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endometrial hyperplasia

妇产

关键词妇产 疾病 生殖内分泌疾病

词汇介绍

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解析

endometrial  [ɛndʌ'mɛtrɪəl]

       adj. [解剖] 子宫内膜的

同根词  词根: endometrium

n.endometriosis [妇产] 子宫内膜异位 endometrium [解剖] 子宫内膜

       However, the use of hormone therapy can increase the risk of blood clots, endometrial cancer and, possibly, breast cancer. 但使用激素疗法会增加血凝块、子宫内膜癌风险,它也可能会增加乳腺癌的风险。

 

hyperplasia  英 [,haɪpə'pleɪzɪə]  美 [,haɪpɚ'pleʒə]

       n. [病理] 增生;畸形生长

       Cancer cell why can infinite hyperplasia? 癌细胞为什么能无限增殖?

概述

子宫内膜增生是指内膜腺体的不规则增殖,同时伴有腺体/间质比例的增加。子宫内膜增生是子宫内膜癌的癌前病变,其发病率至少比子宫内膜癌高出3倍,若不加以干预,有可能进展为子宫内膜癌。子宫内膜增生最常见的首发症状是异常子宫出血,包括月经血量增多、月经间期出血、不规则出血、雌激素补充治疗中无规律的出血以及绝经后子宫出血。它根据是否存在细胞不典型性将子宫内膜增生分为2类:(i)无不典型性的子宫内膜增生(ii)子宫内膜不典型增生 无不典型性的子宫内膜增生的一线用药能够使子宫内膜增生状态获得有效缓

Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities.复制标题

卵巢功能不全和CTNNB1突变驱动PTEN/PI3K活性改变的子宫内膜增生的恶性转化。

发表时间:2019-02-19

影响因子:9.6

作者: Jumpei Terakawa

期刊:Proc. Natl. Acad. Sci. U.S.A.

Endometrioid endometrial carcinomas (EECs) carry multiple driver mutations even when they are low grade. However, the biological significance of these concurrent mutations is unknown. We explored the interactions among three signature EEC mutations: loss-of-function (LOF) mutations in , gain-of-function (GOF) mutations of phosphoinositide 3-kinase (PI3K), and exon 3 mutations, utilizing in vivo mutagenesis of the mouse uterine epithelium. While epithelial cells with a monoallelic mutation in any one of three genes failed to propagate in the endometrium, any combination of two or more mutant alleles promoted the growth of epithelium, causing simple hyperplasia, in a dose-dependent manner. Notably, exon 3 deletion significantly increased the size of hyperplastic lesions by promoting the growth of PTEN LOF and/or PI3K GOF mutant cells through the activation of neoadenogenesis pathways. Although these three mutations were insufficient to cause EEC in intact female mice, castration triggered malignant transformation, leading to myometrial invasion and serosal metastasis.

译文

子宫内膜样子宫内膜癌(EECs)即使在低级别时也会携带多种驱动突变。然而,这些并发突变的生物学意义尚不清楚。我们探讨了三种特征性EEC突变之间的相互作用:功能丧失(LOF)突变,磷酸肌醇3-激酶(PI3K)的功能获得(GOF)突变和外显子3突变,利用体内突变小鼠子宫上皮。虽然在三个基因中的任何一个中具有单等位基因突变的上皮细胞未能在子宫内膜中繁殖,但是两个或更多个突变等位基因的任何组合以剂量依赖性方式促进上皮细胞的生长,引起简单的增生。值得注意的是,外显子3缺失通过激活新生成途径促进PTEN LOF和/或PI3K GOF突变细胞的生长,显着增加了增生性病变的大小。尽管这三种突变不足以在完整的雌性小鼠中引起EEC,但去势引发了恶性转化,导致肌层浸润和浆膜转移。