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脑胶质母细胞瘤患者的血管生成、炎症和凝血的循环标志物。

Circulating markers of angiogenesis, inflammation, and coagulation in patients with glioblastoma.

机构信息

Servicio de Oncología Médica, Hospital Universitario La Fe, Avda. Campanar 21, 46009 Valencia, Spain.

出版信息

J Neurooncol. 2011 Mar;102(1):35-41. doi: 10.1007/s11060-010-0290-x. Epub 2010 Jul 6.

Abstract

Inflammation, angiogenesis, and coagulation are linked to the development of cancer. In glioblastoma, microvascular proliferation is a hallmark, and lymphocytic infiltration is a common finding. Thromboses are frequent in patients with glioblastoma. The objective of this study was to assess presurgical levels of circulating markers of inflammation, angiogenesis, and coagulation in a prospective series of patients with glioblastoma, and to explore their correlations and possible associations with clinical findings. Angiogenesis markers included were vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor-receptor 1 (sVEGFR-1), and thrombospondin-1 (TSP-1). Inflammatory markers included were C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and sialic acid (SA). Coagulation markers included were fibrinogen (Fg), endogen thrombin generation (ETG), prothrombin fragments 1 + 2 (F1 + 2), and tissue factor (TF). Forty-seven patients and 60 healthy subjects were included in the study. Signs of tumor necrosis in presurgical MRI were associated with shorter survival (P < 0.01). All inflammation markers, F1 + 2, ETG, VEGF and sVEGFR-1, were significantly elevated in glioblastoma patients. Correlations were found between ETG and Fg (r = 0.44, P < 0.01). Sialic acid correlated with Fg (r = 0.63, P < 0,001); CPR correlated with SA (r = 0.60, P < 0.001), Fg (r = 0.76, P < 0.001), TNFα (r = 0.56, P < 0.001), and IL-6 (r = 0.65, P < 0.001); and IL-6 also correlated positively with TNFα (r = 0.40, P < 0.02) and Fg (r = 0.45, P < 0.01). Vascular endothelial growth factor inversely correlated with sVEGFR-1 (r = -0.35, P < 0.02). No associations were found between marker levels and survival or progression-free survival.

摘要

炎症、血管生成和凝血与癌症的发展有关。在胶质母细胞瘤中,微血管增殖是一个标志,淋巴细胞浸润是常见的发现。血栓形成在胶质母细胞瘤患者中很常见。本研究的目的是评估一组前瞻性胶质母细胞瘤患者术前循环炎症、血管生成和凝血标志物的水平,并探讨它们与临床发现的相关性和可能的相关性。所包括的血管生成标志物有血管内皮生长因子(VEGF)、可溶性血管内皮生长因子受体 1(sVEGFR-1)和血栓反应蛋白-1(TSP-1)。炎症标志物包括 C 反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNFα)和唾液酸(SA)。凝血标志物包括纤维蛋白原(Fg)、内源性凝血酶生成(ETG)、凝血酶原片段 1+2(F1+2)和组织因子(TF)。47 例患者和 60 例健康对照者纳入研究。术前 MRI 显示肿瘤坏死与生存期较短相关(P<0.01)。所有炎症标志物、F1+2、ETG、VEGF 和 sVEGFR-1 在胶质母细胞瘤患者中均显著升高。ETG 与 Fg 之间存在相关性(r=0.44,P<0.01)。唾液酸与 Fg 相关(r=0.63,P<0.001);CRP 与 SA(r=0.60,P<0.001)、Fg(r=0.76,P<0.001)、TNFα(r=0.56,P<0.001)和 IL-6(r=0.65,P<0.001)相关;IL-6 还与 TNFα(r=0.40,P<0.02)和 Fg(r=0.45,P<0.01)呈正相关。VEGF 与 sVEGFR-1 呈负相关(r=-0.35,P<0.02)。标志物水平与生存或无进展生存期之间无相关性。

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