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Annie Brandt, founder of the International Organization of Integrative Cancer Physicians (IOICP), the Best Answer for Cancer Foundation, and 18-year survivor of breast cancer, brought a great selection of speakers and exhibitors for her 16th annual conference in Orlando, Florida, on May 17-19, 2018. A summary of Day 1 appeared in the August-September 2018 issue and Day 2 appeared in December 2018. This article covers Day 3.
Care and Feeding of Mitochondria
Dr. Nalini Chilkov, LAc, OMD, the founder of the American Institute of Integrative Oncology and author of 32 Ways to Outsmart Cancer: How to Create a Body Where Cancer Cannot Thrive, instructs us that there is more to mitochondrial function and cancer than the Warburg Effect and the shift from oxidative phosphorylation to aerobic glycolysis. Mitochondria are crucial cell monitoring sentinels governing cell death through autophagy, mitophagy, and apoptosis.
The overexpression of the Bcl-gene is associated with cancer cell survival and inhibition of apoptosis. The pro-apoptotic Bcl-2 family members Bax and Bak are recruited to mediate mitochondrial outer membrane permeabilization (MOMP), resulting in pore formation and cytochrome c release from mitochondria into the cytosol to activate caspases, the executors of programmed cell death. Tumor cells escape apoptosis by downregulating pro-apoptotic Bcl-2 genes and/or upregulating anti-apoptotic Bcl-2 genes.
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Phytochemicals in food and spices that promote normal apoptosis by inhibition of Bcl-2 include the following: allicillin, apigenin, carnosol, sulforaphanes, I3C, curcumin, gingerol, chrysin, EGCG, resveratrol, pterostilbene, quercetin, genistein, capsaicin and gallic acid. These compounds are found in garlic, parsley, celery, broccoli, kale, turmeric, ginger, rosemary, oregano, cayenne, grapes, red onions, red apples, pomegranate, red berries, blackberries, blueberries, green tea, soybeans, Botanicals that promote normal apoptosis by inhibition of Bcl-2 include the following: Curcuma longa, Panax ginseng, Polygonum cuspidatum, Rabdosia rubescens, Camelia sinensis, Magnolia cortex, Andrographis paniculata, Taxus brevifolia, Scutellaria baicensis, Salvia miltiorrhiza, Dioscorea spp, Ganoderma lucidum, Pleurotus pulmonarius, Inonotus obliquus, Rosmarinus officinalis, Tanacetum parthenium, Tababueia spp, Zingiber off., Withania somnifera, Berberis vulgaris, Coptis chinensis, and Viscum album.
Nutraceutical supplements that promote normal apoptosis by inhibition of Bcl-2 include the following: curcumin, EGCG, resveratrol, pterostilbene, Honokiol, indole-3-carbinol, quercetin, berberine, Tanshinone, reishi mushroom, chaga mushroom, and chrysin, all in 500-1000 mg tid dosing.
Tumor suppressor gene p53, guardian of the genome, induces apoptosis in response to stress. Upon activation, p53 leads to cell-cycle arrest and promotes DNA repair or induces apoptosis. Loss of wild-type p53 function is often associated with aggressive tumor growth, poor prognosis, and resistance to chemotherapy. Restoration of p53 function in mice suffering from lymphomas or sarcomas has been shown to induce tumor regression.
More than 50 percent of human tumors contain a mutation or deletion of the p53 gene. Natural compounds that normalize p53 function are very similar to the Bcl-2 herbs and include 5-methyl-tetrahydrofolate, tocotrienols and vitamin E succinate.
Hexokinase II derived cell penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro. Resveratrol also induced apoptosis and inhibited tumor growth in mice.
MicroRNA (miRNA) are a class of single-stranded non-coding RNA molecules, approximately 22 nucleotides that play crucial roles in gene expression. The same phytochemicals upregulate these miRNAs, which help regulate apoptosis in cancer cells.
Dr. Chikov's presentation was heavily documented and is available from her study guide, lecture summary notes and lecture slides. Download at www.aiiore.com/ioicp2018. Email: email@example.com.
Creating Genomic Stability in Patients with Cancer by Disabling ENOX2 Proteins and Restoring Microbiota Balance
Mitchell J. Ghen, DO, PhD, discussed the ENOX family of cell surface proteins, which is very complex and has far reaching influences upon certain areas of plant and animal biochemistry. These include being responsible for setting the length of periods of activity and inactivity within cells in the body, acting as an internal biological clock. Over 250 peer-reviewed papers have been published on the ENOX proteins. (Morré &Morré (2013) ECTO-NOX Proteins: Growth, Cancer, and Aging).
