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Dominique Chopin

Publications and source records attributed to Dominique Chopin.

At least 19 recordsLinked to original sources
PubMed2006

Saturation biopsy protocol enhances prediction of pT3 and surgical margin status on prostatectomy specimen.

A 21-samples saturation biopsy procedure (SBP) was developed in order to improve prostate cancer detection rate. Out of 650 patients who underwent this protocol, 150 had a clinically localized prostate cancer and underwent a radical prostatectomy. The number of cores positive for tumor was assessed in the SBP, and also in the sextant component of the SBP (SC) and in the non-sextant component of the SBP (NSC). Numbers of cores positive for tumor on SBP, SC, and NSC were significantly higher in pT3 group versus pT2 (P < 0.001 each) and in positive surgical margins (PSM) group versus no PSM (P < 0.001 each). When comparing area under the curve obtained from SBP with those obtained from NSC and SC, the SBP showed higher accuracy than the NSC and the SC for the prediction of pT3 and PSM. On multivariate analyses, SC and NSC were independent predictors of pT3 and PSM on radical prostatectomy.

Aged↗
PubMed2006

Characterization of ZAG protein expression in prostate cancer using a semi-automated microscope system.

OBJECTIVE: Zinc-alpha-2-glycoprotein 1 (ZAG) is a 41-kD secreted protein that is known to stimulate lipid degradation in adipocytes. The aim of this study was to determine how ZAG protein expression is associated with prostate cancer (PCa). MATERIALS AND METHODS: An immunohistochemistry analysis was performed on a 227 PCa tissue microarray cases. ZAG protein expression was assessed using a semi-automated cellular image analysis system. RESULTS: ZAG expression was associated with tumor stage (pT2 > pT3 > metastasis cases, P < 0.001), and was inversely associated with Gleason score on pathology (P = 0.01). ZAG intensity was predictive of biochemical recurrence (P = 0.002). On multivariate analysis including pT2 patients, the predictive factors of biochemical recurrence were ZAG expression (P = 0.016), Gleason score (P = 0.011), and surgical margin status (P = 0.047). CONCLUSIONS: This study characterized ZAG protein expression in PCa using a semi-automated system. ZAG expression level found to have an independent prognostic value for pT2 patients.

Adipokines↗
PubMed2006

Tumor size improves the accuracy of TNM predictions in patients with renal cancer.

OBJECTIVES: Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS). METHODS: Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size. RESULTS: In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories. CONCLUSIONS: Tumor size represents a highly significant, multivariate, and informative predictor of RC outcomes and may warrant inclusion in future TNM revisions.

Carcinoma, Renal Cell↗
PubMed2006

The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study.

PURPOSE: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. MATERIALS AND METHODS: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6 +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. RESULTS: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. CONCLUSIONS: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus Calmette-Guerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.

Adjuvants, Immunologic↗
PubMed2006

The striated urethral sphincter of the pig shows morphological and functional characteristics essential for the evaluation of treatments for sphincter insufficiency.

PURPOSE: New treatments are currently under investigation for intrinsic sphincter insufficiency. However, animal models in which to study the resting urethral tone generated by the striated urethral sphincter are still lacking. We describe the striated urethral sphincter in the pig. We investigated its participation in resting urethral tone with the aim of developing new tools for evaluating therapies for sphincter insufficiency. MATERIALS AND METHODS: A total of 15 female pigs were used in this study. Anatomy of the striated urethral sphincter was described via transpubic and endoscopic approaches. Participation of the striated urethral sphincter in resting urethral tone was assessed by analysis of urethral pressure profilometry (maximum urethral closure pressure, functional urethral length and area under the curve) before and after curare injection or by destruction of the striated urethral sphincter by endoscopic electrocautery. Serial urethral cross sections were immunostained for slow/fast myosin and digitalized for 3-dimensional reconstructions to determine striated urethral sphincter volume. RESULTS: The striated urethral sphincter was Omega-shaped and it encircled the distal third of the urethra. A mean peak intraurethral pressure +/- SEM of 58.9 +/- 13.4 cm H(2)O was noted in front of the striated urethral sphincter. Curare injection and endoscopic injury decreased maximum urethral closure pressure by 48.4% and 51.1%, functional urethral length by 10.3% and 15.3%, and area under the curve by 47% and 64%, respectively. The striated urethral sphincter consisted of 52% slow and 48% fast myofibers. Its mean volume was 0.87 cm. CONCLUSIONS: The striated urethral sphincter of the female pig shows the morphological and functional features of a tonic muscle. Methods of measuring resting urethral tone generated by the striated urethral sphincter represent original tools for evaluating therapies for intrinsic sphincter insufficiency.

