Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer.
Synergistic efficacy of irinotecan and sunitinib combination in preclinical models of anaplastic thyroid cancer.
复制标题
DOI：
10.1016/j.canlet.2017.09.032
复制
发表时间：
2017-12-28
期刊：
影响因子：
9.7
通讯作者：
Bocci G
中科院分区：
文献类型：
--
作者：
Di Desidero T;Antonelli A;Orlandi P;Ferrari SM;Fioravanti A;Alì G;Fontanini G;Basolo F;Francia G;Bocci G
由于间变性甲状腺癌（ATC）患者生存期短、预后差，迫切需要寻找新的治疗策略。本研究旨在探讨伊立替康/舒尼替尼联合用药对体外ATC细胞生长的影响及体内抗肿瘤作用。将伊立替康活性代谢物SN-38和舒尼替尼联合作用于ATC细胞株72 h，进行增殖试验。舒尼替尼与SN-38同时联用，通过联合指数量化，确定了对ATC细胞的高协同作用，增加了细胞内SN-38浓度。此外，协同联合可显著降低ATC细胞中血管内皮生长因子、集落刺激因子1和atp结合盒转运体G2的基因表达和蛋白水平。与单药治疗相比，伊立替康和舒尼替尼同时联合使用在ATC异种移植物中观察到显著的体内抗肿瘤效果。伊立替康和舒尼替尼同时联合使用，在体外和体内均显示出显著的协同抗ATC活性，这表明该方案可能快速应用于临床。
The identification of new therapeutic strategies is urgently needed for the management of patients affected by anaplastic thyroid cancer (ATC) due to their short survival and poor prognosis. Aim of the study was to determine the activity of the combination irinotecan/sunitinib on ATC cell growth in vitro and the antitumor effects in vivo. Proliferation assays were performed for 72 h on ATC cell lines exposed to the combination of SN-38, the active metabolite of irinotecan, and sunitinib. The simultaneous combination of sunitinib and SN-38, quantified by the combination index, determined a high synergism on ATC cells, increasing the intracellular concentrations of SN-38. Moreover, the synergistic combination greatly decreases the gene expression and the protein levels of vascular endothelial growth factor, colony stimulating factor 1 and ATP-binding cassette transporter G2 in ATC cells. A significant in vivo antitumor effect was observed in ATC xenografts with the simultaneous combination of irinotecan and sunitinib if compared to monotherapy. The simultaneous combination of irinotecan and sunitinib, in vitro and in vivo demonstrated a significant, synergistic ATC antitumor activity, suggesting a possible and rapid translation of this schedule into the clinics.
登录
查看更多内容
影响因子：
4.8
作者：
Canu, Bastianina;Fioravanti, Anna;Bocci, Guido
通讯作者：
Bocci, Guido
影响因子：
5.8
作者：
Bocci, Guido;Fioravanti, Anna;Danesi, Romano
通讯作者：
Danesi, Romano
影响因子：
5.8
作者：
Di Desidero, Teresa;Fioravanti, Anna;Bocci, Guido
通讯作者：
Bocci, Guido
DOI：
10.1158/1078-0432.ccr-10-0994
发表时间：
2010-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Carr LL;Mankoff DA;Goulart BH;Eaton KD;Capell PT;Kell EM;Bauman JE;Martins RG
通讯作者：
Martins RG
影响因子：
5.8
作者：
Bible, Keith C.;Suman, Vera J.;Erlichman, Charles
通讯作者：
Erlichman, Charles