淋巴细胞与单核细胞比值对上皮性卵巢癌预后价值的临床分析

目的 探讨淋巴细胞与单核细胞比值（LMR）在上皮性卵巢癌（EOC）预后评估中的价值。方法 收集2006年2月至2014年4月EOC患者189例,采用受试者工作曲线（ROC）分析EOC患者LMR的最佳诊断值;分析LMR表达与EOC临床病理特征的关系;采用Cox风险比例模型分析影响EOC预后的因素。 结果 根据ROC曲线分析显示,LMR的截断值为1.850;将189例患者分为低LMR组（n=39,LMR≤1.850）和高LMR组（n=150,LMR＞1.850）。LMR水平与年龄、CA125、FIGO分期、中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、白蛋白水平有关（P＜0.05）,与组织学分级、病理类型、血红蛋白含量和残留病灶无关（P＞0.05）。高LMR组、低LMR组的中位无进展生存期分别为91个月和65个月,中位总生存期分别为105个月和67个月,差异均有统计学意义（P＜0001）。Cox风险比例模型分析显示,年龄、CA125、FIGO分期、LMR是影响无进展生存期的独立因素（P＜0.05）,年龄、FIGO分期、LMR是影响总生存期的独立因素（P＜0.05）。结论 LMR是影响EOC患者预后的独立因素,能作为标志物对EOC患者进行预后评估。     

上皮性卵巢癌患者术前外周血中性粒细胞/淋巴细胞比值在诊断及复发预测中的作用

目的:评价上皮性卵巢癌患者术前外周血中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)在诊断及预测复发中的应用价值.方法:回顾性分析在青岛大学附属医院2003年1月至2011年1月收治的147例良性卵巢肿瘤和134例上皮性卵巢癌(epithelial ovarian cancer,EOC)患者的临床病理资料,通过受试者工作特征曲线确定术前外周血NLR诊断EOC的价值并选取最佳截断值;通过单因素及多因素分析寻找患者5年内复发的高危因素.结果:患者术前NLR对诊断EOC最佳截断值为2.04.术前NLR＜2.04组与NLR≥2.04组患者在年龄、FIGO分期、CA125水平、腹水及淋巴结转移等方面均有明显差异(P＜0.05),而与不同病理类型和分化程度无明显差异(P＞0.05).单或多因素分析结果显示,术前NLR≥2.04为EOC患者术后5年内复发的危险因素(P＜0.05).结论:EOC患者术前NLR升高与癌症的存在及多种临床侵袭性指标相关,是影响EOC患者术后复发的独立危险因素.     

Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer

TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%. We are investigating the role of TWIST in mediating these relapses. We demonstrate TWIST-siRNA (siTWIST) and a novel nanoparticle delivery platform to reverse chemoresistance in an EOC model. Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-HAs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with siTWIST-MSN-HA and cisplatin exhibited specific tumor targeting and reduction of tumor burden. This platform has potential application for overcoming clinical challenges of tumor cell targeting, metastasis and chemoresistance in ovarian and other TWIST overexpressing cancers.     

溶血磷脂信号在上皮性卵巢癌微环境中作用的研究进展

卵巢癌是妇科恶性肿瘤死亡的主要原因,发生在肿瘤微环境(TME)中的包括脂质代谢改变在内的代谢重编程是其主要特征。脂质中的几种溶血磷脂（也称癌脂）如溶血磷脂酸（LPA)是TME的重要组成部分,参与了肿瘤发生、发展的各个方面。本文综述了上皮性卵巢癌（EOC）TME中脂质代谢的改变,包括脂肪酸氧化增强、其它几种脂肪酸含量的改变,其次是溶血磷脂信号在EOC中的研究进展,重点介绍了LPA在EOC的TME中的作用:促进卵巢癌细胞的增殖、削弱免疫监测、侵袭转移、对化疗药物的抵抗等。     

Fibroblast activation proteins-α suppress tumor immunity by regulating T cells and tumor-associated macrophages

Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in > 90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment. However, the effect of FAPα on Tregs and TAMs is unknown. The non-enzymatic function of FAPα on Treg and TAM was investigated. In this study, we confirm that FAPα can promote the generation of Tregs and TAMs, which suggests that FAPα plays a immunosuppressive role in the tumor microenvironment and provides evidence for FAP α as a potent immunotherapeutic target for cancer.     

