Inhibitory effects of anti-VEGF antibody on the growth and angiogenesis of estrogen-induced pituitary prolactinoma in Fischer 344 Rats: animal model of VEGF-targeted therapy for human endocrine tumors.
Inhibitory effects of anti-VEGF antibody on the growth and angiogenesis of estrogen-induced pituitary prolactinoma in Fischer 344 Rats: animal model of VEGF-targeted therapy for human endocrine tumors.
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DOI：
10.1267/ahc.09034
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发表时间：
2010-05-01
影响因子：
2.4
通讯作者：
Osamura RY
中科院分区：
文献类型：
--
作者：
Miyajima K;Takekoshi S;Itoh J;Kakimoto K;Miyakoshi T;Osamura RY
雌激素诱导的F344大鼠垂体泌乳素生成瘤（PRLoma）表达高水平的血管内皮生长因子（VEGF），与显著的血管生成和血管扩张相关。为了研究抗VEGF单克隆抗体（G6-31）是否抑制E2诱导的PRLoma中的肿瘤发展，我们评估了肿瘤生长并观察了血管结构。在E2刺激的13周期间的后三周同时用G6-31处理（E2+G6-31组），与仅E2组相比，在E2+G6-31组中观察到对PRLoma的以下抑制作用。在E2+G6-31组中，观察到垂体重量减少的趋势，并且观察到以下显著差异：（1）Ki-67阳性前叶细胞减少，（2）TUNEL阳性前叶细胞增加，和（3）通过CD 34免疫组织化学观察到微血管计数修复。共聚焦激光扫描显微镜三维观察PRLomas特征性的“血湖”得到改善，并被修复的微血管结构所取代。抗VEGF抗体的这些抑制作用可能与VEGF对肿瘤细胞的自分泌/旁分泌作用有关，因为VEGF及其受体在肿瘤细胞上共表达。因此，我们的研究结果表明，抗VEGF抗体发挥抑制作用，垂体肿瘤的发生，在建立E2诱导PRLomas。
Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic “blood lakes” in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas.
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影响因子：
3.2
作者：
Cracchiolo, D;Swick, JW;Wendell, DL
通讯作者：
Wendell, DL
DOI：
10.1097/00022744-200112000-00013
发表时间：
2001-12-01
影响因子：
1.6
作者：
Itoh, J;Kawai, T;Osamura, RY
通讯作者：
Osamura, RY
影响因子：
11.5
作者：
Korsisaari, Nina;Ross, Jed;Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone
影响因子：
3.1
作者：
DAMATO, R;WESLOWSKI, E;SMITH, LEH
通讯作者：
SMITH, LEH
影响因子：
4.8
作者：
ELIAS, KA;WEINER, RI
通讯作者：
WEINER, RI