Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Functional Medicine Forum 2008 Men’s Health: Cancer Prevention Strategies & Adjunctive Naturopathic Treatment Support David B. Wood, BSc, ND Cofounder, President, CEO: Trinity Family Health Clinic, PS (1984 - ) Cofounder, Vice President, CMO: BioGenesis Nutraceuticals, Inc.(2000 - ) Statistics CAFF2006PWSecured.pdf (Cancer Facts and Figures 2006, American Cancer Society) Earlier detection + New Improved Treatments Estimated 5 year survival (cured, relapsed or continuing treatment): 1974-1976 1995-2001 50% 65% 1998-2002 Incidence & Death per 100K 180 160 140 120 Male I Male Death Female I Female Death 100 80 60 40 20 0 Colon Lung Prostate Breast Cancer Facts and Figures 2006 American Cancer Society Surveillance Research 2006 Prevention Strategies Screening exams/labs Diet Lifestyle Nutriceutical Support Genomic Issues (dealt with in Dr Veltman’s lecture) Screening Exams/Labs Colorectal Cancer Colorectal cancer is extremely common. Symptoms include blood in the stool or change in bowel habits. Screening – fecal occult blood testing (hemoccult) In addition to the Hemoccult - Comprehensive Digestive Stool Analysis (CDSA) - screen for nbutyrate levels as part of a overall digestive, fatty acid, flora, inflammatory marker screen. Diagnosis – Colonoscopy/biopsy Standard Treatment – surgical resection + chemotx for nodal involvement Colorectal Cancer Surgery for cure can be attempted in the 70% of patients presenting w/o metastatic disease. Prognosis: 10 year survival Adjuvant Chemotherapy: Typically 5-fluorouracil and leucovorin Improves survival by 10-30% in colon cancer patients with + lymph nodes. Follow up: Limited to the mucosa: approaches 90% Extension through bowel wall: 70-80% Positive lymph nodes: 30-50% Metastatic disease: < 20% Colonoscopy annually for 5 years and every 3 years thereafter if no polyps or tumors are found. Palliation: When curative surgery is not possible Surgical debulking (endoscopic laser treatment, electrocoagulation or held open by stents. Chemotherapy Prognosis: median survival 7 months Colorectal Cancer Staging Stage Tumor (Maximum Penetration) Regional Lymph Node Metastasis Distant Metastasis 0 Tis N0 M0 l T1 or T2 N0 M0 ll T3 N0 M0 lll Any T or T4 lV Any T Any N N0 Any N M0 M0 M1 Lung Cancer Lung carcinoma is a malignant lung tumor usually categorized as small cell or non-small cell. Risk factor: Symptoms include: Suspected: Confirmed: Treatment: cough, chest discomfort, and, less commonly hemoptysis, but many patients are asymptomatic and some present with metastatic disease. Diagnosis: Cigarette smoking is the major risk factor for most types. Radon gas exposure Asbestos, silica, arsenic, chromates, nickel, chloromethyl esthers, beryllium and coke oven emissions. Surgery, Chemotherapy, and/or radiation therapy Prognosis: Chest X-ray or CT scan Biopsy Poor: despite advances in treatment Focus is on early detection and prevention Non - Feature Small Cell Adenocarcinoma Small Cell Squamous Cell Large Cell % of lung cancers 15% 25-35% 30-35% 10-15% Location Submucosa of airways, perihilar mass Peripheral nodule or mass Central, endobronchial Peripheral nodule or mass Risks Smoking (100%) Etoposide or irinotecan or topotecan + carboplatin or cisplatin; Treatment concurrent radiation tx in limited-stage disease; no role for surgery Smoking, occupational exposure (asbestos, radon) Stage l/ll: Surgery with or without adjuvant chemotherapy Stage lllA: Surgery with or without adjuvant therapy or concurrent chemoradiation Stage lllB: Radiation with or without chemotherapy Stage lV: Chemotherapy with or without palliative radiation Feature Small Cell Non – Small Cell Adenocarcinoma Squamous Cell Large Cell Complications Common cause of SVC syndrome, paraneoplastic syndromes Limited Stage l: 57-67% Stage ll: 39-55% Extensive Stage lll: 5-25% Stage lV: <1% Involvement:20% 5-year survival with treatment Hemoptysis, airway obstruction, pneumonia, pleuritic involvement w/pain, pleural effusion, SVC syndrome, Pancoast’s tumor (shoulder or arm pain), hoarseness (laryngeal nerve involvement), neurologic sx from brain mets, pathologic fracture from bone mets, jaundice from liver mets Involvement:< 5% SVC = superior vena cava Superior vena cava (SVC) syndrome/obstruction is a relatively rare condition. Most often it is caused by cancer in the mediastinum (the area of the chest under the breastbone and between the lungs). The types of cancer that can lead to this condition include lymphoma, cancer of the lung that spreads, breast cancer, testicular cancer, thyroid cancer, and thymic tumors. Lung Cancer Staging International Staging System For Lung Cancer Primary tumor (T) Tis Carcinoma in situ T1 Tumor ≤3cm w/o invasion more proximal than the lobar bronchus (ie, not in the main bronchus) T2 Tumor with any one of the following features: T3 T4 > 3 cm Involves main bronchus ≥ 2 cm distal to carina Invades the visceral pleura Atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung Tumor of any size with any one of the following features: Invades chest wall (incl superior sulcus tumors), diaphram, mediastinal pleura, or parietal pericardium Involves main bronchus < 2cm distal to carina but w/o carinal involvement Atelectasis or obstructive pneumonitis of the entire lung Tumor of any size with any of the following features: Invades mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina Malignant pleural or pericardial effusion Satellite tumor nodule(s) within the same lobe as primary tumor Lung Cancer Staging International Staging System For Lung Cancer Regional lymph nodes (N) N0 N1 N2 N3 No regional lymph node metastasis Mets to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes involved by direct extension of the primary tumor Mets to ipsilateral mediastinal and/or subcarinal lymph nodes(s) Mets to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) Distant metastasis (M) M0 M1 No distant mets Distant mets present [includes metastatic tumor nodule(s) in a lobe(s) ipsilateral to but diffferent from the primary tumor] Stage 0 Tis Stage