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Metformin pancreatic cancer

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https://www.readbyqxmd.com/read/28429253/modified-metformin-as-a-more-potent-anticancer-drug-mitochondrial-inhibition-redox-signaling-antiproliferative-effects-and-future-epr-studies
#1
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...
April 21, 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
#2
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
https://www.readbyqxmd.com/read/28382202/mitochondria-targeted-metformins-anti-tumour-and-redox-signalling-mechanisms
#3
REVIEW
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael Dwinell
Reports suggest that metformin exerts anti-cancer effects in diabetic individuals with pancreatic cancer. Thus, metformin is currently being repurposed as a potential drug in cancer treatment. Studies indicate that potent metformin analogues are required in cancer treatment because of the low bioavailability of metformin in humans at conventional antidiabetic doses. We proposed that improved mitochondrial targeting of metformin by attaching a positively charged lipophilic triphenylphosphonium group will result in a new class of mitochondria-targeted metformin analogues with significantly enhanced anti-tumour potential...
April 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28373404/precancer-atlas-to-drive-precision-prevention-trials
#4
Avrum Spira, Matthew B Yurgelun, Ludmil Alexandrov, Anjana Rao, Rafael Bejar, Kornelia Polyak, Marios Giannakis, Ali Shilatifard, Olivera J Finn, Madhav Dhodapkar, Neil E Kay, Esteban Braggio, Eduardo Vilar, Sarah A Mazzilli, Timothy R Rebbeck, Judy E Garber, Victor E Velculescu, Mary L Disis, Douglas C Wallace, Scott M Lippman
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity - basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28274936/no-decreased-risk-of-gastrointestinal-cancers-in-users-of-metformin-in-the-netherlands-a-time-varying-analysis-of-metformin-exposure
#5
Roy G de Jong, Andrea M Burden, Sander de Kort, Myrthe van Herk-Sukel, Pauline A Vissers, Paddy K Janssen, Harm R Haak, Ad A M Masclee, Frank de Vries, Maryska L Janssen-Heijnen
Previous studies on metformin use and gastrointestinal (GI) cancer risk have yielded inconclusive results on metformin's chemoprotective effects. We aimed to evaluate GI cancer risk in users of metformin in The Netherlands using a time-varying approach in a large population-based database. A cohort study was performed using the NCR-PHARMO database. Patients using ≥1 non-insulin anti-diabetic drug (NIAD) during 1998-2011 were included (N=57,621). Exposure to NIADs was modelled time-varyingly. Cox regression analysis estimated hazard ratios (HRs) of GI cancers in current metformin users versus current users of other NIADs...
March 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28272215/no-association-between-metformin-use-and-survival-in-patients-with-pancreatic-cancer-an-observational-cohort-study
#6
Martine A Frouws, Babs G Sibinga Mulder, Esther Bastiaannet, Marjolein M J Zanders, Myrthe P P van Herk-Sukel, Eleonora M de Leede, Bert A Bonsing, J Sven D Mieog, Cornelis J H Van de Velde, Gerrit-Jan Liefers
Several studies have suggested an association between use of metformin and an increased overall survival in patients diagnosed with pancreatic cancer, however with several important methodological limitations. The aim of the study was to assess the association between overall survival, pancreatic cancer, and metformin use.A retrospective cohort study of 1111 patients with pancreatic cancer was conducted using data from The Netherlands Comprehensive Cancer Organization (1998-2011). Data were linked to the PHARMO Database Network containing drug-dispensing records from community pharmacies...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28104298/kr%C3%A3-pple-like-factor-10-regulates-radio-sensitivity-of-pancreatic-cancer-via-uv-radiation-resistance-associated-gene
#7
Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
BACKGROUND AND PURPOSE: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. MATERIALS AND METHODS: Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28079594/impact-of-concurrent-medication-use-on-pancreatic-cancer-survival-seer-medicare-analysis
#8
Muhammad S Beg, Arjun Gupta, David Sher, Sadia Ali, Saad Khan, Ang Gao, Tyler Stewart, Chul Ahn, Jarett Berry, Eric M Mortensen
OBJECTIVES: Preclinical studies have suggested that non-antineoplastic medication use may impact pancreatic cancer biology. We examined the association of several medication classes on pancreatic cancer survival in a large medical claims database. MATERIALS AND METHODS: Histologically confirmed pancreatic adenocarcinoma diagnosed between 2006 and 2009 were analyzed from the Surveillance, Epidemiology, and End Results-Medicare database with available part D data...
