VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues.
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Biomedical subjects
Publications and source records attributed to François Labrousse.
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We report pathological characteristics of screen detected breast cancers versus breast cancers diagnosed outside the official breast screening program. The breast cancer screening program was organised in the county of Haute-Vienne and a pathological record was established in the Association de dépistage des cancers du sein (ADCS 87). Three hundred and thirty three cases were recorded in 50 to 74 years-old women who had been screened (74 were interval cancers), six hundred and eighty seven in 50 to 74 years-old women without screening and three hundred and fifteen in women under 50. No difference in ductal carcinoma in situ or histological type was noted but tumor size and lymph node involvement presented significantly more favorable prognosis in screen detected breast cancers. This study confirms the potential benefit of screening in breast cancer.
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OBJECTIVE: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator involved in several types of cancer in humans. The levels of PAF, lyso-PAF (the PAF precursor), phospholipase A2 activity (PLA2, the enzymatic activity implicated in lyso-PAF formation) and acetylhydrolase activity (AHA, the PAF-degrading enzyme) were investigated in various diseased thyroid tissues. SUBJECTS: Control and diseased tissue of patients with a hyperplastic goitre (n = 14), a benign adenoma (n = 12) and a papillary thyroid carcinoma (n = 15) were investigated. RESULTS: PAF receptor transcripts were found in the human thyroid tissue. PAF, lyso-PAF, PLA2 and AHA were present in control thyroid tissues, their levels being significantly correlated with each other, suggesting tiny regulations of the PAF metabolic pathways inside the thyroid gland. PAF, lyso-PAF, PLA2 and AHA levels remained unchanged in diseased tissues of patients with a hyperplastic goitre, a benign adenoma and a papillary thyroid carcinoma. No difference was found between PAF, lyso-PAF, PLA2 and AHA levels with respect to the TNM tumour status and the histological sub-type of papillary thyroid carcinoma. No correlation was found between tissue PAF levels and those of vascular endothelial growth factor and basic fibroblast growth factor, two angiogenic growth factors involved in thyroid cancer and that mediate their effect through PAF release in breast and colorectal cancer. CONCLUSION: PAF, PAF receptor transcripts and the enzymatic activities implicated in PAF production and degradation are present in the thyroid gland. While the physiological role of PAF is presently unknown in thyroid physiology, this study highlights no evidence for a potentially important role of PAF during human thyroid cancer, a result that markedly differs from breast and colorectal ones.
BACKGROUND AND OBJECTIVES: Small B-cell indolent lymphomas postulated to be of a post-germinal center origin include marginal zone lymphomas of the spleen (S-MZL) or lymph nodes (N-MZL) and mucosa-associated lymphoid tissue (MALT) lymphomas and lymphoplasmacytic lymphomas (LPL). The existence of rather aggressive cases stresses the need for new biological prognostic markers. DESIGN AND METHODS: We analyzed 90 tumors (20 LPL, 41 MALT lymphomas, 12 N-MZL, 17 S-MZL), investigating the expression of CD5, CD10, CD20, CD23, CD27, CD38, CD79a, CD138, Bcl6, cyclin D1, IRF4 and Ki67 antigens by immunohistochemistry. Results were compared to the histology, the standard clinical and biological parameters, and the global survival. RESULTS: Tumors were all positive for CD20 and CD79a, occasionally positive for CD5, CD23, CD138 and cyclin D1, and all negative for Bcl-6 and CD10. CD38, CD27 and IRF4 expression was heterogeneous. IRF4 expression was correlated with plasma-cell differentiation (p=0.0017). Ki67 expression was increased mainly in N-MZL (66%) and LPL (45%). In terms of overall survival, Ki67, IRF4 and C-reactive protein levels were found to be the 3 independent parameters associated with a worse outcome. Lack of both Ki67 and IRF4 expression was associated with a longer survival (median overall survival 9.8+/-1.1 years versus 3.6+/-1.3 years in the other group) (p=0.0011). INTERPRETATIONS AND CONCLUSIONS: Absence of expression of both Ki67 and IRF4 is likely to define a group of memory B-cell lymphomas with a better prognosis. This may have an important impact in the staging of patients since expression of these markers is easily assessed in routine diagnosis.
Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80mg/kg. After a transient aparasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to understand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, megazol plasma profiles in uninfected sheep after a single oral dose of megazol showed a fast megazol lowered absorption associated with a short plasma half-life of drug. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route.
