The combination effects of HER2-targeted antibody therapy and radiotherapy : the elucidation of the most suitable timing that focused its attention on cell cycles.

HER2靶向抗体疗法和放射疗法的联合作用：阐明将注意力集中在细胞周期的最合适时机。

• 批准号: 15591271
• 负责人: NAGATA Kenji
• 金额: $ 2.24万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591271/
• 关键词: 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; 中性子線; c-erb B-2; 腫瘍内薬剤濃度

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.

本研究的目的是评估抗 HER-2 抗体曲妥珠单抗对乳腺癌细胞系增殖、细胞周期分布和放射敏感性的影响。人乳腺癌细胞系 KPL-4 天然过度表达 HER-2，并对抗 HER-2 抗体（曲妥珠单抗）敏感。然后在分析前将细胞暴露于曲妥珠单抗 (0-200 μg/ml) 24、48 或 72 小时。使用带有 Cell Quest 和 ModFit LT 程序的 FACScan 细胞分选仪分析细胞核的 DNA-PI 荧光。分析 DNA 分布以确定细胞周期 G0/G1、S 和 G2/M 期的细胞群。使用钴60伽马射线照射器对细胞进行剂量为2、4或8Gy的伽马射线照射。使用和不使用曲妥珠单抗之间的细胞周期分布和照射效率没有可检测到的差异。 KPL-4细胞在1％DCC-FBS培养基中培养48小时。然后将细胞暴露于曲妥珠单抗 (0-200 μg/ml) 和含有 10% FBS 的培养基中 24、48 或 72 小时，然后进行分析。曲妥珠单抗诱导细胞周期 G0/G1 期细胞比例的浓度依赖性增加。这种 G0/G1 停滞与 S 期细胞的浓度依赖性减少有关。 200μg/ml曲妥珠单抗治疗对曲妥珠单抗治疗前在1％DCC-FBS培养基中培养48小时的KPL-4细胞的放射敏感性有累加效应。当KPL-4细胞在10％FBS培养基中培养时，有和没有曲妥珠单抗的照射效率没有可检测到的差异。 KPL-4细胞在含有1% DCC剥离的FBS的培养基中孵育后，曲妥珠单抗诱导细胞周期停滞在G0/G1期，并对放射敏感性具有累加效应。如果曲妥珠单抗能够影响细胞周期，那么曲妥珠单抗加放疗可能对治疗 HER2 过度表达的乳腺癌有效。

项目成果

Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages

• DOI: 10.3171/jns.2005.103.6.1000
• 发表时间: 2005-12-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Miyatake, SI;Kawabata, S;Ono, K
• 通讯作者: Ono, K

Evaluation of hypoxia-specific cytotoxic bioreductive agent-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy.

• DOI: 10.1007/bf02493275
• 发表时间: 2006-02-01
• 期刊: Radiation medicine
• 作者: Masunaga, Shin-Ichiro;Nagasawa, Hideko;Ono, Koji
• 通讯作者: Ono, Koji

Effects of mild temperature hyperthermia and p53 status on the size of hypoxic fractions in solid tumors, with reference to the effect in intratumor quiescent cell populations

温和热疗和p53状态对实体瘤缺氧部分大小的影响，参考对瘤内静止细胞群的影响

• 发表时间: 2004
• 期刊: Int J Radiat Oncol Biol Phys. 60・2
• 作者: Masunaga S;Nagata K et al.
• 通讯作者: Nagata K et al.

Masunaga S, Takahashi A, Ohnishi K, Ohnishi T, Suzuki M, Nagata K: "Effects of p53 status and wortmannin treatment on potentially lethal damage repair, with emphasis on the response of intratumor quiescent cells"Radiat.Med.. 21・3. 120-127 (2003)

Masunaga S、Takahashi A、Ohnishi K、Ohnishi T、Suzuki M、Nagata K：“p53 状态和渥曼青霉素治疗对潜在致命损伤修复的影响，重点是肿瘤内静止细胞的反应”Radiat.Med.. 21・3 .120-127 (2003)

Suzuki M, Sakurai Y, Kinashi Y, Masunaga S, Nagata K, Ono K: "Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors"Int.J.Radiat.Oncol.Biol.Phys.. 58・3.

Suzuki M、Sakurai Y、Kinashi Y、Masunaga S、Nagata K、Ono K：“用硼己酸钠 (BSH)/碘油乳剂 (BSH/碘油-BNCT) 治疗多种肝脏肿瘤的硼中子捕获疗法的剂量学研究”Int .J.Radiat.Oncol.Biol.Phys.. 58・3。