Sano Daisuke, Choi Sungweon, Milas Zvonimir Luka, Zhou Ge, Galer Chad E, Su Ying-Wen, Gule Maria, Zhao Mei, Zhu Zhenping, Myers Jeffrey N
Department of Head and Neck Surgery, Unit 441, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA.
Arch Otolaryngol Head Neck Surg. 2009 Apr;135(4):411-20. doi: 10.1001/archoto.2009.14.
To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the vascular endothelial growth factor receptor (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of the oral tongue (SCCOT).
In vivo study.
A translational research laboratory at a comprehensive cancer center.
Male athymic nude mice aged 8 to 12 weeks.
To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone, cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were administered twice per week for 4 weeks. The in vivo antitumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunofluorescent staining were performed.
Tumor size, bioluminescence, animal survival, and percentage of animals with lymph node metastasis.
At the conclusion of the treatment period, the mean tumor volumes in the cetuximab alone and the DC101 plus cetuximab groups had decreased significantly compared with those that received the placebo control (68% [P = .002] and 84% [P < .001], respectively). Significant effects of the treatment were also observed in bioluminescence imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower incidence of neck lymph node metastases compared with the control group (P = .003).
Treatment with DC101 plus cetuximab inhibited the growth of SCCOT and decreased the incidence of the neck lymph node metastases in vivo. These results suggest that this combination treatment may be an effective strategy against metastatic SCCOT and warrants further preclinical trials.
在原位舌鳞状细胞癌转移裸鼠模型（SCCOT）中，评估联合使用血管内皮生长因子受体单克隆抗体（DC101）和表皮生长因子受体单克隆抗体（西妥昔单抗）进行治疗的疗效。
体内研究。
一家综合癌症中心的转化研究实验室。
8至12周龄的雄性无胸腺裸鼠。
为构建SCCOT原位裸鼠模型，将OSC - 19细胞或表达荧光素酶（Luc）的OSC - 19 - Luc及JMAR - Luc细胞注射到裸鼠舌内。动物被随机分为4组：单独使用DC101组、单独使用西妥昔单抗组、DC101加西妥昔单抗组或安慰剂组，所有治疗每周给药两次，持续4周。通过生物发光成像对体内抗肿瘤活性进行无创监测。在尸检时切除肿瘤，并进行免疫组织化学和免疫荧光染色。
肿瘤大小、生物发光、动物存活率以及出现淋巴结转移的动物百分比。
在治疗期结束时，单独使用西妥昔单抗组和DC101加西妥昔单抗组的平均肿瘤体积与接受安慰剂对照的组相比显著减小（分别为68%[P = 0.002]和84%[P < 0.001]）。在生物发光成像中也观察到了治疗的显著效果。与对照组相比，接受DC101加西妥昔单抗治疗的小鼠存活时间更长，颈部淋巴结转移发生率更低（P = 0.003）。
DC101加西妥昔单抗治疗在体内抑制了SCCOT的生长并降低了颈部淋巴结转移的发生率。这些结果表明，这种联合治疗可能是对抗转移性SCCOT的有效策略，值得进一步进行临床前试验。
