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Metformin pancreatic cancer

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https://www.readbyqxmd.com/read/29434877/metformin-synergizes-with-rapamycin-to-inhibit-the-growth-of-pancreatic-cancer-in-vitro-and-in-vivo
#1
Jia-Wei Zhang, Fan Zhao, Qing Sun
Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin specifically targets mTOR. In the present study, the efficacy of metformin and rapamycin in isolation and combination were investigated for the treatment of PC. The efficacy of metformin and rapamycin in reducing the proliferation of PC cell line SW1990 in vitro and in vivo was evaluated...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29424813/survival-benefits-from-metformin-use-in-pancreatic-cancer-a-systemic-review-and-meta-analysis
#2
Kamonkiat Wirunsawanya, Veeravich Jaruvongvanich, Sikarin Upala
No abstract text is available yet for this article.
March 2018: Pancreas
https://www.readbyqxmd.com/read/29420223/oxidative-phosphorylation-as-an-emerging-target-in-cancer-therapy
#3
Thomas M Ashton, W Gillies McKenna, Leoni A Kunz-Schughart, Geoff S Higgins
Cancer cells have upregulated glycolysis compared to normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers.  However, recent studies have shown that OXPHOS can be also upregulated in certain cancers, including leukemias, lymphomas, pancreatic ductal adenocarcinoma, high OXPHOS subtype melanoma and endometrial carcinoma, and that this can occur even in the face of active glycolysis.  OXPHOS inhibitors could therefore be used to target cancer subtypes in which OXPHOS is upregulated, and to alleviate therapeutically adverse tumor hypoxia...
February 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29415987/oncogenic-hsp60-regulates-mitochondrial-oxidative-phosphorylation-to-support-erk1-2-activation-during-pancreatic-cancer-cell-growth
#4
Chao Zhou, Hongwei Sun, Chen Zheng, Jing Gao, Qingzi Fu, Nianqi Hu, Xiaoli Shao, Yingying Zhou, Jingting Xiong, Ke Nie, Huaibin Zhou, Lijun Shen, Hezhi Fang, Jianxin Lyu
HSP60 is a mitochondrial localized quality control protein responsible for maintaining mitochondrial function. Although HSP60 is considered both a tumor suppressor and promoter in different types of cancer, the role of HSP60 in human pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, we demonstrated that HSP60 was aberrantly expressed in human pancreatic cancer tissues and cell lines. Analysis of the Cancer Genome Atlas database revealed that HSP60 expression is positively correlated with pancreatic cancer...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29374343/preliminary-results-that-assess-metformin-treatment-in-a-preclinical-model-of-pancreatic-cancer-using-simultaneous-18f-fdg-pet-and-acidocest-mri
#5
Joshua M Goldenberg, Julio Cárdenas-Rodríguez, Mark D Pagel
PURPOSE: We sought to determine if the synergy between evaluations of glucose uptake in tumors and extracellular tumor acidosis measured with simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) can improve longitudinal evaluations of the response to metformin treatment. PROCEDURES: A standard 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET protocol that evaluates glucose uptake in tumors, and a standard acidoCEST MRI protocol that measures extracellular pH (pHe) in tumors, were simultaneously performed to assess eight vehicle-treated (control) mice and eight metformin-treated mice 1 day before treatment, 1 day after initiating daily treatment with metformin, and 7 days after initiating treatment...
January 26, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#6
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29304290/effects-of-metformin-on-insulin-resistance-and-metabolic-disorders-in-tumor-bearing-rats-with-advanced-cachexia
#7
Flaviane de Fatima Silva, Milene Ortiz-Silva, Winny Beatriz de Souza Galia, Priscila Cassolla, Francemilson Goulart da Silva, Maria Fernanda Rodrigues Graciano, Angelo Carpinelli, Helenir Medri de Souza
Metformin (MET) is widely used in the correction of insulin (INS) resistance and metabolic abnormalities in type 2 diabetes. However, its effect on INS resistance and metabolic disorders associated with cancer cachexia is not established. We investigated the MET effects, isolated or associated with INS, on INS resistance and metabolic changes induced by Walker-256 tumor in rats with advanced cachexia. MET (500 mg.kg-1, oral) and MET + INS (NPH, 1.0 IU.kg-1, sc) were administered during 12 days, starting on the day of tumor cell inoculation...
