上皮-间质转化在子宫腺肌病中作用的研究进展

子宫腺肌病(ADS)是子宫内膜腺体及间质侵入子宫肌层导致的以子宫局灶或弥漫性增大为主要改变的良性疾病,其具体发病机制尚不清楚。目前多数研究者认为ADS是基底层内膜细胞增生、侵入到肌层间质的结果。在上皮-间质转化(EMT)过程中,上皮细胞失去细胞极性,细胞间紧密连接和黏附连接减弱,获得了浸润性和游走迁移能力,成为具有间质细胞功能和特性的细胞。EMT在肿瘤形成中赋予细胞迁移、浸润的能力,而ADS发生、发展过程中子宫内膜细胞侵入肌层的生物学行为与之非常相似。已有研究表明EMT在ADS形成中具有重要作用。目前ADS的临床治疗面临较多的挑战,因此阐明ADS的发生机制是寻求临床早期预防、治疗ADS有效方法的关键。     

细胞黏附因子在子宫腺肌病发病机制中作用的研究进展

子宫腺肌病(ADS)是严重影响育龄妇女生殖健康的难治性疾病。细胞黏附分子(CAM)是介导细胞连接的主要细胞因子,其在细胞与细胞、细胞与细胞外基质间的连接黏附中发挥重要作用。ADS是一种良性疾病,但具有黏附、侵袭和转移等恶性特征。研究发现,CAM在异位子宫内膜向子宫肌层侵袭迁移的过程中起着重要作用。本文对CAM在ADS发病中作用机制的研究进展进行综述。     

子宫腺肌病诊治及其与子宫内膜癌关系的研究进展

子宫腺肌病(adenomyosis)是以子宫内膜腺体及间质侵入子宫肌层而导致的以月经过多和进行性痛经为主的一种临床常见疾病,严重影响患者的生活质量,多发生于育龄期经产妇。该病的发病机制尚不明确,目前存在子宫内膜损伤内陷学说、上皮间质转化学说和干细胞学说等各种学说。组织学检查是其诊断的金标准,但临床上常根据患者的临床表现及影像学检查作出初步诊断。子宫腺肌病可导致不孕,并且对整个妊娠过程产生不利影响。子宫腺肌病虽然是一种良性疾病,但近年越来越多报道证实了该病有恶变的风险。研究显示合并子宫腺肌病的子宫内膜癌患者,子宫腺肌病对癌症的侵袭浸润起到保护作用,这类患者往往临床预后更好。子宫腺肌病的治疗包括药物治疗和手术治疗,目前尚无根治性药物,手术是其主要的治疗手段。     

苍白细胞与子宫腺肌病的研究北大核心CSCD

子宫腺肌病是常见妇科良性疾病,目前诊治方面已有很大进展,发病机制尚不明确。研究者们提出诸多理论,然更为认可＂子宫腺肌病因内膜基底层向下浸润生长嵌入肌层所致＂。内膜如何嵌入肌层仍在探讨,很多学者认为子宫内膜嵌入子宫肌层与子宫内膜-肌层结合带的自我损伤与自我修复密切相关。最近,有学者提出子宫腺肌病发病机制新观点,即苍白细胞主动迁移至基底子宫内膜,继而至子宫肌层形成病灶。     

表皮生长因子受体在子宫腺肌病中的表达及其临床意义

目的：研究表皮生长因子受体（ＥＧＦＲ）在子宫腺肌病中的组织定位和表达；探讨ＥＧＦＲ表达与子宫腺肌病发生的关系，寻求经调控ＥＧＦ／ＥＧＦＲ治疗子宫腺疾病的新途径。方法：应用免疫组织化学ＡＢＣ法检测子宫内膜组织１０份和子宫腺肌病组织３０份标本的ＥＧＦＲ定位和表达以及月经周期中内膜组织的ＥＧＦＲ表达强度变化。结果：正常子宫内膜和子宫腺肌病病灶均存在ＥＧＦＲ表达；ＥＧＦＲ位于内膜腺上皮和间质及平滑肌细胞上；表达强度：腺体＞间质＞平滑肌；子宫内膜＞异位内膜，但无统计学差异；ＥＧＦＲ表达无周期性变化，异位内膜侵入程度与临床症状有相关性。结论：正常子宫内膜和子宫腺肌病异位内膜存在ＥＧＦＲ共同表达；提示两者具有组织同源性；异位内膜中ＥＧＦＲ表达可能与子宫腺肌病发生机制有关。经降调节ＥＧＦ／ＥＧＦＲ表达可望成为治疗子宫腺肌病的新途径。     

