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Cancer AND Metformin

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https://www.readbyqxmd.com/read/28641310/potentiating-the-effects-of-radiotherapy-in-rectal-cancer-the-role-of-aspirin-statins-and-metformin-as-adjuncts-to-therapy
#1
K J Gash, A C Chambers, D E Cotton, A C Williams, M G Thomas
BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28624799/effects-of-metformin-on-survival-outcomes-of-pancreatic-cancer-a-meta-analysis
#2
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/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#3
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 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
#4
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 aged 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...
June 15, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28619690/metformin-the-aspirin-of-the-21-st-century-its-role-in-gestational-diabetes-prevention-of-preeclampsia-and-cancer-and-the-promotion-of-longevity
#5
REVIEW
Roberto Romero, Offer Erez, Maik Hüttemann, Eli Maymon, Bogdan Panaitescu, Agustin Conde-Agudelo, Percy Pacora, Bo Hyun Yoon, Lawrence I Grossman
Metformin is everywhere. Originally introduced in clinical practice as an anti-diabetic agent, its role as a therapeutic agent is expanding to include treatment of pre-diabetes, gestational diabetes, polycystic ovarian disease, and more recently, experimental studies, as well as observations in randomized clinical trials, suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes, reviews the results of meta-analyses of metformin in gestational diabetes, and the treatment of obese non-diabetic pregnant women to prevent macrosomia...
June 12, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28618116/differences-in-p53-status-significantly-influence-the-cellular-response-and-cell-survival-to-1-25-dihydroxyvitamin-d3-metformin-cotreatment-in-colorectal-cancer-cells
#6
Mohamed A Abu El Maaty, Wendy Strassburger, Tooba Qaiser, Yasamin Dabiri, Stefan Wölfl
Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC cell lines HCT116 wild-type (wt), HCT116 p53-/- and HT-29 (mutant; R273H) were employed, covering 3 different p53 variations...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28618017/curcumin-and-metformin-mediated-chemoprevention-of-oral-cancer-is-associated-with-inhibition-of-cancer-stem-cells
#7
Gangotri Siddappa, Safeena Kulsum, Doddathimmasandra Ramanjanappa Ravindra, Vinay V Kumar, Nalini Raju, Nisheena Raghavan, Holalugunda Vittalamurthy Sudheendra, Anupam Sharma, Sumsum P Sunny, Tina Jacob, Binu T Kuruvilla, Merina Benny, Benny Antony, Mukund Seshadri, Padma Lakshminarayan, Wesley Hicks, Amritha Suresh, Moni A Kuriakose
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin, are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4NQO (4-nitro-quinoline-oxide) induced, mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven, oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40 to 100 fold) and protein levels (p≤0...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28616837/a-phase-ib-study-of-everolimus-combined-with-metformin-for-patients-with-advanced-cancer
#8
Remco J Molenaar, Tim van de Venne, Mariëtte J Weterman, Ron A Mathot, Heinz-Josef Klümpen, Dick J Richel, Johanna W Wilmink
Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78)...
June 15, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#9
N V Rajeshkumar, Shinichi Yabuuchi, Shweta Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fatima 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 anti-tumor efficacy of metabolic inhibitors in a panel of patient-derived PDAC xenograft models (PDXs), and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors. <p>Experimental Design: Mice with PDAC tumors from six to thirteen individual PDXs were randomized and treated, once daily for 4 weeks, with either PBS (vehicle) or the glutaminase inhibitor BPTES, transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), 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/28606929/targeting-oxygen-sensing-prolyl-hydroxylase-phd-for-metformin-associated-lactic-acidosis-treatment
#10
Tomoko Oyaizu-Toramaru, Tomohiro Suhara, Noriyo Hayakawa, Takashi Nakamura, Akiko Kubo, Shizuka Minamishima, Kyoji Yamaguchi, Takako Hishiki, Hiroshi Morisaki, Makoto Suematsu, Yoji Andrew Minamishima
Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anti-cancer and anti-aging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate transcription factor HIF (hypoxia-inducible factor) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels...
June 12, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28601826/study-protocol-of-a-phase-ib-ii-clinical-trial-of-metformin-and-chloroquine-in-patients-with-idh1-mutated-or-idh2-mutated-solid-tumours
#11
Remco J Molenaar, Robert Js Coelen, Mohammed Khurshed, Eva Roos, Matthan Wa Caan, Myra E van Linde, Mathilde Kouwenhoven, Jos Am Bramer, Judith Vmg Bovée, Ron A Mathôt, Heinz-Josef Klümpen, Hanneke Wm van Laarhoven, Cornelis Jf van Noorden, W Peter Vandertop, Hans Gelderblom, Thomas M van Gulik, Johanna W Wilmink
INTRODUCTION: High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine...