IIB T2N1M0 or T3N0M0 Stage IAT1N0M0 Stage IIIA T3N1M0 or T1-3N2M0 Stage IIB T2N0M0 Stage IIIB any TN3M0 or T4 Any NM0 Stage IIA T1N1M0 Stage IV Any T Any N M1 Screening Exams/Labs Prostate Cancer DRE, serum PSA (annual > 50 yo), Men’s health questionnaires TRUS (transrectal ultrasound) may include needle biopsy (“guided biopsy”) Biopsy: If (+) for Cancer – staging (define extent of tumor) PSA – PSA velocity important. T1, T1a, b or c, T2, T2a, b or c, T3, T3a, b or c, T4 Define based on resemblance of tumor architecture to normal glandular structure: Gleason score: grading of histologic heterogenicity of tumor. Well differentiated 2-4, to mod differentiated 5-7, to undifferentiated 8-10. Scores are based on the most prevalent pattern and the next most prevalent pattern. The lower the score, the less aggressive and invasive is the tumor and the better is the prognosis. PC staging T1 Clinically inapparent by palpation or imaging T1a Incidentally found in ≤5% of resected tissue T1b Incidentally found in >5% of resected tissue T1c Identified by needle biopsy done for elevated PSA level T2 Is Palpable or reliably visible by imaging; confined to prostate T2a Involves ½ of one lobe or less T2b Involves > ½ of one lobe but not both lobes T2c Involves both lobes T3 Extends through the prostatic capsule T3a Extends through the prostatic capsule unilaterally or bilaterally T3b Invades seminal vesicles T4 Is fixed or invades adjacent structures other than seminal vesicles PC con’t Prognosis (standard allopathic) Depends on stage and grade Generally very good for localized High grade (T score), poorly differentiated (Gleason score) = poor prognosis. Metastatic cancer has no cure; median life expectancy is 1-3 years, although some patients live for many years Treatment: Varies (watchful waiting, hormonal ablation Tx, cryotherapy, surgery, chemotx, brachytherapy (radio seed implants), radiotx (external beam)) Cytotoxic and biologic drugs (eg, genetically designed vaccines, antisense therapy, monoclonal antibodies), angiogenesis inhibitors (eg, thalidomide, endostatin), and matrix metalloproteinase inhibitors are being studied and may provide palliation and prolong survival, but their superiority over corticosteroids alone has not been proved. Reference for Cancer Staging: The Merck Manual 18th Ed. 2006 Cancer Prevention Diet Avoid or minimize exposure to carcinogens (trans fatty acids, hydrogenated oils, rancid fats, deep fried, grilled meats, + reduce exposure to high glycemic foods, white sugar, white flour, artificial colors, dyes, etc.) Eat a well balanced organic whole food unprocessed/minimally processed low glycemic diet with many colors for best food based antioxidant/flavonoid exposure. Eat from the rainbow. Balance protein, fat and carbohydrates from organic whole foods. Eat cold water ocean fish. Increase Omega 3 fatty acid foods and reduce Omega 6 fatty acid foods. Drink clean water. Don’t overlook the importance of being well hydrated with clean water. It makes everything function better. Many people suffer from dehydration. Work towards 40-50 grams of fiber intake per day. Fiber reduces the risk of colon cancer, but also does so many other things (bowel movement regulation, toxin clearance, flora and fatty acid regulation, hormone and cholesterol clearance (minimize enterohepatic recirculation) Get some unprocessed “raw” foods everyday. Fresh fruit, vegies, sprouts are good candidates. Eat Lycopenes/Carotenoids (tomatoes and other ‘red’ fruits/vegies) Eat Cruciferous vegetables (broccoli, cauliflower, brussels sprouts, cabbage) Eat fermented foods (cabbage, kefir, yogurt, low fat/skim cheese, miso, tempeh, pickles, vinegar) Lifestyle Exercise moderately on a regular basis. Vary the exercise from aerobic to weights to walk/run, cycle, etc. Have fun with it and make it part of your lifestyle. Use your morning on waking pulse to determine tolerance and recovery time. Get regular exposure to sun to enhance Vitamin D and melatonin production. Protect skin with antioxidant sunscreen after 15 minutes of unprotected exposure. Wear sunglasses that protect eyes from UVA/B/C induced solar damage. Expose eyes indirectly (unprotected) to sunrise and sunset rays to enhance circadian rhythm regulation and allow beneficial full spectrum exposure Decompress. Let go of emotional garbage. Forgive. Use of prayer and/or meditation can be helpful. Get a pet! Animals give love unconditionally and can be a great loyal companion. Many studies show that people with pets tend to be happier, healthier and live longer. Don’t dwell on yourself. “Give and it shall be given unto you” is so true. Bless others! It is great fun and makes life a much more rewarding experience. Standing on the Shoulders of Giants Max Gerson William Donald Kelly Oxidative phosphorylation Keith Brewer Enzymes Otto Warburg Raw foods, juicing, Na/K ratio, thyroid High alkaline pH Angelo P. John, Sr. ? Molecular biologist and cancer scientist, controlled amino acid therapy (CAAT), glycolysis vs. oxidative phosphorylation strategies Otto Warburg Nobel Prize in Medicine 1931: discovery of oxygen transferring enzyme of cell respiration Nobel Prize in Medicine 1944: discovery of the active groups of hydrogen transferring enzymes His main interests: Chemistry and Physics of Life No scientists have been more successful “Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in the normal body cells by a fermentation of sugar. All normal body cells meet their energy needs by respiration of oxygen, whereas cancer cells meet their energy needs in great part by fermentation. All normal body cells are thus obligate aerobes, whereas all cancer cells are partial anaerobes. From the standpoint of the physics and chemistry of life this difference between normal and cancer cells is so great that one can scarcely picture a greater difference. Oxygen gas, the donor of energy in plants and animals is dethroned in the cancer cells and replaced by an energy yielding reaction of the lowest living forms, namely, a fermentation of glucose.” Otto Warburg in “The Prime Cause and