Measurement of the hypoxic cell fraction in human tumors using a comet assay

使用彗星测定测量人类肿瘤中的缺氧细胞分数

• 批准号: 11470191
• 负责人: SASAKI Keisuke
• 金额: $ 4.8万
• 依托单位: JUNTENDO UNIVERSITY (2000-2001)Kyoto University (1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470191/
• 关键词: comet-assay; hypoxic cell fraction; tumor hypoxia; pancreatic cancer; osteosarcoma; IORT; PO_2; 子宮頸癌; 腔内照射; 子宮頚癌

Purpose : The prediction of tumor radiosensitivity is very important in radiation therapy for malignant diseases. We have developed our own method and image analysis system for a comet assay to identify hypoxic fractions. We tested our system using a cultured tumor cell line, and compared the hypoxic cell fractions in murine tumors detected by this assay with those determined by a radiobiological assay. In this study, we further confirmed whether the comet assay is clinically useful for estimating hypoxic fractions of solid tumors. Material and Methods : Under permission of the Internal Review Board, 17 patients (5 with uterine cervical cancers, 6 with pancreatic cancers and 6 with osteosarcomas) were enrolled in this study. Patients with uterine cervical cancers were treated with external beam irradiation and intracavital irradiation, and other patients were treated with intraoperative irradiation. Just after the intracavital or intraoperative irradiation, we obtained a small sample from the tumors and analysed the hypoxic cell fraction using the comet-assay. Results : From 9 of 16 tumors, we could obtain sufficient cells to perform the comet-assay. Although it was possible to determine the hypoxic cell fraction clearly in the in vitro and in vivo experiments, it was very difficult to detect hypoxic cell fraction in the clinical material. Therefore, we only identified radioresistant cell fractions in this study. These fractions comprised between 4.2 and 21%. We will compare these results with clinical outcomes in the future. ;

目的：肿瘤放射敏感性的预测在恶性肿瘤的放射治疗中具有重要意义。我们已经开发了自己的方法和图像分析系统的彗星试验，以确定缺氧馏分。我们使用培养的肿瘤细胞系测试了我们的系统，并将通过该测定检测的小鼠肿瘤中的缺氧细胞分数与通过放射生物学测定测定的那些进行了比较。在这项研究中，我们进一步证实了彗星试验是否是临床上有用的估计缺氧分数的实体瘤。材料和方法：在内部审查委员会的许可下，17例患者（5例宫颈癌，6例胰腺癌和6例骨肉瘤）入组本研究。宫颈癌患者采用体外照射和腔内照射，其余患者采用术中照射。就在腔内或术中照射后，我们从肿瘤中获得了一小部分样品，并使用彗星试验分析了缺氧细胞部分。结果：从16个肿瘤中的9个中，我们可以获得足够的细胞进行彗星试验。虽然在体外和体内实验中可以清楚地确定缺氧细胞分数，但在临床材料中检测缺氧细胞分数是非常困难的。因此，我们在本研究中仅鉴定了抗辐射细胞组分。这些分数在4.2和21%之间。我们将在未来将这些结果与临床结果进行比较。;

项目成果

Tachiiri S, Sasai K, Oya N, Hiraoka M.: "Enhanced cell killing by overexpression of dominant-negative phosphatidylinositol 3-kinase subunit, Deltap85, following genotoxic stresses"Jpn J Cancer Res. 91(12). 1314-1318 (2000)

Tachiiri S、Sasai K、Oya N、Hiraoka M.：“在基因毒性应激后，通过显性负性磷脂酰肌醇 3 激酶亚基 Deltap85 的过度表达增强细胞杀伤作用”Jpn J Cancer Res。

Sasai K et al: "Head and neck stages I and II extranodal non-Hodgkin's hymphoma RFAL classification and selection for treatment modulity"Int.J.Radiat.Oncol.Biol.Phys. 48(1). 153-160 (2000)

Sasai K 等人：“头颈 I 期和 II 期结外非霍奇金淋巴瘤 RFAL 分类和治疗模式选择”Int.J.Radiat.Oncol.Biol.Phys。

Sasai K, Yamabe H, Dodo Y, Kashii S, Nagata Y, Hiraoka M: "Non-Hodgkin's lymphoma of the ocular adnexa"Acta Onclogica. 40(4). 485-490 (2001)

Sasai K、Yamabe H、Dodo Y、Kashii S、Nagata Y、Hiraoka M：“眼附件非霍奇金淋巴瘤”Acta Onclogica。

Kokubo M,Nishimura Y,Shibamoto Y.Sasai K et al: "Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer."Oncol Rep. 7(4). 773-776 (2000)

Kokubo M，Nishimura Y，Shibamoto Y.Sasai K 等：“同步放化疗联合术中放疗治疗局部晚期胰腺癌。”Oncol Rep. 7(4)。

Kokubo M,Nishimura Y,Shibamoto Y.Sasai K et al: "Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer"Int.J Radiat.Oncol.Biol.Phys. 48(4). 1081-1087 (2000)

Kokubo M、Nishimura Y、Shibamoto Y.Sasai K 等人：“接受宏观治愈性切除胰腺癌的患者术中放疗的临床益处分析”Int.J Radiat.Oncol.Biol.Phys。