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P Bedossa

Publications and source records attributed to P Bedossa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Deletion mapping of the tumor suppressor locus involved in colorectal cancer on chromosome band 8p21.

Several somatic genetic alterations have been described in colorectal carcinoma (CRC). Recurrent chromosomal deletions have suggested the presence of tumor suppressor genes (TSG) specifically involved in colorectal carcinogenesis. For one of them, two non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The short arm of chromosome 8 has been extensively studied in colorectal cancer and in other cancer types. Both regions have been reported as candidate loci for a TSG. In order to delineate a reliable region of deletional overlap on chromosome arm 8p in CRC, a series of 365 CRC samples was selected for the absence of microsatellite instability (RER, replication error); tumor and normal matched DNAs were studied for 54 microsatellite polymorphisms distributed on 8p using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, complete allelic losses on 8p were observed in 48% of cases. Measurement of the DNA index showed that 88% of RER tumors were hyperploid. Complete allelic losses of only part of the short arm were observed on 26 occasions. These data allowed us to define a 1 cM interval of common deletion, flanked by the loci D8S1771 and NEFL, where a putative TSG may be localized.

Animals↗
PubMed1999

Expression of connective tissue growth factor in experimental rat and human liver fibrosis.

Connective tissue growth factor (CTGF) stimulates in vitro fibroblast proliferation and extracellular matrix synthesis. The aim of this study was to assess the role of CTGF in liver fibrogenesis. CTGF expression was investigated both at the protein and mRNA level in biopsies of chronic liver diseases, in experimental models of liver fibrosis, and in hepatic stellate cells in culture. CTGF immunostaining was observed in most human liver biopsies with significant fibrosis. An increase of CTGF immunostaining was associated with a higher score of fibrosis both in the group of chronic hepatitis C (chi(2) = 9.3; P <.01) and in the non-hepatitis C group (chi(2) = 7.2; P <.02). In situ hybridization showed CTGF mRNA expression in spindle cells in both the fibrous septa and sinusoidal lining. In experimental models of liver fibrosis, CTGF accumulated in parallel with the development of septal fibrosis and cirrhosis. Quantification of CTGF mRNA by a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay showed a significant increase of CTGF mRNA in both CCl(4)-induced and bile duct-ligated rat models of liver fibrosis. Expression of CTGF protein and mRNA was definitively assigned to hepatic stellate cells, because CTGF was detected by Western blot both in lysate and supernatant of a hepatic stellate cell line derived from rats. These cells also displayed CTGF protein and mRNA as shown by immunohistochemistry and in situ hybridization. In conclusion, this study shows that CTGF is strongly expressed during liver fibrogenesis, and hepatic stellate cells seem to be the major cellular sources of CTGF in the liver.

Adolescent↗
PubMed1999

Chester-Erdheim disease: a neoplastic disorder.

Chester-Erdheim disease is a rare non-langerhans cell histiocytosis characterized by a xanthomatous infiltration of foamy macrophages. The cause and pathogenesis remain unclear. The aim of the present study was to determine whether Chester-Erdheim disease is a polyclonal reactive disease or a clonal neoplastic disorder. The clonal status of samples obtained from five patients with Chester-Erdheim disease was studied. DNA was extracted from fixed and paraffin-embedded sections after microdissection and clonal status was studied using the Xchromosome inactivation pattern of the human androgen receptor gene (HUMARA assay). One patient was homozygous for the HUMARA gene and noninformative. Three other cases were monoclonal. One was polyclonal, and this case showed a dense reactive infiltrate in association with spumous macrophages. This study suggests strongly that Chester-Erdheim disease is a monoclonal lesion consistent with neoplastic disorder. Thus, Chester-Erdheim disease may be considered as the "macrophage" counterpart of Langerhan's cell histiocytosis in the histiocytosis spectrum. Further studies are needed to establish the origin of this clonal proliferation.

Adult↗
PubMed1999

Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis.

BACKGROUND/AIMS: Evaluation of the degree of hepatic fibrosis is especially important in patients with chronic liver disease. Our aim was to study the diagnostic accuracy of abdominal ultrasonography for cirrhosis or fibrosis. METHODS: Twenty-three clinical (n=12) and Doppler ultrasonic (n=11) variables were recorded in 243 patients with chronic (alcoholic and viral) liver disease under conditions close to those of clinical practice. Fibrosis was classified into six grades by two pathologists. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables, then by stepwise analysis. RESULTS: A) Diagnosis of cirrhosis: 1) whole group (n=243): diagnostic accuracy was globally 84%, and 84% with two variables: spleen length, portal velocity; 2) compensated chronic liver disease (n=191): diagnostic accuracy was globally 85%, and 82% with two variables: liver surface, liver length (right kidney); 3) alcoholic compensated chronic liver disease (n=109): diagnostic accuracy was globally 86%, and 88% with two variables: spleen length, liver length (middle clavicle); 4) viral compensated chronic liver disease (n= 83): diagnostic accuracy was globally 86% and 86% with one variable: liver surface. By subtracting the proportion of patients who could not be investigated due to anatomical limitations, the highest calculated univariate diagnostic accuracy decreased by 7%. B) Diagnosis of fibrosis: diagnostic accuracy was globally 84% for extensive fibrosis. CONCLUSIONS: Cirrhosis can be correctly diagnosed in 82-88% of patients with chronic liver disease using a few ultrasonographic signs. However, the diagnostic accuracy of ultrasound is decreased by the anatomical limitations of this technique.

