Polin L, Valeriote F, White K, Panchapor C, Pugh S, Knight J, LoRusso P, Hussain M, Liversidge E, Peltier N, Golakoti T, Patterson G, Moore R, Corbett T H
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, USA.
Invest New Drugs. 1997;15(2):99-108. doi: 10.1023/a:1005856605726.
Both the PC-3 and the TSU-PR1 prostate tumor models were found to be satisfactory for chemotherapeutic investigations in ICR-SCID mice. The 30 to 60 mg fragments implanted took in all mice (as judged by 100% takes in the controls of all experiments as well as the passage mice). The tumor volume doubling time was 4.0 days for PC-3 and 2.5 days for TSU-PR1. Nine agents were evaluated IV against early stage subcutaneous PC-3 tumors, with Nano-piposulfan being the only agent highly active (4.9 log kill). Three other agents were moderately active: Taxol (1.5 log kill), Cryptophycin-8 (1.6 log kill), Vinblastine (1.0 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and Cyclophosphamide. Ten agents were evaluated IV against early stage subcutaneous TSU-PR1 tumors. Three agents were highly active, producing > 6 log kill and cures: Taxol (5/5 cures), Cryptophycin-8 (5/5 cures), Vinblastine (2/4 cures). Two other agents were moderately active: Nano-piposulfan (1.2 log kill), and Cyclophosphamide (1.1 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and BCNU. In part, activity was determined by the ability of the SCID mice to tolerate meaningful dosages of the agents. Agents producing granulocyte toxicity (e.g., Adriamycin) were poorly tolerated and appeared less active than expected. Vinblastine, producing little or no granulocyte toxicity was very well tolerated and appeared to be more active than expected.
PC-3和TSU-PR1前列腺肿瘤模型均被发现适用于在ICR-SCID小鼠中进行化疗研究。植入的30至60mg肿瘤片段在所有小鼠中均成功生长(根据所有实验的对照组以及传代小鼠100%的成功率判断)。PC-3肿瘤体积倍增时间为4.0天,TSU-PR1为2.5天。对9种药物进行静脉注射评估,用于治疗早期皮下PC-3肿瘤,其中纳米哌泊舒凡(Nano-piposulfan)是唯一具有高活性的药物(杀伤对数为4.9)。其他三种药物具有中等活性:紫杉醇(Taxol,杀伤对数为1.5)、隐藻素-8(Cryptophycin-8,杀伤对数为1.6)、长春碱(Vinblastine,杀伤对数为1.0)。五种药物无活性:依托泊苷(VP-16)、阿霉素(Adriamycin)、顺铂(CisDDPt)、5-氟尿嘧啶(5-FUra)和环磷酰胺(Cyclophosphamide)。对10种药物进行静脉注射评估,用于治疗早期皮下TSU-PR1肿瘤。三种药物具有高活性,产生大于6个对数杀伤并实现治愈:紫杉醇(5/5治愈)、隐藻素-8(5/5治愈)、长春碱(2/4治愈)。另外两种药物具有中等活性:纳米哌泊舒凡(杀伤对数为1.2)和环磷酰胺(杀伤对数为1.1)。五种药物无活性:依托泊苷、阿霉素、顺铂、5-氟尿嘧啶和卡莫司汀(BCNU)。部分活性取决于SCID小鼠耐受有效剂量药物的能力。产生粒细胞毒性的药物(如阿霉素)耐受性差,活性似乎低于预期。长春碱产生很少或不产生粒细胞毒性,耐受性非常好,活性似乎高于预期。