Detection of tumor-associated neoangiogenesis by Doppler ultrasonography during early-stage ovarian cancer in laying hens: a preclinical model of human spontaneous ovarian cancer.

Detection of tumor-associated neoangiogenesis by Doppler ultrasonography during early-stage ovarian cancer in laying hens: a preclinical model of human spontaneous ovarian cancer.
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DOI:
10.7863/jum.2010.29.2.173
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发表时间:
2010-02
期刊:
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
影响因子:
--
通讯作者:
Abramowicz JS
Abramowicz JS
中科院分区:
其他
文献类型:
--
作者:
Barua A;Bitterman P;Bahr JM;Bradaric MJ;Hales DB;Luborsky JL;Abramowicz JS

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肿瘤相关新血管生成(TAN)是卵巢肿瘤生长最早的事件之一,是早期发现卵巢癌(OVCA)的潜在靶点。由于早期OVCA患者很难识别,本研究的目的是探索一种可通过多普勒超声(DUS)检测到的早期OVCA患者的自发性卵巢TAN动物模型。白来航产蛋鸡每隔15周至45周经阴道扫描一次。记录卵巢的灰度级、形态特征和多普勒指数。母鸡在被诊断为超声形态/血管异常时或在研究结束时(那些保持正常的)被安乐死。观察卵巢的形态和组织学特征。免疫组织化学方法检测血管内皮细胞生长因子和αvβ3整合素的表达。将多普勒超声观察结果与组织学和免疫组织化学结果进行比较,以确定DUS检出卵巢TAN的能力。卵巢从正常到肿瘤的转变过程中,卵巢血流参数发生了显著变化(P<0.05)。在通过灰阶检测到肿瘤之前,DUS已发现与肿瘤相关的卵巢血管改变。血管内皮生长因子和αvβ3-整合素的高表达与肿瘤的发生有关。在母鸡中,卵巢Tan先于肿瘤进展。提示卵巢TAN可能是OVCA早期检测的有效指标。蛋鸡也可以用来研究卵巢TAN的检测和抑制,这些方法包括对比剂的效果、靶向分子成像和抗血管生成治疗。
Tumor-associated neoangiogenesis (TAN) is one of the earliest events in ovarian tumor growth and represents a potential target for early detection of ovarian cancer (OVCA). Because it is difficult to identify patients with early stage OVCA, the goal of this study was to explore a spontaneous animal model of in vivo ovarian TAN associated with early-stage OVCA detectable by Doppler ultrasound (DUS). White Leghorn laying hens were scanned transvaginally at 15-week intervals up to 45 weeks. Gray scale ovarian morphologic characteristics and Doppler indices were recorded. Hens were euthanized at diagnosis for ultrasonographic morphologic/vascular abnormalities or at the end of the study (those that remained normal). Ovarian morphologic and histologic characteristics were evaluated. Vascular endothelial growth factor (VEGF) and αvβ3-integrins expression was assessed by immunohistochemistochemical analysis. Doppler ultrasonographic observations were compared with histologic and immunohistochemistochemical findings to determine the ability of DUS to detect ovarian TAN. Significant changes in ovarian blood flow parameters were observed during transformation from normal to tumor development in the ovary (P<0.05). Tumor-related changes in ovarian vascularity were identified by DUS before the tumor became detectable by gray scale. Increased expression of VEGF and αvβ3-integrins was associated with tumor development. Ovarian TAN preceded tumor progression in hens. The results suggest that ovarian TAN may be an effective target for the detection of early-stage OVCA. The laying hen may also be useful to study the detection and inhibition of ovarian TAN using various means including the efficacy of contrast agents, targeted molecular imaging and antiangiogenic therapies.
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