Adult↗
PubMed1999

Non-invasive diagnosis of esophageal varices in chronic liver diseases.

BACKGROUND/AIMS: The primary prevention of bleeding from esophageal varices is a major therapeutic issue requiring early screening of esophageal varices. Our aim was to study the diagnostic accuracy of non-endoscopic means for the diagnosis of esophageal varices. METHODS: Sixty-three clinical, biochemical, endoscopic and Doppler ultrasound variables were prospectively recorded in 207 consecutive patients with chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables with diagnostic accuracy > or = 65% in univariate analysis, then by stepwise regression. RESULTS: A) whole group (n=207), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 81%, and 81% with 1 variable: irregular liver surface at ultrasound, 2) Diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 80%, and 79% with 2 variables: prothrombin index, gamma-globulins. B) patients with cirrhosis (n=116), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 71%, and 72% with 2 variables: platelet count, prothrombin index, 2) diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 71%, and 72% with 3 variables: platelet count, prothrombin index, spider naevi. The ROC curve showed that the best threshold for the diagnostic accuracy of platelet count was 160 G/l providing a sensitivity of 80% and a specificity of 58%. Platelet count > or = 260 G/l has a negative predictive value > or = 91%. CONCLUSIONS: Using a few non-endoscopic criteria, esophageal varices can be correctly diagnosed in 81% of patients with chronic liver disease and in 71% of patients with cirrhosis. These results show that the non-invasive screening of patients who are candidates for the primary prevention of variceal bleeding is possible, but should be improved before being used in a clinical setting.

Analysis of Variance↗
PubMed1999

A short induction regimen of interferon-alpha is not effective for treatment of relapse in chronic hepatitis C: a randomized trial. For the multicentre GER-CYT-01 group.

The aim of this work was to assess the effect of a high-dose (10 million units, MU) short-duration (14 weeks) interferon-alpha2b (IFN-alpha2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty-eight non-cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high-dose, short-duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high-dose, short-duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively (P = NS). At the end of the 72-week follow-up, in the high-dose, short-duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group (P = NS). There was less fibrosis improvement in the high-dose, short-duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) (P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high-dose, short-duration treatment with IFN-alpha has no advantage when compared to a 6-month treatment with 3 MU IFN t.i.w.

Adult↗
PubMed1999

Detection of telomerase in hepatocellular carcinomas using a PCR ELISA assay: comparison with hTR expression.

BACKGROUND: While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected in many immortal cell lines and various cancers. AIM: To investigate telomerase expression in hepatocellular carcinoma, and to assess the expression of the RNA component of telomerase, hTR. METHODS: 39 hepatocellular carcinomas were studied using a telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay, which does not require radioactive PCR amplification and yields a semiquantitative measurement. Expression of hTR was also assessed by a non-radioactive in situ hybridisation procedure. The correlations between these two markers and the clinicopathological data were analysed. RESULTS: Telomerase activity was detected in 23 of 39 hepatocellular carcinoma specimens (59%). Comparison of hepatocellular carcinoma with and without telomerase expression, or with high and low telomerase (10 cases v 13 cases), showed no differences in the principal clinicopathological data. Although median survival was lower in the group with detectable telomerase activity than in that with undetectable activity (510 v 720 days) the difference was not significant (log-rank test, p = 0.08). hTR expression was detected in 11 of 14 cases of hepatocellular carcinoma tested (78%) and in four of 12 samples of adjacent non-cancerous tissue (33%). Five tumours and four non-cancerous tissues were positive for hTR, whereas no telomerase activity was detected in these. CONCLUSIONS: The presence of telomerase activity in hepatocellular carcinomas is confirmed. No correlation was observed between clinicopathological data and telomerase expression in hepatocellular carcinoma, but survival seemed better in the absence of telomerase expression. hTR seems to be more widely expressed than telomerase.

Adult↗
PubMed1999

CD44 is an independent prognostic factor in conventional renal cell carcinomas.

