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Cancer AND Metformin

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https://www.readbyqxmd.com/read/28324269/metformin-sensitizes-triple-negative-breast-cancer-to-proapoptotic-trail-receptor-agonists-by-suppressing-xiap-expression
#1
Elena Strekalova, Dmitry Malin, Harisha Rajanala, Vincent L Cryns
PURPOSE: Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. METHODS: Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28319830/anti-proliferative-effect-of-metformin-on-a-feline-injection-site-sarcoma-cell-line-independent-of-mtor-inhibition
#2
J Pierro, C Saba, K McLean, R Williams, E Karpuzoglu, R Prater, K Hoover, R Gogal
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8...
March 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28296186/changes-in-periprostatic-adipose-tissue-induced-by-5%C3%AE-reductase-inhibitors
#3
D Taussky, M Barkati, S Campeau, K Zerouali, A Nadiri, F Saad, G Delouya
There is increasing interest in periprostatic fat and its influence on prostate cancer aggressiveness. In vitro data suggest that adipose stromal/stem cells (ASCs) can increase production of cytokines and growth factors resulting in invasive growth and metastasis in prostate cancer. The objective of the study was to determine the interaction between 5α-reductase inhibitors (5ARIs) and periprostatic adipose tissue (PPAT) and factors of prostate cancer aggressiveness. In this retrospective study, we identified 61 patients treated with 5ARIs for a period of ≥12 months before undergoing radiation therapy (brachytherapy or external beam radiotherapy)...
March 10, 2017: Andrology
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
#4
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/28274796/dual-functional-lipomet-mediates-envelope-type-nanoparticles-to-combinational-oncogene-silencing-and-tumor-growth-inhibition
#5
Kai Shi, Yi Zhao, Lei Miao, Andrew Satterlee, Matthew Haynes, Cong Luo, Sara Musetti, Leaf Huang
The success of small interfering RNA (siRNA)-mediated gene silencing for cancer therapy is still limited because of its instability and poor intracellular internalization. Traditional cationic carriers cannot adequately meet the need for clinical application of siRNA. We herein report a dual-functional liposome containing a cholesterol derivative of metformin, i.e., LipoMET, which takes advantage of the fusogenic activity as well as intrinsic tumor apoptosis inducing ability of biguanide moiety to achieve a combinational anti-oncogenic effect...
March 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28274614/metformin-represses-glucose-starvation-induced-autophagic-response-in-microvascular-endothelial-cells-and-promotes-cell-death
#6
Samson Mathews Samuel, Suparna Ghosh, Yasser Majeed, Gnanapragasam Arunachalam, Mohamed M Emara, Hong Ding, Chris R Triggle
Metformin, the most frequently administered drug for the treatment of type 2 diabetes, is being investigated for its potential in the treatment of various types of cancer; however, the cellular basis for this putative anti-cancer action remains controversial. In the current study we examined the effect of metformin on endoplasmic reticulum (ER) stress and autophagy in glucose-starved micro-vascular endothelial cells (MECs). The rationale for our experimental protocol is that in a growing tumor MECs are subjected to hypoxia and nutrient/glucose starvation that results from the reduced supply and relatively high consumption of glucose...
March 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28272215/no-association-between-metformin-use-and-survival-in-patients-with-pancreatic-cancer-an-observational-cohort-study
#7
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/28271326/the-impact-of-metformin-use-on-survival-in-kidney-cancer-patients-with-diabetes-a-meta-analysis
#8
Yang Li, Liyi Hu, Qinghong Xia, Yongqiang Yuan, Yonghua Mi
PURPOSE: The effects of metformin on the prognosis of kidney cancer patients with diabetes are in controversial. The present study is conducted to classify the association of metformin use with the survival of patients with kidney cancer. METHODS: Electronic databases, namely PubMed and Web of Science, were used to search the eligible studies up to December, 2016. Pooled hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were calculated. It was considered as statistically significant when P value was <0...
March 7, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28271076/metformin-improves-overall-survival-of-colorectal-cancer-patients-with-diabetes-a-meta-analysis
#9
REVIEW
Fanqiang Meng, Li Song, Wenyue Wang
Introduction. Diabetic population has a higher risk of colorectal cancer (CRC) incidence and mortality than nondiabetics. The role of metformin in CRC prognosis is still controversial. The meta-analysis aims to investigate whether metformin improves the survival of diabetic CRC patients. Methods. PubMed, EMBASE, and Cochrane Library were searched till July 1, 2016. Cohort studies were included. All articles were evaluated by Newcastle-Ottawa Scale. Hazard Ratios (HRs) with 95% confidence intervals (CIs) for each study were calculated and pooled HRs with corresponding 95% CIs were generated using the random-effects model...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28260041/metformin-suppresses-the-expression-of-sonic-hedgehog-in-gastric-cancer-cells
#10
Zhou Song, Bo Wei, Canrong Lu, Xiaohui Huang, Peiyu Li, Lin Chen
The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC‑27 and MKN‑45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma‑associated oncogene (Gli)‑1, Gli‑2 and Gli‑3 were examined using western blot and reverse transcription‑quantitative polymerase chain reaction analyses...
