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Establishment of evaluating system for the efficacy of the prostate cancer gene therapy using orthotopic mouse tumor model

原位小鼠肿瘤模型前列腺癌基因治疗疗效评价体系的建立

基本信息

批准号：
11671556
负责人：
NASU Yasutomo
金额：
$ 2.3万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671556/
关键词：
gene therapy prostate cancer ultrasonography 同所移植

项目摘要

The mouse orthotopic prostate tumor model has been recognized as an ideal preclinical animal model simulating the anatomical and biological milieu of the prostate. In comparison with the subcutaneous tumor model, the only disadvantage of this model is the difficulty of chronological tumor growth monitoring. We have applied the resent endoluminal ultrasound technology, transrectal ultrasonography (TRUS), to monitoring of mouse orthotopic prostate tumors.METHODS : A6 Fr. 20MHz catheter-based radial scan probe was used and TRUS was performed without any prior preparation including anesthesia. Orthotopic tumors were initiated by inoculation of 5000 RM-9 cells (provided by Dr.Thompson) into the dorsal prostate of 12-week-old C57/B6 male mice. The tumor growth was monitored by TRUS from Day 3 to Day 21. In addition, TRUS was performed to detect tumor growth suppression after intraperitoneal administration of cis-diamminedichloroplatinum (CDDP).RESULTS : Ultrasonically, tumors became detectable 7 days after tumor cell inoculation. TRUS images were clear and parallel to actual tumor growth. The estimated tumor volume (X) calculated by TRUS correlated significantly with the actual tumor weight (Y) measured at autopsy ; Y=101.653+1.174X (R=0.930, P<0.001). Similarly, tumor growth suppression induced by CDDP was clearly detected with reasonable accuracy.CONCLUSIONS : A high resolution TRUS allows simple and reliable monitoring of in situ tumor growth and growth suppression, making the mouse orthotopic prostate tumor model more efficient.

小鼠原位前列腺肿瘤模型被认为是模拟前列腺解剖和生物学环境的理想临床前动物模型。与皮下肿瘤模型相比，该模型的唯一缺点是难以按时间顺序监测肿瘤生长。我们应用了最新的腔内超声技术，经直肠超声检查（TRUS）来监测小鼠原位前列腺肿瘤。方法：A6 Fr。使用基于 20MHz 导管的径向扫描探头，无需任何事先准备（包括麻醉）即可进行 TRUS。通过将 5000 个 RM-9 细胞（由汤普森博士提供）接种到 12 周龄 C57/B6 雄性小鼠的背侧前列腺中来引发原位肿瘤。从第3天到第21天通过TRUS监测肿瘤生长。此外，进行TRUS以检测腹腔内施用顺式二氯二氨铂(CDDP)后肿瘤生长抑制。结果：在肿瘤细胞接种后7天，超声检查可以检测到肿瘤。 TRUS 图像清晰且与实际肿瘤生长平行。 TRUS计算出的估计肿瘤体积（X）与尸检时测量的实际肿瘤重量（Y）显着相关； Y=101.653+1.174X（R=0.930，P<0.001）。同样，CDDP 诱导的肿瘤生长抑制也以合理的准确度被清晰地检测到。结论：高分辨率 TRUS 可以简单可靠地监测原位肿瘤生长和生长抑制，使小鼠原位前列腺肿瘤模型更加有效。