Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York.
Biology PhD Program, The Graduate Center, The City University of New York, New York, New York.
Cancer Med. 2019 Aug;8(9):4304-4314. doi: 10.1002/cam4.2322. Epub 2019 Jun 13.
There are few effective treatments for patients with advanced clear cell renal cell carcinoma (CCRCC). Recent findings indicate that ruthenium-gold containing compounds exhibit significant antitumor efficacy against CCRCC in vitro affecting cell viability as well as angiogenesis and markers driving those 2 phenomena. However, no in vivo preclinical evaluation of this class of compounds has been reported.
Following the dose-finding pharmacokinetic determination, NOD.CB17-Prkdc SCID/J mice bearing xenograft CCRCC Caki-1 tumors were treated in an intervention trial for 21 days at 10 mg/kg/72h of RANCE-1. At the end of the trial, tumor samples were analyzed for histopathological and changes in protein expression levels were assessed.
After 21 days of treatment there was no significant change in tumor size in the RANCE-1-treated mice as compared to the starting size (+3.87%) (P = 0.082) while the vehicle treated mice exhibited a significant tumor size increase (+138%) (P < 0.01). There were no signs of pathological complications as a result of treatment. Significant reduction in the expression of VEGF, PDGF, FGF, EGFR, and HGRF, all key to the proliferation of tumor cells and stromal cells serving protumorigenic purposes was observed.
The tumor growth inhibition displayed and favorable pathology profile of RANCE-1 makes it a promising candidate for further evaluation toward clinical use for the treatment of advanced CCRCC.
晚期透明细胞肾细胞癌（CCRCC）患者的有效治疗方法甚少。最近的研究结果表明，含钌金的化合物在体外对 CCRCC 具有显著的抗肿瘤疗效，影响细胞活力以及血管生成和驱动这两种现象的标志物。然而，尚未报道此类化合物的体内临床前评估。
在剂量发现药代动力学测定后，荷异体 CCRCC Caki-1 肿瘤的 NOD.CB17-Prkdc SCID/J 小鼠在干预试验中以 10mg/kg/72h 的 RANCE-1 进行治疗，共 21 天。试验结束时，分析肿瘤样本的组织病理学变化，并评估蛋白表达水平的变化。
与起始大小相比（+3.87%）（P=0.082），经过 21 天的治疗后，RANT-1 治疗组的肿瘤大小没有明显变化，而载体治疗组的肿瘤大小则显著增加（+138%）（P<0.01）。治疗没有导致任何病理并发症的迹象。观察到 VEGF、PDGF、FGF、EGFR 和 HGRF 的表达显著减少，所有这些都是肿瘤细胞增殖和支持肿瘤发生的基质细胞的关键，具有促进肿瘤生长的作用。
RANT-1 显示的肿瘤生长抑制作用和有利的病理学特征使其成为进一步评估用于治疗晚期 CCRCC 的有前途的候选药物。
