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Biomedical subjects

F Penault-Llorca

Publications and source records attributed to F Penault-Llorca.

At least 55 records · Page 3Linked to original sources

FGF7 protein expression in human breast carcinomas.

FGFs, especially FGF7, are thought to play an important role in the stroma-epithelium interactions that take place in several tissues, including the prostate and mammary glands. Using an immunohistochemistry approach, FGF7 protein expression was measured in a series of 80 human breast carcinomas. FGF7 was found to be expressed in two-thirds of cases studied, either in the stroma or in the tumour cells. Although it did not reach significance level, a tendency was noted for FGF7 expression to be associated with the most differentiated and least aggressive tumours.

Antibodies, Monoclonal↗

Analysis of BAX expression in human tissues using the anti-BAX, 4F11 monoclonal antibody on paraffin sections.

BAX, a heterodimer partner of BCL-2, is an apoptosis inducer. We aimed to characterize the distribution of the BAX protein in normal adult human tissues using immunohistochemistry (IHC). The monoclonal antibody anti-BAX 4F11 was used on paraffin sections: immunodetection of BCL-2 was performed simultaneously on serial sections. The specificity of BAX IHC staining was verified by Western blot analysis. IHC positivity was correlated with the detection of a specific 21 kDa band on Western blots. BAX immunostaining was mainly cytosolic and occasionally on the nuclear membrane. Amounts of BAX protein were high in liver, renal tubules, endocrine islets of the pancreas, gastric glands, cardiac muscle, epididymis, lymph node germinal centers, and neurons; intermediate in the colon, stomach, bronchus. Fallopian tube, salivary gland, breast, thymus, spleen, and testis; low or undetectable in the other tissues. BAX IHC positivity correlated with apoptotic features in neurons and germinal center lymphocytes. There was no strict correlation between the IHC profiles of BAX and BCL-2 expression, although a reciprocal pattern of staining was observed in lymph node and colon. This report shows the usefulness the monoclonal antibody anti-BAX 4F11 on paraffin sections and demonstrates that the human BAX tissular distribution is close to, but not similar, to the profile observed in the mouse. The widespread BAX expression suggests that BAX alone is insufficient to trigger cell death in human tissues. BAX may either modulate the role of other regulators of apoptosis or carry out functions unrelated to apoptosis.

Animals↗

High-dose chemotherapy and haematopoietic stem cell transplantation for inflammatory breast cancer: pathologic response and outcome.

Inflammatory breast cancer still has a poor prognosis despite improvements related to the introduction of neoadjuvant chemotherapy. The purpose of this study was to evaluate pathologic response rate and outcome of patients receiving high-dose chemotherapy with haematopoietic stem cell support for IBC. Seventeen consecutive patients with IBC received an association of mitoxantrone (36 mg/m2), cyclophosphamide (120 mg/kg), melphalan (140 mg/m2), with stem cell transplantation (SCT) following four to five cycles of cyclophosphamide (1000 mg/m2), doxorubicin (75 mg/m2) and 5FU (500 mg/m2). Mastectomy was performed a median of 2 months (range 1.5-45) after high-dose chemotherapy and was followed by radiotherapy. Macroscopic and microscopic pathologic complete response rates were respectively 56 and 39%. With a median follow-up of 36 months (range 17-52) 10 patients remain alive free of disease and seven patients have relapsed. Two relapses occurred in the group of patients with pathologic CR and five in the group with residual tumour. These results show that high-dose chemotherapy (HDC) with alkylating agents followed by SCT allows a very high tumour eradication in inflammatory breast cancer, suggesting a possible global benefit in progression-free survival and survival which remains to be demonstrated prospectively.

Adult↗

Pathology of sporadic breast tumors with LOH at the BRCA1 locus: correlation with histopathological features specific to familial BRCA1 tumors and absence of microsatellite instability.

