The study of clinically relevant radioresistant cells for the development of more effective tumor radiotherapy

• Project/Area Number: 21710055
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tohoku University
• Principal Investigator: KUWAHARA Yoshikazu 東北大学, 加齢医学研究所, 助教 (00392225)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 放射線耐性 / オートファジー細胞死 / ラパマイシン / 臨床的放射線耐性 / ドセタキセル / ABCトランスポーター / 血管新生 / RAD001 / 臨床的放射線耐性細胞 / 抗がん剤

Research Abstract

X-ray induced autophagic cell death is suppressed in radioresistant cells. Administration of rapamycin, an induced of autophagy, sensitized radioresistant cells. Induction of autophagy would be the effective modality to overcome radioresistant tumor.

Research Products

• [Journal Article] Targeting the AKT/GSK3β/Cyclin D1/Cdk4 Survival Signaling Pathway for Eradication of Tumor Radioresistance Acquired by Fractionated Radiotherapy (2011)
  • Author(s): Shimura T, Kakuda S, Ochiai Y, Kuwahara Y, Takai Y, Fukumoto M
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 80 Pages: 540-548
  • Peer Reviewed
• [Journal Article] Targeting the AKT/GSK3β/cyclin D1/Cdk4 survival signaling pathway for eradication of tumor radioresistance acquired by fractionated radiotherapy (2011)
  • Author(s): Shimura T, Kakuda S, Ochiai Y, Kuwahara Y, Takai Y, Fukumoto M
  • Journal Title: Int J Radiat Oncol Biol Phys Volume: (未定)(印刷中)
  • Peer Reviewed
• [Journal Article] The uneven irradiation of a target cell and its dynamic movement can mathematically explain incubation period for the induction of cancer by internally deposited radionuclides (2010)
  • Author(s): Yamamoto Y, Usuda N, Oghiso Y, Kuwahara Y, Fukumoto M
  • Journal Title: Health Phys. Volume: 99 Pages: 388-393
  • Peer Reviewed
• [Journal Article] Acquired radioresistance of human tumor cells by DNA-PK/AKT/GSK3beta-mediated cyclin D1 overexpression (2010)
  • Author(s): Shimura T, Kakuda S, Ochiai Y, Nakagawa H, Kuwahara Y, Takai Y, Kobayashi J, Komatsu K, Fukumoto M
  • Journal Title: Oncogene Volume: 29 Pages: 4826-4837
  • Peer Reviewed
• [Journal Article] X-radiation-induced down-regulation of the EGF receptor in primary cultured rat hepatocytes (2010)
  • Author(s): Maruko A, Ohtake Y, Kawaguchi M, Kobayashi T, Baba T, Kuwahara Y, Nakagawa H, Shimura T, Fukumoto M, Ohkubo Y
  • Journal Title: Radiat Res. Volume: 173 Pages: 620-628
  • Peer Reviewed
• [Journal Article] The modified high-density survival assay is the useful tool to predict the effectiveness of fractionated radiation exposure (2010)
  • Author(s): Kuwahara Y, Mori M, Oikawa T, Shimura T, Ohtake Y, Mori S, Ohkubo Y, Fukumoto M
  • Journal Title: J Radiat Res. Volume: 51 Pages: 297-302
  • NAID: 10026471144
  • Peer Reviewed
• [Journal Article] The uneven irradiation of a target cell and its dynamic movement can mathematically explain incubation period for the induction of cancer by internally deposited radionuclides (2010)
  • Author(s): Yamamoto Y, Usuda N, Oghiso Y, Kuwahara Y, Fukumoto M
  • Journal Title: Health Phys Volume: 99 Pages: 388-393
  • Peer Reviewed
• [Journal Article] X-radiation-induced down-regulation of the EGF receptor in primary cultured rat hepatocytes (2010)
