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https://www.readbyqxmd.com/read/29774060/metformin-prevents-nerve-growth-factor-dependent-proliferative-and-proangiogenic-effects-in-epithelial-ovarian-cancer-cells-and-endothelial-cells
#1
Maritza P Garrido, Carolina Vera, Margarita Vega, Andrew F G Quest, Carmen Romero
Background: Epithelial ovarian cancer (EOC) is characterized by exacerbated angiogenesis regulated by proangiogenic and growth factors. Nerve growth factor (NGF) is overexpressed in EOC where it promotes proliferation as well as survival and is considered a proangiogenic factor. Metformin, a drug commonly used in the treatment of diabetes, is attributed to antineoplastic effects, but the underlying mechanisms remain unknown. Given that current therapies yield modest results in EOC patients, the aim of this study was to determine the effects of metformin on NGF-enhanced proliferation of EOC cells and the angiogenic potential of endothelial cells...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29772687/metformin-induces-apoptosis-and-alters-cellular-responses-to-oxidative-stress-in-ht29-colon-cancer-cells-preliminary-findings
#2
Paola Sena, Stefano Mancini, Marta Benincasa, Francesco Mariani, Carla Palumbo, Luca Roncucci
Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anti-cancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM for 24/48 h. We performed immunofluorescence experiments by means of confocal microscopy and western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29770821/a-size-shrinkable-nanoparticle-based-combined-anti-tumor-and-anti-inflammatory-strategy-for-enhanced-cancer-therapy
#3
Zhengze Lu, Yang Long, Xingli Cun, Xuhui Wang, Jianping Li, Ling Mei, Yiliang Yang, Man Li, Zhirong Zhang, Qin He
Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy...
May 17, 2018: Nanoscale
https://www.readbyqxmd.com/read/29766544/dipeptidyl-peptidase-4-inhibitor-use-is-associated-with-decreased-risk-of-fracture-in-patients-with-type-2-diabetes-a-population-based-cohort-study
#4
Wen-Hsuan Hou, Kai-Cheng Chang, Chung-Yi Li, Huang-Tz Ou
AIMS: To investigate the putative link between dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of fracture in patients with type 2 diabetes. METHODS: This propensity-score-matched population-based cohort study was performed between 2009 and 2013 on patients with type 2 diabetes who were stable metformin users. A total of 3,996 patients with type 2 diabetes used DPP-4i as a second-line antidiabetic drug. The same number of matched non-DPP-4i users were followed up until fracture occurrence, health insurance policy termination, or the end of 2013...
May 16, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#5
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764225/initial-combination-therapy-with-vildagliptin-plus-metformin-in-drug-na%C3%A3-ve-patients-with-t2dm-a-24-week-real-life-study-from-asia
#6
Manoj Chawla, Tae Ho Kim, Roberto C Mirasol, Pathan Faruque, Kathryn Cooke, Peggy Hours-Zesiger, Abhijit Shete
AIMS: To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM). METHODS: INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c) ≥7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29763426/environmental-concentrations-of-metformin-exposure-affect-aggressive-behavior-in-the-siamese-fighting-fish-betta-splendens
#7
Ronald David MacLaren, Kathryn Wisniewski, Christina MacLaren
Metformin, the medicine most commonly prescribed for treatment of Type II diabetes, is among the most abundant pharmaceuticals being introduced into the environment. Pharmaceuticals are increasingly found in wastewater and surface waters around the world, often due to incomplete metabolism in humans and subsequent excretion in human waste. Risk analyses and exposure studies have raised concerns about potential negative impacts of pharmaceuticals at current environmental levels. Results of the present study indicate that metformin at concentrations in the range of what has been documented in freshwater systems and waste-water effluent (40 μg/L) affects aggressive behavior in adult male Betta splendens...
2018: PloS One
https://www.readbyqxmd.com/read/29762537/the-cardioprotective-effect-of-metformin-in-doxorubicin-induced-cardiotoxicity-the-role-of-autophagy
#8
Rita Zilinyi, Attila Czompa, Andras Czegledi, Andrea Gajtko, Dora Pituk, Istvan Lekli, Arpad Tosaki
The molecular mechanisms underlying doxorubicin-induced cardiotoxicity are still being investigated, but are known to involve oxidative stress, mitochondrial dysfunction, and the dysregulation of autophagy. The objective of the current study was to examine the protective role of metformin and its effect on autophagy in doxorubicin-induced cardiotoxicity. Sprague⁻Dawley rats were divided into four groups at random. The doxorubicin-treated group received doxorubicin (3 mg/kg every second day) intraperitoneally...
