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https://www.readbyqxmd.com/read/28533436/metformin-synergizes-with-bcl-xl-bcl-2-inhibitor-abt-263-to-induce-apoptosis-specifically-in-p53-defective-cancer-cells
#1
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the pro-apoptotic machineries in various p53-defective cancer cells...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28529553/progress-in-the-application-and-mechanism-of-metformin-in-treating-non-small-cell-lung-cancer
#2
Chan Li, Yang Xue, Yu-Rong Xi, Ke Xie
At present, the incidence and mortality of lung cancer demonstrate an increasing trend. Non-small cell lung cancer (NSCLC) accounts for ~80-85% of all lung cancer cases. Therefore, developing novel and more effective treatments is of great importance. The use of combination therapies, where several anticancer agents are used together, is a promising strategy. Recent studies demonstrate that metformin, which has been utilized for treating diabetes mellitus for >50 years, has antitumor effects in numerous types of cancer including NSCLC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28526182/pharmacologic-management-of-type-2-diabetes-mellitus-available-therapies
#3
James Thrasher
Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin...
May 12, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28514891/synergistic-effect-of-rapamycin-and-metformin-against-age-dependent-oxidative-stress-in-rat-erythrocyte
#4
Abhishek Kumar Singh, Geetika Garg, Sandeep Singh, Syed Ibrahim Rizvi
Erythrocytes are particularly vulnerable towards age-dependent oxidative stress mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy for the maintenance of redox balance as well as effective treatment of age associated diseases. Herein, we have investigated the beneficial effect of co-treatment of CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an anti-diabetic biguanide and activator of adenosine monophosphate kinase) against aging-induced oxidative stress in erythrocytes and plasma of aging rats...
May 17, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#5
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499531/gestational-diabetes-diagnosis-classification-and-clinical-care
#6
REVIEW
Lynn R Mack, Paul G Tomich
Gestational diabetes mellitus (GDM) affects approximately 6% of pregnant women, and prevalence is increasing in parallel with the obesity epidemic. Protocols for screening/diagnosing GDM are controversial with several guidelines available. Treatment of GDM results in a reduction in the incidence of preeclampsia, shoulder dystocia, and macrosomia. If diet and lifestyle changes do not result in target glucose levels, then treatment with metformin, glyburide, or insulin should begin. It is generally recommended that pregnancies complicated by GDM do not go beyond term...
June 2017: Obstetrics and Gynecology Clinics of North America
https://www.readbyqxmd.com/read/28498475/targeting-hexokinase-2-inhibition-promotes-radiosensitization-in-hpv16%C3%A2-e7-induced-cervical-cancer-and-suppresses-tumor-growth
#7
Yuan Liu, Tracy Murray-Stewart, Robert A Casero, Ioannis Kagiampakis, Lihua Jin, Jiawen Zhang, Huihui Wang, Qi Che, Huan Tong, Jieqi Ke, Feizhou Jiang, Fangyuan Wang, Xiaoping Wan
In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT...
May 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28497664/insulin-sensitizers-in-adolescents-with-polycystic-ovary-syndrome
#8
Trang N LE, Edmond P Wickham Iii, John E Nestler
Polycystic ovary syndrome (PCOS) is the most common disorder of androgen excess in women of reproductive age. The diagnosis of PCOS can be more challenging in adolescents than in adult women given significant overlap between normal puberty and the signs of PCOS, including acne, menstrual irregularity, and polycystic ovarian morphology. Optimal treatments for adult women with PCOS vary depending on patient risk factors and reproductive goals, but mainly include hormonal contraception and insulin sensitizers...
May 11, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28495567/transporters-involved-in-metformin-pharmacokinetics-and-treatment-response
#9
Xiaomin Liang, Kathleen M Giacomini
Metformin, widely used as first-line treatment for type 2 diabetes, exists primarily as a hydrophilic cation at physiological pHs. As such, membrane transporters play a substantial role in its absorption, tissues distribution, and renal elimination. Multiple organic cation transporters are determinants of the pharmacokinetics of metformin, and many of them are important in its pharmacological action, as mediators of metformin entry into target tissues. Further, a recent genomewide association study (GWAS) in a large multi-ethnic population implicated polymorphisms in SLC2A2, encoding the glucose transporter, GLUT2, as important determinants of response to metformin...
May 8, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28491145/combination-of-metformin-and-curcumin-targets-breast-cancer-in-mice-by-angiogenesis-inhibition-immune-system-modulation-and-induction-of-p53-independent-apoptosis
#10
Rabah Rashad Falah, Wamidh H Talib, Seba Jamal Shbailat
BACKGROUND: The effects of metformin (MET) and curcumin (CUR) single treatments have been tested against breast cancer; however, their combination has not been explored. Here, we evaluated the antitumor activity of MET and CUR combination against breast cancer in mice. MATERIALS AND METHODS: The antiproliferative activity of single and combined treatments against breast cancer cell lines was determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was examined in EMT6/P cells...