Prevention of Cancer” Lecture Lindau, Germany 1966. English Ed. Published by Dean Burk, National Cancer Institute, Bethesda, Maryland. Otto Warburg Director, Max Planck Institute for Cell Physiology, Berlin-Dahlem “To prevent cancer it is therefore proposed first to keep the speed of the blood stream so high that the venous blood still contains sufficient oxygen; second, to keep high the concentration of hemoglobin in the blood; third to add always to food, even in healthy people, the active groups of the respiratory enzymes; and to increase the doses of these groups, if a precancerous state has already developed. If at the same time exogenous carcinogens are excluded rigorously, then most cancers may be prevented today.” Otto Warburg Wiesenhof, August 1966 in: “The Prime Cause and Prevention of Cancer” Naturopathic Adjunctive Support Options Cancer Cell Physiology Specialized Diets Individualized: Foundational nutrition Digestion/elimination Cytochrome P450/Phase I/II conjugation support Pulsed antioxidants Antimetastatics Antiangiogenesis Matrix metalloprotease Inhibition Immune enhancement Enhanced phagocytosis & macrophage debris field cleanup “Recently, The Journal of Clinical Oncology reported that an increasing number of cancer patients are using complementary therapies as part of their treatment regimen such as Controlled Amino Acid Therapy (CAAT). Also, The Journal of the American Medical Association dedicated an entire issue to integrative and complementary cancer Treatments. The effects of biological targeted therapies like CAAT which interfere with specific functions in cancer cells, causing them to die, has also been reported in The New England Journal of Medicine, The Journal of the National Cancer Institute, Clinical Cancer Research and The Journal Of Cellular Biochemistry. It is now evident that not only drugs, but specific biological compounds, such as those employed by CAAT, can attack such sites on cancer cells. • Dr Albert B. Lorincz of the University of Chicago conducted several trials with cancer patients, reducing tumor size in most of them who were fed a formula reduced in certain amino acids, the treatment employed by CAAT. • Dr. Chi Van Dang, of the Johns Hopkins School of Medicine, and Dr. Douglas Spitz of the University of Iowa report how carbohydrate deprivation, a part of the CAAT protocol, kills cancer cells while having no effect on normal cells. Dr. Pascal J. Goldschmidt of the Johns Hopkins Medical School reports that scientifically supported dietary supplements, such as those included in CAAT, may be helpful in treating certain cancers. Dr. Marco Rabinowitz of the National Cancer Institute reports that amino acid deprivation, such as Controlled Amino Acid Therapy (CAAT), inhibits phosphofructokinase, shuts down energy supply to cancer cells and thereby enhances the benefits of chemotherapy. Dr. Joel Evans, Honorary Co-Chairman of the Physicians Advisory Board to the U.S. Congress, lectured at Yale’s Cancer Center on cancer and nutrition, discussing Controlled Amino Acid Therapy and citing the notable recovery his patient experienced since using CAAT….” Angelo P. John, Sr. Underline emphasis mine Cancer Cell Physiology Cancer cell Healthy cell Krebs Cycle Defective Krebs Cycle Normal Energy Almost all from Glycolysis (80+ %) fermentation Energy from Krebs Cycle (70%) Energy in Absence of Oxygen Energy Most from Oxygen (oxidative phosphorylation) Growth & Reproduction Requires certain amino acids (glycine, serine, glutaminc acid and aspartic acid) phosphorus and Vitamin B6 Growth & Reproduction not glycine dependent Glycine not an essential amino acid for healthy cells Angiogenesis (regulated by Matrix Uses existing circulation Metalloprotease) Stimulation of rather than stimulating feeder requires these same amino acids vessels Further information at: www.apjohncancerinstitute.org Cancer Cell Physiology Diet/Nutriceutical intervention should: Inhibit: Glycolysis CHO restriction Angiogenesis as well as growth and reproduction of cancer cells Essential Fatty Acids from Fish, Perilla and Olive (squalene, oleic) Epithelial Growth Factors Limonene (Citrus Fruits) inhibition of Ras cancer gene (Avoid Grapefruit) Prostaglandin E2 Diet Low in Glycine (key amino acid to restrict), Phosphorus and Vitamin B6 Ras cancer gene (overactive in 90% of all cancers) 20% restriction to inhibit cell growth and reproduction 40% restriction to see cancer cell apoptosis (cancer cell death) Parsley extract Support: Oxidative Phosphorylation (Krebs Cycle) Increase Citric Acid and Acetic Acid intake Citrus Fruits (lemon, esp.) and Vinegar (2 T with lunch, dinner) Supports healthy cell function and promotes apoptosis of cancer cells DCA Dichloroacetic Acid New synthetic analog of natural acetic acid IUPAC name Dichloroacetic acid (all vinegars) Other names Dichloroethanoic acid Cancer trials Dichloroacetate Potential cancer Molecular formula CHCl2COOH applications Cancer cells generally use glycolysis rather than oxidation for energy (the Warburg effect), as a result of hypoxia in tumors and damaged mitochondria.The body often kills damaged cells by apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells. A study published in January 2007 by researchers at the University of Alberta, testing DCA on in vitro cancer cell lines and a rat model, found that DCA restored mitochondrial function, thus restoring apoptosis, killing cancer cells in vitro, and shrinking the tumors in the rats. These results received extensive media attention, beginning with an article in New Scientist titled "Cheap, Safe Drug Kills Most Cancers". Subsequently, the American Cancer Society and other medical organizations have received a large volume of public interest and questions regarding DCA. Reports have since pointed out that although the study results are promising, no formal clinical trials in humans with cancer have yet been conducted, emphasizing the need for caution in interpreting the preliminary results, though some doctors are treating patients with DCA "off-label," and under a cloud of controversy. The New Scientist