Ohara Tatsuru, Kiguchi Kazushige, Tsukikawa Satoshi, Sato Sojiro, Kobayashi Yoichi, Ishizuka Bunpei, Kubota Sunao
Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-city, Kanagawa, Japan.
Hum Cell. 2005 Sep;18(3):171-80. doi: 10.1111/j.1749-0774.2005.tb00008.x.
TGP (thermo-reversible gelation polymer) is a high molecular compound that has so-gel transmitting temperature of 221C Since solid cancer tissue grows in this polymer three-dimensionally, and fibroblasts scarcely grow in it, TGP is suitable for chemosensitivity assays for solid tumors. In this study, a chemosensitivity test using TGP was applied to recurrent gynecologic cancer patients in order to evaluate its utility and efficacy. In some ovarian cancer cases, expression of anticancer drug resistance-related proteins was also analyzed.
Recurrent tumor tissues were surgically obtained with informed consent. After these tissues were minced and incubated for 4 days with CDDP, mitomycin C, 5-fluorouracil, paclitaxel, and CPT-11, the sensitivity against these drugs was estimated. Western blotting was performed in 8 recurrent ovarian cancer tissues in order to analyze the expression of Bcl-2, MRP2, BCRP, and GST-pi.
The total evaluability rate of this assay was 90.6% (29/32). Sensitive drugs could be determined in 5 of 7 ascites samples (71.4%) and in 2 of 3 intra-tumoral fluid samples (66.7%). The overall clinical response rate of chemotherapy determined by these results was 50.0%. There were significant correlations between the IC50 of CDDP and Bcl-2, BCRP, GST-pi, and between that of 5-FU and MRP 2.
Although this was a preliminary study, the chemosensitivity test using this new material appears to be useful for designing 'made-to order' salvage chemotherapy for pretreated recurrent gynecologic patients. In order to overcome multidrug resistance, the mechanisms of multidrug resistance should be further investigated.
热可逆凝胶化聚合物（TGP）是一种高分子化合物，其溶胶-凝胶转变温度为22℃。由于实体癌组织能在这种聚合物中三维生长，而成纤维细胞几乎不能在其中生长，因此TGP适用于实体瘤的化学敏感性测定。在本研究中，对复发性妇科癌症患者应用了使用TGP的化学敏感性试验，以评估其效用和疗效。在一些卵巢癌病例中，还分析了抗癌药物耐药相关蛋白的表达。
在获得知情同意后，手术获取复发性肿瘤组织。将这些组织切碎并与顺铂、丝裂霉素C、5-氟尿嘧啶、紫杉醇和伊立替康一起孵育4天，然后评估对这些药物的敏感性。对8例复发性卵巢癌组织进行蛋白质印迹分析，以分析Bcl-2、多药耐药相关蛋白2（MRP2）、乳腺癌耐药蛋白（BCRP）和谷胱甘肽S-转移酶π（GST-π）的表达。
该试验的总可评估率为90.6%（29/32）。在7份腹水样本中的5份（71.4%）和3份瘤内液样本中的2份（66.7%）中可确定敏感药物。根据这些结果确定的化疗总体临床缓解率为50.0%。顺铂的半数抑制浓度（IC50）与Bcl-2、BCRP、GST-π之间，以及5-氟尿嘧啶的IC50与MRP2之间存在显著相关性。
虽然这是一项初步研究，但使用这种新材料的化学敏感性试验似乎有助于为预处理的复发性妇科患者设计“定制”的挽救性化疗。为了克服多药耐药性，应进一步研究多药耐药的机制。