  • Author(s): Maruko A, Ohtake Y, Kawaguchi M, Kobayashi T, Baba T, Kuwahara Y, Nakagawa H, Shimura T, Fukumoto M, Ohkubo Y
  • Journal Title: Radiat Res Volume: 173 Pages: 620-628
  • Peer Reviewed
• [Journal Article] The modified high-density survival assay is the useful tool to predict the effectiveness of fractionated radiation exposure (2010)
  • Author(s): Kuwahara Y, Mori M, Oikawa T, Shimura T, Ohtake Y, Mori S, Ohkubo Y, Fukumoto M
  • Journal Title: J Radiat Res Volume: 51 Pages: 297-302
  • NAID: 10026471144
  • Peer Reviewed
• [Journal Article] The modified high-density survival assay is the useful tool to predict the effectiveness of fractionated radiation exposure (2010)
  • Author(s): Y KUWAHARA, M MORI, T OIKAWA, T SHIMURA, Y OHTAKE, S MORI, Y OHKUBO, M FUKUMOTO
  • Journal Title: Journal of Radiation Research (in press)
  • NAID: 10026471144
  • Peer Reviewed
• [Journal Article] Cell lines derived from a medaka radiation-sensitive mutant have defects in DNA double-strand break responses (2010)
  • Author(s): M HIDAKA, S ODA, Y KUWAHARA, M FUKUMOTO, H MITANI
  • Journal Title: Journal of Radiation Research 51 Pages: 165-171
  • NAID: 10025914643
  • Peer Reviewed
• [Journal Article] Histological type of Thorotrast-induced liver tumors associated with the translocation of deposited radionuclides (2010)
  • Author(s): Y YAMAMOTO, J CHIKAWA, Y UEGAKI, N USUDA, Y KUWAHARA, M FUKUMOTO
  • Journal Title: Cancer Science 101 Pages: 336-340
  • NAID: 10026587581
  • Peer Reviewed
• [Journal Article] Long incubation period for the induction of cancer by thorotrast is attributed to the uneven irradiation of liver cells at the microscopic level (2009)
  • Author(s): Y YAMAMOTO, N USUDA, T TAKATSUJI, Y KUWAHARA, M FUKUMOTO
  • Journal Title: Radiation Research 171 Pages: 494-503
  • Peer Reviewed
• [Journal Article] Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays (2009)
  • Author(s): Y KUWAHARA, L LI, T BABA, H NAKAGAWA, T SHIMURA, Y YAMAMOTO, Y OHKUBO, M FUKUMOTO
  • Journal Title: Cancer Science 100 Pages: 747-752
  • NAID: 10025144817
  • Peer Reviewed
• [Journal Article] Stabilities of ^<67>Ga- and ^<111>In-labeled transferrin in vitro (2009)
  • Author(s): Y OHTAKE, A MARUKO, Y KUWAHARA, M FUKUMOTO, Y OHKUBO
  • Journal Title: Protein Peptide Letter 16 Pages: 138-142
  • Peer Reviewed
• [Journal Article] Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
  • Author(s): Kuwahara Y, Oikawa T, Ochiai Y, Roudkenar MH, Fukumoto M, Shimura T, Ohtake Y, Ohkubo Y, Mori S, Uchiyama Y, Fukumoto M
  • Journal Title: Cell Death and Disease Volume: (in press)
  • Peer Reviewed
• [Journal Article] Neutrophil gelatinase-associated lipocalin: A new antioxidant that exerts its cytoprotective effect independent on Heme Oxygenase-1
  • Author(s): Roudkenar MH, Halabian R, Bahmani P, Roushandeh AM, Kuwahara Y, Fukumoto M
  • Journal Title: Free Radical Research Volume: (in press)
  • Peer Reviewed
• [Presentation] Identification and Analysis of Biological Markers for Tritium Exposure (2010)
  • Author(s): Fukumoto M, Shimura T, Kuwahara Y, Umata T
  • Organizer: 9th International Conference on Tritium Science and Technology TRITIUM2010
  • Place of Presentation: 奈良
