Sci Transl Med：药物组合阻止侵袭性脑癌细胞的移动

3月28日，Sci Transl Med在线发表佐治亚理工学院研究人员的研究论文，研究人员发现一种叫做丙咪嗪蓝或IB的药物可阻止脑癌或神经胶质瘤的扩散。 当与常用抗癌药阿霉素合用时，IB可延长有病大鼠的生命，提示这一组合可能会在人体内成功地阻止脑胶质瘤的浸润。 传统的化疗几乎没有可能治疗脑胶质瘤这种通过入侵周围健康脑组织而快速生长的侵袭性的脑肿瘤。

大多数的脑胶质瘤患者会在诊断后几年死于该疾病。 癌细胞会迁徙到远离原发肿瘤的位置，这使得脑胶质瘤难以用手术和化疗来治疗。 Jennifer Munson及其同事们设计了一种可将IB轻易地递送给组织但不会损伤组织或触发炎症的方法。 他们将药物装入脂质体中，脂质体是一种由脂质制备的可帮助将IB输送入癌细胞的圆形囊泡。 在给罹患显示有人脑癌关键性特征的一种侵袭型胶质瘤的大鼠以含有IB的脂质体之后，研究人员注意到，得到治疗的大鼠比对照组大鼠的肿瘤要更为密实。 接着，该团队将含有IB的脂质体与阿霉素结合，并对患病大鼠进行这一组合治疗。

所有这些大鼠都存活了180天。 相反，只有33%的仅接受阿霉素的大鼠活了如此长的时间。 Munson及其同事们还探索了IB获得成功后面的机制，并提出该分子是通过破坏细胞的肌动蛋白装置（细胞需要肌动蛋白纤维才能移动）而中止了胶质瘤细胞的迁徙。 这些结果提示，这一强有力的化合物已经做好了在更多动物模型中进行测试的准备，并最终会在临床试验中对它进行测试。（生物谷 bioon.com）

doi:10.1126/scitranslmed.3003016
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Anti-Invasive Adjuvant Therapy with Imipramine Blue Enhances Chemotherapeutic Efficacy Against Glioma

Jennifer M. Munson, Levi Fried, Sydney A. Rowson, Michael Y. Bonner, Lohitash Karumbaiah, Begoa Diaz, Sara A. Courtneidge, Ulla G. Knaus, Danie J. Brat, Jack L. Arbiser，Ravi V. Bellamkonda

The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can “contain” GBM and increase the efficacy of chemotherapy. We report a new anti-invasive small molecule, Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested against several models. IB inhibits NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase–mediated reactive oxygen species generation and alters expression of actin regulatory elements. In vivo, liposomal IB (nano-IB) halts invasion of glioma, leading to a more compact tumor in an aggressively invasive RT2 syngeneic astrocytoma rodent model. When nano-IB therapy was followed by liposomal doxorubicin (nano-DXR) chemotherapy, the combination therapy prolonged survival compared to nano-IB or nano-DXR alone. Our data demonstrate that nano-IB–mediated containment of diffuse glioma enhanced the efficacy of nano-DXR chemotherapy, demonstrating the promise of an anti-invasive compound as an adjuvant treatment for glioma.