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Harnessing the Power of Nutrition to Complement Brain Tumor Care

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Presentation by Jeanne M. Wallace, PhD, CNC, at the 1st Annual Brains Matter conference (Sept 2012 in Seattle), sponsored by the Chris Elliott Foundation. Learn how nutrition can play a powerful role to influence the terrain (environment) surrounding cancer cells. Discover foods that can "talk" to your genes, suppressing oncogenes and turning on tumor suppressor genes. Explore simple diet and lifestyle changes you can make to nourish your wellness when facing a brain tumor diagnosis.

Published in: Health & Medicine

Harnessing the Power of Nutrition to Complement Brain Tumor Care

  1. 1. Chris Elliott Foundation’s 1st Annual Brains Matter Conference Sept 21, 2012 • Seattle,WA Jeanne M.Wallace, PhD, CNC Nutritional Solutions eMail: nutritionalsolutions@comcast.net Web: www.nutritional-solutions.net Harnessing The Power of Nutrition Integrative Diet & Nutrition To Complement Brain Tumor Care
  2. 2. What we do ✦ Nutrition consulting for cancer patients & oncologists since 1997 ✦ Referrals from major cancer centers across the U.S. & abroad ✦ Evidence-based written reports of translational research ✦ Consulting via phone, fax, Skype & email ✦ Complement medical care (surgery, radiotherapy, chemotherapy, immunotherapy & gene therapies) ✦ Lab testing to guide protocol individualization and monitor efficacy Who we are 2 Jeanne M. Wallace, PhD, CNC Clinical Nutrition Consultant Translational Research Michelle Gerencser, MS Clinical Nutrition Consultant Master Science / Holistic Nutrition
  3. 3. 3 Who we work with Brain Tumor Clients 1997-2011 Brain Tumor Clients 1997-2011 GBM IV 512 AA II-III 233 Oligo II-III 188 Adult BSG 19 Pediatric (BSG, JPA, Medulloblastoma, PNET, Ependymomas) 234 Benign Tumors (Meningioma,Acoustic Neuromas, NF2) 20 TOTAL 1,206
  4. 4. ➤ N=341 consecutive cases, 1997-2004, pathology confirmed GBM IV, from NCI NCCAM Best Case Series submission ➤ Published survival rates for GBM IV [Shaw et al., 2003] Comparison of Survival Glioblastoma multiforme IV 0% 25% 50% 75% 100% 1 yr 3 yr 5 yr 4 SOURCE: Shaw, E et al: Reexamining the radiation therapy oncology group (RTOG) recursive partitioning analysis (RPA) for glioblastoma multiforme (GBM) patients. Intl J Radiat Onc Biol Physiol, 2003:57:S135–6.
  5. 5. Diet & Nutrition? For Brain Tumors? “With our most aggressive weapons, we aren’t winning the War Against Cancer. How could some wimpy foods have any effect?” 5
  6. 6. Oncology’s New Paradigm 6 Previous Model New Model The Problem
  7. 7. Tumor cells don’t exist in isolation... COX-2 CRP LOX-5 melatonin leptin adiponectin VEGF IGF-1 ↑NFkß 5-HETE cortisol VEGF bFGF IL-6 TNF-α ↓ SHBG ↑ Copper IL-10 fibrin ↓ Antioxidants insulin PDGF ↑ Iron ↓ Vit D ↓ Zinc 7 They’re influenced by factors in their environment.
  8. 8. COX-2 CRP LOX-5 melatonin leptin adiponectin VEGF IGF-1 ↑NFkß 5-HETE cortisol VEGF bFGF IL-6 TNF-α ↓ SHBG ↑ Copper IL-10 fibrin ↓ Antioxidants insulin PDGF ↑ Iron Hyper- coagulability Inflammation Insulin Resistance Hormone Imbalance Nutrient Imbalances Immune Incompetence Angiogenesis ↓ Vit D ↓ Zinc 8 Gene Instability “Oncometabolic Milieu”
  9. 9. COX-2 CRP LOX-5 melatonin leptin adiponectin VEGF IGF-1 ↑NFkß 5-HETE cortisol VEGF bFGF IL-6 TNF-α ↓ SHBG ↑ Copper IL-10 fibrin ↓ Antioxidants insulin PDGF ↑ Iron Hyper- coagulability Inflammation Insulin Resistance Hormone Imbalance Nutrient Imbalances Immune Incompetence Angiogenesis ↓ Vit D ↓ Zinc 9 Gene Instability Today, we’ll cover 3 of these factors.
