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Simultaneously Blocking Glycolysis and Fat Metabolism Can the use of DCA and a fatty acid metabolism blocker together force more cancer cells into using aerobic metabolism? Tim McGough used green tea extract, which contains EGCG, in his fantastic response. DCA works by reactivating mitochondria and shifts metabolism from glycolysis to glucose oxidation. Hopefully the cancer cell will then undergo apoptosis. However, cancer cells have an alternate energy source: fat metabolism. This page explores to possibility of blocking fat metabolism to help force the cell into apoptosis. Oral squamous cell carcinoma is a cancer that does not respond well to DCA. This study, Head and Neck Cancer Cell Lines Are Resistant to Mitochondrial-Depolarization-Induced Apoptosis states: "Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane-depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.(head and neck squamous cell carcinoma)" Note that although the cell lines were depolarized, apoptosis did not occur. So I checked to see if fatty acid metabolism is used by squamous cell carcinoma.

Dietary vitamin D and cancers of the oral cavity and esophagus. Lipworth L, Rossi M, McLaughlin JK, Negri E, Talamini R, Levi F, Franceschi S, La Vecchia C. Ann Oncol. 2009 Sep;20(9):1576-81. Epub 2009 Jun 1. PMID: 19487490 Conclusion: We observed inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol.

Maté: a risk factor for oral and oropharyngeal cancer. Goldenberg D. Oral Oncol. 2002 Oct;38(7):646-9. Review. PMID: 12167417

Li N, Sood S, Wang S, Fang M, Wang P, Sun Z, Yang CS, Chen X. Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib. Clin Cancer Res. 2005 Mar 1;11(5):2089-96. PMID

An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day. Grant WB, Garland CF, Gorham ED. Recent Results Cancer Res. 2007;174:225-34. Review. PMID: 17302200

Derived from the bulb or clove of the plant. Garlic is used as a spice and to treat hyperlipidemia, hypertension, atherosclerosis, cancer, and infections. Processing can have a substantial effect on the chemical content in garlic; the volatile oil components are sensitive to heat and certain enzymes are acid-labile. Several oral garlic formulations are available, and clinical studies have addressed a variety of the proposed claims. Placebo-controlled trials on the cholesterol lowering effect of garlic yielded mixed results (16) (17) (18) (21) (22) (26). Studies evaluating the antithrombotic effects repeatedly have shown modest reduction in platelet aggregation, but varying levels of fibrinolytic activity. Research shows mixed effects with regard to reductions in blood glucose, blood pressure, or risk of cardiovascular disease (23). Frequently reported adverse events include bad breath, headache, fatigue, GI upset, diarrhea, sweating, and possible hypoglycemia (9). Because garlic is known to decrease platelet aggregation and potentially elevate the INR, it should not be used with anticoagulants or in patients with platelet dysfunction (15). Garlic appears to induce cytochrome p450 3A4 and may enhance metabolism of many medications (e.g. cyclosporin and saquinavir) (12). An analysis of several case-control studies in Europe suggests an inverse association between garlic consumption and risk of common cancers (25).

Grant WB, Garland CF, Gorham ED. An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day. Recent Results Cancer Res. 2007;174:225-34. PMID: 17302200 [PubMed - in process]

