Pilot study of vitaxin—an angiogenesis inhibitor—in patients with advanced leiomyosarcomas
Pilot study of vitaxin—an angiogenesis inhibitor—in patients with advanced leiomyosarcomas
复制标题
维生素A（一种血管生成抑制剂）在晚期平滑肌肉瘤患者中的初步研究
作者：
Shreyaskumar R Patel;Jan Jenkins R.N.;N. Papadopolous;M. Burgess;C. Plager;J. Gutterman;R. Benjamin
平滑肌肉瘤是一种罕见的异质性肿瘤，称为软组织肉瘤，是常见的组织学亚群之一。平滑肌肉瘤的生物学行为因其起源部位而异。起源于胃肠道(GI)的肿瘤属于一类更广泛的肿瘤，称为GI间质瘤，对阿霉素和异环磷酰胺等标准化疗药物无效。那些起源于胃肠道外的肿瘤，特别是来自子宫的肿瘤，反过来确实对这些标准的化疗药物敏感。不幸的是，标准药物最初治疗失败后挽救化疗的选择非常有限，因此需要积极研究新的策略。血管生成对肿瘤的生长和发展至关重要。这是一个复杂的过程，由几种作为血管生成分子的蛋白酶和生长因子的表达启动。内皮细胞的迁移依赖于它们通过被称为整合素的各种细胞黏附受体与细胞外基质蛋白(如Vitronectin)的黏附。整合素avb3在血管生成过程中的作用已经确定。因此，通过抑制anb3整合素来阻断新的血管生成可以产生抗肿瘤活性。我们在一组晚期平滑肌肉瘤患者身上测试了Vitaxin，一种针对内皮细胞和B3整合素的人源化单抗，目的是测试可行性和安全性，并更好地评估在加州圣地亚哥Sidney Kimmel癌症中心进行的Vitaxin I期研究中观察到的一名平滑肌肉瘤肝转移患者的抗肿瘤活性。门诊部静脉注射维生素A，固定剂量为0.25 mg/kg。
Leiomyosarcomas comprise one of the common histologic subsets of a rare and heterogenous group of tumors called soft tissue sarcomas. Leiomyosarcomas have a variable biologic behavior depending on their site of origin. Tumors originating in the gastrointestinal (GI) tract belong to a broader class of tumors called GI stromal tumors and are refractory to standard chemotherapeutic agents such as doxorubicin and ifosfamide. Those originating outside the GI tract, especially the ones arising from the uterus, conversely are indeed sensitive to these standard chemotherapeutic agents. Unfortunately, the options for salvage chemotherapy after failure of initial therapy with standard agents are very limited, and therefore newer strategies need to be investigated aggressively. Angiogenesis is critical for the growth and development of tumor. It is a complicated process initiated by the expression of several proteases and growth factors acting as angiogenic molecules. The migration of endothelial cells is dependent on their adhesion to extracellular matrix proteins, such as vitronectin, through a variety of cell adhesion receptors known as integrins. The role of the integrin avb3 in the angiogenic process has been established. Blocking neoangiogenesis by inhibiting the anb3 integrin therefore can result in antitumor activity. We tested Vitaxin, a humanized monoclonal antibody targeted against the endothelial cell anb3 integrin in a group of patients with advanced leiomyosarcomas with an intent to test feasibility and safety and to better estimate the antitumor activity that was observed in one patient with liver metastases from a leiomyosarcoma in the Phase I study of Vitaxin performed at the Sidney Kimmel Cancer Center in San Diego, California. Vitaxin was administered intravenously as an outpatient at a fixed dose of 0.25 mg/kg over 9
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA