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Metformin lung disease

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https://www.readbyqxmd.com/read/29659176/nrf2-attenuates-inflammatory-response-in-copd-emphysema-crosstalk-with-wnt3a-%C3%AE-catenin-and-ampk-pathways
#1
Wenhui Cui, Zhihui Zhang, Panpan Zhang, Jiao Qu, Cheng Zheng, Xiaoting Mo, Wencheng Zhou, Liang Xu, Hongwei Yao, Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway...
April 16, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29619987/comorbidities-of-bullous-pemphigoid-in-a-finnish-cohort
#2
Anna Pankakoski, Harri Sintonen, Annamari Ranki, Nicolas Kluger
The incidence of bullous pemphigoid (BP) is increasing in Finland. To investigate the clinical presentation, comorbidities, and medications in a cohort of Finnish patients with confirmed BP managed in a university hospital setting. An observational retrospective study of all consecutive patients diagnosed with BP in 2012-2013 at the Department of dermatology, HUCH. The prevalence of the most common comorbidities was compared to that in a sample population aged over 30 years. Seventy patients were included (mean age: 77 years at diagnosis)...
April 5, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29558957/prognostic-value-of-metformin-for-non-small-cell-lung-cancer-patients-with-diabetes
#3
Tongbai Xu, Dongsheng Li, Yuan He, Fuliang Zhang, Man Qiao, Yanhua Chen
BACKGROUND: The anti-cancer role of metformin has been reported in many different kinds of solid tumors, but how it affects non-small cell lung cancer (NSCLC) is currently elusive. The aim of this study was to investigate the influence of metformin treatment on diabetic NSCLC. METHODS: Two hundred fifty-five patients of diabetic NSCLC receiving therapy in our hospital from 2014 to 2016 were enrolled in our study. The information on clinical diagnosis, pathology, and prognosis as well as the influence of metformin in diabetic NSCLC were collected and assessed...
March 20, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29489653/effect-of-hypoglycemic-agents-on-survival-outcomes-of-lung-cancer-patients-with-diabetes-mellitus-a-meta-analysis
#4
Wen-Xiu Xin, Luo Fang, Qi-Lu Fang, Xiao-Wei Zheng, Hai-Ying Ding, Ping Huang
BACKGROUND: To assess the association between hypoglycemic agents and prognosis of lung cancer patients with diabetes. METHODS: A comprehensive literature search was performed in PubMed, Web of Science, Embase, and Cochrane Library until May 2017. The search yielded 2593 unique citations, of which 18 articles met inclusion criteria. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by a fixed-effects or random-effects model. RESULTS: The pooled HRs favoring metformin users were 0...
March 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29487223/a-randomized-phase-ii-study-of-metformin-plus-paclitaxel-carboplatin-bevacizumab-in-patients-with-chemotherapy-na%C3%A3-ve-advanced-or-metastatic-nonsquamous-non-small-cell-lung-cancer
#5
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
https://www.readbyqxmd.com/read/29258504/dipeptidyl-peptidase-4-inhibitor-decreases-the-risk-of-atrial-fibrillation-in-patients-with-type-2-diabetes-a-nationwide-cohort-study-in-taiwan
#6
Chia-Yu Chang, Yung-Hsin Yeh, Yi-Hsin Chan, Jia-Rou Liu, Shang-Hung Chang, Hsin-Fu Lee, Lung-Sheng Wu, Kun-Chi Yen, Chi-Tai Kuo, Lai-Chu See
BACKGROUND: Whether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear. This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes. METHODS: Over a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan's National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled...
