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Biomedical subjects

R Plagne

Publications and source records attributed to R Plagne.

At least 19 recordsLinked to original sources

Effect of epidermal growth factor in HLA class I and class II transcription and protein expression in human breast adenocarcinoma cell lines.

The spontaneous expression of HLA class I and class II molecules in two human breast carcinoma cell lines (MCF7, T47D) and their modulation during epidermal growth factor treatment are reported. Transcription was analysed by Northern blot and hybridisation with HLA class II and class I cDNA specific probes. The expression of cell surface determinants was examined by internal protein labelling with 35s-methionine, immunoprecipitation with monoclonal antibodies specific for HLA class I or class II, followed by isolation of the immune complex on protein A-Sepharose; at least a quantification of glycoprotein was performed by chromatofocusing. Glycoprotein quantification showed a significant increase of HLA class I and class II (DR) antigen expression after stimulation by epidermal growth factor (0.02 microgram ml-1) in the two cell lines, when compared with untreated cell controls. However, with epidermal growth factor treatment of MCF7 and T47D cells, low increases in the amounts of HLA class I and class II RNA were obtained. These differences between expressed antigens and correspondent RNA amounts would be explained by the fact that EGF in these two cell lines acts more in post-transcription for HLA class I and class II antigens.

Adenocarcinoma

Genotypic analyses of Richter's syndrome.

The authors report the immunogenotype of two cases of Richter's syndrome. The immunoglobulin gene rearrangement pattern obtained on Southern Blot analysis was found in both cases to be the same in leukemic blood cells and in the tissue involved by the lymphoma. The beta chain and gamma chain T-cell receptor gene rearrangement pattern exhibited a germ-line configuration in the peripheral blood cells and in the lymph node in Case 2, whereas in Case 1 the lymph node had a gene rearrangement in the beta chain, as well as in the gamma chain T-cell receptor, and the leukemic cells from bone marrow were found to be in a germ-line configuration for T-cell receptors (beta and gamma chains).

Aged

Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma.

In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem

Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency.

We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma.

Brain Neoplasms

Presence of reverse transcriptase in human leukemias and lymphomas.

Reverse transcriptase (RT) transcribes viral RNA into DNA to be integrated into the host genome. To study epidemiological aspects of human leukemias and lymphomas which are known to express retroviruses, clinical specimens in this report were assayed for divalent cation-dependent viral-specific RT. The assay was carried out with cells solubilized with a detergent to release RT enzyme. RT was purified with poly(U)-Sepharose which fixed all DNA polymerases and assayed with 4 synthetic homopolymers, oligonucleotide primed-templates, poly(rA)-oligo(dT)12-18 or poly(dA)-oligo(dT)12-18 with Mg2+, poly(rC)-oligo(dG)12-18 or poly(rCm)-oligo(dG)12-18 with Mn2+ as divalent cation and [methyl-3H]thymidine 5'-triphosphate or deoxy[8-3H]guanosine 5-triphosphate respectively. Radioactivity incorporation of the precipitate allows quantitation of RT activity. One Hodgkin's disease, one out of 2 B lymphomas, one out of 2 T lymphomas, eight out of 12 leukemias were found to be positive for RT activity as well as acquired immunodeficiency syndrome (AIDS) patients, known to express RT. The obtained RT activity in hematological malignancies was found to be comparable to positive controls such as RT enzymes purified from avian myeloblastosis and Moloney murine leukemia viruses.

Acquired Immunodeficiency Syndrome

Effects of cyclosporine A on Ia antigen expression in N-nitroso-N-methylurea-induced rat mammary tumors.

Cyclosporine A (an immunosuppressive agent) decreases Ia lymphoid differentiation marker in female Sprague-Dawley rats with N-nitroso-N-methylurea-induced mammary tumors. Presence of lymphoid differentiation antigens was determined on mammary tumor cells and lymphoid cells from bone marrow, spleen, and peripheral blood by flow cytometric analysis. Quantification of Ia antigen expression was also performed by affinity chromatography and chromatofocusing in mammary tumors. A significant decrease in Ia antigen expression by mammary tumors of animals treated with cyclosporine A was noted with the two different methods. Cyclosporine A acts as an antagonist to prolactin receptors in such hormone-dependent mammary cancer. Our results should prove very useful in understanding the mechanisms of prolactin regulation of Ia antigen in tumorigenesis of the mammary gland.

Animals

[Adjuvant medical treatment].