February 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258677/metformin-its-potential-anti-cancer-and-anti-aging-effects
#11
Monika Podhorecka, Blanca Ibanez, Anna Dmoszyńska
The generally accepted mechanism of metformin's effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin's beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28253286/colon-cancer-modulation-by-a-diabetic-environment-a-single-institutional-experience
#12
Isabel Prieto, Laura Del Puerto-Nevado, Nieves Gonzalez, Sergio Portal-Nuñez, Sandra Zazo, Marta Corton, Pablo Minguez, Carmen Gomez-Guerrero, Jose Miguel Arce, Ana Belen Sanz, Sebastian Mas, Oscar Aguilera, Gloria Alvarez-Llamas, Pedro Esbrit, Alberto Ortiz, Carmen Ayuso, Jesus Egido, Federico Rojo, Jesus Garcia-Foncillas
BACKGROUND: Multiple observational studies suggest an increased risk of colon cancer in patients with diabetes mellitus (DM). This can theoretically be the result of an influence of the diabetic environment on carcinogenesis or the tumor biologic behavior. AIM: To gain insight into the influence of a diabetic environment on colon cancer characteristics and outcomes. MATERIAL AND METHODS: Retrospective analysis of clinical records in an academic tertiary care hospital with detailed analysis of 81 diabetic patients diagnosed of colon cancer matched with 79 non-diabetic colon cancer patients...
2017: PloS One
https://www.readbyqxmd.com/read/28252027/combining-metformin-and-nelfinavir-exhibits-synergistic-effects-against-the-growth-of-human-cervical-cancer-cells-and-xenograft-in-nude-mice
#13
Chenglai Xia, Ruihong Chen, Jinman Chen, Qianqian Qi, Yanbin Pan, Lanying Du, Guohong Xiao, Shibo Jiang
Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#14
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28241849/metformin-potentiates-the-effect-of-arsenic-trioxide-suppressing-intrahepatic-cholangiocarcinoma-roles-of-p38-mapk-erk3-and-mtorc1
#15
Sunbin Ling, Haiyang Xie, Fan Yang, Qiaonan Shan, Haojiang Dai, Jianyong Zhuo, Xuyong Wei, Penghong Song, Lin Zhou, Xiao Xu, Shusen Zheng
BACKGROUND: Arsenic trioxide (ATO) is commonly used in the treatment of acute promyelocytic leukemia (APL), but does not benefit patients with solid tumors. When combined with other agents or radiation, ATO showed treatment benefits with manageable toxicity. Previously, we reported that metformin amplified the inhibitory effect of ATO on intrahepatic cholangiocarcinoma (ICC) cells more significantly than other agents. Here, we investigated the chemotherapeutic sensitization effect of metformin in ATO-based treatment in ICC in vitro and in vivo and explored the underlying mechanisms...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28239823/inhibitory-effect-and-mechanism-of-metformin-on-human-ovarian-cancer-cells-skov-3-and-a2780
#16
J Huo, X-H Bian, Y Huang, Z-C Miao, L-H Song
OBJECTIVE: Ovarian cancer is the most common malignant tumor in female reproductive system. Metformin is an orally taken hypoglycemic agent, which is extensively applied in the clinic. Clinical trials find that there may be a certain degree of action of the metformin in inhibiting malignant tumors. This paper aims to investigate the inhibitory effect and mechanism of metformin on human ovarian cancer cells. MATERIALS AND METHODS: Through in vitro cell experiment, the influences of metformin on the proliferation, colony formation and apoptosis of ovarian carcinoma cells were studied...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239505/statins-and-metformin-use-is-associated-with-lower-psa-levels-in-prostate-cancer-patients-presenting-for-radiation-therapy
#17
Xiaonan Liu, Jing Li, Steven E Schild, Michael H Schild, William Wong, Sujay Vora, Michael G Herman, Mirek Fatyga
BACKGROUND: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy...
February 2017: Journal of Cancer Therapy
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#18
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28210856/the-effect-of-metformin-on-the-recurrence-of-colorectal-adenoma-in-diabetic-patients-with-previous-colorectal-adenoma
#19
Min Seok Han, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Il Kim
PURPOSE: Existing studies suggest that metformin lowers the risk and mortality of colorectal cancer. However, the effect of metformin on the suppression and prevention of colorectal adenomas is not clear. The aim of this study was to evaluate the effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma. METHODS: Among 423 diabetic patients who underwent surveillance colonoscopy after resection of colorectal adenoma between 2005 and 2011, 257 patients were retrospectively reviewed...
February 16, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#20
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
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