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Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Ye-Jin Lee, Sung Koo Han, Ju Hee Park, Jung Kyu Lee, Deog Keom Kim, Hee Soon Chung, Eun Young Heo
Background/Aims: Patients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM. Methods: This retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012...
March 16, 2018: Korean Journal of Internal Medicine
Mohamed Waseem Osman, Mintu Nath, Asma Khalil, David R Webb, Thompson G Robinson, Hatem A Mousa
BACKGROUND: Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase AIM: To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls. METHODOLOGY: Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control...
March 7, 2018: Diabetes Research and Clinical Practice
Ke Li, Ting-Ting Zhang, Feng Wang, Bing Cui, Chen-Xi Zhao, Jiao-Jiao Yu, Xiao-Xi Lv, Xiao-Wei Zhang, Zhao-Na Yang, Bo Huang, Xia Li, Fang Hua, Zhuo-Wei Hu
Metformin has beneficial effects of preventing and treating cancers on type 2 diabetic patients. However, the role of metformin in non-diabetic cancer patients and the precise molecular mechanisms against cancer have not yet been sufficiently elucidated. We recently reported that the pseudokinase protein TRIB3 acts as a stress sensor linking metabolic stressors to cancer promotion by inhibiting autophagy and ubiquitin-proteasomal degradation systems; genetically abrogating of TRIB3 expression reduces tumourigenesis and cancer progression...
March 9, 2018: Oncogene
Qiongli Su, Ting Tao, Lei Tang, Jun Deng, Kwame Oteng Darko, Sichun Zhou, Mei Peng, Shanping He, Qing Zeng, Alex F Chen, Xiaoping Yang
Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non-muscle-invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches...
March 7, 2018: Journal of Cellular and Molecular Medicine
Xibiao Ye, Geng Zhang, Christiaan Righolt, James B Johnston, Versha Banerji, Spencer B Gibson, Salaheddin M Mahmud
BACKGROUND: Several epidemiological studies have shown a positive association between diabetes and increased risk of non-Hodgkin lymphoma (NHL), but the effect of diabetic treatment drugs such as metformin on the risk is unknown. METHODS: We conducted a population-based nested case-control study involving 878 NHL cases and 4,364 controls diagnosed with diabetes. Use of metformin and other medications prior to diagnosis and medical condition histories were assessed using administrative databases...
March 6, 2018: Cancer Epidemiology, Biomarkers & Prevention
Cinzia Antognelli, Rodolfo Cecchetti, Francesca Riuzzi, Matthew J Peirce, Vincenzo N Talesa
Metastasis is the primary cause of death in prostate cancer (PCa) patients. Effective therapeutic intervention in metastatic PCa is undermined by our poor understanding of its molecular aetiology. Defining the mechanisms underlying PCa metastasis may lead to insights into how to decrease morbidity and mortality in this disease. Glyoxalase 1 (Glo1) is the detoxification enzyme of methylglyoxal (MG), a potent precursor of advanced glycation end products (AGEs). Hydroimidazolone (MG-H1) and argpyrimidine (AP) are AGEs originating from MG-mediated post-translational modification of proteins at arginine residues...
March 5, 2018: Journal of Cellular and Molecular Medicine
Masoud Najafi, Mohsen Cheki, Saeed Rezapoor, Ghazale Geraily, Elahe Motevaseli, Carla Carnovale, Emilio Clementi, Alireza Shirazi
The diabetes drug metformin can mitigate the genotoxic effects of cytotoxic agents and has been proposed to prevent or even cure certain cancers. Metformin reduces DNA damage by mechanisms that are only incompletely understood. Metformin scavenges free radicals, including reactive oxygen species and nitric oxide, which are produced by genotoxicants such as ionizing or non-ionizing radiation, heavy metals, and chemotherapeutic agents. The drug may also increase the activities of antioxidant enzymes and inhibit NADPH oxidase, cyclooxygenase-2, and inducible nitric oxide synthase, thereby limiting macrophage recruitment and inflammatory responses...
March 2018: Mutation Research
Pedro-Antonio Regidor, Adolf Eduard Schindler, Bernd Lesoine, Rene Druckman
Introduction The use of 2 × 2000 mg myo-inositol +2 × 200 μg folic acid per day is a safe and promising tool in the effective improvement of symptoms and infertility for patients with polycystic ovary syndrome (PCOS). In addition, PCOS is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Typically, PCOS patients suffer of poor quality oocytes. Patients and methods In an open, prospective, non-blinded, non-comparative observational study, 3602 infertile women used myo-inositol and folic acid between 2 and 3 months in a dosage of 2 × 2000 mg myo-inositol +2 × 200 μg folic acid per day...
March 2, 2018: Hormone Molecular Biology and Clinical Investigation
Liv Guro Engen Hanem, Solhild Stridsklev, Pétur B Júlíusson, Øyvind Salvesen, Mathieu Roelants, Sven M Carlsen, Rønnaug Ødegård, Eszter Vanky
Context: Metformin is used in pregnancy in women with gestational diabetes mellitus, polycystic ovary syndrome (PCOS) and obesity. Metformin passes the placenta. Objective: To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age. Design: Follow-up study of two randomized, double blind, placebo-controlled trials. Setting: Secondary care centers. Eleven public hospitals in Norway...
