Background: The advanced phases of chronic myeloid leukemia (CML) are known to be more resistant to therapy. This resistance has been associated with the overexpression ofABCB1, which gives rise to the multidrug resistance (MDR) phenomenon. MDR is characterized by resistance to nonrelated drugs, and P-glycoprotein (encoded byABCB1) has been implicated as the major cause of its emergence. Wnt signaling has been demonstrated to be important in several aspects of CML. Recently, Wnt signaling was linked toABCB1regulation through its canonical pathway, which is mediated by β-catenin, in other types of cancer. In this study, we investigated the involvement of the Wnt/β-catenin pathway in the regulation ofABCB1transcription in CML, as the basal promoter ofABCB1has several β-catenin binding sites. β-catenin is the mediator of canonical Wnt signaling, which is important for CML progression.Methods: In this work we used the K562 cell line and its derived MDR-resistant cell line Lucena (K562/VCR) as CML study models. Real time PCR (RT-qPCR), electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), flow cytometry (FACS), western blot, immunofluorescence, RNA knockdown (siRNA) and Luciferase reporter approaches were used.Results: β-catenin was present in the protein complex on the basal promoter ofABCB1in both cell linesin vitro, but its binding was more pronounced in the resistant cell linein vivo. Lucena cells also exhibited higher β-catenin levels compared to its parental cell line.Wnt1andβ-catenindepletion and overexpression of nuclear β-catenin, together with TCF binding sites activation demonstrated thatABCB1is positively regulated by the canonical pathway of Wnt signaling.Conclusions: These results suggest, for the first time, that the Wnt/β-catenin pathway regulatesABCB1in CML.

Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). Methods: CA-CRC was induced in P2X7R^+/+ and P2X7R^−/− mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). In a therapeutic protocol, P2X7R^+/+ mice were treated with a P2X7R-selective inhibitor (A740003). Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. Results: The P2X7R^+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R^−/− and the P2X7R^+/+ mice treated with A740003. The P2X7R^+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. Microbial changes were observed in the P2X7R^−/− and P2X7R^+/+-induced mice, partially reversed by the A740003 treatment. Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development.

A mamaplastia de aumento com implantes revestidos de poliuretano (PU) é amplamente utilizada devido à sua aderência aos tecidos e menor incidência de contratura capsular. Este estudo retrospectivo analisou as indicações para troca desses implantes em 20 pacientes atendidos no Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ) e em clínica privada, avaliando os principais motivos e tendências temporais. Os resultados mostraram que aumento de volume foi o motivo mais frequente para a troca (8 casos), predominantemente nos primeiros 10 anos, refletindo demandas estéticas contínuas. A contratura capsular, complicação tardia relacionada a processos fibróticos crônicos, foi o segundo motivo mais comum (7 casos), com maior incidência após 10 anos. Motivos menos prevalentes incluíram simetrização e diminuição (2 casos cada), geralmente associadas a correções precoces, e um único caso de exposição do implante após 96 meses. A análise temporal identificou que contraturas predominam em implantes com mais de 10 anos (Grupo 3), enquanto o aumento e ajustes técnicos ocorrem mais precocemente (Grupos 1 e 2). Comparados aos implantes lisos e texturizados, os revestidos de PU apresentam vantagens, como menor mobilidade e taxas de contratura mais baixas (0-3% em 10 anos). Em conclusão, a troca de implantes revestidos de PU ocorre por motivos distintos conforme o tempo. O aumento predomina no início, enquanto a contratura capsular é o principal motivo tardio, destacando a importância do acompanhamento a longo prazo para prevenir e tratar complicações.