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

针对癌症的多变性和个体化，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（HDRA）和基因表达（RT-PCR）对头颈癌患者使用的抗癌药物的敏感性。1) 33例头颈部鳞状细胞癌（HNSCC）患者接受顺铂(CDDP)/5-FU化疗。CDDP和5FU分别在20 μg/ml和120 μg/ml浓度下检测其敏感性。抑制率的临界值为50%。33例肿瘤化疗患者的临床有效率为51%。所有患者均可评估CDDP的敏感性。真阳性率78%，真阴性80%，总准确率79%。更多的病例可评价5FU的敏感性。真阳性率50%，真阴性80%，总准确率64%。两种药物的真阴性率均较高，CDDP和5FU的HDRA可用于预测无效病例。2)采用RT-PCR方法研究肿瘤对5FU的敏感性与胸腺苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD） mRNA水平的相关性，以及CDDP敏感性与谷胱甘肽s -转移酶(GST)-pi mRNA水平的相关性。肿瘤对5FU的敏感性与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-pi无关。本研究结果提示，DPD mRNA水平是预测5-FU在hnscc中抗肿瘤活性的有用指标。3)为了器官保存和降低分期，我们对26例口腔癌和下咽癌患者给予联合化疗（FP）（5FU 600 mg/m2/天，第1-6天，CDDP 80 mg/m2/天，第7天）作为新辅助化疗。22例患者部分或完全缓解，有效率为85%。因此，这种联合化疗的高有效率和在器官保存方面的意义得到了证明。少

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