April 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28483786/faster-aspart-versus-insulin-aspart-as-part-of-a-basal-bolus-regimen-in-inadequately-controlled-type-2-diabetes-the-onset-2-trial
#11
Keith Bowering, Christopher Case, John Harvey, Michael Reeves, Michael Sampson, Robert Strzinek, Ditte-Marie Bretler, Rikke Beck Bang, Bruce W Bode
OBJECTIVE: This multicenter, double-blind, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in adults with type 2 diabetes receiving basal insulin and oral antidiabetic agents. RESEARCH DESIGN AND METHODS: The primary end point was HbA1c change from baseline after 26 weeks' treatment. After an 8-week run-in to optimize basal insulin, subjects were randomized (1:1) to mealtime faster aspart (n = 345) or IAsp (n = 344), titrated using a simple daily patient-driven algorithm, plus insulin glargine U100 and metformin...
May 8, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28480051/metformin-suppresses-triple-negative-breast-cancer-stem-cells-by-targeting-klf5-for-degradation
#12
Peiguo Shi, Wenjing Liu, Tala, Haixia Wang, Fubing Li, Hailin Zhang, Yingying Wu, Yanjie Kong, Zhongmei Zhou, Chunyan Wang, Wenlin Chen, Rong Liu, Ceshi Chen
Out of the breast cancer subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis without effective targeted therapies. Metformin, a first-line drug for type 2 diabetes mellitus, was demonstrated to target breast cancer stem cells selectively. However, the efficiency and the mechanism of action of metformin in TNBC are unclear. In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Krüppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28465792/effects-of-intermittent-fasting-on-health-markers-in-those-with-type-2-diabetes-a-pilot-study
#13
Terra G Arnason, Matthew W Bowen, Kerry D Mansell
AIM: To determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM). METHODS: We describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase...
April 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28464864/metformin-produces-growth-inhibitory-effects-in-combination-with-nutlin-3a-on-malignant-mesothelioma-through-a-cross-talk-between-mtor-and-p53-pathways
#14
Kengo Shimazu, Yuji Tada, Takao Morinaga, Masato Shingyoji, Ikuo Sekine, Hideaki Shimada, Kenzo Hiroshima, Takao Namiki, Koichiro Tatsumi, Masatoshi Tagawa
BACKGROUND: Mesothelioma is resistant to conventional treatments and is often defective in p53 pathways. We then examined anti-tumor effects of metformin, an agent for type 2 diabetes, and combinatory effects of metformin and nutlin-3a, an inhibitor for ubiquitin-mediated p53 degradation, on human mesothelioma. METHODS: We examined the effects with a colorimetric assay and cell cycle analyses, and investigated molecular events in cells treated with metformin and/or nutlin-3a with Western blot analyses...
May 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28459432/metformin-inhibits-suv39h1-mediated-migration-of-prostate-cancer-cells
#15
T Yu, C Wang, J Yang, Y Guo, Y Wu, X Li
Prostate cancer (PCa) is a leading cause of cancer-related death among men, largely due to incurable distant metastases. Metformin, the most common used anti-type-2 diabetes medicine, has been linked to reduced cancer risk and better diagnosis. We found that metformin was able to inhibit PCa cell migration, which correlates with tumor metastatic capability. The pathogenesis and progression of tumors are closely related to dysregulated gene expression in tumor cells through epigenetic alterations such as DNA methylation and histone modifications...
May 1, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28459036/consensus-statement-on-dose-modifications-of-antidiabetic-agents-in-patients-with-hepatic-impairment
#16
REVIEW
Kalyan Kumar Gangopadhyay, Parminder Singh
Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia...
March 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28451709/a-dosing-algorithm-for-metformin-based-on-the-relationships-between-exposure-and-renal-clearance-of-metformin-in-patients-with-varying-degrees-of-kidney-function
#17
Janna K Duong, M Y A M Kroonen, S S Kumar, H L Heerspink, C M Kirkpatrick, G G Graham, K M Williams, R O Day
PURPOSE: The aims of this study were to investigate the relationship between metformin exposure, renal clearance (CLR), and apparent non-renal clearance of metformin (CLNR/F) in patients with varying degrees of kidney function and to develop dosing recommendations. METHODS: Plasma and urine samples were collected from three studies consisting of patients with varying degrees of kidney function (creatinine clearance, CLCR; range, 14-112 mL/min). A population pharmacokinetic model was built (NONMEM) in which the oral availability (F) was fixed to 0...
April 28, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28445726/sirtuin-1-activation-controls-tumor-growth-by-impeding-th17-differentiation-via-stat3-deacetylation
#18
Emeric Limagne, Marion Thibaudin, Romain Euvrard, Hélène Berger, Pauline Chalons, Frédérique Végan, Etienne Humblin, Romain Boidot, Cédric Rébé, Valentin Derangère, Sylvain Ladoire, Lionel Apetoh, Dominique Delmas, François Ghiringhelli
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28444922/regulation-of-organelle-function-by-metformin
#19
REVIEW
Jeongho Kim, Young-Jai You
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28440424/therapeutic-potential-of-the-antidiabetic-drug-metformin-in-small-bowel-adenocarcinoma
#20
Taiga Chiyo, Kiyohito Kato, Hisakazu Iwama, Shintaro Fujihara, Koji Fujita, Tomoko Tadokoro, Kyoko Ohura, Eri Samukawa, Yoshimi Yamana, Nobuya Kobayashi, Tae Matsunaga, Noriko Nishiyama, Maki Ayaki, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Tsutomu Masaki
Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects...
April 20, 2017: International Journal of Oncology
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