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胃癌中 Multimerin-2 和 EMILIN-2 表达缺失与血管生成改变有关。

Loss of Multimerin-2 and EMILIN-2 Expression in Gastric Cancer Associate with Altered Angiogenesis.

机构信息

Dipartimento della Ricerca e della Diagnostica Avanzata dei Tumori, Divisione di Oncologia Molecolare, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

Dipartimento di Oncologia Clinica, Gastroenterologia Oncologica Sperimentale, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

出版信息

Int J Mol Sci. 2018 Dec 11;19(12):3983. doi: 10.3390/ijms19123983.

Abstract

Gastric cancer is a deadly tumor and a relatively common disease worldwide. Surgical resection and chemotherapy are the main clinical options to treat this type of disease, however the median overall survival rate is limited to one year. Thus, the development of new therapies is a highly necessary clinical need. Angiogenesis is a promising target for this tumor type, however clinical trials with the use of anti-angiogenic drugs have so far not met expectations. Therefore, it is important to better characterize the expression of molecules whose expression levels may impact on the efficacy of the treatments. In this study the characteristics of the gastric tumor associated blood vessels were first assessed by endomicroscopy. Next, we analyzed the expression of Multimerin-2, EMILIN-2 and EMILIN-1, three molecules of the EMI Domain ENdowed (EDEN) protein family. These molecules play important functions in the tumor microenvironment, affecting cancer progression both directly and indirectly impinging on angiogenesis and lymphangiogenesis. All the molecules were highly expressed in the normal mucosa whereas in a number of patients their expression was altered. We consider that better characterizing the gastric tumor microenvironment and the quality of the vasculature may achieve effective patient tailored therapies.

摘要

胃癌是一种致命的肿瘤,也是全球范围内较为常见的疾病。手术切除和化疗是治疗这种疾病的主要临床选择,然而,中位总生存期仅限于一年。因此,开发新的治疗方法是非常必要的临床需求。血管生成是这种肿瘤类型的一个有前途的靶点,然而,迄今为止,使用抗血管生成药物的临床试验并未达到预期效果。因此,更好地表征表达水平可能影响治疗效果的分子的表达是非常重要的。在这项研究中,首先通过内窥镜评估了胃癌相关血管的特征。接下来,我们分析了 Multimerin-2、EMILIN-2 和 EMILIN-1 的表达,这三种分子都属于 EMI 结构域富含蛋白(EDEN)家族。这些分子在肿瘤微环境中发挥着重要的功能,直接或间接地影响着肿瘤的进展,影响着血管生成和淋巴管生成。所有这些分子在正常黏膜中都有高表达,但在一些患者中它们的表达发生了改变。我们认为,更好地描述胃癌肿瘤微环境和血管质量可能实现有效的个体化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa5/6321373/2eb932ea06d4/ijms-19-03983-g001.jpg

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