To investigate the coordinated occurrence of loss of heterozygosity (LOH) at the BRCA1 locus and microsatellite instability (MI) in sporadic breast carcinomas, 56 tumors were analysed for both genetic alterations. The comparison of clinicopathological features with the obtained data revealed that LOH at the BRCA1 locus was significantly correlated with features specific for familial BRCA1 tumors and with absence of hormone receptors. No correlation was found between LOH and MI. These results suggest that sporadic and familial breast tumors, where BRCA1 is altered, could display similar clinicopathological features and that LOH and MI are distinct genetic events in sporadic breast carcinogenesis.

Adult↗

[Natural history of ovarian adenocarcinomas: from epidemiology to experimentation].

The ovarian carcinogenesis is not well known because the diagnosis is usually delayed to an advanced stage with a lot of chromosomic abnormalities. On the other hand, there is a lack of animal models and preneoplastic patterns are discussed. Different ways of studying are in progress. Prophylactic oophorectomy in women with BRCA1 mutation provides ovaries that can be compared to a control group. Epithelial or stromal changes are observed in the familial risk group more frequently than in the controls and could be preneoplastic. An experimental approach has been developed in order to confirm the Fathalla's theory of the incessant ovulation by culturing cells of rat surface ovarian epithelium with a high proliferative pressure. These cells become malignant in 10 out of 30 cases (after 10 cultures). The transformed tumor cells are a syngeneic tumor model that can be transplanted in the animal and analysed by molecular biology technics. This allowed to show the loss of a potentially tumor suppressor gene, lot 1, in the transformed cells and on the other hand the overexpression of a gene coding for a protease enzyme the cathepsin B, which is a marker of an aggressive metastatic power.

Adenocarcinoma↗

[In vitro and in vivo models developed from human prostatic cancer].

The possibility of maintaining and studying human prostatic cancers in an in vitro and in vivo environment has allowed the development of rare but essential tools to study many aspects of the biology of these cancers. Although none of the available models is perfect, the sum of the studies conducted with these models over more than 20 years constitutes the basis for major progress in our understanding of this disease. The most widely used cell lines (cultured in vitro) are PC-3, DU-145 and LNCaP. They are limited by the fact that they are essentially androgen-independent cell lines, derived from metastatic sites. Due to the slow growth of prostatic cancers, it is very difficult to obtain cancer cell lines which can be transplanted in immunodeficient animals (such as athymic mice) and only a few xenografts are currently available, some of which, like PCV-82, LuCaP 23, CWR-22, are androgen-dependent or sensitive. These models can be used to study host-tumour interactions as well as endocrinological interactions, stroma-tumour cell interactions, and to analyse molecular phenomena related to stages of hormone dependence and hormone resistance. In vitro and in vivo models of metastatic prostatic cancer have also been developed and appear to have a crucial impact on the understanding of metastatic mechanisms and new therapeutic approaches. This paper describes the main experimental models developed from human prostatic cancers, their main characteristics, their value compared to clinical cancers and some of the major studies conducted with these models. Due to the exponential progress in molecular biology techniques and oncogenetics, it appears essential to increase the number and diversity of experimental models of prostatic cancer in order to advance research concerning the crucial phenomena occurring during the course of this disease, from oncogenesis to currently incurable metastatic stages.

Androgens↗

[Clear cell sarcoma of the kidney relapsing after 10 years of asymptomatic evolution].

We report the case of a kidney tumor occurring in a thirteen year-old girl. This tumor was first diagnosed and treated as a benign one. After ten years without recurrence, a relapse occurred. The diagnosis was recurrent clear cell sarcoma of the kidney. The course in our case is uncommon because clear cell sarcoma of the kidney is a rare and aggressive pediatric neoplasm, usually characterized by a predilection for bone metastases, and a mid survival rate of 30 months without treatment.

Adolescent↗

[Pancreatic and duodenal somatostatinoma. Two clinico-pathologic entities].

