» Potentiation TherapyKinder Therapy
Insulin Potentiation Therapy (IPT) manipulates the mechanisms of malignancy to therapeutic advantage by employing insulin as a biologic response modifier of cancer cells molecular biology. The proliferation of malignancy is supported by secretion of insulin for glucose/energy uptake by cancer cells, and a similar elaboration of cellular factors to stimulate cancer growth. Among these, insulin-like growth factors (IGF) have been identified as the most potent cellular growth factors for cancer cells. Of primary importance for IPT, a cancer cells membrane has six times more insulin receptors and ten times more IGF receptors than the membranes of normal cells. Insulin also cross-reacts with and activates cancer cell IGF receptors. Thus, a cancer cell has sixteen times more insulin-sensitive receptors than normal tissues. As ligand effect is a function of receptor concentration, these facts serve to differentiate cancer from normal cells - a vital consideration for the safety of cancer chemotherapy.
In light of these revelations, exogenous insulin acts to enhance anti-cancer drug effectiveness and safety. Insulin promotes the following beneficial effects: 1) a membrane permeability effect to increase the intracellular dose intensity of the drugs, 2) an effect of metabolic modification to increase the S-phase fraction in cancer cells, enhancing their susceptibility to cell-cycle phase-specific agents, and 3) an effect of biochemical differentiation based on insulin receptor concentration that focuses the first two insulin effects predominantly on cancer cells, sparing host normal tissues. Significantly less drug can thus be targeted more specifically and more effectively to cancer cells that are more susceptible to the chemotherapy drug effects, all this occurring with a virtual elimination of the dose-related side effects of these powerful drugs.
Because of this favorable side effect profile, cycles of low-dose chemotherapy with IPT may be done more frequently. There is good patient acceptance of the low blood sugar (hypoglycemic) side effect of insulin in this protocol, and the "rescue phenomenon" occasioned by the timely administration of hypertonic glucose actually serves to provide patients with an experiential metaphor for the rapid recovery of their well being. It is widely known that cancer chemotherapy treatment can often be debilitating for patients. In those undergoing treatment with IPT, an overall gentler experience also promotes their use of other important elements in a program of Integrative Cancer Care, which includes nutrition and mind-body medicine to support a healing consciousness.
Insulin is one of the most powerful hormones in human biochemistry and it is also the single most studied molecule in medical history. What is known about its effects on the human body fills books. However, what is not generally appreciated about insulin by American medicine is the role that this hormone plays in the mechanisms of malignancy. Here are some scientific facts: Insulin increased the cell-killing effects of the chemotherapy drug methotrexate in a population of human breast cancer cells in tissue culture by a factor of up to ten thousand. Cancer cells manufacture and secrete their own insulin, and they do so without paying any attention to those higher levels of integrated control that keep a rein on levels of normal insulin secretion from the pancreas. Insulin operates via a complex interaction with specific insulin receptors on cell membranes – and cancer cells have fifteen times more insulin-sensitive receptors on their cell membranes than normal tissues do. And there is a law in physiology which dictates that hormone effects (insulin is a hormone) are a function of receptor concentration; so the more receptors per cell, the more effect of the hormone on that cell. Cancer cells have fifteen times more insulin sensitive receptors than normal tissues.
Thus, insulin and cancer are intimately connected. And insulin and cancer chemotherapy can also be intimately connected. Pre-treating a cancer patient with insulin allows doctors to use a greatly reduced dosage of chemotherapy drugs to treat the cancer. Insulin creates circumstances that facilitate drug entry into cancer cells, and because there are so many more insulin-sensitive receptors on cancer cell membranes compared to normal tissues, the drug potentiating effect of insulin affects the cancer cells to a much greater extent than the normal cells. Since chemotherapy drug side effects are usually dose-related, lowering the dose is an important idea - especially when the lower dose has the augmented cancer cell killing effect indicated from the tissue culture experiment cited above (“up to ten thousand fold increase”).
IPT chemotherapy is not more effective than standard dose chemotherapy; both IPT chemotherapy and standard dose chemotherapy will be seen to work in one particular situation, and both will not work in another situation. Why some cancers do not respond to any method of chemotherapy continues to be a modern medical mystery. However, the dose related chemotherapy side effects from higher dose standard chemotherapy can even kill a severely ill cancer patient. That is much less likely to happen with IPT chemotherapy. Knowing that IPT chemotherapy treatments can deliver the benefit of these powerful cell-killing chemotherapy drugs with a ninety to ninety-five percent reduction in side effects is a very reassuring thought for the cancer patient and their family. However, IPT is not for everyone. Standard approved therapy for newly diagnosed disease is always indicated. For those patients who refuse all conventional forms of standard medical cancer care, IPT is a realistic and excellent alternative.
SUMMARY
In insulin potentiation therapy the hormone insulin is used as an adjunct in the medical management of the chronic degenerative diseases, including cancer.1-10 The endogenous molecular biology of cancer cells involves secretion of insulin and insulin-like growth-factors I and II. These biological response modifiers are necessary for the cancer cell for energy production and growth stimulation. These activities confer on cancer its malignant potential, working as they do autonomously, free from higher levels of integrated control. Taking advantage of cancer's mechanisms of malignancy by employing therapeutic insulin as a biologic response modifier, it is possible to potentiate the cytotoxic effects of chemotherapeutic agents for the less toxic treatment of cancer. The physiological action of insulin of increasing cell membrane permeability is taken advantage of to potentiate the pharmacological actions of medications administered in the therapy. A synergy between certain membrane and metabolic effects of insulin on cancer cell molecular biology increases anticancer drug efficacy, while decreasing drug toxicity and side-effects.
REFERENCES
1. S. G. Ayre, D. Perez Garcia y Bellon and D. Perez Garcia, Jr. IPT: A New Concept in the Management of Chronic Degenerative Disease . Medical Hypotheses 20(2):199-210, 1986.
ADVANCE \d42. Steven G. Ayre, Donato Perez Garcia y Bellon and Donato Perez Garcia, Jr. Neoadjuvant Low-Dose Chemotherapy with Insulin in Breast Carcinomas. European Journal of Cancer; 26(11-12):1262-3, 1990
3. S.G. Ayre, D.P. Garcia y Bellon, D.P. Garcia Jr. Insulin, Chemotherapy and the Mechanisms of Malignancy: The Design and the Demise of Cancer. Medical Hypotheses; 55(4): 330-334, 2000
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ADVANCE \d45. Wong M, Holdaway IM. Insulin binding by normal and neoplastic colon tissue. Int J Cancer 35:335-341, 1985
ADVANCE \d46. Mountjoy KG, Holdaway IM, Finlay GJ. Insulin receptor regulation in cultured human tumor cells. Cancer Research 43:4537-4542, 1983
7. Cullen JK, Yee D, Sly WS, et al. Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res 50:48-53, 1990
ADVANCE \d48. Papa V, Pezzino V, Constantino A, et al. Elevated insulin receptor content in human breast cancer. J Clin Invest 86:1503-1510, 1990
ADVANCE \d49. Alabaster O, Vonderhaar BK, Shafie SM. Metabolic modification by insulin enhances methotrexate cytotoxicity in MCF-7 human breast cancer cells. Eur J Cancer Clin Oncol 17:1223-1228, 1981
ADVANCE \d410. Schilsky RL, Bailey BD, Chabner BA. Characteristics of membrane transport of methotrexate by cultured human breast cancer cells. Biochem Pharmacol 30:1537-1542, 1981
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