Thompson Henry J, McGinley John N, Knott Katrina K, Spoelstra Nicole S, Wolfe Pamela
Center for Nutrition in the Prevention of Disease, AMC Cancer Research Center, 1600 Pierce Street, Denver, CO 80214, USA.
Carcinogenesis. 2002 May;23(5):847-54. doi: 10.1093/carcin/23.5.847.
Given the mounting interest in studying the effects of various cancer preventive regimes on the angiogenic process in autochthonously growing mammary tumors, the experiment reported here was conducted to identify factors that should be considered in the collection of data from experiments in which a primary endpoint is the measurement of blood vessel density as a reflection of angiogenic activity. Female Sprague-Dawley rats were injected i.p. with 50 mg 1-methyl-1-nitrosourea (MNU)/kg body weight at 21 days of age. Tumor-bearing rats were killed 35 days post-carcinogen. Immunohistochemical detection of blood vessels using antiserum directed against the CD31 epitope was performed on paraffin sections of 36 carcinomas representing four histological types. Census counting was used to detect all blood vessels that were subsequently divided into one of five vessel size categories. Vessels were counted in both the intra-tumoral region and in a 50 microm width band of mammary tissue circumscribing each tumor; the circumscribed area was referred to as the extra-tumoral region. Vascular density was reported in units of vessel counts or vessel area per unit of assessed area. Overall, vascular density was observed to be highly variable and was not affected by tumor histology. Vascular density in the extra-tumoral region was significantly higher than in the intra-tumoral region. Correlation analyses indicated that similar information was obtained when vascular density was reported as either vessel counts or vessel area; however, correlations across vessel size categories and between the intra-tumoral and extra-tumoral regions were low and generally not statistically significant. Collectively, the data provide a complete description of vascularization in autochthonously growing mammary tumors, and a reference for comparison in studies of various cancer preventive agents that modulate the angiogenic process.
鉴于对研究各种癌症预防方案对自发生长的乳腺肿瘤血管生成过程影响的兴趣日益浓厚，本文报告的实验旨在确定在以血管密度测量作为血管生成活性反映的实验数据收集中应考虑的因素。在21日龄时，给雌性Sprague-Dawley大鼠腹腔注射50mg/kg体重的1-甲基-1-亚硝基脲（MNU）。致癌剂注射后35天处死荷瘤大鼠。使用针对CD31表位的抗血清对代表四种组织学类型的36例癌的石蜡切片进行血管免疫组织化学检测。采用普查计数法检测所有血管，随后将其分为五个血管大小类别之一。在肿瘤内区域和围绕每个肿瘤的50微米宽的乳腺组织带中计数血管；该限定区域称为肿瘤外区域。血管密度以每单位评估面积的血管计数或血管面积为单位报告。总体而言，观察到血管密度高度可变，且不受肿瘤组织学影响。肿瘤外区域的血管密度显著高于肿瘤内区域。相关分析表明，当血管密度以血管计数或血管面积报告时，获得的信息相似；然而，不同血管大小类别之间以及肿瘤内和肿瘤外区域之间的相关性较低，且一般无统计学意义。总体而言，这些数据提供了自发生长的乳腺肿瘤血管化的完整描述，并为各种调节血管生成过程的癌症预防剂研究提供了比较参考。
