Lee Hak Jong, Hwang Sung Il, Byun Jonghoe, Kong Hoon Young, Jung Hyun Sook, Kang Mira
Department of Radiology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Molecular Biology, Dankook University, Cheonan, Korea.
Ultrasonography. 2017 Oct;36(4):370-377. doi: 10.14366/usg.17015. Epub 2017 Feb 14.
The purpose of this study was to assess tumor angiogenesis using contrast-enhanced ultrasonography (CEUS) of human prostate cancer cells (PC3) that were implanted in mice before and after paclitaxel injection.
Twelve mice were injected with human PC3. The mice were grouped into two groups; one was the paclitaxel-treated group (n=6) and the other was the control group (n=6). Before administering paclitaxel into the peritoneal cavity, baseline CEUS was performed after the administration of 500 μL (1×108 microbubbles) of contrast agent. The area under the curve (AUC) up to 50 seconds after injection was derived from the time-intensity curves. After injection of paclitaxel or saline, CEUS studies were performed at the 1-week follow-up. Changes in tumor volume and the AUC in both two groups were evaluated. After CEUS, the microvessel density (MVD) was compared between the groups.
In the paclitaxel-treated group, the AUC from CEUS showed a significant decrease 1-week after paclitaxel administration (P=0.030), even though the tumor volume showed no significant changes (P=0.116). In the control group, there was no significant decrease of the AUC (P=0.173). Pathologically, there was a significant difference in MVD between both groups (P=0.002).
The AUC from the time intensity curve derived from CEUS showed an early change in response to the anti-cancer drug treatment that preceded the change in tumor size. The findings of CEUS could serve as an imaging biomarker for assessing tumor responses to anti-cancer drug treatment.
本研究旨在通过对注射紫杉醇前后植入小鼠体内的人前列腺癌细胞(PC3)进行超声造影(CEUS)来评估肿瘤血管生成。
给12只小鼠注射人PC3细胞。将小鼠分为两组;一组为紫杉醇治疗组(n = 6),另一组为对照组(n = 6)。在向腹腔注射紫杉醇之前,在注射500μL(1×108微泡)造影剂后进行基线CEUS。从时间-强度曲线得出注射后50秒内的曲线下面积(AUC)。注射紫杉醇或生理盐水后,在1周随访时进行CEUS研究。评估两组肿瘤体积和AUC的变化。CEUS检查后,比较两组之间的微血管密度(MVD)。
在紫杉醇治疗组中,紫杉醇给药1周后CEUS的AUC显著降低(P = 0.030),尽管肿瘤体积无显著变化(P = 0.116)。在对照组中,AUC无显著降低(P = 0.173)。病理上,两组之间的MVD有显著差异(P = 0.002)。
CEUS得出的时间强度曲线的AUC显示,在肿瘤大小变化之前,抗癌药物治疗后有早期变化。CEUS的结果可作为评估肿瘤对抗癌药物治疗反应的成像生物标志物。