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Purpose. To evaluate the results and quality of life of patients with resistant of castration-resistant tumors previously treated with Insulin-potentiation therapy (IPT) combined with hormone therapy. Materials and methods. Sixteen patients with metastasis prostate tumors after bilateral castration, androgenic blockade, and progression of the disea...
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... About 80% of these patients demonstrated remission and improved quality of life. Our experience with IPT up to now, and its use, made IPT leading method in our medical practice [5][6][7][8]. ...
... 2 thus obtained demonstrated the possibility to suspend the tumour's growth and improve the patients' quality of life in about 80% of the cases [7][8][9]. ...
... The complementary treatment included dietary therapy, antioxidant therapy, immunotherapy, ozone therapy and Pulsed Electromagnetic Field (PEMF) therapy. The methodology of IPT application was described in our prior publications [7][8][9]. ...
... The conflicting results regarding the effect of insulin on the PI3K pathway may be explained due to the relatively short duration of action. Moreover, the concentration of insulin used in the in vitro experiment was higher than circulating concentrations observed in a clinical setting or concentrations used in the previous studies [9][10][11][12][13][14][15][16] . Higher doses of insulin are known to activate IGF1R-related signaling and affect the propensity for invasion and metastasis. ...
The present state of cancer chemotherapy is unsatisfactory. New anticancer drugs that marginally improve the survival of patients continue to be developed at an unsustainably high cost. The study aimed to elucidate the effects of insulin (INS), an inexpensive drug with a convincing safety profile, on the susceptibility of colon cancer to chemotherapeutic agents: 5-fluorouracil (FU), oxaliplatin (OXA), irinotecan (IRI), cyclophosphamide (CPA) and docetaxel (DOC). To examine the effects of insulin on cell viability and apoptosis, we performed an in vitro analysis on colon cancer cell lines Caco-2 and SW480. To verify the results, we performed in vivo analysis on mice bearing MC38 colon tumors. To assess the underlying mechanism of the therapy, we examined the mRNA expression of pathways related to the signaling downstream of insulin receptors (INSR). Moreover, we performed Western blotting to confirm expression patterns derived from the genetic analysis. For the quantification of circulating tumor cells in the peripheral blood, we used the maintrac method. The results of our study show that insulin-pretreated colon cancer cells are significantly more susceptible to commonly used chemotherapeutics. The apoptosis ratio was also enhanced when INS was administered complementary to the examined drugs. The in vivo study showed that the combination of INS and FU resulted in significant inhibition of tumor growth and reduction of the number of circulating tumor cells. This combination caused a significant downregulation of the key signaling substrates downstream of INSR. The results indicate that the downregulation of PIK3CA (phosphatidylinositol 3-kinase catalytic subunit alpha), which plays a critical role in cell signaling and GRB2 (growth factor receptor-bound protein 2), a regulator of cell proliferation and differentiation may be responsible for the sensitizing effect of INS. These findings were confirmed at protein levels by Western blotting. In conclusion, these results suggest that INS might be potentially applied to clinical use to enhance the therapeutic effectiveness of chemotherapeutic drugs. The findings may become a platform for the future development of new and inexpensive strategies for the clinical chemotherapy of tumors.
... Giving insulin just prior to the infusion of low dose chemotherapeutic agents, usually in a combination designed to intervene at several sites of the cell cycle, causes much less side effects and can hold the cancer at bay while buying time to reconstitute an effective immune response or integrate another therapeutic strategy. IPT has been in development and clinical use since the 1930s and has been used to help treat other chronic diseases as well [40][41][42][43][44][45][46][47][48]. ...
Over the years, the treatment of patients with cancer has varied widely as much because of recent advancements in science and medicine as the philosophies that belie their use. This paper briefly describes many of the prevailing approaches in use today with an attempt to offer some perspective of how to apply these disparate methodologies so that they may be more effectively integrated, resulting in consistently better clinical responses.
... About 80% of these patients demonstrated remission and improved quality of life. Our experience with IPT up to now, and its use, made IPT leading method in our medical practice [5][6][7][8]. ...
