2003 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)
Co-Investigator(Kenkyū-buntansha)	石川仁群馬大学, 医学部, 助手 (70344918)
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,放射線の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,旅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.実験腫瘍を用いた放射線と温熱の併用研究では,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た.薬剤により熱耐性を抑制することにより,温熱の効果のみならず,放射線と温熱の併用効果も増強することが明らかとなった.熱耐性抑制による増感の機序は,HSPの発現抑制と熱感受性のS期細胞の増加が関与していた.レーザー顕微鏡による解析では,温熱開始直後からHSPの核内への移行と経時的な細胞質への再分布が明らかであったが,HSPの発現抑制により細胞質へのHSPの再分布が抑制された.臨床的には,胸壁浸潤型肺癌や難治性肉腫などにおいて,放射線と温熱の併用が有用であることを明らかにした. 放射線と温熱の効果に重大な影響を与える低酸素腫瘍の解析においては,子宮頸癌と食道癌を用いて,HIF-1,p53,p21,BAXなどの因子を解析し,HIF-1の高発現が治療効果に影響することを明らかにした.p53の変異などの腫瘍側の因子に関しては,影響は軽微であった.このため治療前の腫瘍の低酸素状態の非侵襲的定量化が今後の重要な研究課題と考えられたため,種々の低酸素評価法を実験腫瘍を用いて試みた.電極を腫瘍内に挿入し直接酸素濃度を測定する方法や,31P-MRSなどの方法と比較して,低酸素細胞マーカーであるβ-D-IAZGPは,副作用も軽微で,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,臨床上も有用性が高いと考えられた.

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Sohda M: "Pretreatment evaluation of combined HIF-1alpha, p53, and p21 expression is a useful and sensitive indicator of response to radiation and chemotherapy in esophageal cancer"Int J Cancer. (in press).
[Publications] Sakurai H: "A 104-year-old woman with advanced cervical carcinoma of the uterus"Gyn Oncol. 92・2. 713-715 (2004)
[Publications] Suzuki Y: "A case of rhabdomyosarcoma of the vagina in an elderly woman"Eur J Gyn Oncol. (in press).
[Publications] Saitoh J-I: "A persistent retroperitoneal synovial sarcoma -Effect of hyperthermia alone-"Jpn J Hyperthermic Oncology. (in press).
[Publications] Ishikawa H: "Comparable outcomes of radiation therapy without high-dose methotrexate for patients with primary central nervous system lymphoma"Jpn J Clin Oncol. 33・9. 443-449 (2003)
[Publications] Hasegawa M: "Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification"Int J Radiat Oncol Biol Phys. 57・1. 172-176 (2003)
[Publications] Kitamoto Y: "Caffeine diminishes cytotoxic effects of paclitaxel on a human lung adenocarcinoma cell line"Cancer Letter. 191. 101-107 (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] 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 Oncolo Biol Phys. 54・3. 23-31 (2001)
[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. 3143-3148 (2002)
[Publications] Imai R: "Signal transduction pathway to low-dose radiation-induced apoptosis in peripheraql PNET cells"Anticancer Res. 22. 2741-2748 (2001)
[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. 17・1. 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.Radiation Oncology 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 with inoperable or unresectable non- small cell lung cancer"Lung Cancer. 32. 81-88 (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)

2003 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] Sohda M: "Pretreatment evaluation of combined HIF-1alpha, p53, and p21 expression is a useful and sensitive indicator of response to radiation and chemotherapy in esophageal cancer"Int J Cancer. (in press).

[Publications] Sakurai H: "A 104-year-old woman with advanced cervical carcinoma of the uterus"Gyn Oncol. 92・2. 713-715 (2004)

[Publications] Suzuki Y: "A case of rhabdomyosarcoma of the vagina in an elderly woman"Eur J Gyn Oncol. (in press).

[Publications] Saitoh J-I: "A persistent retroperitoneal synovial sarcoma -Effect of hyperthermia alone-"Jpn J Hyperthermic Oncology. (in press).

[Publications] Ishikawa H: "Comparable outcomes of radiation therapy without high-dose methotrexate for patients with primary central nervous system lymphoma"Jpn J Clin Oncol. 33・9. 443-449 (2003)

[Publications] Hasegawa M: "Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification"Int J Radiat Oncol Biol Phys. 57・1. 172-176 (2003)

[Publications] Kitamoto Y: "Caffeine diminishes cytotoxic effects of paclitaxel on a human lung adenocarcinoma cell line"Cancer Letter. 191. 101-107 (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] 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 Oncolo Biol Phys. 54・3. 23-31 (2001)

[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. 3143-3148 (2002)

[Publications] Imai R: "Signal transduction pathway to low-dose radiation-induced apoptosis in peripheraql PNET cells"Anticancer Res. 22. 2741-2748 (2001)

[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. 17・1. 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.Radiation Oncology 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 with inoperable or unresectable non- small cell lung cancer"Lung Cancer. 32. 81-88 (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)

桜井英幸群馬大学, 医学部, 講師 (50235222)