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Cancer AND Metformin

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https://www.readbyqxmd.com/read/29788487/the-effects-of-metformin-and-weight-loss-on-biomarkers-associated-with-breast-cancer-outcomes
#1
Ruth E Patterson, Catherine R Marinac, Dorothy D Sears, Jacqueline Kerr, Sheri J Hartman, Lisa Cadmus-Bertram, Adriana Villaseñor, Shirley W Flatt, Suneeta Godbole, Hongying Li, Gail A Laughlin, Jesica Oratowski-Coleman, Barbara A Parker, Loki Natarajan
Background: This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis. Methods: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG)...
May 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29788134/novel-insights-into-the-impact-of-lifestyle-based-weight-loss-and-metformin-on-obesity-associated-biomarkers-in-breast-cancer
#2
Ana Elisa Lohmann, Isabel Pimentel, Pamela J Goodwin
No abstract text is available yet for this article.
May 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29780974/metformin-targets-glucose-metabolism-in-triple-negative-breast-cancer
#3
R S Wahdan-Alaswad, S M Edgerton, H S Salem, A D Thor
Metformin is the most widely administered anti-diabetic agent worldwide. In patients receiving metformin for metabolic syndrome or diabetes, it reduces the incidence and improves the survival of breast cancer (BC) patients. We have previously shown that metformin is particularly potent against triple negative breast cancer (TNBC), with a reduction of proliferation, oncogenicity and motility, inhibition of pro-oncogenic signaling pathways and induction of apoptosis. These BCs are well recognized to be highly dependent on glucose/glucosamine (metabolized through anaerobic glycolysis) and lipids, which are metabolized for the production of energy and cellular building blocks to sustain a high rate of proliferation...
2018: Journal of Oncology Translational Research
https://www.readbyqxmd.com/read/29774060/metformin-prevents-nerve-growth-factor-dependent-proliferative-and-proangiogenic-effects-in-epithelial-ovarian-cancer-cells-and-endothelial-cells
#4
Maritza P Garrido, Carolina Vera, Margarita Vega, Andrew F G Quest, Carmen Romero
Background: Epithelial ovarian cancer (EOC) is characterized by exacerbated angiogenesis regulated by proangiogenic and growth factors. Nerve growth factor (NGF) is overexpressed in EOC where it promotes proliferation as well as survival and is considered a proangiogenic factor. Metformin, a drug commonly used in the treatment of diabetes, is attributed to antineoplastic effects, but the underlying mechanisms remain unknown. Given that current therapies yield modest results in EOC patients, the aim of this study was to determine the effects of metformin on NGF-enhanced proliferation of EOC cells and the angiogenic potential of endothelial cells...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29772687/metformin-induces-apoptosis-and-alters-cellular-responses-to-oxidative-stress-in-ht29-colon-cancer-cells-preliminary-findings
#5
Paola Sena, Stefano Mancini, Marta Benincasa, Francesco Mariani, Carla Palumbo, Luca Roncucci
Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anti-cancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM for 24/48 h. We performed immunofluorescence experiments by means of confocal microscopy and western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29770821/a-size-shrinkable-nanoparticle-based-combined-anti-tumor-and-anti-inflammatory-strategy-for-enhanced-cancer-therapy
#6
Zhengze Lu, Yang Long, Xingli Cun, Xuhui Wang, Jianping Li, Ling Mei, Yiliang Yang, Man Li, Zhirong Zhang, Qin He
Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy...
May 17, 2018: Nanoscale
https://www.readbyqxmd.com/read/29770171/risk-of-gastric-cancer-development-after-eradication-of-helicobacter-pylori
#7
REVIEW
Ka-Shing Cheung, Wai K Leung
Helicobacter pylori ( H. pylori ) infection is the most important risk factor for gastric cancer (GC) development through the Correa's gastric carcinogenesis cascade. However, H. pylori eradication alone does not eliminate GC, as pre-neoplastic lesions (atrophic gastritis, intestinal metaplasia and dysplasia) may have already developed in some patients. It is therefore necessary to identify patients at high-risk for gastric cancer after H. pylori eradication to streamline the management plan. If the patients have not undergone endoscopy with histologic assessment, the identification of certain clinical risk factors and non-invasive testing (serum pepsinogen) can predict the risk of atrophic gastritis...
May 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#8
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761175/anti-tumoral-effects-of-exercise-on-hepatocellular-carcinoma-growth
#9
Uttara Saran, Maria Guarino, Sarai Rodríguez, Cedric Simillion, Matteo Montani, Michelangelo Foti, Bostjan Humar, Marie V St-Pierre, Jean-François Dufour
Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression. Here, we investigated the effects of exercise on HCC progression and assessed whether any beneficial effects would be evident under sorafenib treatment and could be mimicked by metformin. American Cancer Institute rats with orthotopic syngeneic HCC derived from Morris Hepatoma-3924A cells were randomly assigned to exercise (Exe) and sedentary groups, or sorafenib±Exe groups or sorafenib±metformin groups...
May 2018: Hepatology communications
https://www.readbyqxmd.com/read/29755998/application-of-a-pharmacokinetic-model-of-metformin-clearance-in-a-population-with-acute-myeloid-leukemia
#10
Alice C Ceacareanu, Geoffrey W Brown, Hoda A Moussa, Zachary A P Wintrob
Objective: We aimed to estimate the metformin-associated lactic acidosis (MALA) risk by assessing retrospectively the renal clearance variability and applying a pharmacokinetic (PK) model of metformin clearance in a population diagnosed with acute myeloid leukemia (AML) and diabetes mellitus (DM). Methods: All adults with preexisting DM and newly diagnosed AML at Roswell Park Cancer Institute were reviewed (January 2003-December 2010, n = 78). Creatinine clearance (CrCl) and total body weight distributions were used in a two-compartment PK model adapted for multiple dosing and modified to account for actual intra- and inter-individual variability...