June 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28599404/neoadjuvant-chemotherapy-for-pancreatic-cancer-effects-on-cancer-tissue-and-novel-perspectives
#12
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/28581641/clk1-regulated-aerobic-glycolysis-is-involved-in-gliomas-chemoresistance
#13
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In the present study, we investigated the role of Clk1, which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to BCNU while was expressed in BCNU resistant cells such as glioma cancer stem cells: T98G, U87MG and U251 glioma cells at low levels. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin- induced cell apoptosis whereas the proliferative activity and the expression of multi-drug resistance -related genes including MDR1, MGMT and GSTP1 were not changed...
June 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28580793/rationale-and-protocol-of-metnet-2-trial-lanreotide-autogel-plus-metformin-in-advanced-gastrointestinal-or-lung-neuroendocrine-tumors
#14
Sara Pusceddu, Natalie Prinzi, Giuseppe Lo Russo, Daniela Femia, Massimo Milione, Federica Perrone, Elena Tamborini, Laura Concas, Iolanda Pulice, Claudio Vernieri, Francesca Corti, Roberto Buzzoni, Filippo de Braud
Metformin (MET) has recently emerged as a potentially active agent in cancer prevention and treatment. MET is thought to exert its antitumor effects either via modification of systemic metabolism or through cell-autonomous effects (e.g., activation of AMPK and inhibition of the mTOR pathway). Preliminary findings of the PRIME-NET study suggest that the addition of MET to treatment with everolimus (EVE) and/or somatostatin analogs (SSAs) can provide clinical benefit in diabetic neuroendocrine tumor (NET) patients...
June 5, 2017: Future Oncology
https://www.readbyqxmd.com/read/28576465/metformin-and-caffeic-acid-regulate-metabolic-reprogramming-in-human-cervical-carcinoma-siha-htb-35%C3%A2-cells-and-augment-anticancer-activity-of-cisplatin-via-cell-cycle-regulation
#15
Malgorzata Tyszka-Czochara, Karolina Bukowska-Strakova, Marcin Majka
Metformin shows benefits in anticancer prevention in humans. In this study, normal human fibroblasts (FB) and metastatic cervical cancer cells (SiHa) were exposed to 10 mM Metformin (Met), 100 μM Caffeic Acid (trans-3,4-dihydroxycinnamic acid, CA) or combination of the compounds. Both drugs were selectively toxic towards cancer cells, but neither Met nor CA treatment suppressed growth of normal cells. Met and CA regulated metabolic reprogramming in SiHa tumor cells through different mechanisms: Met suppressed regulatory enzymes Glurtaminase (GLS) and Malic Enzyme 1 (ME1) and enhanced pyruvate oxidation via tricarboxylic acids (TCA) cycle, while CA acted as glycolytic inhibitor...
May 30, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28571774/modulatory-effects-of-metformin-on-mutagenicity-and-epithelial-tumor-incidence-in-doxorubicin-treated-drosophila-melanogaster
#16
Victor Constante Oliveira, Sarah Alves Rodrigues Constante, Priscila Capelari Orsolin, Júlio César Nepomuceno, Alexandre Azenha Alves de Rezende, Mário Antônio Spanó
Metformin (MET) is an anti-diabetic drug used to prevent hepatic glucose release and increase tissue insulin sensitivity. Diabetic cancer patients are on additional therapy with anticancer drugs. Doxorubicin (DXR) is a cancer chemotherapeutic agent that interferes with the topoisomerase II enzyme and generates free radicals. MET (2.5, 5, 10, 25 or 50 mM) alone was examined for mutagenicity, recombinogenicity and carcinogenicity, and combined with DXR (0.4 mM) for antimutagenicity, antirecombinogenicity and anticarcinogenicity, using the Somatic Mutation and Recombination Test and the Test for Detecting Epithelial Tumor Clones in Drosophila melanogaster...
May 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28566532/risk-and-protective-factors-for-the-occurrence-of-sporadic-pancreatic-endocrine-neoplasms
#17
Roberto Valente, Alastair J Hayes, Sven-Petter Haugvik, Per Hedenström, Darko Siuka, Emilie Korsæth, Daniel Kaemmerer, Stuart Michael 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 heterogenous. AIM: To investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions...
May 31, 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
#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)...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548953/from-rapalogs-to-anti-aging-formula
#19
Mikhail V Blagosklonny
Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548941/withdrawn-prognostic-role-of-anti-diabetic-drugs-in-pancreatic-cancer-a-systematic-review-and-meta-analysis
#20
Lei Zheng, Shinan Yin, Fenghua Yao, Hua Bai, Danqing Jing
Ahead of Print article withdrawn by publisher.
May 10, 2017: Oncotarget
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