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がん関連遺伝子が及ぼす放射線効果への影響

Research Project

Project/Area Number 09307015
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research Institution福井医科大学

Principal Investigator

加納 永一  福井医科大学, 医学部, 教授 (70065910)

Co-Investigator(Kenkyū-buntansha) 三橋 紀夫  群馬大学, 医学部, 助教授 (20008585)
大西 武雄  奈良県立医科大学, 医学部, 教授 (60094554)
西村 恭昌  近幾大学, 医学部, 教授 (00218207)
片山 寛次  福井医科大学, 医学部, 助教授 (30204431)
林 幸子  福井医科大学, 医学部, 助手 (00218570)
上田 公介  名古屋市立大学, 医学部, 助教授 (20128648)
新部 英男  群馬大学, 医学部, 教授 (90008293)
井上 俊彦  大阪大学, 医学部, 教授 (70028512)
増田 康治  九州大学, 医学部, 教授 (10037377)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥37,700,000 (Direct Cost: ¥37,700,000)
Fiscal Year 2000: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1999: ¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1998: ¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1997: ¥13,300,000 (Direct Cost: ¥13,300,000)
Keywords温熱感受性 / 放射線感受性 / 集学的制がん実験 / p53遺伝子及び蛋白 / Hsp72 / 細胞周期応答 / 熱帯産生薬成分
Research Abstract

加納・林等はマウスMT158-8細胞のp53 deficient株、wild type(wt)p53及びmutant(m)p53株を用いてそのHydroxyurea(HU)による細胞位相同調を比較した。その結果p53 deficient株及びwt-p53株はHUにより高品位にG^1〜S境界に同調されたが、m-p53株の同調品位ははるかに低かっか。この3細胞株の温熱感受性はいづれもS期で高かったが、deficient株とwt-p53株の2株はm-53株に比べて温熱高感受性であった。p53 geneは温熱感受性を規定するgenesの内の少なくとも一つとなっている。Japanese J.Hyperthermic Oncology 16:107-115,2000
西村等はTirapazamine(TPZ)、Ortho-chloracetyl carbamoyl fumagillol(TNP470)、40℃60分加温(MHT)、ガンマ線照射、シスプラチン、Brdu等の難解複雑な併用処理を行い、その後cytochalasine B等を指示薬として用い、照射やシスプラチンにかかわらずTPZとMHTの併用効果を認めた。
Int.J.Radiat.Oncol.Biol.Phys.47:799-807,2000
大西等はヒト膠芽腫細胞を用い、放射線による温熱感受性の増感はその放射線のlinear energy transfer(LET)とp53 statusの両方に依存している事を観察した。Int.J.Radiat.Oncl.Biol.Phys.47:489-494,2000
三橋等は52例の子宮頚がん(当然の事ながら偏平上皮がん)患者にいづれも外部放射線と3回の膣腔内brachytherapyを行った。HPVの16,18及び33型についてPCR法で鑑別した。又、p53についてはPCR-SSCP法でそのstatusを検定した。HPVは76.9%の患者に出現し、p53 statusがmutantであった患者は26.9%であった。HPVの存在とp53 statusの間には有意相関があった。mutant p53の患者はその50%で再発し、wt-p53の患者はその80%で局所制御された。p53のmutationは局所再発と有意に相関した。またp53 statusは、再発なしの生存率曲線と局所制御率との間で有意差を示し、StageIIIB子宮頚がん患者の放射線治療における予測因子となり得るようである。Cancer 91:80-89,2001
片山等は進行胃がんの腹膜転移の予防と治療のための持続的腹膜温湯潅流(CHPP)を32例の進行がんに根治的摘除術及びCHPPを行った。その内15例では腹腔転移の予防(腹膜浸潤が疑わしい症例)をはかり、17例(腹膜浸潤の疑いの低い症例)についてはCHPPをほどこして治療的効果を期待した。これらの患者を手術のみの対照群と術後腹膜再発について比較した。予防的CHPPによる腹膜再発と発生率は各々26%と35%で、手術のみの対象群が各々42%と17%であるのに比べて有意に高かった。therapeutic CHPP処理群の中心生存率は11ヶ月、これに対し摘除術後のみの群は6ヶ月で、対照群より長期に渡って生存した。予防的CHPPの研究ではCHPPは独立の予後因子ではあるが、治療的CHPPにおける独立の予後因子は、むしろ完全な摘除術であることが解った。CHPPはすでに発生した腹腔内転移には特段の根治的効果はないが、腹腔内転移を予防するための治療法としては有効である事が解った。更に術後のランドマイズドトライアルが必要であろう。Oncology 57:106-114,1999

