Research of increase radiosensitivity targeting DNA repair mechanism in treatment-resistant cells

提高耐药细胞放射敏感性靶向DNA修复机制的研究

• 批准号: 15591276
• 负责人: SASAKI Ryohei
• 金额: $ 2.24万
• 依托单位: Kobe 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 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591276/
• 关键词: Resistant tumor; Rad51; Radiosensitivity; Radioresistance; FDG-PET; Prostate Cancer; Combination therapy; Isofravinol; RNAi

Inhibition of Rad51, a DNA repair protein in homologus recombination after DNA damage, leads to an increase of radiosensitivity in prostate cancer cells in vitro. In this study, we used several antisense oligonucleotide to decrease Rad51 protein function, and evaluate Rad51 dysfunction with using comet assay, which is an analysis for DNA repair ability after DNA damage.In the next step, we first established several radioresistant clones from parental colon cancer cell lines (HCT116 p53+/+, p53 -/-). We are now applying Rad51 inhibition to those sets of parental and radioresistant clones.On the other hand, we investigated an novel combination therapy, which are consisted of natural product of isoflavinol and ionizing radiation. We found that treatment of an isoflavinol, genistein, increase radiosensitivity in radioresistant prostate cancer cells by promoting apoptosis (Asian J Androl. 2004;6(4):285-290.)To apply these findings, we investigated efficacy of FDG-PET in non-small cell lung cancer as an clinical model. We found and reported that tumor in which FDG were accumulated showed radioresistant characteristics, and metastatized frequently.(J Clin Oncol. 2005;23(6): 1136-1143).

Rad51（一种 DNA 损伤后同源重组中的 DNA 修复蛋白）的抑制可导致体外前列腺癌细胞的放射敏感性增加。在本研究中，我们使用几种反义寡核苷酸来降低 Rad51 蛋白功能，并使用彗星试验评估 Rad51 功能障碍，彗星试验是对 DNA 损伤后 DNA 修复能力的分析。下一步，我们首先从亲代结肠癌细胞系 (HCT116 p53+/+、p53 -/-) 中建立了几个抗辐射克隆。我们现在正在将 Rad51 抑制应用于这些亲本和抗辐射克隆组。另一方面，我们研究了一种新型联合疗法，该疗法由异黄醇天然产物和电离辐射组成。我们发现，异黄醇、金雀异黄素的治疗可通过促进细胞凋亡来增加放射抗性前列腺癌细胞的放射敏感性（Asian J Androl. 2004；6(4):285-290。）为了应用这些发现，我们研究了 FDG-PET 作为临床模型在非小细胞肺癌中的疗效。我们发现并报道了FDG积聚的肿瘤表现出抗放射特性，并且经常发生转移。(J Clin Oncol. 2005;23(6): 1136-1143)。

项目成果

MR angiography with sensitivity encoding (SENSE) for suspected pulmonary embolism: Comparison with MDCT and ventilation-perfusion scintigraphy

• DOI: 10.2214/ajr.183.1.1830091
• 发表时间: 2004-07-01
• 期刊: AMERICAN JOURNAL OF ROENTGENOLOGY
• 影响因子: 5
• 作者: Ohno, Y;Higashino, T;Sugimura, K
• 通讯作者: Sugimura, K

Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays

• DOI: 10.1016/j.radonc.2004.03.008
• 发表时间: 2004-05-01
• 期刊: RADIOTHERAPY AND ONCOLOGY
• 影响因子: 5.7
• 作者: Demizu, Y;Kagawa, K;Sugimura, K
• 通讯作者: Sugimura, K

Transthoracic CT-guided biopsy with multiplanar reconstruction image improves diagnostic accuracy of solitary pulmonary nodules

• DOI: 10.1016/s0720-048x(03)00216-x
• 发表时间: 2004-08-01
• 期刊: EUROPEAN JOURNAL OF RADIOLOGY
• 影响因子: 3.3
• 作者: Ohno, Y;Hatabu, H;Sugimura, K
• 通讯作者: Sugimura, K

粒子線治療:陽子線治療と炭素イオン線治療

粒子束治疗：质子束治疗和碳离子束治疗

• 发表时间: 2005
• 期刊: Mebio Oncology 2
• 作者: 山本憲;伏見育崇;三木幸雄;富樫かおり;村上 昌雄
• 通讯作者: 村上 昌雄

頭頚部腫瘍に対する炭素イオン線治療の電子クリニカルパス作成

创建碳离子治疗头颈肿瘤的电子临床路径

• 发表时间: 2005
• 期刊: 日本放射線腫瘍学会誌 17
• 作者: 山本憲;伏見育崇;三木幸雄;富樫かおり;村上 昌雄;戎谷 明日香
• 通讯作者: 戎谷 明日香