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Predictability of chemosensitivity of histoculture drug response assays and status of p53 gene for organ preservation therapy using neoadjuvant chemotherapy in patients with head and neck carcinomas

头颈癌患者新辅助化疗器官保存治疗中组织培养药物反应测定的化疗敏感性和 p53 基因状态的预测

基本信息

批准号：
11671719
负责人：
HASEGAWA Yasuhisa
金额：
$ 1.98万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671719/
关键词：
Chemosensitivity test Head and Neck Cancer CDDP 5FU TS DPD GSTπ HDRA Cisplatin

项目摘要

The future direction of anticancer chemotherapy is toward personalized chemotherapy corresponding to the variability and individuality of cancers. For this, the prediction of chemosensitivity (1, 2) and development of combined chemotherapy (3) are issues that need to be examined, In the present study, therefore, we investigated the sensitivity of histoculture drug response assay (HDRA) and gene expression (RT-PCR) for anticancer agents administered in case of head and neck cancer. 1) Thirty-three patients with head and neck squamous cell carcinoma (HNSCC) received cisplatin(CDDP)/5-FU chemotherapy. The sensitivity of CDDP was assessed at a concentration of 20 μg/ml, and that of 5FU at a concentration of 120 μg/ml. The cut off value of the inhibition rate was 50%. The clinical response rate for the anticancer chemotherapy ill these 33 cases was 51%. All patients were evaluable for the sensitivity of CDDP.The true positive rate was 78%, true negative rate 80%, and total accuracy 79%. Ele … More ven cases were evaluable for the sensitivity of 5FU.The true positive rate was 50%, true negative rate 80%, and total accuracy 64%.The true negative rate was high for both drugs, and HDRA of CDDP and 5FU was useful for the prediction of ineffectual cases. 2) We investigated the correlation between tumor sensitivity to 5FU and mRNA levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), and also between CDDP sensitivity and glutathione S-transferase (GST)-pi mRNA levels, using RT-PCR.The tumor sensitivity to 5FU was significantly correlated with DPD mRNA levels, However, there was no correlation between TS level and 5-FU sensitivity, and CDDP sensitivity was unrelated to GST-pi. The results of this study suggest that the DPD mRNA level is a useful indicator in predicting the antitumor activity of 5-FU in HNSCC.3) With the aim of organ preservation and downstaging, we administered combined chemotherapy (FP)(5FU 600 mg/m2/day, day 1-6, CDDP 80 mg/m2/day, day 7) in 26 cases of oro- and hypopharyngeal cancer as a neoadjuvant chemotherapy. It produced a partial or complete response in 22 cases, for a response rate was 85%. The high response rate and significance in terms of organ preservation of this combined chemotherapy were thus demonstrated. Less

根据肿瘤的变异性和个体性，个性化化疗是未来抗癌化疗的发展方向。因此，化疗敏感性的预测（1，2）和联合化疗的发展（3）是需要研究的问题。因此，在本研究中，我们研究了组织培养药物反应试验（HSP70）和基因表达（RT-PCR）对头颈部癌给予抗癌药物的敏感性。1)33例头颈部鳞状细胞癌（HNSCC）患者接受顺铂（CDDP）/5-FU方案化疗。CDDP的敏感性为20 μ g/ml，5 FU的敏感性为120 μ g/ml。抑制率的临界值为50%。33例患者化疗有效率为51%。CDDP诊断乳腺癌的敏感性为78%，真阴性率为80%，总准确率为79%。ele ...更多信息 5-FU敏感性评价10例，真阳性率50%，真阴性率80%，总准确率64%，两药真阴性率均较高，顺铂和5-FU联合应用可预测无效病例。2)我们用RT-PCR方法研究了胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）mRNA水平与肿瘤对5-FU敏感性的关系，以及谷胱甘肽S-转移酶（GST）-π mRNA水平与肿瘤对顺铂敏感性的关系，发现肿瘤对5-FU敏感性与DPD mRNA水平显著相关，而TS水平与5-FU敏感性无相关性。CDDP敏感性与GST-π无关。本研究结果提示，DPD mRNA水平可作为预测5-FU对HNSCC抗肿瘤活性的一个有用指标。3）为了达到器官保护和降低肿瘤分期的目的，我们对26例口咽癌患者进行了联合化疗（5FU 600 mg/m2/day，第1-6天; CDDP 80 mg/m2/day，第7天）作为新辅助化疗。部分或完全缓解22例，有效率85%。结果表明，该联合化疗方案具有较高的有效率和器官保存的意义。少