Application of a new drug screening method for clinical chemotherapy

一种新药筛选方法在临床化疗中的应用

• 批准号: 63870051
• 负责人: TANIGAWA Nobuhiko
• 金额: $ 3.78万
• 依托单位: Fukui Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63870051/
• 关键词: Drug screening assay; In vitro assay; Scintillation assay; Fresh human tumors; Successful rate of assay; Clinical correlations; In vitro制癌剤感受性試験; Human Tumor Clonogenic Assay; Seintillation Assay; 胃癌; 大腸癌; 感受性試験成功率

We have developed the in vitro drug screening assay, scintillation assay. With this assay we can assess the chemosensitivity of solid human tumors during the 5 days following tumor resection. We found that 41%(117/569) of the human tumors gave evaluable chemosensitivity results. In vitro sensitivity was associated with clinical responses in 14 of 33 cases (42%), while in vitro resistance was associated with clinical progressive diseases in 41 of 44 cases (93%). These clinical correlation data were similar to other reports with different types of drug screening assay. we consider that tumor cell heterogeneity is one of the main reasons for low true positive accuracy in the drug screening assays. Our studies with nude mice xenografts of fresh human tumors have demonstrated that fresh human tumors are composed of heterogeneous subpopulations of cells with varying chemosensitivities and varying DNA indexes. This heterogenetic nature of human tumor cells means that a single biopsy specimen may not comprehensively define the chemosensitivity of the remaining tumor cells.

我们开发了体外药物筛选试验，闪烁试验。通过这种方法，我们可以评估实体人肿瘤切除后5天内的化学敏感性。我们发现41%（117/569）的人类肿瘤具有可评估的化学敏感性结果。33例患者中有14例（42%）体外敏感性与临床反应相关，而44例患者中有41例（93%）体外耐药性与临床进展性疾病相关。这些临床相关数据与其他不同类型药物筛选试验的报道相似。我们认为肿瘤细胞的异质性是药物筛选试验中真阳性准确性低的主要原因之一。我们对新鲜人肿瘤裸鼠异种移植的研究表明，新鲜人肿瘤是由具有不同化学敏感性和不同DNA指数的异质细胞亚群组成的。人类肿瘤细胞的这种异质性意味着单个活检标本可能无法全面确定剩余肿瘤细胞的化学敏感性。

项目成果

Nobuhiko Tanigawa et al: "The Sigmificance of Postoperative Early Chemotherapy for Locoregional Lymph Node Metastases of Gastric and Colorectal Cancer" Oncology.

Nobuhiko Tanikawa 等人：“胃癌和结直肠癌局部淋巴结转移术后早期化疗的意义”肿瘤学。

Nobuhiko Tanigawa et al.: "Comparative study on chemosensitivity for gastric and colorectal cancer assessed with human tumor clonogenic assay(HTCA)and thymidine incorporation assay(TIA)" Cancer(Phil.). submitted.

Nobuhiko Tanikawa 等人：“用人肿瘤克隆形成试验（HTCA）和胸苷掺入试验（TIA）评估胃癌和结直肠癌化疗敏感性的比较研究”癌症（Phil.）。

Nobuhiko Tanigawa et al.: "Comparative study on chemosensitivity for gastric and colorectal cancer assessed with human tumor clonogenic assay (HTCA) and thymidine incorporation assay (TIA)" Cancer(Phil.).

Nobuhiko Tanikawa 等人：“用人肿瘤克隆形成试验 (HTCA) 和胸苷掺入试验 (TIA) 评估胃癌和结直肠癌化疗敏感性的比较研究”Cancer(Phil.)。

Nobuhiko Tanigawa, Hideki Morimoto: "The Significance of Postoperative Early Chemotherapy for Locoregional Lymph Node Metastases of Gastric and Colorectal Cancer." Oncology,.

Nobuhiko Tanikawa、Hideki Morimoto：“术后早期化疗对胃癌和结直肠癌局部淋巴结转移的意义”。

谷川允彦: 癌と化学療法. 16. (1989)

谷川正彦：癌症与化疗。16。（1989）