Identification of androgen-independent progression-relate gene and its clinical application for gene therapy in the prostate cancer
| Project/Area Number |
12307035
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Teikyo University |
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Principal Investigator |
SATO Naohide Teikyo University, School of Medicine, Lecturer, 医学部, 講師 (50287017)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRASAWA Hiroshi Chiba University, School of Medicine, Professor, 医学部, 教授 (00216194)
市川 智彦 千葉大学, 医学部, 助教授 (20241953)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥33,190,000 (Direct Cost: ¥31,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2003: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2002: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2001: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2000: ¥25,000,000 (Direct Cost: ¥25,000,000)
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| Keywords | prostate cancer / gene therapy / androgen-independent progression / prostate-specific antigen / KAII / CD82 gene / intermittent androgen suppression / cancer-specific survival / quality of life / アンドロゲン非依存癌 / プログレッション / QOLの改善 |
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| Research Abstract |
We had tried to identity androgen-independent progression-related genes in human prostate cancer by using DNA microarray techniques. As a result, KAI1/CD82 gene seemed a candidate of genes that diminished or lost in the process of androgen-independent progression. We have constructed adenovirus vectors that overexpressed KAI1/CD82 gene, and introduced them into androgen-independent metastatic human prostate cancer PC-3 and DU-145 cells to see inhibitory effects against metastatic ability. Unfortunately, this vector did not fully infected into these human prostate cancer cells.
Intermittent androgen suppression (IAS) had been developed as a new clinical approach to delay androgen-independent progression of human prostate cancer. We have investigated the clinical effect of IAS via multi-center prospective study. Fifty-eight prostate cancer patients were registered and treated with a combination of leuprolide acetate and flutamide for 36 weeks. When serum prostate-specific antigen (PSA) le
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vels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until PSA reached 15 ng/mL or pre-treatment level. This cycle of on- and off-treatment was repeated until PSA failure or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire. Forty-nine patients including 26 stage C and 23 stage D were enrolled. Mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1,6 finished cycle 2, and 3 finished cycle 3. Mean off-treatment periods in cycle 1, 2, and 3, were 46.1, 36.9, and 23.3 weeks, respectively. In off-treatment period, significant improvements in QOL score were observed in the categories of potency, physical, social/family, and functional well-being when compared to those in on-treatment period. In conclusion, our analysis indicates that QOL is remarkably improved during off-treatment period. IAS would be a viable option for treatment of advanced prostate cancer, although randomized controlled study is required to determine whether IAS prolongs cancer-specific survival time. Less
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Report
(5 results)
Research Products
(4 results)
