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Träfflista för sökning "WFRF:(Joniau Steven) "

Sökning: WFRF:(Joniau Steven)

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1.
  • Dadaev, Tokhir, et al. (författare)
  • Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.
  • 2018
  • Ingår i: ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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  • Castiglione, Fabio, et al. (författare)
  • Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 70:6, s. 1032-1041
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p
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  • Castiglione, Fabio, et al. (författare)
  • Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/IRatio in a Rat Model of Chronic Peyronies Disease
  • 2019
  • Ingår i: SEXUAL MEDICINE. - : ELSEVIER SCI LTD. - 2050-1161. ; 7:1, s. 94-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Previous studies have shown that the injection of adipose tissue-derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of Peyronies disease (PD) prevents the development of fibrosis. Aim: To investigate, using an animal model, whether local injection of human ADSCs (hADSCs) can alter the degree of fibrosis in the chronic phase of PD. Methods: 27 male, 12-week-old rats were divided into 3 equal groups: sham, PD without treatment, and PD treated with hADSCs 1 month after disease induction. Sham rats underwent 2 injections of vehicle into the TA 1 month apart. PD rats underwent transforming growth factor beta 1 (TGF beta 1) injection and injection of vehicle 1 month later. PD-hADSC rats underwent TGF beta 1 injection followed by 1 million hADSCs 1 month later. 1 week after treatment, n = 3 animals/group were euthanized, and the penises were harvested for quantitative polymerase chain reaction. 1 month after treatment, the other animals, n = 6 per group, underwent measurement of intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of the cavernous nerve. After euthanasia, penises were again harvested for histology and Western blot. Main Outcome Measure: The primary outcome measures included (a) gene expression at one week post-injection; (b) measurement of ICP/MAP upon cavernous nerve stimulation as a measure of erectile function; (c) elastin, collagen I and III protein expression; and (d) Histomorphometric analysis of the penis. Means where compared by analysis of variance (ANOVA) followed by a Student-Newman-Keuls test for post hoc comparisons or Mann-Whitney test when applicable. Results: No significant difference was noted in ICP or ICP/MAP in response to cavernous nerve electrostimulation between the 3 groups at 2.5, 5, and 7.5 V (Pamp;gt;.05 for all voltages). PD animals developed tunical and subtunical areas of fibrosis with a significant upregulation of collagen III protein. The collagen III/I ratio was higher in the PD (4.6 +/- 0.92) group compared with sham (0.66 +/- 0.18) and PD-hADSC (0.86 +/- 0.06) groups (Pamp;lt;.05) These fibrotic changes were prevented when treated with hADSCs. Compared with PD rats, PD-hADSC rats demonstrated a decreased expression of several fibrosis-related genes. Conclusion: Injection of hADSCs reduces collagen III expression in a rat model of chronic PD. Copyright (C) 2018, International Society for Sexual Medicine. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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6.
  • Castiglione, Fabio, et al. (författare)
  • Intratunical Injection of Human Adipose Tissue–Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease
  • 2019
  • Ingår i: Sexual Medicine. - : Elsevier Inc.. - 2050-1161. ; 7:1, s. 94-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Previous studies have shown that the injection of adipose tissue–derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of Peyronie's disease (PD) prevents the development of fibrosis. Aim: To investigate, using an animal model, whether local injection of human ADSCs (hADSCs) can alter the degree of fibrosis in the chronic phase of PD. Methods: 27 male, 12-week-old rats were divided into 3 equal groups: sham, PD without treatment, and PD treated with hADSCs 1 month after disease induction. Sham rats underwent 2 injections of vehicle into the TA 1 month apart. PD rats underwent transforming growth factor β1 (TGFβ1) injection and injection of vehicle 1 month later. PD-hADSC rats underwent TGFβ1 injection followed by 1 million hADSCs 1 month later. 1 week after treatment, n = 3 animals/group were euthanized, and the penises were harvested for quantitative polymerase chain reaction. 1 month after treatment, the other animals, n = 6 per group, underwent measurement of intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of the cavernous nerve. After euthanasia, penises were again harvested for histology and Western blot. Main Outcome Measure: The primary outcome measures included (a) gene expression at one week post-injection; (b) measurement of ICP/MAP upon cavernous nerve stimulation as a measure of erectile function; (c) elastin, collagen I and III protein expression; and (d) Histomorphometric analysis of the penis. Means where compared by analysis of variance (ANOVA) followed by a Student-Newman-Keuls test for post hoc comparisons or Mann-Whitney test when applicable. Results: No significant difference was noted in ICP or ICP/MAP in response to cavernous nerve electrostimulation between the 3 groups at 2.5, 5, and 7.5 V (P > .05 for all voltages). PD animals developed tunical and subtunical areas of fibrosis with a significant upregulation of collagen III protein. The collagen III/I ratio was higher in the PD (4.6 ± 0.92) group compared with sham (0.66 ± 0.18) and PD-hADSC (0.86 ± 0.06) groups (P < .05) These fibrotic changes were prevented when treated with hADSCs. Compared with PD rats, PD-hADSC rats demonstrated a decreased expression of several fibrosis-related genes. Conclusion: Injection of hADSCs reduces collagen III expression in a rat model of chronic PD. Castiglione F, Hedlund P, Weyne E, et al. Intratunical Injection of Human Adipose Tissue–Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease. Sex Med 2018;XX:XX–XX.