January 2018: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/29753740/2-deoxy-d-glucose-increases-gfat1-phosphorylation-resulting-in-endoplasmic-reticulum-related-apoptosis-via-disruption-of-protein-n-glycosylation-in-pancreatic-cancer-cells
#11
Kousuke Ishino, Mitsuhiro Kudo, Wei-Xia Peng, Shoko Kure, Kiyoko Kawahara, Kiyoshi Teduka, Yoko Kawamoto, Taeko Kitamura, Takenori Fujii, Tetsushi Yamamoto, Ryuichi Wada, Zenya Naito
The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines. To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment. Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated. Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29740925/metformin-directly-targets-the-h3k27me3-demethylase-kdm6a-utx
#12
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Pares, Salvador Fernández-Arroyo, Fedra Luciano-Mateo, Noemí Cabré, Jan Stursa, Lukas Werner, Begoña Martin-Castillo, Benoit Viollet, Jiri Neuzil, Jorge Joven, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Javier A Menendez
Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29739273/angiogenic-dysregulation-in-pregnancy-related-hypertension-a-role-for-metformin
#13
Nerolen Soobryan, Saravanakumar Murugesan, Arunagiri Pandiyan, Jagidesa Moodley, Irene Mackraj
In the face of escalating maternal and fetal health threats, hypertensive pregnancy disorders (HPDs) is one of the leading cause of maternal and fetal morbidity and mortality. The range of HPDs include white-coat hypertension, chronic hypertension, gestational hypertension, mild-to-moderate and severe preeclampsia and eclampsia. Current evidence implicates an imbalance of circulating anti- and angiogenic factors in HPDs emanating from the placental vasculature, impacting on angiogenesis. Delivery of the fetus is thus far the only curative measure, albeit with increased risk...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29737584/metformin-increases-the-cytotoxicity-of-oxaliplatin-in-human-dld-1-colorectal-cancer-cells-through-down-regulating-hmgb1-expression
#14
Wen-Shih Huang, Chien-Tsong Lin, Cheng-Nan Chen, Shun-Fu Chang, Hsin-I Chang, Ko-Chao Lee
Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent...
May 8, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29729227/metformin-and-risk-of-developing-nasopharyngeal-cancer-in-patients-with-type-2-diabetes-mellitus
#15
Chin-Hsiao Tseng
BACKGROUND: Metformin has anticancer effects, but whether it can reduce the risk of nasopharyngeal cancer (NPC) is not known. METHODS: A total of 15,486 ever-users and 15,486 never-users of metformin matched by propensity score were enrolled from among patients with new-onset type 2 diabetes mellitus diagnosed during the period 1999-2005 and who were found in the reimbursement database of Taiwan's National Health Insurance. The patients were followed until December 31, 2011...
May 2, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29728105/identifying-risk-factors-for-l-hermitte-s-sign-after-imrt-for-head-and-neck-cancer
#16
Hannah M Laidley, David J Noble, Gill C Barnett, Julia R Forman, Amy M Bates, Richard J Benson, Sarah J Jefferies, Rajesh Jena, Neil G Burnet
BACKGROUND: L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high. METHODS: One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded...
May 4, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29726618/metformin-s-antitumour-and-anti-angiogenic-activities-are-mediated-by-skewing-macrophage-polarization
#17
Ji-Chang Wang, Xin Sun, Qiang Ma, Gui-Feng Fu, Long-Long Cong, Hong Zhang, De-Fu Fan, Jun Feng, Shao-Ying Lu, Jian-Lin Liu, Guang-Yue Li, Pei-Jun Liu
Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells...
May 4, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29725482/metformin-inhibits-the-proliferation-and-metastasis-of-osteosarcoma-cells-by-suppressing-the-phosphorylation-of-akt
#18
Zuohong Li, Lesheng Wang, Nan Luo, Yantao Zhao, Jiazhi Li, Qiwei Chen, Yu Tian
Metformin (Met) is a therapeutic agent for the treatment of type 2 diabetes mellitus. There is evidence that Met may reduce the risk of cancer in patients with type 2 diabetes mellitus by inhibiting tumor cell growth, prolonging the overall survival time in patients with various types of malignancy. However, the function and mechanism of Met have not been fully elucidated in osteosarcoma (OS). The present study evaluated the anti-proliferative effect of Met on MG63 and U2OS OS cells, identifying that it acted in a dose- and time-dependent manner...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29716927/a-cohort-study-of-metformin-and-colorectal-cancer-risk-among-patients-with-diabetes-mellitus
#19
Marie C Bradley, Assiamira Ferrara, Ninah Achacoso, Samantha F Ehrlich, Charles P Quesenberry, Laurel A Habel
Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these biases. Methods: A cohort study was conducted among 47,351 members of Kaiser Permanente Northern California with diabetes and no history of cancer or metformin use. Follow-up for incident colorectal cancer occurred from January 1, 1997, until June 30, 2012...
May 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29716926/studying-the-effects-of-nonindicated-medications-on-cancer-etiologic-versus-action-focused-analysis-of-epidemiologic-data
#20
John W Jackson, Xabier García-Albéniz
The study of nonindicated medications on cancer outcomes is challenged by potential time-related biases. The literature has strongly advocated for treating the exposure as time-varying and summarizing the outcomes through a dose-response model (an etiologic-focused analysis). An alternative is to refashion the data to resemble a hypothetical randomized trial of drug use (an action-focused analysis). To our knowledge, their relative treatment of time-related bias and aspects of interpretation have not been compared...
May 2018: Cancer Epidemiology, Biomarkers & Prevention
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