later editorialized, "The drug may yet live up to its promise as an anti-cancer agent - clinical trials are expected to start soon. It may even spawn an entirely new class of anti-cancer drugs. For now, however, it remains experimental, never yet properly tested in a person with cancer. People who self-administer the drug are taking a very long shot and, unlikely as it may sound, could even make their health worse." The historical likelihood that a promising agent in preclinical (i.e., cell-line killing) experiments will become an effective human cancer drug is 5%,and the likelihood of an FDA approval for any given drug entering Phase I testing is reportedly 8-11%. DCA has been used historically to treat patients with lactic acidosis, and therefore, could arguably enter phase 2 trials in patients with cancer. DCA is non-patentable as a compound, though a patent has been filed for its use in cancer treatment. Concerns have been raised that without strong intellectual property protection, the financial incentive for pharmaceutical industry interest is reduced, and therefore clinical trials of DCA may not be funded. However, other sources of funding exist; previous studies of DCA have been funded by government organizations such as the National Institutes of Health, the Food and Drug Administration, the Canadian Institutes of Health Research and by private charities (e.g. the Muscular Dystrophy Association). Drs Michelakis and Archer have applied for a patent on the use of DCA in the treatment of cancer. Side effects of DCA: Reports in the lay press after the 2007 University of Alberta announcement claim that dichloroacetate "has actually been used safely in humans for decades", but the limited scholarly literature suggests side effects of pain, numbness and gait disturbances in some patients. A clinical trial where DCA was given to patients of MELAS (a form of genetically inherited lactic acidosis) at 25 mg/kg/day was ended prematurely due to excessive peripheral nerve toxicity. Dichloroacetate can also have anxiolytic or sedative effects. Animal studies suggest that the neuropathy and neurotoxicity during chronic dichloroacetate treatment may be partly due to depletion of thiamine, and thiamine supplementation in rats reduced these effects. However, more recent studies in humans suggest that peripheral neuropathy is a common side effect during chronic DCA treatment, even with coadministration of oral thiamine. An additional study reported that 50 mg/kg/day DCA treatment resulted in unsteady gait and lethargy in two patients, with symptoms occurring after one month for one patient and two months for the second. Gait disturbance and consciousness were recovered with cessation of DCA, however sensory nerve action potentials did not recover in one month. Studies of the trichloroethylene (TCE) metabolites dichloroacetic acid (DCA), trichloroacetic acid (TCA), and chloral hydrate suggest that both DCA and TCA are involved in TCE-induced liver tumorigenesis and that many DCA effects are consistent with conditions that increase the risk of liver cancer in humans. Acetic Acid Cancer Cell, Vol 11, 37-51, January 2007 A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth Sébastien Bonnet,1 Stephen L. Archer,1,2 Joan AllalunisTurner,3 Alois Haromy,1 Christian Beaulieu,4 Richard Thompson,4 Christopher T. Lee,5 Gary D. Lopaschuk,5,6 Lakshmi Puttagunta,7 Sandra Bonnet,1 Gwyneth Harry,1 Kyoko Hashimoto,1 Christopher J. Porter,8 Miguel A. Andrade,8 Bernard Thebaud,1,6 and Evangelos D. Michelakis1, 1 Pulmonary Hypertension Program and Vascular Biology Group, University of Alberta, Edmonton, AB T6G 2B7, Canada 2 Department of Physiology, University of Alberta, Edmonton, AB T6G 2B7, Canada 3 Department of Oncology, University of Alberta, Edmonton, AB T6G 2B7, Canada 4 Department of Biomedical Engineering, University of Alberta, Edmonton, AB T6G 2B7, Canada 5 Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2B7, Canada 6 Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2B7, Canada 7 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2B7, Canada 8 Ontario Genomics Innovation Centre, Ottawa Health Research Institute, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (ΔΨm) and low expression of the K+ channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases ΔΨm, increases mitochondrial H2O2, and activates Kv channels in all cancer, but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent. Cheap, safe drug kills most cancers 20 January 2007 NewScientist.com news service Remember Acetic Acid from Vinegar! Andy Coghlan References to DCA (taken from www.wikipedia.org) Lide, D. R. (Ed.) (1990). CRC Handbook of Chemistry and Physics (70th Edn.). Boca Raton (FL):CRC Press. Stacpoole P, Henderson G, Yan Z, James M (1998). "Clinical pharmacology and toxicology of dichloroacetate". Environ Health Perspect 106 Suppl 4: 989–94. PMID 9703483. Free full text Stacpoole P (1989). "The pharmacology of dichloroacetate". Metabolism 38 (11): 1124-44. PMID 2554095. Stacpoole P, Lorenz A, Thomas R, Harman E (1988). "Dichloroacetate in the treatment of lactic acidosis". Ann Intern Med 108 (1): 58-63. PMID 3337517. Stacpoole P, Kerr D, Barnes C, Bunch S, Carney P, Fennell E, Felitsyn N, Gilmore R, Greer M, Henderson G, Hutson A, Neiberger R, O'Brien R, Perkins L, Quisling R, Shroads A, Shuster J, Silverstein J, Theriaque D, Valenstein E (2006). "Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children". Pediatrics 117 (5): 1519-31. PMID 16651305. Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano M, Shungu D, Millar W, Hong X, Gooch C, Mao X, Pascual J, Hirano M, Stacpoole P, DiMauro S, De Vivo D (2006). "Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial". Neurology 66 (3): 324-30. PMID 16476929. Stacpoole P, Wright E, Baumgartner T, Bersin R, Buchalter S, Curry S, Duncan C, Harman E, Henderson G, Jenkinson S (1992). "A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group". N Engl J Med 327 (22): 1564-9. PMID 1435883. 