707. doi: 10.1126/scitranslmed.aay8707.
48. Franziska Böttger et al. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer: J Exp Cain Cancer Res 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y.
49. Manuela Giansanti et al: High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients Cancers (Basel) 2021 Mar 20;13(6):1428. doi: 10.3390/cancers13061428.
References for IVC monotherapy in palliative care and quality of life (EOL)
1. Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, et al. High dose parenteral Ascorbate inhibited pancreatic Cancer growth and metasta‐ sis: mechanisms and a phase I/IIa study. Sci Rep. 2017;7(1):17188.
2. Takahashi H, Mizuno H, Yanagisawa A. High‐dose intravenous vitamin C improves quality of life in cancer patients. Pers Med Universe. 2012;1(1):49–53.
3. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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;25(6):983–90.
4. 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. 2007;22(1):7.
Intravenous Mistletoe
1. Kienle G., Kiene H. (2003) Verträglichkeit, Nebenwirkungen, Überempfindlichkeitsreaktionen, Toxizität. In: Kienle G., Kiene H., Die Mistel in der Onkologie. Fakten und konzeptionelle Grundlagen. Stuttgart: Schattauer 2003, 591–607.
2. Büssing A: Biological and pharmacological properties of Viscum album L. In Büssing A (Ed): Mistletoe – The Genus Viscum. Harwood Academic Publishers, Amsterdam, 124-182 (2000).
3. Kienle GS, Kiene H, Albonico HU: Anthroposophic Medicine: Effectiveness, Utility, Costs, Safety. Stuttgart, New York: Schattauer Verlag; 2006.
4. Struh CM, Jager S, Schempp CM, et al. A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells. Phytother Res. Oct 2012;26(10):1507-1512. doi: 10.1002/ptr.4604
5. Beuth J, Ko HL, Schneider H, et al. Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model. Anticancer Res. Nov-Dec 2006;26(6B):4451-4456.
6. Shen JJ, Chiang MS, Kuo ML, et al. Partially purified extract and viscolin from Viscum coloratum attenuate airway inflammation and eosinophil infiltration in ovalbumin-sensitized mice. J Ethnopharmacol. Jun 1 2011;135(3): 646-653. doi: 10.1016/j.jep.2011.03.065
7. Troger W, Galun D, Reif M, et al. Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival. Eur J Cancer. Dec 2013;49(18):3788-3797. doi: 10.1016/j.ejca.2013.06.043
8. Troger W, Galun D, Reif M, et al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Dtsch Arztebl Int. Jul 21 2014;111(29-30):493-502, 433 p following 502.
9. Bar-Sela G, Wollner M, Hammer L, et al. Mistletoe as complementary treatment in patients with advanced non- small- cell lung cancer treated with carboplatin-based combinations: a randomised phase II study. Eur J Cancer. Mar 2013;49(5):1058-1064. doi: 10.1016/j.ejca.2012.11.007
10. Friedel WE, Matthes H, Bock PR, et al. Systematic evaluation of the clinical effects of supportive mistletoe treatment within chemo- and/or radiotherapy protocols and long-term mistletoe application in nonmetastatic colorectal carcinoma: multicenter, controlled, observational cohort study. J Soc Integr Oncol. Fall 2009;7(4): 137-145.
11. Troger W, Zdrale Z, Stankovic N, et al. Five-year follow-up of patients with early stage breast cancer after a randomized study comparing additional treatment with Viscum album (L.) extract to chemotherapy alone. Breast Cancer (Auckl). 2012;6:173-180. doi: 10.4137/bcbcr.s10558
12. Ostermann T, Raak C, Bussing A. Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review. BMC Cancer. 2009;9:451. doi: 10.1186/1471-2407-9-451
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Intravenous Helleborus
- “Bufadienolides and ecdysteroids from the whole plants of Helleborus niger and their cytotoxicity.” Yokosuka A, et al. J Nat Med. 2021 Mar;75(2):393-402. doi: 10.1007/s11418-021-01481-6. Epub 2021 Jan 27
- “Comparative Evaluation of the Potential Antitumor of Helleborus purpurascens in Skin and Breast Cancer.” Pilut C et al; Plants (Basel). 2022 Jan 12;11(2):194. doi: 10.3390/plants11020194
- “Two new bufadienolides from the rhizomes of Helleborus thibetanus with inhibitory activities against prostate cancer cells.” Cheng W et al; Nat Prod Res. 2014;28(12):901-8. doi: 10.1080/14786419.2014.891200. Epub 2014 Apr 4
- “Minor regression and long-time survival (56 months) in a patient with malignant pleural mesothelioma under Viscum album and Helleborus niger extracts-a case report.” Werthmann PG et al; J Thorac Dis. 2017 Dec;9(12):E1064-E1070. doi: 10.21037/jtd.2017.11.56
- “Study of potent cytotoxic activity of Helleborus cyclophyllus Boiss against a human adenocarcinoma cell line.” Yfanti P et al; Cytotechnology. 2020 Oct 9;72(6):819-31. doi: 10.1007/s10616-020-00425-4