Many cancers reduce oxygen to protect themselves in 6 ways. Vitamin D stops all 6 ways – March 2022

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Vitamin D and Hypoxia: Points of Interplay in Cancer

Cancers (Basel). 2022 Mar 31;14(7):1791. doi: 10.3390/cancers14071791.
Ioanna-Maria Gkotinakou 1, Ilias Mylonis 1, Andreas Tsakalof 1

Vitamin D is a hormone that, through its action, elicits a broad spectrum of physiological responses ranging from classic to nonclassical actions such as bone morphogenesis and immune function. In parallel, many studies describe the antiproliferative, proapoptotic, antiangiogenic effects of calcitriol (the active hormonal form) that contribute to its anticancer activity. Additionally, epidemiological data signify the inverse correlation between vitamin D levels and cancer risk. On the contrary, tumors possess several adaptive mechanisms that enable them to evade the anticancer effects of calcitriol. Such maladaptive processes are often a characteristic of the cancer microenvironment, which in solid tumors is frequently hypoxic and elicits the overexpression of Hypoxia-Inducible Factors (HIFs). HIF-mediated signaling not only contributes to cancer cell survival and proliferation but also confers resistance to anticancer agents. Taking into consideration that calcitriol intertwines with signaling events elicited by the hypoxic status cells, this review examines their interplay in cellular signaling to give the opportunity to better understand their relationship in cancer development and their prospect for the treatment of cancer.
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• 198. Bougatef, F.; Quemener, C.; Kellouche, S.; Naïmi, B.; Podgorniak, M.-P.; Millot, G.; Gabison, E.E.; Calvo, F.; Dosquet, C.; Lebbé, C.; et al. EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2a-mediated regulation of soluble VEGF isoforms and their Receptor VEGFR-2. Blood 2009,114, 5547-5556. [CrossRef]
• 199. Imura, S.; Miyake, H.; Izumi, K.; Tashiro, S.; Uehara, H. Correlation of vascular endothelial cell proliferation with microvessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in hepatocellular carcinoma. J. Med. Investig. 2004, 51, 202-209. [CrossRef]
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• 201. Chiang, K.-C.; Chen, T.C. The anti-cancer actions of vitamin D. Anti Cancer Agents Med. Chem. 2013,13,126-139. [CrossRef]
• 202. Ben-Shoshan, M.; Amir, S.; Dang, D.T.; Dang, L.H.; Weisman, Y.; Mabjeesh, N.J. 1 a,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol. Cancer Ther. 2007, 6, 1433-1439. [CrossRef]
• 203. Whitfield, G.K.; Lenore, S.R.; Peter, W.J.; Heike, Z.; Anish, K.O.; Hope, T.L.D.; Carol, A.H.; Michael, A.G.; Michelle, L.T.; Carlos Encinas, D.; et al. Functionally relevant polymorphisms in the human nuclear vitamin D Receptor gene. Mol. Cell. Endocrinol. 2001,177,145-159. [CrossRef]
• 204. Uitterlinden, A.G.; Fang, Y.; van Meurs, J.B.; Pols, H.A.; van Leeuwen, J.P. Genetics and biology of vitamin D Receptor polymorphisms. Gene 2004, 338,143-156. [CrossRef]
• 205. Raimondi, S.; Johansson, H.; Maisonneuve, P.; Gandini, S. Review and meta-analysis on vitamin D Receptor polymorphisms and cancer risk. Carcinogenesis 2009, 30,1170-1180. [CrossRef]
• 206. Ben-Eltriki, M.; Deb, S.; Guns, E.S.T. Calcitriol in Combination Therapy for Prostate Cancer: Pharmacokinetic and Pharmacodynamic Interactions. J. Cancer 2016, 7, 391-407. [CrossRef]
• 207. Hu, K.; Callen, D.F.; Li, J.; Zheng, H. Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies. Integr. Cancer Ther. 2018,17, 217-225. [CrossRef]
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• 211. Ma, R.; Gu, Y.; Zhao, S.; Sun, J.; Groome, L.J.; Wang, Y. Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. Am. J. Physiol. Metab. 2012, 303, E928-E935. [CrossRef]
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• 213. Osborn, J.L.; Schwartz, G.G.; Smith, D.C.; Bahnson, R.; Day, R.; Trump, D.L. Phase II trial of oral 1,25-dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancer. Urol. Oncol. Semin. Orig. Investig. 1995,1,195-198. [CrossRef]
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• 217. Guan, X.; Ding, Y.; Qi, T. Safety and efficacy of high dose pulse calcitriol and docetaxel for androgen-independent prostate cancer. Med. Case Rep. Study Protoc. 2021,2, e0151. [CrossRef]
• 218. Sanghani, N.S.; Haase, V.H. hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience. Adv. Chronic Kidney Dis. 2019, 26, 253-266. [CrossRef]
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Google Scholar Search (hypoxia cancer "vitamin d") 5,600 items as of April 2022