Report

(3 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] M.Hatashita,E.Kano,S.Hayashi,H.Matsumoto,T.Ohtsubo,Z.H.Jin and H.Itoh: "Effect of the p53 gene on synchronization of cells with hydroxyurea and on the cell phase response to hyperthermia in vitro."Japanese J.Hyperthermic Oncology. 16. 107-115 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Takahashi,K.Ohnishi,X.Wang,M.Kobayashi,H.Matsumoto,T.Tamamoto,H.Aoki,Y.Furusawa,T.Ohnishi: "The dependence of p53 on the radiation enhancement of thermosensitivity at different let."Int.J.Radiat.Oncl.Biol.Phys.. 47. 489-494 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Ishikawa,N.Mitsuhashi,H.Sakurai,K.Maebayashi,H.Niibe: "The effects of p53 status and human papillomavirus infection on the clinical outcome in stage III cervical cancer treated with radiation therapy alone."Cancer. 61. 80-89 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Masunaga,K.Ono,Y.Nishimura,S.Kanamori,T.Saga,M.Suzuki,Y.Kinashi,M.Takagaki,S.Kasai,H.Nagasawa,Y.Uto,H.Hori: "Combined effects of tirapazamine and mild hyperthermia on anti-angiogenic agent (TNP-470) treated tumors ; reference to the effect on intratumor quiescent cells."Int.J.Radiat.Oncol.Biol.Phys.. 47. 799-807 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] To.Inoue,Ta.Inoue: "High-dose rate interstitial brachytherapy for mobile tongue cancer. Part 2.Phase III trial of HDR versus LDR interstitial brachytherapy for T_1-T_2 No carcinoma of the mobile tongue."Jpn.J.Cancer Chemother.. 27. 291-295 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Ueda,Y.Itu,N.Kawai,K.Tozawa,K.Kohri,E.Kano: "Imporoved quality of life in patients with advanced prostatic carcinoma treated with local hyperthermia."Japanese J.Hyperthermic Oncology. 15. 123-127 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Hirose,K.Katayama,A.Iida,A.Yamaguci,C.Nakagawara,S.Umeda,Y.Kusaka: "Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis andtreatment of peritoneal metastasis of advanced gastric cancer : evaluation by multivariate regression analysis"Oncology. 57. 106-114 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Hayashi,E.Kano,M.Hatashita,T.Ohtsubo,K.Katayama,K.Katayama and H.Matsumoto: "Thermotherapy for Neoplasia, Inflammation, and Pain"Schmidt K.L.,Simon E. et.al.. 335-345 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Ohtsubo,E.Kano,S.Hayashi,M.Hatashita,H.Matsumoto,R.Kitai,T.Saito,H.Saito: "Thermotherapy for Neoplasia, Inflammation, and Pain"Schmidt K.L.,Simon E. et.al.. 451-455 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H. Matsumoto, S. Hayashi, M. Hatashita, K. Ohnishi, T. Ohtsubo, R. Kitai, T. Ohnishi and E. Kano: "Nitric oxide is an initiator of intercellular signal transduction for stress response after hyperthermia in mutant p53 cells of human glioblastoma."Cancer Res.. 59. 3239-3244 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Hayashi, E. Kano, H. Matsumoto, M. Hatashita, T. Ohtsubo, T. Nishida, H. Shioura and R. Kitai: "Thermosensitivity, incidence of apoptosis and accumulations of hsp72 and p53 proteins of murine L cells in wild type status of p53 gene."J. Exp. Clin. Cancer Res.. 18. 181-189 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Ohnishi, H. Matsumoto, X. Wang, A. Takahashi, T. Tamamoto, K. Ohnishi: "Restration of p53-dependent apoptosis in the cells bearing the mutant p53 gene by glycerol."Int. J. Radeat. Biol.. 75. 