To improve platinum drug resistance of ovarian clear cell carcinoma with antisense oligonucleotides including artificial nucleic acid
| Project/Area Number |
17H06847
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
Nakagawa Satoshi 大阪大学, 医学系研究科, 特任助教(常勤) (30650593)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Annexin A4 / 卵巣癌 / 核酸医薬 / プラチナ抵抗性 / 明細胞癌 / アンチセンス / antisense / ovarian carcinoma / annexin / platinum resistance |
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| Outline of Final Research Achievements |
Ovarian clear cell carcinoma (OCCC) is highly resistant to platinum based cancer chemotherapytreatment. We previously reported that Annexin (Anx) A4 protein was overexpressed in OCCC tissues and associating with chemoresistance to platinum-based cancer drugs. To overcome the platinum chemoresistance, we thought antisense oligonucleotides (ASOs) to be a good therapeutic option in a way of highly specific therapy for improving chemoresistance by suppressing the expression of Annexin A4 in cancer cells. We generated ASO targeting Anx A4 with 2’, 4’-bridged nucleic acid. By transfection of Anx A4 ASO, platinum resistance have improved both in vitro and in vivo. AnxA4 have associated with efflux of platinum anti-tumor drug. In conclusion, We are currently in the process of developing the drug delivery system, developing nucleic acid drugs which has higher binding affinity to target RNA in a clinical settings. Anx A4 could be a therapeutic option for ovarian OCCC with platinum resistance.
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| Academic Significance and Societal Importance of the Research Achievements |
卵巣癌の本邦での罹患数、死亡者数はともに増加傾向にある。進行期で発見されることが多く、手術後、あるいは再発してからの抗癌剤治療の効果が患者の予後を決定する最大の要因である。抗癌剤治療の中心はプラチナ製剤であり、プラチナ感受性の場合にはプラチナ製剤投与を受けながら社会復帰する患者さんも多数存在する。本研究で用いているAnxA4アンチセンスは、プラチナ耐性を改善することが証明され、臨床応用が可能になれば抗癌剤治療の効果を上げるとともに、薬剤の使用量の減量やQOLの向上に寄与する可能性がある。また、人工核酸は人工的に合成できることから、大量生産が可能であり、質の均一化や価格の面で将来性が期待される。
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Report
(3 results)
Research Products
(4 results)
