Ali Naiim S, Akudugu John M, Howell Roger W
Division of Radiation Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
Department of Radiology, University of Vermont Medical Center, Burlington, VT 05401, USA.
World J Nucl Med. 2019 Jan-Mar;18(1):18-24. doi: 10.4103/wjnm.WJNM_9_18.
Triple-negative breast cancer often has devastating outcomes and treatment options remain limited. Therefore, different treatment combinations are worthy of testing. The efficacy of a cocktail of paclitaxel, doxorubicin, and I-anti-epithelial cell adhesion molecule (EpCAM) (9C4) to treat breast cancer was tested. Efficacy was tested with an MDA-MB-231 human breast cancer xenograft model. Anti-EpCAM (9C4) was demonstrated to bind to MDA-MB-231 human adenocarcinoma cells . Subsequently, mice-bearing MDA-MB-231× enografts were treated with either I-anti-EpCAM (9C4), unlabeled anti-EpCAM (9C4), paclitaxel, doxorubicin, or a cocktail of all of the agents. Tumor volume was measured for up to 70-day postinjection. Exponential regression was performed on tumor growth curves for each of the therapy groups. Statistical comparison of the growth constants λ of the regression models for each of the treatment groups with that of the cold antibody and control groups was done using extra sum-of-square F-tests. Biexponential clearance of I-anti-EpCAM (9C4) was observed with biological clearance half-times of 1.14 and 17.6 days for the first and second components, respectively. The mean growth rate of the tumors in animals treated with a cocktail of all of the agents was slower than in those treated with unlabeled anti-EpCAM (9C4) ( = 0.022). These preliminary data suggest that a cocktail of I-anti-EpCAM (9C4), paclitaxel, and doxorubicin may be suitable for treating breast cancers with high expression of EpCAM.
三阴性乳腺癌往往会导致毁灭性的后果,且治疗选择仍然有限。因此,不同的治疗组合值得一试。我们测试了紫杉醇、阿霉素和I-抗上皮细胞粘附分子(EpCAM)(9C4)联合用药治疗乳腺癌的疗效。通过MDA-MB-231人乳腺癌异种移植模型来测试疗效。已证实抗EpCAM(9C4)能与MDA-MB-231人腺癌细胞结合。随后,用I-抗EpCAM(9C4)、未标记的抗EpCAM(9C4)、紫杉醇、阿霉素或所有这些药物的联合用药治疗携带MDA-MB-231移植瘤的小鼠。在注射后长达70天内测量肿瘤体积。对每个治疗组的肿瘤生长曲线进行指数回归分析。使用额外平方和F检验对每个治疗组回归模型的生长常数λ与冷抗体组和对照组的生长常数λ进行统计学比较。观察到I-抗EpCAM(9C4)的双指数清除,第一和第二成分的生物清除半衰期分别为1.14天和17.6天。用所有药物联合治疗的动物肿瘤平均生长速度比用未标记的抗EpCAM(9C4)治疗的动物慢(P = 0.022)。这些初步数据表明,I-抗EpCAM(9C4)、紫杉醇和阿霉素联合用药可能适用于治疗高表达EpCAM的乳腺癌。