May 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29761830/itc-commentary-on-metformin-clinical-drug-drug-interaction-study-design-that-enables-an-efficacy-and-safety-based-dose-adjustment-decision
#9
Maciej J Zamek-Gliszczynski, Xiaoyan Chu, Jack A Cook, Joseph M Custodio, Aleksandra Galetin, Kathleen M Giacomini, Caroline A Lee, Mary F Paine, Adrian S Ray, Joseph A Ware, Matthias B Wittwer, Lei Zhang
Metformin drug-drug interaction (DDI) studies are conducted during development of drugs that inhibit organic cation transporters and/or multidrug and toxin extrusion proteins (OCTs/MATEs). Monitoring solely changes in systemic exposure, the typical DDI study endpoint appears inadequate for metformin, which is metabolically stable, has poor passive membrane permeability, and undergoes transporter-mediated tissue distribution and clearance. Evaluation of renal clearance, antihyperglycemic effects, and potentially lactate as an exploratory safety marker, can support rational metformin dose adjustment...
May 15, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29754323/the-effects-of-exenatide-and-metformin-on-endothelial-function-in-newly-diagnosed-type-2-diabetes-mellitus-patients-a-case-control-study
#10
Yanjin Hu, Jia Liu, Guang Wang, Yuan Xu
INTRODUCTION: Exenatide is a new antidiabetic glucagon-like peptide-1 receptor agonist. In addition to its hypoglycemic effect, exenatide may have a potential protective benefit on vascular endothelial function. This study attempted to compare the effects of exenatide and traditional antidiabetic drug metformin treatment on endothelial function in overweight patients with type 2 diabetes. METHODS: Ninety overweight patients with newly diagnosed type 2 diabetes were recruited; 45 patients received exenatide (Exe) treatment and 45 patients received metformin (Met) treatment for 12 weeks...
May 12, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29752759/metformin-targets-brown-adipose-tissue-in-vivo-and-reduces-oxygen-consumption-in-vitro
#11
Peter Breining, Jonas B Jensen, Elias I Sundelin, Lars C Gormsen, Steen Jakobsen, Morten Busk, Lars Rolighed, Peter Bross, Paula Fernandez-Guerra, Lasse K Markussen, Nanna E Rasmussen, Jacob B Hansen, Steen B Pedersen, Bjørn Richelsen, Niels Jessen
Metformin is the most widely prescribed oral antidiabetic drug worldwide. Despite well-documented beneficial effects on health outcomes in diabetic patients, the target organs that mediate the effects of metformin remain to be established. In adult humans, brown adipose tissue (BAT) can influence basic metabolic rate, making BAT an attractive target for treatment of type 2 diabetes. Under the hypothesis that BAT is a metformin target tissue, we investigated in vivo uptake of [11 C]-metformin tracer in mice and studied in vitro effects of metformin on cultured human brown adipocytes...
May 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29748091/development-and-validation-of-a-hydrophilic-interaction-liquid-chromatography-tandem-mass-spectrometry-method-for-the-quantification-of-the-antidiabetic-drug-metformin-and-six-others-pharmaceuticals-in-wastewater
#12
Reinhard Oertel, Julien Baldauf, Julia Rossmann
A rapid and sensitive hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of the antidiabetic drug metformin and six further pharmaceuticals (atenolol, gabapentin, levofloxacin, ciprofloxacin, propranolol and trimethoprim) in influent and effluent wastewater. Five deuterated related compounds were used as internal standards in order to control the extraction, injection and ionization variability. Two solid phase extraction methods and Oasis HLB 1cc cartridge, using only 1 mL sample with acid or basic pH-value were optimized and compared in order to match the specificity of both influent and effluent wastewater matrixes...