• [Presentation] オートファジー誘導による臨床的放射線耐性の克服 (2010)
  • Author(s): 桑原義和、及川利幸、森美由紀、福本基、志村勉、福本学
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 臨床的放射線耐性細胞に新規血管新生阻害薬RAD001は有効か? (2010)
  • Author(s): 桑原義和、福本基、山本陽一朗、福本学
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 放射線治療のもう1R、獲得耐性 resistance はあるか (2010)
  • Author(s): 志村勉、桑原義和、福本学
  • Organizer: 第12回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
• [Presentation] Are radioresistant cells chemoresistant?: Examined by clinically relevant radioresistant cells (2009)
  • Author(s): KUWAHARA Y, OIKAWA T, MORI M, FUKUMOTO M, KURIHARA A, SHIMURA T, FUKUMOTO M
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Establishment of clinically relevant radioresistant cells and quest for the potential target to conquer tumor radioresistance (2009)
  • Author(s): M FUKUMOTO, L LI, Y KUWAHARA, T SHIMURA
  • Organizer: 4th Medical Biotech Forum
  • Place of Presentation: Dalian, China
• [Presentation] Long incubation period from the induction of cancer by Thorotrast is attributed to the uneven irradiation of hepatocytes at the microscopic level (2009)
  • Author(s): Y YAMAMOTO, N USUDA, T TAKATSUJI, Y KUWAHARA, M FUKUMOTO
  • Organizer: Health Effects of Incorporated Radionuclides
  • Place of Presentation: Santa Fe, New Mexico, United States
• [Presentation] 臨床的放射線耐性細胞の樹立と形質解析 (2009)
  • Author(s): 福本学、桑原義和、志村勉
  • Organizer: 日本放射線腫瘍学会第22回学術大会
  • Place of Presentation: 京都
• [Presentation] DNA-PK/AKT/GSK3b/cyclinD1経路を標的としたヒトがん細胞における放射線耐性の克服 (2009)
  • Author(s): 志村勉、角田智、高井良尋、桑原義和、福本学
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] 長期分割放射線被ばくによるがん細胞の放射線耐性の獲得 (2009)
  • Author(s): 志村勉、落合泰史、桑原義和、福本学
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] 新規血管新生阻害薬RAD001は臨床的な放射線耐性細胞に有効か? (2009)
  • Author(s): 森美由紀、桑原義和、志村勉、及川利幸、福本基、越後成志、福本学
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] AKT阻害剤による腫瘍細胞の獲得放射線耐性の克服 (2009)
  • Author(s): 角田智、志村勉、桑原義和、落合泰史、高井良尋、福本学
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] 放射線耐性細胞はどの抗がん剤と交差耐性を示すのか? (2009)
  • Author(s): 桑原義和、及川利幸、森美由紀、志村勉、福本学
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] 長期放射線被ばくによるサイクリンD1過剰発現はDNA二重鎖切断を誘導する (2009)
  • Author(s): 落合泰史、志村勉、桑原義和、山本和生、福本学
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
• [Presentation] Long incubation time of Thorotrast-induced liver cancer is attributed to the uneven irradiation at the microscopic level (2009)
  • Author(s): 福本学、山本和生、桑原義和
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Are radioresistant cells chemoresistant? : Examined by clinically relevant radioresistant cells (2009)
  • Author(s): Y KUWAHARA, T OIKAWA, M MORI, M FUKUMOTO, A KURIHARA, T SHIMURA, M FUKUMOTO
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Does chronic exposure to ionizing radiation induce somatic mutations in the D-loop of mitochondrial DNA (2009)
  • Author(s): A KURIHARA, Y KUWAHARA, T SHIMURA, M FUKUMOTO
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] より有効な放射線療法を目指した臨床的放射線耐性細胞の樹立とその解析 (2009)
  • Author(s): 桑原義和、森美由紀、及川利幸、志村勉、福本学
  • Organizer: 第48回 日本医学放射線学会生物部会学術大会
  • Place of Presentation: 富山
• [Remarks]
  • URL: http://www.idac.tohoku.ac.jp/dep/path/
• [Remarks]
  • URL: http://www.idac.tohoku.ac.jp/dep/path/