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Metformin pancreatic cancer

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https://www.readbyqxmd.com/read/29663879/anti-cancer-effects-of-metformin-recent-evidences-for-its-role-in-prevention-and-treatment-of-cancer
#1
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Warda Kamal, Mohammad A Kamal
Metformin is widely used for the management of type 2 diabetes mellitus (T2DM). Recently growing evidence has shown its anti-cancer effects. The results are mainly obtained from observational studies and thus, little information is available concerning the mechanisms of action. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in the mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects, whereas the decrease in glucose level, hyperinsulinemia, and Insulin-like growth factor 1 (IGF-1) level was considered its indirect effects...
April 16, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29655834/metformin-use-associates-with-longer-progression-free-survival-of-patients-with-diabetes-and-pancreatic-neuroendocrine-tumors-receiving-everolimus-and-or-somatostatin-analogues
#2
Sara Pusceddu, Claudio Vernieri, Massimo Di Maio, Riccardo Marconcini, Francesca Spada, Sara Massironi, Toni Ibrahim, Maria Pia Brizzi, Davide Campana, Antongiulio Faggiano, Dario Giuffrida, Maria Rinzivillo, Sara Cingarlini, Francesca Aroldi, Lorenzo Antonuzzo, Rossana Berardi, Laura Catena, Chiara De Divitiis, Paola Ermacora, Vittorio Perfetti, Annalisa Fontana, Paola Razzore, Carlo Carnaghi, Maria Vittoria Davì, Carolina Cauchi, Marilina Duro, Sergio Ricci, Nicola Fazio, Federica Cavalcoli, Alberto Bongiovanni, Anna La Salvia, Nicole Brighi, Annamaria Colao, Ivana Puliafito, Francesco Panzuto, Silvia Ortolani, Alberto Zaniboni, Francesco Di Costanzo, Mariangela Torniai, Emilio Bajetta, Salvatore Tafuto, Silvio Ken Garattini, Daniela Femia, Natalie Prinzi, Laura Concas, Giuseppe Lo Russo, Massimo Milione, Luca Giacomelli, Roberto Buzzoni, Gianfranco Delle Fave, Vincenzo Mazzaferro, Filippo de Braud
BACKGROUND & AIMS: Metformin seems to have anti-cancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with NETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy, from 1999 through 2015...
April 12, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29609037/%C3%AE-cyano-4-hydroxycinnamate-impairs-pancreatic-cancer-cells-by-stimulating-the-p38-signaling-pathway
#3
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29601127/lkb1-obliterates-snail-stability-and-inhibits-pancreatic-cancer-metastasis-in-response-to-metformin-treatment
#4
Lele Song, Jingyu Guo, Renxu Chang, Xiaobo Peng, Jie Li, Xiaorong Xu, Xianbao Zhan, Lixing Zhan
Metastasis to distant organs is a particularly ominous feature of most malignant cancer. LKB1 (also known as STK11) has been identified as a tumor suppressor in several types of cancers. Here, we show that LKB1 is at low level and negatively associated with poor clinical outcomes in pancreatic cancer (PC). LKB1 is inversely correlated with Snail protein in PC, in which loss of LKB1 facilitates metastasis through elevating Snail protein level. Furthermore, LKB1 boosts Snail interacting with E3 ligase FBXL14, leading to increasing ubiquitin-mediated Snail degradation...
March 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29587290/chemoprevention-and-treatment-of-pancreatic-cancer-update-and-review-of-the-literature
#5
Julia Benzel, Volker Fendrich
BACKGROUND: Pancreatic ductal adenocarcinoma is one of the most lethal types of cancer with a 5-year survival rate of around 7%. Due to the relatively poor prognosis, the potential need of an effective chemoprevention is highly needed. SUMMARY: Different risk factors like smoking or hereditary tumour syndromes should be known for early detection of pancreatic intraepithelial neoplasia. Chemopreventive dietary agents include curcumin, capsaicin and flavonoid, whereas potential chemopreventive drugs compromise aspirin, metformin or statins...
March 27, 2018: Digestion
https://www.readbyqxmd.com/read/29545399/specificity-protein-transcription-factors-and-cancer-opportunities-for-drug-development
#6
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29482945/metformin-influences-drug-sensitivity-in-pancreatic-cancer-cells
#7
Saverio Candido, Stephen L Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Matilde Y Follo, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes...
February 12, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29468063/effects-of-metformin-on-survival-outcomes-of-pancreatic-cancer-patients-with-diabetes-a-meta-analysis
#8
Wenxiu Xin, Luo Fang, Qilu Fang, Xiaowei Zheng, Ping Huang
Pancreatic cancer risk is reduced by metformin treatment in patients with diabetes. However, the effect of metformin on pancreatic cancer overall survival is unclear. The aim of the present study was to determine the association between metformin and clinical outcomes of pancreatic cancer patients with diabetes. An electronic and manual search was conducted using PubMed, Web of Science, Medline-Ovid and Cochrane Library databases between the beginning and March 31, 2017. A total of 8 studies consisting of 4,293 patients with pancreatic cancer with diabetes were included, comprising 2,033 patients who had received metformin and 2,260 patients who had not...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29434877/metformin-synergizes-with-rapamycin-to-inhibit-the-growth-of-pancreatic-cancer-in-vitro-and-in-vivo
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
Flaviane de Fatima Silva, Milene Ortiz-Silva, Winny Beatriz de Souza Galia, Priscila Cassolla, Francemilson Goulart da Silva, Maria Fernanda Rodrigues Graciano, Angelo Rafael 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 (1.0 IU·kg-1 , s.c.) were administered for 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
#16
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
#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)...
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
#18
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
#19
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
#20
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
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