References of "Waltregny, David"
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See detailHistone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility
Waltregny, David ULg; Glenisson, Wendy; Tran, Syv Li et al

in FASEB Journal (2005), 19(8), 966-968

Although originally characterized as nuclear enzymes controlling the stability of nucleosomes, histone deacetylases (HDACs) may also exert their activity within the cytosol. Recently, we have demonstrated ... [more ▼]

Although originally characterized as nuclear enzymes controlling the stability of nucleosomes, histone deacetylases (HDACs) may also exert their activity within the cytosol. Recently, we have demonstrated that HDAC8, a class I HDAC, is a novel, prominently cytosolic marker of smooth muscle differentiation. As HDAC8 displays a striking stress fiber-like pattern of distribution and is coexpressed in vivo with smooth muscle alpha-actin (alpha-SMA) and smooth muscle myosin heavy chain, we have explored the possible participation of this HDAC in smooth muscle cytoskeleton regulation. Cell fractionation assays performed with primary human smooth muscle cells (HSMCs) showed that HDAC8, in contrast to HDAC1 and HDAC3, was enriched in cytoskeleton-bound protein fractions and insoluble cell pellets, suggesting an association of HDAC8 with the cystoskeleton. Coimmunoprecipitation experiments using HSMCs, NIH-3T3 cells, and human prostate tissue lysates further demonstrated that HDAC8 associates with alpha-SMA but not with beta-actin. HDAC8 silencing through RNA interference strongly reduced the capacity of HSMCs to contract collagen lattices. Mock transfections had no effect on HSMC contractily, and transfections with small interfering RNAs (siRNAs) specific for HDAC6, a cytosolic HDAC that functions as an alpha-tubulin deacetylase, resulted in a weak contraction inhibition. Although mock- and HDAC6 siRNA-transfected HSMCs showed no noticeable morphological changes, HDAC8 siRNA-transfected HSMCs displayed a size reduction with diminished cell spreading after replating. Altogether, our findings indicate that HDAC8 associates with the smooth muscle actin cytoskeleton and may regulate the contractile capacity of smooth muscle cells. [less ▲]

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See detailHistone deacetylase HDAC8 associates with smooth muscle alpha–actin and is essential for smooth muscle cell contractility
Glénisson, Wendy; Waltregny, David ULg; Tran, Syv Li et al

Conference (2005)

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See detailAbnormalities of smooth muscles in human GI motility disorders revealed by novel immunomarkers
Wedel, Theo; van Eys, G.; Glénisson, Wendy et al

Poster (2005)

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See detailRéponse à : Chirurgie de l'incontinence urinaire a l'effort feminine par voie transobturatrice: dehors dedans ou dedans dehors? etude anatomique comparative.
de Leval, Jean ULg; Bonnet, Pierre ULg; Waltregny, David ULg et al

in Progrès en Urologie : Journal de l'Association Française d'Urologie et de la Société Française d'Urologie (2005), 15(6), 1161-2

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See detailExpression of dentin sialophosphoprotein in human prostate cancer and its correlation with tumor aggressiveness
Waltregny, David ULg; Chaplet, Michael; Detry, Cédric et al

Conference (2005)

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See detailDentin sialophosphoprotein expression correlates with progression markers in human prostate cancer
Chaplet, Michael; Waltregny, David ULg; Detry, Cédric et al

Conference (2005)

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See detailLignées de carcinome prostatique et apoptose: état de la question
Califice, Stéphane ULg; Waltregny, David ULg; Castronovo, Vincenzo ULg et al

in Revue Médicale de Liège (2004), 59(12), 704-10

Prostate cancer is a major pathology in industrialized countries. Tumor growth usually results from increased cell proliferation, conjugated with an inhibition of programmed cell death (apoptosis). In ... [more ▼]

Prostate cancer is a major pathology in industrialized countries. Tumor growth usually results from increased cell proliferation, conjugated with an inhibition of programmed cell death (apoptosis). In this paper, after a short description of the apoptotic mechanisms and their methods of investigation, we review the present knowledge of the implication of different molecular actors in the regulation of apoptosis in prostate cancer cells. This review notably summarizes the present knowledge of the (de)regulation of the effects of androgens, p53, Bcl-2, Bcl-xL, Bax, Akt, PTEN, Par-4, clusterine, caspases and NF-kappaB in prostate adenocarcinoma cell lines and provides an appraisal of their therapeutic potential. A better knowledge of the apoptotic pathways in these cells could indeed allow the development of new selective and effective anti-cancer strategies. [less ▲]

