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      Diazoxide for Lowering Insulin Levels in Breast Cancer Patients

      , a , b

      The Oncologist

      AlphaMed Press

      Breast neoplasms, Insulin, IGF‐1, Diazoxide, Acarbose, Ketogenic diet

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          Abstract

          Diazoxide is a nondiuretic benzothiadiazine that produces hyperglycemia by lowering insulin levels through activation of ATP‐sensitive K1‐channels and stimulating insulin degradation in the lysosomal system. Its effect on cancer growth is discussed.

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          Most cited references 6

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          Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis

          Background Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. Methods We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). Conclusions There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.
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            Dietary and pharmacological modification of the insulin/IGF-1 system: exploiting the full repertoire against cancer

             R J Klement,  M Fink (2016)
            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.
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              Pretreatment Insulin Levels as a Prognostic Factor for Breast Cancer Progression.

              Based on the hypothesis that impaired glucose metabolism might be associated with survival outcomes independently of overt diabetes, we sought to investigate the prognostic value of routinely used glycemic parameters in a prospective study of breast cancer (BC) patients.
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                Author and article information

                Contributors
                fink-fuerth@t-online.de
                Journal
                Oncologist
                Oncologist
                10.1002/(ISSN)1549-490X
                The Oncologist
                oncologist
                theoncologist
                The Oncologist
                AlphaMed Press
                1083-7159
                1549-490X
                April 2017
                April 2017
                : 22
                : 4 ( doiID: 10.1002/onco.v22.4 )
                : 491
                Affiliations
                [ a ]Onkologische Praxis , Fuerth, Germany
                [ b ] Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt , Schweinfurt, Germany
                Author notes
                [* ]Correspondence: Michael K. Fink, Ph.D., Onkologische Praxis, D‐90766 Fuerth, Germany. Telephone: +49‐911‐7540803; e‐mail: fink-fuerth@ 123456t-online.de
                Article
                ONCO12084
                10.1634/theoncologist.2016-0402
                5388385
                28400489
                © AlphaMed Press 2017
                Page count
                Pages: 2
                Product
                Categories
                3
                Letters to the Editor

                Oncology & Radiotherapy

                breast neoplasms, ketogenic diet, acarbose, diazoxide, igf‐1, insulin

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