子宫腺肌病保守性手术治疗进展

子宫腺肌病是子宫内膜腺体和间质侵入子宫肌层而引起的子宫肌层增生性病变，好发育龄期妇女，发病率8．8％～31％不等。长期以来，子宫腺肌病一直没有较理想的治疗方法，常采用药物和子宫内膜切除。但是子宫腺肌病药物治疗效果差，手术治疗一直是最常用而且最有效的治疗方法。手术治疗包括根治手术和保守手术。根治性手术即全子宫切除术，保守性手术包括腺肌病病灶（腺肌瘤）切除术、子宫内膜及肌层切除术、子宫病灶电凝术、介入治疗、盆腔去神经支配治疗、腹腔镜下子宫动脉阻断术等。现对子宫腺肌病保守性手术治疗的应用进展做一综述，为子宫腺肌病的各种保守性手术治疗方法提供理论依据。     

子宫腺肌病的若干问题

<正>子宫内膜异位症(简称内异症)是指子宫内膜腺体和间质出现在子宫腔被覆内膜以外的部位(不包括子宫肌层),生长、浸润、反复出血,继而引发疼痛、不孕及结节或包块等症状的疾病。子宫腺肌病(简称腺肌病)是指子宫肌层内出现子宫内膜腺体和间质,在激素的影响下发生出血、肌纤维结缔组织增生,形成的弥漫性病变或局限性病变,也可局灶形成子宫腺肌瘤病灶。关于腺肌病,存在很多迷惑和问题,有很多模糊和争论。早在4000多年前的希波克拉底时代,     

子宫腺肌病231例临床分析

子宫腺肌病（adenomyosis）是子宫内膜腺体及间质侵入子宫肌层,伴随周围肌层细胞代偿性肥大和增生,以往曾称为内在性内异症,多见于40岁以上经产妇[1],近年来,其发病率呈明显上升且有年轻化的趋势,甚至有癌变的可能[2],但其发病原因和机制尚不十分清楚[1]。本文回顾性分析了中国人民解放军总医院妇产科2009年10月至2011年3月231例经病理证实为子宫腺肌病患者的临床资料,并对其发病情况、临床表现以及诊断等情况予以分析,旨在提高对子宫腺肌病的诊断正确率。     

UBE3C在雌激素促进子宫内膜癌细胞迁移及侵袭中的作用机制研究

目的:探讨泛素连接酶E3C(UBE3C)在雌激素(E_2)诱导子宫内膜癌细胞发生迁移、侵袭及上皮间质转化(EMT)过程中的作用。方法:免疫组化法检测子宫内膜癌组织中UBE3C表达情况。qRT-PCR及Western blot法检测UBE3C在子宫内膜癌细胞株、子宫内膜间质细胞株及正常子宫内膜上皮细胞中的表达。雌激素以浓度及时间梯度处理Ishikawa细胞,qRT-PCR及Western blot法检测UBE3C mRNA和蛋白表达。雌激素处理siNC或siUBE3C转染的Ishikawa细胞,划痕试验和Transwell侵袭实验检测细胞迁移、侵袭能力,Western blot法检测EMT相关蛋白E-cadherin、N-cadherin、snail及slug表达。结果:UBE3C在子宫内膜癌组织及细胞中高表达。雌激素能上调Ishikawa细胞UBE3C mRNA及蛋白表达,且在一定范围内呈剂量时间依赖性。雌激素刺激增强Ishikawa细胞的迁移、侵袭能力,促进EMT;si-UBE3C干扰能显著抑制上述作用,且能减弱雌激素对Ishikawa细胞迁移、侵袭能力的增强及EMT的促进。结论:UBE3C与雌激素能增强子宫内膜癌细胞的迁移、侵袭能力,促进上皮间质转化,UBE3C可能是雌激素下游重要的靶基因之一,介导雌激素诱导子宫内膜癌细胞的迁移、侵袭及上皮间质转化。     

子宫内膜异位症和细胞迁移

子宫内膜异位症（EMs）是常见妇科疾病,其病因仍未清楚。预防EMs的发生是当前备受关注的课题之一。子宫内膜组织细胞迁移是EMs患者异位病灶形成的前提条件,调节子宫内膜细胞的迁移很可能会影响子宫内膜组织异位病灶的形成。深入了解细胞迁移和EMs形成间的相关机制非常重要。综述国内外关于子宫内膜组织细胞迁移的研究方法以及正常人群和EMs患者子宫内膜组织细胞的迁移能力的差异及其可能机制等相关研究,以期为EMs的预防提供思路。     

Normal endometrial stromal cells regulate 17β-estradiol-induced epithelial-mesenchymal transition via slug and E-cadherin in endometrial adenocarcinoma cells in vitro

Stroma–tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17β-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17β-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17β-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17β-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17β-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17β-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.     