PURPOSE: CD44 is a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions. De novo expression of CD44 and its variant isoforms has been associated with aggressive behavior in various tumors. Since few data are available concerning the role of CD44 in the biological behavior of locally confined renal tumors, we analyzed the expression of CD44 in a large set of conventional renal cell carcinomas to determine its prognostic value in association with other clinicopathologic variables. MATERIALS AND METHODS: Ninety-one patients with locally confined conventional renal cell carcinomas were studied. CD44 standard form (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin-embedded tumor tissue by immunohistochemistry. The prognostic value of the usual clinicopathological variables and CD44 expression was tested using Kaplan-Meier plots by the log rank test and Cox multiple hazard regression analysis. RESULTS: No immunostaining was observed in normal renal tissue. Thirty-two of the 66 conventional renal cell carcinomas (48%) showed CD44H membranous staining of the tumor cells. Only 2 cancers displayed CD44v6 immunostaining. Among the different clinicopathological variables analyzed, tumor stage (p = 0.001), nuclear grade (p = 0.01), size (p = 0.02), vascular (p = 0.05) and perirenal adipose tissue invasion (p = 0.005), and CD44H expression (p = 0.01) were found to be significant prognostic parameters for survival using univariate analysis. Moreover, multivariate analysis indicated stage, nuclear grade and CD44 expression as independent prognostic factors both for overall and disease-free survival. CONCLUSION: CD44 can be considered as a useful prognostic parameter in conventional renal cell carcinoma and may be used in evaluation of the outcome of these tumors.

Adult↗
PubMed1999

In situ detection of lipid peroxidation by-products as markers of renal ischemia injuries in rat kidneys.

PURPOSE: Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. In renal transplantation, this mechanism is triggered by ischemia/reperfusion and may be of relevance in graft failure. MATERIALS AND METHODS: Using specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, we investigated, in situ, by means of an immunohistochemical procedure, the occurrence of lipid peroxidation during different warm ischemic periods of 0, 15, 30, 45 and 60 minutes in rat kidneys prior to reperfusion. The same experiments included followup of the rats after nephrectomy and reperfusion for 10 days. RESULTS: We observed superficial and deep cortex immunostaining with both antibodies against MDA and HNE after 30 minutes of warm ischemia. This immunostaining was observed in the absence of any histological lesions, as assessed by routine staining. After 45 and 60 minutes of warm ischemia, lipid peroxidation byproducts were detected both in the cortex and in the medulla, which is associated with 33% and 66% of rat deaths respectively. CONCLUSIONS: This study confirms the involvement of the lipid peroxidation process in kidney damage during anoxia before reperfusion, and its extension to the whole organ. Lipid peroxidation byproducts were detectable in warm ischemic kidney, and the presence of medulla immunostaining was associated with the animals' death. Lipid peroxidation immunostaining might thus be useful as a sensitive tool to detect ischemic damage after warm ischemia prior to reperfusion, as well as in the decision to carry out kidney transplantation in humans.

Aldehydes↗
PubMed1999

[Morphological aspects of the normal and pathological liver].

Although the liver is a complex organ connected to vascular and duct network, it reacts to insults in a fairly unvarying manner. Correlations between tissue damage severity and abnormalities in clinical and laboratory test findings are usually poor, and as a result, liver biopsy remains a key investigation for the diagnosis and follow-up of chronic liver diseases. Systematic analysis of the type, severity and distribution of lesions of the parenchyma, portal triads and centrolobular veins usually allows to suggest a cause and to evaluate the prognosis. This requires comparison to normal liver histology. The normal histological features and main elemental lesions seen in the human liver are discussed in this article.

Biopsy↗
PubMed1998

Clonal analysis of macronodules in cirrhosis.

Several arguments suggest that most hepatocellular carcinomas (HCCs) occurring in human cirrhotic livers arise from large hepatocellular nodules or macronodules. Except for nodules with obvious features of HCC, there exist no consistent criteria enabling the differentiation between benign regenerative and neoplastic, potentially malignant macronodules. Surrogate markers able to accurately discriminate those lesions that will evolve toward a HCC are required. In this study, we investigated the clonality of 26 macronodules isolated from eight cases of explanted cirrhotic livers in women by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each macronodule, a large set of pathological features was evaluated and used to classify the macronodules into four groups: entirely benign-looking nodule (type 1), low-grade dysplastic nodule (type 2), high-grade dysplastic nodule (type 3), and HCC (type 4). Clonal analysis showed that 14 macronodules (54%) were monoclonal and 12 (46%) were polyclonal. Monoclonality was detected in 5 of 11 (45%) nodules from groups of entirely benign-looking and low-grade dysplastic nodules (types 1 and 2) and in 9 of 15 (60%) nodules from the group of high-grade dysplastic nodule and HCC (types 3 and 4). Neither the etiology of cirrhosis nor the size or histological classification of macronodules was correlated with the clonal status. In conclusion, clonal analysis of macronodules enables the differentiation between mono- and polyclonal macronodules in cirrhosis. Because monoclonal macronodules are prone to evolve to HCC, the determination of the clonal status of a macronodule could provide additional information for evaluating the prognosis of these lesions.

