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Biomedical subjects

L Dazord

Publications and source records attributed to L Dazord.

At least 19 recordsLinked to original sources
PubMed1991

[The diagnostic value and therapeutic perspectives of monoclonal antibodies in bronchopulmonary cancer].

Monoclonal antibodies (AcM) have opened up new perspectives in the study of cancer. The production of murine AcM has been well described in the past. The characterisation of the antigen which they recognise and their in vitro and in vivo biological properties has led to their use in diagnosis and in due course to therapeutic possibilities. The specificity of AcM "vis a vis" certain molecules or tumour associated antigens enables their utilisation for diagnosis and their widespread use for the labelling of tumour markers. AcM may in difficult cases be more accurate in specifying the histological type of a bronchopulmonary or pleural tumour; by coupling the antibody to a radio isotope and injecting it into the circulation. This enables the detection of tumours in vivo by immunoscintigraphy. The numerous problems linked to the technique and above to biology of AcM limits its clinical value in assessing the degree of extension either locally or regionally of bronchopulmonary tumours. The therapeutic applications are at this stage experimental and above all studies have shown the limits of AcM used alone or coupled to a radio isotope, a toxin or a drug. The limits of the technique are linked to numerous factors, such as accessibility of the antigen site, the heterogeneity of tumour markers and non specific fixation and immunogenicity of the AcM. The experimental clinical stage should be continued in order to define the most effective utilisation of AcM in therapy which will doubtless be complementary to other forms of treatment.

Animals↗
PubMed1990

Immunoscintigraphy of human lung squamous cell carcinoma using an iodine-131 labelled monoclonal antibody (Po66).

Monoclonal antibody (McAb) Po66 has been obtained by immunisation of mice against a human lung squamous cell carcinoma. The in vitro reactivity of the antibody with cancer cells and its ability to localise in human lung cancer xenografts growing in nude mice have been reported earlier. Presented here is the first clinical evaluation of the antibody for scintigraphic detection of tumours. Thirty-three patients with histologically confirmed primary non-small cell lung carcinoma were investigated. Twenty-seven of them were explored at the preoperative stage and six at 6 months after surgery. Biodistribution results were obtained from seven operated patients by combining injections of 131I-radiolabelled Po66 and of 125I-labelled unrelated immunoglobulin. The localisation index was three times higher for this specific antibody. Immunoscintigraphy detected 78% of primary tumours and 100% of recurrences. In this short series of patients, immunoscintigraphy proved helpful in the assessment of tumour spread in four patients by visualising localisations in the mediastinum or the contralateral lung which the CT scan had failed to demonstrate. Immunoscintigraphy was also more efficient than plain chest X-ray for the detection of local tumour recurrences.

Adult↗
PubMed1989

Characterization of the antigen identified by Po66. A monoclonal antibody raised against a lung squamous cell carcinoma.

The mouse monoclonal antibody (mAb) Po66 has been shown in previous work to be localized in nude mice xenografts of human lung tumours when injected intravenously [Dazord L et al. (1987) Cancer Immunol Immunother 24: 263-268] and to be suitable for the scintigraphic detection of lung cancers in patients [Dazord L, et al. (1987) in Klapdor (ed) New tumour markers and their monoclonal antibodies. Georg Thieme, Stuttgart, New York, pp 444-450]. The nature of the antigen recognized by Po66 has been investigated in the present work and comparisons are made with antigens recognized by other mAbs prepared in the laboratory. These mAbs were raised either against lung squamous cell carcinoma (mAbs Po43, Po60), or against a bronchio-alveolar carcinoma (mAbs BAM33, BAM45, BAM54 and BAM69). Radioiodinated purified Po66 did not compete for cell binding with any other mAb. All Po and BAM mAbs reacted with tumour cells both cultured in vitro and grown in vivo. They recognized cytoplasmic antigens as judged by immunofluorescence examination of fixed cells or by immunoperoxidase staining of cancer tissues, but could never be visualized by immunofluorescence on the surface membrane of culture cells. The mAbs of the BAM series reacted with vimentin as demonstrated by immunofluorescence staining, showing alterations in the aspect of the filaments under the effect of colchicine. Radiolabelled mAbs Po43, BAM33 and BAM45 bound to partially purified cytoplasmic cytoskeleton components. In contrast, Po66 was never seen associated with intermediary filaments. The sensitivity to enzyme digestion of the antigen associated with Po66 was studied in comparison with those associated with Po43, BAM33 and BAM45. All antigens were sensitive to protease digestion while only the Po66-identified antigen was sensitive to periodate, neuraminidase and alpha-fucosidase. Thus, mAb Po66 identified an antigen of 47 kDa (as determined before) present in the cytoplasm but not related to the cytoskeleton, not detected on the cell surface and glycoprotein in nature.

