Prostate tumor markers: diagnosis, prognosis and management.

Prostate cancer (PCA) is the second most common type of cancer in the world. Nevertheless, diagnosis is still based on nonspecific methods, or invasive methods which makes clinical decision and diagnosis difficult, generating risk of both underdiagnosis and overdiagnosis. Given the high prevalence, morbidity and mortality of PCA, new strategies are needed for its diagnosis. A review of the literature on available biomarkers for PCA was performed, using the following terms: prostate cancer AND marker OR biomarker. The search was carried out in Pubmed, Science Direct, Web of Science and Clinical Trial. A total of 35 articles were used, and PHI (Prostate Health Index) and the 4Kscore tests were identified as the best well-established serum markers. These tests are based on the evaluation of expression levels of several molecules. For analysis of urine samples, Progensa, ExoDXProstate, and Mi Prostate Score Urine Test are available. All these tests have the potential to help diagnosis, avoiding unnecessary biopsies, but they are used only in association with digital rectal examination and PSA level data. The search for biomarkers that can help in the diagnosis and therapeutic management of PCA is still in its initial phase, requiring more efforts for an effective clinical application.

Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines.

BACKGROUND: Hematological malignancies are a heterogeneous group of tumors with increased proliferative and auto-replicative capacity. Despite treatment advances, post-treatment quality of life remains highly affected. Studies addressing the molecular mechanisms of these diseases are critical for the development of effective, rapid and selective therapies, since few therapeutic strategies succeed in being effective without triggering high-grade toxicities or debilitating late effects. Our aim of this study was to verify changes in the expression of genes involved in the malignant phenotype of hematological malignancies, by treating human cell lines in vitro with classic chemotherapeutic agents and the demethylating agent, decitabine. METHODS: KASUMI-1 and K-562 human myeloid leukemia cell lines were plated at a density of 3 × 104 cells/well and treated with increasing concentrations of different chemotherapeutic agents commonly used in the clinical setting. After 24 and 48 h of treatment, cell viability was tested, and RNA was extracted. Complementary DNA (cDNA) was synthesized and quantitative real-time polymerase chain reaction (qPCR) was performed to evaluate the gene expression of IDH2, TET2 and KDM2B. RESULTS: A modulation in gene expression was observed before and after treatment with classic chemotherapeutic agents. It was possible to demonstrate a difference in gene expression when cells were treated with chemotherapeutic agents or decitabine alone when compared to chemotherapeutic agents in association with decitabine. CONCLUSIONS: The genes tested, and the modulation of their expression during in vitro treatments suggest that IDH2, TET2, and KDM2B should be further investigated as potential biomarkers for ongoing treatment response and follow-up for patients diagnosed with hematological malignancies of the myeloid lineage.

DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid Leukemia and Myelodysplastic Syndrome.

During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome. Here, we report that distinct changes in DNA methylation may alter gene function and drive malignant cellular transformation during several stages of leukemogenesis. Most of these modifications occur at an early stage of disease and may predict myeloid/lymphoid transformation or response to therapy, which justifies its use as a biomarker for disease onset and progression. Methylation patterns, or its dynamic change during treatment, may also be used as markers for patient stratification, disease prognosis, and response to treatment. Further investigations of methylation modifications as therapeutic biomarkers, which may correlate with therapeutic response and/or predict treatment toxicity, are still warranted.

Perfil dos beneficiários do Instituto Nacional do Seguro Social aposentados por invalidez no Estado do Rio Grande do Sul no período de 2010 a 2015 / Profile of the National Institute of Social Security beneficiaries retired due to disability in Rio Grande do Sul from 2010 to 2015

Resumo Introdução O presente estudo investigou o perfil epidemiológico dos aposentados por invalidez no Estado do Rio Grande do Sul durante o período de 2010 a 2015. Método Foi realizada uma pesquisa descritiva e quantitativa, utilizando o método de levantamento de corte transversal de dados secundários obtidos pelo Sistema Único de Benefícios (Suibe). As variáveis utilizadas para este estudo foram: faixa etária; sexo; tempo de contribuição antes da aposentadoria; faixa salarial do aposentado após a invalidez; e Classificação Internacional de Doenças (CID-10). Resultados Do total de 94.670 aposentados por invalidez, 55,6% eram do sexo masculino, 64,4% estavam na faixa de 40 a 59 anos, 44,3% possuíam média salarial de 1 salário-mínimo e 25,3% das concessões foram associadas a doenças do sistema osteomuscular e do tecido conjuntivo. Conclusão A partir das patologias identificadas pelo estudo, pode-se direcionar o desenvolvimento de ações que frisem a importância da prevenção, do diagnóstico precoce e correto tratamento, a fim de evitar as patologias e/ou o seu agravamento, bem como o afastamento do mercado de trabalho.

Abstract Introduction The present study investigated the epidemiological profile of disability retirees in Rio Grande do Sul from 2010 to 2015. Method A descriptive and quantitative research was carried out using the cross-sectional survey method based on secondary data obtained by Sistema Único de Benefícios (SUIBE). The variables used for this study were age, sex, contribution period before retirement, salary range of the retiree after the disability, and International Classification of Diseases (ICD-10). Results Of the total of 94,670 disability retirees, 55.6% were male, 64.4% were between 40 and 59 years old, 44.3% had an average income of 1 minimum wage and 25.3% of concessions were associated to musculoskeletal system and connective tissue diseases. Conclusion From the pathologies identified in the study, it is possible to direct the development of actions to emphasize the importance of prevention, early diagnosis and correct treatment, in order to avoid pathologies and/or their aggravation, as well as the withdrawal from the labor market.

Calyptranthes grandifolia O.Berg (Myrtaceae) ethanolic extract inhibits TNF-α gene expression and cytokine release in vitro.

Anti-tumor therapies based on anti-inflammatory effects have been considered in cancer treatment. Survival, proliferation and, resultantly, invasion and metastasis of tumor cells are regulated by local inflammatory mediators. Primary inflammatory cytokines, such as tumor necrosis factor (TNF), are targets for anticancer therapy. Several anti­inflammatory agents isolated from natural products are becoming important chemopreventive and therapeutic agents for cancer. The present study aimed to investigate the expression of TNF­α, nuclear factor­κΒ (NF­κΒ) and p38α mitogen-activated protein kinase (p38α) genes, associated with proliferation and inflammation in the Caco­2 cell line treated with ethanolic and hexanic extracts of Calyptranthes grandifolia O.Berg (Myrtaceae). Caco­2 cells were cultured and treated with plant extract at different concentrations (25, 50, 100 and 200 µg/ml) and stimulated with lipopolysaccharide (LPS). For gene expression, analysis was performed by total RNA extraction followed by synthesis of complementary DNA and analysis by quantitative polymerase chain reaction. The release of TNF­α cytokine was evaluated by ELISA in RAW 264.7 murine macrophages activated by LPS. Among the evaluated genes, there was a decrease in TNF-α expression at 100 and 200 µg/ml concentrations only with the ethanolic extract (P<0.025). The p38α gene exhibited a tendency to increase expression only when treated with ethanolic extract and the NF­κΒ gene did not significantly differ compared with the positive control when treated with either analyzed extract. The inhibition of TNF-α cytokine in the RAW 264.7 cell line was significant (P<0.05) in ethanolic extract at 200 µg/ml compared with the positive control (LPS 1 µg/ml). In conclusion, the ethanolic extract may exhibit an anti­inflammatory activity by inhibiting TNF­α. However, further studies are required to confirm its potential anti-inflammatory effects.