  10. 10. Modulating Gene Expression 10
  11. 11. Chromosome DNA Gene Understanding Genes Encyclopedia Recipe Word Letters 11
  12. 12. ✦ Men with prostate cancer not electing treatment (surgery, radiation, hormone therapy) enrolled ✦ Gene expression compared after 3 months on diet ✦ Expression of 500+ genes changed ✦ Oncogenes were down-regulated ✦ Tumor Suppressor Genes up-regulated Ornish D, et al: Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci USA. 2008 Jun 17;105(24): 8369-74. 12 Epigenetics: Nutrition Regulates Gene Expression BEFORE AFTER
  13. 13. Cancer’s “Master Switch” 13 Aggarwal B, et al: Nuclear Factor-kß:A holy grail in cancer prevention and therapy. Curr SignalTransduc Ther, 2006:1:25-52. • Van Waes C: Nuclear factor- kappaß in development, prevention, and therapy of cancer. Clin Cancer Res, Feb 15, 2007;13(4):1076-82. ACTIVATES 400+ genes involved in tumor proliferation, survival, angiogenesis & invasion NFkß TRIGGERS: carcinogens oxidation viral infection inflammation radiation chemotherapy stress
  14. 14. Spices Inhibit NFkß Aggarwal B & Shishodia S: Suppression of the nuclear factor-kappaß activation pathway by spice derived phytochemicals: reasoning for seasoning. Ann NY Acad Sci, Dec 2004;1030:434-41. The reason to season? To talk to your genes! anise basil black pepper caraway cardamom chili pepper cinnamon clove coriander cumin fennel fenugreek flaxseed garlic ginger Holy basil lemongrass licorice mint mustard seed nutmeg oregano parsley rosemary saffron tamarind turmeric 14
  15. 15. Methyl groups prevent the DNA strand from being UNZIPPED Histone deacetylase (HDAC) UNWRAPS the DNA strand 15 Hardy TM & Tollefsbol TO: Epigenetic diet: impact on the epigenome and cancer. Epigenomics 2011;3(4):503-18. Delage B & Dashwood RH: Dietary manipulation of histone structure and function. Ann Rev Nutr. 2008;28:347-66. KEEP GENE WRAPPED HDAC Inhibitors Sulforaphane Isothiocyanates Allyl sulfides Genistein Quercetin Resveratrol Curcumin Luteolin Selenium Theophylline Vitamin E Butyrate KEEP GENE ZIPPED Methylation Folate Vitamin B12 Vitamin B6 Betaine Choline Magnesium Zinc
  16. 16. Spices (combinations: curry, chai) Broccoli sprouts (sulforaphane) Brassica veggies (sulforaphane) Dark leafy greens (folate) Garlic, onions, leeks, chives, shallots Parsley, celery, red pepper (luteolin) Peanuts/boiled, red grapes/wine (resveratrol) Red onions and capers (quercetin) Green tea (theophylline, EGCG) Fish, eggs, cheese, sunflower seeds, asparagus, almonds (B vitamins) Top Foods to Modify Gene Expression 16
  17. 17. 17 Insulin Resistance & Cancer
  18. 18. Blood Sugar & Brain Tumor Survival Survival (months) Mean Blood Glucose Level (mg/dl) 0 4 8 11 15 65-93 94-137 ≥ 138 14.5 mo 9.1 mo Derr R, et al., Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol, 2009 Mar 1;27(7):1082-6. 18
  19. 19. ✦ ↑ Post-Op Loss of Function - pts with ↑ glucose 2x likely to have new post-op neurological deficits ✦ ↑ Recurrence - ↑ risk of recurrence in 5 yrs in low grade glioma in pts with hyperglycemia (5- yr survival 43% vs 84%) ✦ Immune Suppression - ↑ risk of infection in pts undergoing intensive chemotherapy ✦ ↑ Seizures - case reports link ↑ seizures with hyperglycemia Link TW, et al: Hyperglycemia is independently associated with post- operative function loss in patients with primary eloquent glioblastoma. J Clin Neurosci 2012:19, 996–1000. Chaichana KL, et