Laboratory of Molecular Therapeutics Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, Japan.
World J Surg Oncol. 2013 Jan 22;11:11. doi: 10.1186/1477-7819-11-11.
The use of standard chemotherapy regimens has changed the application of chemosensitivity tests from all chemotherapy-eligible patients to those who have failed standard chemotherapy, which includes patients with highly advanced, relapsed, or chemoresistant tumors.
We evaluated a total of 43 advanced primary and relapsed gastric cancers for chemosensitivity based on drug dose response curves to improve the objectivity and quality of quantitative measurements. The dose response curves were classified based on seven expected patterns. Instead of a binary chemosensitivity evaluation, we ranked drug sensitivity according to curve shapes and comparison with the peak plasma concentration (ppc) of each drug.
A total of 193 dose response curves were obtained. The overall informative rate was 67.4%, and 85.3% for cases that had a sufficient number of cells. Paclitaxel (PXL)and docetaxel tended to show a higher rank, while cisplatin (CIS) and 5-fluorouracil (5-FU) tended to show resistance, particularly among the 20 cases (46.5%) that had recurrent disease after receiving chemotherapy with CIS and S-1 (5-FU). As such, we speculate that the resistant pattern of the chemosensitivity test suggests that cells with acquired drug resistance were selected by chemotherapy. Indeed, we observed a change in the chemosensitivity pattern of a sample before and after chemotherapy in terms of PXL sensitivity, which was used after primary chemotherapy.
These results suggest that: (i) the dose-response pattern provides objective information for predicting chemosensitivity; and (ii) chemotherapy may select resistant cancer cell populations as a result of the therapy.
标准化疗方案的应用改变了化疗敏感性测试的应用范围，从所有适合化疗的患者扩展到那些已经对标准化疗无效的患者，包括高度晚期、复发或化疗耐药的肿瘤患者。
我们根据药物剂量反应曲线评估了总共 43 例晚期原发性和复发性胃癌的化疗敏感性，以提高定量测量的客观性和质量。根据七种预期模式对剂量反应曲线进行分类。我们没有进行二元化疗敏感性评估，而是根据曲线形状和与每种药物的峰值血浆浓度（ppc）的比较对药物敏感性进行排名。
共获得 193 条剂量反应曲线。总体信息率为 67.4%，对于有足够细胞数的病例为 85.3%。紫杉醇（PXL）和多西他赛（DOC）往往显示出更高的等级，而顺铂（CIS）和 5-氟尿嘧啶（5-FU）往往显示出耐药性，尤其是在接受 CIS 和 S-1（5-FU）化疗后复发的 20 例（46.5%）病例中。因此，我们推测化疗敏感性试验的耐药模式表明，细胞已经通过化疗选择了获得性耐药。事实上，我们观察到一个样本在接受原发性化疗后使用 PXL 敏感性方面的化疗敏感性模式发生了变化。
这些结果表明：（i）剂量反应模式为预测化疗敏感性提供了客观信息；（ii）化疗可能会选择耐药的癌细胞群体作为治疗的结果。