3:20 PM Xu R, Pelicano H, Zhou Y, Carew J, Feng L, Bhalla K, Keating M, Huang P (2005). "Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia". Cancer Res 65 (2): 613-21. PMID 15695406. Bonnet S, Archer S, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee C, Lopaschuk G, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter C, Andrade M, Thebaud B, Michelakis E (2007). "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth". Cancer Cell 11 (1): 37-51. PMID 17222789. Cheap, safe drug kills most cancers. New Scientist (2007-01-17). Retrieved on 2007-01-17. "DCA: Cancer Breakthrough or Urban Legend?". From ABC News, 5 February 2007. Accessed 15 Feb 2007. "No Wonder Drug", letter to New Scientist from Ralph Moss Lemont. Published February 3, 2007. Accessed 16 Feb 2007. http://www.nationalreviewofmedicine.com/issue/poll/featured_artic le.html "Editorial: Gambling with your life", New Scientist, 31 March 2007 Food&Drug Packaging, August, 2004 Nature Reviews Drug Development, August 2004 A Letter from Dr. Evangelos Michelakis http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070120/DCA_feature_070 121/20070122?hub=Health "Small molecule offers big hope against cancer", by Ryan Smith. From ExpressNews, a University of Alberta publication. Published January 16, 2007. Accessed 15 Feb 2007. Researchers launch website on new cancer research, CTV.ca, 22 January 2007 A Method of Treating Cancer Using Dichloroacetate, Application to the European Patent Office, 19 October 2006 "Long-used drug shows new promise for cancer", The Globe and Mail, 2007-01-17. Retrieved on 2007-01-17. Kaufmann P, Engelstad K, Wei Y et al. (2006). "Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial". Neurology 66 (3): 324–30. PMID 16476929. Stacpoole P, Harwood H, Cameron D, Curry S, Samuelson D, Cornwell P, Sauberlich H (1990). "Chronic toxicity of dichloroacetate: possible relation to thiamine deficiency in rats". Fundam Appl Toxicol 14 (2): 327–37. PMID 2318357. Kurlemann G, Paetzke I, Moller H, Masur H, Schuierer G, Weglage J, Koch HG (1995). "Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy". Eur J Pediatr 154 (11): 928–32. PMID 8582409. Spruijt L, Naviaux RK, McGowan KA, Nyhan WL, Sheean G, Haas RH, Barshop BA (2001). "Nerve conduction changes in patients with mitochondrial diseases treated with dichloroacetate". Muscle Nerve 24 (7): 916–24. PMID 11410919. Oishi K, Yoshioka M, Ozawa R, Yamamoto T, Oya Y, Ogawa M, Kawai M (2003). "Dichloroacetate treatment for adult patients with mitochondrial disease". Rinsho Shinkeigaku 43 (4): 154–61. PMID 12892050. Environ Health Perspect. 2006 Sep;114(9):1457-63 PMID 16966105 (free full text) Andrea Sands. "Experts caution against patients compiling own data on unapproved cancer drug", Edmonton Journal, March 18, 2007. Cancer therapy: When all else fails, Linda Geddes. New Scientist (28 March 2007). Design Custom Diet You can easily design a custom diet: Make it: CHO restricted 20% reduction decreases cancer cell reproduction 40% reduction increases cancer cell death via apoptosis (inhibits glycolysis) Glycine restricted Phosphorus and Vitamin B6 reduced Essential Fatty Acid enhanced Citrus enhanced Parsley approved Vinegar approved (natural source of acetic acid) Via www.foodpharmacy.com Eat high fiber low glycemic foods high alkaline foods, esp. foods high in potassium foods high in Selenium foods high in Niacin foods high in Vitamin D foods high in Oleic acid, Alpha Linolenic acid (ALA) and foods high in omega 3 fatty acids foods high in Phytosterols Restrict Carbohydrates (20-40%) High, medium glycemic foods L-Glycine high Phosphorus foods foods high in Vitamin B6 •Meat/Poultry - beef, buffalo, lamb, venison, chicken (dark meat), cornish hen, elk, pork (bacon), duck, turkey (dark meat) •Seafood – abalone, catfish, caviar, grouper, lobster, oysters, rockfish, scallop, shark, shrimp, tuna, cod, crayfish •Legumes – azuki beans, black beans, fava beans, great northern beans, green beans, green peas, lentils, lima beans, mung beans, red beans, tofu •Beverages – vegetable juices, water (carbonated, distilled, pure bottled or tap filtered), almond milk, beer, coffee (caffeinated, decaf steam), liquor, oat milk, tea (green, black, herbal), wine (red, white) •Dairy and Eggs – camembert, cheddar, edam, eggs (chicken – yolk), milk (whole), roquefort, swiss, whey, blue cheese, brie, buttermilk, colby, cottage cheese (reg or lite), cream (half and half), cream cheese, eggs (chicken – white), eggs (duck – whole), feta, goat cheese, gouda, gruyere, ice cream, milk (skim), monterey jack, mozzarella, muenster, neufchatel, parmesan, provolone, ricotta, romano sour cream, yogurt •Nuts and Seeds – almonds, brazil nuts, cashews, chestnuts, filberts, hickory nuts, macadamia nuts, peanuts, pecans, pine nuts, walnuts, poppy seeds, sesame seeds •Grains – Ø (no ideal or neutral) •Greens – Beet greens, kale, lettuce (bibb, iceberg, loose-leaf, romaine), sprouts (alfalfa), swiss chard, watercress, arugula, cilantro, collard greens, dandelion greens, endive, mustard greens, radicchio, spinach, sprouts (bean), turnip greens Vegetables – artichokes, asparagus, avocado, bamboo shoots, broccoli, brussels sprouts, cabbage, carrot, cauliflower, celery, cucumber, daikon, kohlrabi, mushroom (all edible varieties), olive (all varieties), onion, parsnip, radish, rutabaga, tomato, bok choy, eggplant, fennel, garlic, ginger root, jerusalem, artichoke, jicama, leek, okra, pepper (bell, all colors), pepper (hot, all colors), pumpkin, shallot, turnip, water chestnuts, zucchini Sea Vegetables – Kelp, agar, irish moss, laver, wakame Fruits – apples, blackberries, blueberries, cherries, coconut, elderberries, grapes, guava, kumquat, lemons, limes, oranges, peaches, plums, pomegranates, raspberries strawberries, tangerines, boysenberries, cranberries, gooseberries, kiwi, loganberries, mango, nectarines, papaya, rhubarb Oils and Fats – almond oil, black currant oil, butter (salted), canola oil, coconut oil, corn oil, fish oil, flax oil, hemp oil, olive oil, peanut oil, safflower oil, sesame oil, sunflower oil, wheat germ oil, borage oil, butter (unsalted), evening primrose oil, ghee (clarified