Immunostimulation by Brucella abortus. Role of surface antigenicity of the bacteria.
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Animals↗
Biomedical subjects
L Dazord
Publications and source records attributed to L Dazord.
Purification of a tumoral marker recognized by monoclonal antibody Po66 and associated with human lung squamous cell carcinoma.
Monoclonal antibody (MAb) Po66, a murine IgG1, was raised by immunization against human lung squamous cell carcinoma. When injected intravenously, Po66 showed prolonged retention in the tumor. It recognized an intracellular antigen. The human lung squamous carcinoma cell line SK-MES-1 expresses the antigen recognized by MAb Po66 and was used as a source of biological material for its purification. The SK-MES-1 cell line was labeled in culture with [35S]methionine and its lysate was immunoprecipitated with Po66 immobilized on Protein G-Sepharose. The precipitate contained three proteins (47, 50 and 69 kDa) absent in the controls. The 69 kDa polypeptide was further purified by anion exchange and immunoaffinity chromatographies. To date, no other tumor marker expressed in non-small cell lung cancer with these characteristics has been described and as such this marker is interesting for future use in immunotherapy and in diagnosis.
Animals↗
Expression of Po66-CBP, a galectin-8, in different types of primary and secondary broncho-pulmonary tumors.
The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.
Adult↗
Expression of Po66-CBP, a type-8 galectin, in different healthy, tumoral and peritumoral tissues.
UNLABELLED: A monoclonal antibody, Po66, recognized an antigen named Po66 carbohydrate binding protein (PO66-CBP), which was homologous to the galectin-8 protein. Two additional isoforms previously not described were characterized. The aim of this study was to compare the expression of Po66-CBP and its isoforms in different healthy, tumoral and peritumoral tissues and at last to determine the localization of the protein in tumors and distant tissues. MATERIALS AND METHODS: Reverse transcriptase PCR of Po66-CBP was performed on total RNA extract from eleven healthy and eleven tumoral and peritumoral tissue specimens. Antibody Po66 was used to localize the protein in the tumors and distant tissues by an immunohistochemistry method. RESULTS: Po66-CBP was expressed by half of the healthy tissues. One of the isoforms, the last often present in healthy tissues, was found in all tumoral and peritumoral tissues studied. Immunohistochemistry evidenced a gradient of protein expression in normal cells depending on the vicinity of tumoral tissue. Po66-CBP expression was modified in cancerous tissue, suggesting the implication of galectins in carcinogenesis.
Base Sequence↗
Sodium butyrate induces growth inhibition and modulates galectin-8 expression in human lung carcinoma cells.
Galectins are animal lectins, which may play a role in neoplastic transformation. Po66-Carbohydrate Binding Protein (Po66-CBP) belongs to the galectin-8 family and is expressed in lung tumor cells but not in normal ones. Recent studies showed that galectin-8 could be used for human lung squamous cell carcinoma radioimmunotherapy. To optimize this method of treatment, we attempted to increase galectin-8 expression in human lung tumor cells. A human lung squamous (SK-MES-1) or adeno (A 549) carcinoma cell line was grown with or without sodium butyrate. Cell growth, morphology, transcriptional, expression translational expression and cellular localization of galectin-8 were studied. 3 mM of sodium butyrate inhibited the two cell lines' growth after 48 hours of treatment, but only in SK-MES-1 cells galectin-8 expression is modulated without any secretion and cellular localization modifications, apoptosis or necrosis. Sodium butyrate could be an interesting tool in optimizing the radioimmunotherapy of human lung squamous carcinoma, but not of adenocarcinoma.
Adenocarcinoma↗
Is magnetic resonance imaging texture analysis a useful tool for cell therapy in vivo monitoring?
Assessment of anti-tumor treatment efficiency is usually done by measuring tumor size. Treatment may however induce changes in the tumor other than tumor size. Magnetic Resonance Imaging Texture Analysis (MRI-TA) is presently used to follow activated lymphocyte cell therapy. We used a 7T microimager to acquire high-resolution MR images of an experimental liver metastasis from colon carcinoma in rats treated (n = 4) or not (n = 3) with a cell therapy product. MRI-TA was then performed with Linear Discriminant Analysis and showed: i) a significant variation of tumor texture with tumor growth and ii) a significant modification in the texture of tumors treated with activated lymphocytes compared with untreated tumors. T2-weighted images or volume calculation did not evidence any difference. MRI-TA appears as a promising method for early detection and follow-up of response to cell therapy.
Adenocarcinoma↗
Uptake and release of radiolabelled monoclonal antibody Po66 by multicellular aggregates obtained from a lung squamous carcinoma cell line.
Po66, a monoclonal antibody (MAb) directed against lung squamous cell carcinoma, has been shown, when injected intravenously, to be retained for a long time in tumors. This property encouraged trials to use Po66 as an agent of metabolic radiotherapy. The suitability of multicellular spheroids to reproduce the in vivo conditions of irradiation of tumors by Po66 was investigated in the present work. Spheroids were formed from the lung carcinoma cell line SK-MES-1. They resembled morphologically small carcinoma nodules with desmosome-like intercellular junctions at the periphery and a central necrotic core. The cells expressing the antigen recognized by Po66 had a heterogeneous distribution and were predominant in the outer layers of the cell aggregates. Spheroids were exposed to radiolabelled Po66. The MAb diffused slowly and reached a maximal incorporation after 4-12 hours incubation. A control unrelated antibody did not penetrate appreciably. Autohistoradiographic experiments suggested that the antibody accumulated in most cells expressing the antigen. The rate of MAb release from the spheroids was very low (T 1/2 = 163 h). Taken together, the data indicate that spheroids might be a relevant model to investigate the parameters controlling Po66-mediated immunoradiotherapy.
Animals↗
Serum and tissue distribution of a fragment of cytokeratin 19 (cyfra 21-1) in lung cancer patients.
A sensitive and relatively specific tumoral marker for lung epidermoid carcinomas could be used to identify patients likely to benefit from new therapeutic protocols. The cyfra 21-1 fragment of cytokeratin 19 has raised much hope in this regard amongst both technologists and clinicians. In a study of 195 subjects, we have shown by means of a serum assay that the usual cut-off value for this marker (3.3 ng/ml) can be lowered to 1.5 ng/ml without loss of specificity, and with an increase in sensitivity. There was a good correlation between serum marker level and tumor extension, but though cyfra 21-1 was not predictive of the suitability of a patient for surgery. A decrease of cyfra-21-1 was observed after complete resection of the tumor. There was no relation between serum assay results and immunohistochemical findings.
Adenocarcinoma↗