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INTRODUCTION: Basal-like Breast Cancer (BLBC) represents an important molecular subtype of breast cancer characterized by an aggressive behavior, molecular pathology poorly understood and a limited treatment. OBJECTIVE: We aim to search for molecular differences between non-BLBC and BLBC tumors in order to propose possible diagnostic and prognostic biomarkers using databases. Metodology: Microarray processed data were downloaded from GEO database considering non-BLBC and BLBC. Enrichment analysis was evaluated using GO consortium and Ingenuity, protein-protein interaction, gene Ontology and co-expression analysis using STRING. Gene expression data was extracted using TCGA, METABRIC and Breast Cancer Gene-Expression Miner v4.2 databases. The Survival was evaluated using The Kaplan-Meier plotter. RESULTS: Were identified 58 upregulated and 58 downregulated genes enriched in signaling pathways like PDGF, Angiogenesis, Integrin and WNT. AGR2 and AGR3 expression were reduced in BLBC in relation to non-BLBC tumors, patients aged ≤51 years, and with negativity of ER, PR and HER-2 and nodal status. Low expression of AGR2 and AGR3 were associated with worse OS and RFS for all breast cancer cases. But according to the molecular stratification, low AGR2 conferred worst OS in luminal A, worst RFS in BLBC and good OS and RFS in luminal B. High AGR3 conferred worse OS and RFS in BLBC, but low AGR3 attributed worse OS in luminal A. CONCLUSION: AGR2 and AGR3 expression were able to differentiate non-BLBC from BLBC. Downregulation of AGR2 and AGR3 was associated with BLBC clinical phenotype. Furthermore, both genes behave different when considering prognosis and molecular stratification.

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Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment. Some of the top gene networks generated from the differentially expressed genes were related to the wingless­type MMTV integration 1 (WNT) canonical (WNT/ß-catenin) and non­canonical (ß­catenin­independent) pathways. The Human WNT signaling pathway RT2 profiler™ PCR array was used to validate the effects of PAR4 on the expression pattern of genes involved in the WNT pathway. CACNAD2A3, GDF5 and IL6 were upregulated and NANOG was downregulated in the MCF7 breast cancer cells expressing increased levels of PAR4 after treatment with docetaxel, likely indicating inactivation of the WNT/ß-catenin pathway. Upregulation of FGF7, LEF1 and TWIST1 indicated activation of the WNT/ß­catenin pathway. Although preliminary, our findings could be of particular interest for understanding the action of PAR4 in chemosensitivity, particularly to increase the specificity and effectiveness of drug treatment and overcome resistance to chemotherapy. Further studies are needed to better understand the biological roles of PAR4 in the regulation of WNT pathways in breast cancer cells in response to docetaxel and other chemotherapeutic agents.

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Tobacco and alcohol are the leading environmental risk factors in the development of human diseases, such as cancer, cardiovascular disease, and liver injury. Despite the copious amount of research on this topic, by 2030, 8.3 million deaths are projected to occur worldwide due to tobacco use. The expression of noncoding RNAs, primarily microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), is modulated by tobacco and alcohol consumption. Drinking alcohol and smoking cigarettes can modulate the expression of miRNAs and lncRNAs through various signaling pathways, such as apoptosis, angiogenesis, and inflammatory pathways-primarily interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), which seems to play a major role in the development of diseases associated with these risk factors. Since they may be predictive and prognostic biomarkers, they can be used both as predictors of the response to therapy and as a targeted therapy. Further, circulating miRNAs might be valuable noninvasive tools that can be used to examine diseases that are related to the use of tobacco and alcohol. This review discusses the function of noncoding RNAs in cancer and other human tobacco- and alcohol-associated diseases.

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O objetivo deste estudo foi avaliar o valor preditivo do teste de avidez de IgG no diagnóstico precoce da toxoplasmose congênita (TC) no recém-nascido (RN). O grupo de estudo foi constituído por 68 pares de puérperas e seus RN, sendo 43 com toxoplasmose aguda durante a gravidez e 25 com IgM negativo para Toxoplasma gondii (grupo controle). As pacientes pariram os RN na Maternidade do Hospital das Clínicas da Universidade Federal de Goiás. Foram avaliados os níveis séricos de IgM e IgG anti-T. gondii e avidez de IgG. Os RN do grupo de estudo foram divididos em RN com baixa avidez (BA) e RN com elevada avidez (EA). Foi verificada a concordância do teste de avidez dos RN e das puérperas. A infecção pelo T. gondii foi observada em 94,1% dos RN com BA e 42,3% dos RN com EA. Os níveis de IgG e de IgM dos RN com BA e de suas puérperas infectadas foram elevados e apresentaram diferença quando comparados com os RN com EA (p=0,0001) e os RN não infectados (p=0,0001) e suas respectivas puérperas. A sintomatologia da TC foi observada em 56% dos RN com BA e em 18% dos RN com EA. Nossos dados mostram que RN com BA apresentaram aumento de IgM e IgG e sintomas severos da TC. Assim, o teste de avidez poderia ser utilizado em conjunto com a detecção de IgM e IgG no diagnóstico precoce da TC no RN

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