RÉSUMÉ
Abstract Objective: Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. Methods: This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. Results: EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. Conclusion: The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.
RÉSUMÉ
As infecções de transmissão sexual constituem importante problema de saúde pública, por apresentarem taxas elevadas de prevalência, de transmissibilidade e de complicações. Adquirem importância por acarretarem aumento na transmissibilidade do vírus da imunodeficiência humana (HIV). A infecção de transmissão sexual mais frequente é a infecção pelo Papilomavírus humano (HPV). Esta acarreta, nestas faixas de idade, na maioria das vezes, anormalidade citológicas de baixo grau, que tendem à regressão espontânea. A segunda infecção de maior prevalência é a infecção, pela Chlamydia trachomatis (C trachomatis). Dentre as complicações associadas a essa infecção têm destaque a doença inflamatória pélvica, a gravidez ectópica, a infertilidade tubária e a transmissão vertical. As outras infecções de transmissão sexual, embora de menor prevalência, são também preocupantes. Os fatores de risco para aquisição destas infecções são o número de parceiros, a idade jovem e o sexo feminino. Estes dados apontam para a necessidade de um programa de educação integrado a uma abordagem em saúde pública direcionados à prevenção primária e ao rastreamento, com ênfase nas infecções pelo HPV e C trachomatis entre adolescentes e adultos jovens.(AU)
Sexually transmitted infections are major public health problems because they have high prevalence and transmission rates, and number of complications and sequelae. As a consequence of increased in HIV transmission, this condition is of most importance. The most frequent sexually transmitted disease is the human papillomavirus (HPV) infection. Cytological abnormalities induced by HPV infection are low-grade and tend to regression in young adult group. The second most prevalent disease is Chlamydia trachomatis (C. trachomatis) infection. The complications associated with C. trachomatis infection are pelvic inflammatory disease, ectopic pregnancy, tubal infertility, and vertical transmission. Other sexually transmitted infections, though less prevalent, are also worrying. The risk factors for these infections are the number of sexual partners, young age, and female sex. These data point to the need for an integrated education program to a public health approach, aimed at primary prevention and screening, with emphasis on the C. trachomatis infection among adolescents and young people.(AU)