The Identification of CELSR3 and Other Potential Cell Surface Targets in Neuroendocrine Prostate Cancer.

Unlabelled: Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a significant subset of patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine prostate cancer (NEPC)]. On the basis of RNA sequencing (RNA-seq) data from a clinical cohort of tissue from benign prostate, locally advanced prostate cancer, metastatic castration-resistant prostate cancer and NEPC, we developed a multi-step bioinformatics pipeline to identify NEPC-specific, overexpressed gene transcripts that encode cell surface proteins. This included the identification of known NEPC surface protein CEACAM5 as well as other potentially targetable proteins (e.

Current and emerging therapies for Achondroplasia: The dawn of precision medicine.

Achondroplasia is a rare disease affecting bone growth and is caused by a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. In the past few years, there were multiple experimental drugs entering into clinical trials for treating achondroplasia including vosoritide, the first precision medicine approved for this indication. This perspective presents the mechanism of action, benefit, and potential mechanistic limitation of the drugs currently being evaluated in clinical trials for achondroplasia.

[Is diabetes a risk factor of urinary tract infection in patients with ureteral obstruction? Results of a retrospective study].

The goal of this retrospective study is to assess if diabetic patients are more likely to develop urinary tract infection (UTI) within the context of ureteral obstruction. 804 patients that had received an emergency treatment by double J placement for ureteral stone were selected between January 2004 and December 2014 at the Clinique Saint Pierre d'Ottignies, Ottignies-Louvain-La-Neuve,Belgium. They were divided in two groups : patients with UTI associated and the control group with the non infected ones.

Satisfaction and surgical outcomes in patients undergoing penile prosthesis implantation for drug-refractory erectile dysfunction: mid-term results in a single center French cohort.

Introduction: To investigate the mid-term results of penile prosthesis (PP) implantation in patients with erectile dysfunction (ED) from a "real-life" historic cohort in a French academic center.

Materials And Methods: All patients receiving an inflatable PP between 2004 and 2014 in our institution were included in this study. ED was assessed preoperatively using the IEEF-5 questionnaire.

N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer.

Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset of castration resistant prostate cancers become androgen receptor (AR) signaling-independent and develop neuroendocrine prostate cancer (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease and poor prognosis, are driven, in part, by aberrant expression of N-Myc, through mechanisms that remain unclear.

Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer.

Histologic transformation to small cell neuroendocrine prostate cancer occurs in a subset of patients with advanced prostate cancer as a mechanism of treatment resistance. Rovalpituzumab tesirine (SC16LD6.5) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) and was initially developed for small cell lung cancer.

A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers.

Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth.

Unusual Case of Testicular Tuberculosis.

We describe an unusual case of miliary tuberculous epididymo-orchitis following a BCG-therapy, mimicking malignancy at initial presentation. Genitourinary tuberculosis in a miliary pattern is rare and this case report emphasizes the importance of meticulous analysis of the patient's clinical history combined with imaging findings in order to ensure an adequate diagnosis and treatment.

N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer.

The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established.

A Computational Drug Repositioning Approach for Targeting Oncogenic Transcription Factors.

Mutations in transcription factor (TF) genes are frequently observed in tumors, often leading to aberrant transcriptional activity. Unfortunately, TFs are often considered undruggable due to the absence of targetable enzymatic activity. To address this problem, we developed CRAFTT, a computational drug-repositioning approach for targeting TF activity.

Ultrasonographic Pattern of Testicular Metastasis of Clear Cell Renal Cell Carcinoma with Pathological Correlation.

Two cases of testicular metastases of a clear cell renal cell carcinoma sharing a very similar ultrasonographic pattern are reported. The observed pattern - masses containing multiple tiny cyst-like areas - is very similar to that of a previously described ovarian metastasis of clear cell renal parenchymal tumor and can be explained by histopathologic features. Despite the small number of cases, this ultrasonographic pattern of testicular mass may be specific for metastasis of clear cell renal cell carcinoma origin.

The Ddx5 and Ddx17 RNA helicases are cornerstones in the complex regulatory array of steroid hormone-signaling pathways.

Estrogen and androgen receptors (ER and AR) play key roles in breast and prostate cancers, respectively, where they regulate the transcription of large arrays of genes. The activities of ER and AR are controlled by large networks of protein kinases and transcriptional coregulators, including Ddx5 and its highly related paralog Ddx17. The Ddx5 and Ddx17 RNA helicases are also splicing regulators.

Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness.

Both epigenetic and splicing regulation contribute to tumor progression, but the potential links between these two levels of gene-expression regulation in pathogenesis are not well understood. Here, we report that the mouse and human RNA helicases Ddx17 and Ddx5 contribute to tumor-cell invasiveness by regulating alternative splicing of several DNA- and chromatin-binding factors, including the macroH2A1 histone. We show that macroH2A1 splicing isoforms differentially regulate the transcription of a set of genes involved in redox metabolism.

Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor.

Ddx5 and ddx17 are two highly related RNA helicases involved in both transcription and splicing. These proteins coactivate transcription factors involved in cancer such as the estrogen receptor alpha, p53 and beta-catenin. Ddx5 and ddx17 are part of the splicing machinery and can modulate alternative splicing, the main mechanism increasing the proteome diversity.

Cotranscriptional exon skipping in the genotoxic stress response.

Pre-mRNA splicing is functionally coupled to transcription, and genotoxic stresses can enhance alternative exon inclusion by affecting elongating RNA polymerase II. We report here that various genotoxic stress inducers, including camptothecin (CPT), inhibit the interaction between Ewing's sarcoma proto-oncoprotein (EWS), an RNA polymerase II-associated factor, and YB-1, a spliceosome-associated factor. This results in the cotranscriptional skipping of several exons of the MDM2 gene, which encodes the main p53 ubiquitin ligase.

Estrogen regulation and physiopathologic significance of alternative promoters in breast cancer.

Alternative promoters (AP) occur in >30% protein-coding genes and contribute to proteome diversity. However, large-scale analyses of AP regulation are lacking, and little is known about their potential physiopathologic significance. To better understand the transcriptomic effect of estrogens, which play a major role in breast cancer, we analyzed gene and AP regulation by estradiol in MCF7 cells using pan-genomic exon arrays.