Braumann Chris, Stuhldreier Benedikt, Bobrich Eva, Menenakos Charalambos, Rogalla Stephan, Jacobi Christoph A
Department of General, Visceral, Vascular, and Thoracic Surgery, Humboldt University, Berlin, Germany.
J Surg Res. 2005 Nov;129(1):129-35. doi: 10.1016/j.jss.2005.03.012.
The antitumor agent taurolidine (TRD) affects tumor growth in animals. Thus far, no animal studies have been published concerning the systemic or local toxicity and the effectiveness of long-term intraperitoneal (i.p.) and intravenous (i.v.) administration on advanced tumor growths.
In a first experiment (A) the systemic toxicity of the liver and kidneys was examined only after i.v. treatment in 40 rats (BD IX). For local toxicity the superior vena cava (SVC) was histologically analyzed. In a second study (B) 20,000 colon adenocarcinoma cells (DHD/K12/TRb) were initially applied i.p. after laparotomy in 80 rats (BD IX). After 28 days a port catheter system was placed in the SVC and left for 1 week. The animals were randomized into eight groups (n = 10) and received a 7-day treatment (eight hourly, 1 ml): 1, 2, 3% TRD or Ringer's solution (control group) either i.p. or i.v. Total i.p. tumor weight was measured 4 weeks after the end of the therapy. Side effects on differential blood counts and animal weight changes were examined.
No organ lesions were detected in liver, kidneys, and SVC in experiment A. The i.v. administration of 2% TRD (P = 0.034) and 3% TRD (P = 0.05) as well the i.p. application of 2% TRD (P = 0.05) decreased the development of advanced i.p. tumor lesions. No changes of differential blood count nor relevant animal weight changes resulted. Three port catheter-related infections were examined.
TRD does not impair the liver tissue, kidneys, SVC, and leucopoiesis. The intravenous therapy of 2% TRD is safe and anti-tumorigenic in advanced local tumor growth in rats.
抗肿瘤药物牛磺罗定（TRD）可影响动物肿瘤生长。迄今为止，尚未发表有关长期腹腔内（i.p.）和静脉内（i.v.）给药对晚期肿瘤生长的全身或局部毒性及有效性的动物研究。
在第一个实验（A）中，仅在对40只大鼠（BD IX）进行静脉内治疗后检查肝脏和肾脏的全身毒性。对于局部毒性，对 superior vena cava（上腔静脉，SVC）进行组织学分析。在第二项研究（B）中，在80只大鼠（BD IX）剖腹术后最初经腹腔注射20,000个结肠腺癌细胞（DHD/K12/TRb）。28天后，在SVC中放置一个端口导管系统并留置1周。将动物随机分为八组（n = 10），并接受为期7天的治疗（每八小时1 ml）：1%、2%、3%的TRD或林格氏液（对照组），经腹腔内或静脉内给药。在治疗结束4周后测量腹腔内肿瘤总重量。检查对血细胞分类计数和动物体重变化的副作用。
在实验A中，未在肝脏、肾脏和SVC中检测到器官病变。静脉内给予2%的TRD（P = 0.034）和3%的TRD（P = 0.05）以及腹腔内给予2%的TRD（P = 0.05）均减少了晚期腹腔内肿瘤病变的发展。血细胞分类计数无变化，动物体重也无相关变化。检查了三例与端口导管相关的感染。
TRD不会损害肝组织、肾脏、SVC和白细胞生成。2%的TRD静脉内治疗对大鼠晚期局部肿瘤生长是安全且具有抗肿瘤作用的。
