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Nutrition and Cancer Oct 2017Much of the recent research in neoplasia has been focusing on the epigenetics of cancer cells, particularly as regards the search for potential molecular biomarkers that... (Review)
Review
Much of the recent research in neoplasia has been focusing on the epigenetics of cancer cells, particularly as regards the search for potential molecular biomarkers that could be used for early diagnosis, effective treatment, and prognosis of several types of cancer. Carcinogenesis often starts with mutations in oncogenes and tumor suppressor genes, and it leads to anomalies in cellular processes as vital as cell cycle regulation and apoptosis. Because malignant changes arise as a result of genetic as well as epigenetic mechanisms, one possible means of intervention involves reprogramming gene expression, so as to-at least in part-revert the molecular alterations. DNA methylation and demethylation, acetylation and deacetylation of histones, and microRNAs are a few examples of the epigenetic mechanisms responsible for tumor development and progression. Many biologically active compounds present in food-including sulforaphane, curcumin, and epigallocatechin-have been found to modulate those processes. We here systematically review information on the effects of such bioactive dietary compounds on human breast cancer cell lines, and explore the mechanisms underlying those effects with a view to their potential therapeutic application.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Catechin; Cell Cycle; Cell Line, Tumor; Curcumin; Epigenesis, Genetic; Female; Humans; Isothiocyanates; Sulfoxides; Telomerase
PubMed: 28872903
DOI: 10.1080/01635581.2017.1359322 -
Journal of Chromatography. B,... Jul 2017Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have... (Review)
Review
Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have been reported to possess anticancer, immunomodulator, antidiabetic, anti-inflammatory and antioxidant activities. The phytochemical investigations have revealed diverse chemical constituents, including phenolics [anthraquinones, anthrones, pyrones, chromones and coumarins], polysaccharides [arborans [(1-4) linked glucomannans, polysaccharide (A, B and C): (A: a linear (1-6)-O-α-glucan, B: a branching (1-2)-O-l-arabinose with (1-2)-O-d-galactose linkages and C: (1-4)-O-β-mannan with 18% acetyl group)]], glycoproteins and carboxypeptidase enzyme. There are many reports, describing the different methodologies developed to perform chemical analysis as well as, separation, detection and identification of these constituents. Different chromatographic techniques were applied such as gas chromatography (GC), high-performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization coupled with mass spectroscopy (LC-ESI/MS/MS) and gel filtration chromatography. Also the isolated compounds were identified based on the spectroscopic analysis; ultraviolet-visible spectroscopy (UV-vis), infra-red spectroscopy (IR), mass spectroscopy (MS) and nuclear-magnetic resonance (NMR). This study aims to pinpoint the active components besides finding out new structural leads for future drugs. Therefore, the review is targeted to provide evidence reported in the relevant literature on qualitative and quantitative research to assist scientists in isolation and characterization of bioactive compounds in A. arborescens.
Topics: Aloe; Chromatography, Gas; Chromatography, High Pressure Liquid; Glycoproteins; Phenols; Plant Extracts; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 28535423
DOI: 10.1016/j.jchromb.2017.04.044 -
European Journal of Endocrinology May 2017To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research. (Review)
Review
OBJECTIVE
To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research.
DESIGN
Systematic review.
METHODS
We performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016.
RESULTS
We identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring.
CONCLUSION
The current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.