1095-1098 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Kanamori, Y. Nishimura, Y. Okuno, N. Hori, T. Saga and M. Hiraoka: "Induction of vascular endothelial growth factor (VEGF) by hyperthermia and/or an angiogenesis."Int. J. Hyperthermia. 15. 267-278 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M. Ihara, A. Suwa, K. Komatsu, T. Shimasaki, K. Okaichi, E. A. Hendrickson and Y. Okumura: "Heat sensitivity of double-stranded DNA-dependent protein kinase (DNA-PK) activity"Int. J. Radeat. Biol.. 75. 253-258 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Saito, N. Mitsuhashi, H. Sakurai, H. Ishikawa, M. Hasegawa, T. Akimoto, K. Hayakawa and H. Niibe: "Apoptosis and appearace of Trp53-positive micronuclei in murine tumors with different radioresponses in vivo."Radiat. Res.. 152. 462-467 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Ueda, Y. Itou, N. Kawai, K. Tozawa, K. Kohri and E. Kano: "Improved quality of life in patients with advanced prostatic carcinoma treated with local hyperthermia."Jpn. J. Hyperthermic Oncol.. 15. 123-128 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Hayashi, E. Kano, M. Hatashita, T. Ohtsubo, K. Katayama and H. Matsumoto: "Thermotherapy: Principles and Practice"Schmidt K. L., Simon E. et al. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Ohtsubo, E. Kano, S. Hayashi, M. Hatashita, H. Matsumoto, R. Kitai, T. Saito, H. Saito: "Thermotherapy: Principles and Practice"Schmidt K. L., Simon E. et al. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Matsumoto, S.Hayashi, H.Shioura, T.Ohtsubo, T.Ohnishi, E.Kano: "Suppression of heat-induced hsp72 accumulation by cisplatin in human glioblastoma cells." CANCER LETTERS. 110. 253-257 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Hayashi, H.Matsumoto, H.Shioura, R.Kitai, M.Huimin and E.Kano: "Contribution of the p53 gene to heat-induced apoptosis." Proceedings of the 14th Annual Meeting of Japanese Society of Hyperthermic Oncology "Hyperthermic Oncology in Japan'97 Kyoto". (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] P.Picha, W.Naengchamnong, E.Kano, S.Hayashi, T.Ohtsubo, H.Matsumoto, H.Shioura and S,Ondee: "Effect of a natural pure compound,curculathyrane B,from Jatropha Curcas on thermosensitivity and development of thermotolerance in chinese hamster V-79 cells in vitro." CURRENT ADVANCES IN NATURAL PRODUCT RESEARCH. 27-29 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Shioura, S.Hayashi, H.Matsumoto, R.Kitai., T.Ohtsubo T.Nishida, S.W.Zhang, M.yoshida, Y.Ishii and E.Kano: "The effects of combined treatments with Low hyper-thermia and bleomycin on survivals of murine L cells" JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. 16. 147-152 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.hasegawa, N.Mitsuhashi, H.Nibe, et al.: "p53 protein expression and radiation-induced apoptosis in human tumors transplanted to nude mice." RADIATION MEDICINE. 15. 171-176 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Nishimura, Y.Nagata, K.Okajima, et al.: "Radiation therapy for T1,2 glottic carcinoma : inpact of overall treatment time on local control." Radiotherapy and Oncology. 40. 225-232 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Matsumoto, A.Takahashi, X.Wang, K.Ohnishi & T.Ohnishi: "Transfection of p53-knokout mouse fibroblasts with wild-type p53 increases the thermosensitivity and stimulates apoptosis by heat stress." INTERNATIONAL JOURNAL RADIATION ONCOLOGY. 38. 1089-1095 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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