Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma.
Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma.
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DOI：
10.1371/journal.pone.0060021
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bryan BA
中科院分区：
文献类型：
--
作者：
Stiles JM;Amaya C;Rains S;Diaz D;Pham R;Battiste J;Modiano JF;Kokta V;Boucheron LE;Mitchell DC;Bryan BA
β-肾上腺素能受体的治疗靶向最近在治疗婴儿血管瘤等良性血管肿瘤中显示出显着的疗效。据报道，婴儿血管瘤表达高水平的 β 肾上腺素能受体，我们检查了这些受体在更具侵袭性的血管肿瘤（如血管内皮瘤和血管肉瘤）上的表达，揭示了 β1、2 和 3 受体确实存在，因此侵袭性血管肿瘤可能同样表现出对 β 阻断的抑制作用的敏感性增加。使用一组血管内皮瘤和血管肉瘤细胞系，我们证明β肾上腺素能抑制以剂量依赖性方式阻断细胞增殖并诱导细胞凋亡。与正常内皮细胞相比，β 阻断对血管肿瘤细胞具有选择性，并且与标准化疗或细胞毒性药物联合使用时具有协同作用。我们证明，抑制β肾上腺素能信号传导会引起血管肿瘤整体基因表达模式的大规模变化，包括已建立的细胞周期和凋亡调节因子表达的改变。使用体内肿瘤模型，我们证明β阻断剂作为单一药物在减少血管肉瘤肿瘤的生长方面显示出显着的功效。总之，这些实验证明了β肾上腺素能抑制对恶性血管肿瘤的选择性细胞毒性和肿瘤抑制能力，并为人类血管肉瘤的有前景的治疗奠定了基础。
Therapeutic targeting of the beta-adrenergic receptors has recently shown remarkable efficacy in the treatment of benign vascular tumors such as infantile hemangiomas. As infantile hemangiomas are reported to express high levels of beta adrenergic receptors, we examined the expression of these receptors on more aggressive vascular tumors such as hemangioendotheliomas and angiosarcomas, revealing beta 1, 2, and 3 receptors were indeed present and therefore aggressive vascular tumors may similarly show increased susceptibility to the inhibitory effects of beta blockade. Using a panel of hemangioendothelioma and angiosarcoma cell lines, we demonstrate that beta adrenergic inhibition blocks cell proliferation and induces apoptosis in a dose dependent manner. Beta blockade is selective for vascular tumor cells over normal endothelial cells and synergistically effective when combined with standard chemotherapeutic or cytotoxic agents. We demonstrate that inhibition of beta adrenergic signaling induces large scale changes in the global gene expression patterns of vascular tumors, including alterations in the expression of established cell cycle and apoptotic regulators. Using in vivo tumor models we demonstrate that beta blockade shows remarkable efficacy as a single agent in reducing the growth of angiosarcoma tumors. In summary, these experiments demonstrate the selective cytotoxicity and tumor suppressive ability of beta adrenergic inhibition on malignant vascular tumors and have laid the groundwork for a promising treatment of angiosarcomas in humans.
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DOI：
10.1111/j.1349-7006.2002.tb01313.x
发表时间：
2002-07
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Hasegawa H;Saiki I
通讯作者：
Saiki I
影响因子：
3.7
作者：
Lichtenstein, N;Geiger, B;Kam, Z
通讯作者：
Kam, Z
影响因子：
2.5
作者：
Mosoia, Liviu;Mabrut, Jean-Yves;Baulieux, Jacques
通讯作者：
Baulieux, Jacques
影响因子：
7.3
作者：
Perez Pinero, C.;Bruzzone, A.;Luethy, I. A.
通讯作者：
Luethy, I. A.
影响因子：
--
作者：
De Giorgi, Vincenzo;Gandini, Sara;Geppetti, Pierangelo
通讯作者：
Geppetti, Pierangelo