2002 Fiscal Year Annual Research Report

31P-MRSと低酸素細胞イメージングによる腫瘍内再酸素化機構の解析

Research Project

Project/Area Number	13670918
Research Institution	Gunma University
Principal Investigator	桜井英幸群馬大学, 医学部, 講師 (50235222)
Keywords	低酸素細胞 / 腫瘍 / 放射線 / 再酸素化 / MR Spectroscopy / ^<31>P-MRS / HIF-1
Research Abstract	腫瘍の低酸素状態は,放射線抵抗性を誘導するばかりでなく,腫瘍自体の転移や浸潤といった悪性化を引き起こすとされている.腫瘍内の低酸素状態を非侵襲的に評価することにより,癌治療の個別化を図れる可能性が広がる.このため,実験腫瘍を用いて低酸素分画の定量化を種々の方法で試みた.まず始めに,酸素濃度測定用電極を腫瘍内に刺入して実際の酸素濃度を測定した結果,大きな腫瘍では,腫瘍内酸素濃度は有意に低下していた.^<31>P-MRSによる腫瘍内の高エネルギー燐酸代謝は,腫瘍内低酸素状態を間接的に反映するとされている.この方法は感度が高いが,小さな腫瘍では正常組織の信号が混入するためばらつきが大きく,また1g以上の大きな腫瘍では無機燐の信号が大きくなるため詳細なエネルギー代謝の評価は困難であった.次に低酸素細胞マーカーであるβ-D-IAZGPの投与により低酸素細胞分画の評価を行った.シンチグラムを撮像した結果,24時間後に腫瘍に特異的な集積が認められた.腫瘍内の低酸素細胞マーカーの取り込みは血液の約8倍を示し,他臓器に比べ中枢神経への分布が有意に低かった.種々の大きさの腫瘍で,薬剤の取り込みについて見ると,大きな腫瘍は低酸素細胞マーカーの取り込みが有意に高かった.担癌マウスの腫瘍組織に放射線照射を行い,in vitroで放射線感受性を評価した結果,大きな腫瘍は低酸素細胞分画を多く含み,放射線抵抗性であることが明らかとなった.低酸素状態と腫瘍の悪性度との関連を明らかにするために,III期子宮頸部扁平上皮癌の生検組織を用いて,HIF-1αの発現と放射線治療効果について検討した.5年非再発生存率は,HIF-1陽性群で41.2%,陰性群で75.6%であり,有意な差が認められた.特に遠隔転移率において,強い相関が認められ,HIF-1の発現がIII期子宮頸癌の悪性度と相関が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. 101-107 (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] Akimoto T: "Heat shock protein 90 (Hsp9O) 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. 3143-3148 (2002)
[Publications] Imai R: "Signal transduction pathway to low-dose radiation-induced apoptosis in peripheraql PNET cells"Anticancer Res. 22. 2741-2748 (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 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 pathways"Int.J.Radiat.Oncol.Biol.Phys.. 50・1. 195-201 (2001)
[Publications] Ishikawa H: "The effects of p53 status and human papillomavirus intection 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. 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

31P-MRSと低酸素細胞イメージングによる腫瘍内再酸素化機構の解析

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. 101-107 (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] Akimoto T: "Heat shock protein 90 (Hsp9O) 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. 3143-3148 (2002)

[Publications] Imai R: "Signal transduction pathway to low-dose radiation-induced apoptosis in peripheraql PNET cells"Anticancer Res. 22. 2741-2748 (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 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 pathways"Int.J.Radiat.Oncol.Biol.Phys.. 50・1. 195-201 (2001)

[Publications] Ishikawa H: "The effects of p53 status and human papillomavirus intection 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. 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)