Glucocorticoid receptor (GR) is a transcription factor that plays a crucial role in cancer biology. In this study, we utilized an in silico ‐designed GR activity signature to demonstrate that GR relates to the proliferative capacity of numerous primary cancer types. In breast cancer, the GR activity status determines luminal subtype identity and has implications for patient outcomes. We reveal that GR engages with estrogen receptor (ER), leading to redistribution of ER on the chromatin. Notably, GR activation leads to upregulation of the ZBTB16 gene, encoding for a transcriptional repressor, which controls growth in ER‐positive breast cancer and associates with prognosis in luminal A patients. In relation to ZBTB16 's repressive nature, GR activation leads to epigenetic remodeling and loss of histone acetylation at sites proximal to cancer‐driving genes. Based on these findings, epigenetic inhibitors reduce viability of ER‐positive breast cancer cells that display absence of GR activity. Our findings provide insights into how GR controls ER‐positive breast cancer growth and may have implications for patients' prognostication and provide novel therapeutic candidates for breast cancer treatment.

Introdução: O câncer gástrico (CG) acomete principalmente o sexo masculino e faixa etária mais avançada podendo levar ao óbito. O principal fator de risco para o desenvolvimento desse tumor é a infecção pela bactéria H.pylori. Sabe-se que o diagnóstico e tratamento precoce resulta em um melhor prognóstico para o paciente. Objetivo: Investigar a incidência e a mortalidade pelo CG no Brasil e na Bahia nos últimos 10 anos. Método: Trata-se de um estudo descritivo, exploratório e série temporal. Os dados coletados são de domínio público e foram obtidos do Registro de Câncer de Base Populacional do Instituto Nacional de Câncer José de Alencar Gomes da Silva (INCA) e Sistema de Informações sobre Mortalidade (SIM) do Ministério da Saúde (DATASUS/MS) no período de 2009 a 2020. Resultados: Observou-se um aumento na taxa de incidência e mortalidade pelo CG no Brasil no período analisado, sendo a maior taxa de incidência na região Sudeste e Sul (média: 3.424,6 e 2.243,7 casos novos/ano, respectivamente) e maior taxa de mortalidade nas regiões Sudeste e Nordeste (média: 6.593,7 e 3.164 óbitos/ano, respectivamente). No quesito faixa etária e sexo, observou-se maior incidência entre 60 e 69 anos (média: 2.647,6 casos novos/ano) e maior número de óbitos entre 70 e 79 anos (média: 3.705,8 óbitos/ano) com predomínio no sexo masculino em todas as faixas etárias consideradas no Brasil, tanto na incidência (média: 5.372,8 casos novos/ano) quanto na mortalidade (média: 9.039,3 óbitos/ano). Conclusão: A partir dos resultados foi possivel identificar a necessidade de uma maior investigação da neoplasia gástrica no sistema de saúde, especialmente em pacientes com característica descritas nesse perfil. Introduction: Gastric cancer (GC) affects mainly males and older age groups and can lead to death. The main risk factor for the development of this tumor is infection by the H.pylori bacteria. It is known that early diagnosis and treatment results in a better prognosis for the patient. Aims: To analyze the incidence and mortality from GC in Brazil and Bahia in the last 10 years. Method: This is a descriptive, exploratory and time series study. The data collected are in the public domain and were obtained from the Population-Based Cancer Registry of the José de Alencar Gomes da Silva National Cancer Institute (INCA) and the Mortality Information System (SIM) of the Ministry of Health (DATASUS/MS) in period from 2009 to 2020. Results: There was an increase in the incidence and mortality rate from GC in Brazil in the analyzed period, with the highest incidence rate in the Southeast and South regions (average: 3,424.6 and 2,243.7 new cases/ year, respectively) and a higher mortality rate in the Southeast and Northeast regions (average: 6,593.7 and 3,164 deaths/year, respectively). Regarding age group and sex, there was a higher incidence between 60 and 69 years (average: 2,647.6 new cases/year) and a higher number of deaths between 70 and 79 years (average: 3,705.8 deaths/year) with predominance of in males in all age groups considered in Brazil, both in terms of incidence (average: 5,372.8 new cases/year) and mortality (average: 9,039.3 deaths/year). Conclusion: Based on the results, it was possible to identify the need for further investigation of gastric cancer in the health system, especially in patients with the characteristics described in this profile. Introducción: El cáncer gástrico (CG) afecta principalmente hombres y grupos de mayor edad y puede conducir a la muerte. El principal factor de riesgo para el desarrollo de este tumor es la infección por la bacteria H.pylori. Se sabe que el diagnóstico y tratamiento tempranos redundan en un mejor pronóstico para el paciente. Objetivo: Analizar la incidencia y mortalidad por CG en Brasil y Bahía en los últimos 10 años. Método: Se trata de un estudio descriptivo, exploratorio y de series temporales. Los datos recabados son de dominio público y fueron obtenidos del Registro Poblacional de Cáncer del Instituto Nacional del Cáncer José de Alencar Gomes da Silva (INCA) y del Sistema de Información de Mortalidad (SIM) del Ministerio de Salud (DATASUS/MS) en el período de 2009 a 2020. Resultados: Hubo aumento en la tasa de incidencia y mortalidad por CG en Brasil en el período analizado, con la mayor tasa de incidencia en las regiones Sudeste y Sur (promedio: 3.424,6 y 2.243,7 nuevos casos/año, respectivamente) y una mayor tasa de mortalidad en las regiones Sudeste y Nordeste (promedio: 6.593,7 y 3.164 muertes/año, respectivamente). En cuanto al grupo de edad y sexo, hubo mayor incidencia entre 60 y 69 años (promedio: 2.647,6 casos nuevos/año) y mayor número de muertes entre 70 y 79 años (promedio: 3.705,8 muertes/año) con predominio del sexo masculino en todos los grupos de edad considerados en Brasil, tanto en términos de incidencia (promedio: 5.372,8 casos nuevos/año) como de mortalidad (promedio: 9.039,3 muertes/año) Conclusión: Con base en los resultados, fue posible identificar la necesidad de profundizar la investigación del cáncer gástrico en el sistema de salud, especialmente en pacientes con las características descritas en este perfil.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3′-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3′-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.

This study aimed to verify whether germline single nucleotide variants (SNV) in CTLA-4 gene, c.-1765C>T, c.-1661A>G, c.-1577G>A, and c.-1478G>A, influence the risk, clinicopathological aspects, and survival of patients with CM, as well as its functional consequences. A total of 432 patients with CM and 504 controls were evaluated. CTLA-4 genotypes were identified by real-time polymerase chain reaction (RT-PCR) and expression of CTLA-4 by quantitative PCR (qPCR) and luciferase assay. Cell cycle, proliferation, apoptosis/necrosis, and migration analyses were performed in SK-MEL-28 and A-375 cell lines modified to present homozygous ancestral or variant genotypes by CRISPR technique. Individuals with the CTLA-4 c.-1577 AA genotype and the combined CTLA-4 c.-1577 and c.-1478 AA + AA genotypes were at 1.60- and 3.12-fold higher risk of developing CM, respectively. The CTLA-4 c.-1577 AA genotype was seen as an independent predictor of worse event-free survival and was also associated with higher gene expression, higher cell proliferation, lower cell apoptosis, and higher cell migration. Our data present, for the first time, evidence that CTLA-4 c.-1577G>A alters the risk and clinical aspects of CM treated with conventional procedures and may be used for selecting individuals for tumor prevention and patients for distinct treatment.