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See detailExpression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues
Waltregny, David ULg; de Leval, Laurence ULg; Glenisson, Wendy et al

in American Journal of Pathology (2004), 165(2), 553-564

Histone deacetylases (HDACs) were originally identified as nuclear enzymes involved in gene transcription regulation. Until recently, it was thought that their activity was restricted within the nucleus ... [more ▼]

Histone deacetylases (HDACs) were originally identified as nuclear enzymes involved in gene transcription regulation. Until recently, it was thought that their activity was restricted within the nucleus, with histones as unique substrates. The demonstration that specific HDACs deacetylate nonhistone proteins, such as p53 and alpha-tubulin, broadened the field of activity of these enzymes. HDAC8, a class I HDAC, is considered to be ubiquitously expressed, as suggested by results of Northern blots performed on tissue RNA extracts, and transfection experiments using various cell lines have indicated that this enzyme may display a prominent nuclear localization. Using immunohistochemistry, we unexpectedly found that, in normal human tissues, HDAC8 is exclusively expressed by cells showing smooth muscle differentiation, including visceral and vascular smooth muscle cells, myoepithelial cells, and myofibroblasts, and is mainly detected in their cytosol. These findings were confirmed in vitro by nucleo-cytoplasmic fractionation and immunoblot experiments performed on human primary smooth muscle cells, and by the cytosolic detection of epitope-tagged HDAC8 overexpressed in fibroblasts. Immunocytochemistry strongly suggested a cytoskeleton-like distribution of the enzyme. Further double-immunofluorescence staining experiments coupled with confocal microscopy analysis showed that epitope-tagged HDAC8 overexpressed in murine fibroblasts formed cytoplasmic stress fiber-like structures that co-localized with the smooth muscle cytoskeleton protein smooth muscle alpha-actin. Our works represent the first demonstration of the restricted expression of a class I HDAC to a specific cell type and indicate that HDAC8, besides being a novel marker of smooth muscle differentiation, may play a role in the biology of these contractile cells. [less ▲]

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See detailNovel surgical technique for the treatment of female urinary incontinence: Transobturator vaginal tape inside-out
de Leval, Jean ULg; Bonnet, Pierre ULg; Reul, Olivier ULg et al

in European Urology Supplements (2004, February), 3(2), 226

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See detailNovel surgical technique for the treatment of female stress urinary incontinence: Transobturator vaginal tape inside-out
de Leval, Jean ULg; Bonnet, Pierre ULg; Reul, Olivier ULg et al

Poster (2004)

Introduction and Objective: To describe a new, simple surgical technique for the treatment of female stress urinary incontinence (SUI) and to evaluate its feasibility. Methods: We have developed a novel ... [more ▼]

Introduction and Objective: To describe a new, simple surgical technique for the treatment of female stress urinary incontinence (SUI) and to evaluate its feasibility. Methods: We have developed a novel surgical treatment of SUI, the transobturator inside-out tension-free urethral suspension, which uses specifically designed surgical tools: a pair of stainless steel helical passers, two plastic tubes with a pointed distal end and one guide. Using these instruments, a synthetic tape is passed from underneath the urethra, through the obturator foramens, towards the thighs, without entering the pelvic region at any time during the procedure. The tubes bear a lateral opening, which allows the insertion of the helical passer into its lumen. The proximal end of each tube is attached to a non-absorbable synthetic tape. The guide acts as a shoe-horn to ease the introduction of the tubes assembled onto the helical passers from the perineal space through the obturator foramen. After perforation of the obturator membrane, a rotational movement of the helical passer around the upper part of ischio-pubic ramus allows the exit of the pointed tip of the tube and, further, of the tape at the level of the thigh on either side. The tape is positioned without tension under the junction between mid and distal urethra. Results: The procedure was carried out in 210 consecutive patients (mean age = 62 years) using the same operative protocol in all case subjects, independently of the patient’s size and weight. Mean operative time was 14 min (range = 6 to 20) in case of isolated SUI treatment. No bladder or urethra injury and no vascular (hematoma or bleeding) or neurological complication were observed. Conclusions: The results of this study indicate that our novel transobturator inside-out surgical technique for treating SUI is feasible, accurate, and quick. This technique avoids damage to the urethra and bladder and, therefore, makes cystoscopy not necessary. Further prospective studies are currently ongoing to determine the efficacy of our new surgical approach for treating SUI. [less ▲]

