3月28日,，Sci Transl Med在線發(fā)表佐治亞理工學院研究人員的研究論文,，研究人員發(fā)現(xiàn)一種叫做丙咪嗪藍或IB的藥物可阻止腦癌或神經(jīng)膠質(zhì)瘤的擴散。 當與常用抗癌藥阿霉素合用時,，IB可延長有病大鼠的生命,，提示這一組合可能會在人體內(nèi)成功地阻止腦膠質(zhì)瘤的浸潤。 傳統(tǒng)的化療幾乎沒有可能治療腦膠質(zhì)瘤這種通過入侵周圍健康腦組織而快速生長的侵襲性的腦腫瘤,。
大多數(shù)的腦膠質(zhì)瘤患者會在診斷后幾年死于該疾病,。 癌細胞會遷徙到遠離原發(fā)腫瘤的位置，這使得腦膠質(zhì)瘤難以用手術和化療來治療,。 Jennifer Munson及其同事們設計了一種可將IB輕易地遞送給組織但不會損傷組織或觸發(fā)炎癥的方法,。 他們將藥物裝入脂質(zhì)體中，脂質(zhì)體是一種由脂質(zhì)制備的可幫助將IB輸送入癌細胞的圓形囊泡,。 在給罹患顯示有人腦癌關鍵性特征的一種侵襲型膠質(zhì)瘤的大鼠以含有IB的脂質(zhì)體之后,，研究人員注意到，得到治療的大鼠比對照組大鼠的腫瘤要更為密實,。 接著,，該團隊將含有IB的脂質(zhì)體與阿霉素結合，并對患病大鼠進行這一組合治療,。
所有這些大鼠都存活了180天,。 相反，只有33%的僅接受阿霉素的大鼠活了如此長的時間,。 Munson及其同事們還探索了IB獲得成功后面的機制,，并提出該分子是通過破壞細胞的肌動蛋白裝置（細胞需要肌動蛋白纖維才能移動）而中止了膠質(zhì)瘤細胞的遷徙。 這些結果提示,，這一強有力的化合物已經(jīng)做好了在更多動物模型中進行測試的準備,，并最終會在臨床試驗中對它進行測試。（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.