Why ENOX2? Research has detected ENOX2 proteins four to ten years before development of clinical symptoms. It is cancer specific, elevated early, and useful for screening early intervention. (Morré et al. (2016) Clin. Proteom. 13:2). ENOX2 comes from thiol interchange/cell enlargement in cancer cell membranes to promote unregulated growth. EGCg is a polyphenol that binds to ENOX2 receptor sites, disables them, and is synergistic with the vanilloid component of a specific chili pepper. Ghen gives a summary of outpatient infusion protocol for Capsol-T/ElimENOX2.
Dr. Ghen also reviewed the role of bacteria causing toxic carcinogenic metabolites, increased inflammation, antigen driven lymphoproliferation, and induction of hormones that increase epithelial proliferation. Microbial waste products and mycotoxins weaken the immune system and are causative in prostate cancer, chronic prostatitis, cervical cancer-chlamydia, (HPV), PAL (pyothorax associated lymphoma), Hodgkin's B cell lymphoma, leukemia, and MALT lymphomas. EBV is found in 70-85% of the PAL tumors in Asia. Ghen lists over 300 pathogens capable of enhancing or relating to oncogenesis, including H. pylori, Chlamydophilia psittaci, Borrelia burgdorferi, and mycoplasma.
Treatment with silver hydrosol products has two key advantages: they are broad-spectrum antibiotics and are not yet associated with drug resistance. (Lansdown AB, "Silver. I: Its Antibacterial Properties and Mechanism of Action." J Wound Care. 2002 Apr 11:125-30) Size makes a difference; at 23 parts per million (ppm), there may be over 300,000,000 particles of active silver in every drop of pharmaceutical-grade silver. Silver improves or stimulates the rate of bone marrow WBC production. Indirect mechanisms of action include an increased production of reactive oxygen species, and it induces or catalyzes increased WBC production of myeloperoxidase. Silver has an excellent safety record in these nanosized particles.
Without removal of microbes, the cancer can return. He emphasizes no raw meat, no sushi and reduce sugar. Microbe-killing foods and spices include onion, garlic, allspice, oregano, thyme, tarragon, curcumin, clove, bay leaf, and cayenne pepper.
In summary, cancer treatment aims to block ENOX2 proteins, restore microbiome, decrease inflammation, decrease free radicals, increase nutrition, decrease blood viscosity, disrupt reproductive cycle, improve healthy stem cell function and immune response, and institute positive lifestyle changes.
Contact Mitchell Ghen, DO, PhD, in Boca Raton, Florida, Email: firstname.lastname@example.org.
The Unmet Need
Travis Christofferson has degrees in molecular biology, material engineering, and science. He is the author of the best-selling Tripping Over the Truth: How the Metabolic Theory of Cancer is Overturning One of Medicine's Most Entrenched Paradigms. He is the founder of the Foundation for Metabolic Cancer Therapies, and the CEO of Care Oncology USA. He spoke about off label uses for common drugs in cancer therapy
Christofferson commences with the quote from Lewis Cantley, the director of the Cancer Center at Weill Cornell Medicine: "Metformin may have already saved more people from cancer deaths than any drug in history." Nobel laureate James Watson (of DNA-structure fame), who takes metformin off-label for cancer prevention, once suggested that the drug appeared to be "our only real clue into the business" of fighting the disease.
Metformin may have broad utility in cancer treatment. Researchers at MD Anderson found that among 2,529 women with early-stage breast cancer, the pathological complete response rate after chemotherapy was higher by 24% in diabetic patients who had received metformin than in diabetic patients who had not received metformin (8%) and in nondiabetic patients (16%). In the second study, a group in Department of Gastrointestinal Medical Oncology found that among 255 diabetic patients, the risk of developing pancreatic cancer was 62% lower in those who received metformin than in those who did not. Studies at the University of Pennsylvania reported dramatic improvement in local recurrence in 16 lung cancer patients who received chemoradiation while taking metformin. A study followed 87,344 men diagnosed with prostate cancer between 2000 and 2008. The median overall survival for non-diabetic (not taking metformin), diabetics on metformin, and diabetics not on metformin was 7.1, 9.1, and 7.4 years, respectively. The study concluded that both overall survival and cancer-specific survival was significantly prolonged among the diabetics on metformin.
