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https://www.readbyqxmd.com/read/28933290/nutraceuticals-and-repurposed-drugs-of-phytochemical-origin-in-prevention-and-interception-of-chronic-degenerative-disease-and-cancer
#1
Adriana Albini, Barbara Bassani, Denisa Baci, Katiuscia Dallaglio, Matteo Gallazzi, Paola Corradino, Antonino Bruno, Douglas M Noonan
Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For many of these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy, thus the validation of novel (chemo)preventive and interceptive approaches, of new or repurposed agents, alone or in combination with registered drugs, are urgently required. Phytochemicals (triterpenoids, flavonoids, retinoids) and their derivatives, non-steroidal anti-inflammatory drugs (aspirin) as well as biguanides (metformin and phenformin) originally developed from phytochemical backbones, are multi-target agents showing anti-angiogenic and anti-anti-inflammatory proprieties...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28927103/lack-of-chemopreventive-efficacy-of-metformin-in-rodent-models-of-urinary-bladder-head-and-neck-and-colon-intestine-cancer
#2
Matthew D Thompson, Ronald A Lubet, David L Mccormick, Margie L Clapper, Ann M Bode, M Margaret Juliana, Fariba Moeinpour, Clinton J Grubbs
Metformin is a biguanide employed in treating type II diabetes. Its potential efficacy for treating cancer has been demonstrated epidemiologically (lower cancer incidence in metformin users compared with users of sulfonylureas or insulin) and mechanistically, primarily in cell culture. Metformin decreases the levels of insulin-like growth factor 1 and secondarily inhibits the mammalian target of rapamycin pathway to exhibit anticancer effects. The current study examined its cancer preventive efficacy in multiple standard in situ arising cancer models...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#3
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markela Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28917544/effects-on-the-incidence-of-cardiovascular-events-of-the-addition-of-pioglitazone-versus-sulfonylureas-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-tosca-it-a-randomised-multicentre-trial
#4
Olga Vaccaro, Maria Masulli, Antonio Nicolucci, Enzo Bonora, Stefano Del Prato, Aldo P Maggioni, Angela A Rivellese, Sebastiano Squatrito, Carlo B Giorda, Giorgio Sesti, Paolo Mocarelli, Giuseppe Lucisano, Michele Sacco, Stefano Signorini, Fabrizio Cappellini, Gabriele Perriello, Anna Carla Babini, Annunziata Lapolla, Giovanna Gregori, Carla Giordano, Laura Corsi, Raffaella Buzzetti, Gennaro Clemente, Graziano Di Cianni, Rossella Iannarelli, Renzo Cordera, Olga La Macchia, Chiara Zamboni, Cristiana Scaranna, Massimo Boemi, Ciro Iovine, Davide Lauro, Sergio Leotta, Elisabetta Dall'Aglio, Emanuela Cannarsa, Laura Tonutti, Giuseppe Pugliese, Antonio C Bossi, Roberto Anichini, Francesco Dotta, Antonino Di Benedetto, Giuseppe Citro, Daniela Antenucci, Lucia Ricci, Francesco Giorgino, Costanza Santini, Agostino Gnasso, Salvatore De Cosmo, Donatella Zavaroni, Monica Vedovato, Agostino Consoli, Maria Calabrese, Paolo di Bartolo, Paolo Fornengo, Gabriele Riccardi
BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy...
September 12, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28915708/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#5
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905939/curcumin-administration-suppresses-collagen-synthesis-in-the-hearts-of-rats-with-experimental-diabetes
#6
Shuang Guo, Xiang-Wen Meng, Xiao-Song Yang, Xiu-Fen Liu, Chang-Han Ou-Yang, Chao Liu
Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of low-dose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg(-1)·d(-1)) for 16 weeks...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28900491/the-clinical-effect-of-metformin-on-the-survival-of-lung-cancer-patients-with-diabetes-a-comprehensive-systematic-review-and-meta-analysis-of-retrospective-studies
#7
Xun Cao, Zhe-Sheng Wen, Xu-Dong Wang, Yong Li, Kui-Yuan Liu, Xin Wang
Preclinical investigations have revealed an anti-cancer effect of metformin. Several studies of metformin treatment have demonstrated the improved clinical outcomes of lung cancer patients with diabetes; however, the results have been inconsistent among studies. Our systematic review and meta-analysis aimed to summarize the up-to-date effects of metformin on diabetic lung cancer patients. A systematic search was performed for studies published. Then, these studies were evaluated for inclusion, and relevant data was extracted...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28892924/comparison-of-pioglitazone-and-metformin-efficacy-against-glucocorticoid-induced-atherosclerosis-and-hepatic-steatosis-in-insulin-resistant-rats
#8
I M Nagendra Nayak, Koyagura Narendar, Patil Ashok M, M G Jamadar, V Hemanth Kumar
INTRODUCTION: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities. AIM: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891142/network-meta-analysis-of-lorcaserin-and-oral-hypoglycaemics-for-patients-with-type-2-diabetes-mellitus-and-obesity
#9
L M Neff, M S Broder, D Beenhouwer, E Chang, E Papoyan, Z W Wang
In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments...
September 10, 2017: Clinical Obesity
https://www.readbyqxmd.com/read/28866649/weight-loss-for-overweight-and-obese-individuals-with-gout-a-systematic-review-of-longitudinal-studies
#10
Sabrina M Nielsen, Else M Bartels, Marius Henriksen, Eva E Wæhrens, Henrik Gudbergsen, Henning Bliddal, Arne Astrup, Filip K Knop, Loreto Carmona, William J Taylor, Jasvinder A Singh, Fernando Perez-Ruiz, Lars E Kristensen, Robin Christensen
OBJECTIVES: Weight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout. METHODS: We searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions...