ILK enhances migration and invasion abilities of human endometrial stromal cells by facilitating the epithelial–mesenchymal transition

Abstract

Epithelial–mesenchymal transition (EMT) plays a significant part in the pathogenesis of endometriosis by facilitating the migration and invasion abilities of cells. Integrin-linked kinase (ILK) increases the cell migration and invasion abilities by inducing the EMT. Eutopic and control endometrial stromal cells (EuSCs and CSCs) were isolated and cultured. Cell migration and invasion abilities were detected by transwell assays. Levels of proteins were detected by Western blot. EuSCs showed higher levels of ILK, N-cadherin, vimentin and stronger migration and invasion abilities. After transfection of siRNA-ILK, E-cadherin and keratin levels were increased while N-cadherin and vimentin levels were decreased in EuSCs. Besides that, the migration and invasion abilities of EuSCs were significantly decreased after transfection of siRNA-ILK. On the contrary, levels of ILK, N-cadherin and vimentin were increased while levels of E-cadherin and keratin were decreased simultaneously after transfecting CSCs with pEGFP-C1-ILK. Simultaneously, the migration and invasion abilities of CSCs were increased after transfection of pEGFP-C1-ILK. Our study verified that high expression of ILK enhanced the migration and invasion abilities of ESCs by facilitating the EMT. Given that ILK played crucial roles in the pathogenesis of endometriosis, it may be considered as a promising targeted therapy for endometriosis.     

Upregulation of S100A6 in patients with endometriosis and its role in ectopic endometrial stromal cells

S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion. Moreover, knockdown of S100A6 suppressed p38/MAPK activity in ectopic ESCs, which can be partially attenuated by CacyBP/SIP phosphorylation inhibitor. In conclusion, our results suggest that the abnormal expression of S100A6 may contribute to the pathogenesis of endometriosis and the S100A6/CacyBP/p38 signaling may provide as a promising treatment target.     

Prognostic value of peritoneal fluid cytology in patients with endometrial cancer stage I

With increasing depth of invasion of the endometrial adenocarcinoma in the myometrium an increasing number and percentage of patients with endometrial adenocarcinoma cells in the pouch of Douglas are found. The presence or absence of endometrial tumour cells can be used as an indicator of the depth of invasion in the myometrium. Survival is correlated with the presence of endometrial adenocarcinoma cells in cases with deep invasion; 50% recurrent disease was observed when the fluid was positive, no recurrent disease when negative. No correlation between survival and presence or absence of tumour cells in the Douglas fluid was found in cases with superficial invasion of the tumour in the myometrium.     

Molecular assessment of depth of myometrial invasion in stage I endometrial cancer: a model based on K-ras mutation analysis

INTRODUCTION: Overall nearly 20% of endometrial cancer (EC) patients die of the disease and over half of these had initially presented with clinical stage I disease. There is a strong correlation between disease mortality and depth of myometrial invasion. Current assessment of depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Molecular techniques have a great potential in the detection of such isolated cells. OBJECTIVE: The objective was to develop a model for the application of molecular techniques to advance the assessment of risk status in patients with clinical stage I EC. METHODS:The study sample included 21 stage I ECs with a documented K-ras mutation from two series of 96 and 106 ECs from the United Kingdom and Norway, respectively. K-ras was documented using heteroduplex mobility analysis and amplified created restriction site, followed by sequencing to identify the specific base substitution at codon 12 and 13 of K-ras oncogene. For each case with a K-ras mutation, a modified mutant allele-specific amplification technique was carried out on a series of tissue strips microdissected at increasing depths from the myometrium underlying tumor. The microdissected myometrium had been previously examined histologically for absence of infiltrating tumor cells on light microscopy. Presence of K-ras mutations was used to identify the tumor cells within the histologically normal myometrium. Correlations between submicroscopic myometrial tumor cell infiltration and clinicopathological factors were studied. RESULTS: Of 21 cases with K-ras mutation, 6 cases (28%) showed molecular evidence of tumor cell infiltration beyond the histological boundary. The depth of submicroscopic myometrial infiltration was found to be variable. The staging of the tumors would have changed in 3 cases (14%) if tumor cells been detected histologically. A borderline significant correlation between presence of submicroscopic myometrial invasion and depth of myometrial invasion was noted (P = 0.053). The recurrence rate and survival of patients without submicroscopic invasion were better than those with, although it did not reach statistical significance (recurrence rate P = 0.13, recurrence free survival P = 0.14, cause-specific survival P = 0.12, and total survival P = 0.2). CONCLUSIONS: Molecular assessment of depth of myometrial invasion using K-ras mutation is feasible and may add information to conventional light microscopy. Further prospective studies are required to define the clinical significance of this technology.     