January 10, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28077783/association-between-metformin-use-and-mortality-in-patients-with-type-2-diabetes-mellitus-and-localized-resectable-pancreatic-cancer-a-nationwide-population-based-study-in-korea
#9
Won Il Jang, Mi-Sook Kim, Shin Hee Kang, Ae Jung Jo, Yun Jung Kim, Ha Jin Tchoe, Chan Mi Park, Hyo Jeong Kim, Jin A Choi, Hyung Jin Choi, Eun-Kyung Paik, Young Seok Seo, Hyung Jun Yoo, Jin-Kyu Kang, Chul Ju Han, Yeon Ju Kim, Sang Beom Kim, Min Jung Ko
BACKGROUND: Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection. RESULTS: A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28065547/comparison-of-the-diabetes-guidelines-from-the-ada-easd-and-the-aace-ace
#10
Susan Cornell
OBJECTIVE: To compare recent diabetes guideline updates from the American Diabetes Association-European Association for the Study of Diabetes (ADA/EASD) and the American Association of Clinical Endocrinologists-American College of Endocrinology (AACE/ACE). SUMMARY: The ADA/EASD guideline continues to advocate a stepwise approach to glycemic control that initiates with metformin and intensifies treatment incrementally to dual and triple therapy at 3-month intervals until the patient is at their individualized goal...
March 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/27984722/an-ancient-unified-mechanism-for-metformin-growth-inhibition-in-c-%C3%A2-elegans-and-cancer
#11
Lianfeng Wu, Ben Zhou, Noriko Oshiro-Rapley, Man Li, Joao A Paulo, Christopher M Webster, Fan Mou, Michael C Kacergis, Michael E Talkowski, Christopher E Carr, Steven P Gygi, Bin Zheng, Alexander A Soukas
Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27773749/desmoplasia-suppression-by-metformin-mediated-ampk-activation-inhibits-pancreatic-cancer-progression
#12
Wanxing Duan, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiahui Li, Jianjun Lei, Qinhong Xu, Jiguang Ma, Xuqi Li, Liang Han, Zheng Wang, Zheng Wu, Fengfei Wang, Erxi Wu, Qingyong Ma, Zhenhua Ma
Emerging evidence suggests that metformin, an activator of AMP-activated protein kinase (AMPK), may be useful in preventing and treating pancreatic ductal adenocarcinoma (PDAC). However, whether metformin has an effect on the stromal reaction of PDAC remains unknown. In this study, we first evaluated the expression of AMPK and phosphorylated-AMPK (P-AMPK) in normal and PDAC tissues, our data indicate that reduced P-AMPK expression is a frequent event in PDAC and correlated with poor prognosis and the dense stromal reaction...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27766700/use-of-statins-offsets-insulin-related-cancer-risk
#13
A Kautzky-Willer, S Thurner, P Klimek
AIM: There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. METHODS: Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins...
October 21, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27765848/mitochondrial-targeting-of-metformin-enhances-its-activity-against-pancreatic-cancer
#14
Stepana Boukalova, Jan Stursa, Lukas Werner, Zuzana Ezrova, Jiri Cerny, Ayenachew Bezawork-Geleta, Alena Pecinova, Lanfeng Dong, Zdenek Drahota, Jiri Neuzil
Pancreatic cancer is one of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells three to four orders of magnitude more efficiently than found for the parental compound...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27745828/efficacy-and-safety-of-dpp-4-inhibitors-in-patients-with-type-2-diabetes-meta-analysis-of-placebo-controlled-randomized-clinical-trials
#15
MULTICENTER STUDY
M B Rehman, B V Tudrej, J Soustre, M Buisson, P Archambault, D Pouchain, H Vaillant-Roussel, F Gueyffier, J-L Faillie, M-C Perault-Pochat, C Cornu, R Boussageon
BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial...
