2006 Fiscal Year Final Research Report Summary
Modification of radiation sensitivity in radiation therapy by combination of molecular target therapy
| Project/Area Number |
16390334
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Gunma University |
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Principal Investigator |
NAKANO Takashi GUNMA UNIVERSITY, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20211427)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Hideyuki Gunma University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 助教授 (50235222)
NONAKA Tetsuo Gunma University, Faculty of Medicine, Research Associate, 医学部, 助手 (40375556)
SUZUKI Yoshiyuki Gunma University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (60334116)
ISHIKAWA Hitoshi Gunma University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (70344918)
KATO Shingo National Institute of Radiological Sciences, Researcher, 放射線医学総合研究所, 研究員 (00370875)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Cervical cancer / Hypoxia / Radiation / Prognosis / HIF1α / p53 |
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| Research Abstract |
Correlations between radiation response and various biological parameters including oncogenes, apoptosis relating gene expressions of tumors and hypoxia relating proteins were investigated for prediction of radiation sensitivity predominantly relating local control probability following radiation therapy.
Immunohistochemical study and various DNA/RNA analysis for human specimens were performed for obtaining parameters relating to radiation sensitivity as well as analysis for tumor cell lines and experimental animals as materials. Prognosis was analyzed by various parameters including p21, p27, p53 protein expression, inducible NOS (iNOS), Hypoxia-inducible factor-1α (HIF-1α) and Cyclooxygenase-2 (Cox-2).
Of 38 patients, high expression of HIF-1α, p53, bax, and bcl-2 were seen in 17 (45%), 22 (58%), 15 (39%), and 15 (39%) patients, respectively, and 28 patients (74%) showed the positive infection with HPV. There was a significant positive correlation between high HIF-1α expression and dis
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ease recurrence (p<0.05). Furthermore, HIF-1α had a significant correlation with the recurrence free survival rate (p=0.04). No statistical significance was noted between high HIF-1α expression and local control rate (p=0.17), whereas HIF-1α status predicted distant metastasis with strong significance (p=0.03). Conversely, other factors demonstrated no impact on clinical outcome of patients with stage IIIB cervical carcinoma. HIF-1α is an important prognostic factor, especially for predicting future metastasis after radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix.
Cyclooxygenase-2 (Cox-2) impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis.
COX-2 plays a pivotal role in regulation of radiation-induced apoptosis. The relationship between COX-2 expression and postradiotherapy outcomes of patients with cervical cancer was analyzed for biopsy specimens from 47 consecutive patients who had undergone definitive radiotherapy alone or radiotherapy combined with chemotherapy. The COX-2 expression rate of the pretreatment samples was 46.1% +/- 21.0%, and the apoptotic index (AI) 1 week after start of radiotherapy was 2.1% +/- 0.9%. There was a significant negative correlation between the pretreatment COX-2 expression and the AI during radiotherapy (r=-0.52, p=0.0002). Complete response rates were 59% for COX-2 positive patients compared with 80% for COX-2 negative patients (p=0.12). The 2-year local control rate for COX-2 positive patients was 71.3%, whereas the corresponding rate for COX-2 negative patients was 96.0% (p=0.06). these results firstly prove clinically that COX-2 can make cervical squamous cell carcinomas more refractory to radiotherapy by inhibition of radiation-induced apoptosis. Furthermore, expression of COX-2 may be a good indicator to predict local tumor control after radiotherapy.
Bystander responses of human lung cancer cell line induced by high LET heavy-ion irradiation.
Lung cancer cells were irradiated with a collimated heavy-ion microbeam single cell irradiation system, which allows selected cells to be individually hit with defined number of heavy charged particles at JAERI-Takasaki. This system has been developed to study radiobiological processes in hit cells and bystander cells exposed to low dose and low dose-rate high-LET radiations, in ways that cannot be achieved using conventional broad-field exposures. The individual cultured cells grown in special dishes were irradiated in the atmosphere with a single or defined numbers of carbon beams. Bystander effect was induced by carbon irradiation and blocked by addition of gap inhibitor. Less
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[Journal Article] Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis.2006
Author(s)
Ishikawa H, Ohno T, Kato S, Wakatsuki M, Iwakawa M, Ohta T, Imai T, Mitsuhashi N, Noda SE, Nakano T, Tsujii H
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Journal Title
Int J Radiat Oncol Biol Phys. Dec1;66(5)
Pages: 1347-1355
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Dose Escalation Study of Carbon Ion Radiotherapy for Locally Advanced Carcinoma of the Uterine Cervix.2006
Author(s)
Kato S, Ohno T, Tsujii H, Nakano T, Mizoe JE, Kamada T, Miyamoto T, Tsuji H, Kato H, Yamada S, Kandatsu S, Yoshikawa K, Ezawa H, Suzuki M, Working Group of the Gynecological Tumor.
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Journal Title
Int J Radiat Oncol Biol Phys. Jun 1;65(2)
Pages: 388-397
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis.2006
Author(s)
Ishikawa H, Ohno T, Kato S, Wakatsuki M, Iwakawa M, Ohta T, Imai T, Mitsuhashi N, Noda SE, Nakano T, Tsujii H.
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Journal Title
Int J Radiat Oncol Biol Phys. 66(5)
Pages: 1347-1355
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dose Escalation Study of Carbon Ion Radiotherapy for Locally Advanced Carcinoma of the Uterine Cervix.2006
Author(s)
Shingo KATO, Tatsuya OHNO, Hirohiko TSUJI, Takashi NAKANO, Jun-etsu MIZOE, Tadashi KAMADA, Tadaaki MIYAMOTO, Hiroshi TSUJI, Hirotoshi KATO, Shigeru YAMADA, Susumu KANDATSU, Kyosan YOSHIKAWA, Hidefumi EZAWA, Michiya SUZUKI FOR THE WORKING GROUP OF THE GYNECOLOGICAL TUMOR
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Journal Title
Int J Radiat Oncol Biol Phys. 65(2)
Pages: 388-397
Description
「研究成果報告書概要(欧文)」より
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