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Titolo:
Suppression of colorectal cancer growth using an adenovirus vector expressing an antisense K-ras RNA
Autore:
Nakano, M; Aoki, K; Matsumoto, N; Ohnami, S; Hatanaka, K; Hibi, T; Terada, M; Yoshida, T;
Indirizzi:
Natl Canc Ctr, Res Inst, Div Genet, Chuo Ku, Tokyo 1040045, Japan Natl Canc Ctr Tokyo Japan 1040045 v Genet, Chuo Ku, Tokyo 1040045, Japan Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan Keio Univ Tokyo Japan 1608582 nal Med, Shinjuku Ku, Tokyo 1608582, Japan
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 491 - 499
SICI:
1525-0016(200104)3:4<491:SOCCGU>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILD-TYPE P53; CELL LUNG-CANCER; GENE-TRANSFER; IN-VIVO; RECOMBINANT ADENOVIRUS; MESSENGER-RNA; NEOPLASTIC PHENOTYPE; TUMOR ANGIOGENESIS; COLON-CANCER; PHASE-I;
Keywords:
colorectal cancer; antisense; K-ras; in vivo gene transfer; adenovirus vector;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Yoshida, T Natl Canc Ctr, Res Inst, Div Genet, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045,Japan Natl Canc Ctr 5-1-1 Tsukiji Tokyo Japan 1040045 1040045,Japan
Citazione:
M. Nakano et al., "Suppression of colorectal cancer growth using an adenovirus vector expressing an antisense K-ras RNA", MOL THER, 3(4), 2001, pp. 491-499

Abstract

In human colorectal cancer, K-ras point mutations occur in approximately 40-50% of the cases, a frequency second only to pancreatic cancer (80-90%). Unlike pancreatic and lung cancers, however, the tumor-suppressive effect of antisense K-ms RNA expression has not been examined for colorectal cancers. A recombinant adenovirus vector expressing an antisense or sense K-ras gene fragment (AxCA-AS-K-ras or AxCA-S-K-ras) was first transduced into seven human colorectal cancer cell lines. Stable expression of antisense or sense K-ros RNA was detected by RNA blot analysis. Western blot analysis confirmed a reduction of up to 25% of K-ras-specific p21 protein in the antisense K-ras-transduced HCT-15 cells. In contrast to our previous findings on pancreatic cancer, the status of K-ros point mutations was not correlated with the growth-suppressive effect of the antisense K-ras vector: both the K-ras-mutation-positive and -negative colorectal cancer cell lines were suppressed for their growth in vitro. There was no growth-inhibitory effect on normal cells such as hepatocytes. Next, to test the efficacy in vivo, HCT-15 cells were inoculated subcutaneously into the left flank of SCID mice, and AxCA-AS-K-ras was injected intratumorally three times after the tumor mass was established. The infection of AxCA-AS-K-ras, but not the control AxCA-S-K-ras, significantly suppressed the growth of the HCT-15 subcutaneous tumor. This study shows that the adenovirus-mediated in vivo gene transfer of the antisense K-ras construct may be a useful therapeutic strategy for colorectal cancer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/02/20 alle ore 10:37:00