Somatostatinomas are endocrine tumors with predominant secretion of somatostatin. The majority occur in the pancreas and the duodenum. However, distinctive clinico-pathologic features are reported for both of them. The features of pancreatic somatostatinomas are a larger size, a more frequent clinical expression, a female predominance and a poorer prognosis. Duodenal somatostatinomas are characterized by psammoma bodies at histologic examination. We report here two cases of pancreatic and ampullary somatostatinomas, focusing on the main diagnostic problems and on the characteristics of each tumoral localization.

Aged↗

Expression of FGF and FGF receptor genes in human breast cancer.

The family of FGF growth factors is involved in several biological processes and might play an important role in tumorigenesis. We have studied the respective expression of 8 of the 9 characterized FGF genes, and of the 4 known FGF receptor genes, in a panel of 10 tumor-cell lines and 103 breast-tumor samples, using RT-PCR and Northern-blot analyses. FGF1 and FGF2 were expressed in almost all samples, while expression of FGF5, FGF6, FGF7, and FGF9 was more restricted. FGFR1, FGFR2 and FGFR4 were expressed at high levels in respectively 22%, 4% and 32% of tumors. FGFR3 expression was not detected. The transcript encoding an FGFR1 isoform with 2 immunoglobulin-like domains was the most prevalent.

Base Sequence↗

Expression of the FGFR1 gene in human breast-carcinoma cells.

Fibroblast growth factors (FGF) constitute a family of at least 9 members which act through high-affinity tyrosine-kinase receptors encoded by 4 distinct genes. In humans, the FGFR1 gene is located in chromosomal region 8p12. Its amplification and expression were examined in a panel of 110 breast carcinoma samples by Southern- and Northern-blot analyses. FGFR1 was amplified in 9% and overexpressed in about 15% of the tumors studied. In situ hybridization experiments were performed on tissue sections of normal breast and tumors with a high level of FGFR1 expression. In both normal and tumoral tissues, FGFR1 RNA was detected in the epithelial cells. Overexpression of FGFR1 seems to be associated with small, well-differentiated diploid tumors.

Blotting, Northern↗

The Heregulin gene can be included in the 8p12 amplification unit in human breast cancer.

The Heregulin (HGL) gene, encoding a ligand for a member of the ERBB receptor family, is located at 8p12-p22, in or close to a region frequently amplified in breast carcinoma. Amplification of HGL was detected in three of 83 (3.6%) cases of breast tumors. No overexpression of the gene was observed in the amplified tumors. This and the low incidence of amplification suggest that HGL is not the key gene of the 8p12 amplification but may be used as a marker of large amplification units.

Breast Neoplasms↗

Optimization of immunohistochemical detection of ERBB2 in human breast cancer: impact of fixation.

In an attempt to standardize the immunohistochemical detection of ERBB2, we evaluated six normal breast samples and 58 breast carcinomas for (1) the effect of four different fixatives (Bouin's fluid, buffered formalin, alcoholic formalin, and methacarn), and (2) the sensitivity and specificity of eight commercially available antibodies. ERBB2 gene copy numbers and RNA transcripts were measured by Southern and Northern blot analysis in all samples. The BT-474 and MCF7 cell lines were processed in the same way as the tissue samples and used a s references of activation or the normal state of the ERBB2 gene, respectively. Complete concordance between immunohistochemistry and molecular biology was observed in 43/58 cases (74 per cent). However, fixation and processing protocols significantly affected the reactivity of the antigenic determinants. The most consistent results were obtained with NCLCB11 on frozen sections and with Tab250 on paraffin-embedded sections. For prospective studies, the use of alcoholic formalin in association with a highly specific antibody (Tab250, 9G6, NCLCB11, or OA-11-854) gave the best results. Methacarn appears to be a reliable fixative, but was studied in only 28 cases. For retrospective studies, the most important parameter to take into account is the sensitivity of the antibody. Thus, with Bouin's fixation, 3B5 was the only reliable antibody, whereas with buffered formalin, Tab250 gave the most consistent results. This study will help inter-laboratory comparisons, and in determining the prognostic significance of ERBB2 expression in breast carcinomas using a standardized methodology.

Antibodies, Monoclonal↗