Kim Seungwon, Yazici Yasemin D, Barber Samantha E, Jasser Samar A, Mandal Mahitosh, Bekele B Nebiyou, Myers Jeffrey N
Department of Head and Neck Surgery, Unit 441, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
Head Neck. 2006 May;28(5):389-99. doi: 10.1002/hed.20369.
A preclinical evaluation of CPT-1 (Camptosar, irinotecan) and PTK787/ZK222584, a vascular endothelial growth factor receptor (VEGFR-2) tyrosine kinase inhibitor, as therapeutic agents against anaplastic thyroid carcinoma (ATC) was performed in vitro and in an orthotopic model of ATC in nude mice.
The cytotoxic and cytostatic effects of CPT-11 on ATC cell lines were evaluated. The antitumor effects of CPT-11 in combination with PTK787/ZK222584 on orthotopic ATC xenografts in nude mice were also studied.
CPT-11 demonstrated significant antiproliferative effects on ATC cell lines. In vivo, PTK787/ZK222584, CPT-11, and the two agents together produced 61%, 82%, and 89% decrease in tumor growth, respectively. The differences in tumor volume between CPT-11 and CPT-11 + PTK787/ZK222584 groups were not statistically significant. PTK787/ZK222584 inhibited the phosphorylation of VEGFR-2 on tumor endothelium and decrease the tumor microvessel density.
The camptothecin class of chemotherapeutic agents and antiangiogenic agents such as PTK787/ZK222584 warrant further study as novel therapeutic agents against ATC.
在体外以及裸鼠间变性甲状腺癌（ATC）原位模型中，对CPT-1（开普拓，伊立替康）和血管内皮生长因子受体（VEGFR-2）酪氨酸激酶抑制剂PTK787/ZK222584作为抗间变性甲状腺癌（ATC）治疗药物进行了临床前评估。
评估了CPT-11对ATC细胞系的细胞毒性和细胞生长抑制作用。还研究了CPT-11与PTK787/ZK222584联合对裸鼠原位ATC异种移植瘤的抗肿瘤作用。
CPT-11对ATC细胞系显示出显著的抗增殖作用。在体内，PTK787/ZK222584、CPT-11以及两者联合使用分别使肿瘤生长减少了61%、82%和89%。CPT-11组与CPT-11 + PTK787/ZK222584组之间的肿瘤体积差异无统计学意义。PTK787/ZK222584抑制肿瘤内皮细胞上VEGFR-2的磷酸化并降低肿瘤微血管密度。
喜树碱类化疗药物和抗血管生成药物如PTK787/ZK222584作为抗ATC的新型治疗药物值得进一步研究。