Topics: Animals; Blood Glucose; Diabetes, Gestational; Endocrinology; Epigenesis, Genetic; Female; Histones; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 28232369
DOI: 10.1530/EJE-16-1017 -
PharmacoEconomics Jul 2017As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring... (Review)
Review
As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring Pharmaceuticals) to submit evidence for the clinical and cost effectiveness of degarelix for the treatment of advanced hormone-dependent prostate cancer. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The evidence, which included a randomised controlled trial (RCT) of degarelix versus leuprorelin, found that degarelix was non-inferior to leuprorelin for reduction of testosterone levels and that degarelix achieved a more rapid suppression of prostate-specific antigen levels and subsequently decreased incidences of testosterone flare associated with luteinising hormone releasing-hormone (LHRH) agonists. However, protection against testosterone flare for the comparators in the clinical trials was not employed in line with UK clinical practice. Further claims surrounding overall survival, cardiovascular adverse events and clinical equivalence of the comparator drugs from six RCTs of degarelix should be regarded with caution because of flaws and inconsistencies in the pooling of trial data to draw conclusions. The cost-effectiveness evidence included a de novo economic model. Based on the ERG's preferred base case, the deterministic incremental cost-effectiveness analysis (ICER) for degarelix versus 3-monthly triptorelin was £14,798 per quality-adjusted life-year (QALY) gained. Additional scenario analyses undertaken by the ERG resulted in ICERs for degarelix versus 3-monthly triptorelin ranging from £17,067 to £35,589 per QALY gained. Subgroup analyses undertaken using the Appraisal Committee's preferred assumptions suggested that degarelix was not cost effective for the subgroup with metastatic disease but could be cost effective for the subgroup with spinal metastases. The company submitted further evidence to NICE following an initial negative Appraisal Committee decision. Further analyses from the Decision Support Unit found that that, whilst some evidence indicated that degarelix could be cost effective for a small subgroup of people with spinal cord compression (SCC), data on the potential size of this subgroup and the rate of SCC were insufficient to estimate an ICER based on the evidence submitted by the company and a separately commissioned systematic review. NICE recommended degarelix as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases, only if the commissioner can achieve at least the same discounted drug cost as that available to the UK NHS in June 2016.
Topics: Cost-Benefit Analysis; Evidence-Based Practice; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasms, Hormone-Dependent; Oligopeptides; Prostatic Neoplasms
PubMed: 27943135
DOI: 10.1007/s40273-016-0481-1 -
Environmental Science and Pollution... Oct 2016Cadmium (Cd) is a well-known nephrotoxic contaminant, and N-acetyl-β-D-glucosaminidase (NAG) is considered to be an early and sensitive marker of tubular dysfunction.... (Meta-Analysis)
Meta-Analysis
Cadmium (Cd) is a well-known nephrotoxic contaminant, and N-acetyl-β-D-glucosaminidase (NAG) is considered to be an early and sensitive marker of tubular dysfunction. The link between Cd exposure and NAG level enables us to derive the benchmark dose (BMD) of Cd. Although several reports have already documented urinary Cd (UCd)-NAG relationships and BMD estimations, high heterogeneities arise due to the sub-populations (age, gender, and ethnicity) and BMD methodologies being employed. To clarify the influences that these variables exert, firstly, a random effect meta-analysis was performed in this study to correlate the UCd and NAG based on 92 datasets collected from 30 publications. Later, this established correlation (Ln(NAG) = 0.51 × Ln(UCd) + 0.83) was applied to derive the UCd BMD of 1.76 μg/g creatinine and 95 % lower confidence limit of BMD (BMDL) of 1.67 μg/g creatinine. While the regressions for different age groups and genders differed slightly, it is age and not gender that significantly affects BMD estimations. Ethnic differences may require further investigation given that limited data is currently available. Based on a comprehensive and systematic literature review, this study is a new attempt to quantify the UCd-NAG link and estimate BMD.
Topics: Acetylglucosaminidase; Benchmarking; Biomarkers; Cadmium; Creatinine; Environmental Exposure; Environmental Pollutants; Female; Humans; Male; Middle Aged; Random Allocation; beta 2-Microglobulin
PubMed: 27464656
DOI: 10.1007/s11356-016-7214-z -
Medicine Jul 2016Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced... (Comparative Study)
Comparative Study Meta-Analysis Review
Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78-1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26-1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix.
Topics: Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Staging; Oligopeptides; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 27399062
DOI: 10.1097/MD.0000000000003845 -
The British Journal of Nutrition Aug 2016Legume consumption plays a pivotal role in the prevention and treatment of the metabolic syndrome (MetS). This systematic review aimed to highlight the beneficial... (Review)
Review
Legume consumption plays a pivotal role in the prevention and treatment of the metabolic syndrome (MetS). This systematic review aimed to highlight the beneficial effects of legume interventions for the prevention and/or improvement of parameters related to the MetS and the implicated metabolic pathways so far reported. The methodology involved a search in four electronic databases (Medline, Web of Science, Scopus, Cochrane Library) from January 2007 to December 2014, considering as descriptors 'Metabolic Syndrome' and 'Fabaceae' and adequately adjusting the equation in each one of them. In total, forty-one studies were finally included. The majority of the studies described a regulating effect on glucose and lipid metabolism due to legume administration, whereas effects on blood pressure and renal parameters are not fully described. Regarding the metabolic pathways involved, they include the up-regulation of genes related to β-oxidation and acetyl-CoA degradation and the down-regulation of glycolytic and lipogenesis genes, as well as those associated with the acetyl-CoA synthesis. The ameliorating effects of legume consumption on the alterations associated with the MetS are clearly reported and coincide with changes in the expression of protein and genes involved in lipid and glucose metabolism. More research needs to be conducted including more legume species that are highly consumed as part of a healthy dietary pattern.
