The role of glucocorticoid in mitochondria-dependent resistance to anticancer therapy

• Project/Area Number: 24501353
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Osaka City University
• Principal Investigator: KASAHARA EMIKO 大阪市立大学, 医学(系)研究科(研究院), 講師 (30468269)
• Co-Investigator(Kenkyū-buntansha): KUBO Shuji 兵庫医科大学, 医学部, 准教授 (10441320)
• Co-Investigator(Renkei-kenkyūsha): SEKIYAMA Atsuo 大阪大学, 薬学研究科, 教授 (30403702)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: グルココルチコイド / ミトコンドリア / 抗がん剤 / ストレス / 中皮腫 / シスプラチン / 薬剤耐性 / 抗がん剤耐性

Outline of Final Research Achievements

Those intense stress by a side effect of chemotherapy as well as the pain with the cancer also influence the therapeutic effects of the anticancer agents.
However, little is known about the mechanisms of these untoward actions. In this study, we investigated the influence of glucocorticoids, which is a stress-related hormone on anticancer drug actions. Our results suggest that stress-induced glucocorticoids attenuate the action of anticancer drug through the alteration of mitochondrial function.

Research Products

• [Journal Article] Stress-Induced Glucocorticoid Release Upregulates Uncoupling Protein-2 Expression and Enhances Resistance to Endotoxin-Induced Lethality (2015)
  • Author(s): Kasahara E, Sekiyama A, Hori M, Kuratsune D, Fujisawa N, Chida D, Hiramoto H, Li J, Okamura H, Inoue M, Kitagawa S.
  • Journal Title: Neuroimmunomodulation Volume: ー Issue: 5 Pages: 279-292
  • DOI: 10.1159/000368802
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cross-talk between HPA-axis-increased glucocorticoids and mitochondrial stress determines immune responses and clinical manifestations of patients with sepsis. (2015)
  • Author(s): Kasahara E, Inoue M.
  • Journal Title: Redox Rep. Volume: 20 Issue: 1 Pages: 1-10
  • DOI: 10.1179/1351000214y.0000000107
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Haploinsufficiency of the c-myc transcriptional repressor FIR, as a dominant negative-alternative splicing model, promoted p53-dependent T-cell acute lymphoblastic leukemia progression by activating Notch1. (2015)
  • Author(s): Matsushita K, Kitamura K, Rahmutulla B, Tanaka N, Ishige T, Satoh M, Hoshino T, Miyagi S, Mori T, Itoga S, Shimada H, Tomonaga T, Kito M, Nakajima-Takagi Y, Kubo S, Nakaseko C, Hatano M, Miki T, Matsuo M, Fukuyo M, Kaneda A, Iwama A, Nomura F.
  • Journal Title: Oncotarget Volume: 10 Pages: 5102-17
  • Peer Reviewed
• [Journal Article] Brain Vascular Pericytes Following Ischemia Have Multipotential Stem Cell Activity to Differentiate into Neural and Vascular Lineage Cells. (2015)
  • Author(s): Nakagomi T, Kubo S, Nakano-Doi A, Sakuma R, Lu S, Narita A, Kawahara M, Taguchi A, Matsuyama T.
  • Journal Title: Stem Cells. Volume: ー Issue: 6 Pages: 1962-1974
  • DOI: 10.1002/stem.1977
  • Peer Reviewed / Open Access
• [Journal Article] Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/ cyclinE and Ku86/ XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway. (2014)
  • Author(s): Rahmutulla B, Matsushita K, Satoh M, Seimiya M, Tsuchida S, Kubo S, Shimada H, Ohtsuka M, Miyazaki M, Nomura F.
  • Journal Title: Oncotarget Volume: 15 Pages: 2404-17
  • Peer Reviewed
• [Journal Article] Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses. (2014)
  • Author(s): Takagi-Kimura M, Yamano T, Tagawa M, Kubo S
  • Journal Title: Cancer Gene Ther. Volume: 21 Issue: 3 Pages: 126-32
  • DOI: 10.1038/cgt.2014.7
  • Peer Reviewed
• [Presentation] Role of stress-induced glucocorticoids in innate immune response (2014)
  • Author(s): 笠原恵美子、関山敦生、堀美香、井上正康
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Comparative evaluation of suicide gene therapy using retroviral peplicating vectors in an experimental model of human malignant mesothelioma. (2014)
  • Author(s): Kubo Shuji, Kasahara Noriyuki.
  • Organizer: iMig 2014
  • Place of Presentation: Cape town (South Africa)
  • Year and Date: 2014-10-21 – 2014-10-24
• [Presentation] 自然免疫応答におけるHPA軸の役割とミトコンドリアの関与 (2013)
  • Author(s): 笠原恵美子、関山敦生、堀美香、千田大、井上正康、北川誠一
  • Organizer: 第66回 臨床酸化ストレス学会
  • Place of Presentation: ウインク愛知（名古屋市）
• [Presentation] Role of the HPA-axis and mitochondria in LPS-induced septic shock (2013)
  • Author(s): E Kasahara, A. Sekiyama, M. Hori, D. Chida, H. Okamura, M Inoue, S Kitagawa.
  • Organizer: 6th Joint Meeting of the Societies for Free Radical Research
  • Place of Presentation: Mercure Sydney Hotel (SYDNEY Australia)
  • Invited
• [Presentation] ストレス応答とミトコンドリア代謝 (2012)
  • Author(s): 笠原恵美子
  • Organizer: 第3回 生殖ミトコンドリア研究会
  • Place of Presentation: IVFなんばクリニック マーメードホール（大阪市）
  • Invited
• [Presentation] ミトコンドリアと癌医療 (2012)
  • Author(s): 笠原恵美子
  • Organizer: 第29回 臨床フリーラジカル会議
  • Place of Presentation: けぶり河 多目的ホール（京都府亀岡市）
  • Invited
• [Presentation] ストレス負荷による自然免疫抑制機構とミトコンドリアの関与 (2012)
  • Author(s): 笠原恵美子、関山敦生、堀美香、千田大、井上正康、北川誠一
  • Organizer: 第85回 日本生化学会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡市）