| Project/Area Number |
24590958
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NAKAGAWA Mina 東京医科歯科大学, 医歯学融合教育支援センター, 准教授 (30401342)
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| Co-Investigator(Kenkyū-buntansha) |
ASAHINA Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (00422692)
WATANABE Mamoru 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
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| Co-Investigator(Renkei-kenkyūsha) |
SAKAMOTO Naoya 北海道大学, 医学研究科, 教授 (10334418)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 治療抵抗性機序 / C型慢性肝炎 / インターロイキン6 / 治療抵抗性 / 肝発癌 / インターロイキン６ / コア変異株 / コア変異 / DAA製剤 / 小胞体ストレス |
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| Outline of Final Research Achievements |
Our previous study described the association of serum IL-6 levels and ER stress and drug-resistance using JFH1 genotype 2a cell culture system. Based on the pTPF1-M170T (LC011929), we constructed full-length 1b clones that expressed core mutant viruses which were clinically resistant to IFN. Although TPF1-M170T clones are not currently allowed in drug-screening tests, perhaps this unique character can assist in establishing the molecular mechanism of HCV replication. We conducted a cohort study to investigate whether serum IL-6 levels influenced treatment outcomes of TVR/PEG-IFN/RBV triple therapy. Our results suggest that baseline low levels of IL-6, as well as their transient increase and decline during early stage of treatment, are correlated to good response to treatment, whereas sustained high levels of serum IL-6 are correlated to treatment resistance in most cases. Taken together, serum IL-6 levels correlate with resistance to treatment also with DAA combination therapy.
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