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软组织肉瘤患者的血清内皮抑素水平升高。

Serum endostatin levels are elevated in patients with soft tissue sarcoma.

作者信息

Feldman A L, Pak H, Yang J C, Alexander H R, Libutti S K

机构信息

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Cancer. 2001 Apr 15;91(8):1525-9. doi: 10.1002/1097-0142(20010415)91:8<1525::aid-cncr1161>3.0.co;2-p.

Abstract

BACKGROUND

Solid tumors are angiogenesis dependent, and elevated levels of proangiogenic cytokines have been reported in a variety of histologies. Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII. Because antiangiogenic protein fragments may be generated by tumor-derived proteases, the authors sought to determine whether circulating levels of endostatin were elevated in patients with localized soft tissue sarcoma.

METHODS

The authors analyzed preoperative serum levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate using a competitive enzyme immunoassay. Serum levels were compared with levels from 34 age-matched and gender-matched volunteer blood donors.

RESULTS

Endostatin levels were significantly higher in sera from sarcoma patients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002; Mann-Whitney U test). Significant elevations also were noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels > 2 standard deviations above the control mean (55 ng/mL) were associated with an increased risk of tumor recurrence after resection (P = 0.047; log-rank test).

CONCLUSIONS

Serum endostatin, VEGF, and bFGF levels are elevated in patients with soft tissue sarcoma. Elevated endostatin levels appear to be associated with tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as potential targets for therapy warrants further study.

摘要

背景

实体瘤依赖血管生成,并且在多种组织学类型中均有报道促血管生成细胞因子水平升高。内皮抑素是基底膜蛋白ⅩⅧ型胶原的一种抗血管生成片段。由于抗血管生成蛋白片段可能由肿瘤衍生的蛋白酶产生,作者试图确定局限性软组织肉瘤患者循环中的内皮抑素水平是否升高。

方法

作者分析了25例软组织肉瘤患者(14例男性和11例女性;平均年龄44岁)术前血清中的内皮抑素、血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)水平。对于每份血清样本,使用竞争性酶免疫测定法对两个等分试样进行重复检测。将血清水平与34名年龄和性别匹配的志愿献血者的水平进行比较。

结果

肉瘤患者血清中的内皮抑素水平显著高于健康对照组(分别为43.0 ng/mL和25.8 ng/mL;P = 0.0002;Mann-Whitney U检验)。VEGF和bFGF水平也有显著升高(分别为P = 0.0002和P = 0.0001)。此外,内皮抑素水平高于对照平均值2个标准差以上(55 ng/mL)与切除术后肿瘤复发风险增加相关(P = 0.047;对数秩检验)。

结论

软组织肉瘤患者血清中的内皮抑素、VEGF和bFGF水平升高。内皮抑素水平升高似乎与肿瘤侵袭性相关。这些细胞因子在肉瘤血管生成中的作用以及作为潜在治疗靶点的作用值得进一步研究。

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