title: A triple suicide gene strategy that improves therapeutic effects and incorporates multimodality molecular imaging for monitoring gene functions.
abstract: Gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, has shown promise in clinical trials. In this preclinical study using stable cell lines and xenograft tumor models, we show that a triple-suicide-gene GDEPT approach produce enhanced therapeutic efficacy over previous methods. Importantly, all the three genes (thymidine kinase, cytosine deaminase and uracil phosphoribosyltransferase) function simultaneously as effectors for GDEPT and markers for multimodality molecular imaging (MMI), using positron emission tomography, magnetic resonance spectroscopy and optical (fluorescent and bioluminescent) techniques. It was demonstrated that MMI can evaluate the distribution and function/activity of the triple suicide gene. The concomitant expression of these genes significantly enhances prodrug cytotoxicity and radiosensitivity in vitro and in vivo.
authors.affiliation: Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: L
authors.initials: L
authors.lastname: Xing
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Deng
authors.forename: K
authors.initials: K
authors.lastname: Kotedia
authors.forename: P B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: E
authors.initials: E
authors.lastname: Ackerstaff
authors.forename: J A
authors.initials: JA
authors.lastname: Koutcher
authors.forename: C C
authors.initials: CC
authors.lastname: Ling
authors.forename: G C
authors.initials: GC
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D043525:Cytosine Deaminase / Q000235:genetics / Q000627:therapeutic use*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010430:Pentosyltransferases / Q000235:genetics / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011355:Prodrugs / Q000627:therapeutic use; D011878:Radiotherapy; D013937:Thymidine Kinase / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection
chemical_list: D011355:Prodrugs; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D013937:Thymidine Kinase; D043525:Cytosine Deaminase