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Titolo:
Intraarterial delivery of genetic vectors for the treatment of malignant brain tumors
Autore:
Cohen, ZR; Duvdevani, R; Nass, D; Hadani, M; Ram, Z;
Indirizzi:
Chaim Sheba Med Ctr, Dept Neurosurg, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Chaim Sheba Med Ctr, Inst Pathol, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 21 Tel Hashomer, Israel Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel Tel Aviv Univ Tel Aviv Israel IL-69978 ac Med, IL-69978 Tel Aviv, Israel
Titolo Testata:
ISRAEL MEDICAL ASSOCIATION JOURNAL
fascicolo: 2, volume: 3, anno: 2001,
pagine: 117 -
SICI:
1565-1088(200102)3:2<117:IDOGVF>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
IRON-OXIDE PARTICLES; BARRIER DISRUPTION; HERPESVIRUS; ADENOVIRUS; EXPRESSION; THERAPY; GROWTH; CELLS;
Keywords:
gene therapy; retrovirus; vascular; ganciclovir; carotid artery;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
11
Recensione:
Indirizzi per estratti:
Indirizzo: Ram, Z Chaim Sheba Med Ctr, Dept Neurosurg, IL-52621 Tel Hashomer, Israel Chaim Sheba Med Ctr Tel Hashomer Israel IL-52621 Hashomer, Israel
Citazione:
Z.R. Cohen et al., "Intraarterial delivery of genetic vectors for the treatment of malignant brain tumors", ISR MED ASS, 3(2), 2001, pp. 117

Abstract

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense preclinical and clinical research in recentyears, Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cellpopulation. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma, However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothelial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer. Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature. Methods: As a model for this approach we delivered concentrated retroviralvectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir), was evaluatedResults: No acute or long-term toxicity was observed after intraarterial infusion of the vector, Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature, This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain. Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising newgene therapy strategies for the treatment of brain tumors.

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Documento generato il 29/03/20 alle ore 08:24:33