DNA double strand break and fusion gene formation in tumorigenesis of sarcoma.

• Project/Area Number: 24592250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: National Hospital Organization, Kyushu Cancer Center
• Principal Investigator: TANAKA Kazuhiro 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 客員研究員 (10274458)
• Co-Investigator(Kenkyū-buntansha): ODA Shinya 独立行政法人国立病院機構九州がんセンター, 臨床研究センター, 腫瘍遺伝学研究室長 (40333372)
• 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肉腫 / 骨軟部腫瘍 / 染色体転座 / DNA修復 / 癌

Outline of Final Research Achievements

Using DNA microarray approaches, expression of the genes functioning in DNA double strand break (DSB) repair was explored in cell lines or tissue specimens derived from Ewing sarcomas and the other human soft tissue neoplasms with disease-specific chromosomal translocations. Expression of several DSB repair genes was similarly induced in these sarcoma cells. Furthermore, expression and subcellular localization of the DSB repair proteins were observed using immunocytochemistry, the results revealing an enhanced nuclear foci-formation in some DSB repair factors, which strongly suggest that the induction of the genes does reflect functional responses to DSBs occurred in cells.

Research Products

• [Journal Article] Tumor-suppressive microRNA-let-7a inhibits cell proliferation via targeting of E2F2 in osteosarcoma cells. (2015)
  • Author(s): Iwasaki T, Tanaka K, Kawano M, Itonaga I, Tsumura H
  • Journal Title: Int J Oncol Volume: 46 Issue: 4 Pages: 1543-1550
  • DOI: 10.3892/ijo.2015.2867
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Perioperative chemotherapy with high-dose ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities: Japan Clinical Oncology Group Study JCOG0304. (2015)
  • Author(s): Tanaka K, Mizusawa J, Fukuda H, Araki N, Chuman H, Takahashi M, Ozaki T, Hiruma T, Tsuchiya H, Morioka H, Hatano H, Wada T, Hosaka M, Yoshida Y, Toguchida J, Abe S, Matsumine A, Yokoyama R, Iwamoto Y
  • Journal Title: Jpn J Clin Oncol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Dendrotic cells combined with immunogenic cell death induced by doxorubicin exhibits antitumor effects in osteosarcoma. (2015)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Miyazaki M, Ikeda S, Tsumura H
  • Journal Title: Oncol Let Volume: 印刷中
  • Peer Reviewed
• [Journal Article] 骨軟部肉腫に対するGemcitabine+Docetaxel併用療法の効果 (2015)
  • Author(s): 細山嗣晃、田仲和宏、糸永一朗、河野正典、岩崎達也、津村弘
  • Journal Title: 整形外科と災害外科 Volume: 64 Pages: 176-181
  • Peer Reviewed
• [Journal Article] Dynamic Modulation of Thymidylate Synthase Gene Expression and Fluorouracil Sensitivity in Human Colorectal Cancer Cells. (2015)
  • Author(s): Wakasa K, Kawabata R, Nakao S, Hattori H, Taguchi K, Uchida J, Yamanaka T, Maehara Y, Fukushima M, Oda S.
  • Journal Title: PLoS One Volume: 10 Issue: 4 Pages: e0123076-e0123076
  • DOI: 10.1371/journal.pone.0123076
  • Peer Reviewed / Open Access
• [Journal Article] A randomized phase II/III trial of perioperative chemotherapy with adriamycin plus ifosfamide vs gemcitabine plus docetaxel for high-grade soft tissue sarcoma: Japan Clinical Oncology Group study JCOG1306. (2014)
  • Author(s): Kataoka K, Tanaka K, Mizusawa J, Kimura A, Hiraga H, Kawai A, Matsunobu T, Matsumine A, Araki N, Oda Y, Fukuda H, Iwamoto Y
  • Journal Title: Jpn J Clin Oncol Volume: 44 Issue: 8 Pages: 765-769
  • DOI: 10.1093/jjco/hyu080
  • Peer Reviewed
• [Journal Article] 示指基節骨に発生した巨大軟骨肉腫の一例 (2014)
  • Author(s): 曽根嵩史、糸永一朗、田仲和宏、河野正典、岩崎達也、津村弘
  • Journal Title: 整形外科と災害外科 Volume: 63 Pages: 653-655
