Superior Therapeutic Efficacy of Nanoparticle Albumin Bound Paclitaxel Over Cremophor-Bound Paclitaxel in Experimental Esophageal Adenocarcinoma.
Superior Therapeutic Efficacy of Nanoparticle Albumin Bound Paclitaxel Over Cremophor-Bound Paclitaxel in Experimental Esophageal Adenocarcinoma.
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DOI：
10.1016/j.tranon.2018.01.022
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发表时间：
2018-04
影响因子：
5
通讯作者：
von Holzen U
中科院分区：
文献类型：
--
作者：
Hassan MS;Awasthi N;Li J;Williams F;Schwarz MA;Schwarz RE;von Holzen U
食管腺癌（EAC）是西方世界增长最快的癌症，EAC的总体5年生存率低于20%。大多数EAC患者存在局部晚期或广泛转移性疾病，目前的治疗基本无效。因此，迫切需要新的治疗方法。白蛋白结合型紫杉醇（nab-paclitaxel）是一种新的白蛋白稳定的、不含Cremophor的水溶性紫杉醇纳米颗粒制剂，并且nab-paclitaxel的潜在作用尚未在实验EAC中测试。在这里，我们测试了白蛋白结合型紫杉醇作为单一疗法和组合疗法在体外以及在人EAC的小鼠皮下异种移植物和腹膜转移性存活模型中的抗增殖和抗肿瘤功效以及存活优势。蛋白结合型紫杉醇显著抑制体外细胞增殖，与紫杉醇或卡铂治疗相比，在单药和联合治疗中具有更高的体内抗肿瘤功效和生存益处。白蛋白结合型紫杉醇治疗增加了有丝分裂纺锤体相关磷酸化stathmin的表达，降低了增殖标记物的表达，并增强了凋亡。本研究表明，白蛋白结合型紫杉醇在实验性EAC中具有比当前标准化疗剂更强的抗增殖和抗肿瘤活性，这支持其在EAC中临床使用的基本原理。
Esophageal adenocarcinoma (EAC) is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20%. Most patients with EAC present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel albumin-stabilized, cremophor-free and water soluble nanoparticle formulation of paclitaxel, and the potential role of nab-paclitaxel has not been tested yet in experimental EAC. Here we tested the antiproliferative and antitumor efficacy with survival advantage of nab-paclitaxel as monotherapy and in combinations in in-vitro, and in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. Nab-paclitaxel significantly inhibited in-vitro cell proliferation with higher in-vivo antitumour efficacy and survival benefit compared to paclitaxel or carboplatin treatments both in mono- and combination therapies. Nab-paclitaxel treatment increased expression of mitotic-spindle associated phospho-stathmin, decreased expression of proliferative markers and enhanced apoptosis. This study demonstrates that nab-paclitaxel had stronger antiproliferative and antitumor activity in experimental EAC than the current standard chemotherapeutic agents which supports the rationale for its clinical use in EAC.
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影响因子：
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作者：
Kresty LA;Weh KM;Zeyzus-Johns B;Perez LN;Howell AB
通讯作者：
Howell AB
影响因子：
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作者：
Awasthi, Niranjan;Scire, Emily;Schwarz, Roderich E.
通讯作者：
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通讯作者：
Ferri, Lorenzo E.
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4.6
作者：
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通讯作者：
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