2005 Fiscal Year Final Research Report Summary
Neovasculature-targeting Gene Therapy for Urogenital Cancers
| Project/Area Number |
16591604
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
UCHIDA Atsushi University of the Ryukyus, University Hospital, Assistant Professor, 医学部附属病院, 講師 (80245571)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Yoshihide University of the Ryukyus, Faculty of Medicine, Professor, 医学部, 教授 (50051719)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Angiogenesis / Endothelial cells / Prostate cancer / Gene therapy |
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| Research Abstract |
Mechanism of altered cellular phenotype in relation to PSMA expression
Prostate-Specific Membrane Antigen (PSMA) is expressed by the neovasculature in various cancers, as well as prostate cancer. We observed that PSMA expression was negatively correlated to the expression of rTSβ in the prostate cancer LNCaP cells. Therefore we planned to investigate the physiological role of rTSβ, especially in relation to Thymidylate Synthase (TS) function and PSMA in prostate cancer and endothelial cells.
We cloned rTSβ gene from normal human lymphocyte, and produced the plasmid for controlled expression in mammalian cells. In the prostate cancer cell line LNCaP, forced expression of rTSβ inhibited TS expression and sensitized 5-FU toxicity. Forced expression of rTSβ also altered the structure of the cells from simple spindle to neuron-like appearance, which might be a reflection of the altered distribution or expression of extra cellular matrices. We are currently investigating the mechanism of this phenomenon.
Cloning and characterization of the Cystosine Deaminase gene derived from Sacchatomyses serevisiae (FCY1) as a tool for suicide gene therapy
It was recently reported that Cytosine Deaminase derived from yeast (FCY1) is better in use of suicide gene therapy compared with that derived from E.Coli (CodA). Expecting in our gene therapy model, we verified the activity of FCY1 in catalyzing 5-FC in the cancer cell lines. We cloned FCY1 gene from the wild type of FCY1 and built the expression plasmid to compare the utility between FCY1 and CodA.
We found that the stability of CodA at body temperature was better than FCY1, although latter had potentially superior catalyzing activity of 5-FC in the adequate condition (at 4℃).
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Research Products
(78 results)