Adjuvant medical treatments (chemotherapy or endocrine therapy) are now used in the vast majority of women with breast cancer. They delay recurrences and reduce their number, the increase in survival being particularly marked in limited forms. They also reinforce local treatment and increase the possibility of breast conservation. Their indications can be better determined by precise analysis of prognostic factors, notably tumoral cells.

Adjuvants, Pharmaceutic

[Stage III and IV epithelial cancer of the ovary. Prognostic role of surgical tumor reduction].

We report the results of surgical excision prior to chemotherapy in 180 cases of advanced epithelial ovarian carcinoma. In this retrospective study, the mean survival rate at 5 years was 22 percent. It was 40 percent in patient with stage III carcinoma, divided into 60 percent for micronodular carcinomas (stages IIIa + b) and 30 percent for macronodular carcinomas (stage IIIc). However, in cases with optimal initial excision the overall survival rate was the same in patients with macronodular carcinoma as in those with micronodular carcinoma. This finding suggests that surgical excision itself has a favourable effect on the prognosis of this disease.

Adult

Detection of Epstein-Barr viral genomes in lymph nodes of Hodgkin's disease patients.

Previous studies using Southern blot analysis or in situ hybridization have shown that approximately 20% of patients with Hodgkin's disease have Epstein-Barr virus (EBV) in involved tissues. We used the more sensitive polymerase chain reaction (PCR) technique to determine if a higher percentage of EBV could be detected. Of the 16 Hodgkin's disease patients studied, the PCR technique detected EBV in eight (50%). No prognostic significance was associated with the presence of EBV in the eight EBV-positive patients, and the presence of EBV was not associated with B cell monoclonality.

Adolescent

Dual genotype in cutaneous T-cell lymphomas and pseudolymphomas.

Genomic DNA digests of skin biopsies from 20 patients with cutaneous T-cell lymphomas and pseudolymphomas were studied by hybridization, using probes for the constant region of the T-cell receptor beta chain and the joining region of the immunoglobin heavy chain gene. Skin biopsies from all 20 patients contained a monoclonal T-cell population. In addition, DNA from 5 patients contained an immunoglobulin gene rearrangement. These results demonstrate that cutaneous T-cell lymphomas are clonal T-cell malignancies that frequently express a dual genotype, which may sometimes reflect the clonotypic heterogeneity of these disorders.

Gene Rearrangement, beta-Chain T-Cell Antigen Rece

Genotypic analyses of Hodgkin's disease.

In spite of the use of molecular biology, the cellular lineage and clonality of Reed-Sternberg cells, the abnormal cells of Hodgkin's disease, remain an enigma. We studied the pattern of rearrangements at immunoglobulin and T-cell receptor loci in 23 patients suffering from Hodgkin's disease. Two out of 23 patients exhibited immunoglobulin gene rearrangements. No rearrangements of the T-cell receptor beta-chain gene were detected in any patient examined. Our results showed no correlation between the presence of rearranged bands and the number of Reed-Sternberg cells.

Antigens, CD

[High doses of alkylating agents and bone marrow autograft in ovarian cancer with poor prognosis: a retrospective analysis of 40 patients treated in France].

Reviewed in this study are 40 patients treated by high-doses of alkylating agents followed by autologous marrow rescue for ovarian cancers. All patients received this therapy after extensive surgery and a median of 6 cycles of CDDP containing regimens (CAP or CHAP). All patients, except 4, who showed evidence of progression, had a second surgical exploration before the high dose chemotherapy. Conditioning regimens consisted of: melphalan at a dosage greater than 140 mg/m2 for all patients; in addition, 2 received Endoxan 120 mg/kg and 1 busulfan 16 mg/kg. Autologous marrow rescue was infused 24 h after the conditioning regimen. Severe, but reversible aplasia and mucositis were the most common toxicities. Three patients died from this procedure, 2 from infection and 1 from secondary leukemia. Twelve out of 15 patients evaluated responded (80%) showing evidence of activity in patients who did not respond to first line chemotherapy. Duration of response was short, especially for patients treated for progressive disease rather than in partial or complete response at the time of high doses chemotherapy. With a median follow up of 23 months (range 8.54) 19 patients survived (15 with non-evolutive disease) leading to a projected survival rate of 39% between 27 months and 5 years. These results are encouraging for poor risk patients who failed to respond to initial chemotherapy. For patients who have small or no residual disease after initial therapy, the place of such intensification should be confirmed prospectively in a larger cohort of patients.

Adenocarcinoma, Mucinous

[Epithelial cancer of the ovary. Contribution of the experiences of a treatment facility to the current data of prognosis and treatment].

