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同步放化疗对胶质母细胞瘤侵袭潜能的影响

Effect of Concomitant Radiochemotherapy on Invasion Potential of Glioblastoma.

作者信息

Hutóczki Gábor, Bognár László, Tóth Judit, Scholtz Beáta, Zahuczky Gábor, Hanzély Zoltán, Csősz Éva, Reményi-Puskár Judit, Kalló Gergő, Hortobágyi Tibor, Klekner Almos

机构信息

Department of Neurosurgery, University of Debrecen, Clinical Center, Nagyerdei krt. 98, Debrecen, 4032, Hungary.

Department of Oncology, University of Debrecen, Clinical Center, Nagyerdei krt. 98, Debrecen, 4032, Hungary.

出版信息

Pathol Oncol Res. 2016 Jan;22(1):155-60. doi: 10.1007/s12253-015-9989-5. Epub 2015 Oct 9.

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults with inevitable recurrence after oncotherapy. The insufficient effect of "gold standard" temozolomide-based concomitant radiochemotherapy may be due to the inability to prevent tumor cell invasion. Peritumoral infiltration depends mainly on the interaction between extracellular matrix (ECM) components and cell membrane receptors. Changes in invasive behaviour after oncotherapy can be evaluated at the molecular level by determining the RNA expression and protein levels of the invasion-related ECM components. The expression of nineteen ECM molecules was determined at both RNA and protein levels in thirty-one GBM samples. Fifteen GBM samples originated from the first surgical procedure on patients before oncotherapy, and sixteen GBM samples were collected at the second surgery due to local recurrence after concomitant chemoirradiation. RNA expressions were measured with qRT-PCR, and protein levels were determined by quantitative analysis of Western blots. Only MMP-9 RNA transcript level was reduced (p < 0.05) whereas at protein level, eight molecules showed changes concordant with RNA expression with significant decrease in brevican only. The results suggest that concomitant radiochemotherapy does not have sufficient impact on the expression of invasion-related ECM components of glioblastoma, oncotherapy does not significantly affect its invasive behavior. To avoid the spread of tumors into the brain parenchyma, supplementation of antiproliferative treatment with anti-invasive agents may be worth consideration in oncotherapy for glioblastoma.

摘要

胶质母细胞瘤(GBM)是成人中最常见的原发性脑肿瘤,放化疗后不可避免会复发。基于“金标准”替莫唑胺的同步放化疗效果不佳,可能是由于无法阻止肿瘤细胞侵袭。瘤周浸润主要取决于细胞外基质(ECM)成分与细胞膜受体之间的相互作用。放化疗后侵袭行为的变化可以通过测定侵袭相关ECM成分的RNA表达和蛋白质水平在分子水平上进行评估。在31个GBM样本中,测定了19种ECM分子在RNA和蛋白质水平的表达。15个GBM样本来自患者放化疗前的首次手术,16个GBM样本是在同步放化疗后因局部复发在第二次手术时采集的。用qRT-PCR测量RNA表达,通过蛋白质印迹定量分析确定蛋白质水平。只有MMP-9 RNA转录水平降低(p < 0.05),而在蛋白质水平上,8种分子的变化与RNA表达一致,仅短蛋白聚糖显著减少。结果表明,同步放化疗对胶质母细胞瘤侵袭相关ECM成分的表达影响不足,放化疗对其侵袭行为没有显著影响。为避免肿瘤扩散到脑实质,在胶质母细胞瘤的放化疗中,考虑用抗侵袭药物补充抗增殖治疗可能是值得的。

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