Preclinical Development ABT-898 Induces Tumor Regression and Prolongs Survival in a Mouse Model of Epithelial Ovarian Cancer
Preclinical Development ABT-898 Induces Tumor Regression and Prolongs Survival in a Mouse Model of Epithelial Ovarian Cancer
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临床前开发 ABT-898 在上皮性卵巢癌小鼠模型中诱导肿瘤消退并延长生存期
DOI：
10.1016/j.toxlet.2015.10.008
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发表时间：
2011
影响因子：
3.5
通讯作者：
J. Petrik
中科院分区：
文献类型：
--
作者：
N. Campbell;J. Greenaway;J. Henkin;J. Petrik
上皮性卵巢癌(EOC)是妇科最致命的恶性肿瘤，由于其无症状，通常要到晚期才被诊断出来。确诊为EOC的妇女通常会在手术后进行化疗，但往往会复发。在这项研究中，我们评估了血栓反应蛋白-1模拟肽ABT-898在人卵巢癌小鼠模型中逆转已建立的晚期肿瘤的能力。诱导卵巢肿瘤，并在代表疾病晚期的时间点开始ABT-898治疗，以研究肿瘤的消退。与对照组相比，ABT-898可诱导肿瘤消退，降低动物发病率。对ABT-898治疗动物的肿瘤分析显示，异常肿瘤血管减少，促血管生成化合物VEGF的表达减少，肿瘤组织缺氧减少。与对照动物相比，在疾病晚期开始的ABT-898治疗也显著延长了无病生存期。这项研究的结果表明，ABT-898能够在该疾病的动物模型中逆转已建立的卵巢肿瘤。由于大多数女性是在卵巢癌晚期被检测到的，ABT-898可能会改善我们对卵巢癌的治疗。摩尔癌症疗法；10(10)；1876-85。2011 AACR。
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and is often not diagnosed until late stages due to its asymptomatic nature.Women diagnosedwith EOC typically undergo surgical debulking followed by chemotherapy; however, disease recurrence often occurs. In this study,we evaluated the ability of the thrombospondin-1 mimetic peptide, ABT-898, to regress established, late-stage tumors in a mouse model of human EOC. Ovarian tumors were induced and ABT-898 treatment was initiated at time points that were representative of late stages of the disease to study tumor regression. ABT-898 induced tumor regression and reduced the morbidity of treated animals compared with controls. Analysis of tumors from ABT-898–treated animals showed reduced abnormal tumor vasculature, decreased expression of the proangiogenic compound VEGF, and reduced tumor tissue hypoxia. ABT-898 treatment initiated at late-stage disease also significantly prolonged disease-free survival compared with control animals. Results from this study show that ABT-898 is capable of regressing established ovarian tumors in an animal model of the disease. As most women are detected at advanced stage EOC, ABT-898 may improve our treatment of ovarian cancer. Mol Cancer Ther; 10(10); 1876–85. 2011 AACR.
影响因子：
3.6
作者：
Dawson, DW;Volpert, OV;Bouck, NP
通讯作者：
Bouck, NP
影响因子：
11.2
作者：
T. Browder;C. Butterfield;B. Kräling;B. Shi;B. Marshall;M. O’Reilly;J. Folkman
通讯作者：
T. Browder;C. Butterfield;B. Kräling;B. Shi;B. Marshall;M. O’Reilly;J. Folkman