Adenovirus-mediated wild-type p53 gene transfer induces apoptosis and inhibits in vivo tumor growth of human mesothelioma cells

M. Giuliann, I. Marinacci, E. Messina, M. C. Capogrossi, C. Cirielli, H. I. Pass, A. Modesti, M. Carbone, A. Procopio

Research output: Contribution to journalArticle

Abstract

Conventional therapy of human malignant mesothelioma (MM) is largerly ineffective. The localized nature, the accessibility of the disease, and the relative lack of distant métastases make MM a particularly attractive candidate for somatic gene therapy. To lest the effect of a replication-deficient adenovirus (Ad) vector carrying wild-type p53 cDNA (AdCMV.p53) a panel of 4 human pleural MM cell lines (H-mcso I-IV) was used. H-ineso cells infected with the control virus AdCMV.Null. and un in fee led were used as controls. All H-meso cell lines were susceptible to Ad infection and expressed avβ3 and avβ5 integrins (Ad acceptors). In vitro infection of H-meso cells with AdCMV.p53 enhanced expression of p53, and induced expression of wafl/cip21 and cell apoptosis, inhibited cell proliferation and suppressed soft agar colony formation regardless of wheather cells express wild-type or mutated endogenous p53. To test the ex vivo effect of AdCMV.p53 vector nude mice were injected subcutaneousfy or i.p. with 4X106 H-meso cells infected with 25 pfu/cell AdCMVp53 or with control vectors. Suppression of tumor growth was observed up to two months after cell inoculation in the experimental group only. Finally, inhibition of tumor cell growth was observed only after in vivo infection of MM tumors with AdCMV.p53 vector. These results suggest that Ad-mediated gene transfer strategies are potentially effective in the treatment of human malignant mesothelioma.

Original languageEnglish
JournalJournal of Investigative Medicine
Volume44
Issue number3
Publication statusPublished - 1996

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Gene transfer
Mesothelioma
p53 Genes
Adenoviridae
Tumors
Cells
Apoptosis
Growth
Gene therapy
Neoplasms
Cell proliferation
Cell growth
Viruses
Integrins
Agar
Complementary DNA
Adenoviridae Infections
Cell Line
Fees and Charges
Infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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Adenovirus-mediated wild-type p53 gene transfer induces apoptosis and inhibits in vivo tumor growth of human mesothelioma cells. / Giuliann, M.; Marinacci, I.; Messina, E.; Capogrossi, M. C.; Cirielli, C.; Pass, H. I.; Modesti, A.; Carbone, M.; Procopio, A.

In: Journal of Investigative Medicine, Vol. 44, No. 3, 1996.

Research output: Contribution to journalArticle

Giuliann, M, Marinacci, I, Messina, E, Capogrossi, MC, Cirielli, C, Pass, HI, Modesti, A, Carbone, M & Procopio, A 1996, 'Adenovirus-mediated wild-type p53 gene transfer induces apoptosis and inhibits in vivo tumor growth of human mesothelioma cells', Journal of Investigative Medicine, vol. 44, no. 3.
Giuliann, M. ; Marinacci, I. ; Messina, E. ; Capogrossi, M. C. ; Cirielli, C. ; Pass, H. I. ; Modesti, A. ; Carbone, M. ; Procopio, A. / Adenovirus-mediated wild-type p53 gene transfer induces apoptosis and inhibits in vivo tumor growth of human mesothelioma cells. In: Journal of Investigative Medicine. 1996 ; Vol. 44, No. 3.
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