Therapeutic Challenges to a Rat Brain Tumor Model
Therapeutic Challenges to a Rat Brain Tumor Model
复制标题
大鼠脑肿瘤模型的治疗挑战
DOI：
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发表时间：
1976
期刊：
影响因子：
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通讯作者：
K. Nomura
中科院分区：
文献类型：
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作者：
T. Hoshino;E. Tel;M. Barker;M. Rosenblum;K. Nomura
将4×104个培养的9 L肿瘤细胞立体定向植入大鼠大脑半球，制备脑肿瘤模型。荷瘤大鼠在两周后表现出体重减轻，几天后出现神经系统症状，并在植入后19-20天死亡。肿瘤摄取率为100%，致死肿瘤重量为279 mg。肿瘤的倍增时间为39.5小时。植入后14-16天通过PLM曲线分析测定的细胞动力学参数为：TC-19.3小时; TG 1 -8.6小时; TS-7.6小时; TG 2 -2.9小时;和TM-0.2小时。生长分数为0.55，细胞损失因子为0.24。根据生存率、肿瘤大小和集落形成效率分析了综合疗法对该模型的有效性。在植入后第16天给予BCNU产生122%的ILS，而在第10天处理产生仅60%的ILS，这分别对应于3-3.5 log细胞杀灭和2-2.5 log细胞杀灭。在植入后第13天和第16天显微手术切除肿瘤产生28%（1 log细胞杀灭）和56%（2 log细胞杀灭）的ILS。在BCNU治疗前或治疗后3天以上进行手术，在第16天的疗效低于BCNU单药治疗。BCNU在给药前1小时或1小时和12小时给药，ILS均超过200%（< 7 log杀灭率）。在第16天进行手术后。BCNU在手术过程中给药无效。扰动和未扰动的肿瘤细胞群的细胞动力学参数可用于设计甚至更有效的联合模式治疗。
A rat brain tumor model was prepared by stereotactically implanting 4×104 cultured 9L tumor cells in the cerebral hemisphere. The tumor bearing rats exhibited weight loss after two weeks, developed neurological symptoms several days later and died 19-20 days post-implant. Tumor take was 100% and the lethal tumor weighed 279 mg. The tumors had a doubling time of 39.5 hours. Cell kinetic parameters determined by PLM curve analysis 14-16 days post-implant were: TC-19.3 hrs.; TG1-8.6 hrs.; TS-7.6 hrs.; TG2-2.9 hrs.; and TM-0.2 hrs. The growth fraction was 0.55 and the cell loss factor was 0.24. The effectiveness of combined modality therapy on this model was analyzed in terms of survival, tumor size and colony forming efficiency. BCNU administered on day 16 post-implant produced an ILS of 122% while treatment on day 10 produced an ILS of only 60%, which corresponded to a 3-3.5 log cell kill and 2-2.5 log cell kill, respectively. Microsurgical removal of tumors on days 13 and 16 post-implant produced an ILS of 28% (1 log cell kill) and 56% (2 log cell kill). Surgery performed more than 3 days before or after BCNU therapy was less effective than BCNU alone on day 16. An ILS of over 200% (< 7 log kill) was achieved when BCNU was given 1 hr. before or 1 hr. and 12 hrs. after surgery performed on day 16. BCNU was not effective when administered during the surgical procedure. Cell kinetic parameters of both perturbed and unperturbed tumor cell populations can be used to design even more effective combined modality therapy.