Adenocarcinoma↗
PubMed1989

Distribution of radiolabelled monoclonal antibody Po66 after intravenous injection into nude mice bearing human lung cancer grafts.

Monoclonal antibody Po66, produced by immunization against a patient's lung squamous cell carcinoma was found suitable for the scintigraphic detection of human tumours. Surprisingly, the cellular antigen recognized by Po66 was abundant in the cytoplasm of tumour cells but could not be detected on the surface membrane. In the present work the biodistribution of radiolabelled Po66 and of an unrelated immunoglobulin were studied comparatively after intravenous injection into nude mice bearing lung squamous cell carcinoma grafts. Radioactivity distribution among mouse organs and tumour was analysed by gamma counting and autohistoradiography. After injection, radiolabelled Po66 decreased rapidly from the blood in tumour-bearing animals whereas, in controls, it remained at a level comparable to that of the unrelated immunoglobulin. The antibody seemed slowly trapped by the tumour and, 12 days after its injection, distribution ratios between tumour and mouse organs reached values of 20-30 as against 1 in animals injected with the non-specific immunoglobulin. Autohistoradiographic investigations in the tumour confirmed the slow diffusion rate of the antibody, which remained in the vascular spaces up to the 24th hour after injection and diffused afterwards throughout the clusters of tumor cells. Furthermore, radioactivity was detected in cells which, unexpectedly, seemed morphologically unaltered. These cells, the viability of which remains to be determined, were predominant in the central area of the tumours. The results presented constitute new evidence of the ability of an in vivo injected monoclonal antibody to reach a cytoplasmic target inside non-necrotic cells and suggest that the cells permeable to the antibody might be in defective nutritional conditions.

Animals↗
PubMed1988

Ornithine decarboxylase basal activity in liver, oesophagus and lung of vitamin A deficient rats, and the effect of retinoic acid.

Ornithine decarboxylase (ODC, EC 4.1.1.17) activity was measured, without exogenous stimulation, in the liver, oesophagus and lung of Wistar rats which were vitamin A deficient or supplemented with retinol or retinoic acid. The enzyme basal activity in such deficiency conditions was higher, when compared with controls, in the oesophagus and especially in the lungs. Retinoic acid normalized enzyme activity only at high doses (300 micrograms/day). In the liver, initial retinol deficiency did not sensitively modify ODC activity, and retinoic acid then stimulated the enzyme abnormally. This phenomenon could not be observed at later stages of vitamin deficiency (but there again without cytological abnormalities or thymidine incorporation disturbances): liver ODC response then became comparable to that of other tissues. These results highlight the particular basal hyperactivity of pulmonary ODC during the initial stages of vitamin A deficiency, indicative of an enhanced tendency to cell proliferation. A special stimulating effect of retinoic acid on ODC, contemporary with early deficiency, was observed in the liver; this effect was not observed at a later stage in normally fed rats.

Animals↗
PubMed1987

A monoclonal antibody (Po66) directed against human lung squamous cell carcinoma immunolocalization of tumour xenografts in nude mice.

Po66, a mouse IgG1 monoclonal antibody, was produced by immunization against a patient lung squamous cell carcinoma. The tissue reactivity of the antibody was measured by a radioimmunological assay with enzymatically dissociated cells, by an immunofluorescence test on frozen tissue sections and by peroxidase-staining of paraffin sections. The antibody bound to lung squamous cell carcinoma, oesophagus carcinoma and, inconsistently to lung adenocarcinoma but not to the other tumours tested. Some normal tissues also reacted positively, in particular bronchial serous glands, oesophagus epithelium and renal distal and collecting tubules. In normal and malignant tissues showing epithelioid differentiation, Po66 bound to the intermediate maturation area. The antigen immunoprecipitated by Po66 from lung squamous cell carcinoma appeared as a single band with a molecular weight 47,000 to 50,000 daltons. Purified monoclonal antibody Po66 and an unrelated IgG1 immunoglobulin were labelled with radioactive iodine and injected i.v. into nude mice bearing subcutaneous xenografts of human lung squamous cell carcinoma. The localization index in the tumour was 3.3. Antibody labelled with 131I allowed gamma-scintigraphic imaging of the xenografts which were clearly outlined by days 9 to 11.

