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Metformin lung disease

Xiao-Yu Cheng, Yang-Yang Li, Cheng Huang, Jun Li, Hong-Wei Yao
Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM)...
April 4, 2017: Oncotarget
Kun-Lin Li, Li Li, Peng Zhang, Jun Kang, Yu-Bo Wang, Heng-Yi Chen, Yong He
We present the rationale and study design of the CGMT (combined gefitinib and metformin therapy) trial ( Identifier: NCT01864681), which is aimed at treating locally advanced non-small-cell lung cancer. The CGMT trial is a multicenter, phase II randomized, double-blinded, and placebo-controlled study, which is designed to evaluate the safety and efficacy of metformin in combination with gefitinib as first-line therapy in patients presenting with stage IIIb-IV non-small-cell lung cancer expressing the epidermal growth factor receptor mutant...
December 22, 2016: Clinical Lung Cancer
Oscar Arrieta, Edgar Varela-Santoyo, Enrique Soto-Perez-de-Celis, Roberto Sánchez-Reyes, Martha De la Torre-Vallejo, Saé Muñiz-Hernández, Andrés F Cardona
BACKGROUND: Previous population-based studies have demonstrated an association between metformin use and improved survival among diabetic patients with cancer. We sought to analyze the effects of diabetes and its treatment in terms of the survival of patients with lung cancer. METHODS: Overall, 1106 patients with non-small cell lung cancer (94.3 % with stage IV disease) were included. The outcomes were compared between the patients with (n = 186) and without diabetes (n = 920)...
2016: BMC Cancer
Roshni Joshi, Sudhir Venkatesan, Puja R Myles
Background. Cholesterol lowering drugs HMG-CoA reductase inhibitors (statins) and PPARα activators (fibrates) have been shown to reduce host inflammation via non-disease specific immunomodulatory mechanisms. Recent studies suggest that commonly prescribed drugs in general practice, statins and fibrates, may be beneficial in influenza-like illness related mortality. This retrospective cohort study examines the association between two lipid lowering drugs, statins and fibrates, and all-cause 30-day mortality following a medically attended acute respiratory illness (MAARI)...
2016: PeerJ
Yong-Syu Lee, Barbara B Doonan, Joseph M Wu, Tze-Chen Hsieh
Aging in humans is a multi-factorial cellular process that is associated with an increase in the risk of numerous diseases including diabetes, coronary heart disease and cancer. Aging is linked to DNA damage, and a persistent source of DNA damage is exposure to ultraviolet (UV) radiation. As such, identifying agents that confer protection against DNA damage is an approach that could reduce the public health burden of age-related disorders. Metformin and resveratrol have both shown effectiveness in preventing several age-related diseases; using human A549 cells, we investigated whether metformin or resveratrol, alone or combined, prevent UVC-induced DNA damage...
June 2016: Oncology Reports
Guoxing Wan, Xiongjie Yu, Ping Chen, Xianhe Wang, Dongfeng Pan, Xuanbin Wang, Linjun Li, Xiaojun Cai, Fengjun Cao
The purpose of this study is to summarize the currently available evidence regarding the concerned issue by performing a comprehensive meta-analysis. Relevant publications reporting the association of metformin use with survival of lung cancer patients with diabetes were electronically searched to identify eligible studies. The meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures for disease-free survival(DFS) and overall survival(OS) estimates. A total of 17 individual studies from 10 publications were included in the meta-analysis...
June 7, 2016: Oncotarget
Semiha Bahceci Erdem, Hikmet Tekin Nacaroglu, Ozlem Bag, Canan Sule Unsal Karkiner, Huseyin Anil Korkmaz, Demet Can
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started...
2015: Central-European Journal of Immunology
Wishwanath R A Patkee, Georgina Carr, Emma H Baker, Deborah L Baines, James P Garnett
Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P...
April 2016: Journal of Cellular and Molecular Medicine
Hengyi Chen, Wenxiu Yao, Qian Chu, Rui Han, Yubo Wang, Jianguo Sun, Dong Wang, Yongsheng Wang, Mengshu Cao, Yong He
BACKGROUND: Acquired resistance has become the bottleneck affecting the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. Studies have shown that the antidiabetic drug metformin could effectively increase the sensitivity of TKI-resistant lung cancer cells to EGFR-TKI. This study aimed to evaluate the effect of metformin in combination with EGFR-TKI on the prognosis of non-small cell lung cancer (NSCLC) patients with diabetes mellitus type 2 (DM2)...
December 1, 2015: Cancer Letters
Elizabeth Osei, Susanne Fonville, Adrienne A M Zandbergen, Paul J A M Brouwers, Laus J M M Mulder, Hester F Lingsma, Diederik W J Dippel, Peter J Koudstaal, Heleen M den Hertog
BACKGROUND: Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients...
2015: Trials
Xueyu Chen, Frans J Walther, Rozemarijn M A Sengers, El Houari Laghmani, Asma Salam, Gert Folkerts, Tonio Pera, Gerry T M Wagenaar
Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic option for BPD by reducing pulmonary inflammation and fibrosis and improving vascularization. We investigated the therapeutic potential of daily treatment with 25 and 100 mg/kg metformin, injected subcutaneously in neonatal Wistar rats with severe experimental BPD, induced by continuous exposure to 100% oxygen for 10 days...