December 19, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29246951/metformin-mediates-protection-against-legionella-pneumonia-through-activation-of-ampk-and-mitochondrial-reactive-oxygen-species
#7
Chiaki Kajiwara, Yu Kusaka, Soichiro Kimura, Tetsuo Yamaguchi, Yuta Nanjo, Yoshikazu Ishii, Heiichiro Udono, Theodore J Standiford, Kazuhiro Tateda
In Legionella pneumophila infection, macrophages play a critical role in the host defense response. Metformin, an oral drug for type 2 diabetes, is attracting attention as a new supportive therapy against a variety of diseases, such as cancer and infectious diseases. The novel mechanisms for metformin actions include modulation of the effector functions of macrophages and other host immune cells. In this study, we have examined the effects of metformin on L. pneumophila infection in vitro and in vivo. Metformin treatment suppressed growth of L...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29192176/pgc-1alpha-levels-correlate-with-survival-in-patients-with-stage-iii-nsclc-and-may-define-a-new-biomarker-to-metabolism-targeted-therapy
#8
Alberto Cruz-Bermúdez, Ramiro J Vicente-Blanco, Raquel Laza-Briviesca, Aránzazu García-Grande, Sara Laine-Menéndez, Lourdes Gutiérrez, Virginia Calvo, Atocha Romero, Paloma Martín-Acosta, José Miguel García, Mariano Provencio
Lung cancer remains the leading cause of cancer-related death worldwide, with one-third diagnosed with locally advanced (stage III) disease. Preoperative induction chemo-radiotherapy is key for the treatment of these patients, however conventional cisplatin based approaches has apparently reached a plateau of effectiveness. In the search for new therapies, the targeting of tumor metabolism is revealed as an interesting option to improve the patient's responses. Here we describe the importance of PGC-1alpha and GAPDH/MT-CO1 ratio levels as surrogates of the Warburg effect from a series of 28 stage III NSCLC patients, on PFS, OS and PET uptake...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026839/missing-the-benefit-of-metformin-in-acute-myeloid-leukemia-a-problem-of-contrast
#9
Alice C Ceacareanu, George K Nimako, Zachary A P Wintrob
OBJECTIVE: To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. METHODS: Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR])...
July 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28988825/pgc-1%C3%AE-promotes-breast-cancer-metastasis-and-confers-bioenergetic-flexibility-against-metabolic-drugs
#10
Sylvia Andrzejewski, Eva Klimcakova, Radia M Johnson, Sébastien Tabariès, Matthew G Annis, Shawn McGuirk, Jason J Northey, Valérie Chénard, Urshila Sriram, David J Papadopoli, Peter M Siegel, Julie St-Pierre
Metabolic adaptations play a key role in fueling tumor growth. However, less is known regarding the metabolic changes that promote cancer progression to metastatic disease. Herein, we reveal that breast cancer cells that preferentially metastasize to the lung or bone display relatively high expression of PGC-1α compared with those that metastasize to the liver. PGC-1α promotes breast cancer cell migration and invasion in vitro and augments lung metastasis in vivo. Pro-metastatic capabilities of PGC-1α are linked to enhanced global bioenergetic capacity, facilitating the ability to cope with bioenergetic disruptors like biguanides...
November 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28962576/statistically-controlled-identification-of-differentially-expressed-genes-in-one-to-one-cell-line-comparisons-of-the-cmap-database-for-drug-repositioning
#11
Jun He, Haidan Yan, Hao Cai, Xiangyu Li, Qingzhou Guan, Weicheng Zheng, Rou Chen, Huaping Liu, Kai Song, Zheng Guo, Xianlong Wang
BACKGROUND: The Connectivity Map (CMAP) database, an important public data source for drug repositioning, archives gene expression profiles from cancer cell lines treated with and without bioactive small molecules. However, there are only one or two technical replicates for each cell line under one treatment condition. For such small-scale data, current fold-changes-based methods lack statistical control in identifying differentially expressed genes (DEGs) in treated cells. Especially, one-to-one comparison may result in too many drug-irrelevant DEGs due to random experimental factors...
September 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28936567/metformin-as-a-repurposed-therapy-in-advanced-non-small-cell-lung-cancer-nsclc-results-of-a-phase-ii-trial
#12
Anish B Parikh, Peter Kozuch, Nicholas Rohs, Daniel J Becker, Benjamin P Levy
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity...