Actins↗
PubMed2005

Serum bioavailable testosterone: assayed or calculated?

BACKGROUND: Bioavailable testosterone (BT), circulating testosterone not bound to sex hormone-binding globulin (SHBG), is thought to easily penetrate cells. We compared BT measurements obtained by assays with those obtained by calculation with different testosterone association constants. METHODS: We obtained sera from 2 groups of hypogonadal men [group 1 (G1), 1421 samples; group 2 (G2), 170 samples] and a group of healthy men [group 3 (G3), 109 samples]. We added minute doses of [3H]testosterone to the sera, precipitated the SHBG-bound fraction of testosterone with ammonium sulfate (50% saturation), and then assayed serum BT (ABT) as %BT x total. Calculated BT (CBT) was determined with theoretical association constants of testosterone for SHBG (Ks = 1 x 10(9) L/mol) and albumin (Ka = 3.6 x 10(4) L/mol) and paired optimal Ks and Ka values obtained by use of Microsoft Excel software. RESULTS: CBT calculated with theoretical constants differed from ABT by >30% in 85.7% (G1), 84.1% (G2), and 77.9% (G3) of samples, and the mean CBT/ABT ratios were 1.57 (G1), 1.85 (G2), and 1.50 (G3) in spite of fairly good correlations. CBT calculated with paired optimal K(s) and K(a) differed from ABT by <30% in 87.4% (G1), 87.5% (G2), and 97.5% (G3) of samples, and mean CBT/ABT ratios were 0.95-1.04. CONCLUSIONS: To obtain CBT values as close as possible to ABT, optimal paired association constants determined for each studied population must be used instead of the theoretical association constants. Considering the uncertainty of calculating BT, however, use of the ammonium sulfate precipitation method for determining BT is advisable.

Androgens↗
PubMed2005

Oncogenic properties of the mutated forms of fibroblast growth factor receptor 3b.

Germinal activating mutations of FGFR3 are responsible for several forms of dwarfism due to the inhibitory effect of FGFR3 on bone growth. Surprisingly, identical somatic activating mutations have been found at the somatic level in tumours: at high frequency in benign epithelial tumours (seborrheic keratosis, urothelial papilloma) and in low-grade, low-stage urothelial carcinomas, and at a lower frequency in other types of urothelial carcinoma, in cervix carcinoma, and in haematological cancer, multiple myeloma. FGFR3 exists as two isoforms, FGFR3b and FGFR3c, differs in ligand specificity and tissue expression. FGFR3b is the main form in epithelial cells and derived tumours, whereas FGFR3c is the main form in mesenchyme-derived cells and multiple myeloma. Several lines of evidence suggest that mutated FGFR3c has transforming properties. Although mutated FGFR3b is mostly found in benign epithelial tumours or carcinomas of low malignant potential, we present evidence here that mutated FGFR3b is oncogenic. All bladder tumours presenting FGFR3 mutations expressed this receptor more strongly than normal urothelium or non-mutated tumours. NIH-3T3 cells transfected with a mutated form of FGFR3b--FGFR3b-S249C, the most common mutation in bladder tumours--presented a spindle-cell morphology, grew in soft agar and gave rise to tumours when xenografted into nude mice. We identified one line of 17 bladder cell lines tested (MGH-U3) that expressed a mutated form of FGFR3b, FGFR3b-Y375C. We showed using siRNA and SU5402, an FGFR inhibitor, that the tumour properties of MGH-U3 depended on mutated receptor activity. Thus, in two different models, mutated FGFR3b presents oncogenic properties.

Animals↗
PubMed2005

What information are urologists extracting from prostate needle biopsy reports and what do they need for clinical management of prostate cancer?