The current presentation displays chronologically our summarized and updated results of more than 12 years of the accumulated experience of integrative oncology application in our medical practice. Based on our concept of systemic approach, we have created treatment protocol for cancer patients with leading method of administering Insulin Potentiation Therapy (IPT). For the past 12 years period we treated more than 1100 cancer patients, greater part of which (94%) were patients with advanced metastatic tumors (Т2-Т4) and more than 80% of them experienced failure of previous conventional treatment for cancer with chemo-and radiotherapy. The achieved treatment results demonstrated remission in about 80% of the patients, and were presented in our earlier publications. In search for new opportunities of improvement of our treatment efficiency since April 2018, we created treatment method which includes combination of IPT with Biomagnetic therapy with magnetic pairs. (IPT & BMP). Until August 2019 this specific treatment has been applied to 33 cancer patients with advanced metastatic tumors (Т2-Т4) in which 19 out of 23 (82%) experienced failure of previous standard treatment. Twenty-three patients have completed their treatment and were followed up by us. Out of them, 5 patients (21%) have achieved complete remission, and 17 patients (74%) have achieved stabilization. The average remission period is 10 months up till now. Registered failed treatment is present in only one case. Illustrating the opportunities of the new method, we present herewith two new cases with the results of complete clinical remission. In our opinion, the results are an illustration of the opportunities of the Integrative oncology, and the need for change in the concept for cancer patients' treatment.
... Its impact on cellular uptake of many compounds including glucose by facilitated diffusion has been documented [20]. The use of insulin for cancer-specific treatment has been tested in several studies [21][22][23][24][25]. ...
... Due to its complex influence on malignant cell metabolism, insulin has been exploited as a potential sensitizing agent in cancer therapy. Several in vitro and clinical studies have found that the inhibitory effect of various cytotoxic agents can be enhanced in the presence of insulin [21][22][23][24][25]. ...
The rationale for the implementation of novel therapies should be based on hallmarks of cancer. Two novel compounds labelled as thioglycoside A and B were designed and evaluated on breast and colon cancer cell lines. We assessed their cytotoxic effect after sensitizing cancer cells with insulin. In order to explore the underlying mechanisms, we performed tests to assess cell migration and motility, apoptosis, expression of glucose transporter 1 and proapoptotic proteins. Both compounds proved to have an antitumor effect which was significantly enhanced in combination with insulin. Linking glucose and anticancer agent presents an approach that exploits the Warburg effect. Targeting dysfunctional glycometabolism and increased glucose absorption is emerging as a promising anticancer strategy.
... 52 It follows that the antitumor activity of insulin may allow this hormone to be used in combination with chemotherapy to treat cancer. [53][54][55] Conclusion l-Glutamine supplementation of diet for 10 days in a cancer cachexia animal model promoted increased PEPCK expression in the jejunum that was associated with a significant elevation of glycemia and insulinemia, suggesting a beneficial effect on energy balance. An indirect effect on insulin secretion by l-glutamine is likely to prevent catabolism, thus reducing the harmful effects of cachexia. ...
We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor–bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed. Protein expression levels of key enzymes of gluconeogenesis, that is, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, were analyzed by western blot and immunohistochemical techniques. In addition, plasma corticosterone, glucose, insulin, and urea levels were evaluated. The WTG group showed significantly increased plasma glucose and insulin levels (p < 0.05); however, plasma corticosterone and urea remained unchanged. Moreover, the WTG group showed increased immunoreactive staining for jejunal phosphoenolpyruvate carboxykinase and increased expression of duodenal glucose-6-phosphatase. Furthermore, the WTG group presented with less intense cancer cachexia and slower tumor growth. These results could be attributed, at least partly, to increased intestinal gluconeogenesis and insulinemia, and better glycemia maintenance during fasting in Walker-256 tumor rats on a diet supplemented with l-glutamine.
... 186 Currently, insulin potentiation therapy is practiced by over 400 therapists worldwide, and the few data available indicate that it could allow a reduction of chemotherapeutic doses without compromising efficacy. 187 Reduction of insulin levels with diazoxide Diazoxide is a nondiuretic benzothiadiazine that has an antihypertensive effect and produces hyperglycemia via lowering insulin levels by activation of ATP-sensitive K + -channels, which have a key function in the control of insulin release. 188,189 In addition, diazoxide stimulates insulin degradation in the lysosomal system. ...
