RESUMO
This article generally reviews new original two-stage approach to an effective treatment of solid cancers by killing tumour cells by the activation of a prodrug after the gene encoding for an activating enzyme has been targeted to the malignant cell. The experimental data concerning gene therapy for malignant tumours by using oxazaphosphorines and cytochrome P450 in a novel combined chemotherapy/cancer gene therapy strategy discussed.
Assuntos
Antineoplásicos/uso terapêutico , Sistema Enzimático do Citocromo P-450/genética , Terapia Genética , Neoplasias/genética , Neoplasias/terapia , Animais , Terapia Combinada , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Experimentais/genética , Neoplasias Experimentais/terapia , Pró-Fármacos/uso terapêuticoRESUMO
A molecular-genetic characterization of deletions in part of chromosome 8q24.1 was performed in patients with Langer-Giedion syndrome (six patients) and triho-rhino-phalangeal syndrome type I (three patients) by means of Southern blot hybridization analysis, restriction fragment length polymorphism and single-strand conformation polymorphism, analysis. Four families with multiple exostosis chondrodysplasia (MECD) also underwent the same analysis. Results of deletion mapping allowed determination of the probable region of localization of the proposed gene of MECD at D8S67 locus. By means of a polymorphic DNA probe obtained from the locus an additional hybridization signal was revealed only in patients with MECD. Other polymorphic DNA probes and microsatellite sequences confirmed the results of deletion mapping and detected haplotypes on the chromosomes with a mutation in the proposed MECD gene.