1997 Fiscal Year Annual Research Report

放射線感受性予測の基礎研究

Research Project

Project/Area Number	09255102
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	The University of Tokyo
Principal Investigator	鈴木紀夫東京大学, 大学院・医学系研究科, 教授 (10010050)
Co-Investigator(Kenkyū-buntansha)	奥村寛長崎大学, 医学部, 教授 (00073130) 平岡真寛京都大学, 大学院・医学研究科, 教授 (70173218) 小川恭弘高知医科大学, 医学部, 助教授 (90152397) 小松賢志広島大学, 原爆放射能医学研究所, 教授 (80124577) 大西武雄奈良県立医科大学, 医学部, 教授 (60094554)
Keywords	放射線感受性 / 先行指標 / p53 / DNA-PK / 細胞死(アポトーシス) / 放射線誘導タンパク / リン酸化・脱リン酸化 / 感受性修飾
Research Abstract	腫瘍細胞の浸潤性のため、標的である腫瘍組織の周辺を含め、かなり大きな照射野で正常組織も照射を受けることは回避できず、その障害は照射線量限界となる。治療成績を向上させるためには個々の患者腫瘍に最適な照射法・線源を選択する指標、いわゆる先行指標又は、predictive assayと呼ばれる方法の確立が重要である。細胞の放射線感受性のメカニズムの解明を進め、放射線応答の特徴を測定する新しい方法や感受性を操作する新たな手段を開発し、治療効果の向上を目指す。細胞固有の放射線感受性は腫瘍の放射線感受性の一因子にすぎず、組織の生理的因子(pO_2,血流など)、腫瘍組織としての増殖能力(増殖細胞数、増殖細胞分画の大小、増殖速度、細胞消失率)、宿主との関係などを総合的に考慮して病理組織(各種抗体染色)及び臨床的な立場(ハイパーサーミア、化療等の集学的な視点)も含め総合的な検討が必要である。本年は特に、医科のことが進展した。照射跡のシグナル伝達経路(P13キナーゼ,p53,WAF1)の解明、がん抑遺伝子p53と放射線感受性、DNA二重鎖切断修復に重要なDNA-PK(DNA依存性プロテインキナーゼの放射線温熱感受性への関与のメカニズム)、及び放射線誘導遺伝子発現を中心に、放射線感受性のメカニズムの解明研究を行った。応用として有用な指標の開発、感受性の修飾法、特にプロテインキナーゼ阻害剤、治療抵抗性となる場合の変異型p53の正常野生型への変換、温熱による放射線感受性の修飾メカニズムの研究が進んだ。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Matsumoto,Y.et al.: "A possible mechanism for hyperthermic radiosensitization mediated through hyperthermic lability of Ku subunits in DNA-dependent protein kinase." Biochemical and Biophysical Research Communications. 234. 568-572 (1997)
[Publications] Ohtsubo,T, et al.: "p53-dependent induction of Wafl by low pH culture condition in human glioblastoma cells." Cancer Res.57. 3910-3913 (1997)
[Publications] Matsumoto,H.et al.: "Transfection of p53-knockout mouse fibroblasts with wild-type p53 increases the thermosensitivity and stimulates apoptosis by heat stress." Int.J.Radiat.Oncol.Biol.Phys.38. 1089-1095 (1997)
[Publications] Matsumoto,H.et al.: "Induction of cdk2 after γ-ray irradiation is dependent on p53 status." Int.J.Oncol.10. 1257-1260 (1997)
[Publications] Ogawa,Y.et al.: "Expression of fas(CD95/APO-1)antigen induced by radiation therapy for diffuse B-cell lymphoma:Immunohistochemical study." Clinical Cancer Res.3. 2211-2216 (1997)
[Publications] Ogawa,Y.et al.: "Immunohistochemical study of c-fos-positive lymphocytes of the head and neck during radiation therapy and its clinical significance." Clinical Cancer Res.3. 2301-2307 (1997)
[Publications] Matsuura,S.et al.: "Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24." Am.J.Hum.Genet.60. 1487-1494 (1997)
[Publications] Imai,H.et al.: "Minisatellite instability in severe combined immunodeficiency mouse cells." Proc.Natl.Acad.Sci.USA.94. 10817-10820 (1997)
[Publications] Masunaga,S.et al.: "Reduction of hypoxic cells solid tumours induced by mild hyperthermia:special reference to diffrernces in changes in the hypoxic fraction between total and quiescent cell populations." Br.J.Cancer. 76. 588-593 (1997)
[Publications] Murata R.et al.: "An anti-angiogenic agent(TNP-470)inhibited reoxygenation during fractionated radiotherapy of murime mammary carcinoma." Int.J.Radiat.Biol.Phys.37. 1107-1113 (1997)
[Publications] Takai,Y.et al.: "Single dose radiocurability of four murine solid tumors and a predicitive assay for the curability in situ." J.Radiat.Res.38. 233-240 (1997)
[Publications] Sakai,K.et al.: "Effects of an inhibitor of protein kinases on the response to heat treatment in cultured mammalian cells." Int.J.Hyperthermia. 13. 535-545 (1997)