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See detailInside-out transobturator vaginal tape (TVT-O): Short-term results of a prospective study
Waltregny, David ULg; Reul, Olivier ULg; Bonnet, Pierre ULg et al

in International Urogynecology Journal & Pelvic Floor Dysfunction (2004)

Hypothesis / aims of study The aim of this study was to prospectively evaluate the efficacy of the TVT-O inside-out procedure for the treatment of female stress urinary incontinence (SUI). Study design ... [more ▼]

Hypothesis / aims of study The aim of this study was to prospectively evaluate the efficacy of the TVT-O inside-out procedure for the treatment of female stress urinary incontinence (SUI). Study design, materials and methods From March 2003 through September 2003, 53 patients with clinical evidence of SUI participated in this prospective clinical trial. Preoperative evaluation included complete history, physical examination, multichannel urodynamics, urine analysis, and cystoscopy. None of the patients presented the following exclusion criteria: post-void residual volume (PVR) ≥ 100 cc, detrusor overactivity or acontractility, contraindication to anesthesia, pregnancy, neurological pathology, or active urinary or vaginal infection. All patients met the following inclusion criteria: age > 25 and < 85 years, clinically demonstrated SUI, positive Ulmsten test, and maximum cystometric capacity ≥ 300 mL. In all patients, a sub-urethral tape (Gynecare®) was inserted by one single surgeon via an inside-out transobturator approach (TVT-O), as previously described (1). Evaluation of SUI, urgency/urge incontinence, daytime urinary frequency/nocturia, and lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction/retention was carried out using the Measurement of Urinary Handicap scale questionnaire (2). The importance of urinary incontinence was assessed with a visual analog scale graded from 0 to 10. Quality of life (QoL) assessment was performed using the validated Ditrovie self-administered questionnaire. Outpatient follow-up was perfomed at 1 and 6 months, and every 6 months thereafter. Follow-up evaluation included physical examination with a stress test, uroflowmetry, PVR, and symptom, visual analog, and QoL scales scoring. Cure was defined as no leakage based on both symptom scale scoring and physical examination. Improvement was defined as at least a 50% decrease in symptoms based on the questionnaire’s evaluation. Chart review was conducted by a physician not associated with the surgical procedure. The specific protocol used in this study was approved by the Medical Ethics committee of our Institution. All patients had given their written informed consent. Methods, defintions,and units conform to the standards recommended by the ICS. Results Mean age of the patients was 61.2 years (36 to 80). Of the 53 patients, 20 had undergone previous pelvic surgery. Forty-eight patients suffered from SUI. Five patients did not complain of SUI but had clinical evidence of SUI after reduction of pelvic organ prolapse (POP) during vaginal examination. The TVT-O procedure was associated with POP cure (performed before TVT-O) in 12 patients. Maximal urethral closure pressure was < 30 cm H20 in 6 patients. Follow-up time was ≥ 6 months in all women (max = 12.5; mean = 8). A total of 33 and 20 women received spinal and general anesthesia, respectively. Intraoperative blood loss was < 100 cc in all cases. No vaginal wall, urethral, or bladder perforation was encountered. No hematoma, neurological complication, fistula, vaginal or urethral erosion, or tape rejection was observed. Some patients reported pain symptoms, directly after the procedure, mainly located in the thigh regions (either uni- or bilaterally). Pain was always mild, never requiring opioid antalgics. No patient complained of persistent pain; indeed, pain had completely vanished within the first post-operative month in all cases. At the latest follow-up visit, PVR was < 100 cc and max flow rate was ≥ 10 mL/sec in 49 (92.4%) and 39 (73.6%) patients, respectively. One patient underwent an immediate tape release procedure for complete retention 2 days after TVT-O. Thereafter, the patient had no PVR and was completely dry. The tape was sectioned in 2 patients for chronic retention and/or urgency associated with bladder outlet obstruction, 4 and 7 months after the operation. Based on the SUI questionnaire evaluation and physical examination, 50 (94.3%) patients were cured. SUI symptoms had improved in 1 patient and had not changed in another. One patient with POP not complaining of SUI preoperatively (but with clinically demonstrated SUI following POP reduction) developed SUI after POP cure associated with TVT-O. Analysis of the urgency questionnaire’s results revealed that among the 53 patients, 32 did not complain of any urgency before the operation. Of these 32 patients, 3 patients developed de novo urgency, with one of them requiring tape sectioning because of obstruction-associated urge incontinence. Among the 21 patients with preoperative urge symptoms, 15 of them reported disappearance of urgency after the procedure. Urge symptoms were unchanged in the remaining 6 patients. Daytime frequency/nocturia symptoms scale scoring showed that 4 patients had a worsening of these symptoms while all other patients were either improved or unchanged. LUTS suggestive of bladder outlet obstruction/retention appeared or worsened in 3 patients, amongst which the 2 patients who required tape sectioning. These symptoms were unchanged or decreased (mainly in patients with associated POP cure) in all other patients. Analysis of the urinary incontinence visual analog and QoL scale scores demonstrated that the majority of patients reported disappearance of urinary leakage together with significant improvement of their QoL (Figures 1 and 2). Interpretation of results As already suggested by the results of a recent feasibility study (1), TVT-O appears to be associated with a minimal risk of peri-operative complications. Indeed, in our present prospective study, no injury to the bladder, vagina, or urethra was encountered and we have not observed any vascular, digestive or neurological complication. Our data suggest that TVT-O is associated with high objective and subjective SUI cure rates and a low incidence of post-operative complications. Longer follow-up times are required to determine the long-term efficacy of TVT-O. Concluding message The short term results of this prospective study suggest that TVT-O is a safe and efficient surgical procedure for the treatment of female SUI. References 1. Novel surgical technique for the treatment of female stress urinary incontinence: Transobturator vaginal tape inside-out. Eur Urol 44:724-730, 2003 2. Elaboration and validation of a specific quality of life questionnaire for urination urgency in women. Prog Urol 7:56-63, 1997 [less ▲]

