EphB4 as a therapeutic target in mesothelioma.
EphB4 as a therapeutic target in mesothelioma.
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EPHB4作为间皮瘤的治疗靶标。
DOI：
10.1186/1471-2407-13-269
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发表时间：
2013-05-30
期刊：
影响因子：
3.8
通讯作者：
Krasnoperov V
中科院分区：
文献类型：
--
作者：
Liu R;Ferguson BD;Zhou Y;Naga K;Salgia R;Gill PS;Krasnoperov V
恶性胸膜间皮瘤 (MPM) 通常在接触石棉数十年后发生。目前最好的疗法仅对一半患者产生反应，并且这种疗法的中位生存期仍低于一年。新靶点和治疗方法的研究正在进行中，最近确定的靶点包括 VEGF、Notch 和 EphB4-Ephrin-B2。这些靶点均具有双重活性，促进肿瘤细胞生长和肿瘤血管生成。我们通过免疫组织化学研究了 39 例人间皮瘤组织中的 EphB4 表达。用人间皮瘤细胞建立的异种移植肿瘤用 EphB4 抑制剂（与人血清白蛋白融合的单体可溶性 EphB4，或 sEphB4-HSA）进行治疗。还研究了sEphB4-HSA和生物制剂的组合效应。 EphB4 在 72% 的间皮瘤组织中过度表达，其中 85% 的上皮样亚型和 38% 的肉瘤样亚型过度表达。 EphB4 抑制剂 sEphB4-HSA 作为单一药物具有高度活性，可抑制肿瘤生长，并伴随肿瘤细胞凋亡和抑制 PI3K 和 Src 信号传导。 sEphB4-HSA 和抗 VEGF 抗体（贝伐珠单抗）的组合优于每种药物单独使用，并导致肿瘤完全消退。 EphB4 是间皮瘤的潜在治疗靶点。有必要对 sEphB4-HSA 作为单一药物以及与 VEGF 抑制剂联合进行临床研究。
Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis. We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied. EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression. EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted.
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影响因子：
5.7
作者：
Spannuth WA;Mangala LS;Stone RL;Carroll AR;Nishimura M;Shahzad MM;Lee SJ;Moreno-Smith M;Nick AM;Liu R;Jennings NB;Lin YG;Merritt WM;Coleman RL;Vivas-Mejia PE;Zhou Y;Krasnoperov V;Lopez-Berestein G;Gill PS;Sood AK
通讯作者：
Sood AK
影响因子：
3.8
作者：
Lee YC;Perren JR;Douglas EL;Raynor MP;Bartley MA;Bardy PG;Stephenson SA
通讯作者：
Stephenson SA
影响因子：
2.8
作者：
Wu, QH;Suo, ZH;Nesland, JM
通讯作者：
Nesland, JM
受体酪氨酸激酶EPHB4在卵巢癌中过表达，提供生存信号并预测结果不佳。
影响因子：
8.8
作者：
Kumar, S. R.;Masood, R.;Spannuth, W. A.;Singh, J.;Scehnet, J.;Kleiber, G.;Jennings, N.;Deavers, M.;Krasnoperov, V.;Dubeau, L.;Weaver, F. A.;Sood, A. K.;Gill, P. S.
通讯作者：
Gill, P. S.
影响因子：
16
作者：
Gerety, SS;Wang, HU;Anderson, DJ
通讯作者：
Anderson, DJ