1997 Fiscal Year Annual Research Report

放射線感受性予測の基礎研究

Principal Investigator

鈴木 紀夫 東京大学, 大学院・医学系研究科, 教授 (10010050)

Research Products

[Publications] Matsumoto,Y.et al.: "A possible mechanism for hyperthermic radiosensitization mediated through hyperthermic lability of Ku subunits in DNA-dependent protein kinase." Biochemical and Biophysical Research Communications. 234. 568-572 (1997)

[Publications] Ohtsubo,T, et al.: "p53-dependent induction of Wafl by low pH culture condition in human glioblastoma cells." Cancer Res.57. 3910-3913 (1997)

[Publications] Matsumoto,H.et al.: "Transfection of p53-knockout mouse fibroblasts with wild-type p53 increases the thermosensitivity and stimulates apoptosis by heat stress." Int.J.Radiat.Oncol.Biol.Phys.38. 1089-1095 (1997)

[Publications] Matsumoto,H.et al.: "Induction of cdk2 after γ-ray irradiation is dependent on p53 status." Int.J.Oncol.10. 1257-1260 (1997)

[Publications] Ogawa,Y.et al.: "Expression of fas(CD95/APO-1)antigen induced by radiation therapy for diffuse B-cell lymphoma:Immunohistochemical study." Clinical Cancer Res.3. 2211-2216 (1997)

[Publications] Ogawa,Y.et al.: "Immunohistochemical study of c-fos-positive lymphocytes of the head and neck during radiation therapy and its clinical significance." Clinical Cancer Res.3. 2301-2307 (1997)

[Publications] Matsuura,S.et al.: "Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24." Am.J.Hum.Genet.60. 1487-1494 (1997)

[Publications] Imai,H.et al.: "Minisatellite instability in severe combined immunodeficiency mouse cells." Proc.Natl.Acad.Sci.USA.94. 10817-10820 (1997)

[Publications] Masunaga,S.et al.: "Reduction of hypoxic cells solid tumours induced by mild hyperthermia:special reference to diffrernces in changes in the hypoxic fraction between total and quiescent cell populations." Br.J.Cancer. 76. 588-593 (1997)

[Publications] Murata R.et al.: "An anti-angiogenic agent(TNP-470)inhibited reoxygenation during fractionated radiotherapy of murime mammary carcinoma." Int.J.Radiat.Biol.Phys.37. 1107-1113 (1997)

[Publications] Takai,Y.et al.: "Single dose radiocurability of four murine solid tumors and a predicitive assay for the curability in situ." J.Radiat.Res.38. 233-240 (1997)

[Publications] Sakai,K.et al.: "Effects of an inhibitor of protein kinases on the response to heat treatment in cultured mammalian cells." Int.J.Hyperthermia. 13. 535-545 (1997)

鈴木紀夫東京大学, 大学院・医学系研究科, 教授 (10010050)