Histopathological study of placental bed biopsy in placenta previa

BACKGROUND: To study placental bed biopsy changes in placenta previa and normally implanted placenta. SUBJECT AND METHOD: Fifty placental bed biopsies from 50 patients with placenta previa and 50 placental bed biopsies from normally implanted placenta were taken at cesarean section. Placental bed biopsy was stained with hematoxyline and eosin for histological examination. Both the groups were compared for trophoblastic invasion and vascular changes of placental bed spiral arteries. Statistical analysis was done by Chi-square test. RESULTS: Placenta bed biopsy was representative in 42/50 (84%) biopsy samples of the study group (placenta previa) and 35/50 (70%) of the control group (normally located placenta). Trophoblastic giant cell migration into decidua was present in 100% of representative samples of both the groups while migration into myometrium was seen in 66.67% and 51.14% of samples of study and control group. Average number of trophoblastic giant cells per sample was significantly higher in placenta previa (decidua 41.3%, myometrium 52%) than the control group (decidua 17.4%; myometrium 14.5%). Trophoblastic giant cell infiltration into myometrial spiral arterioles was higher in placenta previa (81.83 cells per vessel). Percentage of myometrial spiral arterioles showing physiological changes was significantly higher in the study group (50.39%) compared to the control group (21.14%). Incidence of inflammatory cell infiltration was higher in the study group (42.86%). Hemorrhage into decidua and myometrium were seen in biopsy samples of the placenta previa. CONCLUSION: Placenta previa is associated with significantly higher trophoblastic giant cell infiltration and physiological changes of the myometrial spiral arterioles.     

A rare case of low grade endometrial stromal sarcoma of the uterus

Endometrial stromal sarcoma (ESS) is a rare disease. Low-grade endometrial stromal sarcoma (LGESS) is characterized by proliferations composed of cells with endometrial stromal cell differentiation and typically show extensive worm-like vessel invasion. We present a case of a 38-year-old woman with complaints of abdominal pains and ultrasound findings of a tumour formation in the pelvis. The biopsy examination showed a low-grade endometrial stromal sarcoma (LGESS), with a primary location in the uterine corpus and a tumour infiltration in the myometrium and cervix of the uterus, with tumour emboli in the lymph vessels and tumour methastases in the peritoneum--FIGO III Stage. The patient underwent postoperative polychemotherapy and radiotherapy. The gynecological and ultrasound examination found no pathological changes in the pelvic region five years after the operation.     

上皮-间质转化在子宫内膜异位症发病机制中的作用

子宫内膜异位症(endometriosis,EMs)是一种育龄期妇女常见的慢性炎症性、雌激素依赖性疾病,严重影响着广大女性的身心健康及生活质量。虽然目前已提出各种病因学说,但其起源仍不清楚。近年研究发现,上皮-间质转化(epithelial-mesenchymal transition,EMT)可能在EMs的发生发展中起重要作用。EMT是指上皮细胞失去极性和紧密连接,从而获得间质细胞的侵袭和运动能力的过程,这些改变也被认为是EMs病变最初建立的先决条件。然而,目前还没有确切的研究表明EMs中发生哪种类型的EMT。此外,缺氧和雌激素刺激信号可以通过不同的途径激活EMs中EMT过程,同时这些途径涉及许多细胞因子及信号转导通路,最终导致细胞增殖和迁移。本文对在EMs发生发展过程中参与的EMT类型、刺激信号、细胞因子及信号转导通路进行综述,以期为发现EMs临床诊疗提供新的思路。     

LGR5在子宫内膜癌中的表达及其意义

目的:探讨富含亮氨酸重复序列G蛋白偶联受体5(LGR5)在子宫内膜癌中的表达情况及其与临床病理因素的关系。方法:采用免疫组织化学SABC法检测90例子宫内膜癌及30例正常子宫内膜组织中LGR5表达情况,并分析其与临床病理因素的关系。结果:LGR5在子宫内膜癌组织中的阳性表达率(63.3%)显著高于正常子宫内膜(23.3%)(P0.001)。LGR5在1/2肌层浸润组的阳性表达率(72.5%)显著高于≥1/2肌层浸润组(33.3%)(P=0.001)。LGR5的阳性表达率在年龄、病理类型、组织学分级、宫颈累及、淋巴结转移、FIGO分期组间差异均无统计学意义(P0.05)。多因素分析发现LGR5是子宫内膜癌有无肌层浸润的独立影响因素(OR=0.163,95%CI 0.034~0.772,P=0.022)。结论:LGR5在子宫内膜癌组织中表达上调,提示与肌层浸润深度相关,可能在子宫内膜癌的发生中起一定作用。