2005 Fiscal Year Final Research Report Summary
The combination effects of HER2-targeted antibody therapy and radiotherapy : the elucidation of the most suitable timing that focused its attention on cell cycles.
| Project/Area Number |
15591271
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kyoto University |
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Principal Investigator |
NAGATA Kenji Kyoto Univ., Res. Reactor Inst., Associate Professor, 原子炉実験所, 助手 (30247928)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Kouji Kyoto Univ., Res. Reactor Inst., Assistant Professor, 原子炉実験所, 教授 (90122407)
MASUNAGA Shin-ichiro Kyoto Univ., Res. Reactor Inst., Assistant Professor, 原子炉実験所, 助教授 (80238914)
SUZUKI Minoru Kyoto Univ., Res. Reactor Inst., Assistant Professor, 原子炉実験所, 助手 (00319724)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Brest cancer / Radiotherapy / Cell cycles / HER2-targeted antibody / c-erb B-2 / Chemotherapy / 硼素中性子捕捉療法 / イムノリポソーム |
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| Research Abstract |
The purpose of this study was to evaluate the effect of an anti-HER-2 antibody trastuzumab on the proliferation, cell cycle distribution, and radiosensitivity of breast cancer cell line.
The human breast cancer cell line, KPL-4, which naturally overexpresses HER-2 and is sensitive to anti-HER-2 antibody (trastuzumab). The cells were then exposed to trastuzumab (0-200 g/ml) for 24, 48, or 72 h before analysis. The nuclei were analyzed for DNA-PI fluorescence using a FACScan cell sorter with the Cell Quest and ModFit LT programs. The DNA distribution was analyzed to determine the population of cells in G0/G1, S, and G2/M phases of the cell cycle. The cells received gamma ray irradiation at a dose of 2, 4 or 8 Gy using a cobalt-60 gamma ray irradiator.
There were no detectable differences in the distribution of cell cycle and the efficiency of irradiation between with and without trastuzumab. KPL-4 cells were cultured for 48 h in 1% DCC-FBS medium. The cells were then exposed to trastuzumab (0-200 g/ml) with medium containing 10% FBS for 24, 48, or 72 h before analysis. Trastuzumab induced concentration-dependent increase in the fraction of cells in G0/G1 phase of the cell cycle. This G0/G1 arrest was associated with concentration-dependent decrease of cells in S phase. Treatment with 200 g/ml trastuzumab had additive effect on the radiosensitivity of KPL-4 cells were cultured for 48 h in 1% DCC-FBS medium before trastuzumab treatment.
There were no detectable differences in the efficiency of irradiation between with and without trastuzumab, when KPL-4 cells were cultured in 10% FBS medium. After KPL-4 cells incubated in medium with 1% DCC-stripped FBS, trastuzumab induced of cell cycle arrest in G0/G1 phase in the cells and had additive effect on the radiosensitivity. If trastuzumab be able to have an influence on cell cycle, trastuzumab plus irradiation may be effective for the treatment of breast cancer with HER2 overexpression.
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Author(s)
Masunaga S, Nagasawa H, Gotoh K, Sakurai Y, Uto Y, Hori H, Nagata K, Suzuki M, Maruhashi A, Kinashi Y, Ono K.
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Journal Title
Radiation Medicine 24(2)
Pages: 98-107
Description
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[Journal Article] The usefulness of mild temperature hyperthermia combined with a newly developed hypoxia-oriented ^<10>B conjugate compound, TX-2100, for boron neutron capture therapy.2006
Author(s)
Masunaga S, Nagasawa H, Sakurai Y, Uto Y, Hori H, Nagata K, Suzuki M, Maruhashi A, Kinashi Y, Ono K.
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Journal Title
International Journal of Hyperthermia 22(4)
Pages: 287-299
Description
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[Journal Article] Combination of the antivascular agent ZD6126 with hypoxic cytotoxin treatment, with reference to the effect on the quiescent tumor cells and the dependency on p53 status of tumor cells.2005
Author(s)
Masunaga S, Nagasawa H, Uto Y, Hori H, Ohnishi K, Takahashi A, Ohnishi T, Suzuki M, Nagata K, Kinashi Y, Ono K.
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Pages: 393-400
Description
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[Journal Article] Modified boron neutron capture therapy for malignant gliomas performedusing epithermal neutron and two boron compounds with different accumulation mechanisms : an efficacy study based on findings on neuroimages.2005
Author(s)
Miyatake S, Kawabata S, Kajimoto Y, Aoki A, Yokoyama K, Yamada M, Kuroiwa T, Tsuji M, Imahori Y, Kirihata M, Sakurai Y, Masunaga S, Nagata K, Maruhashi A, Ono_K.
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Description
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