al: Persistent outpatient hyperglycemia is independently associated with survival, recurrence and malignant degeneration following surgery for hemispheric low grade gliomas. Neurol Res 2010;32, 442–448. Derr R, et al: Antecedent hyperglycemia is associated with an increased risk of neutropenic infections during bone marrow transplantation. Diabetes Care, 2008 Oct;31(10):1972-7. Hennis A, et al: Focal seizures and non- ketotic hyperglycaemia. J Neurol Neurosurg Psychiatry 1992;55:195-197. High Blood Sugar: Other Findings 19
  20. 20. Cowey S & Hardy RW:The metabolic syndrome:A high-risk state for cancer? Am J Pathol, 2006 Nov;169(5): 1505-22. How Insulin Resistance Influences Cancer Abbreviations: • E, estrone • E2, estradiol • A, androgens; • mito, mitochondria; • ROS, reactive oxygen species • SHBG, sex hormone- binding globulin; • FFA, free or nonesterified fatty acids • TG, triglycerides • IGFBPs, insulin-like growth factor-binding proteins. Used with permission 20 EFFECTS
  21. 21. Is your body “apple” shaped? Indicator Functional Reference* Waist-Hip Ratio women > 0.8, men >1.0 Waist Circumference women ≥ 35, men ≥ 40” A1c > 5.0-5.2% Triglycerides > 110 mg/dL HDL cholesterol < 50-55 mg/dL Blood pressure > 120/80 Glucose fasting > 60-90 mg/dL post-prandial > 120 mg/dL Uric Acid > 5.5 mg/dL *NOT STANDARD REFERENCE RANGES. Target ranges based on optimal, Functional Medicine ranges and/or cut-off points associated with improved prognosis in cancer patients. 21 Indicators of the Need to Address Glycemic Control
  22. 22. Insulin Resistance: Contributing Factors ✦ DIET - excess caloric intake; ↑ refined carbs (foods with ↑ Glycemic Load) ✦ MEDICATIONS - steroids (Decadron) ✦ STRESS - ↑ cortisol ✦ LACK OF EXERCISE - ↓ muscle mass ✦ NUTRIENT DEFICIENCIES - vitamin D, zinc, magnesium, chromium, CLA, carnitine, biotin, vanadium 22 BEWARE! These wholesome- appearing foods may be problematic for you!
  23. 23. Foods with High Glycemic Load ( > 10) 23 Bread, white Bread, whole wheat Cereal Oatmeal Crackers Muffins Bagels Cookies Pancakes Waffles Soda pop Fruit Juice Dried fruits Candy Chips Sugar Honey Flour, white Flour, whole wheat Corn Cornmeal Pasta Potatoes Potato chips Pretzels Rice, white Rice, brown Fat-free foods www.nutritiondata.com 5 grams =
  24. 24. 24 Low Glycemic Substitutions INSTEAD OF THIS...INSTEAD OF THIS... TRY THIS...TRY THIS... Food (1 cup serving) Glycemic Load* Food (1 cup serving) Glycemic Load White flour Whole wheat flour 76 44 Almond Flour 0White flour Whole wheat flour 76 44 Coconut Flour 0 Corn, sweet yellow 35 Baby Corn 5 Hamburger bun 18 Rice paper wrap 4 Hamburger bun 18 Portobello mushrooms 3Hamburger bun 18 Romaine lettuce “wrap” 0 Brown rice 22 Cauliflower “rice” 2 Pasta noodles 22 Spaghetti Squash 2 Pasta noodles 22 Zucchini “noodles” 1Pasta noodles 22 Miracle Noodles 0 Mashed Potatoes 16 Mashed Cauliflower 4 * Low GL ≤ 10
  25. 25. Cinnamon Berries: blueberries, goji, blk currant Chamomile tea Allium family: garlic, onions, leeks, chives Parsley Avocado Olive oil Flaxseed meal Oat bran (soluble fiber) Lemon Top Foods to Support Glycemic Control 25 Kaushik G, Satya S, Khandelwal RK, Naik SN. Commonly consumed Indian plant food materials in the management of diabetes mellitus. Diab Metabol Syndr: Clin Res Rev. 2010;4(1):21-40. Yeh GY et al: Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diab Care 2003 Apr;26(4):1277-94.
