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https://www.readbyqxmd.com/read/29334602/high-dose-metformin-plus-temozolomide-shows-increased-anti-tumor-effects-in-glioblastoma-in-vitro-and-in-vivo-compared-with-monotherapy
#1
Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang
Purpose: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo. Materials and Methods: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5x105 U87 cells and treated with metformin, TMZ, and the combination for 4 weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway...
January 10, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29320602/when-metformin-is-not-enough-pros-and-cons-of-sglt2-and-dpp-4-inhibitors-as-a-second-line-therapy
#2
REVIEW
Angelo Avogaro, Elías Delgado, Ildiko Lingvay
The newer oral therapies for type 2 diabetes (T2DM); dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have advantages over older agents. DPP-4 inhibitors are weight neutral, and have few adverse effects. SGLT2 inhibitors have additional benefits; weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. SGLT2 inhibitors, have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis...
January 10, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29319171/the-key-genes-underlying-pathophysiology-association-between-the-type-2-diabetic-and-colorectal-cancer
#3
Wen-Fang Peng, Feng Bai, Kan Shao, Li-Sha Shen, Hui-Hua Li, Shan Huang
Althoughdiabetes mellitus (DM) is reported as an independent risk factor for colorectal cancer (CRC) in many researches, the underlying pathophysiology is still unclear. We investigated the differentiallyexpressedgenes (DEGs)for the diabetes and CRC to reveal the underlying pathophysiological association between the type 2-diabetic (T2D) and CRC. Gene expression profiles for T2D (GSE55650), CRC (GSE8671) and Metformin treated cell lines (GSE67342) were downloaded from GEO database. The DEGs between T2D samples and their control samples were identified with t-test and variance analysis...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29312591/metformin-sensitizes-lung-cancer-cells-to-treatment-by-the-tyrosine-kinase-inhibitor-erlotinib
#4
Xiaofei Wang, Keqiang Chen, Ying Yu, Yi Xiang, Jae Hong Kim, Wanghua Gong, Jiaqiang Huang, Guochao Shi, Qingyun Li, Min Zhou, Thomas Sayers, Poonam Tewary, Beili Gao, Ji Ming Wang
Lung cancer is one of the deadliest malignant tumors with limited treatment options. Although targeted therapy, using tyrosine-kinase inhibitors such as erlotinib (Erlo), has shown therapeutic benefit, only 15 % patients with mutated epidermal growth factor receptor (EGFR) in lung cancer cells are sensitive. Therefore, additional therapeutic strategy should be developed. In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305964/in-vitro-and-in-vivo-characterization-of-stem-like-cells-from-canine-osteosarcoma-and-assessment-of-drug-sensitivity
#5
Monica Gatti, Agnese Solari, Alessandra Pattarozzi, Chiara Campanella, Stefano Thellung, Lorella Maniscalco, Raffaella De Maria, Roberto Würth, Alessandro Corsaro, Adriana Bajetto, Alessandra Ratto, Angelo Ferrari, Antonio Daga, Federica Barbieri, Tullio Florio
CSC self-renewing and drug resistance cause treatment failure and tumor recurrence. Osteosarcoma is an aggressive bone tumor characterized by biological and molecular heterogeneity, possibly dependent on cancer stem cells (CSCs). CSC identification in osteosarcoma and their efficient targeting are still open questions. Spontaneous canine osteosarcoma shares clinical and biological features with the human tumors, representing a model for translational studies. We characterized three CSC-enriched canine osteosarcoma cultures...
January 3, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29286158/metformin-inhibits-hacat-cell-viability-via-the-mir-21-pten-akt-signaling-pathway
#6
Yue Deng, Weiyuan Ma
Substantial preclinical evidence has indicated out a direct anti‑proliferation effect of metformin on various solid tumors; however, further and more detailed exploration into its molecular mechanism remains to be performed. The present study aimed to investigate the effect of metformin on cell viability and its underlying mechanism, in the cultured human skin keratinocyte cell line, HaCaT. In addition, it aimed to clarify the role of the microRNA-21(miR-21)/phosphatase and tensin homolog (PTEN)/AKT serine/threonine kinase 1 (Akt) signaling pathway, which has been hypothesized to be involved in the molecular mechanism of this drug...