As more and more links between cancer and metabolism are discovered, new approaches to treat cancer using these mechanisms are considered. Dietary restriction of either calories or macronutrients has shown great potential in animal studies to both reduce the incidence and growth of cancer, and to act synergistically with other treatment strategies. These studies have also shown that dietary restriction simultaneously targets many of the molecular pathways that are targeted individually by anticancer drugs. The insulin/insulin-like growth factor-1 (IGF-1) system has thereby emerged as a key regulator of cancer growth pathways. Although lowering of insulin levels with diet or drugs such as metformin and diazoxide seems generally beneficial, some practitioners also utilize strategic elevations of insulin levels in combination with chemotherapeutic drugs. This indicates a broad spectrum of possibilities for modulating the insulin/IGF-1 system in cancer treatment. With a specific focus on dietary restriction, insulin administration and the insulin-lowering drug diazoxide, such modifications of the insulin/IGF-1 system are the topic of this review. Although preclinical data are promising, we point out that insulin regulation and the metabolic response to a certain diet often differ between mice and humans. Thus, the need for collecting more human data has to be emphasized.
... In previous IPT clinical trials [110,111], cancer patients were administered insulin 0.3 to 0.4 U per kg body weight intravenously, followed by chemotherapy at lower doses than usual, starting 20 min after insulin administration or sooner if symptoms of hypoglycemia were observed. In another case study [112], a woman with breast cancer was treated with IPT. ...
Introducing a new drug to the market is a time-consuming process, is complex, and involves consumption of a lot of resources. Therefore, discovering new uses for the old drugs (i.e. drug repurposing) benefits the patients by providing them time-tested drugs. With developments in insulin therapy still happening, it is worth keeping up to date on trends in the use of this powerful glucose-lowering agent. The aim of this article is to explore the potential non-diabetic clinical applications of insulin.
Literature survey was carried out through the various scientific journals publishing experimental and clinical research papers regarding the diverse applications of insulin other than in diabetes mellitus. These applications include both therapeutic as well as diagnostic uses of insulin. The relevant information collected from these publications was paraphrased in the present paper.
On studying the literature, the non-diabetic uses of insulin include the following: wound healing, parenteral nutrition, antiaging, body building, cardioprotection in acute coronary syndromes, insulin tolerance test to test the hypothalamo-pituitary-adrenal axis functioning, cell culture, cancer treatment, organ preservation, and management of septic shock, calcium channel, β blocker overdose and other critical illnesses in intensive care units.
This review attempts to survey some interesting new applications of insulin other than in diabetes mellitus.
... Calorie restriction [97][98][99][100] and even insulin potentiation therapy [101,102] may be considered as an adjuvant to our new approach, not only to decrease the toxicity to the normal cells but also to potentiate the efficacy on the cancer cells and to prevent progression toward moredreadful forms. This is because cancer cells consume a much larger amount of glucose than normal cells [103] and produce a highly acidic microenvironment that in turn makes cancer cells more malignant [104,105]. ...
Chemotherapy is the only option for oncologists when a cancer has widely spread to different body sites. However, almost all currently available chemotherapeutic drugs will eventually encounter resistance after their initial positive effect, mainly because cancer cells develop genetic alterations, collectively coined herein as mutations, to adapt to the therapy. Some patients may still respond to a second chemo drug, but few cases respond to a third one. Since it takes time for cancer cells to develop new mutations and then select those life-sustaining ones via clonal expansion, "run against time for mutations to emerge" should be a crucial principle for treatment of those currently incurable cancers. Since cancer cells constantly change to adapt to the therapy whereas normal cells are stable, it may be a better strategy to shift our focus from killing cancer cells per se to protecting normal cells from chemotherapeutic toxicity. This new strategy requires the development of new drugs that are nongenotoxic and can quickly, in just hours or days, kill cancer cells without leaving the still-alive cells with time to develop mutations, and that should have their toxicities confined to only one or few organs, so that specific protections can be developed and applied.
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
