Periodontitis prevalence and associated factors: a comparison of two examination protocols

La variabilidad en la definición epidemiológica de la periodontitis y los protocolos de evaluación afectan la medición de la prevalencia y su asociación con ciertos factores. Si bien, el patrón oro para el examen periodontal es el registro de boca completa, que evalúa la pérdida de inserción (CAL, por sus siglas en inglés) y profundidad de sondaje (PS, por sus siglas en inglés), los recursos no siempre están disponibles para los sistemas de vigilancia epidemiológica. Objetivo: En este estudio se compararon diferentes protocolos y definiciones de periodontitis evaluando la prevalencia y la asociación de factores relacionados en pacientes adultos que solicitaron atención en la Facultad de Odontología de la UdelaR

Hedgehog driven regulatory network sustains chemoresistance and mesenchymal phenotype in Colorectal Cancer cells

Title: Hedgehog driven regulatory network sustains chemoresistance and mesenchymal phenotype in Colorectal Cancer cells. Authors: A. Citarella, G. Catanzaro, S. ZM Besharat, F. Barbagallo, S. Trocchianesi, C. Sabato, T. M. Autilio, A. Asquino, A. Vacca, M. Venneri, E. Ferretti, A. Po. Background: Colorectal cancer (CRC) is a leading cause of mortality and morbidity. CRC is characterized by frequent development of chemoresistance, achieved by the modulation of signaling pathways that regulate cell survival. Thus, understanding mechanisms related to aggressive features remains one of the most important goal for the development of more efficient strategies. The deregulation of different oncogenic pathways is involved in the acquisition of aggressive features and chemoresistance. In this context of CRC, we previously showed that the Hedgehog pathway regulates chemoresistance by up-regulating ABC transporters. Together with HH another important pathway involved in stemness features of normal colonic mucosa and is Notch1 pathway. Recent studies highlight the crosstalk between Notch1 and HH-GLI1 signaling is fundamental in different development contexts. The aim of our work was to investigate the role of Hedgehog-GLI1 together with Notch1 pathway in CRC resistance to chemotherapy. Methods: We performed our experiments in different cellular models derived from two CRC HT29 and HCT116 cell lines. Cells cultured in 2D and 3D (organoids) conditions were treated with 5-Fluoruracil, Notch1 inhibitor (DAPT), and HH-GLI1 inhibitor (GANT-61) and Arsenic Trioxide (ATO) inhibitor of both pathways. Proteins and RNA levels were evaluated. Results: First, we found that HT29 cells (BRAF mut) and HCT116 (KRAS mut) expressed Notch1 and GLI1 and that the HH and Notch1 inhibitors were able to downregulate the signaling but were not able to induce apoptosis, while the combinatory treatments induce apoptosis. Moreover, the inhibition of HH-GLI1 and Notch1 was able to induce chemosensitivity to 5- Fluoruracil, by increasing cell death. The combined inhibition of HH and Notch1 together with 5fu treatment induces differentiation markers axin, e-cadherin and klf4. In organoids we observed that the combined inhibition of HH-GLI1 and Notch1 together with 5- Fu impaired the protein expression of the Epithelial to Mesenchymal Transition (EMT) marker Vimentin. CONCLUSIONS Our data highlight the role of HH- GLI1 pathway together with Notch1 signaling in regulating cell death differentiation and mesenchymal phenotype in CRC cellular models