OBJECTIVES: This survey-based study examines what information urologists are extracting from prostate needle biopsy reports, and what they need for clinical management of prostate cancer (PC) patients. METHODS: A questionnaire was used to investigate several topics related to PC biopsy reporting. Two different clinical situations were separately explored, depending on whether the urologist intended a curative or a palliative therapy. RESULTS: 110 of the 300 (37%) urologists responded to the questionnaire and returned anonymous responses. The mean age of respondents was 47.5 years old (range 27-66). On average, they performed 31 (range 0-182) radical prostatectomies per year. Before proposing a curative therapy, several biopsy parameters were requested by the majority of respondents, including number of positive biopsies (104/110 or 95%), Gleason score (103/110 or 94%), highest Gleason grade (94/110 or 85%), localization of positive biopsies (80/110 or 73%), length of tumor on biopsy (58/110 or 53%), presence of extraprostatic extension (66/110 or 60%). In a palliative situation, only three parameters were requested by the majority of respondents: Gleason score (101/110 or 92%), highest Gleason grade (67/110 or 61%) and number of positive biopsies (59/110 or 54%). In prostate needle biopsies harboring cancer on multiple cores from separately designated locations, 77% (68/88) of respondents used the highest Gleason score, regardless of the overall percentage involvement, to determine their treatment plan. PIN (Prostatic Intraepithelial Neoplasia) on biopsy without PC was considered sufficient to re-biopsy by 77% (85/110) of respondents. Thirty six percent (40/110) of the respondents considered ASAP (Atypical Small Acinar Proliferation) to be equivalent to PIN. There was no significant association between the demographic data and the type of information requested on the biopsy report. CONCLUSIONS: In this sample of 110 French and Belgian urologists there was high variability in the way clinicians use prostate needle biopsy pathology report. Results of this survey should improve communication between urologists and pathologists and should help evaluate what data should be included in routine pathology reports.

Adult↗
PubMed2005

[The p53 gene].

Explore the source record for details and available documents.

Genes, p53↗
PubMed2004

Constitutive activation of the androgen receptor by a point mutation in the hinge region: a new mechanism for androgen-independent growth in prostate cancer.

Androgen receptor (AR) mutations that modify both the ligand binding and the transactivation capacities of the AR represent one of the mechanisms involved in the transition of prostate cancer (PCa) from androgen-dependent to androgen-independent growth. We use a yeast-based functional assay to detect and analyze mutant ARs in PCa. We report the detection of 2 different mutant ARs within the same metastatic tumour sample harvested in a patient with advanced PCa who had escaped androgen deprivation. Concomitantly to the widely described T877A mutant AR, we identified an additional double mutant AR harboring the nonsense mutation Q640Stop just downstream the DNA binding domain together with the T877A point mutation. This type of mutation, which leads to a c-terminal truncated AR, has not been described yet in PCa. Using luciferase reporter assays we demonstrated that this truncated AR exhibited constitutive transactivation properties. In conclusion, our data suggest that mutation-induced constitutive activation of the AR could be a mechanism used by PCa cells to escape androgen deprivation.

Adenocarcinoma↗
PubMed2004

Frequency, clinical presentation and evolution of renal oncocytomas: multicentric experience from a European database.

OBJECTIVES: To understand the clinical behavior of renal oncocytoma in a retrospective analysis of a European multicentric nephrectomies database. METHODS: The records of 891 patients who underwent surgical resection of renal neoplasm were reviewed. Relevant clinical and pathological data for each patient were retrieved in a database. RESULTS: Thirty-two (3.6%) cases of renal oncocytoma were identified. Twenty patients (62.5%) were asymptomatic. No case of lymphatic invasion or metastatic disease, nor any evidence of vascular or fat tissue invasion was found. Thirty-one cases (96%) exhibited low mitotic activity. In one case the presence of renal clear cell carcinoma (diameter: 1.5cm) was found. After a median follow-up of 42 months, 87.5% of patients were alive with no evidence of tumor, while 9.3% of patients had died for non-malignant causes. One patient had not treated the tumor surgically and was disease-free at a 27-month follow-up. CONCLUSIONS: Renal oncocytoma is a benign neoplasm, characterized by slow growth and excellent prognosis after surgery. Nephron sparing techniques may be adequate for tumor removal.

Adenocarcinoma, Clear Cell↗
PubMed2004

Profiles of the 2 INK4a gene products, p16 and p14ARF, in human reference urothelium and bladder carcinomas, according to pRb and p53 protein status.