  • NAID: 130004713205
  • Peer Reviewed
• [Journal Article] 軟部腫瘍の化学療法 (2013)
  • Author(s): 田仲和宏
  • Journal Title: 関節外科 Volume: 32 Pages: 870-877
  • Peer Reviewed
• [Journal Article] 整形外科における臨床試験のデザインのあり方 (2013)
  • Author(s): 田仲和宏
  • Journal Title: 臨床整形外科 Volume: 49 Pages: 1017-1024
  • NAID: 40019814881
  • Peer Reviewed
• [Journal Article] The activity of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group.
  • Author(s): Iwamoto Y and Tanaka K
  • Journal Title: Jpn J Clin Oncol Volume: 42 Issue: 6 Pages: 467-470
  • DOI: 10.1093/jjco/hys059
  • Peer Reviewed
• [Presentation] Tumor-suppressive microRNA-let-7a inhibits cell proliferation via targeting of E2F2 in osteosarcoma cells. (2015)
  • Author(s): Kawano M, Tanaka K, Itonaga I, Iwasaki T, Tsumura H
  • Organizer: 2015 Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2015-03-28 – 2015-03-31
• [Presentation] Multicenter clinical trials for sarcomas in Bone and Soft Tissue Tumor Study Group (BSTTSG) of Japan Clinical Oncology Group (JCOG): Difficulties and future direction. (2015)
  • Author(s): Tanaka K
  • Organizer: The 1st International Symposium on Recent Global Advances in Cancer Research
  • Place of Presentation: Tokyo
  • Year and Date: 2015-02-12 – 2015-02-13
• [Presentation] Ewing肉腫細胞におけるmiR-138によるFAK発現調節と腫瘍転移能の解析 (2014)
  • Author(s): 河野正典、田仲和宏、岩崎達也、糸永一朗、津村弘
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] 骨肉腫細胞株におけるlet-7aによるE2F2発現と腫瘍増殖能の解析 (2014)
  • Author(s): 河野正典、田仲和宏、津村弘
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ヒト子宮体癌にみられるマイクロサテライト不安定性の異なる2つのモード (2014)
  • Author(s): 織田信弥
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 高悪性度軟部肉腫に対する補助化学療法の臨床試験（JCOG0304）における 予後因子解析 (2014)
  • Author(s): 田仲和宏、長谷川匡、水澤純基、荒木信人、中馬広一、高橋満、尾崎敏文、 比留間徹、土屋弘行、森岡秀夫、畠野宏史、和田卓郎、保坂正美、福田治彦、 岩本幸英
  • Organizer: 第52回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-08-28 – 2014-08-30
  • Invited
• [Presentation] 骨転移に対する手術治療戦略：JCOG骨軟部腫瘍グループでのアンケート調査結果を 中心に (2014)
  • Author(s): 荒木信人、中馬広一、松延知哉、田仲和宏、畠野宏史、大野貴敏、国定俊之、 阿部哲士、森井健司、杉浦英志、比留間徹、平岡弘二、西田佳弘、福田治彦、 岩本幸英
  • Organizer: 第52回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-08-28 – 2014-08-30
  • Invited
• [Presentation] 骨肉腫細胞株におけるlet-7aによるE2F2発現調節と腫瘍増殖能の解析 (2014)
  • Author(s): 河野正典、田仲和宏、岩崎達也、糸永一朗、津村弘
  • Organizer: 第47回日本整形外科学会骨･軟部腫瘍学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] 当科におけるパゾパニブの臨床使用経験 (2014)
  • Author(s): 糸永一朗、田仲和宏、河野正典、岩崎達也、津村弘
  • Organizer: 第47回日本整形外科学会骨･軟部腫瘍学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] Prognostic factors for high-grade soft tissue sarcomas (STS) in the extremities treated by perioperative chemotherapy with ifosfamide (IFO) and adriamycin (ADM): Using data from Japan Clinical Oncology Group trial (JCOG0304). (2014)
  • Author(s): Tanaka K, Hasegawa T, Mizusawa J, Araki N, Chuman H, Takahashi M, Ozaki T, Hiruma T, Tsuchiya H, Morioka H, Hatano H, Wada T, Hosaka M, Yoshida Y, Toguchida J, Abe S, Matsumine A, Yokoyama K, Fukuda H, Iwamoto Y
  • Organizer: 2014 Annual Meeting of American Society of Clinical Oncology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] マイクロサテライト不安定性をもたらすDNAポリメラーゼ校正機能異常 (2013)
  • Author(s): 織田信弥
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Presentation] Ewing肉腫細胞におけるDNA二本鎖切断修復因子の発現異常 (2012)
  • Author(s): 田仲 和宏
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Book] 肉腫化学療法マスターコース (2015)
  • Author(s): 田仲和宏
  • Total Pages: 366
  • Publisher: 南山堂
• [Book] がん治療認定医教育セミナーテキスト (2014)
  • Author(s): 中馬広一、田仲和宏
  • Total Pages: 225
  • Publisher: 日本がん治療認定医機構