miR-143 Interferes with ERK5 Signaling, and Abrogates Prostate Cancer Progression in Mice

Abstract Background: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo. Results: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5) activity. We show here that ERK5 is a miR-143 target in prostate cancer. Conclusions: miR-143 is as a new target for prostate cancer treatment

Tumeurs urologiques de novo chez le transplanté rénal (à propos de 19 cas sur une série de 1045 transplantations rénales)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Morbidité du prélèvement rénal chez le donneur vivant et suivi à long terme

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Les greffes rénales itératives

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

La transplantation rénale à partir de donneur âgé (expérience et résultats du C.H.U. de Montpellier)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Prostate cancer in renal transplant recipients.

International audienceBACKGROUND: We conducted a retrospective multi-centre study to determine the characteristics of prostate cancer in renal transplant recipients (RTR) and to analyse the relation with immunosuppressive maintenance therapies. METHODS: Patients from 19 French transplant centres diagnosed with prostate cancer at least 1 year after kidney transplantation were included in this study. Data regarding demographics, kidney transplantation, prostate cancer and immunosuppressive treatment were analysed. RESULTS: Sixty-two patients met the eligibility criteria for this study. Thirty-eight patients (61.3%) received calcineurin inhibitors (CNI) and azathioprine (AZA) with or without steroids, twenty received CNI with or without steroids (32.2%) and four received CNI and mycophenolate mofetil (6.5%). Patients with CNI and AZA immunosuppressive therapy presented more high-stage cancer (T3 and T4) when compared to patients receiving CNI alone (47.5% versus 15%, respectively, P = 0.03). A non-significant increase in lymph node invasion was found in patients receiving CNI and AZA compared to patients receiving CNI alone (21% versus 5%, P = 0.16). In the multivariate analysis, the immunosuppressive regimen with CNI and AZA was the only independent risk factor for locally advanced disease (P = 0.007). CONCLUSION: Our results showed that RTR are at risk for early occurrence and for locally advanced prostate cancer, especially when they received a CNI and AZA maintenance immunosuppressive therapy

Troubles urinaires et sexuels après traitement du cancer localisé de la prostate : résultats d’une étude de population de moins de 65ans

International audienceIntroduction: An increasing number of patients with prostate cancer (PC) are diagnosed and treated. The aim of this study was to investigate urinary incontinence (UI) and sexual dysfunction (SD) two years after treatment for localized prostate cancer (PC).Methods: This study followed all cases of localized PC diagnosed between 2008 and 2009 in men aged≤65years old and still alive two years after treatment. In total, 437 men were recruited. Data were collected using a standardized questionnaire and by cross-checking with data from the cancer registry. Descriptive and comparative analyses were performed to evaluate persisting UI and SD at 2years.Results: At two years after treatment, UI was persistent in 48.8%; 41.2% had used urinary protections, and 39.2% had used at least 1 pad/day; 55.2% reported financial difficulties for purchasing protective pads. In total, 22.7% did not consult a specialist for UI. SD was persistent in 82.8%; 30.4% did not consult a specialist for SD. SD had a negative impact on the sex life of patients and their partners. After adjustment for cancer stage, prostatectomy was significantly associated with persisting UI and SD at two years.Conclusion: Two years after treatment, rates of persisting UI and/or SD remain high. Treatment by prostatectomy was significantly associated with an increased risk of persisting adverse effects at two years. The different toxicities between treatments should be presented to patients before initiating therapy in order to encourage the patient to contributed to shared treatment decision-making

Long-term Outcome of Renal Transplantation in Patients with Congenital Lower Urinary Tract Malformations: A Multicenter Study

International audienceRenal insufficiency can occur in patients with congenital lower urinary tract malformations (LUTM) even when managed during infancy. Data in the current literature concerning this subject remain sparse. The aim of this study was to report the feasibility and long-term results of renal transplantation during adulthood in patients with a congenital LUTM.Methods: A retrospective multicenter study from 3 French renal transplant centers was conducted, including 123 transplantations on 112 patients with LUTM (1996-2016). Graft survival, patient survival, and complications were analyzed. Results were stratified according to the underlying uropathy and the type of initial management during childhood or before transplantation.Results: In this study, patients suffering from posterior urethral valves (n = 49), spina bifida (n = 21), central neurogenic bladder (n = 13), bladder exstrophy (n = 14), prune belly syndrome (n = 12), Hinman syndrome (n = 6), urogenital sinus (n = 4), and other pathologies (n = 4) were included. The mean age at transplantation was 32.1 years old (±11.2). The mean follow-up period was 7.2 years. Patient survival at 1, 5, 10, and 15 years was 97.4%, 93.0%, 89.4%, and 80.0%, respectively. Graft survival at 1, 5, 10, 15, and 20 years was 96.6%, 87.6%, 77.3%, 60.6%, and 36.4%, respectively. Enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis (P = 0.02). There was no difference in graft survival when transplantation was performed on an enterocystoplasty or urinary diversions compared with a native bladder, provided a well-conducted bladder management.Conclusions: Even though enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute graft pyelonephritis, patient and graft survival rates in LUTM at 10 years were similar to other kidney transplantations on native bladders

Les facteurs pronostiques du cancer du rein. [Prognostic factors in renal cell carcinoma.]

International audienceIdentification of prognostic factors in renal cell carcinoma is very important today for three goals: providing patient information, giving appropriate treatments and selecting patients for adapted treatment schedules as well as new clinical trials. Prognostic factors in RCC include: anatomical (TNM classification), histological (Fuhrmann grade and histological subtype), clinical (symptoms and performance status) and molecular factors. For improving predicative accuracy of prognostic systems such as the TNM classification, new prognostic algorithms or nomograms have been designed combining independent prognostic variables. UISS and SSIGN are the 2 most effective prognostic systems within localized RCC. In metastatic disease, the two main systems that have been used for predicting response to immunotherapy are the model of the French Group of Immunotherapy and the Motzer model. With the arrivals of new molecular factors, these systems will perhaps have to evaluate: these new systems will require further validation as part of large prospective clinical trials