E. Chabannes

Differential regulation of vascular endothelial growth factor expression by peroxisome proliferator-activated receptors in bladder cancer cells

The growth of any solid tumor depends on angiogenesis. Vascular endothelial growth factor (VEGF) plays a prominent role in vesical tumor angiogenesis regulation. Previous studies have shown that the peroxisome proliferator-activated receptor γ (PPARγ) was involved in the angiogenesis process. Here, we report for the first time that in two different human bladder cancer cell lines, RT4 (derived from grade I tumor) and T24 (derived from grade III tumor), VEGF (mRNA and protein) is differentially up-regulated by the three PPAR isotypes. Its expression is increased by PPARα, β, and γ in RT4 cells and only by PPARβ in T24 cells via a transcriptional activation of theVEGF promoter through an indirect mechanism. This effect is potentiated by an RXR (retinoid-X-receptor), selective retinoid LG10068 providing support for a PPAR agonist-specific action on VEGF expression. While investigating the downstream signaling pathways involved in PPAR agonist-mediated up-regulation of VEGF, we found that only the MEK inhibitor PD98059 reduced PPAR ligand-induced expression of VEGF. These data contribute to a better understanding of the mechanisms by which PPARs regulate VEGF expression. They may lead to a new therapeutic approach to human bladder cancer in which excessive angiogenesis is a negative prognostic factor.

Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility

OBJECTIVE To determine whether expansion of CAG repeats in exon 1 of the androgen receptor is correlated with impaired spermatogenesis in patients with male idiopathic infertility. DESIGN A retrospective study. SETTING Medical school in Besançon, France. PARTICIPANT(S) Thirty-seven infertile patients with azoospermia or oligospermia and 50 fertile controls. INTERVENTION(S) History, physical, hormonal assays, semen analysis, and collection of blood samples in order to study the androgen receptors gene. MAIN OUTCOME MEASURE(S) Blood samples were collected from each infertile patient and control. The length of the CAG repeat segment was evaluated by using polymerase chain reaction (PCR) electrophoresis in exon 1 and PCR single-strand conformation polymorphism in exons 2-8. RESULT(S) The mean length of the CAG repeats was significantly different between infertile and fertile patients (23.91 +/- 0.5 vs. 22.20 +/- 0.4). No mutation was detected in exons 2-8 of the androgen receptor gene in infertile patients. CONCLUSION(S) Expansion of the CAG repeat segment of the androgen receptor is correlated with male idiopathic infertility. The number of CAG repeats may therefore have a modulatory effect on normal androgen receptor function.

Ureterorenoscopy with Holmium-Yttrium-Aluminum-Garnet Fragmentation Is a Safe and Efficient Technique for Stone Treatment in Patients with a Body Mass Index Superior to 30 kg/m2

PURPOSE The aim of the study was to analyze results and morbidity after flexible ureterorenoscopy in patients with a body mass index (BMI) >30 kg/m(2) and to compare with results obtained in a large cohort of nonobese patients. PATIENTS AND METHODS We conducted a retrospective study including all flexible ureterorenoscopy performed for stone retrieval in our institution between January 2004 and December 2008. During the study period, 224 procedures were performed, of which 18 had to be excluded because of missing BMI data. Thus, a total of 206 procedures were included in the final analysis (34 in 29 obese patients, 172 in 149 nonobese patients). Characteristics of the patients (age, BMI, previous treatment), stones (nature, location, number), and procedures (operating time, morbidity, outcome) were analyzed. Success was defined as clear imaging (completely stone free) on renal tomography and ultrasonography at 1, 3, and 6 months follow-up. RESULTS Mean BMI was 34±0.6 kg/m(2) in obese patients (OP) and 24±0.2 kg/m(2) in nonobese patients (NOP). Mean stone size, location, and composition were not significantly different between groups. Operative time was also similar in OP and NOP (102.5±6.1 min vs 103±3.4 min, P=NS). The rate of minor complications (fever, hematuria, flank pain) was similar in OP (11.8%) and NOP (11.4%). No major complication necessitating prolonged hospital stay or new surgical procedure was observed. The overall stone-free rate was not significantly different between OP (79.4%) and NOP (70%). CONCLUSION Flexible ureterorenoscopy is an appropriate treatment for use in obese patients and achieves excellent stone-free rates with low morbidity.

