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D K Chopin

Publications and source records attributed to D K Chopin.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Evaluations of protein p53 overexpression in cancer of the bladder: prognostic value].

Management of Transitional Cell Carcinoma (TCC) of the bladder depends on clinicopathological parameters at initial presentation. These criteria are insufficient predictors because of tumor heteterogeneity. Progress in tumor biology suggest that molecular markers may be used to dismember bladder cancer according to their biological behavior. Evidences have accumulated that cancer result from accumulation of molecular defect specially on tumor suppressor genes. In this respect we studied by mean of immunohistochemistry the prognostic value of p53 nuclear overexpression using monoclonal antibody P1801. The study was performed on 114 TTC and 13 normal bladders. Nuclear straining was quantified using an eye piece reticule at magnification 400x. Scoring was determined counting 500 nuclei in 3 to 5 arbitrary fields. Results between stage, grade and percentage of stained nuclei are as follow: TA 0,92-T1 0,144-T2 0,354-T4 0,622-G1 0,105-G2 0,212-G3 0,406. Comparison of mean nuclear straining between group with and without progression indicates a threshold of 16% for p53 nuclear overexpression. Using this limit there is a significant progression free survival rate for the all group (p < 0,0001) and for the group of superficial tumors (p = 0,0007). Multivariate analysis using stepvise logistic regression indicate a p53 prognostic value independent from stage and grade (OR 23,4). This result indicates that p53 overexpression which can be determined on routine preparation has a strong prognostic value and a certain clinical utility.

Adult↗
PubMed1995

Prognostic value of epidermal growth factor-receptor, T138 and T43 expression in bladder cancer.

Tumour-associated markers defined by monoclonal antibodies have proven useful to phenotype bladder tumours. In order to evaluate the prognostic value of such markers, we performed an immunohistochemical study on 57 transitional cell carcinomas (23 infiltrative and 34 superficial tumours) and ten healthy bladders using monoclonal antibodies against the external domain of the epidermal growth factor receptor (EGFR) and against the tumour-associated antigens T43, 19A211 and T138. Immunohistochemistry was performed on frozen sections using a two-step alkaline phosphatase method. The staining pattern obtained with each antibody was analysed according to the TNM classification, and results were analysed according to the subsequent clinical course. 19A211 preferentially stained superficial tumours, and T43, T138 and EGFR preferentially stained invasive tumours. Three monoclonal antibodies appeared to have prognostic value, since progression rate survival was significantly (log-rank test) associated with their expression of EGFR (P = 0.017), T138 (P = 0.0009) and T43 (P = 0.031). T138 expression was found to have an independent significant prognostic value using a stepwise logistic regression. T138 antibody may add significant information to classical pathological parameters.

Antibodies, Monoclonal↗
PubMed1995

Consecutive use of hormonally defined serum-free media to establish highly differentiated human renal proximal tubule cells in primary culture.

Highly differentiated human proximal tubule (HPT) cells in primary culture were established from heterogeneous suspension of tubules prepared from the human renal cortex by an original two-step procedure. First, gluconeogenic-competent HPT cells were selected by using a hormonally defined serum-free medium without glucose or insulin; then, the selected HPT cells were grown in a medium containing a low concentration of glucose (1 mM) and insulin (0.5 micrograms/mL) but no antibiotics. HPT cells grown on plastic support formed confluent, cobblestone-like monolayers with numerous mitochondria and pinocytosis vacuoles, solitary cilia, junctional complexes, and a well-developed brush border consisting of densely packed microvilli. Compared with cell monolayers on plastic support, HPT cells grown on porous filter membranes showed better morphologic differentiation. HPT cell monolayers expressed the following differentiated functions of the proximal tubule in situ: a low-affinity, high-capacity Na(+)-dependent glucose transport system inhibited by phlorizin, a high-affinity Na(+)-dependent phosphate transport system, a basolateral organic cation uptake inhibited by mepiperphenidol, parathyroid hormone-sensitive cAMP synthesis, brush-border hydrolase activities, gluconeogenesis-associated enzymes, glutathione-S-transferases and N-acetyl-beta-D-glucosaminidase. The medium containing low glucose and insulin concentrations markedly limited the increase in glycolysis but did not prevent the falls in gluconeogenesis and brush-border hydrolase activity at any time of the culture period. Similar decreases of brush border enzyme activities were obtained for HPT cells grown either on plastic or on porous filter membrane. A thorough characterization study demonstrated that this simple and preparative experimental approach makes it possible to establish highly differentiated HPT cells in primary culture suitable for investigating human renal proximal tubular cell function.

