Targeted toxins for glioblastoma multiforme: pre-clinical studies and clinical implementation.
Targeted toxins for glioblastoma multiforme: pre-clinical studies and clinical implementation.
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DOI：
10.2174/187152011797378689
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发表时间：
2011-10
影响因子：
2.8
通讯作者：
Castro MG
中科院分区：
文献类型：
--
作者：
Candolfi M;Kroeger KM;Xiong W;Liu C;Puntel M;Yagiz K;Muhammad AG;Mineharu Y;Foulad D;Wibowo M;Assi H;Baker GJ;Lowenstein PR;Castro MG
多形性胶质母细胞瘤（GBM）是成人最常见的原发性脑肿瘤。GBM是非常积极的，由于其差的细胞分化和侵袭性，这使得完全手术切除几乎是不可能的。因此，GBM的侵入性以及其对当前治疗方式的内在抗性使其成为独特的治疗挑战。对人类GBM标本的广泛检查发现，这些肿瘤过度表达各种受体，这些受体在周围的非肿瘤性脑中几乎不存在。人GBM过表达细胞因子、生长因子、肝配蛋白、尿激酶型纤溶酶原激活物（uPA）和转铁蛋白的受体，其可以通过将其配体与高细胞毒性分子（如白喉毒素和假单胞菌外毒素A）连接而以高特异性靶向。本文综述了GBM靶向毒素的临床前开发和临床转化。鉴于临床经验，我们的结论是，虽然这些是非常有前途的治疗方式GBM患者，努力应集中在改善所使用的输送系统，以实现更好的分布的免疫毒素在肿瘤/切除腔。使用病毒载体递送靶向毒素也将极大地受益于改进的局部递送策略。
Glioblastoma multiforme (GBM) is most common primary brain tumor in adults. GBM is very aggressive due to its poor cellular differentiation and invasiveness, which makes complete surgical resection virtually impossible. Therefore, GBM’s invasive nature as well as its intrinsic resistance to current treatment modalities makes it a unique therapeutic challenge. Extensive examination of human GBM specimens has uncovered that these tumors overexpress a variety of receptors that are virtually absent in the surrounding non-neoplastic brain. Human GBMs overexpress receptors for cytokines, growth factors, ephrins, urokinase-type plasminogen activator (uPA), and transferrin, which can be targeted with high specificity by linking their ligands with highly cytotoxic molecules, such as Diptheria toxin and Pseudomonas exotoxin A. We review the preclinical development and clinical translation of targeted toxins for GBM. In view of the clinical experience, we conclude that although these are very promising therapeutic modalities for GBM patients, efforts should be focused on improving the delivery systems utilized in order to achieve better distribution of the immuno-toxins in the tumor/resection cavity. Delivery of targeted toxins using viral vectors would also benefit enormously from improved strategies for local delivery.
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影响因子：
3.6
作者：
Candolfi M;Kroeger KM;Muhammad AK;Yagiz K;Farrokhi C;Pechnick RN;Lowenstein PR;Castro MG
通讯作者：
Castro MG
影响因子：
5.7
作者：
Debinski, W;Gibo, DM
通讯作者：
Gibo, DM
影响因子：
4.8
作者：
DEBINSKI, W;OBIRI, NI;PURI, RK
通讯作者：
PURI, RK
影响因子：
2.9
作者：
CONNOR, JR;FINE, RE
通讯作者：
FINE, RE
DOI：
10.1073/pnas.82.13.4553
发表时间：
1985-01-01
影响因子：
11.1
作者：
HILL, JM;RUFF, MR;PERT, CB
通讯作者：
PERT, CB