2001 Fiscal Year Annual Research Report

放射線照射ならびに温熱に対するストレス応答機構の基礎的解析

Research Project

Project/Area Number	13218015
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (C)
Research Institution	Gunma University
Principal Investigator	桜井英幸群馬大学, 医学部, 講師 (50235222)
Keywords	放射線 / 温熱 / 耐熱性 / 増感 / p53 / HSP
Research Abstract	放射線照射と温熱による増感機構について解析するとともに,最近開発されたHSPインヒビターを用いて,そのストレス応答シグナル伝達に関わる分子の変化と細胞周期の変化について解析した.特にHSPインヒビターによる熱耐性の抑制が,放射線増感効果をもたらすかどうか,その有効な併用方法とその分子生物学的機構について検討を行うことを目的とした.まず低線量率照射と温熱の併用効果を算出した.増感効果は,40度から41.5度で高く,42度を超えるとむしろ低下していった.またマイルドハイパーサーミアで認められる慢性熱耐性は,持続照射の併用により部分的に抑制された.G1ブロックによる放射線抵抗性のS期細胞の減少と熱耐性蛋白の発現抑制が増感機構として証明された.またカフェインを低濃度で照射,温熱とともに作用させると細胞死は増加し,この効果は変異型P53細胞で顕著であった,HSPインヒビターは,41度の温熱時に誘導される慢性熱耐性を抑制し,細胞の温度感受性を増強した.このとき熱感受性のS期細胞が増加する傾向が認められた.ウエスタンブロットによる解析では,HSPの発現抑制が明らかであったが,HSF-1の活性化は抑制されていなかった.また,低線量率照射の効果は,温熱を加えなくともHSPインヒビター投与により明らかな増感が認められた.これまでの基礎研究をもとに,最も増感効果が高いとされる放射線照射と温熱の同時併用の可能性について,腔内照射と腔内加温をモデルとしてその最適な条件を検討し,進行食道癌を対象に良好な局所効果を確認した.また,難治性再発腫瘍を対象として,同時併用のすぐれた局所効果を確認した.

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Sakurai H: "Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone patterns of recurrence, latent periods and prognosis"Int. J. Radiat. Oncol. Biol. Phys.. 50・5. 1136-1144 (2001)
[Publications] Sakurai H: "Clinical application of low dose-rate brachytherapy combined with simultaneous mild temperature hyperthermia"Anticancer Res.. 21. 679-684 (2001)
[Publications] Sakurai H: "A challenge for Non-small cell lung cancer using hyperthermia"Jpn. J. Hyperthermic Oncol.. 171. 23-31 (2001)
[Publications] Akimoto T: "Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro : possible involvement of inhibition of survival signal transduction pathway"Int. J. Radiat. Oncol. Biol. Phys.. 50・1. 195-201 (2001)
[Publications] Ishikawa H: "The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone"Cancer. 91・1. 80-89 (2001)
[Publications] Hayakawa K: "High-dose radiation therapy for elderly patients woth inoperable or unresectable non-small cell lung canner"Lung Cancer. 32. 81-88 (2001)
[Publications] Islam MS: "Hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro"Oncology Reports. 8. 501-407 (2001)
[Publications] Kurosaki H: "Biological cell survival mapping for radiofrequency intracavitary hyperthermia combined with simultaneous high dose-rate intracavitary irradiation"Jpn. J. Cancer Res. 92・1. 95-102 (2001)
[Publications] Tsukiyama I: "Multi-institutional phase I and II trial of simultaneous intra-cavitary hyperthermia and brachytherapy for advanced esophageal cancer"J Brachytherapy International. (in press).
[Publications] Imai R: "Small cell lung cancer with a brain metastasis controlled for 5 years : a case report"Jpn J Clin Oncol. 31・3. 116-118 (2001)
[Publications] Fujita K: "The combined effect of preoperative hyperthermia and radiation therapy on advanced rectal cancer"Jpn J of Hyperthermic Oncol.. 17・3. 151-159 (2001)
[Publications] Mogi A: "Intrathoracic thermochemotherapy for the treatment of post-operative malignant pleural effusion in primary lung carcinoma-Report of a cese"Jpn J of Hyperthermic Oncol.. 17・3. 159-164 (2001)

2001 Fiscal Year Annual Research Report

放射線照射ならびに温熱に対するストレス応答機構の基礎的解析

Principal Investigator

桜井 英幸 群馬大学, 医学部, 講師 (50235222)

Research Products

[Publications] Sakurai H: "Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone patterns of recurrence, latent periods and prognosis"Int. J. Radiat. Oncol. Biol. Phys.. 50・5. 1136-1144 (2001)

[Publications] Sakurai H: "Clinical application of low dose-rate brachytherapy combined with simultaneous mild temperature hyperthermia"Anticancer Res.. 21. 679-684 (2001)

[Publications] Sakurai H: "A challenge for Non-small cell lung cancer using hyperthermia"Jpn. J. Hyperthermic Oncol.. 171. 23-31 (2001)

[Publications] Akimoto T: "Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro : possible involvement of inhibition of survival signal transduction pathway"Int. J. Radiat. Oncol. Biol. Phys.. 50・1. 195-201 (2001)

[Publications] Ishikawa H: "The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone"Cancer. 91・1. 80-89 (2001)

[Publications] Hayakawa K: "High-dose radiation therapy for elderly patients woth inoperable or unresectable non-small cell lung canner"Lung Cancer. 32. 81-88 (2001)

[Publications] Islam MS: "Hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro"Oncology Reports. 8. 501-407 (2001)

[Publications] Kurosaki H: "Biological cell survival mapping for radiofrequency intracavitary hyperthermia combined with simultaneous high dose-rate intracavitary irradiation"Jpn. J. Cancer Res. 92・1. 95-102 (2001)

[Publications] Tsukiyama I: "Multi-institutional phase I and II trial of simultaneous intra-cavitary hyperthermia and brachytherapy for advanced esophageal cancer"J Brachytherapy International. (in press).

[Publications] Imai R: "Small cell lung cancer with a brain metastasis controlled for 5 years : a case report"Jpn J Clin Oncol. 31・3. 116-118 (2001)

[Publications] Fujita K: "The combined effect of preoperative hyperthermia and radiation therapy on advanced rectal cancer"Jpn J of Hyperthermic Oncol.. 17・3. 151-159 (2001)

[Publications] Mogi A: "Intrathoracic thermochemotherapy for the treatment of post-operative malignant pleural effusion in primary lung carcinoma-Report of a cese"Jpn J of Hyperthermic Oncol.. 17・3. 159-164 (2001)

桜井英幸群馬大学, 医学部, 講師 (50235222)