Development of the practical methods to predict radiosensitivity of tumors with immunohistchemistry

开发免疫组织化学预测肿瘤放射敏感性的实用方法

• 批准号: 12670892
• 负责人: SAKATA Koh-ichi
• 金额: $ 2.3万
• 依托单位: SAPPORO MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670892/
• 关键词: DNA-PK; radiosensitivity; immunohistochemistry; DNA double-strand breaks; Cancer

Purpose : DNA-dependent protein kinase (DNA-PK), a serine/theronine kinase composed of p470 catalytic subunit (DNA-PKcs) and p85/p70 heterodimer (Ku antigen), is considered a critical enzyme in the repair of the DNA double-strand breaks (DSB) which are the major lethal lesions induced by ionizing radiation. We investigated the expression of DNA-PK subunits in human tumors.Materials and Methods : We examined immunohistochemically the biopsy specimens of 46 patients with oropharyngeal carcinoma and 24 patients with hypopharyngeal carcinoma who had been treated with radiotherapy.Results : Immunopositivity to Ku70, Ku85, and DNA-PKcs was found in all patients. The staining of Ku70, Ku85, and DNA-PKcs was nuclear, with none of the normal epithelial cells or malignant cells exhibiting cytoplasmic or membrane immunoreactivity. Normal epithelial cells were all stained intensely. In tumors, intense nuclear staining of Ku70 or DNA-PKcs was seen in 69 of 70 tumors and that of Ku 85 was seen in all 70 patients. The radiation responses of the primary tumors which stained weakly with Ku70 or DNA-PKcs were excellent.Conclusion : Low expression of DNA-PK could be related to the decline of its catalytic activity and of capability to repair radiation-induced DSB. These results suggest that defects in DNA-PK activity might contribute to clinical radiosensitivity.

目的：DNA依赖性蛋白激酶（DNA-PK）是由p470催化亚基（DNA-PKcs）和p85/p70异源二聚体（Ku抗原）组成的丝氨酸/苏氨酸激酶，被认为是电离辐射引起的主要致死性损伤DNA双链断裂（DSB）修复的关键酶。材料与方法：采用免疫组化方法检测46例口咽癌和24例下咽癌放疗后活检组织中Ku 70、Ku 85和DNA-PKcs的表达。Ku 70、Ku 85和DNA-PKcs的染色均为细胞核染色，正常上皮细胞或恶性细胞均无胞浆或胞膜免疫反应性。正常上皮细胞均呈强染色。在肿瘤中，Ku 70或DNA-PKcs在70例肿瘤中的69例中观察到强烈的核染色，Ku 85在所有70例患者中观察到。Ku 70或DNA-PKcs弱染色的原发性肿瘤的放射反应良好。结论：DNA-PK的低表达可能与其催化活性和修复辐射诱导的DSB能力的下降有关。这些结果表明，DNA-PK活性的缺陷可能有助于临床放射敏感性。

项目成果

K.-I.Sakata,Y.Matsumoto,H.Tauchi,M.Satoh,A.Oouchi,H.Nagakura,K.Koito,Y.Hosoi,N.Suzuki,K.Komatsu,and M.Hareyama: "Expression of Genes Involved in Repair on DNA Double-strand Reuks in Normal and Tumor Tissues"International Journal of Radiation Oncology, Bio

K.-I.Sakata、Y.Matsumoto、H.Tauchi、M.Satoh、A.Oouchi、H.Nagakura、K.Koito、Y.Hosoi、N.Suzuki、K.Komatsu 和 M.Hareyama：“表达

H.Yamauchi: "Nuclear BAG-1 localization and the risk of recurrence after rediation therapy in layngeal carcinomos"Cancer Let. 165(1). 103-110 (2001)

H.Yamauchi：“核 BAG-1 定位和喉癌再放射治疗后的复发风险”Cancer Let。

H.Yamauchi: "Nuclear BAG-1 localization and the risk of recurrence after radiation therapy in laryngeal carcinomas"Cancer Let. 165(1). 103-110 (2001)

H.Yamauchi：“核 BAG-1 定位和喉癌放射治疗后复发的风险”Cancer Let。

K.Sakata: "Clinical studies of immunohistochemical staining of DNA-dependent protein kinase in oropharyngeal and hupopharyngeal cacinomas"Radiation medicine. 19(2). 93-97 (2001)

K.Sakata：“口咽癌和湖咽癌中 DNA 依赖性蛋白激酶的免疫组织化学染色的临床研究”放射医学。

K.Sakata: "Clinical studies of immunohistochemical staining of DNA-dependent protein kinase in oropharyngeal and hypopharyngeal cacinomas"Radiation medicine. 19(2). 93-97 (2001)

K.Sakata：“口咽癌和下咽癌中 DNA 依赖性蛋白激酶的免疫组织化学染色的临床研究”放射医学。