Non Diabetic use of insulin in the management of chronic disease and cancer. Insulin Potentiation Therapy Technique. Experimental and pseudo_sience: NO WAY

 The disease, almost any, occurs within the cell. The cell is the basic unit of our organism. Each cell is made up of small microscopic organites that are in charge of making and processing the different chemical substances that other cells require to continue functioning. Cells are grouped into tissues and these make up organs. Within each specialized cell or tissue, multiple chemicals are made that are interacting with each other to keep the body functioning. These chemicals are taken from food and are nutrients. Inside the cell, in the nucleus, is the genetic material that has the information for that cell to perform its functions correctly and depends on the adequate nutrients reaching the cell so that it performs its correct functions and thus maintains the balance or equilibrium and the body is healthy. The disease in most people begins when there are alterations with the nutrients that, when processed inside the cells, stop secreting chemical substances or they come out altered and this leads to alterations in the tissue, which are the disease.
Medications are chemical substances that are going to correct the alterations created or at present or suppress a biochemical function so that the chemical alteration that gives a symptom is stopped. We use and make medicine with symptomatic treatments. We are not going to the root of the problem. As we know today, there is still no real and complete picture of the human cell and although many biochemical functions that occur in the cell are known, beginning with the permeabilization of the cell membrane to allow the exit or entry of chemical substances, there is a lack of Know more details about what each cellular component does, how you interact and its deficiency, what alterations it produces.
What is an experimental treatment: it is the use of a chemical substance manufactured by man and that must have a positive response to correct some symptom and at the same time must have few or no side effects. These treatments are done when the effectiveness of the chemical substance is going to be verified and they are done in a group of patients with clear rules of what can be expected as well as possible side effects. This is how all the drugs we have have been tested, they began as experimental treatments. Many medicines failed to solve the problem for which they were investigated or had adverse effects that put the patient's life at risk.
In the case of the insulin potentiation therapy procedure, it is not an experimental therapy, since a new chemical substance is not being tested for the first time. It is a medical procedure in which modifications are made to the doses or quantity of medicines already approved to be administered following a protocol that has been improved since the non-diabetic use of insulin began in the 1930s. Medicines have been used already approved, only modifying its dose because the use of insulin previously generates a drop in blood sugar, called hypoglycemia, which, as it is controlled, has no risk: it is safe. Therefore it is possible to make corrections of the cause (or raid) of the diseases. It is documented in various medical articles published in scientific journals that insulin potentiates the effect of many chemical substances. So the use of insulin in IPT is not experimental. The Agency for Medicines and Drugs (FDA) in the USA since April 1982 (in its own bulletin) confirms the authorization for the use not specified in the label of the medicine made by the doctor as long as it is done following the safety regulations. Therefore, “off label” uses (unlabeled indications) are allowed under the responsibility of the treating physician. The FDA Agency regulates that medicines for use in humans and animals are safe and effective. Many medications are used to treat symptoms of other diseases that are not on the label and it has been seen that when prescribed for the indicated symptom they have had the improvement of other symptoms as a side effect and this has led to the initial induction dose being Modify for other symptoms.The IPT procedure does not experiment with any new drugs or substances. It is not pseudoscience because nothing is invented and above all there is sufficient evidence written by different medical authors from many countries that documents the potentiating effect of insulin and Diabetes patients who administer insulin know that they must be careful with the dose of other medications that need to be taken. IPT is a modification of the dose of already approved medicines and many are combined following the same recommendations made by the manufacturer or the results reported in studies carried out in Hospitals but with a different dose, because insulin potentiates, that is, it increases the effect inside the cell that is where it refers to acting and that is why it goes to the root of the disease. The next time you read that IPT is experimental or pseudoscience, it is surely an opinion that only reflects the ignorance of the author of said article about the biochemistry, biophysics and pharmacology of drugs, insulin and cell metabolism.
By Donato Perez Garcia, MD

Publications and Essays on IPT, also Supportive Studies – Published clinical and in-vitro studies that support the use of insulin as a biologic response modifier.
off-label use of the drug
1)Poster Presentation at the Third Annual Comprehensive Cancer Management Conference, Washington, DC June 2000
Primary Breast Conserving Treatment for Breast Cancer Using Biologic Response Modification with Insulin in Combination with Non-Toxic Low-Dose Chemotherapy. Steven G. Ayre, M.D.