  26. 26. Inflammation and Cancer 26
  27. 27. Inflammation & Cancer Survival McMillan DC, et al: Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer. Nutr Cancer, 2001;41(1-2):64-9. 27 0% 20% 40% 60% 80% 100% 0 200 400 600 800 1000 % patients surviving Time (in days) Low CRP High CRP
  28. 28. ✦ ↓ BT Risk 50-65% ↓ risk of developing GBM brain tumors in people regularly taking anti-inflammatory drugs (aspirin or ibuprofen) ✦ Poor prognosis - ↑ inflammatory compounds was the strongest predictor of poor outcome for glioma patients ✦ Toxicity of Chemotherapy - more severe low blood counts ✦ Fatigue - ↑ fatigue, poorer QOL Sivak-Sears NR, et al: Case-control study of use of nonsteroidal antiinflammatory drugs and glioblastoma multiforme. Am J Epidemiol 2004;159, 1131–1139. Shono T, et al: Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res 2001;61, 4375–4381. Alexandre J, et al: Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy. Ann Oncol, 2003;14:36-41. Mohmoud FA, Rivera NI: The role of C- reactive protein as a prognostic indicator in advanced cancer. Curr Oncol Rep, May 2002;4(3):250-5. Inflammation: Other Findings 28
  29. 29. 29 Dietary Fats & Inflammation OMEGA-6 FATS •Commercially-raised meat, poultry, dairy, eggs •Trans & Hydrogenated fats •Vegetable oils—corn, safflower, soy, grapeseed (not olive oil) ANTI-INFLAMMATORY Compounds Inhibit tumor growth & progression Anti-angiogenesis Complement radiation & chemo OMEGA-3 FATS •Grass-fed/pastured meat, poultry, dairy, eggs •Cold-water fish •Blk walnuts, flaxseeds •Oils of flax, hemp and canola (not advisable) PRO-INFLAMMATORY Compounds Foster tumor growth & progression Promote angiogenesis Suppress immune function ↑ INSULIN Wallace JM (2002). Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy. Integr CancerTher 1, 7–37; discussion 37.
  30. 30. ✦ Vegetable oils (peanut, corn, soy, sunflower, canola, etc) ✦ Bottled salad dressing ✦ Baked goods (store-bought pies, cakes, muffins, donuts, cookies) ✦ Fried foods (trans fats) ✦ Chips, crackers, processed snack foods ✦ Mayonnaise ✦ Conventionally-raised (corn-fed) meats & dairy ✦ Margarine, spreads, dips ✦ Granola, breakfast cereals Fats that Increase Inflammation 30 Good Fats Olive oil Butter (organic, pastured) Coconut oil Avocados
  31. 31. ✦ Ratio of ω-6:3 fats about 1:1 to 3:1 ✦ ↓Vegetable oils, margarine, commercially- raised meat, poultry, dairy, eggs ✦ ↑ Cold-water fish, organic grass-fed meat, poultry, dairy and omega-3 rich eggs, walnuts, hemp, chia and flaxseed meal, leafy greens ✦ ↑ Intake of fruits & vegetables (8+ servings/day) ✦ Low glycemic diet (↓ insulin-driven inflammation) Diet to Address Inflammation Find sources for grass-fed foods at www.eatwild.com 31
  32. 32. Spices (esp. curry, ginger, garlic, parsley) Wild, cold-water fish Grass-fed (pastured) meat, dairy, eggs Hot peppers Olive oil Leafy green veggies (spinach, chard, kale) Cruciferous vegetables Pumpkin, butternut squash, yam, carrot Dark chocolate (flavanols) Berries (blueberries, cherries, raspberries) Top Foods to Quench Inflammation 32 www.nutritiondata.com • Reinagel M: The Inflammation Free Diet Plan, McGraw-Hill, 2007. • Hamed MS, et al. Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South Med J, 2008; 101(12):1203-1208.