Biological Transport↗
PubMed1995

Fibroblast growth factors and their specific binding sites in normal urothelium and transitional cell carcinoma (TCC) of the human bladder.

In order to further investigate the involvement of FGF1 and FGF2 in the transitional cell carcinoma of the bladder (TCC), we compared the expression of FGF1, FGF2 and their membrane binding sites by biochemical and immunological methods in both human normal urothelium and transitional cell carcinoma of the bladder. Using a specific enzyme immunoassay (EIA), we observed that neoplastic tissue exhibited a lower FGF2 content than normal tissue. FGF1 and FGF2 Western-blot analysis revealed in both types of tissues a major FGF1 form with a low molecular weight (14 kDa) and a single FGF2 form (21 kDa). Immunohistological studies showed that FGF1 was specifically located in normal or transformed urothelial cells, while FGF2 was associated with bladder stroma. Binding analysis in tissue membrane preparations revealed a dramatic drop in both high and low affinity binding sites for FGF2 in TCC bladder in comparison to normal bladder. FGF2 cross-linking experiments illustrated a qualitative modification of FGF2 binding complexes in tumors. These data suggest that invasive bladder carcinoma is associated with modifications of FGF1 and FGF2 tissue levels and alterations in the characteristics of the FGF2 membrane binding sites.

Binding Sites↗
PubMed1995

Magnetic resonance imaging of penile rupture: aid to diagnosis.

We report on a patient with atypical clinical findings in whom magnetic resonance imaging confirmed the suspicion of penile rupture. The tear appeared as an obvious discontinuity of the low signal intensity of the tunica albuginea and was associated with a hematoma. We conclude that magnetic resonance imaging is useful for confirming the diagnosis of penile rupture when clinical findings are atypical, indicating surgical repair.

Adult↗
PubMed1994

A comparison of direct and liposomal antibody conjugates of sulfonated aluminum phthalocyanines for selective photoimmunotherapy of human bladder carcinoma.

There is a need to improve the selectivity of photodynamic therapy and for better targeting of tumor cells within specific tumor compartments. Selective in vitro phototoxicity of a human bladder carcinoma cell line 647V has been achieved by targeting sulfonated aluminum phthalocyanines (AlSPc) with monoclonal antibodies. Aluminum tetra-3 sulfonyl chloride phthalocyanine (PC) or rhodamine sulfonyl chloride were directly coupled to antibodies by a sulfonamide linkage and AlSPc or carboxyfluorescein were encapsulated in liposomes of the small unilamellar vesicle type (SUV) bearing antibody. Antibody E7 (IgM subclass), which recognized an antigenic determinant expressed on 647V but was absent on T24 a control human bladder carcinoma cell line, and a control IgM antibody were used. The effects of the two types of conjugate were compared. Immunofluorescence studies on living cells demonstrated specific cell surface localization of conjugates at 4 degrees C and internalization at 37 degrees C. Phototoxicity was measured by 3-(4,5-dimethylthiazol-2-5-diphenyltetrazolium) bromide assay after exposing AlSPc-sensitized cells to red light. Significant AlSPc dose-dependent phototoxicity of the order 4 degrees C < 4 degrees C plus 37 degrees C < 37 degrees C was observed with E7-SUV and E7-PC in the range 1-8 microM AlSPc. At equimolar AlSPc doses absolute toxicity was similar for the two conjugate types, but at equimolar antibody doses, the liposomal conjugate was more effective by up to 13-fold. Addition of urine during illumination decreased toxicity, which was attributed to the presence of protective elements. The results suggest that photosensitizers such as AlSPc could be used for antibody-directed therapy and in particular for selectively damaging tumor cells of the epithelial cell compartment in bladder carcinoma by intrabladder administration. The therapeutic ratio, which takes into account both specific and nonspecific toxicity, was greater for the liposome conjugate than for the direct conjugate indicating their greater suitability for in vivo instillation.

Aluminum↗
PubMed1994

Computer assisted image analysis of bladder tumour nuclei for morphonuclear and ploidy assessment.