Statins have also been associated with cancer risk reductions. Several observational studies and meta-analyses have shown reduction in risk of multiple cancers with statin therapy. A recent Danish study showed a 15% reduction in all-cause and cancer specific mortality in statin users as compared to non-users. Improved survival with statin exposure was seen in 13/17 cancer subtypes, including the four most common cancers; lung, prostate, colorectal and breast.
Statins could reduce risk of breast cancer death by 38%, research shows. Overall statin use was associated with a 27% reduction in both cancer-specific and overall mortality. However, those who took the same drugs for more than four years did not appear to show the same protective association, with only a 16% reduction in cancer-specific death, or death from all other causes. A VA retrospective case-control study of 483,733 patients from 1998 to 2004 showed a reduction of lung cancer by 55%. Statins appear to be protective against the development of lung cancer.
Pravastatin seems to be more effective than Simvastatin on the growth of tumor cells from different organ sites. Pravastatin increased survival time in unresectable hepatocellular carcinoma. Median survival was 18 months in the pravastatin group versus 9 months in controls. (Kawata S. et al. Br J Cancer. 2001 Apr 6;84(7):886-91).
Statins (HMG-CoA reductase inhibitors) are well know cholesterol-depleting agents. It has been shown the statins may inhibit the cell cycle by influencing both expression and activity of proteins involved in cell-cycle progression such as cyclins and cyclin dependent kinases. By inhibition of the synthesis of cholesterol, statins may destabilize the cell membrane. The following study reviews several other proposed mechanisms for anti-cancer activity: Matusewicz, et al. The effect of statins on cancer cells – a review. Tumor Biol. 2015 Jul; 36 (7): 4889-904.
The combined metformin-statin program reduced hepatitis B risk for developing cancers nearly in half.
Targeting cancer stem cells with antibiotics is another new treatment modality. Antibiotics that target mitochondria effectively eradicate cancer stem cells across multiple tumor types, treating cancer like an infectious disease. New analysis shows that four to five different classes of FDA approved drugs can be used to eradicate cancer stem cells across 12 different cancer cell lines, including breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma. These five classes of mitochondrially targeted antibiotics include the erythromycins, the tetracyclines, the glyclycyclines, as well as the anti-parasitic drug chloramphenicol. Data were presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol. Mebendazole and a non-steroidal anti-inflammatory combined to reduce tumor initiation in a colon cancer preclinical model (Williamson T, et al. Oncotarget. 2016 Oct 18;7(42):68571-68584).
An oncology clinic from the UK developed COC ProtocolTM, using metformin, atorvastatin, doxycycline, and mebendazole. Using individualized doses of the above medications gave improved results in a METRICS trial on glioblastoma. Two-year overall survival was 55% in the standard of care + COC protocolTM versus a 28.7% survival in the standard of care alone group. Advantages to the proprietary off label protocol include the following: decades of clinical use establishing safety, targets ubiquitous metabolic dysregulation, provides critical need for adjunctive therapy, provides a treatment option when no other exists or has been exhausted and provides a treatment option to prevent recurrence.
"Even James Watson, one of the fathers of molecular biology, is convinced that targeting metabolism is a more promising avenue in current cancer research than gene centered approaches. At his office at the Cold Spring Harbor Laboratory in Long Island, Watson, 88, sat beneath one of the original sketches of the DNA molecule and told me that locating the genes that cause cancer has been 'remarkably unhelpful'. If he were going into cancer research today, Watson said, he would study biochemistry rather than molecular biology." (An Old Idea Revived: Starve Cancer to Death. New York Times, 2016)
Cannabinoids and Terpenoids
Dr. Steve Ottersberg is the founder of Green Lab Solutions Company (Durango, Colorado), operating as Colorado's 11th certified cannabis testing laboratory. He has a BS in biochemistry and an MS in biochemistry from Arizona State University and has an honorary ND from Southwest College of Naturopathic Medicine. He shared his knowledge of human genetic testing in medicine to an audience of physicians, expanding understanding of the biochemical connections between polymorphisms of key enzymes associated with multiple disease states.
Figure: Cannabinoid Receptors
Figure: Neurotransmitter Pathways
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