butter) Herbs, Spices and Seasonings – chili powder, cinnamon, curry powder, ginger, salt (sea salt, unrefined), vinegar (apple cidar, balsamic, rice, wine), anise, basil, bay leaf, caraway, cardamom, carob, cayenne, chervil, chive, cloves, coriander, cumin, dill weed, fennel seed, fenugreek, garlic powder, horseradish, ketchup, mace, marjoram, mayonnaise, molasses (black unsulphured, small quantities) mustard, mustard seed, nutmeg, oregano, paprika, parsley, pepper (black), peppermint, rosemary, saffron, sage, salt (iodized or low sodium types), savory, soy sauce, spearmint, tarragon, thyme, turmeric, vanilla (extract), wasabi Meat/Poultry - beef (heart), pork (ham, chops), kidney (beef), liver (beef), rabbit, chicken (white meat), goose, pheasant, quail, turkey (white meat) Seafood – anchovy, bass (freshwater), clams, crab, halibut, herring, mussels, perch, pompano, roughy, sardine, squid, swordfish, trout, whitefish, bass (sea), mackerel, mahi mahi, octopus, salmon, snapper Legumes – black-eyed peas, garbanzo beans, navy beans, pink beans, pinto beans, soy beans, white beans Beverages – fruit juices, rice milk, soft drinks, soy milk Dairy and Eggs – goats milk, milk (2%), sherbet Nuts and Seeds – sunflower seeds, pistachios, pumpkin seeds Grains – oats, wheat, wild rice, amaranth, barley, buckwheat, kamut, millet, quinoa, rice (basmati, brown, white), rye, spelt, triticale Greens – Ø (no restrictions) Vegetables – beet, squash (summer, winter), sweet potato, yam, corn, potato (all varieties) Sea Vegetables - dulse Fruits – cantaloupe, pineapple, apricots, banana, casaba melon, currents, dates, figs, grapefruit, honeydew melon, pears, persimmon, prunes, raisins, watermelon Oils and Fats - cottonseed oil, margarine, palm kernel oil Herbs, Spices and Seasonings – chocolate, honey, sugar (brown, brown unrefined, turbinado, white) Suggested Meal Plan: Three meals per day + one snack a meal = 2 servings from each group a snack = 1 serving from each group Avoid fried foods and foods high in sugar. Eat foods raw, steamed, baked or broiled, juiced or sprouted. Eat organic whenever possible CHO (carbohydrates: beverages, grains, greens, vegetables, sea vegetables, fruits): 1 cup (note: greens and all “ideal” vegetables can be eaten in unlimited quantities. Vegetable juice is allowed at 3 glasses per day in addition to your Alcohol should be limited to 1 glass (wine) twice weekly. Grains (oats, wheat, wild rice) are only allowed once weekly and only in whole unprocessed forms.) PRO (proteins: meats, poultry, seafood, legumes, dairy, eggs): 4 ounces FAT (fats: nuts/seeds, oils & fats): 2 tablespoons Herbs, Spices & Seasonings: are allowed in unlimited quantities except for salt which should be used minimally to taste. Water/Tea allowance. It is also recommended that you drink 4 glasses of pure water daily and 3 cups of green tea daily. Make Sure You Cover These Basics Foundational Nutrition Digestion/Elimination Cytochrome p450/phase l/ll conjugation support Pulsed antioxidants Antimetastatics Matrix metalloprotease Inhibition (MMP up-regulate angiogenesis) Glycine is needed for angiogenesis! Immune Enhancement Adjunctive Nutraceuticals Calcium D-Glucurate Use in hormone mediated cancers to enhance glucuronidation Inhibit Isoprenylation with: D-Limonene Block Isoprenylation which is necessary for tumor cell growth (RAS gene, Epithelial Growth Factor, Tyrosine Kinase, Insulin-Like-Growth-Factor) Tocotrienols Inhibit isoprenylation via inhibition of HMG-2, assists DLimonene Niacin Also inhibits RAS gene Depletion of L-Glycine (Cancer cells need to synthesize DNA) Choline Assist Liver metabolism of Niacin Selenium Interfere with Cancer promoter genes and support cancer cell apoptosis DIM Melatonin Inhibit Leukotriene (Boswellia also) stimulation of cancer cells Enhance Thymic hormonal maturation of T cells Vitamin D and Curcumin In hormone mediated cancers - Inhibit hormone stimulation of cancer cell growth and reproduction (Aromatase Inhibition) Inhibit Kinases (critical to cancer cell growth and reproduction) via phosphatase activation Green Tea, Curcumin, White Willow Bark Cox2 inhibition, Phospholipase A2 inhibition – inhibition of Matrix Metaloprotease induced angiogenesis. Inhibition of VEGF (vascular endothelial growth factor) A Word About… Prenylation or isoprenylation is the addition of hydrophobic molecules to a protein to facilitate its attachment to the cell membrane. The result is similar to that of all lipid anchored proteins (e.g. the GPI anchor). All isoprenylation chains are products of the HMG-CoA reductase pathway: geranylgeraniol (GG), farnesol and dolichol. en.wikipedia.org/wiki/Isoprenylation Case History Colon Cancer 63 y.o. male. Dx primary Colon Cancer ~ 12/05. Positive Colonoscopy with abnormal cells (6 cm pelvic mass with several small ~ 1cm perirectal masses) just inside rectum. CT scan positive for tiny spots on liver and lungs. Ø night sweats or weight loss. Hx: smoker x 23 years 1 pack/day, quit 20 y ago, Dx emphysema x 3-4 years, Dx Hypertension controlled with Benzapril) Tx: Initially Ø surgery. 1/06 – 6/06 Chemo Tx (5FU,leucovorin). Ø Radiation Tx. Chemo decreased tumor bulk by 67%. Surgery scheduled for 8/06. Nat. Tx started 12/05. 8/06 f/u CT lungs unchanged, may not be Ca. Could be nodule or lymph node enlargment due to Hx of particle board exposure. Lungs: doing better. Hiking. Less SOB. Bowels: increased BMs due to chem. At worst was up to 15x/day. Alternating diarrhea/constipation. Much better now. Colon Cancer Case Surgery 8/06: removed ~ 1 foot of colon. Reconnected. Spot on Liver: scar tissue. ROC f/u 10/06: Bowel movements now 3-4x/day Working on increased fiber in diet. Helps Emphysema. Not sure if accurate dx. No inhalers since 7/06. Breathing fine. Nose clearer, breathing better since Nasal Polyps removed. Particle board exposure X 33 years (10 years longer than hx of smoking) ROC f/u 1/07: CT scan good. Spot on liver smaller. ? Cyst. Ø nausea or bloating. Some intestinal gas. Stools 3 per day nl color and consistency. Breathing: no need for combivent/flovent since 7/06. Hikes in Mtns w/o problem. No SOB. Walks 3-4x/wk. Snowmobiling with no cold air problems. Gained 8-10 lbs. Current 70 inches and 175 lbs. No recent infections. ROC f/u 7/07: Recent Colonoscopy (7/09/07) – normal. (no sign of Ca. “Even areas where incision done in past are hard to tell. Looks very good”) Weight stable at 175 Nocturia 1x/night occ 2x. Stools remain normal with frequency of 3/day. Hiking 4-6x/wk 4-6 miles each occurrence. Ø SOB. Case History Lung Cancer Significant labs that needed support: ESR: ranged from 56 to 20. Trended down with adjunctive support even while prednisone was being tapered. 