August 1, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Fanming Kong, Fangfang Gao, Honggen Liu, Liwei Chen, Rongxiu Zheng, Jianchun Yu, Xiaojiang Li, Geli Liu, Yingjie Jia
Metformin has been reported having potential anticancer effect on kinds of solid tumors, but its role in combined small-cell lung cancer (C-SCLC) remains indistinct. This study aimed to explore whether metformin use has a prognosis benefit in diabetic C-SCLC patients. A total of 259 C-SCLC patients with diabetes were enrolled in our study. The clinicopathological parameters and survival data were collected and analyzed. The correlation between metformin use and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of metformin use for C-SCLC...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Alexis Lacout, Pierre Yves Marcy, Mostafa El Hajjam, Pascal Lacombe
Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations. Pulmonary arteriovenous malformations may either rupture or be responsible for a right-to-left shunting leading to paradoxical embolism causing stroke or cerebral abscess. Metformin may harbor a pleiotropic action, (a) decreasing inflammation (via anti COX 2 pathway and other mechanism), (b) decreasing COX 2 and VEGF mediated angiogenesis, (c) increasing negative angiogenic regulation pathway by stimulating SMAD 2/3 expression either directly or via the AMPK pathway and preventing from pulmonary hypertension development and (d) diminushin oxidative stress...
September 2015: Medical Hypotheses
Anne C Melzer, Jane Uman, David H Au
RATIONALE: Diabetes and hypertension are common among patients with airflow limitation and contribute to cardiovascular (CV) mortality, one of the leading causes of death among patients with airflow limitation. OBJECTIVES: Our goal was to examine the association of severity of airflow limitation with adherence to medications for hypertension and diabetes. METHODS: We identified 7,359 veterans with hypertension and/or diabetes in the Veterans Integrated Service Network-20...
June 2015: Annals of the American Thoracic Society
Juan Zheng, Shih-Lung Woo, Xiang Hu, Rachel Botchlett, Lulu Chen, Yuqing Huo, Chaodong Wu
Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D...
June 2015: Frontiers of Medicine
Stefano Indraccolo, Giovanni Randon, Elisabetta Zulato, Margherita Nardin, Camillo Aliberti, Fabio Pomerri, Alessandra Casarin, Maria Ornella Nicoletto
Recurrent type I endometrial cancer (EC) has poor prognosis and demands novel therapeutic approaches. Bevacizumab, a VEGF-A neutralizing monoclonal antibody, has shown clinical activity in this setting. To our knowledge, however, although some diabetic cancer patients treated with bevacizumab may also take metformin, whether metformin modulates response to anti-VEGF therapy has not yet been investigated. Here, we report the case of a patient with advanced EC treated, among other drugs, with bevacizumab in combination with metformin...
2015: Cancer Biology & Therapy
V S Baranov, O S Glotov, E V Baranova
The overview represents the recent most conspicuous findings in aging studies. It includes new data on the whole genome association studies (GWAS) in big cohort of centenaries, recently found mutation protecting from Alzheimer disease, discovery of hypothalamus as a command center of human aging, very important data on the negative effect of common antioxidants in the treatment of lung cancer as well as new data concerning antiaging and anticancer effects of common drugs such as rapamycine and metformin. Substantial part of the review is devoted to the epigenetic problems of senescence and feasible impact of basic epigenetic mechanisms (methylation of DNA and histone proteins, DNA heterochromatization) in regulation of gene expression, long-term genome reprogramming during early childhood, and transgeneration transmission of epigenetic traits...
2014: Advances in Gerontology, Uspekhi Gerontologii
Morena Fasano, Carminia Maria Della Corte, Annalisa Capuano, Ferdinando Carlo Sasso, Federica Papaccio, Liberato Berrino, Fortunato Ciardiello, Floriana Morgillo
We present the rationale and study design of the METAL (METformin in Advanced Lung cancer) trial (EudraCT number: 2014-000349-59), a multicenter, open label phase II study, designed to evaluate the safety and activity of metformin combined with erlotinib as second-line therapy in patients with stage IV non-small-cell lung cancer. This is a 2-part trial, consisting of a safety run-in part followed by a phase II part. The primary end point for the first part is the maximum tolerated dose and the identification of the recommended phase II dose of metformin in combination with erlotinib...
January 2015: Clinical Lung Cancer
Floris H Groenendijk, Wouter W Mellema, Eline van der Burg, Eva Schut, Michael Hauptmann, Hugo M Horlings, Stefan M Willems, Michel M van den Heuvel, Jos Jonkers, Egbert F Smit, René Bernards
The multikinase inhibitor sorafenib is under clinical investigation for the treatment of many solid tumors, but in most cases, the molecular target responsible for the clinical effect is unknown. Furthermore, enhancing the effectiveness of sorafenib using combination strategies is a major clinical challenge. Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. We further show in a phase II clinical trial in KRAS mutant advanced non-small cell lung cancer (NSCLC) with single agent sorafenib an improved disease control rate in patients using the antidiabetic drug metformin...
March 15, 2015: International Journal of Cancer. Journal International du Cancer
Giacomo Zuccarini, Marialuisa Bocchino, Luca Rosario Assante, Gaetano Rea, Alessandro Sanduzzi
Interstitial lung disease (ILD) may be caused by a wide panel of recognized drugs. Despite the increasing number of reports in the literature, high-lightings of ILD related to oral hypoglycemic drugs are very infrequent.  Herein, we describe the case of a 78-yr-old Caucasian diabetic woman who developed mild dyspnoea at rest, asthenia and fever while on treatment with oral metformin (2000 mg/day) and glibenclamide (12.5 mg/day). On hospital admission, pulmonary function testing (PFT), chest x-ray and thorax high resolution computed tomography (HRCT) were consistent with a diagnosis of ILD...
2014: Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG
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