Comparison between `in vivo' and `in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model

Comparison between `in vivo' and `in vitro' methods for evaluating tumor angiogenesis using cervical carcinoma as a model
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以宫颈癌为模型评估肿瘤血管生成的“体内”和“体外”方法的比较

DOI:
10.1023/a:1026575725754
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发表时间:
2004
期刊:
影响因子:
9.8
通讯作者:
F. Hsieh
F. Hsieh
中科院分区:
医学1区
文献类型:
--
作者:
W. Cheng;Chien;Chi;J. Chu;C. C. S. Kung;C. Hsieh;F. Hsieh

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血管生成在肿瘤发生中的作用已被广泛接受。因此,必须开发一种临床上有用的方法来评估肿瘤血管生成。本研究旨在比较评估血管生成的“体内”和“体外”方法,并使用宫颈癌作为模型评估其临床应用。 90 名患有 IB-IIA 期宫颈癌的女性参加了这项研究,这些女性经阴道超声检查显示出可见的宫颈肿瘤。所有患者均接受根治性腹部子宫切除术和盆腔淋巴结清扫术。通过能量多普勒超声和定量图像处理系统评估血管指数(VI)。通过免疫组织化学方法评估切除肿瘤的微血管密度(MVD)。采用酶联免疫分析和免疫组织化学方法评估肿瘤组织中血管内皮生长因子(VEGF)的蛋白水平。在深部间质浸润(厚度≥1/2)的肿瘤中检测到显着较高的 VI、MVD 和胞质 VEGF 浓度(11.43 ± 7.25 vs. 5.87 ± 6.81,P < 0.001;53.0 vs. 37.0,P = 0.006、550.0 vs. 86.0 pg/mg,P < 0.001)、淋巴管侵犯(12.21 ± 7.89 vs. 6.86 ± 6.29,P < 0.001;53.0 vs. 40.0,P = 0.038;930.0 vs. 110.0 pg/mg,P = 0.002)和盆腔淋巴结转移(17.15 ± 8.58) 7.83 ± 6.41,P < 0.001;54.0 与 39.0,P = 0.02;964.0 与 131.0 pg/mg,P = 0.002)。通过免疫组织化学检测到的富含 VEGF 的肿瘤还显示较高的 VI(12.26 ± 7.96 vs. 8.05 ± 7.62,P = 0.012)、MVD(53.0 vs. 37.5,P = 0.01)和胞质 VEGF 水平(745.0 vs. 98.0 pg/mg,P = 0.002)。 VI 值、MVD 值和胞质 VEGF 浓度之间呈线性关系(VI 与 MVD,r = 0.38,P < 0.001;VI 与 VEGF,r = 0.78,P < 0.001;MVD 与 VEGF,r = 0.29,P = 0.006)。受试者工作特征(ROC)曲线分析显示,VI在预测淋巴结转移方面优于MVD和VEGF。总之,组织学、分子和临床证据支持 VI 作为肿瘤血管生成的有用“体内”指标,特别是用于预测宫颈癌的淋巴结转移。
The role of angiogenesis in tumorigenesis is widely accepted. Therefore, it is mandatory to develop a clinically useful method for assessing tumor angiogenesis. This study was designed to compare the `in vivo' and `in vitro' methods for assessing angiogenesis and to evaluate their clinical application using cervical carcinoma as a model. Ninety women with stages IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were enrolled in this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Vascularity index (VI) was assessed by power Doppler ultrasound and a quantitative image processing system. The microvessel density (MVD) of the excised tumors was immunohistochemically assessed. Both the enzyme immunoassay and immunohistochemistry methods were performed for assessing the protein levels of vascular endothelial growth factor (VEGF) in tumor tissues. Significantly higher VI, MVD and cytosol VEGF concentrations were detected in tumors with deep stromal invasion (≥1/2 thickness) (11.43 ± 7.25 vs. 5.87 ± 6.81, P < 0.001; 53.0 vs. 37.0, P = 0.006, 550.0 vs. 86.0 pg/mg, P < 0.001), lymphatic invasion (12.21 ± 7.89 vs. 6.86 ± 6.29, P < 0.001; 53.0 vs. 40.0, P = 0.038; 930.0 vs. 110.0 pg/mg, P = 0.002), and pelvic lymph node metastasis (17.15 ± 8.58 vs. 7.83 ± 6.41, P < 0.001; 54.0 vs. 39.0, P = 0.02; 964.0 vs. 131.0 pg/mg, P = 0.002). VEGF-rich tumors detected by immunohistochemistry also revealed higher VI (12.26 ± 7.96 vs. 8.05 ± 7.62, P = 0.012), MVD (53.0 vs. 37.5, P = 0.01) and cytosol VEGF levels (745.0 vs. 98.0 pg/mg, P = 0.002). The relationships between VI values, MVD values and cytosol VEGF concentrations were linear (VI vs. MVD, r = 0.38, P < 0.001; VI vs. VEGF, r = 0.78, P < 0.001; MVD vs. VEGF, r = 0.29, P = 0.006). As revealed by the receiver operating characteristic (ROC) curve analysis, VI is better than MVD and VEGF in predicting lymph node metastasis. In conclusion, there is histological, molecular and clinical evidence supporting VI as a useful `in vivo' indicator of tumor angiogenesis, particularly for predicting lymph node metastases in cervical carcinomas.
DOI: --
发表时间: 1995-07
期刊: The American journal of pathology
影响因子: --
作者:
N. Weidner
通讯作者: N. Weidner
DOI: 10.1056/nejm199101033240101
发表时间: 1991-01-03
影响因子: 158.5
作者:
WEIDNER, N;SEMPLE, JP;FOLKMAN, J
通讯作者: FOLKMAN, J
DOI: 10.1016/0046-8177(95)90119-1
发表时间: 1995-01-01
期刊: HUMAN PATHOLOGY
影响因子: 3.3
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通讯作者: SCHNITT, SJ
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发表时间: 1999-09-01
影响因子: 6
作者:
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通讯作者: Hendrix, MJC
DOI: 10.1016/0046-8177(92)90344-3
发表时间: 1992-07-01
期刊: HUMAN PATHOLOGY
影响因子: 3.3
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通讯作者: SILVERMAN, ML