6/02 CRP 777 (50-300) 9/02 0.16 (<0.80) Macrocytic anemia. Corrected with nutritional support Occ Leukocytosis, elevated TC, granulocytosis dealt with nutritionally By 5/98 program reduced to ½ and patient continues to improve. Melatonin 20 mg PO QD before bed added 8/98 Side of effects of Radiation to lungs has been Radiation pneumonia. MD have had patient on Rx prednisone. Dose now has been lowered to 10 mg per day. By 11/98 prednisone lowered to 5 mg QD CT scan 5/98. Tumor almost gone! 8/00: No sign of tumor or metastatic spread. 10/05: No sign of return. Patient in excellent overall health. Ongoing Asthma continues but minimal and does not interfere with full activity. Mild DJD in hips, shoulder and knees. Case History Prostate Cancer #1 66 yo retired Engineer CC: Prostate cancer (Dx 6/98, PSA 5.58), High Blood Pressure. HPI: History palpable ‘spot’ on prostate 1995 w/PSA of 3.19) Ultrasound guided biopsy 6/98. Gleason score 7. No regional lymph node evaluation despite CT scan showing 1 enlarged node near prostate Tx: External beam radiation (11/12 – 12/14/98), followed by radio seed implants (1/14/99) and Hormonal ablation with Lupron shots q 3 months Naturopathic Tx: FOC 12/2/98. Program included dietary modification (glycemic balancing, etc.) + prostate support nutrients, immune support, enzyme tx, MCPectin tx, antiangiogenesis tx (S cartilage), EFA (EPA/DHA), Hypertension support (garlic, Mg, EPA/DHA, kidney botanicals) Patient tolerating Tx well. Added Phytosterol support, Soy Isoflavones and Yeast extract to support Krebs cycle oxidative phosphorylation. PSA (2/9/99) <0.1 Slt increase in nocturia after seed implants (~ 3x per night) BP improving now at 146/68. O: noted slt pansystolic murmur. By 3/99 blood pressure down to 124-136/68-74. Lupron tx completed 12/98. PSA 4/14/99 < 0.1. PSA 7/6/99 <0.1. PSA 10/99 <0.1. 4/00 < 0.1 Notes: high dose phytosterols creating a flush around eyes. Decreased dose well tolerated 4/00 Health great. No infections, weight stable, energy good 9/00 Decreasing dosages on Nat Tx protocol to minimum support 12/01 PSA <0.1. Health remains good. 8/03 PSA <0.1 nocturia ~ 1x/night BP well controlled with Rx med and Nat. Tx (Cardio HTN). Bare minimum Prostate support 3/05 PSA <0.1. (age 73) recent dx of NIDDM. Fasting BS 121, Hgb A1C 6.3. Rx Diabetone. 9/06 PSA <0.1 (age 74) Hgb A1C 5.9%, BS 95. BP well controlled. Mild knee arthritis (Rx ArthroGenx + Vit D1000) PSA summary 1995 3.19 6/98 (Dx, tx begins, ext beam + 5.58 2/99 (seed implants 1/14/99) <0.1 4/99 <0.1 7/99 <0.1 10/99 <0.1 4/2000 <0.1 12/01 <0.1 8/03 <0.1 3/05 <0.1 9/06 <0.1 Lupron) (Nat Tx starts 12/98) Comments: Tx effective. PC cured Nat Tx: adjunctive. Sharp decline in PSA probably from Radiation (beam + seeds) and 3 shots of Lupron. Was Nat Tx needed or helpful? Perhaps – recovered quickly from radio Tx side effects. No infections during or after treatment for several years! Strength and energy good. Weight stable. Patient felt ‘in control and participating in his tx’. Don’t discount the importance of this! This is a case where the benefit of our tx is less obvious but intuitively I believe that it was complementary. Case History Prostate Cancer #2 61 y.o. male law enforcement April 2005 DRE exam positive for 2 hard nodules. PSA 3.55. Biopsy (+) for PC. CT scan/Bone Scan Ø mets. Gleason score 7. Overall health good. Exercises regularly. Dietary habits good. Started Naturopathic Adjunctive Support 5/05 Patient elected to have local beam radiation followed by seed implants. Started radio Tx 7/05. Staging T2b. Adjusted Gleason 5a. Seed implants 8/05. 11/05 Overall health remains good. Appetite good. Weight stable. Experiencing some fatigue, urethritis and prostatitis sx as would be expected following radio Tx. Vitals signs (ht, wt, bp, HEENT, Lymph, Heart (slt irreg rhythm). Lungs Neuro, Spine, Abd are normal 1/06, 3/06 PSA 0.8 Overall health good. Urethritis and Prostatitis resolving 2/07 Patient not seen in 11 months. Returns for f/u. Rx’d Food Pharm Custom diet for PC. PSA 8/06 0.3, 11/06 0.39 (oncologists goal <0.5) Bone/CT scan remain (-), Lymph nodes (-). Overall health good. Energy good. Playing golf, racketball, cross-country skiing, and doing weight training.. Prostatitis (-). 4/07 PSA checked in 3/07 down to 0.22. No physical health complaints 7/07 health remains good. PSA 6/07 0.20, 11/07 PSA 0.067! PSA summary: 4/05 – 11/07 3.55 – 1.8 – 0.53 – 0.3 – 0.39 – 0.22 – 0.20 – 0.067 Additional Laboratory: Leukopenia (specifically lymphocytopenia), anemia (macrocytic) – near resolution mild hyperlipidemia (215 – 222 range with HDL 70’s) improved to ~200 TC mild hyperglycemia (~102 fasting) improved to fasting 89 TSH (4.49, high nl with low oral/axillary temps) improved to 1.07 Vit D (25 OH) 39 improved to 69-99 range. (excellent!) Overall adjunctive Naturopathic care: Lycopenes (Tomato extract), Vitamin D, EPA/DHA, DIM Pro Plus, Melatonin 20 mg, BioInflammatory caps, TriZinc, MycoPotent Immune drops, BioAlkalizer, Methylcobalamin/Folinic acid (sublingual), Thyroid 60 mg, CholeLVR, UltraHematinic, UltaPure Whey Protein. Custom Cancer Diet. How BioGenesis Products Fit In Primary Support: (Announcing New Support Products!) Aromatase Inhibition (hormone mediated cancers of the breast, prostate, ovaries, cervix, uterus): BioCleanse powder/caps, BioInflammatory powder/caps Additional COX 2 inhibition(if needed): BioProstate, Intestinal Repair Complex Additional Liver Detox Support (if needed): MycoPotent