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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología terapia génica > DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >

Pancreatic cancer escape variants that evade immunogene therapy through loss of sensitivity to IFNgamma-induced apoptosis
Autor(es) : Mazzolini, G. (Guillermo)
Narvaiza, I. (Íñigo)
Martinez-Cruz, L.A. (L. Alfonso)
Arina, A. (Ainhoa)
Barajas, M. (Miguel)
Galofre, J.C. (Juan Carlos)
Qian, C. (Cheng)
Mato, J.M. (José María)
Prieto, J. (Jesús)
Melero, I. (Ignacio)
Palabras clave : IFNgamma
IL-12
MIP3-alpha
Apoptosis
Tumor-escape-variants
Fecha incorporación: 2003
Editorial : Nature Publishing Group
Versión del editor: http://www.nature.com/gt/journal/v10/n13/full/3301957a.html
ISSN: 1476-5462
Cita: Mazzolini G, Narvaiza I, Martinez-Cruz LA, Arina A, Barajas M, Galofre JC, et al. Pancreatic cancer escape variants that evade immunogene therapy through loss of sensitivity to IFNgamma-induced apoptosis. Gene Ther 2003 Jul;10(13):1067-1078.
Resumen
Combined injections into experimental tumor nodules of adenovirus encoding IL-12 and certain chemokines are capable to induce immune-mediated complete regressions. In this study, we found that the combination of two adenoviruses, one encoding IL-12 and other MIP3alpha (AdCMVIL-12+AdCMVMIP3alpha) was very successful in treating CT-26-derived colon carcinomas. However, in experimental tumors generated from the pancreatic carcinoma cell line Panc02 such combined treatment induces 50% of macroscopic complete regressions, although local relapses within 1 week are almost constant. We derived cell lines from such relapsing tumors and found that experimental malignancies derived from their inoculum were not amenable to treatment in any case with AdCMVIL-12+AdCMVMIP-3alpha. Importantly, relapsing cell lines were insensitive to in vitro induction of apoptosis by IFNgamma, in clear contrast with the original Panc02 cells. Comparative analyses by cDNA arrays of relapsing cell lines versus wild-type Panc02 were performed revealing an important number of genes (383) whose expression levels were modified more than two-fold. These changes grouped in certain gene ontology categories should harbor the mechanistic explanations of the acquired selective resistance to IFNgamma.
Enlace permanente: http://hdl.handle.net/10171/21738
Aparece en las colecciones: DA - Medicina - Endocrinología - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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