Animals↗
PubMed1983

Antitumor activity of living or killed Brucella: modification of the non-specific cytotoxic effector cells.

At various times after injection of living or killed smooth (S) or rough (R) Brucella abortus mice received a graft of the semi-allogenic EL4 lymphoma and their survival was studied. In parallel, the NK activity of spleen and peritoneal cells, the level of serum interferon (IFN), and the cytotoxic activity of peritoneal macrophages were investigated. Protection against the lymphoma lasted longer after injection of R organisms than after S. The parallelism between the in vivo resistance to El4 lymphoma and the augmentation of NK and macrophage activity was satisfactory with R but not with S. IFN production did not seem to be correlated with R antitumor activity. The antitumor effect of Brucella cannot therefore be simply explained on the basis of modification of the non-specific cytotoxic effector mechanisms.

Animals↗
PubMed1979

Resistance to tumor graft in mice treated with inactivated Brucella abortus cultured in smooth or rough phase.

Because killed Brucella abortus organisms cultured in smooth (S) or rough (R) phase were known to differentially influence humoral and cellular immune responses and to differ in their effects on T-dependent responses, the antitumor properties of killed B. abortus organisms, cultured in S- or R-phase and then inactivated, were compared in (C57BL/6 X DBA/2)F1 female mice with the use of 6 different transplantable tumors. In solid tumors, the antitumor effects produced by S-preparations were never improved by R-preparations. However, in ascites tumors, R-preparations gave the best antitumor results. These findings suggested that the defense mechanisms acrivated by immunostimulants may differ according to the site of tumor implantation. Among the other experimental factors studied, the route of B. abortus administration had a prominent role. Local injection at the site of tumor implantation before or after the graft gave better results than did systemic treatment. Systemic treatment could enhance the growth of Lewis tumor when applied 5 or 10 days before tumor graft but generally had an antitumor effect when given 1 day after the graft.

Animals↗
PubMed1978

Influence of the antigenicity of Brucella preparations on modulation of the immune response to sheep erythrocytes.

The relationship between the expression of surface antigenicity of inactivated Brucella and the immunostimulant properties on the sheep erythrocyte response was studied in mice. The agglutinogenic Brucella abortus B19S preparation was compared to two non-agglutinogenic preparations (B19R and PB), using the plaque-forming and rosette-forming cell tests. When Brucella and antigen were injected together, only non-agglutinogenic preparations, even used at low doses, were able to increase the plaque-forming and rosette-forming cell responses measured 4 days after immunization. When the interval between the previous injection of non-agglutinogenic preparations and that of the antigen increased or when they were injected 24 h after the antigen, the modification of those two responses was no longer observed. After day 4, for the simultaneous injection of Brucella and antigen, B19S and PB preparations induced the best responses; this effect was dose dependent. Thus, in the present experimental situation, the modification of the day 4 response appeared independent of those of the ensuing days.

Agglutination↗
PubMed1978

Modulation of immune response by killed Brucella abortus organisms: comparison of the effects of smooth and rough strains on T-dependent responses.

Inactivated Brucella abortus organisms of the smooth (S) or rough (R) strain were tested comparatively on two T-dependent immune responses: mixed-lymphocyte reaction and delayed-type hypersensitivity. The intravenous injection of S organisms depressed the two tests, whereas R organisms increased mixed-lymphocyte reaction and did not alter delayed-type hypersensitivity significantly. This observation may be helpful in understanding the differences in adjuvant properties of S and R brucellae.

Brucella abortus↗
PubMed1975

[Inhibition of antigenic competition by immunostimulants].

The diminution of immune response against SRBC induced in mice, by a prior injection of HRBC was counteracted by addition of certain immunostimulants to SRBC. The intensity of inhibition of antigenic competition was related to the quantity of immunostimulant added to SRBC. Some immunostimulants (B. abortus, lipopolysaccharide) were more active than others (C. parvum, Poly I : C). To inhibit antigenic competition immunostimulant had to be injected after or in mixture with SRBC never before.

Animals↗