May 4, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29744819/comparison-of-glycemic-variability-in-chinese-t2dm-patients-treated-with-exenatide-or-insulin-glargine-a-randomized-controlled-trial
#13
Ting-Ting Yin, Yan Bi, Ping Li, Shan-Mei Shen, Xiao-Lu Xiong, Li-Jun Gao, Can Jiang, Yan Wang, Wen-Huan Feng, Da-Long Zhu
INTRODUCTION: Increasing the frequency of blood glucose monitoring aids the evaluation of glycemic variability and blood glucose control by antidiabetic drugs. It remains unclear, however, whether GLP-1 receptor agonists or basal insulin has a better effect on glycemic variability in type 2 diabetes mellitus (T2DM) patients who are inadequately controlled by metformin. We used a continuous glucose monitoring system (CGMS) to compare patients on a GLP-1 receptor agonist with patients on basal insulin in terms of glycemic variability...
May 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29741792/frontline-science-pathological-conditioning-of-human-neutrophils-recruited-to-the-airway-milieu-in-cystic-fibrosis
#14
Osric A Forrest, Sarah A Ingersoll, Marcela K Preininger, Julie Laval, Dominique H Limoli, Milton R Brown, Frances E Lee, Brahmchetna Bedi, Ruxana T Sadikot, Joanna B Goldberg, Vin Tangpricha, Amit Gaggar, Rabindra Tirouvanziam
RATIONALE: Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies...
May 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29740925/metformin-directly-targets-the-h3k27me3-demethylase-kdm6a-utx
#15
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Pares, Salvador Fernández-Arroyo, Fedra Luciano-Mateo, Noemí Cabré, Jan Stursa, Lukas Werner, Begoña Martin-Castillo, Benoit Viollet, Jiri Neuzil, Jorge Joven, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Javier A Menendez
Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29738843/transporter-dependent-cytotoxicity-of-antiviral-drugs-in-primary-cultures-of-human-proximal-tubular-cells
#16
Lawrence H Lash, Caroline A Lee, Clynn Wilker, Vishal Shah
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively...
May 5, 2018: Toxicology
https://www.readbyqxmd.com/read/29738369/cardioprotective-effects-of-metformin
#17
Christine Driver, Kayode Dominion Samuel Bamitale, Aniessa Kazi, Mehnaaz Olla, Annah Ntsoaki Nyane, Peter Mark Oroma Owira
Metformin, routinely used as first-line drug in the treatment of type 2 diabetes has been shown to have cardioprotective effects beyond its glycemic control. These have been attributed to increases in Akt concentrations and activation of protein kinases in the RISK pathways. which prevent the mitochondrial mPTP from opening and rupturing it and therefore protects myocyte viability. In myocardial infarction and subsequent reperfusion, metformin activation of AMPK promotes glycolysis and keeps the mPTP closed...
May 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29737584/metformin-increases-the-cytotoxicity-of-oxaliplatin-in-human-dld-1-colorectal-cancer-cells-through-down-regulating-hmgb1-expression
#18
Wen-Shih Huang, Chien-Tsong Lin, Cheng-Nan Chen, Shun-Fu Chang, Hsin-I Chang, Ko-Chao Lee
Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent...
May 8, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29737290/pharmacoeconomic-evaluation-of-glimepiride-combined-with-other-drugs-in-the-treatment-of-diabetes
#19
Xiufang Liu, Liping Zeng, Wenchao Xu
The goal of diabetic drug treatment is to stabilize the blood sugar for a long time to close to the normal level, to correct the metabolic disorder and eliminate the symptoms. At present, glimepiride has become commonly used drugs for the treatment of diabetes with obesity. Compared with metformin, acarbose and rosiglitazone, glimepiride has different mechanisms of drug action, clinical combination showed synergistic hypoglycemic effect, good clinical curative effect. So, we use three treatments to study as group A (glimepiride and metformin); group B (glimepiride and acarbose); Group C (glimepiride and rosiglitazone)...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29736297/anti-diabetic-activity-of-quercetin-extracted-from-phyllanthus-emblica-l-fruit-in-silico-and-in-vivo-approaches
#20
Prabhu Srinivasan, S Vijayakumar, Swaminathan Kothandaraman, Manogar Palani
In this study, molecular interactions of the ligands, quercetin, gallic acid, and metformin with various diabetes mellitus-related protein targets, such as glycogen phosphorylase and peroxisome proliferator-activated receptor gamma, were assessed. It was revealed that quercetin possesses good binding affinity to both targets. Quercetin is a major constituent of methanolic extracts of Phyllanthus emblica fruit. The antihyperglycemic effect of quercetin in streptozotocin (STZ)-induced diabetic rats was examined...
April 2018: Journal of Pharmaceutical Analysis
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