2002 Fiscal Year Final Research Report Summary
Antitumoral effect of selective cycloxygenase-2 inhibitor against urological cancer
| Project/Area Number |
13671664
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NOMOTO Takeshi Department of Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 助手 (20301426)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAUCHI Akihiro Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 講師 (90240952)
UKIMURA Osamu Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 助手 (70275220)
MIZUTANI Yoichi Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 講師 (10243031)
MIKI Tsuneharu Urology, Kyoto Prefectural Univ. of Med. Professor, 医学部, 教授 (10243239)
IMAIDA Yoichiro Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 助手 (90203306)
YOKOYAMA Keiichi Pathology, Kyoto Prefectural Univ. of Med. Assistant Professor (10281263)
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| Project Period (FY) |
2001 – 2002
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| Keywords | selective cyclooxygenase-2 inhibitor / renal cell carcinoma / anti-Fas monoclonal antibody / JTE-522 |
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| Research Abstract |
INTRODUCTION AND OBJECTIVE: Cytotoxic chemotherapy has shown little or no antitumor activity against renal cell carcinoma (RCC) and has played no role in either an adjuvant or a neoadjuvant support therapy. Immunoterapy is relatively effective against RCC, but the efficacy is not strong. It has been reported that COX-2 inhibitors prevent carcinogenesis of colon cancer and induce apoptosis in colon cancer, esophageal cancer and hung cancer cells. In the present study, we investigated the expression of COX-2 in RCC, and cytotoxic and cytostatic effects of a selective COX-2 inhibitor (ITE-522) on RCC
METHODS: The expression of COX-2 in RCC cell lines (Caki-1, NC65, and ACHN) and normal renal cell line (RPTEC) were examined by reverse transcription polymerase chain reaction. The cytotoxic and cytostatic effects of JTE-522 on the cell lines were assessed by 1-day and 3-day MTT assay
RESULTS: The expression of COX-2 was observed in all RCC cell lines examined but not RPTEC. JTE-522 was cytotoxic against Caki-1, NC65, and ACHN cells and inhibited their proliferation, but not RPTEC. These was a synergistic cytotoxisc effect of JTE-522 in combination with 5-fluolouracil, adriamycin, cis-diammine-dichloroplatirum, interfelon-α or tumor necrosis factor-α commonly used against RCC resulted in an additive cytotoxic effect on Caki-1 cells
CONCLUSIONS: The present study has demonstrated that a selective COX-2 inhibitor (JTE-522) has cytotoxic and cytostatic effects on RCC but not normal renal cells, and that synergistic cytotoxicity against RCC was obtained with JTE-522 and anti-Fas monoclonal antibody. These results suggest that the treatment with selective COX-2 inhibitors and immunotherapy may be useful in patient with RCC
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