DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

<p>Abstract</p> <p>Background</p> <p>Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.</p> <p>Methods</p> <p>A set of 4 genes, including <it>CDH1 </it>(E-cadherin), <it>SFN </it>(stratifin), <it>RARB </it>(retinoic acid receptor, beta) and <it>RASSF1A </it>(Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters.</p> <p>Results</p> <p><it>CDH1 </it>and <it>SFN </it>genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between <it>RARB </it>and <it>RASSF1A </it>methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for <it>RARB </it>methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for <it>RASSF1A </it>gene, respectively, in relation to the control group.</p> <p>Conclusion</p> <p>Indistinct DNA hypermethylation of <it>CDH1 </it>and <it>SFN </it>genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, <it>RARB </it>and <it>RASSF1A </it>gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of differentially methylated genes in this neoplasia in order to maximize the diagnostic coverage of epigenetic markers, especially in studies aiming at early recurrence detection.</p

Paraquat and Parkinson’s disease: a systematic review protocol according to the OHAT approach for hazard identification

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative condition that has genetic susceptibility, aging, and exposure to certain chemicals as risk factors. In recent decades, epidemiological and experimental studies have investigated the role of pesticides in the development of PD, in particular that of the herbicide paraquat. Here, we, therefore, aim to systematically review the association between paraquat exposure and PD. Methods Observational studies (cohort, case–control, and cross-sectional) eligible for this systematic review will enroll any participant who was occupationally and/or environmentally exposed to paraquat. Experimental studies, including in vivo and in vitro assays designed to assess neurotoxicological endpoints or mechanisms of paraquat neurotoxicity, will also be eligible. Outcomes of interest include the following: PD diagnosis; neurobehavioral, biochemical, and/or morphological alterations; and cellular, biochemical, and/or molecular pathways to oxidative stress. Using terms to include all forms of paraquat combined with PD, the following electronic databases will be searched: PubMed, EMBASE, LILACS, Toxnet, and Web of Science, without restrictions as to language, year, or status of publication. A team of reviewers will independently select potential titles and abstracts, extract data, assess risk of bias, and determine the overall quality of evidence for each outcome using the Office of Health Assessment and Translation (OHAT) approach for systematic reviews and evidence integration. Dichotomous data will be summarized as odds ratios, and continuous data will be given as mean differences, both with their respective 95% confidence intervals. Discussion This is the first time that the OHAT systematic review protocol will be applied to investigate a possible causal association between exposure to paraquat and PD. Results from this study could serve as basis for regulatory agencies to define paraquat levels of concern, supporting its risk assessment process. Systematic review registration PROSPERO CRD4201605086

GLP-1 and GIP receptor agonists in the treatment of Parkinson's disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies.

BackgroundParkinson's disease (PD) is a progressive multifactorial neurodegenerative condition. Epidemiological studies have shown that patients with type 2 diabetes mellitus (T2DM2) are at increased risk for developing PD, indicating a possible insulin-modulating role in this latter condition. We hypothesized that drugs similar to glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), used in the treatment of T2DM2, may play a role in PD.ObjectivesThe purpose of this study is to systematically review and meta-analyze data of preclinical and clinical studies evaluating the efficacy and safety of GLP-1 and GIP drugs in the treatment of PD.MethodsTwo reviewers will independently evaluate the studies available in the Ovid Medline, Ovid Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cinahl, and Lilacs databases. Preclinical rodent or non-human primate studies and randomized controlled human clinical trials will be included, without language or publication period restrictions. Outcomes of interest in preclinical studies will be primarily locomotor improvements and adverse effects in animal models of PD. For clinical trials, we will evaluate clinical improvements rated by the Movement Disorders Society Unified Parkinson's Disease Rating Scale-parts I, II, III, and IV, and adverse effects. The risk of bias of preclinical studies will be assessed by the SYRCLE tool and CAMARADES checklist and the clinical studies by the Cochrane tool; the certainty of the evidence will be rated by GRADE.Discussion and conclusionThere is an urge for new PD treatments that may slow the progression of the disease rather than just restoring dopamine levels. This study will comprehensively review and update the state of the art of what is known about incretin hormones and PD and highlight the strengths and limitations of translating preclinical data to the clinic whenever possible.Systematic review registrationPROSPERO registration number CRD42020223435

B) Positive cytology illustrating a tumor recurrent case during the post-surgical monitoring

× 400, Giemsa staining. C) Comparative MSP results from case 11 in tumor tissue (TCC) and in the exfoliated cells from the correspondent bladder washing for and genes. M – methylated allele; U – unmethylated allele. D) Distribution of MSP results among the third set of samples including 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring and comparison with the cytological analysis.<p><b>Copyright information:</b></p><p>Taken from "DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection"</p><p>http://www.biomedcentral.com/1471-2407/8/238</p><p>BMC Cancer 2008;8():238-238.</p><p>Published online 14 Aug 2008</p><p>PMCID:PMC2527332.</p><p></p

M – methylated allele; U – unmethylated allele; N – normal tissue; T – tumoral tissue

<p><b>Copyright information:</b></p><p>Taken from "DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection"</p><p>http://www.biomedcentral.com/1471-2407/8/238</p><p>BMC Cancer 2008;8():238-238.</p><p>Published online 14 Aug 2008</p><p>PMCID:PMC2527332.</p><p></p