Protein kinase C signalling pathway is involved in the regulation of vascular endothelial growth factor expression in human bladder transitional carcinoma cells

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor associated with the growth and metastasis of various cancers and plays a prominent role in vesical angiogenesis regulation. In this study, we investigated the effect of the phorbol 12-myristate 13-acetate (PMA) on the expression of VEGF in human bladder transitional carcinoma cells (RT4). RT4 cells expressed three VEGF isoforms (VEGF(189), VEGF(165), VEGF(121)). PMA increased VEGF mRNA expression time-dependently with a peak at 4 h. PMA increased the half-life of VEGF mRNA. The amount of VEGF protein in conditioned media was increased by PMA in a dose-dependent manner with a maximal effect at 10(-7) M. Staurosporine and calphostin C (PKC inhibitors) decreased PMA-induced VEGF mRNA expression as opposed to protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. Thus, in RT4 cells, VEGF expression is up-regulated by PMA via the PKC signalling pathway and according to a posttranscriptional mechanism.

Article originalFiabilité des biopsies prostatiques pour l’étude de la topographie tumorale dans le cancer de prostateAccuracy of prostate biopsies to evaluate tumor location in prostate cancer☆

INTRODUCTION The therapeutic approach of prostate cancer depends mainly on pathological criteria obtained through prostate biopsy. The low accuracy of prostate biopsy for Gleason grade determination is well known but its accuracy for bilateral or multifocal tumor has not been evaluated. The goal of this study was to assess the concordance between prostate biopsy and whole prostate specimen obtained after radical prostatectomy especially for bilateral and/or multifocal tumor. METHODS We retrospectively compared the pathological results of prostate biopsy cores to the prostate specimen in patients who underwent radical prostatectomy in our department between the 01/01/1999 and the 31/12/2008. The criteria analyzed were the Gleason score, tumor bilaterality or multifocality. The impact of the number of prostate biopsy cores was also analyzed. RESULTS Two hundred and five complete histological records were studied. Regarding the Gleason score overall concordance was 55%. In 38%, prostate biopsies downgraded the Gleason score. This concordance decreased with tumor differentiation (90.6% for Gleason 6 vs. 31% for Gleason greater than 7). For the tumor bilaterality, 78% of cancers affected both lobes at the definitive specimen analysis while only 49% were bilateral at prostate biopsies, achieving a concordance of 61%. Multifocal disease was observed in 36% at definitive pathology analysis with low concordance with prostate biopsies (36%). The number of biopsies increased the concordance for the Gleason score (60 to 81% for Gleason 7 and from 28 to 50% for Gleason greater than 7) and tumor location (44 to 70%). CONCLUSION Pathological criteria and tumor mapping obtained from prostate biopsies were not very reliable especially when the tumor was poorly differentiated. An increased number of prostate biopsy core improved the sensitivity and specificity for the Gleason score diagnostic and of the tumor mapping.

Fiabilité des biopsies prostatiques pour l'étude de la topographie tumorale dans le cancer de prostate

INTRODUCTION The therapeutic approach of prostate cancer depends mainly on pathological criteria obtained through prostate biopsy. The low accuracy of prostate biopsy for Gleason grade determination is well known but its accuracy for bilateral or multifocal tumor has not been evaluated. The goal of this study was to assess the concordance between prostate biopsy and whole prostate specimen obtained after radical prostatectomy especially for bilateral and/or multifocal tumor. METHODS We retrospectively compared the pathological results of prostate biopsy cores to the prostate specimen in patients who underwent radical prostatectomy in our department between the 01/01/1999 and the 31/12/2008. The criteria analyzed were the Gleason score, tumor bilaterality or multifocality. The impact of the number of prostate biopsy cores was also analyzed. RESULTS Two hundred and five complete histological records were studied. Regarding the Gleason score overall concordance was 55%. In 38%, prostate biopsies downgraded the Gleason score. This concordance decreased with tumor differentiation (90.6% for Gleason 6 vs. 31% for Gleason greater than 7). For the tumor bilaterality, 78% of cancers affected both lobes at the definitive specimen analysis while only 49% were bilateral at prostate biopsies, achieving a concordance of 61%. Multifocal disease was observed in 36% at definitive pathology analysis with low concordance with prostate biopsies (36%). The number of biopsies increased the concordance for the Gleason score (60 to 81% for Gleason 7 and from 28 to 50% for Gleason greater than 7) and tumor location (44 to 70%). CONCLUSION Pathological criteria and tumor mapping obtained from prostate biopsies were not very reliable especially when the tumor was poorly differentiated. An increased number of prostate biopsy core improved the sensitivity and specificity for the Gleason score diagnostic and of the tumor mapping.