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Titolo:
Large nontransplanted hepatocellular carcinoma in woodchucks: Treatment with adenovirus-mediated delivery of interleukin 12/B7.1 genes
Autore:
Putzer, BM; Stiewe, T; Rodicker, F; Schildgen, O; Ruhm, S; Dirsch, O; Fiedler, M; Damen, U; Tennant, B; Scherer, C; Graham, FL; Roggendorf, M;
Indirizzi:
Univ Essen Gesamthsch, Inst Mol Biol, Ctr Canc Res & Canc Therapy, Dept Mol Biol Canc Res, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 Res, D-45122 Essen, Germany Univ Essen Gesamthsch, Dept Virol, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 irol, D-45122 Essen, Germany Univ Essen Gesamthsch, Dept Diagnost Radiol, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 diol, D-45122 Essen, Germany Univ Essen Gesamthsch, Dept Pathol, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 thol, D-45122 Essen, Germany Univ Essen Gesamthsch, Dept Expt Surg, D-45122 Essen, Germany Univ Essen Gesamthsch Essen Germany D-45122 Surg, D-45122 Essen, Germany Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA Cornell Univ Ithaca NY USA 14853 Med, Dept Clin Sci, Ithaca, NY 14853 USA McMaster Univ, Dept Biol & Pathol & Mol Med, Hamilton, ON, Canada McMasterUniv Hamilton ON Canada Pathol & Mol Med, Hamilton, ON, Canada
Titolo Testata:
JOURNAL OF THE NATIONAL CANCER INSTITUTE
fascicolo: 6, volume: 93, anno: 2001,
pagine: 472 -
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIRECT INTRATUMORAL INJECTION; BREAST-CANCER MODEL; TUMOR-REGRESSION; EXPRESSING INTERLEUKIN-12; ANTITUMOR IMMUNITY; HEPATITIS-VIRUS; ESTABLISHED TUMORS; MURINE MODEL; LIVER-CANCER; NK CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Putzer, BM Univ Essen Gesamthsch, Inst Mol Biol, Ctr Canc Res & Canc Therapy, Dept Mol Biol Canc Res, Hufelandstr 55, D-45122 Essen, Germany Univ Essen Gesamthsch Hufelandstr 55 Essen Germany D-45122 any
Citazione:
B.M. Putzer et al., "Large nontransplanted hepatocellular carcinoma in woodchucks: Treatment with adenovirus-mediated delivery of interleukin 12/B7.1 genes", J NAT CANC, 93(6), 2001, pp. 472

Abstract

Background: Cytokine-based gene therapy strategies efficiently stimulate immune responses against many established transplanted tumors, leading to rejection of the tumor. In this study, we investigated the therapeutic potential of cancer immunotherapy in a clinically more relevant model, woodchuckswith primary hepatocellular carcinomas induced by woodchuck hepatitis virus. Methods: Large (2-5 cm), established intrahepatic tumors were given an injection once with 1 X 10(9) plaque-forming units of AdIL-12/B7.1, an adenovirus vector carrying genes for murine interleukin 12 and B7.1, or of AdEGFP, the control virus, and regression of the tumors was then monitored. Fiveanimals were used in total. Results: In four tumor-bearing animals, the antitumor response was assessed by autopsy and histologic analysis within 1-2weeks after treatment. Tn all animals treated with AdIL-12/B7.1 therapy versus AdEGFP therapy, we observed substantial tumor regression (P = .006; two-sided unpaired Student's t test) accompanied by a massive infiltration ofT lymphocytes. These tumors also contained increased levels of CD4(+) and CD8(+) T cells and interferon gamma (IFN gamma). In continuously growing tumor nodules given an injection of the control virus or in nontumoral liver,no such effects (i.e., tumor regression and increased levels of CD4(+) andCD8(+) T cells and IFN gamma) were detected. In the fifth animal, monitored for long-term antitumor efficacy by magnetic resonance imaging (MRI) after intratumoral vector administration by MRI guidance, the tumor was almost completely eliminated (greater than or equal to 95%) 7 weeks after treatment. Conclusion: Adenovirus vector-based immunotherapy appears to be an effective treatment of large nontransplanted (orthotopic) tumors that acquire malignant characteristics in a stepwise process, reflecting the real-world scenario of hepatocellular carcinoma in humans.

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Documento generato il 08/07/20 alle ore 07:51:11