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Biomedical subjects

P Busson

Publications and source records attributed to P Busson.

43 records · Page 3Linked to original sources

Expression of the c-fgr related transcripts in Epstein-Barr virus-associated malignancies.

The proto-oncogene c-fgr is expressed at high levels in cell lines derived from lymphomas which are infected with Epstein-Barr virus (EBV) (Cheah et al., 1986). mRNA extracted directly from biopsies of EBV-infected tissues was analyzed on Northern blots to determine if c-fgr is expressed during lympho-proliferations induced in vivo by EBV and in nasopharyngeal carcinoma (NPC), the epithelial malignancy associated with the virus. Elevated levels of c-fgr expression were detected in all EBV-positive lympho-proliferations in vivo but not in cell lines established by EBV infection in vitro. This indicates that the induction of the c-fgr proto-oncogene is not an essential component of EBV-induced transformation. Although no c-fgr expression was detected in EBV-positive or -negative epithelial cell lines, the 3.0-kb c-fgr mRNA was detected at low levels in mRNA obtained from NPC biopsy specimens. However, NPC tissue, after passage in nude mice (which eliminates infiltrating lymphoid and myeloid cells) did not contain the 3.0-kb c-fgr mRNA. The absence of expression of c-fgr in the malignant epithelial cells infected with EBV contrasts with the elevated level of the proto-oncogene in EBV-infected lymphoma tissue and cell lines established from lymphomas. This suggests differences in the expression of cellular functions in EBV-induced malignancies of these 2 distinct cell types.

Genes, Viral↗

Epstein-Barr virus gene expression in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV), an agent with growth transforming potential for human B cells, is associated with certain B cell lymphomas in man and also with an epithelial tumour, undifferentiated nasopharyngeal carcinoma (NPC). Since B cell growth transformation is associated with the constitutive expression of a small number of EBV-coded latent proteins, the nuclear antigens EBNA 1, EBNA 2, EBNA 3 and EBNA-LP and the latent membrane protein (LMP), the present work sought to determine whether this same pattern of virus gene expression occurred in NPC. Tumour biopsies were taken from NPC patients from three areas of differing tumour incidence (Kenya, Algeria, Britain) and immediately snap-frozen, as were biopsies of non-EBV-related carcinomas for controls. Immunoblotting of PAGE-separated proteins with selected human sera identified 24 NPC biopsies clearly expressing EBNA 1. When the analysis was extended using selected human sera with antibodies against the other EBNAs, there was no detectable expression of EBNA 2, EBNA 3 or EBNA-LP in any of these 24 biopsies; their EBNA 2-negative status was confirmed using a monoclonal antibody (MAb) PE2 which was reactive in immunoblotting and in immunoprecipitation with EBNA 2A and EBNA 2B proteins. Similar experiments with two different LMP-specific MAbs, CS1 to 4 and S12, revealed heterogeneity between NPC biopsies; 9/24 biopsies were demonstrably LMP-positive, the degree of expression varying considerably between individual tumours in a manner which was not related to the level of EBNA 1 expression. None of the 24 NPC biopsies expressed detectable amounts of EBV lytic cycle antigens. A nude mouse-passaged NPC cell line, C15, likewise expressed EBNA 1 and LMP but none of the other EBV latent proteins nor lytic cycle antigens. This work identifies a novel type of EBV-cell interaction in NPC cells which is distinct from that seen in in vitro transformed B cell lines and from that seen to date in EBV-positive B cell lymphomas.

Antibodies, Monoclonal↗

Constitutive expression of HLA class II antigens on EBV positive malignant cells from nasopharyngeal carcinoma: possible involvement in T cell infiltration.

