Search PubMed⌕ Search

Biomedical subjects

G Lemaire

Publications and source records attributed to G Lemaire.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Gene therapy of rat medullary thyroid cancer by naked nitric oxide synthase II DNA injection.

BACKGROUND: Nitric oxide (NO), produced by NO synthase II (NOS II), is the main mediator of the tumoricidal action of activated macrophages. In the present study we examined the potential of the NOS II gene as a suicide gene for medullary thyroid cancer (MTC) therapy. METHODS: We orthotopically transplanted rMTC 6-23 cells into the inbred strain of Wag/Rij rats and constructed a plasmid carrying the NOS II gene under the control of the cytomegalovirus (CMV) promoter. RESULTS: Successive injections of tumor cells (Day 0) and naked DNA (Day 2) caused strong inhibition of tumor growth (50%, p < 0.05). Plasmid injection into established tumors (14-day tumors) resulted in the development of large cavities due to tumor cell destruction, with a significant reduction in tumor tissue volume (35%, p < 0.05). Adjacent quiescent tissues were unaffected. Cell death occurred by apoptosis as demonstrated by specific labeling. Macrophages and CD4+ lymphocytes were recruited in the treated tumors. However, tumor-specific T lymphocytes were undetectable in the spleen of treated rats. In control experiments using Lac Z as a reporter gene, expression of beta-galactosidase was detected in only 1% of the tumor cells. CONCLUSIONS: Despite a low gene transfer efficiency, NOS II plasmid produced a strong anti-tumor action resulting from its marked 'bystander' effect mainly due to NO production and diffusion. Therefore the NOS II gene appears to be a promising suicide gene therapy of human cancer.

Animals↗
PubMedDate not supplied

Quantitation of intercellular binding strength by disruptive centrifugation: application to the analysis of adhesive interactions between P815 tumour cells and activated macrophages.

The cell binding assay described in the present paper provides a quantitative measurement of intercellular binding strengths between P815 mastocytoma cells and macrophages activated for cytotoxicity. Conjugates were submitted to a dislodgement force generated by centrifugation tending to remove radiolabelled probe cells from macrophages adhering to a glass support. Non-specific binding occurred between P815 cells and the glass support, but was negligible on siliconed coverslips. The adhesive interactions macrophage/glass were strong enough to resist up to about 1 X 10(-9) N, the maximal dislodgement force tested. Completion of conjugate formation was reached at 37 degrees C after 45 to 60 min and was inhibited at 4 degrees C or in Ca++-free medium. The strengths of intercellular bonds between P815 cells and macrophages varied from 7 X 10(-11) N (the minimal force applied) to more than 9 X 10(-10) N. No clear-cut separation between weak and strong interactions was observed when the centrifugation step was performed at 4 degrees C. In contrast, when centrifugation was carried out at 37 degrees C, a subpopulation of loosely bound tumour targets could be distinguished from more strongly bound P815 cells.

Animals↗