Morphonuclear analysis using a quantitative image analysis system has been demonstrated to be a potentially useful technique in the prognostic evaluation of bladder carcinoma. The integrated optical density parameter permits DNA content evaluation in addition to 15 other morphonuclear parameters. We assessed the reliability of morphonuclear analysis by image analysis and flow cytometry for 46 bladder carcinomas and 14 normal bladder specimens. Frozen sample material was obtained from endoscopic resection, radical cystectomy and from cadaveric donors. The grade and staging of the tumours according to the World Health Organization was as follows: 8 G1, 18 G2, 20 G3 and 28 T1, 7 T2, 7 T3, 4 T4. Quantitative image analysis was made on imprint smears stained by the Feulgen method. Simultaneously cell suspensions were obtained by mechanical dissociation and stained with propidium iodide for Flow cytometry analysis. There was a good agreement between quantitative image analysis and flow cytometry for DNA content measurement indicating that image analysis is a reliable method for the quantitation of DNA content (P = 0.001). Moreover we found a good correlation between five of the morphonuclear parameters: surface (P < 0.001), chromatin clumps distribution (P < 0.001), frequency of small (P < 0.001) to large chromatin clumps (P < 0.001) and the grade of bladder tumours. These results indicate that morphonuclear analysis may be a valuable method of quantitating DNA and morphonuclear parameters in a single analysis to provide information which may have some prognostic significance for patients with bladder carcinoma.

Cell Nucleus↗
PubMed1993

Prognostic factors in superficial bladder cancer.

A large body of evidence suggests that intravesical prophylaxis using bacillus Calmette-Guérin can favorably alter the natural history of superficial bladder cancer. The search for prognostic factors impacting the clinical alternative between conservative and radical treatment has been the subject of numerous efforts and remains a major objective in improving the carcinological results and the quality of life patients with superficial bladder cancer. In this regard, information is available on three levels: clinicopathological parameters, quantitative analysis, and biological markers. Recent advances in as well as the limitations and pitfalls of the use of three kinds of information in prognostication are reviewed. The proper use of prognostic factors will modify our attitude toward superficial bladder cancer in the near future.

BCG Vaccine↗
PubMed1993

Mechanisms of action of bacillus Calmette-Guérin in the treatment of superficial bladder cancer.

Local immunotherapy with bacillus Calmette-Guérin (BCG) is an effective treatment to prevent recurrence and progression of superficial bladder cancer, but the antitumor mechanism of action of BCG remains unclear. There are some experimental and clinical data suggesting that BCG antigens are processed not only by immunocompetent cells but also by urothelial cells and tumor cells. The foreign antigen may be presented at the cell surface by major histocompatibility complex (MHC) class II molecules and recognized by CD4 cells. The cytotoxic effect could result from the direct activity of CD4 cells or from the cytotoxic effect of released cytokines and the activation of other cytotoxic cells [cytolytic T-lymphocytes CTLs; CD8 cells), macrophages, natural killer (NK) or lymphokine-activated killer (LAK) cells]. These mechanisms are also involved in tumor rejection, and the identification of some specific tumor rejection antigens presented to specific CTLs could provide new therapeutic approaches.

BCG Vaccine↗
PubMed1993

Increased immunodetection of acidic fibroblast growth factor in bladder cancer, detectable in urine.

Acidic fibroblast growth factor is a regulatory peptide involved in cell proliferation, differentiation and motility. We used a polyclonal antiserum raised against purified native bovine acidic fibroblast growth factor, with no cross-reactivity for basic fibroblast growth factor to detect acidic fibroblast growth factor in tissue extracts and urine samples by means of a competitive enzyme immunoassay. Histochemical analysis was also performed on 10 specimens of normal urothelium and 50 of bladder cancer. Acidic fibroblast growth factor immunoreactive material was found in normal urothelium (1.77 +/- 2 ng./gm. tissue) and was increased more than 10-fold in patients with transitional cell carcinoma of the bladder (20.36 +/- 12 ng./gm. tissue). Immunohistochemical analysis localized immunoreactivity in the epithelial compartment of bladder tumors. Acidic fibroblast growth factor was assayed in urine from 579 individuals comprising a control group (114) and patients with benign prostatic hypertrophy (133), carcinoma of the prostate (96) or transitional cell carcinoma of the bladder (236). There was a significant difference in the frequency of urinary acidic fibroblast growth factor detection among the patients with invasive transitional cell carcinoma, the control group (p < 0.001) and the patients with prostatic disease (p < 0.01). The sensitivity was 72% and the specificity was 91%. Furthermore, the frequency of acidic fibroblast growth factor detection by enzyme immunoassay in the urine and the intensity of immunostaining was correlated with the stage of the disease. These data strongly suggest that acidic fibroblast growth factor is a potential marker for bladder tumors that may be of use in the noninvasive followup of patients with bladder cancer. We present a simple and reliable enzyme immunoassay for the detection of acidic fibroblast growth factor in voided urine that might be useful to quantitate this marker.

