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Integrated research for clarification of molecular biological and pharmacogenomic mechanisms of interstitial lung disease induced by molecular targeted drugs

Research Project

Project/Area Number 16K08401
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionKobe University

Principal Investigator

Yamamoto Kazuhiro  神戸大学, 医学部附属病院, 特命講師 (30610349)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
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
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (36 results)

All 2018 2017 2016

All Journal Article (18 results) (of which Peer Reviewed: 16 results,  Open Access: 1 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results)

  • [Journal Article] Basic examination of the electrochemiluminescence immunoassay (ECLIA) method for measuring everolimus blood concentrations2018

    • Author(s)
      大籔 智奈美、佐藤 伊都子、東口 佳苗、山本 和宏、石村 武志、中町 祐司、三枝 淳
    • Journal Title

      Japanese Journal of Medical Technology

      Volume: 67 Issue: 5 Pages: 722-726

    • DOI

      10.14932/jamt.18-39

    • NAID

      130007501067

    • ISSN
      0915-8669, 2188-5346
    • Year and Date
      2018-10-25
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma2018

    • Author(s)
      Yamamoto Kazuhiro、Yano Ikuko
    • Journal Title

      Medical Oncology

      Volume: 35 Issue: 2 Pages: 16-16

    • DOI

      10.1007/s12032-017-1077-0

    • NAID

      120006649621

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 腎臓病薬物療法専門薬剤師の活動と挑戦(編集委員会発トピックス)2018

    • Author(s)
      山本和宏
    • Journal Title

      日本腎臓病薬物療法学会誌

      Volume: 7 Pages: 215-217

    • Related Report
      2018 Annual Research Report
  • [Journal Article] シグナル伝達因子に起因する間質性肺炎発症メカニズム2018

    • Author(s)
      山本和宏,中川勉,矢野育子,平井みどり
    • Journal Title

      メディカル・サイエンス・ダイジェスト

      Volume: 44 Pages: 49-53

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Journal Article] Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma.2018

    • Author(s)
      Yamamoto K., Hara T., Nakagawa T., Hirai M., Miyake H., Fujisawa M., Yano I.
    • Journal Title

      Targeted Oncology

      Volume: 13 Issue: 3 Pages: 371-378

    • DOI

      10.1007/s11523-018-0563-4

    • NAID

      120006649622

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of the PCK2 Gene Polymorphism With New-onset Glucose Intolerance in Japanese Kidney Transplant Recipients2018

    • Author(s)
      Yokoyama N.、Ishimura T.、Oda T.、Ogawa S.、Yamamoto K.、Fujisawa M.
    • Journal Title

      Transplantation Proceedings

      Volume: 50 Issue: 4 Pages: 1045-1049

    • DOI

      10.1016/j.transproceed.2018.01.042

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of CYP2D6 polymorphisms and extrapyramidal symptoms in schizophrenia patients receiving risperidone: a retrospective study.2018

    • Author(s)
      Ito T, Yamamoto K, Ohsawa F, Otsuka I, Hishimoto A, Sora I, Hirai M, Yano I.
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 4 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s40780-018-0126-y

    • NAID

      120006543322

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 485 Issue: 2 Pages: 227-233

    • DOI

      10.1016/j.bbrc.2017.02.107

    • NAID

      120006733140

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 4 Pages: 458-464

    • DOI

      10.1248/bpb.b16-00875

    • NAID

      130005530145

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 9 Pages: 1530-1536

    • DOI

      10.1248/bpb.b17-00386

    • NAID

      130006038784

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs.2017

    • Author(s)
      Mizuta Naomi、Nakagawa Tsutomu、Yamamoto Kazuhiro、Nishioka Tatsuya、Kume Manabu、Makimoto Hiroo、Yano Ikuko、Minami Hironobu、Hirai Midori
    • Journal Title

      Kobe Journal of Medical Sciences

      Volume: 63

    • NAID

      120006329054

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] マルチキナーゼ阻害薬による皮膚障害におけるSTAT3の役割2017

    • Author(s)
      山本和宏
    • Journal Title

      医療薬学

      Volume: 43 Pages: 237-244

    • NAID

      130006733804

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 分子標的治療薬による皮膚障害のSTAT3を標的とした新規治療法の確立2017

    • Author(s)
      山本和宏
    • Journal Title

      薬学研究の進歩

      Volume: 33 Pages: 115-120

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] シグナル伝達因子に起因する間質性肺炎発症メカニズム2017

    • Author(s)
      山本和宏、中川勉、矢野育子、平井みどり
    • Journal Title

      別冊Bio Clinica

      Volume: 6 Pages: 121-125

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 薬剤師による処方設計〈61〉薬剤師主導のバンコマイシン処方設計に向けた取り組み2017

    • Author(s)
      住吉霞美,山本和宏,矢野育子
    • Journal Title

      医薬ジャーナル

      Volume: 53 Pages: 131-135

    • NAID

      40021357274

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists' assessment and intervention based on Screening Tool of Older Persons' Potentially Inappropriate Prescriptions criteria ver.2.2017

    • Author(s)
      Kimura T, Ogura F, Yamamoto K, Uda A, Nishioka T, Kume M, Makimoto H, Yano I, Hirai M
    • Journal Title

      J Clin Pharm Ther.