Immune, Sterol 117, ImmunoGalactans, Liposomal Melatonin Targeted Tissues: Fractionated/Modified Citrus Pectin powder (5-6 grams per day total) Secondary Support: Immune Support: EPA/DHA, Flax Oil Anti-adhesion support: DIM Pro Plus Anti-inflammatory essential fatty acids: Onco-X Onco-Zymes PainX Pulsed Antioxidants: OxyATP (supports Krebs Cycle) Onco-X Onco-X provides maximum adjunctive nutraceutical support for oncology patients. Onco-X functions as a multivitamin and multimineral. Supplies amino acids, antioxidants and specialty ingredients for enhanced cellular/cardiac energy (ATP) production and fatty acid metabolism Antioxidant level compatible with allopathic chemotherapy and radiotherapy treatments Botanicals for adaptogenic support, cellular membrane support and antiinflammatory benefit Methyl donor support via B vitamins to reduce dangerous byproducts of protein metabolism. Blood sugar regulatory support to aide in maintenance of healthy insulincortisol balance. Able to individualize dosage support from light-moderate- high levels easily. Supports Healthy Liver Phase l and ll detoxification pathways including Glucuronidation Supports a healthy immune response with vitamins, minerals, botanicals, IP-6 and Arabinogalactans. Addresses multiple differences in normal vs. abnormal cell physiology simultaneously. Folinc Acid (5 formyl tetrahydrofolic acid) Supports Oxidative Phosphorylation to enhance healthy cell metabolism while simultaneously promoting apoptosis of abnormal cell lines with fully reacted mineral chelates using Krebs cycle organic acids (Citrate) and Acetic Acid. Inhibits Isoprenylation with: D-Limonene: Block Isoprenylation which is necessary for tumor cell growth (RAS gene, Epithelial Growth Factor, Tyrosine Kinase, InsulinLike-Growth-Factor) Tocotrienols: Inhibit isoprenylation via inhibition of HMG-2, assists D-Limonene Niacin: Also inhibits RAS gene Depletion of L-Glycine (Abnormal cells need L-Glycine to synthesize DNA) Note: L-Glycine is essential for abnormal cell growth and reproduction but is a non-essential amino acid for healthy cell metabolism Inhibits abnormal cell growth and reproduction by restricting LGlycine and Vitamin B6. Pyridoxine is a cofactor for L-Glycine metabolism. Inhibits abnormal cell glycolytic energy pathways Inhibits metastasis (spread) of abnormal cells with anti-adhesion properties of modified citrus pectin and curcumin Inhibits Angiogenesis (MMPs) to reduce nutrient delivery to abnormal cells and cell populations Inhibits Kinases (critical to cancer cell growth and reproduction) via phosphatase activation with Vitamin D and Curcumin Continued Onco-Zyme provides enzymes for: •anti-inflammatory •fibrinolytic (antiencapsulation) • circulation support • enhanced phagocytosis and debris field clean up and • immune support • Activate Mitochondrial oxidative phosphorylation to induce apoptosis (Citric and Acetic Acids) Inhibits Kinases (critical to cancer cell growth and reproduction) via phosphatase activation with Vitamin D and Curcumin Activate the Immune system and phagocytosis Inhibit Isoprenylation with: D-Limonene, Tocotrienols, Niacin Additional References Lorincz AB, Kuttner RE. Tumor inhibition limiting amino acid diets (Abstr.) J Am Med Assoc 1967; 200:211 Rabinowitz M. Consequences of amino acid deprivation in combination chemotherapy. J Natl Cancer Inst 1995;87:142 John AP. Dysfunctional mitochondria, not oxygen insufficiency, cause of cancer cells to produce inordinate amounts of lactic acid: the impact of this on the treatment of cancer. Med Hypothesis 2001;57:429-431 Adjei Alex A. Blocking Oncogenic Ras Signaling for Cancer Therapy. J Natl Cancer Inst 2001;93:1062-1072 Ruey Long Hong, William Spohn, Hien-Chie Hung. Curcumin Inhibits Tyrosine Kinase Activity of p185neu and Also Depletes p185neu1. Clin Cancer Res 1999;5:1884-1891 Khafif A Schantz SP. Quantification of chemopreventive synergism between (-) epigallocatechin-3-gallate and curcumin in normal, premalignant human oral epithelial cells. Carcinogenesis 1998;19:419-424. Spitz DR. Glucose Deprivation-induced Oxidative Stress In Human Tumor Cells. Annals of the New York Academy of Sciences. 2000;899:349-362. • Warburg O., "On the Origin of Cancer Cells," Science, 1956;123: 309-14. Broder S., Karp J., "Oncology and Hematology," JAMA, 1994;271: 1694. Kaikobad I., Yong X., Zweier J., "Mitogaenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts," Science, 1997; 275:14. Folkman J., "What is the Evidence that Tumors are Angiogenesis-Dependant?" Journal of National Cancer Institute, 1990; 82: 4-6. Zbigniew W., Hanausek M., Sherman U., Adam A. K., "Antiproliferative Effect of Dietary Glucarate on the Sprague-Dawley Rat Mammary Gland," Cancer Letters, 1990; 49: 51-57. Chandrahar D., Wendy J., Heck B., Downie A. A., Sarroya L.,Webb T. E., "The Effect of Calcium Glucarate on Glucuronidase Activity and Glucarate Content of Certain Vegetables and Fruits,“ Biochemical Medicine and Metabolic Biology, 1990; 43: 83-92. Ellis E. M., "Quest for New and Better Colon Cancer Treatments Picks Up Steam," Journal of the National Cancer Institute, 1998; 90: 1858. Niederhumber J., Brenan M. .F., Menck H., "The National Cancer Data Base Report on Pancreatic Cancer," Cancer, 1995; 76: 1671-7. Burk D., "Symposium on Respiratory Enzymes," Madison, WI: University of Wisconsin Press, 1942; 235. Also - Kidd J. G., Winzler R. J., Burk D., Cancer Research,1944;4: 547. Rabinobitz, M., "Consequences of Amino Acid Deprivation in Combination Chemo therapy," Journal of the National Cancer Institute, 1995; 87:142. Brewer K. “Cancer: Its Nature and A Proposed Treatment” http://www.mwt.net/~drbrewer/brew_art.htm Gerson M. “A Cancer Therapy: Results of 50 Cases”, The Gerson Institute, San Diego, CA, 1990. Kelly WD. “One Answer to Cancer”, 1999. Kritchevsky D., "Can Reducing Caloric Intake Also Help Reduce Cancer?" Journal of the National Cancer Institute, 1998; 90: 1766. The End Contact Information for Dr. David Wood: [email protected] [email protected] “May your practices and your patients be blessed by your care”