Adult↗
PubMed1998

Clonal analysis of renal sporadic angiomyolipomas.

Renal angiomyolipomas are benign tumors composed of variable amounts of mature fat, smooth muscle, and thick-walled blood vessels. They occur either sporadically or in association with tuberous sclerosis. Such tumors are considered as hamartomas, but few data are available concerning their pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital malformation or a neoplastic process. To answer this question, we assessed the clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA methylation pattern at a polymorphic site on the HUMARA gene was studied by polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme digestion. This procedure enables the differentiation between polyclonal and monoclonal lesions according to their X-chromosome inactivation pattern. Five of the seven women included were informative for the HUMARA gene. The mean size of the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus was observed in the inferior vena cava. Clonal analysis showed that all of the angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic disorders. This result strongly supports the hypothesis that angiomyolipomas arise from the clonal proliferation of an uncommited cell, which will further evolve toward different cell types.

Adult↗
PubMed1998

Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores. Comparison with serum markers.

BACKGROUND/AIMS: Liver fibrosis is mainly evaluated by qualitative histological examination. Although histological semi-quantitative scores and quantitative determination with image analysis are now possible, these methods have not been fully validated and compared. Therefore, we evaluated these two methods prospectively in 243 patients with chronic liver disease. METHODS: The semi-quantitative fibrosis score was evaluated by two independent pathologists, using the Knodell fibrosis score and a 6-grade score derived from the Metavir score; the area of fibrosis was measured by image analysis. The serum levels of hyaluronate, N-terminal peptide of procollagen III, laminin, transforming growth factor-beta1, alpha2-macroglobulin, apolipoprotein A1, PGA score and prothrombin index were measured. RESULTS: There was a good correlation between the semi-quantitative fibrosis score and the area of fibrosis (r=0.84, p<10(-4)). Using multiple regression analysis, the semi-quantitative score was predicted by the 8 serum markers with R2=0.69 (R2=0.59 for hyaluronate at the 1st step) while the area of fibrosis was predicted with R2=0.79 (R2=0.76 for hyaluronate at the 1st step), and the Knodell fibrosis score was predicted with R2=0.65 (R2=0.31 for hyaluronate at the 1st step). CONCLUSIONS: The area of fibrosis, as determined by image analysis, and the semi-quantitative score are well correlated. However, for serum markers the correlation is higher with the area of fibrosis than with the semi-quantitative score. Other characteristics such as reproducibility, rapidity, simplicity, adaptability, and exhaustiveness also favor image analysis.

Biomarkers↗
PubMed1998

De novo expression of CD44 in prostate carcinoma is correlated with systemic dissemination of prostate cancer.

AIMS: To evaluate the role of CD44 in early steps in the development of prostate cancer, and to assess the biological significance of preneoplastic lesions in prostate cancer. METHODS: 38 patients with clinically localised prostate cancer were studied. The standard form of CD44 (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin embedded tumour tissue by immunohistochemistry. Disseminated prostatic cells were detected by prostate specific membrane antigen reverse transcriptase polymerase chain reaction in the blood of each patient before radical prostatectomy. RESULTS: In normal or benign prostate glands, only basal cells showed CD44H and v6 labelling. Fourteen of the 38 prostate cancers (37%) had CD44H membranous staining of prostatic tumour cells. In 18 patients (47%), circulating prostatic cells were detected in blood before surgery. Although no correlation between the expression of CD44 and the Gleason score or staging was observed, a significant correlation was found between the expression of CD44H by tumour cells and prostatic cell blood dissemination (p = 0.04). In 28 cases, foci of prostatic intraepithelial neoplasia were observed, and nine had CD44H immunostaining. CONCLUSIONS: De novo expression of CD44 by prostatic tumour cells is associated with systemic dissemination of prostate cells independently of pathological criteria.

Adult↗
PubMed1998

[Pancreatic metastasis of a renal adenocarcinoma. Apropos of 2 cases].

The pancreas is an uncommon site of metastasis for renal cell carcinoma. We report 2 cases of patients who underwent total and subtotal pancreatectomy 13 and 10 years after resection of the primary tumor. One of the patients already had liver and cerebellum metastasis, the second one had a solitary metastasis to the pancreas. In both cases, tumoral proliferation invaded the lumen of the Wirsung, and in one case was prominent through the papillae.

Adenocarcinoma↗