索拉非尼联合脂质体阿霉素治疗甲状腺低分化癌裸鼠移植瘤的疗效观察

LOP/C (≥20%) was significantly correlated with extrathyroid invasion (r=0.302, p=0.014), advanced tumour stage (r=0.256, p=0.017), LNM (r=0.325, p<0.001) and recurrence after surgery (r=0.313, p=0.045). Both extrathyroid invasion and LOP/C were independent significant predictors of LNM. Conclusions LOP/C may be a useful morphological feature of epithelial mesenchymal transition under H&E observation, and it is an important indicator of lymph node metastasis and aggressive clinical behaviour of PTC【Key Words 】papillary thyroid carcinoma lymph node metastasis epithelial mesenchymal transition Loss of cellular polarity/cohesiveness索拉非尼联合脂质体阿霉素治疗甲状腺低分化癌索拉非尼联合脂质体阿霉素治疗甲状腺低分化癌裸鼠移植瘤的疗效观察安常明1 王铮2 韩志楷2 唐平章1 马洁2中国医学科学院 肿瘤医院 肿瘤研究所 北京 1000211头颈外科 2 分子肿瘤学国家重点实验室【摘要摘要摘要】目的目的目的 评估索拉非尼、脂质体阿霉素及两者联合应用治疗甲状腺低分化癌裸鼠移植瘤的疗效。

方法方法方法 用脂质体阿霉素和索拉非尼治疗甲状腺低分化癌裸鼠皮下移植瘤模型，观察肿瘤生长情况，评估两种药物的疗效。

结果结果结果 利用索拉非尼和脂质体阿霉素对甲状腺低分化癌模型进行化疗，效果明显，空白对照组、溶剂对照组、单药脂阿组、索拉非尼组、低量联合组、中量联合组、高量联合组化疗结束后的最终体积分别为1274.13±393.76mm 3、1060.00±469.05mm 3、726.76±488.22mm 3、451.54±97.75mm 3、518.37±164.44mm 3、310.51±210.53mm 3和228.44±129.21mm 3，瘤重分别为1.13±0.42g、0.91±0.39g、0.78±0.45g、0.55±0.17g、0.52±0.19g、0.34±0.21g 和0.19±0.09g，单药脂阿组、索拉非尼组、低量联合组、中量联合组、高量联合组的抑瘤率分别为30.8%、 40.8% 、42.3%、 62.9%和72.6%，高量联合组抑瘤率除与中量联合组无差异外(P =0.357)均高于其余各组，中量联合组优于单药脂阿组（P =0.001），而与索拉非尼组无差异（P =0.192）。

各治疗组平均瘤重均明显低于空白对照组（P <0.05）。

各治疗组均无实验鼠死亡，高量联合组实验鼠体重在治疗过程中较其余各治疗组有明显减轻（P <0.05）。

结论结论结论 脂质体阿霉素和索拉非尼无论单药还是联合应用对本例甲状腺低分化癌移植瘤模型均有明显的抑瘤作用，中量联合疗效明显且副作用小。

【关键词关键词关键词】甲状腺癌；移植瘤；裸鼠；化疗；分子靶向治疗Effects of sorafenib and liposome doxorubicin on human poorly differentiated thyroid carcinoma xenografts in nudemiceAn Changming1Wang Zheng2Han Zhikai2Tang Pingzhang1Ma Jie2Cancer Institute，Cancer Hospital Chinese Academy of Medical Sciences1 Department of head and neck surgery2 State Key Laboratory of Molecular Oncology【Abstract】Objective To evaluate the in vivo effects of sorafenib and liposome doxorubicin on the ectopic nude mice model of poorly differentiated thyroid carcinoma (PDTC).Methods Sorafenib and liposome doxorubicin were used to treat the ectopic model of PDTC in nude mice. The tumor growth were recorded and therapeutic effects were evaluated. Results Sorafenib and liposome doxorubicin exerted significant antitumor activity in the ectopic xenograft model of PDTC. The mice were randomized into seven groups: blank control (A), reagent control(B), single liposome doxorubicin group(C), single sorafenib group(D), combined group with low dosage of sorafenib(E), combined group with medium dosage of sorafenib(F), combined group with high dosage of sorafenib(G). The tumor volumes of seven groups at the end of treatment were 1274.13±393.76mm3, 1060.00±469.05mm3, 726.76±488.22mm3, 451.54±97.75mm3, 518.37±164.44mm3, 310.51±210.53mm3, and 228.44±129.21mm3, separately. The tumor weights of the seven groups were 1.13±0.42g, 0.91±0.39g, 0.78±0.45g, 0.55±0.17g,0.52±0.19g, 0.34±0.21g, and 0.19±0.09g, separately. The tumor inhibition rates of groupC to G were 30.8%, 40.8%, 42.3%, 62.9%, 72.6%, separately. Group G had a significant higher inhibition rate compared with other groups except group F. Group F had better effects than group C (P=0.001) but not groupD (P=0.192). The mean tumor weights of all treatment groups were lower than that of the blank control group. No mice died in the treatment groups and the mice body weights in group G had a significant decline compared with other treatment groups. Conclusions Sorafenib and liposome doxorubicin exhibit significant antitumor activity to the PDTC ectopic mice model in vivo no matter for single agent or in combination.The inhibition effect of single sorafenib is better than that of single liposome doxorubicin in this bined group with medium dosage of sorafenib had a better therapeutic and less side effects compared with other groups.【Key word】thyroid cancer; xenograft; athymic nude mice; chemotherapy; molecular targeted therapy甲状腺未分化癌是头颈部肿瘤中致死率很高的肿瘤之一，目前主要采用综合治疗的方法，能手术的患者尽快性手术治疗，不能手术的患者则行放疗和化疗的综合治疗，治疗后中位生存期仅为2.9-10月[1-3]，生存期较短的原因之一为远处转移率高，初诊时患者就有20%~43%的转移，加上治疗中或随诊中新出现的远处转移最终可使这一比例达70%左右[1, 4, 5]。

因此对于甲状腺未分化癌在进行局部治疗的同时，应采用有效的方法预防和治疗远处转移，化疗药物不仅在协同放疗、手术控制局部上发挥作用，作为全身治疗也在预防和控制转移方面给临床研究者以希望。

甲状腺未分化癌中常用的传统化疗药物有阿霉素、顺铂、博来霉素、5-Fu 等[1, 6-9]，新近又出现的且效果较好的有紫杉醇和泰素帝[10, 11]，目前分子靶向药物索拉非尼、吉非替尼等广泛应用于未分化癌的临床试验研究[12-15]，本研究即探讨脂质体包裹的阿霉素和索拉非尼对甲状腺低分化癌的疗效。