December 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29286156/metformin-induced-activation-of-ampk-inhibits-the-proliferation-and-migration-of-human-aortic-smooth-muscle-cells-through-upregulation-of-p53-and-ifi16
#7
Biao Hao, Yan Xiao, Fang Song, Xiangshu Long, Jing Huang, Maobo Tian, Shiyan Deng, Qiang Wu
The proliferation and migration of vascular smooth muscle cells are significant in the development and progression of atherosclerosis and plaque rupture. Metformin is a widely used antidiabetic drug, which has been reported to inhibit cell growth and migration. The antiproliferative and antimigratory effects of metformin have been attributed to 5' adenosine monophosphate-activated protein kinase (AMPK) activation. The purpose of the present study was to investigate the effects of metformin on primary human aortic muscle cells (HASMCs) in vitro and to clarify the underlying mechanism...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285270/metformin-alleviates-nickel-induced-autophagy-and-apoptosis-via-inhibition-of-hexokinase-2-activating-lipocalin-2-in-human-bronchial-epithelial-cells
#8
Yu-Ting Kang, Wen-Cheng Hsu, Chih-Hsien Wu, I-Lun Hsin, Pei-Ru Wu, Kun-Tu Yeh, Jiunn-Liang Ko
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274062/metformin-beta-cell-development-and-novel-processes-following-beta-cell-ablation-in-zebrafish
#9
Georgia Wyett, Yann Gibert, Megan Ellis, Hozana A Castillo, Jan Kaslin, Kathryn Aston-Mourney
PURPOSE: Type 1 and 2 diabetes are characterized by a loss of insulin-producing beta-cells. Current treatments help maintain blood glucose levels but cannot provide a cure. As such, a vital target for the cure of diabetes is a way to restore beta-cell mass. The drug metformin can protect cultured beta-cells/islets from hyperglycemia-induced dysfunction and death. Further, treatment of pregnant mice with metformin results in an enhanced beta-cell fraction in the embryos; however, whether this occurs via a direct effect is unknown...
December 22, 2017: Endocrine
https://www.readbyqxmd.com/read/29250169/therapeutic-strategies-against-cancer-stem-cells-in-human-colorectal-cancer
#10
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Piotr Spychalski, Zbigniew Kmieć
Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29228671/metformin-ameliorates-skeletal-muscle-insulin-resistance-by-inhibiting-mir-21-expression-in-a-high-fat-dietary-rat-model
#11
Jinyang Wang, Yanbin Gao, Lijun Duan, Suhong Wei, Jing Liu, Liming Tian, Jinxing Quan, Qi Zhang, Juxiang Liu, Jinkui Yang
Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228105/metformin-attenuates-susceptibility-to-inflammation-induced-preterm-birth-in-mice-with-higher-endocannabinoid-levels
#12
Xiaofei Sun, Alexandra Tavenier, Wenbo Deng, Emma Leishman, Heather B Bradshaw, Sudhansu K Dey
Premature decidual senescence is a contributing factor to preterm birth. Fatty acid amide hydrolase mutant females (Faah-/-) with higher endocannabinoid levels are also more susceptible to preterm birth upon lipopolysaccharide (LPS) challenge due to enhanced decidual senescence; this is associated with MAPK p38 activation. Previous studies have shown that mammalian target of rapamycin complex 1 (mTORC1) contributes to decidual senescence and promotes the incidence of preterm birth. In the present study, we sought to attenuate premature decidual aging in Faah-/- females by targeting mTORC1 and p38 signaling pathways...
