| Project/Area Number |
15390512
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
OKAMOTO Aikou The Jikei University School of Medicine, Lecturer, 医学部, 講師 (20204026)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kyosuke The Jikei University School of Medicine, Lecturer, 医学部, 講師 (30230452)
TAKAKURA Satoshi The Jikei University School of Medicine, Assistant, 医学部, 助手 (60256401)
OCHIAI Kazunori The Jikei University School of Medicine, Professor, 医学部, 教授 (20152514)
TANAKA Tadao The Jikei University School of Medicine, Professor, 医学部, 教授 (50110929)
矢内原 臨 東京慈恵会医科大学, 医学部, 助手 (20349624)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | IDO / Paclitaxel / ovarian cancer / cDNA microarray / cDANマイクロアレイ / 卵巣癌 / 卵巣上皮不死化細胞 / cDNAマイクロアレイ / KGF / KGFR / 卵巣上皮不死化細胞株 / cDNAマイクロアレイ解析 |
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| Research Abstract |
Purpose : We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool. Experimental Design : Using 2 newly established PTX-resistant ovarian cancer cell lines from an original PTX-sensitive cell line and 4 super-sensitive and 4 refractory surgical ovarian cancer specimens from PTX-based chemotherapy, molecules associated with chemoresistance were screened with gene expression profiling arrays containing 39,000 genes. We further analyzed 44 genes that showed significantly different expressions between PTX-sensitive samples and PTX-resistant samples with permutation tests, which were common in cell lines and patients' tumors. Results : Eight of these genes showed reproducible results with the real time reverse transcriptase polymerase chain reaction, of which indoleamine 2,3-dioxygenase (IDO) gene expression was the most prominent and consistent. Moreover, by immunohistochemical analysis using a total of 24 serous type ovarian cancer surgical specimens (stage III:n=21,stage IV:n=7) excluding samples used for GeneChip analysis, the Kaplan-Meier survival curve showed a clear relationship between IDO staining patterns and overall survival (log-rank test : P=0.0001). All patients classified as negative survived without relapse. The 50% survival of patients classified as sporadic, focal and diffuse was 41,17 and 11 months, respectively. Conclusion : The IDO screened with the GeneChip was positively associated with PTX resistance and with impaired survival in patients with serous type ovarian cancer.
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