Smith Nataliya, Saunders Debra, Jensen Randy L, Towner Rheal A
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; and.
2Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah.
J Neurosurg. 2019 Oct 18;133(6):1695-1703. doi: 10.3171/2019.7.JNS182435. Print 2020 Dec 1.
High-grade gliomas, such as glioblastoma (GBM), are devastating tumors with a very poor prognosis. Previously the authors have found that the nitrone compound OKN-007 (OKlahoma Nitrone 007; or disodium 4-[(tert-butyl-imino) methyl] benzene-1,3-disulfonate N-oxide) is effective against high-grade gliomas in various GBM rodent and human xenograft models. The purpose of the present study was to assess the levels of the lipopolysaccharide-binding protein (LBP) in rodent gliomas treated with OKN-007 as well as determine the expression of LBP in human gliomas.
Microarray analysis was done to assess altered gene expression following OKN-007 administration in an F98 glioma model. An enzyme-linked immunosorbent assay was incorporated to assess LBP levels in glioma tissues, as well as blood serum, comparing results in OKN-007-treated and untreated tumor-bearing animals. Immunohistochemistry was used to assess LBP levels in varying grades of human glioma tissue sections.
Upon further assessment of gene expression fold changes in F98 gliomas in rats that received or did not receive OKN-007, it was found that the gene for LBP was significantly downregulated by OKN-007. Further investigation was done to see whether levels of LBP were affected by OKN-007 treatment in F98 gliomas. It was found that LBP could be detected not only in glioma tissue but also in blood serum of F98 glioma-bearing rats and that OKN-007 decreased the levels of LBP. It was also found that LBP levels are highly expressed in human high-grade glioma tissues.
LBP could potentially be used as a serum diagnostic marker of treatment response in high-grade gliomas.
高级别胶质瘤，如胶质母细胞瘤（GBM），是预后极差的毁灭性肿瘤。此前作者发现硝酮化合物OKN-007（俄克拉荷马硝酮007；或4-[(叔丁基亚氨基)甲基]苯-1,3-二磺酸钠N-氧化物）在各种GBM啮齿动物和人异种移植模型中对高级别胶质瘤有效。本研究的目的是评估用OKN-007治疗的啮齿动物胶质瘤中脂多糖结合蛋白（LBP）的水平，并确定LBP在人胶质瘤中的表达。
在F98胶质瘤模型中进行微阵列分析，以评估给予OKN-007后基因表达的变化。采用酶联免疫吸附测定法评估胶质瘤组织以及血清中的LBP水平，比较OKN-007治疗组和未治疗的荷瘤动物的结果。免疫组织化学用于评估不同级别人类胶质瘤组织切片中的LBP水平。
在进一步评估接受或未接受OKN-007的大鼠F98胶质瘤中基因表达倍数变化时，发现OKN-007可显著下调LBP基因。进一步研究F98胶质瘤中OKN-007治疗是否会影响LBP水平。结果发现，不仅在F98荷瘤大鼠的胶质瘤组织中，而且在血清中均可检测到LBP，且OKN-007可降低LBP水平。还发现LBP水平在人类高级别胶质瘤组织中高表达。
LBP有可能用作高级别胶质瘤治疗反应的血清诊断标志物。