December 5, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29226720/memantine-induces-apoptosis-and-inhibits-cell-cycle-progression-in-lncap-prostate-cancer-cells
#13
G Albayrak, E Konac, A U Dikmen, C Y Bilen
Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29221717/effect-of-metformin-combined-with-lifestyle-modification-versus-lifestyle-modification-alone-on-proinflammatory-oxidative-status-in-drug-na%C3%A3-ve-pre-diabetic-and-diabetic-patients-a-randomized-controlled-study
#14
Nailya Bulatova, Violet Kasabri, Amenah Qotineh, Taiba Al-Athami, Al-Motassem Yousef, Salah AbuRuz, Munther Momani, Aymen Zayed
BACKGROUND: Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. METHODS: 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline...
November 23, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29210642/antidiabetics-structural-diversity-of-molecules-with-a-common-aim
#15
Jelena B Popovic-Dordevic, Ivana I Jevtic, Tatjana P Stanojkovic
BACKGROUND: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29205344/synergistic-actions-of-vitamin-d-and-metformin-on-skeletal-muscles-and-insulin-resistance-of-type-2-diabetic-rats
#16
REVIEW
Shaimaa N Amin, Usama K Hussein, Hanan D Yassa, Sherif S Hassan, Laila A Rashed
Diabetes Mellitus is a chronic generalized disorder due to insulin insufficiency or resistance. Skeletal muscles represent one of the most important target organs that is affected by insulin signaling. The aim of the current work was to investigate the effect of metformin versus vitamin D (and also simultaneous administration) therapy in type 2 diabetic (T2D) rats on the state of the muscle and insulin sensitivity. Thirty six male rats constituted the animal model and have been divided into five groups: control, Diabetic, Diabetic+Metformin, Diabetic+ VitaminD, Diabetic+Metformin+Vitamin D...
December 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29204687/a-physiologically-based-pharmacokinetic-pbpk-parent-metabolite-model-of-the-chemotherapeutic-zoptarelin-doxorubicin-integration-of-in-vitro-results-phase-i-and-phase-ii-data-and-model-application-for-drug-drug-interaction-potential-analysis
#17
Nina Hanke, Michael Teifel, Daniel Moj, Jan-Georg Wojtyniak, Hannah Britz, Babette Aicher, Herbert Sindermann, Nicola Ammer, Thorsten Lehr
PURPOSE: Zoptarelin doxorubicin is a fusion molecule of the chemotherapeutic doxorubicin and a luteinizing hormone-releasing hormone receptor (LHRHR) agonist, designed for drug targeting to LHRHR positive tumors. The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) parent-metabolite model of zoptarelin doxorubicin and to apply it for drug-drug interaction (DDI) potential analysis. METHODS: The PBPK model was built in a two-step procedure...
December 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29196297/acetylsalicylic-acid-governs-the-effect-of-sorafenib-in-ras-mutant-cancers
#18
Heinz Hammerlindl, Dinoop Ravindran Menon, Sabrina Hammerlindl, Abdullah Al Emran, Joachim Torrano, Katrin Sproesser, Divya Thakkar, Min Xiao, Victoria G Atkinson, Brian Gabrielli, Nikolas K Haass, Meenhard Herlyn, Clemens Krepler, Helmut Schaider
PURPOSE: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. EXPERIMENTAL DESIGN: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#19
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/29188733/investigational-drugs-in-clinical-trials-for-hidradenitis-suppurativa
#20
Peter Theut Riis, Linnea R Thorlacius, Gregor B Jemec
Hidradenitis suppurativa is a chronic skin disease with a significant unmet need for treatment options. Randomized controlled trials are few and only a single drug (adalimumab) has Hidradenitis as a registered indication. Areas covered: The clinicaltrials.gov and the EudraCT clinical trials register for reported trials on Hidradenitis Suppurativa was searched on the 22-06-2017. Trials for upcoming new drugs for HS are reported focusing on drugs in phase I and II trials. Expert opinion: Currently, MABp1, Secukinumab, CJM112, Apremilast and IFX-1 are being investigated in Phase I and II trials and offer theoretical and promising new treatment options...
December 4, 2017: Expert Opinion on Investigational Drugs
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