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瘦素、瘦素受体及缺氧诱导因子1α在人子宫内膜癌中的表达

Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer.

作者信息

Koda Mariusz, Sulkowska Mariola, Wincewicz Andrzej, Kanczuga-Koda Luiza, Musiatowicz Boguslaw, Szymanska Magdalena, Sulkowski Stanislaw

机构信息

Department of General and Clinical Pathomorphology, Medical University of Bialystok, Waszyngtona St. 13, 15-269 Bialystok, Poland.

出版信息

Ann N Y Acad Sci. 2007 Jan;1095:90-8. doi: 10.1196/annals.1397.013.

Abstract

Recent studies suggested that Ob (Ob) and its receptor (ObR) could be involved in the pathogenesis of various human malignancies, among others in endometrial cancer. Moreover, hypoxia, which is associated with solid tumors, might stimulate, through hypoxia-inducible factor 1alpha (HIF-1alpha), expression of Ob and ObR. In this article, we analyzed by immunohistochemistry the expression of Ob, ObR, and HIF-1alpha in 60 cases of human endometrial cancer tissues as well as in 25 cases of normal endometria. Additionally, we assessed correlations among studied proteins as well as relationships with selected clinicopathological features of endometrial cancer. Immunoreactivity for Ob, ObR, and HIF-1alpha protein was observed in 56.7%, 30.0%, and 78.3% of endometrial cancers, respectively. The expression of HIF-1alpha showed a significant positive correlation with Ob (P < 0.0001, r = 0.573) and ObR (P = 0.020, r = 0.299). Moreover, we noted positive correlation between Ob and ObR (P = 0.001, r = 0.429). No statistically significant relationship was revealed between Ob, ObR, and HIF-1alpha protein in regard to patient's age, histological grade, and extent of tumor growth (pT). In conclusion, HIF-1alpha, which is related to tissue hypoxia in endometrial cancer, seems to be associated with overexpression of Ob and ObR. Ob could exert autocrine effect to stimulate endometrial cancer progression. Thus the autocrine Ob loop should be taken into consideration as a novel potential target in endometrial cancer prevention and treatment.

摘要

近期研究表明,肥胖(Ob)及其受体(ObR)可能参与多种人类恶性肿瘤的发病机制,尤其是子宫内膜癌。此外,与实体瘤相关的缺氧可能通过缺氧诱导因子1α(HIF-1α)刺激Ob和ObR的表达。在本文中,我们通过免疫组织化学分析了60例人子宫内膜癌组织以及25例正常子宫内膜中Ob、ObR和HIF-1α的表达。此外,我们评估了所研究蛋白质之间的相关性以及与子宫内膜癌选定临床病理特征的关系。在56.7%、30.0%和78.3%的子宫内膜癌中分别观察到Ob、ObR和HIF-1α蛋白的免疫反应性。HIF-1α的表达与Ob(P < 0.0001,r = 0.573)和ObR(P = 0.020,r = 0.299)呈显著正相关。此外,我们注意到Ob和ObR之间呈正相关(P = 0.001,r = 0.429)。在患者年龄、组织学分级和肿瘤生长范围(pT)方面,未发现Ob、ObR和HIF-1α蛋白之间存在统计学显著关系。总之,与子宫内膜癌组织缺氧相关的HIF-1α似乎与Ob和ObR的过表达有关。Ob可能发挥自分泌作用以刺激子宫内膜癌进展。因此,自分泌Ob环应被视为子宫内膜癌预防和治疗中的一个新的潜在靶点。

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