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肾细胞癌患者围手术期外周血和肾静脉中促血管生成因子和抗血管生成因子水平的评估及其相关性

Evaluation of peri-operative peripheral and renal venous levels of pro- and anti-angiogenic factors and their relevance in patients with renal cell carcinoma.

作者信息

Klatte Tobias, Böhm Malte, Nelius Thomas, Filleur Stephanie, Reiher Frank, Allhoff Ernst Peter

机构信息

Department of Urology, Otto-von-Guericke-Universität, Magdeburg, Germany.

出版信息

BJU Int. 2007 Jul;100(1):209-14. doi: 10.1111/j.1464-410X.2007.06871.x. Epub 2007 Apr 8.

DOI:10.1111/j.1464-410X.2007.06871.x
PMID:17428240
Abstract

OBJECTIVE

To evaluate peri-operative peripheral and renal venous plasma levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor type BB (PDGF-BB), transforming growth factor (TGF)-beta1, endostatin, and thrombospondin-1 (TSP-1) in relation to pathological variables and prognosis, as pro- and anti-angiogenic factors are important for tumour growth and treatment of patients with renal cell carcinoma (RCC).

PATIENTS AND METHODS

The study included 74 consecutive patients with sporadic RCC who had tumour nephrectomy. Peripheral venous blood was drawn 1 day before, immediately and 1, 3 and 5 days after surgery. Renal venous blood was collected in a subgroup of 33 patients during surgery. The variables were analysed using quantitative enzyme-linked immunoassay kits, and associated with pathological variables and disease-specific survival.

RESULTS

Soon after surgery, peripheral venous VEGF, PDGF-BB and TGF-beta1 levels were decreased, whereas endostatin levels were significantly increased. Renal venous VEGF, PDGF-BB and TGF-beta1 levels were higher than in the general venous blood pool. Renal venous VEGF levels were correlated with tumour diameter and associated with grade and vascular invasion. After a mean follow-up of 30 months, higher peripheral preoperative, early peripheral postoperative and renal venous VEGF levels were associated with a poorer prognosis. However, in a multivariate analysis only Tumour-Node-Metastasis stage and Eastern Cooperative Oncology Group performance status were independent prognosticators of disease-specific survival.

CONCLUSIONS

Circulating pro- and anti-angiogenic factors change early after nephrectomy. VEGF, PDGF-BB and TGF-beta1 are higher in the renal vein than in the general venous blood pool. Higher renal venous and peripheral levels of VEGF might be associated with a poorer prognosis.

摘要

目的

评估血管内皮生长因子(VEGF)、血小板衍生生长因子BB型(PDGF-BB)、转化生长因子(TGF)-β1、内皮抑素和血小板反应蛋白-1(TSP-1)在围手术期外周血和肾静脉血浆中的水平与病理变量及预后的关系,因为促血管生成因子和抗血管生成因子对肾细胞癌(RCC)患者的肿瘤生长和治疗至关重要。

患者与方法

本研究纳入74例连续接受肿瘤肾切除术的散发性RCC患者。术前1天、手术即刻以及术后1、3和5天采集外周静脉血。在手术过程中,对33例患者的亚组采集肾静脉血。使用定量酶联免疫分析试剂盒分析这些变量,并与病理变量和疾病特异性生存相关联。

结果

术后不久,外周静脉VEGF、PDGF-BB和TGF-β1水平下降,而内皮抑素水平显著升高。肾静脉VEGF、PDGF-BB和TGF-β1水平高于外周静脉血总体水平。肾静脉VEGF水平与肿瘤直径相关,并与分级和血管侵犯有关。平均随访30个月后,术前外周血、术后早期外周血和肾静脉VEGF水平较高与预后较差相关。然而,在多变量分析中,只有肿瘤-淋巴结-转移分期和东部肿瘤协作组体能状态是疾病特异性生存的独立预后因素。

结论

肾切除术后早期循环中的促血管生成因子和抗血管生成因子会发生变化。肾静脉中的VEGF、PDGF-BB和TGF-β1高于外周静脉血总体水平。肾静脉和外周血中较高的VEGF水平可能与较差的预后相关。

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