Wegener's Granulomatosis: A Rare Cause of Hydronephrosis

A seventy-one-year-old woman was hospitalized at our institution for a right-sided “renal colic” associated with an infectious background. Alithiasic ureterohydronephrosis was diagnosed by imaging. A urinary diversion was thus performed using a double J endoureteral stent. The etiologic assessment of the hydronephrosis showed the presence of a periureteral mass that caused extrinsic ureteral compression. After surgical excision of the ureteral lesion, the Wegener's granulomatosis diagnosis was established. This report is the clinical description of a case of “atypical” Wegener's granulomatosis revealed by the onset of a ureteral disease mimicking a neoplastic process

The Antidiabetic Drug Ciglitazone Induces High Grade Bladder Cancer Cells Apoptosis through the Up-Regulation of TRAIL

International audienceBACKGROUND: Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1) and p27(Kip1) in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. CONCLUSIONS/SIGNIFICANCE: Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers

Insights on distinct pathways of thiazolidinediones (PPARgamma ligand)-promoted apoptosis in TRAIL-sensitive or -resistant malignant urothelial cells.

International audienceThiazolidinediones, including rosiglitazone and troglitazone, are insulin-sensitizing drugs and high-affinity ligands for the peroxisome proliferator-activated receptor gamma (PPARgamma). Apart from their antidiabetic activity, these molecules possess antitumor properties. We investigated their potential apoptotic effects on RT4 (derived from a well-differentiated Grade I papillary tumor) and T24 (derived from an undifferentiated Grade III carcinoma) bladder cancer cells. Rosiglitazone induced G2/M or G0/G1 phase cell cycle arrest in RT4 and T24 cells, respectively. Only troglitazone triggered apoptosis via extrinsic and intrinsic pathways in both cell lines. Interestingly, rosiglitazone amplified TRAIL-induced apoptosis in TRAIL-sensitive RT4 cells or let TRAIL-resistant T24 cells to respond to TRAIL. Thiazolidinediones acted through PPARgamma activation-independent mechanisms. The underlying mechanisms involved for the first time in cancer cells the upregulation of soluble and/or membrane-bound TRAIL. This was associated with increased cell surface death receptor 5 expression and c-FLIP and survivin downregulation, mediated in part through proteasome-dependent degradation in troglitazone-promoted cell death. Therefore, the combination of rosiglitazone and TRAIL could be clinically relevant as chemopreventive or therapeutic agents for the treatment of TRAIL-resistant high-grade urothelial cancers

[Conservative management of Corynebacterium urealyticum encrusted cystitis]

International audienceThe authors report the case of a 75-year-old patient who developed Corynebacterium urealyticum encrusted cystitis six months after open prostatectomy, complicated by vesicocutaneous fistula, which required bladder catheterization for several days. Encrustation of the bladder wall induced marked bilateral ureteropyelocaliceal dilatation without renal failure. Medical treatment by antibiotic therapy and oral acidification of the urine allowed regression of the plaques and resolution of the dilatation

[Conservative management of Corynebacterium urealyticum encrusted cystitis]

International audienceThe authors report the case of a 75-year-old patient who developed Corynebacterium urealyticum encrusted cystitis six months after open prostatectomy, complicated by vesicocutaneous fistula, which required bladder catheterization for several days. Encrustation of the bladder wall induced marked bilateral ureteropyelocaliceal dilatation without renal failure. Medical treatment by antibiotic therapy and oral acidification of the urine allowed regression of the plaques and resolution of the dilatation

[Atypical cysts and risk of renal cancer: value and danger of the Bosniak classification]

International audienceOBJECTIVE: The objective of this study was to devaluate the risk of renal cancer in patients with atypical renal cysts and to compare radiological data used to establish the Bosniak classification with clinical or histological data. MATERIAL AND METHOD: We performed a retrospective study on 37 patients managed in our establishment for atypical renal cyst between January 1995 and April 2003. The following criteria were analysed: gender, age, clinical examination and circumstances of discovery imaging findings, Bosniak classification, treatment modalities and follow-up data. These criteria were compared in two populations according to the presence or absence of associated renal cancer. RESULTS: In this series, 6 patients presented a stage II cyst. No cancer was demonstrated in this group of cysts. Ten patients presented a stage IIF cyst and 2 cancers were detected in this group (i.e. 20%). Fourteen patients presented a stage III cyst, with a cancer in 4 cases (30%) and 7 patients presented a stage IV cyst with 6 cancers (86%). CONCLUSION: The Bosniak classification is currently the reference classification fr the diagnosis of cystic diseases of the kidney. Although stages I and II (cysts with minor changes not requiring surveillance) and stages III and IV (suspicious malignant cysts which require surgical exploration) raise few diagnostic problems, stage IIF (indeterminate cyst requiring radiological surveillance) may be the source of diagnostic difficulties with a risk of missing an associated renal cancer

[Urologic cancer in patients with kidney transplantation]

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Molecular and nanoscale evaluation of N‑cadherin expression in invasive bladder cancer cells under control conditions or GW501516 exposure

International audienceN-cadherin is a transmembrane glycoprotein expressed by mesenchymal origin cells and is located at the adherens junctions. It regulates also cell motility and contributes to cell signaling. In previous studies, we identified that its anomalous expression in bladder carcinoma was a tumor progression marker. A pharmacological approach to inhibit N-cadherin expression or to block its function could be relevant to prevent disease progression and metastasis development. The morphological exploration of T24 invasive bladder cancer cells by atomic force microscopy (AFM) revealed a spindle-like shape with fibrous structures. By engaging force spectroscopy with AFM tip functionalized with anti-E or anti-N-cadherin antibodies, results showed that T24 cells expressed only N-cadherin as also demonstrated by Western blotting and confocal microscopy. For the first time, we demonstrated by RTqPCR and Western blotting analyses that the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) agonist GW501516 significantly decreased N-cadherin expression in T24 cells. Moreover, high non-cytotoxic doses of GW501516 inhibited confluent T24 cell wound healing closure. By using AFM, a more sensitive nanoanalytical method, we showed that the treatment modified the cellular morphology and diminished N-cadherin cell surface coverage through the decreasing of these adhesion molecule-mediated interaction forces. We observed a greater decrease of N-cadherin upon GW501516 exposure with AFM than that detected with molecular biology techniques. AFM was a complementary tool to biochemical techniques to perform measurements on living cells at the nanometer resolution level. Taken together, our data suggest that GW501516 could be an interesting therapeutic strategy to avoid bladder cancer cell spreading through N-cadherin decrease

[Urologic cancer in patients with kidney transplantation]

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