Biomarkers, Tumor↗
PubMed1993

[Pelvic lymphatic excision using laparoscopy. Its value in the staging of tumors of the bladder].

Laparoscopic surgical procedures are being evaluated in urologic diseases including bladder cancer. Patients with apparently localized tumors may have lymph node involvement indicating disseminated disease for which locoregional treatments are inadequate. Laparoscopic lymphadenectomy may be useful for staging, since neither noninvasive procedures nor intraoperative examination of lymph nodes removed during cystectomy are completely reliable. The technique is described in detail. Benefits in bladder cancer patients remain to be determined.

Humans↗
PubMed1993

[Natural history and prognostic factors of superficial tumors of the bladder].

Forty-five patients with superficial bladder cancer managed by transurethral resection alone were studied longitudinally to identify factors associated with progression. Tumor grade, multiple tumor foci, and time to first recurrence were closely correlated with progression. Findings from this study are compared with previous reports. These data are useful to identify patients requiring more aggressive therapy, including intravesical anticancer drugs and BCG, and monitoring with closer-spaced cystoscopies.

Female↗
PubMed1993

[Preventive treatment of superficial tumors of the bladder using intravesical BCG. Review].

Local immunotherapy with BCG was first described by Zbar in an experimental model. The clinical use of BCG in human bladder carcinoma was proposed by Morales in 1976. Since then randomised studies have confirmed the value of BCG against recurrence and progression in superficial transitional cell carcinoma of the bladder (Lamm, Herr). However the optimal protocol has not been defined and the mode of action of BCG remains obscure. In this paper, the authors review the clinical results of BCG and its complications then focus on recent immunological data concerning its mode of action. Finally a practical protocol is proposed.

Administration, Intravesical↗
PubMed1993

[A procedure for bladder replacement using a low-pressure ileal reservoir].

Goals pursued when constructing an ileal pouch after cystectomy include good capacity and distensibility, voluntary control of micturition with no residual urine, a sensation of fullness, and urinary continence. In addition, metabolic disorders due to reabsorption of urine components by the ileal mucosa require control. A bladder replacement technique using a low-pressure ileal reservoir is described and results in eighty patients are reported. Physiologic features of ileal urinary pouches are reviewed.

Cystectomy↗
PubMed1993

[Results of the treatment of bladder tumors infiltrating the muscle].

Recent studies have shown improvements in survival in patients with invasive bladder cancer, perhaps as a result of stage selection and reduced perioperative morbidity rather than of increased effectiveness of treatments. The main ongoing therapeutic trials (combined use of chemotherapy with either surgery or radiation therapy) aim at controlling occult metastases which may be present in up to 50% of apparently localized bladder cancers. Identification of risk factors for metastatic disease is therefore crucial. In this study, factors potentially associated with response to treatment were analyzed on the basis of a review of outcomes reported with current treatments.

Combined Modality Therapy↗
PubMed1993

[The use of monoclonal antibodies in the evaluation of the aggressiveness of tumors of the bladder].

Monoclonal antibodies produced using hybridoma technology have enabled identification of new tumor markers. Targets include tumor-associated antigens, growth factors and their receptors, blood group antigens, cell proliferation antigens, oncogene or tumor suppressor gene products, and markers for drug resistance. Immunohistochemical or flow cytometry studies performed with monoclonal antibodies can be used to determine the immunophenotype of normal and tumoral urothelium; specificity may be primarily for superficial or deep tumors, or for different tumor grades. A number of monoclonal antibodies have been found of prognostic value independently from conventional prognostic criteria. Others have shown diagnostic value. The most promising monoclonal antibodies are reviewed herein.

Antibodies, Monoclonal↗