Onychomatricoma is a rare fibroepithelial lesion of the nail matrix with peculiar clinical and histological features. Clinically, it is characterized by a longitudinal band of yellow thickening of the nail plate with transverse overcurvature and splinter hemorrhages. Nail avulsion exposes a villous tumor of the matrix with filamentous digitations extending into multiple holes of the nail plate. Histologically, a thick keratogenous zone forms a thickened nail plate. The lesion in its proximal portion is characterized by deep epithelial invaginations and by a stroma organized in two layers. The distal zone corresponds to multiple fibroepithelial projections extending into the nail plate. The diagnosis can be difficult in the presence of misleading clinical features or when the specimen is incomplete or examined with an improper orientation. Surgical resection is the recommended treatment.
Brefeldin A (BFA), a fungal metabolite known to affect the structure and function of the Golgi apparatus, has recently been shown to induce apoptosis and cell growth inhibition in various human cell lines. Glioblastomas (GB) are cerebral tumors with poor prognosis, which display resistance to current therapies including radio- and chemotherapy. The objective of this study was to investigate BFA effects in three human GB cell lines (SA4, SA146 and U87MG cells). Compared with control cells, about 60% of cell growth inhibition was observed in BFA (100 ng/ml for 24 h)-exposed cells in the three cell lines. Furthermore, in SA4 and SA146 cells, BFA was able to induce a time- and dose-dependent apoptosis detected by DAPI staining, TUNEL assay and flow-cytometric analysis. Since p53 expression was not modified after BFA exposure, BFA-induced apoptosis may follow a p53-independent pathway, as already reported. In the same way, BFA did not alter Bcl-2, Bax and Mcl-1 expression. Cell cycle analysis revealed a cell cycle arrest in early G0/G1 phase with an increase in G0/G1 cell population (70% in control cells vs. 83% in exposed cells) associated with a decrease in the S cell population (14% in control cells vs. 5.5% in exposed cells). The Ki67 labeling index also confirmed the cell cycle blockade. Our results suggest that BFA may be a potent cell cycle modulator and inducer of apoptosis in GB cell lines, and therefore may become a promising candidate for the chemotherapeutic treatment of gliomas.
Myxopapillary ependymomas represent the most frequent type of ependymomas found at the conus medullaris-cauda equina-terminal filum level. They are neuroectodermal tumors mainly observed during the fourth decade of life. Pediatric cases have been rarely described at an age range of 10 to 13 years. Myxopapillary ependymomas are typically solitary tumors involving the terminal filum. Simultaneous discovery of two tumors located both on the terminal filum has been reported once. The pathogenesis of this focal ependymoma located at the same embryological level, on the terminal filum, is uncertain; it may represent one end of a spectrum, the other end being the giant ependymoma of the terminal filum.
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BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) is a well-known complication of immunosuppression associated with solid organ transplantation. The donor or host origin of PTLD may influence the outcome of the disease as it has been reported that a donor origin may be associated with a better prognosis. The aim of the study was to determine the origin (recipient or donor) of 12 PTLD occurring in kidney transplant recipients and to correlate the results with clinical findings. METHODS: Origin of PTLD was determined using HLA DRB1 molecular typing, analysis of multiple short-tandem repeat microsatellite loci, and HLA class I antigen expression by immunohistochemistry. RESULTS: Combining the three techniques, we found that eight cases originated from the recipient and four cases originated from the donor. The results of the three techniques were concordant and altogether assigned the origin of the tumors. All the donor-origin PTLD were strictly localized to the kidney graft, developed after a mean time of 5 months after transplantation, and regressed after reduction of immunosuppression. In contrast, seven of the eight recipient-origin PTLD presented as multisystemic disease, occurred a mean time of 75.7 months after the transplantation, and had a worse outcome (mortality, five deaths of eight patients, 62.5%). CONCLUSIONS: These results suggest that PTLD originating from the donor arise in the first year after transplantation into the graft, and that recipient-origin PTLD develop later as an invasive disease. Because it permits simultaneously the analysis of cell morphology and tumor origin, immunohistochemistry is a more reliable technique in the case of graft tumors associated with allograft rejection. The determination of the origin of the tumors seems to be of value in the management of PTLD to predict the outcome and to adapt therapy.