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7.
  • Castiglione, Fabio, et al. (författare)
  • Intratunical injection of stromal vascular fraction prevents fibrosis in a rat model of Peyronies disease
  • 2019
  • Ingår i: BJU International. - : WILEY. - 1464-4096 .- 1464-410X. ; 124:2, s. 342-348
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate whether local injection of autologous adipose stromal vascular fraction (SVF) can prevent the development of fibrosis and elastosis in the tunica albuginea (TA) using a rat model of the acute phase of Peyronies disease (PD). Methods A total of 24 male 12-week-old Sprague-Dawley rats were divided into three equal groups: sham; PD without treatment (transforming growth factor-beta [TGF -beta]); and PD treated with SVF 1 day after disease induction. Sham rats received two injections of vehicle into the TA 1 day apart. TGF -beta rats received TGF- beta 1 injection and injection of vehicle 1 day later. SVF rats received TGF-beta 1 injection, followed by SVF 1 day later. One month after treatment, all rats underwent measurement of intracavernosal pressure and mean arterial pressure during electrostimulation of the cavernous nerve. The rats were then killed and penises were harvested for histology and Western blot analysis. Results Erectile function was moderately reduced in the TGF-beta group and was significantly improved after SVF treatment (P amp;lt; 0.05). PD rats developed areas of fibrosis with a significant upregulation of collagen III, collagen I and elastin protein expression. These fibrotic changes were prevented when treated with SVF. Conclusions Local injection of SVF may represent treatment for the acute phase of PD.
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8.
  • Gontero, Paolo, et al. (författare)
  • Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin : Results of a Retrospective Multicenter Study of 2451 Patients
  • 2015
  • Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 67:1, s. 74-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.
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9.
  • Gontero, Paolo, et al. (författare)
  • The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin
  • 2016
  • Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 118:1, s. 44-52
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.
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10.
  • Hakim, Lukman, et al. (författare)
  • Intratunical injection of autologous adipose stromal vascular fraction reduces collagen III expression in a rat model of chronic penile fibrosis
  • Ingår i: International Journal of Impotence Research. - : Nature Publishing Group. - 0955-9930 .- 1476-5489.
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have shown that the injection of adipose stem cells and stromal vascular fraction(SVF) into the tunica albuginea (TA) during the inflammatory phase in a rat model of Peyronie’s disease(PD) prevented the development of TA fibrosis. Our aim was to investigate whether local injection of SVF can reduce established fibrosis in a rat model of chronic phase of PD. Eighteen-male 12-wk-old Sprague-Dawley rats were divided in three equal groups: sham, PD without treatment (PD) and PD treated with SVF(PD-SVF). Sham rats underwent 2 injections of vehicle into the TA one month apart. PD rats underwent TGF-β1 injection and injection of vehicle one month later. PD-SVF rats underwent TGF-β1 injection followed by SVF (1-million cells) one month later. One month after the last treatment, the animals, n = 6 rats per group, underwent measurement of intracorporal and mean arterial pressure during electrostimulation of the cavernous nerve. Following euthanasia, penises were harvested for in-vitro study. Erectile function was not statistically significantly different between groups. PD animals developed subtunical areas of fibrosis and elastosis with upregulation of collagen III protein. These fibrotic changes were reversed after injection of SVF. We provide evidence that local injection of SVF reverses TA fibrosis in a rat model of chronic phase of PD.
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