Cox C, Teknos T N, Barrios M, Brewer G J, Dick R D, Merajver S D
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
Laryngoscope. 2001 Apr;111(4 Pt 1):696-701. doi: 10.1097/00005537-200104000-00024.
To determine whether tetrathiomolybdate (TM), a powerful chelator of copper, is capable of lowering the body stores of copper and suppressing the growth of head and neck squamous cell carcinoma in an orthotopic murine model.
In vivo, murine model.
Twelve 8-week-old male C3H/HeJ mice were assigned to either a TM treatment group (n = 7) or a control group (n = 5). Serum samples were obtained from a single mouse in each group to measure the level of ceruloplasmin as a surrogate marker of total body copper on days 0, 4, and 7. Mice in both groups received a floor-of-mouth injection of 1.5 x 105 SCC VII/SF cells. After 7 to 10 days of tumor growth the treatment group received fresh water daily, to which TM was added to achieve an oral intake of 50 mg per mouse. The control group received only fresh drinking water daily. Tumor volume measurements were obtained every other day. Microvessel density counts were assessed in the tumors by Factor VIII analysis.
Measurable tumor growth was achieved in 100% of the mice by the tenth day. Total body copper was reduced by 28% from baseline levels in mice in the treatment group. The difference in mean tumor volume in the control group was 4.7 times greater than the TM-treated group at the completion of treatment (3004 mm3 and 633mm3, respectively). This accounted for an overall suppression rate of 79% (P =.008; two-tailed Student t test). In addition, microvessel density was reduced by 50% in the TM-treated group.
In this initial study, the first of its kind in head and neck squamous cell carcinoma, we have demonstrated the ability of TM to significantly suppress both the growth of squamous cell carcinoma and tumor vascularity in this orthotopic murine model, suggesting its potential for efficacy in the treatment of this disease in humans.
确定强力铜螯合剂四硫代钼酸盐（TM）是否能够降低小鼠体内的铜储备，并在原位小鼠模型中抑制头颈部鳞状细胞癌的生长。
体内小鼠模型。
将12只8周龄雄性C3H/HeJ小鼠分为TM治疗组（n = 7）或对照组（n = 5）。在第0、4和7天从每组中的一只小鼠采集血清样本，以测量铜蓝蛋白水平作为全身铜的替代标志物。两组小鼠均接受口腔底部注射1.5×105个SCC VII/SF细胞。肿瘤生长7至10天后，治疗组小鼠每天饮用添加了TM的新鲜水，使每只小鼠的口服摄入量达到50毫克。对照组小鼠每天仅饮用新鲜饮用水。每隔一天测量肿瘤体积。通过因子VIII分析评估肿瘤中的微血管密度计数。
到第10天时，100%的小鼠实现了可测量的肿瘤生长。治疗组小鼠的全身铜含量较基线水平降低了28%。治疗结束时，对照组的平均肿瘤体积差异比TM治疗组大4.7倍（分别为3004立方毫米和633立方毫米）。这导致总体抑制率为79%（P = 0.008；双侧Student t检验）。此外，TM治疗组的微血管密度降低了50%。
在这项头颈部鳞状细胞癌的首例初步研究中，我们证明了TM在该原位小鼠模型中显著抑制鳞状细胞癌生长和肿瘤血管生成的能力，表明其在人类治疗该疾病方面具有潜在疗效。