Mango juice Summary of the Health benefits Mango Fruit Juice are rich in iron, thus patients with anemia and pregnant women are advised to consume it regularly. Phenols are presents in Mango Juice and Mango drinks this compound phenol has strong antioxidant and anticancer capacities. mangoes and it's Juice helps in relieving congested pores of the skin. Patients suffering from acidity and weak digestion can benefit from the consumption of mango juice. It is a fruit which is low in carbohydrates and is an rich antioxidant. The rich source of vitamin A (beta-carotene), E and Selenium present in Mangoes helps in protection from heart diseases and other problems. Mango Juice is rich in pre-biotic dietary fiber, vitamins, minerals, and poly-phenolic flavonoid antioxidant compounds. According to new research study, mango fruit juice has been found to protect against colon, breast, leukemia and prostate cancers. Several trial studies suggest that polyphenolic anti-oxidant compounds in mango are known to offer protection against breast and colon cancers. Mango Juice is an excellent source of Vitamin-A and flavonoids like beta-carotene, alpha-carotene,and beta-cryptoxanthin. 100 g of fresh Mango juice provides 765 mg or 25% of recommended daily levels of vitamin A. Together these compounds are known to have antioxidant properties and are essential for vision. Vitamin A is also required for maintaining healthy mucus membranes and skin. Consumption of natural fruits rich in carotenes is known to protect body from lung and oral cavity cancers. Fresh mango Juice is a very rich source of potassium. Potassium is an important component of cell and body fluids that helps controlling heart rate and blood pressure. mango juice is also a very good source of vitamin-B6 (pyridoxine), vitamin-C and vitamin-E. Consumption of foods rich in vitamin C helps body develop resistance against infectious agents and scavenge harmful oxygen free radicals. Vitamin B-6 o

Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial. Barrera JL, Verastegui E, Meneses A, Zinser J, de la Garza J, Hadden JW. Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51. PMID: 10722007 The natural cytokine mixture is a collection of natural human cytokines induced from human peripheral blood mononuclear cells. It contains IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, interferon gamma, tumor necrosis factor , and granulocyte-macrophage and granulocyte colony-stimulating factor in nanogram quantities. It lacks IL-3, IL-4, IL-5, and IL-7. [...] This IRX-2 strategy uses perilymphatic local administration along with contrasuppression with low-dose cyclophosphamide and indomethacin and with zinc replacement therapy (as an immunorestorative). The data presented herein demonstrate that H&N SCC can respond very well to immunotherapy: there was a response rate of 100% in this series of 15 patients, with clinical reduction in tumor (1 complete response, 7 partial responses, and 7 minor responses) and histological evidence of tumor regression of 42%. Overall, the average combined estimated tumor reduction exceeded 70%. Also, patients with oral cancer noted marked analgesic and hemostatic effects from this therapy, with healing of oral lesions. [...] It is important to note that adjuvant chemotherapy is not used at INCAN. Many studies23 indicate that treatment with fluorouracil and cisplatin, the combination most in use, is effective for reducing tumors in the majority of patients; however, with no meaningful impact on survival, their routine use in the United States has recently been questioned.24-25 The expense, toxic effects, and lack of effectiveness of both drugs has made their use in other less affluent countries unwarranted. The current data on the use of IRX-2 in this and other protocols8-10 hint at improved survival, and a phase 3 randomized controlled study comparing this protocol with chemotherapy arm is to be initiat

ScienceDaily (Apr. 10, 2009) - New research from Trinity College Dublin published in this month's Annals of Surgery points to a potentially significant advance in the treatment of patients undergoing major cancer surgery. The study was carried out by the oesophageal research group at Trinity College Dublin and St James's Hospital. A randomised controlled trial showed omega-3 fatty acids given as part of an oral nutritional supplement resulted in the preservation of muscle mass in patients undergoing surgery for oesopahageal cancer, a procedure normally associated with significant weight loss and quality of life issues.

"Berberine is a quaternary ammonium salt from the group of isoquinoline alkaloids. It is found in such plants as Berberis, goldenseal (Hydrastis canadensis), and Coptis chinensis, usually in the roots, rhizomes, stems, and bark. Berberine is strongly yellow colored, which is why in earlier times berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in Northern India Berberine (BBR) is a natural compound with up-regulating activity on both low-density-lipoprotein receptor (LDLR) and insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome.[12] Berberine has been tested and used successfully in experimental[13] and human diabetes mellitus.[14][15][16] Berberine has been shown to lower elevated blood glucose as effectively as metformin.[17] The mechanisms include inhibition of aldose reductase,[18] inducing glycolysis,[19] preventing insulin resistance[20] through increasing insulin receptor expression[14] and acting like incretins. Berberine has drawn extensive attention towards its antineoplastic effects.[43][44] It seems to suppress the growth of a wide variety of tumor cells including breast cancer,[45] leukemia, melanoma,[46] epidermoid carcinoma, hepatoma, oral carcinoma, tongue carcinoma,[47] glioblastoma, prostate carcinoma, gastric carcinoma.[48][49] Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, tumor promotion, tumor invasion,[50][51][52][53][54] prostate cancer,[55][56][57][58] neuroblastoma,[59][60] and leukemia.[34][61] It is a radiosensitzer of tumor cells but not of normal cells

Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator. Pereira CV, Machado NG, Oliveira PJ. Toxicol Sci. 2008 Oct;105(2):408-17. Epub 2008 Jul 3. PMID: 18599498 doi: 10.1124/jpet.107.128017 The data from the present work appear to show that berberine also presents some degree of toxicity to "nontumor" systems, which should be carefully understood. ANT inhibition in nontumor cells by berberine would be responsible for a decrease in energy production and could also result in MPT induction. To the best of our knowledge, no full toxicity assessment exists for berberine in humans, although its use in several commercially available supplements suggests that the compound may present a relatively wide safety interval. In fact, a study with patients with congestive heart failure treated with 1.2 g/day of oral berberine revealed low toxicity and resulted into an average plasma concentration of 0.11 mg/l which would translate into 0.3µM (Zeng and Zeng, 1999Go). Repeated cumulative treatments, alternative forms of formulation (e.g., topical application vs. injection) or more importantly, active mitochondrial accumulation due to its positive charge would be expected to increase its concentration in cells into the range of concentrations used in this study. Empirical data from nontraditional medicines plus the use of extensive clinical assays would allow the use of berberine as a promising antimelanoma agent while maintaining its safety for humans. In radial/vertical forms of melanoma, a possible topical application of berberine would also be possible, thus minimizing side effects on other organs. In conclusion, the present work identifies the ANT as an important target for berberine, with clear relevance for its proposed antitumor effects.

Sun Z, Sood S, Li N, Ramji D, Yang P, Newman RA, Yang CS, Chen X. Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinoge

Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. Lachenmeier DW. J Occup Med Toxicol. 2008 Nov 13;3:26. PMID: 19014531 doi:10.1186/1745-6673-3-26

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration.\nYeom CH, Jung GC, Song KJ.\nJ Korean Med Sci. 2007 Feb;22(1):7-11.\nPMID: 17297243

The beverage maté: a risk factor for cancer of the head and neck. Goldenberg D, Golz A, Joachims HZ. Head Neck. 2003 Jul;25(7):595-601. Review. PMID: 12808663 DOI: 10.1002/hed.10288

Effect of yerba mate (Ilex paraguariensis) tea on topoisomerase inhibition and oral carcinoma cell proliferation. Gonzalez de Mejia E, Song YS, Ramirez-Mares MV, Kobayashi H. J Agric Food Chem. 2005 Mar 23;53(6):1966-73. PMID: 15769122

Not enough vitamin D: health consequences for Canadians. Schwalfenberg G. Can Fam Physician. 2007 May;53(5):841-54. Review PMID: 17872747 Conclusion Low levels of VTD are considered a major public health problem in Canada, especially during the winter. Those with risk factors should be screened for low 25(OH)D levels and repletion therapy instituted if needed. Researchers have estimated that the oral dose of vitamin D3 to attain and maintain 25(OH)D levels >80 nmol/L is 2200 IU/d if baseline levels are 20 to 40 nmol/L, 1800 IU/d if levels are 40 to 60 nmol/L, and 1160 IU/d if levels are between 60 and 80 nmol/L.64 We need to ensure that patients have healthy blood levels of 25(OH)D to prevent levels of parathyroid hormone from rising and to maximize absorption of calcium, magnesium, and phosphate. Positive effects on bone are marginal at best unless patients consume at least 800 IU/d of VTD. The emerging and exciting role of the VTD receptor and the actions of VTD in maintaining health in other cell types have become more apparent during the last decade.