奥沙利铂对口腔鳞状细胞癌的时辰治疗

目的 比较奥沙利铂（L-OHP）在昼夜4个不同时间治疗口腔鳞状细胞癌的疗效和不良反应的差异，并分析其昼夜生物节律特征。方法 将75只裸鼠置于12 h光照/12 h黑暗交替的环境中，将人颊鳞状细胞癌BcaCD885细胞注入裸鼠颊部建立口腔颊鳞状细胞癌模型，3周成瘤后随机分为5组（4个实验组，1个对照组）每组15只。4个实验组分别在24 h内的4个不同时间点，即灯亮后4、10、16、22 h（4 HALO、10 HALO、16 HALO、22 HALO）分别静脉注射L-OHP（17 mg·kg-1），对照组静脉注射相同体积的生理盐水。给药后观察比较各组的疗效（抑瘤率和生存时间）、不良反应（体重、白细胞计数和肛周肿胀）情况，并用余弦分析法检验疗效和不良反应是否具有昼夜节律性。结果 在4、16和22 HALO时间注射L-OHP均获得较好的抑瘤率，但只有在16和22 HALO两个时间给药显著延长了荷瘤鼠的生存时间；在16和22 HALO时间给药，荷瘤鼠的不良反应显著小于4和10 HALO给药；余弦分析表明不同给药时间对小鼠的生存时间、体重和白细胞计数的改变具有明显的昼夜节律变化特征，其中14.88 HALO注射L-OHP荷瘤鼠的生存时间最长。结论 用L-OHP对口腔鳞状细胞癌患者化疗应考虑时间因素，以增效减毒、提高患者生存率和生存质量。

Chronchemotherapy of Oxaliplatin to oral squamous cell carcinoma

Objective  To compare the differences of the efficacy and adverse reaction of Oxaliplatin (L-OHP) treatment to oral squamous cell carcinoma (OSCC) at four different daily time points, and to analyze the characteristics of circadian rhythms. Methods Seventy-five nude mice were placed under 12 h light and 12 h dark cycles. Human OSCC cell line BcaCD885 was inoculated on the cheek of nude mice to establish a nude mice model of OSCC. After 3 weeks, mice were divided into 5 groups (4 experimental groups and 1 control group) , with 15 in each group. L-OHP (17 mg·kg-1) was injected intravenously at 4 different time points during a period of 24 h, including 4 hours after lights on (HALO), 10 HALO, 16 HALO and 22 HALO for 4 experimental groups. The control group received normal saline of the same volume as that of L-OHP. The efficacy (tumor inhibition rate and survival time) and adverse reaction (body weight, white blood cell and perianal swelling) were observed after administration. The circadian rhythms of the efficacy and adverse reaction were examined by cosine analysis. Results  L-OHP injected at 4, 16 and 22 HALO had great tumor inhibition rates, however, only 16 and 22 HALO groups significantly prolonged survival time of mice. The adverse reactions at 4 and 10 HALO were significantly severer than that of 16 and 22 HALO. Cosine analysis showed survival time, body weight and white blood cell counts had significant circadian rhythms. Mice received L-OHP at 14.88 HALO had the longest survival time. Conclusion  The time factor should be considered in L-OHP chronchemotherapy of patients with OSCC in order to increase the efficacy, decrease the adverse reaction of the drug and to improve the life quality of patients with OSCC.