Renal antiporter ClC-5 regulates collagen I/IV through the β-catenin pathway and lysosomal degradation.

Mutations in Cl/H antiporter ClC-5 cause Dent's disease type 1 (DD1), a rare tubulopathy that progresses to renal fibrosis and kidney failure. Here, we have used DD1 human cellular models and renal tissue from DD1 mice to unravel the role of ClC-5 in renal fibrosis. Our results in cell systems have shown that ClC-5 deletion causes an increase in collagen I (Col I) and IV (Col IV) intracellular levels by promoting their transcription through the β-catenin pathway and impairing their lysosomal-mediated degradation.

Case report: Exceptional and durable response to Radium-223 and suspension of androgen deprivation therapy in a metastatic castration-resistant prostate cancer patient.

Despite the development of new therapies in the last few years, metastatic prostate cancer (PCa) is still a lethal disease. Radium-223 (Ra-223) is approved for patients with advanced castration-resistant prostate cancer (CRPC) with bone metastases and no visceral disease. However, patients' outcomes are heterogenous, and there is lack of validated predictive biomarkers of response, while biomarkers for early identification of patients who benefit from treatment are limited.

[Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP].

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results.