  33. 33. 33 Review: Take Home Tips
  34. 34. 34 “Three times a day, day after day, we are eating foods that can influence our genes and help us fight cancer...” —David Servan-Schreiber, MD FOOD IS POWERFUL MEDICINE
  35. 35. QUIZ: Are You Ready to Harness the Power of Your Diet? 35 1. Lessen inflammatory messengers that foster tumor growth and progression? 2. Reduce intake of these to influence cancer at least 5 ways? 3. Block cancer’s “Master Switch” NFkß? 4. Quiet oncogenes by keeping them wrapped/zipped? A B C D
  36. 36. 36 melatoninleptin IGF-1 cortisol ↑ Copper insulinInsulin Resistance Hormone Imbalance Nutrient Imbalances ↓ Vit D ↓ Zinc COX-2 CRP LOX-5↑NFkß VEGF TNF-αIL-10 Inflammation Immune Incompetence Angiogenesis Gene Instability ✦ Individualize nutrition protocols ✦ Navigate nutrition controversies ✦ Prioritize self-care strategies ✦ Complement medical treatments Use model to make informed choices...
  37. 37. Promising Research 37
  38. 38. Boswellia 38 ✦ Gum resin of frankinsence tree ✦ Anti- inflammatory, LOX-5 inhibitor ✦ 6 published reports show efficacy in reducing cerebral edema ✦ May help reduce steroid use Böker D & Winking M: Die Rolle von Boswellia-Säuren in der Therapie maligner Gliome. Deuts Ärzt 1997;94:1197. Janssen G, et al: Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Klin Padiatr 2000;212:189–195. S t r e f f e r J R , e t a l : R e s p o n s e o f radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15. Neurology 2001;56:1219–1221.
  39. 39. 39 Berberine ✦ Yellow plant alkyloid from goldenseal, Oregon grape root ✦ Equally effective as metformin in controlling blood sugar ✦ In animal model: as effective as chemo against BTs, highly synergistic ✦ Radiosensitizer Yount G, et al: Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro. J Exp Ther Oncol 2004;4,:137– 143. Zhang RX, et al: Laboratory studies of berberine used alone and in combination with 1,3-bis(2- chloroethyl)-1-nitrosourea to treat malignant brain tumors. Chin Med J 1990;103:658–665. Chen KT, et al: Effect of berberine alone or in combination with argon ion laser treatment on 9L rat glioma cell line. Chin Med J 1994;107:808– 812. Eom KS, et al: Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction. Biol Pharm Bull 2010;33:1644–1649.