September 2, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28862982/effects-of-the-genetic-variants-of-organic-cation-transporters-1-and-3-on-the-pharmacokinetics-of-metformin-in-jordanians
#11
Nancy Hakooz, Yazun Bashir Jarrar, Malik Zihlif, Amer Imraish, Saja Hamed, Tawfiq Arafat
BACKGROUND: Human response to the antidiabetic metformin is influenced by some factors, such as genetic variants in the SLC22A genes. This study aimed to determine the frequency of main SLC22A1 and SLC22A3 genetic variants and their influence on metformin pharmacokinetics among healthy unrelated Arab Jordanians. PATIENTS AND METHODS: The SLC22A1 and SLC22A3 genes were genotyped by DNA sequencing of exons 1, 3, 7, and 9 in the SLC22A1 gene and exons 6, 7, and 9 in the SLC22A3 gene...
September 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28862803/patient-and-cell-type-specific-heterogeneity-of-metformin-response
#12
Michael K Asiedu, Matthew Barron, Marie Christine Aubry, Dennis A Wigle
Most FDA approved drugs are not equally effective in all patients, suggesting that identification of biomarkers to predict responders to a chemoprevention agent will be needed to stratify patients and achieve maximum benefit. The goal of this study was to investigate both patient-specific and cell-context-specific heterogeneity of metformin response, using fibroblast cell lines and induced pluripotent stem cells differentiated into lung epithelial lineages. We performed cell survival analysis, transcriptome and whole exome sequencing analysis on both patient-derived cell lines and cancer cell lines to assess differential metformin response and identify response genes...
September 1, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28840963/the-enhancement-of-combination-of-berberine-and-metformin-in-inhibition-of-dnmt1-gene-expression-through-interplay-of-sp1-and-pdpk1
#13
Fang Zheng, JingJing Wu, Qing Tang, Qian Xiao, WanYin Wu, Swei Sunny Hann
Berberine (BBR), one of active alkaloid found in the rhizome, exhibited anti-cancer properties. We have showed that BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a). However, the in-depth mechanism underlying the anti-tumor effects still remained to be elucidated. Herein, we further confirmed that BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells. Mechanistically, we observed that BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions...
August 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28837141/metformin-reverses-prostate-cancer-resistance-to-enzalutamide-by-targeting-tgf-%C3%AE-1-stat3-axis-regulated-emt
#14
Qiuli Liu, Dali Tong, Gaolei Liu, Jing Xu, Khang Do, Kyla Geary, Dianzheng Zhang, Jun Zhang, Yao Zhang, Yaoming Li, Gang Bi, Weihua Lan, Jun Jiang
Although the newly developed second-generation anti-androgen drug enzalutamide can repress prostate cancer progression significantly, it only extends the survival of prostate cancer patients by 4-6 months mainly due to the occurrence of enzalutamide resistance. Most of the previous studies on AR antagonist resistance have been focused on AR signaling. Therefore, the non-AR pathways on enzalutamide resistance remain largely unknown. By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28811714/sex-dependent-difference-in-the-effect-of-metformin-on-colorectal-cancer-specific-mortality-of-diabetic-colorectal-cancer-patients
#15
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
#16
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 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28802015/identification-and-characterization-of-metformin-on-peptidomic-profiling-in-human-visceral-adipocytes
#17
Yao Gao, XingYun Wang, FangYan Huang, XianWei Cui, Yun Li, Xing Wang, Yan Cao, PengFei Xu, KaiPeng Xie, RanRan Tang, Le Zhang, ChenBo Ji, LiangHui You, XiRong Guo
To gain insight into the effect of metformin on losing weight from peptidomic perspective and to screen potential active peptides for reducing fat lipid deposition. After determining the proper concentration of metformin on human primary visceral adipocytes, we constructed a comparative peptidomic profiling between control and metformin treatment group (n = 3) using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by liquid chromatography tandem mass spectrometry. We identified and quantified 3065 non-redundant peptides, 304 of which were differentially expressed after metformin treatment, 206 peptides were up regulated and 98 peptides were down regulated significantly...
August 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28790226/effect-of-metformin-on-handgrip-strength-gait-speed-myostatin-serum-level-and-health-related-quality-of-life-a-double-blind-randomized-controlled-trial-among-non-diabetic-pre-frail-elderly-patients
#18
Purwita Wijaya Laksmi, Siti Setiati, Tirza Z Tamin, Pradana Soewondo, Wasilah Rochmah, Nafrialdi Nafrialdi, Joedo Prihartono
BACKGROUND: sarcopenia contributes to the development of frailty syndrome. Frailty syndrome is potentially improved by modifying insulin resistance, inflammation, and myostatin level. This study is aimed to investigate the effect of metformin on handgrip strength, gait speed, myostatin serum level, and health-related quality of life (HR-QoL) among non-diabetic pre-frail elderly patients. METHODS: a double blind randomized controlled trial study was conducted on non-diabetic elderly outpatients aged ≥ 60 years with pre-frail status based on phenotype and/ or index criteria (Cardiovascular Health Study and/ or Frailty Index 40 items) consecutively recruited from March 2015 to June 2016 at Cipto Mangunkusumo Hospital...
April 2017: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28789657/neutrophil-gelatinase-associated-lipocalin-ngal-is-elevated-in-type-2-diabetics-with-carotid-artery-stenosis-and-reduced-under-metformin-treatment
#19
W Eilenberg, S Stojkovic, A Piechota-Polanczyk, A Kaider, N Kozakowski, W J Weninger, J Nanobachvili, J Wojta, I Huk, S Demyanets, C Neumayer
BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics...
August 8, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28760367/effects-of-metformin-on-endometrial-cancer-systematic-review-and-meta-analysis
#20
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
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