January 5, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29079305/kras-yap-and-obesity-in-pancreatic-cancer-a-signaling-network-with-multiple-loops
#8
REVIEW
Guido Eibl, Enrique Rozengurt
Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully invasive PDAC...
October 24, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28977950/prognostic-significance-of-anti-diabetic-medications-in-pancreatic-cancer-a-meta-analysis
#9
Dong-Chu Zhou, Hui Gong, Chong-Qing Tan, Jian-Quan Luo
The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915611/metformin-increases-chemo-sensitivity-via-gene-downregulation-encoding-dna-replication-proteins-in-5-fu-resistant-colorectal-cancer-cells
#10
Sung-Hee Kim, Soon-Chan Kim, Ja-Lok Ku
Metformin is most widely prescribed for type 2 diabetes. Recently, evidences have shown that metformin has anticancer effects on pancreatic-, colorectal-, ovarian-, and other cancers. Because metformin has less adverse effects and is inexpensive, it could be a useful chemo-therapeutic agent with anticancer effects. In this study, we demonstrated metformin inhibited by cell proliferation, cell migration ability, clonogenic ability, and cancer stem cell population. Metformin also induced cell cycle arrest in parental-(SNU-C5), and 5-Fu resistant-colorectal cancer cell line (SNU-C5_5FuR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903435/effects-of-metformin-on-survival-outcomes-of-pancreatic-cancer-a-meta-analysis
#11
Yi-Wei Dong, Yan-Qiang Shi, Li-Wen He, Xi-Yu Cui, Pei-Zhu Su
BACKGROUND AND AIM: Recent epidemiological studies indicated that metformin might improve the survival of various cancers. However, its benefit on pancreatic cancer was controversial. METHODS: We performed this meta-analysis to investigate the benefit of metformin on pancreatic cancer. A comprehensive literature search was performed through PubMed, Cochrane Library and Embase. Relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were pooled...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875433/crucial-micrornas-and-genes-in-metformin-s-anti-pancreatic-cancer-effect-explored-by-microrna-mrna-integrated-analysis
#12
Yilong Li, Le Li, Guangquan Zhang, Yongwei Wang, Hua Chen, Rui Kong, Shangha Pan, Bei Sun
Despite great improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate. Therefore, novel therapeutic strategies for the prevention and treatment of pancreatic cancer are urgently needed. The present study aimed to investigate the mechanisms by which metformin exerts its anticancer effects on the microRNA-mRNA interactions in human pancreatic cancer. Microarray and systematic analyses revealed that the anti-pancreatic cancer effects of metformin were correlated with 3 up-regulated microRNAs and 4 of their target mRNAs...