The INK4a/ARF locus encodes 2 cell cycle regulatory proteins: p16 and p14(ARF). P16 inhibits the activities of cdks, which maintain the retinoblastoma protein (pRb) in its active hypophosphorylated state. P14(ARF) blocks MDM2-induced p53 degradation and transactivational silencing. In this study, we investigated the expression of p16 and p14(ARF) in reference human urothelium and in 51 urothelial carcinomas (UCs) of all stages and grades, by reverse transcription-polymerase chain reaction (RT-PCR). Patterns of p14(ARF) and p16 expression were compared with each other and then with patterns of p53 and pRb protein expression, respectively, as determined by immunohistochemistry. P14(ARF) and p16 mRNAs were present at low levels or were undetectable in reference urothelia and in most superficial tumors, whereas they were present at high levels in a subset of tumors of advanced stage and high grade. The expression profiles of these 2 mRNAs were correlated in all but 4 cases, indicating that the 2 INK4a products may have nonredundant functions. Forty-six of the 51 tumors (90%) presented changes to or a lack of activation of the p14(ARF)-p53 pathway and were p53 positive (n = 10), p14(ARF) negative (n = 23), or both p53 positive and p14(ARF) negative (n = 13), suggesting that these 2 components of the pathway may be altered or nonactivated. Markedly high levels of p16 mRNA (n = 5) were associated with the absence of pRb expression, with the exception of 1 case in which the p16 gene contained a deletion mutation. A lack of p16 mRNA or low levels of this mRNA were associated with pRb detection in all but 1 case. In invasive UCs, the p16-pRb pathway, the p14(ARF)-p53 pathway, or in many cases both pathways were altered or not activated, demonstrating the involvement of these pathways in invasive bladder tumorigenesis.

Carcinoma↗
PubMed2004

Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer.

OBJECTIVE: To evaluate the safety and efficacy of combined docetaxel-zoledronic acid treatment in patients with metastatic hormone-refractory prostate cancer (HRPC), as bisphosphonates are reported have a synergistic antitumoral effect when combined with taxanes. PATIENTS AND METHODS: Between January 2001 and June 2003, 14 patients with HRPC were treated; their mean (range) age was 71 (57-86) years and mean prostate-specific antigen (PSA) level 202 (6-489) ng/mL. Five patients had had previous chemotherapy (cyclophosphamide in two, mitoxantrone-prednisolone in three). The response criteria were the Karnofsky performance status, a positive response in mean daily analgesic consumption (defined as a decrease by more than half), decreased serum PSA (by more than half) at 8 weeks, blood transfusion, bone scan at 6 months, skeletal-related events and survival. RESULTS: Patients received a mean (range) of 7.3 (6-10) cycles of therapy; there was no reported drug-related toxicity and all patients stayed at home for their treatment. Only three patients required a blood transfusion and no bone fractures were reported. At 2 months, six patients requiring analgesic drugs decreased their consumption by more than half (anti-inflammatory, paracetamol, narcotics) and eight had a reduction in PSA by more than half; of these eight with a PSA response at 2 months, six had biochemical progression with a mean delay of 6.2 (3-11) months. At 6 months, five patients had disease progression on bone scan. Nine patients had chemo-naïve hormone-refractory prostate cancer; three had biochemical progression at 2 months and two of these had progression on their bone scan. Two patients died at 7 and 15 months of follow-up; the mean follow-up was 10.2 (6-15) months. Using Kaplan-Meier plots, biochemical progression-free survivals were five of 14 at 6 months and two of 14 at 12 months; overall survival was 12 of 14 at 6 and 12 months. CONCLUSION: Docetaxel-zoledronic acid therapy is safe and decreased the serum PSA by more than half at 2 months in more than half the patients. Prospective randomized trials are needed to assess this new approach.

Aged↗
PubMed2004

[Cell therapy for urethral sphincter incompetence by muscle precursor cell autograft].

This article reviews cell therapy for muscle diseases and describes the development of a treatment for urethral sphincter insufficiency by muscle precursor cell (MPC) autograft. These studies were conducted in several successive steps, comprising: 1) comparative study of the cellular mechanisms of regeneration of skeletal striated muscle and urethral striated sphincter and development of a method of extraction of MPC; 2) creation of an animal model of sphincter injury reproducing chronic denervation lesions and fibrosis responsible for sphincter insufficiency in human; 3) study of the biology of intrasphincteric transplantation of MPC extracted from peripheral muscle, taking into account the interactions between these cells and the peripheral nervous system.

Animals↗