Topics: Animals; Blood Glucose; Diet; Fabaceae; Feeding Behavior; Lipid Metabolism; Metabolic Syndrome; Seeds; Vegetables
PubMed: 27221057
DOI: 10.1017/S0007114516001963 -
Expert Opinion on Drug Metabolism &... Aug 2016Several studies suggested a possible association between certain polymorphisms in the N-acetyl-transferase 2 (NAT2) gene (which encodes a very important enzyme involved... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several studies suggested a possible association between certain polymorphisms in the N-acetyl-transferase 2 (NAT2) gene (which encodes a very important enzyme involved in xenobiotic metabolism) and the risk for Parkinson's disease (PD). As the results of studies on this issue are controversial, we conducted a systematic review and a meta-analysis of eligible studies on this putative association.
AREAS COVERED
The authors revised the relationship between NAT2 polymorphisms and the risk of developing PD using several databases, and performed a meta-analysis using the software Meta-Disc1.1.1. In addition heterogeneity between studies was analyzed. A description of studies regarding gene-gene interactions and gene-environmental interactions involving NAT2 polymorphisms is also made.
EXPERT OPINION
Despite several recent meta-analyses showing an association between several polymorphisms in genes related with detoxification mechanisms such as cytochrome P4502D6 (CYP2D6), and glutathione transferases M1 and T1 (GSTM1, and GSTT1), data on NAT2 gene polymorphisms obtained from the current meta-analysis do not support a major association with PD risk, except in Asian populations. However, data from many studies are incomplete and therefore insufficient data exists to draw definitive conclusions. Several studies suggesting gene-gene and gene-environmental factors involving NAT2 gene in PD risk await confirmation.
Topics: Arylamine N-Acetyltransferase; Asian People; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Genetic; Risk
PubMed: 27216438
DOI: 10.1080/17425255.2016.1192127 -
Nutrition, Metabolism, and... Jul 2016New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition... (Review)
Review
BACKGROUND
New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences.
AIM
To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR).
METHOD AND RESULTS
Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies.
CONCLUSIONS AND RELEVANCE
Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.
Topics: Acetylation; Biomarkers; Blood Glucose; Chromatin Assembly and Disassembly; DNA Methylation; Diabetes Mellitus, Type 2; Epigenesis, Genetic; Female; Gene Expression Regulation; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Histones; Humans; Insulin; Insulin Resistance; Male; Phenotype; Risk Factors
PubMed: 27146363
DOI: 10.1016/j.numecd.2016.04.002 -
Asia-Pacific Journal of Clinical... Mar 2016Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is... (Review)
Review
Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is lost over time due to evolving changes in tumor biology and the development of endocrine resistance. Many agents targeting the intracellular signaling pathways associated with endocrine resistance are in development. Encouraging early results have been seen for agents which directly target the estrogen receptor (ER), inhibitors of co-signaling pathways, inhibitors of ER chaperones, ER antagonists able to inhibit mutated or otherwise activated ERs, and modulators of histone acetylation restoring synthesis of ER signaling components. Following our systematic review of treatments with established benefits in this supplement, we review some of the more promising new strategies for overcoming endocrine resistance, looking at the impact on disease control and quality of life for women with hormone receptor positive, HER2 negative breast cancer. We also examine the biomarkers that may guide selection of the best therapy for the individual.
Topics: Breast Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Meta-Analysis as Topic; Molecular Targeted Therapy; Neoplasm Proteins; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Signal Transduction
PubMed: 27001209
DOI: 10.1111/ajco.12492