Imaging Institute and Department of Bioengineering, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH 44195, USA.
Cardiovasc Intervent Radiol. 2012 Jun;35(3):645-52. doi: 10.1007/s00270-011-0140-z. Epub 2011 Mar 24.
Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR.
A total of 10(6) N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n=5) or IV (n=5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40× magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test.
Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P=0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P=0.18); IA BR and saline (44.49 vs. 33.83%; P=0.66); or IV BR and saline (1.52 vs. 193%; P=0.18).
Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.
苯甲酰胺核苷（BR）可诱导多种细胞系和动物的肿瘤细胞凋亡。本初步研究比较了经肝动脉 BR（IA）或静脉（IV）BR 治疗的大鼠肝癌中的细胞凋亡和肿瘤反应。
将 10（6）N1-S1 细胞置于 15 只 Sprague-Dawley 大鼠的左肝叶中。2 周后，IA（n=5）或 IV（n=5）输注 BR（20mg/kg）。由于技术因素，每组各有 1 只动物被排除在外，无法给予全剂量（1 只 IA 和 1 只 IV）。5 只大鼠接受生理盐水（3 只 IA 和 2 只 IV）。3 周后处死动物。通过 Wilcoxon 秩和检验分析 IA 和 IV 治疗后的肿瘤体积。在 40×放大倍数下，对 TUNEL（末端脱氧核苷酸转移酶 dUTP 缺口末端标记）染色的 10 个切片的肿瘤和正常肝组织凋亡百分比进行计数。通过 Wilcoxon 秩和检验比较 IV 和 IA 给药与生理盐水假处理大鼠之间的凋亡百分比。
IA 治疗后肿瘤较小，但差异无统计学意义（0.14IA 与 0.57IV；P=0.138）。凋亡百分比差异很大，IA 和 IV BR 之间无显著差异（44.49%与 1.52%；P=0.18）；IA BR 和生理盐水（44.49%与 33.83%；P=0.66）；或 IV BR 和生理盐水（1.52%与 193%；P=0.18）。
尽管肿瘤体积的差异没有达到统计学意义，但在这项小型初步研究中，IA BR 治疗后肿瘤体积有小于 IV BR 的趋势。这些治疗方法的比较需要更大的样本量和重复实验。
