Integrated research for clarification of molecular biological and pharmacogenomic mechanisms of interstitial lung disease induced by molecular targeted drugs
| Project/Area Number |
16K08401
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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 |
Medical pharmacy
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 間質性肺疾患 / mTOR阻害薬 / STAT3 / EMT / エベロリムス / mTOR / 上皮間葉転換 / 間質性肺炎 / 分子標的治療薬 / ゲノム薬理 / SNP |
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| Outline of Final Research Achievements |
In this study, we clarify that the patients with CC genotype of STAT3 single nucleotide polymorphism (SNP) rs4796793 have a higher risk of interstitial lung disease induced by mammalian target of rapamycin (mTOR) inhibitor. Moreover, we observed that expression or activity of EMT marker and EMT related signal transduction factor is different from genotype of rs4796793 in human lung cancer cell lines.
Our study suggest that mechanism of molecular targeted drugs-induced interstitial lung disease associate with STAT3. To acumulate the data by further experiments, it is expected that STAT3 polymorphism use as the prediction marker of interstitial lung disease.
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| Academic Significance and Societal Importance of the Research Achievements |
間質性肺疾患はときに致命的な病態となる重大な副作用であり、近年の分子標的型薬剤の開発促進により、その発症者は経年的に増加している。これまで解明されていなかった分子標的治療薬に起因する間質性肺疾患の発症メカニズムにSTAT3と呼ばれるシグナル因子が関連することを明らかにすることができれば、これらのメカニズムに基づく発症予測因子や新規予防・治療方法の確立が期待される。
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Prostaglandin E1 reduces the keratinocyte toxicity of sorafenib by maintaining signal transducer and activator of transcription 3 (STAT3) activity and enhancing the cAMP response element binding protein (CREB) activity.2017
Author(s)
Shichiri H., Yamamoto K., Tokura M., Ishida T., Uda A., Bito T., Nishigori C., Nakagawa T., Hirano T., Yano I., Hirai M.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 485
Issue: 2
Pages: 227-233
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Association of Single Nucleotide Polymorphisms in <i>STAT3</i>, <i>ABCB1</i>, and <i>ABCG2</i> with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients2017
Author(s)
Watanabe A., Yamamoto K., Ioroi T., Hirata S., Harada K., Miyake H., Fujisawa M., Nakagawa T., Yano I., Hirai M.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 40
Issue: 4
Pages: 458-464
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed
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[Journal Article] Effects of Ascorbyl-2-phosphate Magnesium on Human Keratinocyte Toxicity and Pathological Changes by Sorafenib2017
Author(s)
Yamamoto K., Shichiri H., Ishida T., Kaku K., Nishioka T., Kume M., Makimoto H., Nakagawa T., Hirano T., Bito T., Nishigori C., Yano I., Hirai M.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 40
Issue: 9
Pages: 1530-1536
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed
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[Presentation] Association of Single Nucleotide Polymorphisms in STAT3, ABCB1, and ABCG2 with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients2017
Author(s)
Watanabe A, Yamamoto K, Ioroi T, Hirata S, Harada K, Miyake H, Fujisawa M, Nakagawa T, Yano I, Hirai M
Organizer
The 5th International Symposium of Training Plan for Oncology Professionals
Place of Presentation
Osaka
Year and Date
2017-03-11
Related Report
Int'l Joint Research
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[Presentation] Molecular cornifying mechanisms of multi-targeted tyrosine kinase inhibitors-induced hand-foot skin reaction based on genetic differences of STAT32017
Author(s)
Kazuhiro Yamamoto, Takahiro Ishida, Tsutomu Nakagawa, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Hideaki Miyake, Masato Fujisawa, Chikako Nishigori, Ikuko Yano, Midori Hirai
Organizer
The 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT 2017)
Related Report
Int'l Joint Research
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