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https://www.readbyqxmd.com/read/28811714/sex-dependent-difference-in-the-effect-of-metformin-on-colorectal-cancer-specific-mortality-of-diabetic-colorectal-cancer-patients
#1
Jung Won Park, Jin Ha Lee, Ye Hyun Park, Soo Jung Park, Jae Hee Cheon, Won Ho Kim, Tae Il Kim
AIM: To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer (CRC) patients, since the factors related to the effectiveness of metformin have not been identified yet. METHODS: Between January 2000 and December 2010, 413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients' demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28802803/metformin-reduces-all-cause-mortality-and-diseases-of-ageing-independent-of-its-effect-on-diabetes-control-a-systematic-review-and-meta-analysis
#2
REVIEW
Jared M Campbell, Susan M Bellman, Matthew D Stephenson, Karolina Lisy
This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans. Pubmed and Embase were searched along with databases of unpublished studies. Eligible research investigated the effect of metformin on all-cause mortality or diseases of ageing relative to non-diabetic populations or diabetics receiving other therapies with adjustment for disease control achieved. Overall, 260 full-texts were reviewed and 53 met the inclusion criteria. Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio (HR)=0...
August 9, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28802253/the-combination-of-metformin-and-valproic-acid-induces-synergistic-apoptosis-in-the-presence-of-p53-and-androgen-signaling-in-prostate-cancer
#3
Linh N K Tran, Ganessan Kichenadasse, Lisa M Butler, Margaret M Centenera, Katherine L Morel, Rebecca J Ormsby, Michael Z Michael, Karen M Lower, Pamela J Sykes
We investigated the potential of combining the hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA), which act via different biochemical pathways, to provide enhanced anti-tumor responses in prostate cancer. Prostate cancer cell lines (LNCaP and PC-3), normal prostate epithelial cells (PrEC), and patient-derived prostate tumor explants were treated with MET and/or VPA. Proliferation and apoptosis were assessed. The role of p53 in response to MET+VPA was assessed in cell lines using RNA interference in LNCaP (p53(+)) and ectopic expression of p53 in PC-3 (p53(-))...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28802138/inhibition-of-bioenergetic-metabolism-by-the-combination-of-metformin-and-2-deoxyglucose-highly-decreases-viability-of-feline-mammary-carcinoma-cells
#4
María Florencia Arbe, Chiara Fondello, Lucrecia Agnetti, Gabriel Martín Álvarez, Matías Nicolás Tellado, Gerardo Claudio Glikin, Liliana María Elena Finocchiaro, Marcela Solange Villaverde
Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease, especially for the hormone refractory subgroup. Recently, cancer cell metabolism has been described as a hallmark of cancer cells. Here, we investigate the effects and mechanism of metabolic modulation by metformin (MET, anti-diabetic drug), 2-deoxyglucose (2DG, hexokinase inhibitor) or a combination of both drugs, MET/2DG on two established FMC cells lines: AlRB (HER2 (3+) and Ki67<5%) and AlRATN (HER2 (-) and Ki67>15%)...
August 3, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28801373/metformin-and-melatonin-in-adrenocortical-carcinoma-morphoproteomics-and-biomedical-analytics-provide-proof-of-concept-in-a-case-study
#5
Robert E Brown, Jamie Buryanek, Mary F McGuire
Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28800931/molecular-signatures-of-longevity-insights-from-cross-species-comparative-studies
#6
REVIEW
Siming Ma, Vadim N Gladyshev
Much of the current research on longevity focuses on the aging process within a single species. Several molecular players (e.g. IGF1 and MTOR), pharmacological compounds (e.g. rapamycin and metformin), and dietary approaches (e.g. calorie restriction and methionine restriction) have been shown to be important in regulating and modestly extending lifespan in model organisms. On the other hand, natural lifespan varies much more significantly across species. Within mammals alone, maximum lifespan differs more than 100 fold, but the underlying regulatory mechanisms remain poorly understood...
August 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28800002/finding-the-sweet-spot-for-metformin-in-18f-fdg-pet
#7
Michael Morris, Babak Saboury, Wengen Chen, Eliot L Siegel, Bahar Dasgeb
PURPOSE: The effect of oral hypoglycemic agents on fluorine-18-flurodeoxyglucose (F-FDG) uptake is less understood than the effect of exogenous insulin. In this study, the effect of withholding metformin on F-FDG distribution in subsequent PET imaging was evaluated. PATIENTS AND METHODS: A retrospective observational study was carried out. A total of 15 patients taking metformin were grouped according to the time interval from the last dose of metformin to F-FDG-PET...
August 10, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28791738/metformin-promotes-neuronal-differentiation-and-neurite-outgrowth-through-ampk-activation-in-human-bone-marrow-mesenchymal-stem-cells
#8
Min-Ji Ahn, Goang-Won Cho
Metformin is an AMP-activated kinase (AMPK) activator that plays a role in glucose energy metabolism and cell protection. It is widely used to treat several diseases, including type 2 diabetes, cardiovascular diseases, cancer, and metabolic diseases. In this study, we investigated whether AMPK activation upon treatment with metformin may promote neurite outgrowth during the progression of neuronal differentiation in human bone marrow-mesenchymal stem cells (hBM-MSCs). Differentiation of metformin-treated MSCs (Met-MSCs to Met-diMSCs) in the neuronal induction media resulted in an increase in the number of differentiated cells in a metformin concentration-dependent manner...
August 9, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28791376/macc1-induces-autophagy-to-regulate-proliferation-apoptosis-migration-and-invasion-of-squamous-cell-carcinoma
#9
Jian Wu, Dawei Zhang, Jun Li, Xin Deng, Guannan Liang, Yang Long, Xuemei He, Tianyang Dai, Delian Ren
Metastasis-associated colon cancer-1 (MACC1) plays an important role in cancer development, but the role and mechansim of MACC1 in squamous cell carcinoma (ESCC) remain unclear. In this study, we found that MACC1 expression was increased in ESCC, and correlated with lymph node metastasis. MACC1 knockdown suppresed ESCC cell proliferation, metastasis and enchanced cell apoptosis. Moreover, MACC1 knockdown inhibited ESCC cell autophagy, and 3-methyladenine was able to rescue MACC1-induced malignant phenotype of ESCC cells...
August 8, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28791253/potential-role-of-metabolic-intervention-in-the-management-of-advanced-differentiated-thyroid-cancer
#10
Sri Harsha Tella, Anuhya Kommalapati, Mary Angelynne Esquivel, Ricardo Correa
Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98%. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC) die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions, including the use of metformin, ketogenic diet, and high-dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28782285/metformin-enhances-doxorubicin-sensitivity-via-inhibition-of-doxorubicin-efflux-in-p-gp-overexpressing-mcf-7-cells
#11
Vahid Shafiei-Irannejad, Nasser Samadi, Bahman Yousefi, Roya Salehi, Kobra Velaei, Nosratollah Zarghami
Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX) resistant breast cancer (MCF-7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P-gp mRNA/protein expression levels following treatment with metformin was determined using real time polymerase chain reaction (RT-PCR) and western blot analysis, respectively...
August 6, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28776332/sirolimus-and-metformin-synergistically-inhibits-colon-cancer-in-vitro-and-in-vivo
#12
Nadiar Mussin, Seung Cheol Oh, Kwang Woong Lee, Min Young Park, Sooin Seo, Nam Joon Yi, Hyeyoung Kim, Kyung Chul Yoon, Sung Woo Ahn, Hyo Sin Kim, Suk Kyun Hong, Dong Kyu Oh, Kyung Suk Suh
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA)...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28776080/repurposing-metformin-for-the-prevention-of-cancer-and-cancer-recurrence
#13
REVIEW
Brandy M Heckman-Stoddard, Andrea DeCensi, Vikrant V Sahasrabuddhe, Leslie G Ford
Multiple epidemiological studies have documented an association between metformin, used for treatment of type 2 diabetes, and reduced cancer incidence and mortality. Cell line models may not accurately reflect the effects of metformin in the clinical setting. Moreover, findings from animal model studies have been inconsistent, whilst those from more recent epidemiological studies have tempered the overall effect size. The purpose of this review is to examine metformin's chemopreventive potential by outlining relevant mechanisms of action, the most recent epidemiologic evidence, and recently completed and ongoing clinical trials...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770322/metformin-for-diabetes-prevention-insights-gained-from-the-diabetes-prevention-program-diabetes-prevention-program-outcomes-study
#14
REVIEW
Vanita R Aroda, William C Knowler, Jill P Crandall, Leigh Perreault, Sharon L Edelstein, Susan L Jeffries, Mark E Molitch, Xavier Pi-Sunyer, Christine Darwin, Brandy M Heckman-Stoddard, Marinella Temprosa, Steven E Kahn, David M Nathan
