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Titolo:
A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptasegene promoter
Autore:
Komata, T; Koga, S; Hirohata, S; Takakura, M; Germano, IM; Inoue, M; Kyo, S; Kondo, S; Kondo, Y;
Indirizzi:
Mt Sinai Med Ctr, Sch Med, Dept Neurosurg, New York, NY 10029 USA Mt SinaiMed Ctr New York NY USA 10029 Neurosurg, New York, NY 10029 USA Cleveland Clin Fdn, Surg Res Ctr, Dept Biomed Engn, Cleveland, OH 44195 USA Cleveland Clin Fdn Cleveland OH USA 44195 d Engn, Cleveland, OH 44195 USA Cleveland Clin Fdn, Surg Res Ctr, Dept Neurosurg, Cleveland, OH 44195 USA Cleveland Clin Fdn Cleveland OH USA 44195 rosurg, Cleveland, OH 44195 USA Kanazawa Univ, Sch Med, Dept Obstet Gynecol, Kanazawa, Ishikawa 9200934, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9200934 wa, Ishikawa 9200934, Japan
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 5, volume: 19, anno: 2001,
pagine: 1015 - 1020
SICI:
1019-6439(200111)19:5<1015:ANTOHM>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; CELL-SURFACE ANTIGEN; CISPLATIN-INDUCED APOPTOSIS; HUMAN BRAIN-TUMORS; MONOCLONAL-ANTIBODY; CD95 FAS/APO-1; FAS ANTIGEN; IN-VITRO; THERAPY; PROTEIN;
Keywords:
gene therapy; apoptosis; Fas associated protein with death domain; human telomerase reverse transcriptase; malignant glioma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Kondo, Y Mt Sinai Med Ctr, Sch Med, Dept Neurosurg, 1 Gustave L Levy Pl,Box 1136, New York, NY 10029 USA Mt Sinai Med Ctr 1 Gustave L Levy Pl,Box 1136 New York NY USA 10029
Citazione:
T. Komata et al., "A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptasegene promoter", INT J ONCOL, 19(5), 2001, pp. 1015-1020

Abstract

Telomerase activity has a close relationship with malignancies in many cell types and it is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). Utilizing the hTERT promoter, the authors developed a gene delivery system of Fas associated protein with death domain (FADD) (hTERT/FADD). FADD is a protein which plays an important role in the apoptotic pathway of Fas. Overexpression of FADD induces apoptosis in the cells regardless of Fas expression on the cell surface. We hypothesized that we might be able to restrict the expression of FADD in malignant glioma cells if we use the gene transfer system under the control of hTERT promoter. This study was designed to investigate whether the hTERT/FADD construct induces apoptosis effectively in malignant glioma cells while keeping normal cells intact. First, using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we confirmed that hTERT mRNA was expressed in human malignant glioma cells (U373-MG, A172 and GB-1), but not in cultured astrocytes (TEN) or fibroblasts (MRC5). After transient transfection with the hTERT/FADD construct, a significant number of FADD-positive cells and apoptotic cells were detected in hTERT-positive malignant glioma cells. In contrast, hTERT-negative astrocytes and fibroblasts remained intact. Furthermore, subcutaneously implanted U373-MG tumors treated with the hTERT/FADD construct reduced in volume significantly C compared to the conrol treatment (p=0.0001). Gene transfer of FADD under the control of the hTERT promoter may be a novel and promising therapy to kill hTERT-positive malignant glioma cells while sparing normal brain cells lacking hTERT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 07:56:40