September 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819370/metformin-inhibits-gemcitabine-induced-apoptosis-in-pancreatic-cancer-cell-lines
#13
Dietmar Zechner, Ann-Christin Albert, Florian Bürtin, Brigitte Vollmar
Many preclinical and clinical studies are currently evaluating metformin in combination with classical therapeutic agents as anti-cancer therapy. In this study we used three distinct pancreatic cancer cell lines and evaluated cell death by trypan blue assay and Western Blots using antibodies directed against cleaved caspase 3 and PARP. Surprisingly, we observed that 20mM metformin did not enhance, but rather inhibited gemcitabine induced cell death in murine 7265PDA, 6606PDA and 6606l cells. Microenvironmental aspects such as oxygen supply or the pH value did not influence the inhibition of cancer cell apoptosis by metformin...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28738823/metformin-suppresses-cancer-initiation-and-progression-in-genetic-mouse-models-of-pancreatic-cancer
#14
Ke Chen, Weikun Qian, Zhengdong Jiang, Liang Cheng, Jie Li, Liankang Sun, Cancan Zhou, Luping Gao, Meng Lei, Bin Yan, Junyu Cao, Wanxing Duan, Qingyong Ma
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide with an overall five-year survival rate less than 7%. Accumulating evidence has revealed the cancer preventive and therapeutic effects of metformin, one of the most widely prescribed medications for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully elucidated. Herein, we aimed to further study the preventive and therapeutic effects of metformin in genetically engineered mouse models of pancreatic cancer...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28724893/the-effect-of-metformin-on-survival-of-patients-with-pancreatic-cancer-a-meta-analysis
#15
Xiaogang Li, Tong Li, Zhiqiang Liu, Shanmiao Gou, Chunyou Wang
We conducted a meta-analysis to analyse the effect of metformin on survival of pancreatic cancer patients at various stages. We performed a systematic search of PubMed, Embase, Cochrane, and Web of Science to identify all relevant studies. Summary hazard ratios (HR) of survival and 95% confidence intervals (95% CI) were calculated with a fixed or random effects model according to inter-study heterogeneity. Nine retrospective cohort studies and two randomized controlled trials (RCTs) were eligible. There was a significant improvement in survival (HR = 0...
July 19, 2017: Scientific Reports
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
#16
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/28624799/effects-of-metformin-on-survival-outcomes-of-pancreatic-cancer-a-meta-analysis
#17
Yi-Wei Dong, Yan-Qiang Shi, Li-Wen He, Xi-Yu Cui, Pei-Zhu Su
BACKGROUND AND AIM: Recent epidemiological studies indicated that metformin might improve the survival of various cancers. However, its benefit on pancreatic cancer was controversial. METHODS: We performed this meta-analysis to investigate the benefit of metformin on pancreatic cancer. A comprehensive literature search was performed through PubMed, Cochrane Library and Embase. Relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were pooled...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619830/differential-and-joint-effects-of-metformin-and-statins-on-overall-survival-of-elderly-patients-with-pancreatic-adenocarcinoma-a-large-population-based-study
#18
Jian-Yu E, Shou-En Lu, Yong Lin, Judith M Graber, David Rotter, Lanjing Zhang, Gloria M Petersen, Kitaw Demissie, Grace Lu-Yao, Xiang-Lin Tan
Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive.Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files...
August 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#19
N V Rajeshkumar, Shinichi Yabuuchi, Shweta G Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fátima Al-Shahrour, Manuel Hidalgo, Anirban Maitra, Chi V Dang
Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo antitumor efficacy of metabolic inhibitors, as single agents, in a panel of patient-derived PDAC xenograft models (PDX) and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors.Experimental Design: Mice with established PDAC tumors from 6 to 13 individual PDXs were randomized and treated, once daily for 4 weeks, with either sterile PBS (vehicle) or the glutaminase inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), and mitochondrial complex I inhibitor phenformin/metformin...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599404/neoadjuvant-chemotherapy-for-pancreatic-cancer-effects-on-cancer-tissue-and-novel-perspectives
#20
Hidehiro Tajima, Isamu Makino, Yoshinao Ohbatake, Shinichi Nakanuma, Hironori Hayashi, Hisatoshi Nakagawara, Tomoharu Miyashita, Hiroyuki Takamura, Tetsuo Ohta
Chemotherapy for pancreatic cancer has diversified following the addition of more treatment regimens; however, in spite of this, pancreatic cancer remains a fatal disease. Preoperative (neoadjuvant) chemotherapy (NAC) or neoadjuvant chemoradiation therapy (NACRT) has been developed and implemented. For patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), a number of clinical trials have been conducted; NACRT was demonstrated to improve resectability, R0 resection rate, overall survival rate, disease-free survival rate and even an LAPC and BRPC survival advantage over NAC...
June 2017: Oncology Letters
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