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Metformin pancreatic cancer

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https://www.readbyqxmd.com/read/29079305/kras-yap-and-obesity-in-pancreatic-cancer-a-signaling-network-with-multiple-loops
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28566532/risk-and-protective-factors-for-the-occurrence-of-sporadic-pancreatic-endocrine-neoplasms
#14
Roberto Valente, Alastair J Hayes, Sven-Petter Haugvik, Per Hedenström, Darko Siuka, Emilie Korsæth, Daniel Kämmerer, Stuart M Robinson, Patrick Maisonneuve, Gianfranco Delle Fave, Bjorn Lindkvist, Gabriele Capurso
Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions...
August 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28549344/metformin-increases-chemo-sensitivity-via-gene-downregulation-encoding-dna-replication-proteins-in-5-fu-resistant-colorectal-cancer-cells
#15
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)...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548941/withdrawn-prognostic-role-of-anti-diabetic-drugs-in-pancreatic-cancer-a-systematic-review-and-meta-analysis
#16
Lei Zheng, Shinan Yin, Fenghua Yao, Hua Bai, Danqing Jing
Ahead of Print article withdrawn by publisher.
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533491/prognostic-significance-of-anti-diabetic-medications-in-pancreatic-cancer-a-meta-analysis
#17
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)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445955/metformin-is-associated-with-survival-benefit-in-pancreatic-cancer-patients-with-diabetes-a-systematic-review-and-meta-analysis
#18
Ping-Ting Zhou, Bo Li, Fu-Rao Liu, Mei-Chao Zhang, Qian Wang, Yan-Yan Li, Ci Xu, Yuan-Hua Liu, Yuan Yao, Dong Li
BACKGROUND: Pancreatic cancer is a highly lethal disease with a poor prognosis while metformin has been associated with a decreased risk of pancreatic cancer. Although the benefit of metformin was observed for pancreatic cancer prevention, it is not clear whether it can also affect the survival of pancreatic cancer patients with type 2 diabetes mellitus. A systematic review and meta-analysis was conducted to assess the effect of metformin on the survival of pancreatic cancer patients with type 2 diabetes mellitus...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429253/modified-metformin-as-a-more-potent-anticancer-drug-mitochondrial-inhibition-redox-signaling-antiproliferative-effects-and-future-epr-studies
#19
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael B Dwinell
Metformin, one of the most widely prescribed antidiabetic drugs in the world, is being repurposed as a potential drug in cancer treatment. Epidemiological studies suggest that metformin exerts anticancer effects in diabetic patients with pancreatic cancer. However, at typical antidiabetic doses the bioavailability of metformin is presumably too low to exert antitumor effects. Thus, more potent analogs of metformin are needed in order to increase its anticancer efficacy. To this end, a new class of mitochondria-targeted metformin analogs (or mito-metformins) containing a positively-charged lipophilic triphenylphosphonium group was synthesized and tested for their antitumor efficacy in pancreatic cancer cells...
December 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28403788/effect-of-metformin-and-statin-use-on-survival-in-pancreatic-cancer-patients-a-systematic-literature-review-and-meta-analysis
#20
Jian-Yu E, Judith M Graber, Shou-En Lu, Yong Lin, Grace Lu-Yao, Xiang-Lin Tan
BACKGROUND AND OBJECTIVE: Current epidemiological studies report conflicting results for the effect of statin or metformin on pancreatic cancer overall survival. This literature review and meta-analysis summarizes the studies reporting an association between statin or metformin use and overall survival of pancreatic cancer patients. METHODS: We systematically searched for studies about the association between statin or metformin use and pancreatic cancer overall survival in electronic databases (PubMed, ISI Web of Science, MEDLINE, Cochrane, Scopus, Google Scholar)...
April 12, 2017: Current Medicinal Chemistry
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