2)Insulin Shows Promise
Oncology News, 1991, 17(4):1,7
3) Ayre SG, Perez Garcia y Bellon D, Perez Garcia Jr D. Neoadjuvant low-dose chemotherapy with insulin in breast carcinomas. Eur J Cancer. 26:1261-2, 1990
4) Ayre SG, Perez Garcia Y Bellon D, Perez Garcia Jr D. Insulin potentiation therapy: a new concept in the management of chronic degenerative disease. Medical Hypotheses 20:199-210, 1986
5) Lippman ME, Dickson RB, Kasid A, et al. Autocrine and paracrine growth regulation of human breast cancer. J Steroid Biochem 24:147-154, 1986
4) Hilf R. The actions of insulin as a hormonal factor in breast cancer. In: Pike MC, Siiteri PK, Welsch CW, eds. Hormones and Breast Cancer, Cold Spring Harbor Laboratory, 1981, 317-337.
6) 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
6) Holdaway IM, Freisen HG. Hormone binding by human mammary carcinoma. Cancer Res 37:1946-1952, 1977
7) Papa V, Pezzino V, Constantino A, et al. Elevated insulin receptor content in human breast cancer. J Clin Invest 86:1503-1510, 1990
8) Sporn MB, Todaro GJ. Autocrine secretion and malignant transformation of cells. N Engl J Med 308:487-490, 1980
9) Jaques G, Rotsch M, Wegmann C, et al. Production of immunoreactive insulin-like growth factor 1 and response to exogenous IGF-1 in small cell lung cancer cell lines. Exp Cell Res 176:336-343, 1988
10) Nakanishi Y, Mulshine JL, Kasprzyk PG, et al. Insulin-like growth factor-1 can mediate autocrine proliferation of human small cell lung cancer cell lines in vitro. J Clin Invest 82:354-359, 1988
11) Lee PDK, Rosenfeld RG, Hintz RL, Smith SD. Characterization of insulin, insulin-like growth factors I and II, and growth hormone receptors on human leukemic lymphoblasts. J Clin Endocr Metab 62:28-35, 1986
12) Colman PG, Harrison LC. Structure of insulin/insulin-like growth factor-1 receptors on the insulinoma cell, RIN-m5F. Biochem Biophys Res Commun 124:657-662, 1984
13) Zapf J, Froesch ER. Insulin-like growth factors/somatomedins: structure, secretion, biological actions and physiological role. Hormone Res 24:121-130, 1986
14) Papa V, Constance CR, Brunetti A, et al. Progestins increase insulin receptor content and insulin stimulation of growth in human breast carcinomas. Cancer Res 50:7857-7862, 1990
15) Stewart AJ, Johnson MD, May REB, Westley RB. Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem 265:21172-21178, 1990
16) Eppenberger U. New aspects in the molecular growth regulation of mammary tumors. In: Eppenberger U, Goldhirsch A, eds. Recent Results in Cancer Research, Vol. 113: Endocrine Therapy and Growth Regulation of Breast Cancer. Berlin-Heidelberg, 1989, 1-3
17) DeLeon DD, Bakker B, WIlson RL, et al. Demonstration of insulin-like growth factor (IGF-I and IGF-II) receptors and binding protein in human breast cancer cell lines. Biochem Biophys Res Commun 152:398-405, 1988
18) Karey KP, Sirbasku DA. Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17B-estradiol. Cancer Res 48:4083-4092, 1988
19) King GL, Kahn CR, Rechler MM, Nissley SP. Direct demonstration for separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulin-like growth factor) using antibodies to the insulin receptor. J Clin Invest 66:130-140, 1980
20) Jacobs S, Cook S, Svoboda M, Van Wyk JJ. Interaction of the monoclonal antibodies alpha-IR-1 and alpha-IR3 with insulin and somatomedin-C receptors. Endocrinol 118:223-226, 1986
21) Goustin AS, Leof EB, Shipley GD, Moses HL. Growth factors and cancer. Cancer Res 46:1015-1029, 1986
22) Unterburger P, Sinop A, Noder w, et al. Diabetes mellitus and breast cancer: a retrospective follow-up study. Onkologie 13:17-20, 1990