Google Scholar Query Examples

• Hypoxia and cancer Nov 2007PDF
• Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia - July 2021 https://doi.org/10.1002/cbf.3612
• Preclinical Researches of Vitamin D Role in Preventing Malignant Diseased, a Systematic Review 2021 PDF
• Molecular Link between Vitamin D and Cancer Prevention - Sept 2013
  • in VitaminDWiki Molecular Link between Vitamin D and Cancer Prevention – Oct 2013
• Role of hypoxia in cancer therapy by regulating the tumor microenvironment - Nov 2019 PDF
• The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy - 2015 PDF
• Tumor Hypoxia as a Barrier in Cancer Therapy: Why Levels Matter - 2021 PDF
• High altitude and cancer: An old controversy - July 2021 https://doi.org/10.1016/j.resp.2021.103655
  • "Cancer prevalence and mortality is lower in high altitude populations of the United States and China, but higher in high altitude dwellers of Ecuador and India./// Some genetic and molecular modifications that allow for chronic hypoxia tolerance are known to facilitate oncogenesis.// /Lung cancer, lymphoma, colon cancer, esophageal carcinoma may have a decreased incidence at high altitude/// Gallbladder and biliary duct cancer, stomach carcinoma, skin cancer may be more frequent at high altitude."

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VitaminDWiki - Cancer category starts

• Cancer 293 items Overview Cancer and vitamin D
• Cancer and Vitamin D - many studies
• After Cancer Diagnosis 113 items
• Bladder Cancer 28 items
• Breast Cancer 259 items Overview Breast Cancer and Vitamin D
• Colon Cancer 144 items Overview Cancer-Colon and vitamin D
• Leukemia 19 items
• Liver Cancer 17 items
• Lung Cancer 55 items Overview Lung cancer and vitamin D
• Lymphoma Cancer 26 items
• Other Cancer 66 items
• Ovarian Cancer 26 items
• Pancreatic Cancer 57 items
• Prostate Cancer 103 items Overview Prostate Cancer and Vitamin D
• Skin Cancer 121 items Overview Suntan, melanoma and vitamin D
• Childhood Cancers - Vitamin D can help - many studies
• Easiest way to treat cancer – take Vitamin D – Nov 2022
• 13 Cancers are helped by Vitamin D – Biobank July 2023
• 2X increase of 14 cancers in non-seniors in 20 years (low vitamin D) – Sept 2022
• Vitamin D prevents and treats cancer in many ways – May 2021
• Those with recent cancer diagnosis had 7X increased risk of COVID-19 (more if A-A )- Dec 2020
• Deaths from many types of Cancer associated with low vitamin D- review of meta-analyses Sept 2020
• Cancer incidence and mortality is decreased if 40-60 ng of Vitamin D – April 2019
• 8 ways that Cancer might be prevented by Vitamin D - June 2019
• Cancer stem cells and Vitamin D - many studies
• Vitamin D Reduces Cancer Risk - Why Scientists Accept It but Physicians Do Not - Feb 2019
• Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018
• Vitamin D prevents breast cancer, reduces BC mortality, and reduces BC chemotherapy problems – Sept 2018
• Diagnosed with breast cancer – take vitamin D to cut chance of death by half – July 2018
• Melanoma 25 X more likely if low vitamin D – Feb 2018
• Better Cancer survival if higher vitamin D a decade earlier (esp. Melanoma, Kidney, Prostate)– Aug 2018

Cancers get less Vitamin D when there is a poor Vitamin D Receptor

• Vitamin D Receptor pages in VitaminDWiki with CANCER in title 86 as of July 2023
• Cancer and the Vitamin D Receptor, a primer – Sept 2017
• Vitamin D Receptor (Cancers OR Viruses) - many studies
• Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
• Cancer (general) and VDR 23 articles
• Breast Cancer and VDR 24 articles
• Colon Cancer and VDR 13 articles
• Prostate Cancer and VDR 7 articles
• Skin Cancer and VDR 10 articles
  • Note some Health problems, such as some Cancers, protect themselves
    by actively reducing Receptor activation

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VitaminDWiki Vitamin D Receptor pages with CANCER in title (75 as of April 2022)

This list is automatically updated