The largest and longest clinical trial of metformin for the prevention of diabetes is the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS). In this review, we summarise data from the DPP/DPPOS, focusing on metformin for diabetes prevention, as well as its long-term glycaemic and cardiometabolic effects and safety in people at high-risk of developing diabetes. The DPP (1996-2001) was a RCT of 3234 adults who, at baseline, were at high-risk of developing diabetes. Participants were assigned to masked placebo (n = 1082) or metformin (n = 1073) 850 mg twice daily, or intensive lifestyle intervention (n = 1079)...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28769006/mechanistic-study-of-inhibitory-effects-of-metformin-and-atorvastatin-in-combination-on-prostate-cancer-cells-in-vitro-and-in-vivo
#15
Zhen-Shi Wang, Hua-Rong Huang, Lan-Yue Zhang, Seungkee Kim, Yan He, Dong-Li Li, Chelsea Farischon, Kun Zhang, Xi Zheng, Zhi-Yun Du, Susan Goodin
Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28761738/results-of-the-safety-run-in-part-of-the-metal-metformin-in-advanced-lung-cancer-study-a-multicentre-open-label-phase-i-ii-study-of-metformin-with-erlotinib-in-second-line-therapy-of-patients-with-stage-iv-non-small-cell-lung-cancer
#16
Floriana Morgillo, Morena Fasano, Carminia Maria Della Corte, Ferdinando Carlo Sasso, Federica Papaccio, Giuseppe Viscardi, Giovanna Esposito, Raimondo Di Liello, Nicola Normanno, Annalisa Capuano, Liberato Berrino, Giovanni Vicidomini, Alfonso Fiorelli, Mario Santini, Fortunato Ciardiello
PURPOSE: Our previous works demonstrated the ability of metformin to revert resistance to gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in non-small-cell lung cancer (NSCLC) EGFR/LKB1 wild-type (WT) cell lines. However, the optimal dose of metformin to be used in non-diabetic patients still remains to be defined. The phase I-II trial METformin in Advanced Lung cancer (METAL) was designed to identify the maximum tolerated dose and to evaluate safety and activity of metformin combined with erlotinib in second-line treatment of patients with stage IV NSCLC, whose tumours harbour the WT EGFR gene...
2017: ESMO Open
https://www.readbyqxmd.com/read/28760367/effects-of-metformin-on-endometrial-cancer-systematic-review-and-meta-analysis
#17
REVIEW
Cinthia G Meireles, Sidney A Pereira, Luciana P Valadares, Daniela F Rêgo, Luiz A Simeoni, Eliete N S Guerra, Adriana Lofrano-Porto
BACKGROUND: Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients. METHODS: The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science...
July 28, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28758096/type-2-diabetes-mellitus-and-risk-of-hepatocellular-carcinoma-spotlight-on-nonalcoholic-fatty-liver-disease
#18
REVIEW
Alessandro Mantovani, Giovanni Targher
The incidence of both type 2 diabetes mellitus (T2DM) and multiple cancer types are rapidly increasing worldwide. Several studies documented that T2DM is closely associated with an increased incidence of cancer. However, while some methodological considerations preclude a definitive association between T2DM and the risk of certain cancers, the relationship between T2DM and increased risk of incident hepatocellular carcinoma (HCC) remains significant even after adjustment for detection bias and reverse causation, indicating that such association is clinically reliable and robust...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28755883/metformin-insights-into-its-anticancer-potential-with-special-reference-to-ampk-dependent-and-independent-pathways
#19
REVIEW
Shoeb Ikhlas, Masood Ahmad
Metformin has been known for its antidiabetic effects for decades and is used as a first line therapy in type 2 diabetes. But recently its anticancer potential has also been discovered. Metformin targets many pathways that play an important role in cancer cell proliferation and angiogenesis, mTORC1 signaling is a crucial pathway among them. Metformin inhibits mTORC1 via AMPK dependent and AMPK independent pathways, thereby inhibiting cancer cell growth and development. Encouraged by positive results of numerous preclinical studies on various types of cancer, many clinical trials are underway to study metformin's effect in chemoprevention and treatment of cancers in humans...
July 26, 2017: Life Sciences
https://www.readbyqxmd.com/read/28754674/adipose-progenitor-cell-secretion-of-gm-csf-and-mmp9-promotes-a-stromal-and-immunological-microenvironment-that-supports-breast-cancer-progression
#20
Francesca Reggiani, Valentina Labanca, Patrizia Mancuso, Cristina Rabascio, Giovanna Talarico, Stefania Orecchioni, Andrea Manconi, Francesco Bertolini
A cell population with progenitor-like phenotype (CD45-CD34+) resident in human white adipose tissue (WAT) is known to promote the progression of local and metastatic breast cancer and angiogenesis. However, the molecular mechanisms of the interaction have not been elucidated. In this study, we identified two proteins that were significantly up-regulated in WAT-derived progenitors after co-culture with breast cancer: granulocyte-macrophage colony-stimulating factor (GM-CSF) and matrix metallopeptidase 9 (MMP9)...
July 28, 2017: Cancer Research
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