2002 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 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 / 熱耐性 / 熱耐性蛋白 / 増感 / 肺癌 / 低酸素
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,細胞のもつストレス応答シグナルの抑制が,放射線照射効果をどのように修飾するかを明らかにすることにより,放射線照射と温熱の有効な併用方法とその分子生物学的機構を解析することを目的とした.また,放射線照射ならびに温熱の効果に大きな影響を与える低酸素ストレスについて,その意義と治療効果への影響を明らかにすることを目的とした.マイルドハイパーサーミアと放射線照射の併用実験では,熱耐性の抑制や放射線照射からの亜致死障害からの回復阻害など,互いにその効果を高める機構が存在すると考えられ,併用のタイミングが重要なファクターと考えられた.また,HSPを制御することで,マイルドハイパーサーミアの効果が明らかに増感するだけでなく,放射線照射効果をも十分に増強させることができると考えられた.臨床的には,胸壁浸潤型肺癌で放射線照射と温熱の併用が,放射線単独にくらべ有効であることが明らかとなった.放射線と温熱の効果に重要な影響を与える低酸素ストレスの定量化をさまざまな方法で行った.低酸素細胞マーカーであるβ-D-IAZGPは,血液中の約8倍の高濃度で腫瘍に集積が認められた.中枢神経への取り込みが有意に少なく,腫瘍の大きさにかかわらずその取り込みが評価可能であり,非侵襲的な低酸素細胞分画の定量法として,臨床上の有用性が高いと考えられた.III期子宮頸癌の生検組織を用いて,低酸素で誘導されるHIF-1の発現を検討した結果,HIF-1αの高発現した腫瘍は遠隔転移の確率が高く,腫瘍の悪性度を反映する因子であることが明らかとなった.

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Kitamoto Y: "Caffeine diminishes cytotoxic effects of paclitaxel on a human lung adenocarcinoma cell line"Cancer Letter. 191・1. 101-7 (2003)
[Publications] Sakurai H: "Effect of hyperthermia combined with external radiation therapy in primary non-small lung cancer with direct bony invasion"Int J Hyperthermia. 18・5. 472-483 (2002)
[Publications] Akimoto T: "Heat shock protein 90(Hsp90) chaperone complex : A molecular target for enhancement of thermosensitivity and radiosensitivity"Jpn J Hyperthermic Oncol.. 18. 131-142 (2002)
[Publications] Saitoh J-I: "Correlation between in vivo tumor weight, oxygen pressure, 31P NMR spectroscopy, hypoxic microenvironment marking by β-D-iodinated azomycin galactopyranoside(β-D-IAZGP), and radiation sensitivity"Int J Radiat Oncol Biol Phys. 54・3. 903-909 (2002)
[Publications] Tamaki Y: "Combined effect of hyperthermia at 42℃ and irradiation dose of 2 Gy on two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro"Anticancer Res. 22. 3143-8 (2002)
[Publications] Imai R: "Signal transduction pathway to low-dose radiation-induced apoptosis in peripheraql PNET cells"Anticancer Res. 22. 2741-8 (2002)
[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 simulataneous 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 pathways"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 cancer"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. 17. 299-308 (2001)
[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)

2002 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] Kitamoto Y: "Caffeine diminishes cytotoxic effects of paclitaxel on a human lung adenocarcinoma cell line"Cancer Letter. 191・1. 101-7 (2003)

[Publications] Sakurai H: "Effect of hyperthermia combined with external radiation therapy in primary non-small lung cancer with direct bony invasion"Int J Hyperthermia. 18・5. 472-483 (2002)

[Publications] Akimoto T: "Heat shock protein 90(Hsp90) chaperone complex : A molecular target for enhancement of thermosensitivity and radiosensitivity"Jpn J Hyperthermic Oncol.. 18. 131-142 (2002)

[Publications] Saitoh J-I: "Correlation between in vivo tumor weight, oxygen pressure, 31P NMR spectroscopy, hypoxic microenvironment marking by β-D-iodinated azomycin galactopyranoside(β-D-IAZGP), and radiation sensitivity"Int J Radiat Oncol Biol Phys. 54・3. 903-909 (2002)

[Publications] Tamaki Y: "Combined effect of hyperthermia at 42℃ and irradiation dose of 2 Gy on two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro"Anticancer Res. 22. 3143-8 (2002)

[Publications] Imai R: "Signal transduction pathway to low-dose radiation-induced apoptosis in peripheraql PNET cells"Anticancer Res. 22. 2741-8 (2002)

[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 simulataneous 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 pathways"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 cancer"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. 17. 299-308 (2001)

[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)