| Project/Area Number |
21592146
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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 |
Obstetrics and gynecology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
ISAKA Keiichi 東京医科大学, 医学部, 教授 (10201310)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Hirotaka 東京医科大学, 産科婦人科, 講師 (60307345)
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| Co-Investigator(Renkei-kenkyūsha) |
KURODA Masahiko 東京医科大学, 分子病理学, 教授 (80251304)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 癌 / 遺伝子 / 薬学 / 卵巣がん / 子宮体がん / パクリタキセル / 薬剤耐性 / テーラーメード医療 |
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| Research Abstract |
Paclitaxel is often used in clinic to treat gynecologic cancers. Nevertheless, some carcinomas such as breast cancer, ovarian cancer, and non-small cell lung cancer demonstrate resistance to paclitaxel treatment. We screened a lentiviral siRNA library against the entire human genomes to assess the ability of clones to influence the sensitivity of paclitaxel. We identified three paclitaxel-resistant clones, which were determined as targeting for septin 10(SEPT10), ubiquitin-specific protease 15(USP15) and budding uninhibited by benzimidazoles 3(BUB3), respectively. We conducted the present study to investigate whether and how chemosensitivity can be determined by means of genetic diagnosis using these genes in patients with epithelial ovarian cancer. A total of 61 samples were obtained with informed consent from patients who had epithelial ovarian cancer and received first-line chemotherapy, consisting of paclitaxel and carboplatin(TC). The mRNA expression of SEPT10 and USP15 was measured by real-time reverse transcription-polymerase chain reaction. These expressions were showing a tendency to be higher in patients who did not respond to TC therapy. Also, SEPT10 expression was upregulated in serous type carcinoma compared with others. The present study suggests that genetic diagnosis by these genes may be useful to determine chemosensitivity in patients with epithelial ovarian cancer. Furthermore, these genes may candidate a novel cancer therapeutic method for paclitaxel-resistant cancers.
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