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

小鼠原位前列腺肿瘤模型是一种理想的模拟前列腺解剖生物学环境的临床前动物模型。与皮下肿瘤模型相比，该模型唯一的缺点是难以按时间顺序监测肿瘤生长情况。我们将经直肠超声技术（TRUS）应用于小鼠原位前列腺肿瘤的监测。方法：采用A6 Fr. 20MHz导管放射扫描探头，未经麻醉等任何准备行TRUS。将5000个RM-9细胞（Dr.Thompson提供）接种到12周龄C57/B6雄性小鼠的前列腺背侧，引发原位肿瘤。第3 ~ 21天用TRUS监测肿瘤生长情况。此外，采用TRUS检测腹腔注射顺式二胺二氯铂（CDDP）后肿瘤生长抑制情况。结果：肿瘤细胞接种后7 d超声可检出肿瘤。TRUS图像清晰，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)显著相关；Y=101.653+ 1.174x （r =0.930, p <0.001）。同样，CDDP诱导的肿瘤生长抑制也被清楚地检测到，并且具有合理的准确性。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有效。

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.