      Volume: 42 Issue: 2 Pages: 209-214

    • DOI

      10.1111/jcpt.12496

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 「薬剤師外来」における薬学的処方介入とその評価2017

    • Author(s)
      栗村朋子,山本和宏,池田剛久,橋本正良,西岡達也,久米学,槇本博雄,矢野育子,平井みどり
    • Journal Title

      医療薬学

      Volume: 43 Pages: 169-175

    • NAID

      130006470917

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] ゾピクロン錠とエスゾピクロン錠の苦味比較(第2報)‐ランダム化二重盲検クロスオーバー試験‐2017

    • Author(s)
      宇田篤史, 大澤史宜, 山本和宏, 四宮一昭, 平野剛, 平井みどり
    • Journal Title

      日本病院薬剤師会雑誌

      Volume: 53 Pages: 192-196

    • NAID

      120006784499

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 個別化医療のいまとこれからを考える -がんゲノム医療からプライマリ・ケアまで-2018

    • Author(s)
      山本和宏
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] がん分子標的治療による副作用の分子メカニズムの解明と克服法の確立に向けた病院薬剤師の挑戦2018

    • Author(s)
      山本和宏
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Invited
  • [Presentation] エベロリムス長期曝露肺胞上皮細胞の上皮間葉転換に寄与するケモカインの探索2018

    • Author(s)
      岩間弓奈,山本和宏,濵口常男,中川勉,矢野育子
    • Organizer
      医療薬学フォーラム2018 第26回 クリニカルファーマシーシンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎細胞癌患者のスニチニブ治療効果に及ぼす組織STAT3発現の影響2017

    • Author(s)
      山本和宏,劉兵,原琢人,渡邉愛未,西岡達也,久米学,槇本博雄,中川勉,矢野育子,三宅秀明,藤澤正人,平井みどり
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] エベロリムスによる間質性肺疾患発症メカニズムにおけるTGF-βの関与2017

    • Author(s)
      穐原裕奈,山本和宏,渡邉愛未,七里博章,中川勉,濱口常男,矢野育子,平井みどり
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] エルロチニブによる皮膚障害におけるアクアポリン3の発現変動2017

    • Author(s)
      小野ひとみ,山本和宏,七里博章,渡邉愛未,中川勉,矢野育子,尾藤利憲,錦織千佳子,平井みどり
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] mTOR阻害薬によるトリグリセリド合成亢進作用におけるACAA2の役割2017

    • Author(s)
      渡邉愛未,山本和宏,中川勉,矢野育子,平井みどり
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [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
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bench-to-bedside research for the dermatological side effects induced by multiple tyrosine kinase inhibitors2017

    • Author(s)
      Kazuhiro Yamamoto
    • Organizer
      The 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ゲノム情報活用支援システムの有用性の評価と課題2017

    • Author(s)
      山本和宏
    • Organizer
      第27回日本医療薬学会年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 分子標的治療薬の有効性・副作用とSTAT3遺伝子多型の関連2017

    • Author(s)
      山本和宏
    • Organizer
      第15回日本臨床腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 分子標的治療薬の適正使用に向けた遺伝子多型解析の実践2017

    • Author(s)
      山本和宏
    • Organizer
      第11回日本緩和医療薬学会年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 学会発表の次のステップ~エビデンスとして残すために~2017

    • Author(s)
      山本和宏
    • Organizer
      第 1 回 医療薬学教育セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [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
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impact of STAT3 genetic polymorphism on sunitinib-induced stomatitis in Japanese renal cell carcinoma patients2017

    • Author(s)
      Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai
    • Organizer
      The 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子情報を実践的に活用するための連携体制の構築に向けた動向と課題2016

    • Author(s)
      山本和宏
    • Organizer
      第26回日本医療薬学会年会
    • Place of Presentation
      京都
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 奨励賞受賞講演:腎細胞がんに対する分子標的治療薬の有効性・副作用予測因子に関する研究2016

    • Author(s)
      山本和宏
    • Organizer
      第26回日本医療薬学会年会
    • Place of Presentation
      京都
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 分子標的治療薬の適正使用に向けた現場実践型研究の推進 -病院薬剤師の挑戦と責務-2016

    • Author(s)
      山本和宏
    • Organizer
      日本病院薬剤師会東北ブロック第6回学術大会
    • Place of Presentation
      福島
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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