Ishikura H, Kondo K, Miyoshi T, Kinoshita H, Takahashi Y, Fujino H, Monden Y
Second Department of Surgery, School of Medicine, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan.
Clin Cancer Res. 2001 Dec;7(12):4202-8.
The extent of lymphatic metastasis is the most important factor in the prognosis for non-small cell lung cancer (NSCLC). Therefore, suppression of lymphatic metastasis provides an improvement in survival time in lung cancer patients. We established a new patient-like model for lung cancer metastasis by orthotopic implantation in severe combined immunodeficiency (SCID) mice and demonstrated the lymphogenous spread histologically using human NSCLC cell lines. The cardinal features of this model are a simple procedure and a similarity to the metastatic form of human lung cancer. The purpose of this study is to assess the inhibitory action of uracil-tegafur (UFT) and cis-diamminedichloroplatinum(II) (CDDP) on lymphatic metastasis and life span prolongation in our lymphogenous metastatic model system using SCID mice.
The inhibition ratios of mediastinal lymph node metastasis were 86.2, 94, and 92.1% for 12 mg/kg body UFT, 17 mg/kg body UFT, and 10 mg/kg body CDDP, respectively. The administration of anticancer drugs prolonged the life span by 4.6 days (17 mg/kg body UFT) and 8 days (10 mg/kg body CDDP) in MST.
We demonstrated that UFT alone and CDDP alone suppressed mediastinal metastasis and prolonged the life span in our lymphogenous metastatic model. Regardless of the administration route and characteristics of anticancer drugs, cytostatic or cytotoxic, our model is capable of evaluating the inhibitory effect of drugs on lymphatic metastasis. This model should make an important contribution to our understanding of the mechanism and selection of drugs for antilymphatic metastasis in lung cancer.
淋巴转移程度是非小细胞肺癌(NSCLC)预后的最重要因素。因此,抑制淋巴转移可延长肺癌患者的生存时间。我们通过在严重联合免疫缺陷(SCID)小鼠体内原位植入建立了一种新的类似患者的肺癌转移模型,并使用人NSCLC细胞系从组织学上证实了淋巴源性扩散。该模型的主要特点是操作简单且与人肺癌的转移形式相似。本研究的目的是评估尿嘧啶替加氟(UFT)和顺二氨二氯铂(II)(CDDP)对我们使用SCID小鼠的淋巴源性转移模型系统中淋巴转移的抑制作用以及对寿命延长的影响。
对于12mg/kg体重的UFT、17mg/kg体重的UFT和10mg/kg体重的CDDP,纵隔淋巴结转移的抑制率分别为86.2%、94%和92.1%。在中位生存时间(MST)方面,给予抗癌药物使寿命延长了4.6天(17mg/kg体重的UFT)和8天(10mg/kg体重的CDDP)。
我们证明了单独使用UFT和单独使用CDDP均可抑制纵隔转移并延长我们的淋巴源性转移模型中的寿命。无论抗癌药物的给药途径和特性如何,是细胞生长抑制剂还是细胞毒性药物,我们的模型都能够评估药物对淋巴转移的抑制作用。该模型应为我们理解肺癌抗淋巴转移的机制和药物选择做出重要贡献。