Undifferentiated nasopharyngeal carcinoma (NPC) was originally referred to as "lymphoepithelial carcinoma." Two main cell types are constantly associated within these tumors: the malignant epithelial cells which harbor the Epstein-Barr virus (EBV) genome, and the nonmalignant lymphocytes mostly of the T lineage. Three characteristic features of malignant NPC cells might explain T cell migration within NPC tumor tissue: HLA class II molecule expression, IL-1 production, and presence of EBV antigens. Homogeneous suspensions of malignant NPC cells were derived from a nude-mouse transplantable tumor in order to specify the status of HLA class II molecules in these tumors. These suspensions were stained for HLA class II antigens and analyzed by flow cytometry in comparison with other carcinoma cell lines. Three characteristics of transplantable malignant NPC cells were demonstrated: constitutive and coordinate expression of DR, DP, and DQ molecules, and concomitant expression with the CDw40 antigen ("B lymphocyte carcinoma cross-reacting antigen").

Adolescent↗

Epstein-Barr virus-containing epithelial cells from nasopharyngeal carcinoma produce interleukin 1 alpha.

Nasopharyngeal carcinoma (NPC) is a human epithelial cancer that is constantly associated with the Epstein-Barr virus (EBV). Investigations on this tumor have been limited so far by the difficulty of culturing NPC cells for long periods. C15 is an NPC tumor that has been successfully carried in nude mice for greater than 2 yr. C15 cells isolated from the animal were shown to produce a soluble factor with interleukin 1 (IL-1) activity. Its biochemical (Mr, approximately equal to 17,000; pI approximately equal to 5) and immunological properties are identical to those of IL-1 alpha. RNA gel blot analysis showed IL-1 alpha, but not IL-1 beta, transcripts in C15 cells, in sharp contrast to monocytes that express IL-1 beta predominantly. Media from short-term cultures of fresh NPC biopsies also contained a strong IL-1 activity. Several lymphoblastoid cell lines obtained by EBV infection of normal B lymphocytes have been shown to produce IL-1 and use it as an autocrine growth factor. The production of IL-1 by malignant EBV-containing epithelial cells indicates that different types of EBV-infected cells produce IL-1. A relationship might exist between EBV and constitutive production of IL-1. The IL-1 produced by the malignant epithelial cells in vivo could stimulate the development of the pronounced T-cell infiltrate observed in NPC tumors.

Animals↗

[Experimental data on the infestation of the young of 5 species of Lymnaea by Fasciola hepatica L].

The ability of five lymnaeid species (Lymnaea glabra, L. palustris, L. peregra, L. stagnalis, L. truncatula) to act as intermediate hosts of Fasciola hepatica was investigated under controlled conditions. Each snail born in the laboratory (at 23 degrees C) was infected when 1-24-hours-old, using 3 miracidia of F. hepatica. The percentage of infected snails ranged from 15.8% to 64.5% on day 30 post-exposure. The shell height of snails with evolutive infection was significantly reduced than the shell height of snails with abortive infection or controls. The mean number of cercariae produced by the snails with evolutive infection was low: from 12.2 to 18.4 cercariae per snail. The length of the shedding period was one day for 114 snails, two days for 41 snails and 3-31 days for the 54 other snails. We did not observe a distinct rythm in cercarial production of these snails. All infections of guinea-pigs with these metacercariae were positive. The significance of these observations is discussed.

Animals↗

Phase II trial of recombinant interferon gamma in refractory undifferentiated carcinoma of the nasopharynx.

The presence of Epstein-Barr virus (EBV) genomes in the DNA of tumor cells of undifferentiated carcinoma of nasopharyngeal type (UCNT), associated with significant lymphocytic infiltration of tumor led to therapeutic trials with interferon (IFN) because of its antiviral, antiproliferative, and immunomodulatory properties. Fourteen patients with histologically proven UCNT (2 had locoregional disease alone and 12 metastatic disease) who were refractory to conventional chemotherapy, were treated with IFN gamma 20 x 10(6) U twice a week. Treatment was well tolerated. No objective response were achieved in the 13 evaluated patients, and all patients progressed after a median treatment duration of 10 weeks (6-32). IFN gamma seems unable to induce antitumor activity alone in such heavily pretreated patients. Its possible place in the management of UCNT is probably earlier in the natural history of this disease.

Adolescent↗