February 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/27705937/metformin-potentiates-anti-tumor-effect-of-resveratrol-on-pancreatic-cancer-by-down-regulation-of-vegf-b-signaling-pathway
#16
Mengmeng Zhu, Qiong Zhang, Xiaoling Wang, Licheng Kang, Yinan Yang, Yuansheng Liu, Lei Yang, Jing Li, Liang Yang, Jie Liu, Yin Li, Lingling Zu, Yanna Shen, Zhi Qi
Our previous study showed that resveratrol (RSV) exhibited not only anti-tumor effect, but also had potential tumor promotion effect on pancreatic cancer (Paca) cells through up-regulation of VEGF-B. We determined whether metformin (MET) could potentiate the anti-tumor effect of RSV on PaCa in this study. Combination of RSV (100 μmol/l) and MET (20 mmol/l) significantly inhibited tumor growth and increased apoptosis of human PaCa in comparison with RSV or MET alone treatment in PaCa cell lines (Miapaca-2, Panc-1 and Capan-2)...
October 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27567928/aspirin-in-pancreatic-cancer-chemopreventive-effects-and-therapeutic-potentials
#17
REVIEW
Ming-Jie Jiang, Juan-Juan Dai, Dian-Na Gu, Qian Huang, Ling Tian
Pancreatic cancer is one of the most aggressive malignancies with dismal prognosis. Recently, aspirin has been found to be an effective chemopreventive agent for many solid tumors. However, the function of aspirin use in pancreatic cancer largely remains unknown. We herein argued that aspirin could also lower the risk of pancreatic cancer. Importantly, aspirin assumes pleiotropic effects by targeting multiple molecules. It could further target the unique tumor biology of pancreatic cancer and modify the cancer microenvironment, thus showing remarkable therapeutic potentials...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27563018/the-role-of-common-pharmaceutical-agents-on-the-prevention-and-treatment-of-pancreatic-cancer
#18
REVIEW
Sunil Amin, Paolo Boffetta, Aimee L Lucas
Survival from pancreatic cancer remains poor. Conventional treatment has resulted in only marginal improvements in survival compared with survival in the previous several decades. Thus, considerable interest has emerged regarding the potential use of common pharmaceutical agents as chemopreventative and chemotherapeutic options. Aspirin, metformin, statins, β-blockers, and bisphosphonates have biologically plausible mechanisms to inhibit pancreatic neoplasia, whereas dipeptidyl-peptidase 4 inhibitors may promote it...
September 15, 2016: Gut and Liver
https://www.readbyqxmd.com/read/27559084/combination-therapy-with-bptes-nanoparticles-and-metformin-targets-the-metabolic-heterogeneity-of-pancreatic-cancer
#19
Amira Elgogary, Qingguo Xu, Brad Poore, Jesse Alt, Sarah C Zimmermann, Liang Zhao, Jie Fu, Baiwei Chen, Shiyu Xia, Yanfei Liu, Marc Neisser, Christopher Nguyen, Ramon Lee, Joshua K Park, Juvenal Reyes, Thomas Hartung, Camilo Rojas, Rana Rais, Takashi Tsukamoto, Gregg L Semenza, Justin Hanes, Barbara S Slusher, Anne Le
Targeting glutamine metabolism via pharmacological inhibition of glutaminase has been translated into clinical trials as a novel cancer therapy, but available drugs lack optimal safety and efficacy. In this study, we used a proprietary emulsification process to encapsulate bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a selective but relatively insoluble glutaminase inhibitor, in nanoparticles. BPTES nanoparticles demonstrated improved pharmacokinetics and efficacy compared with unencapsulated BPTES...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27499118/inhibitory-effect-of-metformin-combined-with-gemcitabine-on-pancreatic-cancer-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#20
Yuqi Shi, Zhilong He, Zhenyu Jia, Chunfang Xu
Pancreatic cancer is a malignant digestive system tumor with a particularly poor prognosis, and is the fourth leading cause of cancer‑associated mortality in the USA. The anti‑diabetic therapeutic agent, metformin (MET) has been demonstrated to exert anti‑tumor effects. The present study assessed the ability of MET, alone or in combination with gemcitabine (GEM), to inhibit the growth of the human CFPAC‑1 pancreatic cancer cell line in vitro and in vivo. Cell counting kit‑8 assays were performed to measure CFPAC‑1 cell viability and apoptosis was detected with annexin V/propidium iodide...
October 2016: Molecular Medicine Reports
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