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Titolo:
Genetically modified CD34(+) cells exert a cytotoxic bystander effect on human endothelial and cancer cells
Autore:
Arafat, WO; Casado, E; Wang, M; Alvarez, RD; Siegal, GP; Glorioso, JC; Curiel, DT; Gomez-Navarro, J;
Indirizzi:
Univ Alabama, Dept Med, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Pathol, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Surg, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Cell Biol, Birmingham, AL 35294 USA Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Gynecol, Birmingham, AL 35294 USA Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 herapy Ctr, Birmingham, AL 35294 USA Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 Biochem, Pittsburgh, PA 15261 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 11, volume: 6, anno: 2000,
pagine: 4442 - 4448
SICI:
1078-0432(200011)6:11<4442:GMCCEA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-INFILTRATING LYMPHOCYTES; GENE-THERAPY; ANGIOGENESIS; DELIVERY; VEHICLES; TRANSDUCTION; GANCICLOVIR; CARCINOMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Gomez-Navarro, J Univ Alabama, Dept Med, Div Human Gene Therapy, 1824 6th Ave S,WTI 620, Birmingham, AL 35294 USA Univ Alabama 1824 6th Ave S,WTI 620Birmingham AL USA 35294
Citazione:
W.O. Arafat et al., "Genetically modified CD34(+) cells exert a cytotoxic bystander effect on human endothelial and cancer cells", CLIN CANC R, 6(11), 2000, pp. 4442-4448

Abstract

We and others have proposed mammalian cells as gene delivery vehicles withthe potential for overcoming physiological barriers to viral vectors. To that end, we previously have shown the potential of CD34(+) endothelial progenitors for systemic gene delivery in a primate angiogenesis model. Here weseek to explore the utility of CD34+ cells of human origin as vehicles fortoxin genes and, in particular, to measure their capacity to effect a cytotoxic bystander effect in human endothelium and tumor cells. To this end, CD34+ cells were transduced with TOZ.1, a nonreplicative herpes simplex vector encoding thymidine kinase, To test the capacity of CD34+ cells to inducea cytotoxic bystander effect in target cells, we performed mixing experiments, whereby TOZ.1-transduced CD34(+) cells were mixed with either human vascular endothelial cells or human ovarian tumor cells (SKOV3.ip1). Cell viability was measured by the MTS assay. Lastly, mixtures of TOZ.1-transduced CD34+ cells and SKOV3.ip1 tumor cells were injected s.c. to evaluate the bystander effect in vivo. After transduction of CD34(+) cells with TOZ.1, treatment with ganciclovir induced the killing of 99% of cells. In cell-mixingexperiments, a linear correlation was observed between the percentages of TOZ.1-transduced CD34+ cells and total cell killing. For example, when 50% of CD34(+) transduced cells were mixed with nontransduced SKOV3.ip1, >70% of all cells died. Similarly, when the same percentage was mixed with human vascular endothelial cells, >80% of the total number of cells died. In vivostudies showed an abrogation of tumor formation when TOZ.1-transduced CD34(+) cells and ganciclovir were administered. Our observations establish thefeasibility of a method for cell-based toxin gene delivery into disseminated areas of tumor angiogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 17:42:42