23) Yee D, Palk S, Lebovic GS, et al. Analysis of insulin-like growth-factor I gene expression: evidence for a paracrine role in human breast cancer. Mol Endocrinol 3:509-517, 1990
24) Hilf R. Primary and permissive actions of insulin in breast cancer. In: Leung BS, ed. Hormonal regulation of mammary tumors. Montreal, Eden Press, 1982, Vol. 2, 123-137
25) 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
26) Oster JB, Creasey WA. Enhancement of cellular uptake of ellipticine by insulin preincubation. Eur J Cancer Clin Oncol 17:1097-1103, 1981
27) Schilsky RL, Bailey BD, Chabner BA. Characteristics of membrane transport of methotrexate by cultured human breast cancer cells. Biochem Pharmacol 30:1537-1542, 1981
28) Shinitzky M, Henkart P. Fluidity of cell membranes – current concepts and trends. Int Rev Cytol 60:121-147, 1971
29) Jeffcoat R. The biosynthesis of unsaturated fatty acids and its control in mammalian liver. Essays Biochem 15:1-36, 1979
30) Gasparro FP, Knobler RM, Yemul SS, Bisaccia E, Edelson RL. Receptor mediated photo-cytotoxicity: synthesis of a photoactivatable psoralen derivative conjugated to insulin. Biochem Biophys Res Comm 141:502-209, 1986
31) Poznansky MJ, Singh R, Singh B. Insulin: carrier potential for enzyme and drug therapy. Science 223:1304-1306, 1984
32) Ayre SG. New approaches to the delivery of drugs to the brain. Med Hypotheses 29:283-291, 1989
33) Gross GE, Boldt DH, Osborne CK. Perturbation by insulin of human breast cancer cell kinetics. Cancer Res 44:3570-3575, 1984
34) Paridaens R, Klijn JGM, Julien JP, et al. Chemotherapy with estrogenic recruitment in breast cancer: experimental background and clinical studies conducted by the EORTC breast cancer cooperative group. Eur J Cancer Clin Oncol 22:728, 1986
35) Van der Burg B, de Laat SW, van Zoelen EJJ. Mitogenic stimulation of human breast cancer cells in a growth-factor defined medium: synergistic action of insulin and estrogens. In: Brescani F, King RGB, Lippman ME, Raynaud JP, eds. Progress in Cancer Research and Therapy, vol. 35: Hormones and Cancer 3. New York, Raven Press, Ltd. 1988, 231-233.
36) Goldfine ID, Purello F, Vigneri R, and Clawson GA. Direct regulation of nuclear functions by insulin: relationship to mRNA metabolism. In: Czech MP, ed. Molecular Basic of Insulin Action. New York, Plenum Press, 1985, 329-345.
37)Blood Brain Barrier Passage of Azidothyumidine in Rats: Effects of Insulin
Steven G. Ayre (1), Brian Skaletski (2) and Aron D. Mosnaim( 2). 
Research Communications in Chemical Pathology and Pharmacology JANUARY 1989 VOL.63, NO. 1. Departments of Family Medicine and Pharmacology and Molecular Biology , University of Health Sciences/The Chicago Medical School, North Chicago, IL 60064.
38)New Approaches to Delivery of Drugs to the Brain. S.G. Ayre. Medical Hypotheses 29:283-291, 1989
39)Insulin, chemotherapy, and the mechanisms of malignancy: the design and the demise of cancer. S.G. Ayre, M.D., D. P. Garcia Bellon, M.D., D. P. Garcia, Jr., M.D. Medical hypotheses 55.4 (2000): 330-334.
40)Low dose chemotherapy in combination with insulin for the treatment of metastatic tumors: C. Damyanov, M. Radoslavova, V. Gavrilov, D. Stoeva. Medical Center of Integrative Medicine, Sofia, Bulgaria. Journal of BUON 14: 711-15, 2009.
41)Insulin Potentiation Therapy in the treatment of malignant neoplastic diseases: a three year study. Damyanov C, Gherasimova DM, Avramov LA, Masley IK (2012). J Cancer Sci Ther 4: 088-091. doi:10.4172/1948-5956.1000117
42)Low-Dose Chemotherapy with insulin (Insulin Potentiation Therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer. Damyanov, Christo, et al. ISRN urology 2012 (2012).