February 27, 2018: Journal of Clinical Endocrinology and Metabolism
Kristen A Marrone, Xian Zhou, Patrick M Forde, Michael Purtell, Julie R Brahmer, Christine L Hann, Ronan J Kelly, Barbara Coleman, Edward Gabrielson, Gary L Rosner, David S Ettinger
BACKGROUND: In the absence of a targeted oncogenic driver mutation or high programmed death-ligand 1 expression, systemic therapy with platinum-based doublet chemotherapy with or without bevacizumab has been the standard treatment in advanced or metastatic non-small cell lung cancer (NSCLC). Metformin has been shown to have antitumor effects via a variety of insulin-dependent and insulin-independent mechanisms and to be potentially synergistic with chemotherapy. MATERIALS AND METHODS: This open-label single-center phase II study (NCT01578551) enrolled patients with chemotherapy-naïve advanced or metastatic nonsquamous NSCLC and randomized them (3:1) to receive carboplatin, paclitaxel, and bevacizumab with (Arm A) or without (Arm B) concurrent metformin for four to six cycles followed by maintenance therapy with bevacizumab ± metformin continued until disease progression, intolerable toxicity, or study withdrawal...
February 27, 2018: Oncologist
Patrick O Richard, Ardalan E Ahmad, Shaheena Bashir, Alexandre Zlotta, Bimal Bhindi, Ricardo Leao, Madhur Nayan, Aza Mohammed, Neil E Fleshner, Girish S Kulkarni
INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) accounts for 75-85% of all bladder cancers (UBC). Many UBC patients are also afflicted by diabetes mellitus (DM). It has been postulated that several oral hypoglycemic agents could impact disease-specific survival (DSS), but the data are sparse among NMIBC patients. Our primary objective was to evaluate the impact of metformin on DSS and overall survival (OS) in NMIBC patients. METHODS: This is a retrospective, population-based study that used linked administrative databases to identify diabetic patients ≥66 years who were subsequently diagnosed with NMIBC in Ontario, between 1992 and 2012...
February 23, 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Saverio Candido, Stephen L Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Matilde Y Follo, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes...
February 12, 2018: Advances in Biological Regulation
Leon Varjabedian, Mohammad Bourji, Leili Pourafkari, Nader D Nader
Metformin is a biguanide that is widely used as an insulin-sparing agent to treat diabetes. When compared with the general population, diabetics are twice as likely to die from fatal myocardial infarction and congestive heart failure (CHF). There has been a significant concern regarding the use of metformin in patients with CHF because of their higher tendency to develop lactic acidosis. However, large epidemiological trials have reported better cardiovascular prognosis with metformin compared to other glucose-lowering agents among diabetics...
February 24, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
You Kyoung Shin, Yu Shan Hsieh, Soonho Kwon, Hui Su Lee, Geun Hee Seol
Although stress is one of the risk factors of diabetes, few studies have assessed the effects of stress on diabetic rats. This study therefore analyzed differences in cardiovascular-related factors among control, non-stressed diabetic, and stressed diabetic rats, as well as assessed the effects of linalyl acetate (LA) on stressed diabetic rats. Male Sprague-Dawley rats were subjected to immobilization stress throughout the entire experimental period, and diabetes was induced on day 15 by a single injection of streptozotocin...
February 22, 2018: Journal of Applied Physiology
Swapnil Hiremath, Jeanne Françoise Kayibanda, Benjamin J W Chow, Dean Fergusson, Greg A Knoll, Wael Shabana, Brianna Lahey, Olivia McBride, Alexandra Davis, Ayub Akbari
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is defined as worsening of renal function after the administration of iodinated contrast material. In patients with cardiovascular disease, kidney disease, and/or diabetes, renin-angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics, and metformin can increase the risk of CI-AKI when undergoing contrast imaging. Despite CI-AKI being the leading iatrogenic cause of acute kidney injury, there is a lack of sufficient scientific evidence supporting which drugs should be stopped, when they should be stopped, and when they should be resumed...
February 21, 2018: Systematic Reviews
Jun Guo, Yuan Zhou, Yafen Cheng, Weiwei Fang, Gang Hu, Jie Wei, Yajun Lin, Yong Man, Lixin Guo, Mingxiao Sun, Qinghua Cui, Jian Li
BACKGROUND/AIMS: Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. METHODS: The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention...
2018: Cellular Physiology and Biochemistry
Htet Lin Htun, Tsin Wen Yeo, Clarence C Tam, Junxiong Pang, Yee Sin Leo, David C Lye
Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41...
February 20, 2018: Scientific Reports
Ariella De Monte, Davide Brunetti, Luigi Cattin, Francesca Lavanda, Erica Naibo, Maria Malagoli, Giorgio Stanta, Serena Bonin
Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system...
March 2018: Molecular and Clinical Oncology
Steven D Melvin, Oliver A H Jones, Anthony R Carroll, Frederic D L Leusch
Organic carrier solvents are used in aquatic toxicity testing to improve chemical solubility and facilitate the exploration of dose-response relationships. Both water- and solvent-control groups are normally included in these scenarios to ensure that the solvent itself has no effect on the test organism, but this fails to consider possible interactive effects between carrier solvents and contaminants of interest. We explored this topic by exposing Limnodynastes peronii tadpoles to a mixture of common water-soluble pharmaceuticals (diclofenac, metformin and valproic acid) in the presence and absence of the carrier solvent methanol, according to standard developmental bioassay methodology...
February 10, 2018: Chemosphere
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