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See detailScreening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class IHDAC profiles between epithelial and stromal cells
Waltregny, David ULg; North, Brian; Van Mellaert, Frank et al

in European Journal of Histochemistry (2004), 48(3, Jul-Sep), 273-290

Histone deacetylases (HDACs) represent a large family of enzymes identified as key regulators of nucleosomal histone acetylation, a major epigenetic event that controls eukaryotic gene transcription ... [more ▼]

Histone deacetylases (HDACs) represent a large family of enzymes identified as key regulators of nucleosomal histone acetylation, a major epigenetic event that controls eukaryotic gene transcription. Inappropriate deacetylation mediated by HDACs has been associated with profound alterations in cellular biology. We have thus hypothesized that an altered HDAC expression may favor cancer development/progression. To test this possibility, we have sought to screen the expression profiles of several class I and class 11 HDACs (HDAC1-8) in DU-145, PC-3 and LNCaP human prostate cancer cell lines as well as in matched malignant and nonmalignant prostate tissues by use of real time RT-PCR, immunoblot and immunohistochemistry. All HDAC transcripts tested were detected at various levels in all prostate cancer cell lines and tissue samples analyzed. In prostate tissues, the abundance of HDAC1 protein, which was exclusively expressed in the cell nucleus, was similar in normal and malignant epithelial cells, but was usually lower in stromal cells. Unexpectedly, HDAC8, another class I HDAC, was not detected in epithelial cells but was uniquely expressed in the cytoplasm of stromal cells, HDAC5, a class II HDAC involved in myogenesis, was not detected in the tissues. Altogether, our findings indicate that epithelial and stromal cells exhibit distinct class I HDAC expression profiles, and the abundance of HDAC1 is not altered in human prostate cancer. In addition, our observations are the first to demonstrate the prominently cytosolic distribution of a class I HDAC, HDAC8. [less ▲]

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See detailNovel markers reveal focal abnormalities of smooth muscles in human gastrointestinal motility disorders
Wedel, Theo; van Eys, G.; Waltregny, David ULg et al

Conference (2004)

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See detailInside-out transobturator vaginal tape (TVT-O): Short-term results of a prospective study
Waltregny, David ULg; Reul, Olivier ULg; Bonnet, Pierre ULg et al

in Neurourology and Urodynamics (2004), 23(5-6), 428-429

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See detailLa déacétylase d’histones HDAC8 est un nouveau marqueur de différenciation des cellules musculaires lisses
Glénisson, Wendy; de Leval, Laurence ULg; Tran, Syv Li et al

Conference (2004)

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