  40. 40. 40 Zuccoli et al. Nutrition & Metabolism 2010, 7:33 http://www.nutritionandmetabolism.com/content/7/1/33 Open AccessBRIEF COMMUNICATION Brief communication Metabolic management of glioblastoma multiforme using standardtherapy together with a restricted ketogenic diet: Case Report Giulio Zuccoli*1,5, Norina Marcello2, Anna Pisanello2, Franco Servadei3, Salvatore Vaccaro4, Purna Mukherjee6 and Thomas N Seyfried*6 Abstract Background: Management of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI). Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter. Methods: Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a Ketogenic Diets
  41. 41. Krishnan AV & Feldman D: Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011 Feb 10;51:311-36. Teegarden D & Donkin SS:Vitamin D: emerging new roles in insulin sensitivity. Nutr Res Rev. 2009 Jun;22(1):82-92. Hakko H et al: Season of tumor surgery in relation to deaths among brain tumor patients: does sunlight and month of surgery play a role in brain tumor deaths? Acta Neurochir (Wien) 2009;151:1369–1375. Vitamin D ✦ Induces differentiation (revert to normal cell type) ✦ Promotes apoptosis (programmed cell death) ✦ Plays a role in blood sugar regulation and insulin sensitivity ✦ Worse outcome for glioma III- IV pts operated on in darkest months in Finland study 41
  42. 42. 42 Lycopene ✦ Study presented at ASCO 2005 ✦ 50 pts high-grade glioma randomized 8 mg lycopene vs placebo w/ RT Placebo Lycopene Partial Response 24% 40% Complete Response 20% 40% Response Rate 44% 80% TTP 21 wks 39 wks Puri T, et al: Role of natural lycopene and phytonutrients along with radiotherapy and chemotherapy in high grade gliomas. J Clin Onc, 2005 ASCO Ann Meet Proc. 2005; 23(16S): 1561. Tomato soup 1 cup 24 mg Tomato sauce 1/2 cup 23 mg Salsa 1/4 cup 9 mg Tomato paste 1 TBSP 7 mg Ketchup 2 TBSP 6 mg Tomato, fresh 1 large 4 mg
  43. 43. 43 Temodar, MGMT +Methylation ✦ MGMT is a DNA repair gene ✦ Expressed MGMT promotes clinical resistance to TMZ ✦ Silence MGMT to increase efficacy of TMZ ✦ Methylation (folate / greens) silences MGMT ✦ Resveratrol also silences MGMT van den Bent MJ, et al:A hypermethylated phenotype is a better predictor of survival than MGMT methylation in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951. 2011;17, 7148–7155. Hervouet E, et al: Folate supplementation limits the aggressiveness of glioma via the remethylation of DNA repeats element and genes governing apoptosis and proliferation. Clin Cancer Res 2009;15:3519–3529. Zhang X: Resveratrol reverses temozolomide resistance by downregulation of MGMT in T98G glioblastoma cells by the NF-κB-dependent pathway. Oncol Rep; 2012;27(6):2050-6. Nakada M et al:The strategy for enhancing temozolomide against malignant glioma. Front Oncol 2012;2:98.
  44. 44. 44 Curcumin ✦ PubMed, 64 studies published to date ✦ Bioaccumulates in fatty brain tissue ✦ Promotes apoptosis (programmed cell death) ✦ Radiosensitizer, chemosensitizer (potentiates TMZ), but protects healthy cells ✦ Inhibits NFkß ✦ Promotes differentiation ✦ Anti-angiogenic ✦ Inhibits inflammation ✦ Modulates gene expression (HDAC inhibitor) ✦ Inhibits tumor cell migration NFkß
  45. 45. 45 Resveratrol ✦ PubMed, 55 studies(12 on medulloblastoma) ✦ Inhibits NFkß ✦ Modulates gene expression (HDAC inhibitor) ✦ Promotes apoptosis (programmed cell death) ✦ Inhibits angiogenesis ✦ Inhibits tumor cell invasion ✦ Promotes differentiation of GBM ✦ Radiosensitizer, chemosensitizer (potentiates TMZ), but protects healthy cells FOOD SOURCES grapes wine grape juice peanuts (boiled) mulberries cranberries pistachios cocoa / chocolate Yuan Y, et al: Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS NeurosciTher 2012;18:536–46. Lin C-J, et al: Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy. Free Radic Biol Med 2012;52,:377–91. Chen J-C, et al: Resveratrol suppresses angiogenesis in gliomas: evaluation by color Doppler ultrasound. Anticancer Res 2006;26:1237–45.
  46. 46. Nutritional Solutions Jeanne M. Wallace, PhD, CNC, and Michelle Gerencser, MS www.nutritional-solutions.net The environment in your body is talking to your tumor cells... What do you want it to say? Nighty night. Go to sleep... Be Quiet! Hush!

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