December 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28801373/metformin-and-melatonin-in-adrenocortical-carcinoma-morphoproteomics-and-biomedical-analytics-provide-proof-of-concept-in-a-case-study
#13
Robert E Brown, Jamie Buryanek, Mary F McGuire
Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28761738/results-of-the-safety-run-in-part-of-the-metal-metformin-in-advanced-lung-cancer-study-a-multicentre-open-label-phase-i-ii-study-of-metformin-with-erlotinib-in-second-line-therapy-of-patients-with-stage-iv-non-small-cell-lung-cancer
#14
Floriana Morgillo, Morena Fasano, Carminia Maria Della Corte, Ferdinando Carlo Sasso, Federica Papaccio, Giuseppe Viscardi, Giovanna Esposito, Raimondo Di Liello, Nicola Normanno, Annalisa Capuano, Liberato Berrino, Giovanni Vicidomini, Alfonso Fiorelli, Mario Santini, Fortunato Ciardiello
PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. However, the optimal dose of metformin to be used in non-diabetic patients still remains to be defined. The phase I-II trial METformin in Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose and to evaluate safety and activity of metformin combined with erlotinib in second-line treatment of patients with stage IV NSCLC, whose tumours harbour the WT EGFR gene...
2017: ESMO Open
https://www.readbyqxmd.com/read/28669771/antidiabetic-antioxidant-and-anti-inflammatory-properties-of-water-and-n-butanol-soluble-extracts-from-saharian-anvillea-radiata-in-high-fat-diet-fed-mice
#15
Chouaib Kandouli, Mathieu Cassien, Anne Mercier, Caroline Delehedde, Emilie Ricquebourg, Pierre Stocker, Mourad Mekaouche, Zineb Leulmi, Aicha Mechakra, Sophie Thétiot-Laurent, Marcel Culcasi, Sylvia Pietri
ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties...
July 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28628912/liver-kinase-b1-amp-activated-protein-kinase-pathway-activation-attenuated-the-progression-of-endotoxemia-in-the-diabetic-mice
#16
Yan Yang, Ruolan Dong, Danli Hu, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
BACKGROUND/AIMS: Sepsis is a common disease that continues to increase in prevalence worldwide, and diabetes mellitus may make the situation worse. This study was designed to determine the role of Liver Kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in diabetic mice complicated with systemic endotoxemia. METHODS: The effects of LKB1/AMPK signaling pathway activation on endotoxemia were investigated in streptozotocin induced diabetic mice (STZ-mice) and db/db diabetic mice...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28610911/airway-glucose-homeostasis-a-new-target-in-the-prevention-and-treatment-of-pulmonary-infection
#17
REVIEW
Emma H Baker, Deborah L Baines
In health, the glucose concentration of airway surface liquid (ASL) is 0.4 mM, about 12 times lower than the blood glucose concentration. Airway glucose homeostasis comprises a set of processes that actively maintain low ASL glucose concentration against the transepithelial gradient. Tight junctions between airway epithelial cells restrict paracellular glucose movement. Epithelial cellular glucose transport and metabolism removes glucose from ASL. Low ASL glucose concentrations make an important contribution to airway defense against infection, limiting bacterial growth by restricting nutrient availability...
June 10, 2017: Chest
https://www.readbyqxmd.com/read/28472612/acidemia-and-blood-free-fatty-acids-analysis-of-cardiovascular-risk-factors-in-a-new-context
#18
António Heitor Reis
Following a hypothesis developed in an earlier paper, here it is discussed how deviations of blood pH from the normal range (namely states of acidemia) together with high blood levels of free fatty acids (FFA) may offer a rationale for many important risk factors for cardiovascular diseases (CVD) by shaping a context for formation of fatty acid micelles and vesicles with an acidic core, which fuse with the endothelia, disrupt vital cell processes, and thereby may initiate atherosclerotic plaque formation. Acidemia may arise primarily from dysregulation of the systemic buffers that control blood pH, chronic diseases of kidneys and lungs, inappropriate diet, or may be induced by some common drugs...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28186975/amp-activated-protein-kinase-reduces-inflammatory-responses-and-cellular-senescence-in-pulmonary-emphysema
#19
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
https://www.readbyqxmd.com/read/28065465/a-multicenter-double-blind-phase-ii-study-of-metformin-with-gefitinib-as-first-line-therapy-of-locally-advanced-non-small-cell-lung-cancer
#20
MULTICENTER STUDY
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 (www.ClinicalTrials.gov 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...
May 2017: Clinical Lung Cancer
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