43)Metabolic Modification by Insulin Enhances Methotrexate Cytotoxicity in MCF-7 Human Breast Cells. Alabaster, O. Vonderhaar, B. and Shafie, S. Eur J Cancer Clin Oncol. Vol 17, No. 11, pp 1223-1228. 1961. 
44)Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Lundholm K, Körner U, Gunnebo L, Sixt-Ammilon P, Fouladiun M, Daneryd P, Bosaeus I. Clin Cancer Res. 2007 May 1;13(9):2699 706.
45)Long-Term Effect of Diabetes and Its Treatment on Cognitive Function. Jacobson, Alan, et.al. N Engl J Med 2007; 356:1842-52.
46)Preclinical safety and antitumor efficacy of insulin combined with irradiation. Bénédicte F. Jordan, Nelson Beghein, Nathalie Crokart, Christine Baudelet, Vincent Gregoire, Bernard Gallez. Radiotherapy and Oncology 81 (2006) 112–117.
47)Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients. Lasalvio-Prisco, Eduardo, et.al. Cancer Chemother Pharmacol (2004) 53: 220–224.
48)The effect of insulin on chemotherapeutic drug sensitivity in human esophageal and lung cancer cells. Zhonghua Yi Xue Za Zhi. 2003 Feb 10;83(3):195-7. 
49)Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells. Zou K, Ju JH, Xie H. Acta Pharmacol Sin. 2007 May; 28(5):721-30. 
50)A pilot study of Auron Misheil Therapy (AMT) in patients with advanced cervical cancer: tumor response and its correlation with clinical benefit response, and preliminary quality of life data.” Scheele, Jürgen, et al. Oncology reports 22.4 (2009): 877-883.
51)Insulin in endometrial carcinoma chemotherapy: A beneficial addition and not a problem. Sha, Huilan, et al. Journal of Huazhong University of Science and Technology [Medical Sciences] 30 (2010): 631-637.
52) Insulin for Everything. TIME magazine April 10, 1944
53)Long-Term Outcomes of the Treatment of Unresectable (Stage III - IV)Ductal Pancreatic Adenocarcinoma Using Metabolically Supported Chemotherapy (MSCT): A Retrospective Study
Mehmet Salih Iyikesici1, Ayshe Slocum2*, Engin Turkmen3, Ovunc Akdemir4, Abdul Kadir Slocum5, Turgut Ipek6, Erhun Eyuboglu6, Ferhan Bulent Berkarda7
54)Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer. Mehmet Salih İyikesici, Abdul Kadir Slocum, Ayshe Slocum, Ferhan Bulent Berkarda, Miriam Kalamian, andThomas N Seyfried. Cureus. 2017 Jul; 9(7): e1445.Published online 2017 Jul 7. doi:  10.7759/cureus.1445. PMCID: PMC5589510. Monitoring Editor: Alexander Muacevic and John R Adler
55)Integrative Oncology at the Clinicist's Look. Chronology for the Creation and Development of the IPT & BMP Method for Treatment of Oncological Diseases.Nov 22, 2019 in Clinics in Oncology. It is uploaded on the following link: http://https://www.linkedin.com/redir/general-malware-page?url=www%2eclinicsinoncology%2ecom%2Fpdfs_folder%2Fcio-v4-id1671%2epdf%C2%A0%2e We briefly present our clinical experience for the last 12 years, a summary results of treatment of 33 cancer patients, as well as 2 case reports. 
İyikesici M, Slocum A, Slocum A, et al. (July 07, 2017) Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer. Cureus 9(7): e1445. doi:10.7759/cureus.1445

Low dose chemotherapy in combination with insulin for the treatment of advanced metastatic tumors. Preliminary experience. C.Damyanov, M.Radoslavova, V.Gavrilov, D.Stoeva. Journal of BUON 14:711-715,2009.

The insulin potentiated therapy (IPT) in the treatment of chronicle and oncological disease. C.Damyanov, M.Radoslavova, V.Gavrilov. Journal MED info. Nov 2008, N:11, p 55-59.
Insulin Potentiation Therapy in the treatment of malignant diseases: a three year study. Chr. Damyanova, MD, PhD, D. Gerasimova, MD, L. Avramov, PhD, Ass.Prof, D. Dyukmedzhieva, MD. J Cancer Sci Ther 4: 088-091. doi: 10.4172/1948-5956.1000117

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Donato Perez Garcia, MD.