Results obtained by the authors and a review of the literature have made them able to point out recent developments in cases of epithelial cancer of the ovary diagnosed in an advanced stage of the disease. This is the most frequent finding when the diagnosis is made and it is most important in assessing the future prognosis to know how far on the disease has progressed. Cancer of the ovary has long been thought of as a peritoneal disease, but all the same 40% of metastases occur further away and the majority of these are in the pleura or the lung and more rarely in the brain; and all these have been observed. The degree of differentiation is another important element for prognosis. Deciding how differentiated tissue is, is relatively subjective. A scoring protocol is suggested to make the assessment more systematic. The grading can be varied according to the response to treatment. A great majority of authorities believe that reduction of the size of the tumour surgically should be the first procedure but how useful this is has never been proved because there has never been any controlled study. It is possible in most cases to reduce the size of the tumour greatly but often this may need removal of some of the intestines with acceptable morbidity. Chemotherapy with Cisplatin, Cyclophosphamide and in the hands of certain authors, Doxorubicine, has been shown to be helpful in 80% of cases and seems to be the most appropriate treatment.

Carcinoma

High dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinomas: a retrospective analysis of 35 patients treated in France.

We retrospectively evaluated the feasibility and antitumour efficacy of high dose melphalan (HDM) followed by autologous marrow rescue in 35 patients with common epithelial ovarian cancers. All patients initially had advanced disease (FIGO III-IV) and received HDM after extensive surgery and a median of 6 cycles of cis-DDP containing regimens CAP or CHAP. All, except three patients who showed evidence of progression, had a second surgical exploration before high dose chemotherapy. Melphalan was given at a dosage greater than or equal to 140 mg/m2 followed 24 h later by autologous marrow rescue. Severe but reversible aplasia and mucositis were the most common toxicities: three patients died from the procedure, two from infection and one from secondary leukaemia. HDM was effective in 75% of evaluable patients; this was evidence of activity in patients who failed to respond to first line chemotherapy. The duration of response was short, particularly for patients treated with progressive disease at the time of high dose chemotherapy rather than in partial or complete remission. With a median follow-up of 23 months (range 8-54) after high dose chemotherapy, 19 patients are alive (15 with non-progressive disease) with a projected survival of 47% between 2 and 5 years.

Adult

High-dose melphalan and autologous bone marrow support for treatment of ovarian carcinoma with positive second-look operation.

Patients with epithelial ovarian carcinoma (OVCA) and positive second-look operation (SLO) have a poor short-term prognosis. Treatment after SLO is still controversial and pilot studies are justified in an attempt to improve survival of these patients. As OVCA is known to be a chemosensitive tumor, it seems logical to treat these patients with high-dose chemotherapy with the support of an autologous bone marrow transplantation. Fourteen patients underwent primary surgery with tumor debulking followed by cis-platinum-based chemotherapy. SLO was performed in each patient and was microscopically positive in five and macroscopically positive with secondary debulking in nine. All patients were treated after SLO with high-dose melphalan (HDM), 140 mg/m2, and autologous bone marrow support. HDM was well tolerated, with a median time to granulocyte recovery of 21 days. There was no death due to treatment toxicity. The mean follow-up after SLO is 43 months. Five patients (35.7%) are disease free at 30 to 60 months after SLO with no further treatment and, thus, a good quality of life. Four patients are alive with recurrent disease. Five patients died of OVCA; actuarial 3-year survival is 64%. This therapeutic procedure is well tolerated and seems to provide long-term survival for patients with no complete response after first-line chemotherapy. Therefore, it might also be applied to patients at high risk of recurrence after a negative SLO.

Adenocarcinoma

Evidence of 3 beta-hydroxysteroid dehydrogenase activity in several murine embryonal carcinoma cell lines.

This report describes, for the first time to our knowledge, a possible steroidogenic activity in established murine embryonal carcinoma cell lines (PCC3, PCC4, F9), revealed by a 3 beta-hydroxysteroid dehydrogenase activity (revelation of NADH2 by staining, and RIA assessment of delta 4-androstenedione). The remarkable analogy between such totipotent cells and embryonal cells may suggest that this activity could be present before histologic organization of the embryonal testis. Nonmalignant embryonal cells such as fibroblasts (3/A/1/D-3) or myoblasts (T984) were also found to possess a 3 beta-hydroxysteroid dehydrogenase activity, thus suggesting that this enzyme is not specific to hormone-secreting cells, but the sign of a more general phenomenon.

3-Hydroxysteroid Dehydrogenases