miR-139-5p通过靶向Notch1抑制上皮性卵巢癌细胞的增殖与侵袭

目的：探讨miR-139-5p靶向Notch1抑制上皮性卵巢癌（epithelial ovarian cancer,EOC）细胞增殖和侵袭的作用机制。方法：选取2018年1月至2018年12月在河南省南阳市中心医院妇科手术切除的24例EOC患者的癌和相应的癌旁组织标本,以及人卵巢癌细胞系SKOV3、ES2、HEY-T30和人卵巢上皮细胞株IOSE80,用qPCR检测EOC组织和细胞系中miR-139-5p和Notch1 mRNA的表达。将过表达miR-139-5p载体、重组质粒pLV-Notch1转染至SKOV3细胞,并设置空白对照组（Ctrl组）和阴性对照组（NC组）,用双荧光素酶报告基因实验验证miR-139-5p与Notch1 3’-UTR靶向关系,用CCK-8、Transwell、划痕愈合实验分别检测细胞的增殖、侵袭和迁移能力,用Western blotting检测细胞中增殖和迁移相关蛋白的表达。结果：与癌旁组织和IOSE80细胞比较,EOC组织和细胞系中miR-139-5p表达显著降低、Notch1 mRNA表达显著升高（均P<0.01）。双荧光素酶报告基因实验结果证实,Notch1是miR-139-5p的靶基因。与NC组比较,miR-139-5p mimic组3 d时SKOV3细胞的增殖、侵袭、迁移能力和Notch1、NICD、Cyclin D1、Cyclin A1、Snail1、β-catenin及N-cadherin表达水平均明显降低（均P<0.01）,E-cadherin表达水平明显升高（P<0.01）;同时过表达Notch1可逆转miR-139-5p抑制SKOV3细胞增殖、侵袭与迁移的作用。结论：miR-139-5p可靶向Notch1抑制EOC细胞的增殖、侵袭和迁移能力,可能与其下调NICD、Cyclin D1、Cyclin A1、Snail1、β-catenin、N-cadherin而上调E-cadherin的表达水平有关。     

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Objective

To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.

CD117和Nestin在卵巢上皮性癌组织中的表达及临床意义

目的检测CD117及Nestin在卵巢上皮癌（EOC）中的表达水平,并探讨其临床意义。方法选择河北省邯郸市中心医院病理存档的石蜡标本80份,其中20份为正常卵巢标本,60份为卵巢上皮癌标本,采用免疫组化法（SP法）检测其CD117及Nestin的表达水平,并分析其与临床病理因素之间的关系。结果 CD117及Nestin在正常卵巢组织和卵巢上皮癌中的阳性表达率分别为10.0%、65.0%和5.0%、38.3%,差异有统计学意义（P〈0.05）。CD117及Nestin在EOC组中的表达水平与其FIGO分期及病理分级有关,在Ⅲ-Ⅳ期、低分化组（G3）比Ⅰ-Ⅱ期、高中分化（G1、G2）组表达率高（P〈0.05）。通过Kaplan-Meier生存曲线了解CD117和Nestin在预测卵巢癌预后中的价值。结论CD117与Nestin在卵巢上皮性癌中高表达,CD117及Nestin可能促进了卵巢上皮癌的发生、发展,并可能作为卵巢癌干细胞标志物用于判断卵巢上皮性癌的预后。     

IL-6与上皮性卵巢癌分期进展关系及其作用机制的生物信息学分析

目的探讨白细胞介素-6（interleukin-6,IL-6）表达水平在上皮性卵巢癌（epithelial ovarian cancer,EOC）中的临床价值,并基于生物信息学预测IL-6对EOC发生、发展的潜在机制。方法ELISA法检测21例不同国际妇产科联盟（International Federation of Gynecology and Obstetrics,FIGO）手术-病理分期的EOC患者、12例良性卵巢疾病患者和30例健康体检妇女的血清IL-6水平。从公共基因表达（gene expression omnibus,GEO）数据库和癌症基因组图谱（the cancer genome atlas,TCGA）数据库收集共计897例EOC组织样本的基因表达谱,根据IL-6高低表达分组筛选差异基因,进行GO和KEGG通路富集分析。绘制IL-6相关基因所编码蛋白的相互作用网络图,提取IL-6所在的核心网络模块。结果血清IL-6在EOC患者的水平显著高于正常对照组（P=0.031）,与FIGO Ⅰ~Ⅳ期呈正相关（r=0.79,P=0.002）;基于TCGA数据库挖掘的IL-6基因表达水平在发生脉管浸润时上调（P=0.027）,且随FIGO Ⅰ~Ⅲ依次升高;从4个卵巢癌数据集筛选出199个共同差异基因,富集于细胞外基质重塑、细胞粘附、炎性反应、病原体免疫识别等功能和相应的信号通路;初步鉴定出CCL2、PTPRC、CD163可能为IL-6在EOC中发挥作用的关键分子。结论血清IL-6可为EOC的复发和转移提供实验室证据,生物信息学分析提示IL-6相关基因主要与EOC的侵袭和转移等生物学特性有关,IL-6用于评估病情进展的具有临床意义。     

Ensuring effective Essential Obstetric Care in resource poor settings

Although Emergency Obstetric Care (EOC) is globally accepted as a key strategy to improve maternal health and reduce maternal mortality, there is still a lot of debate surrounding its use – What is EOC? Is it evidence-based? How can we measure it? How can we improve access to EOC? This paper attempts to answer these questions. Although there are no randomized controlled trials, there is strong evidence from quasi-experimental, observational and ecological studies that EOC should be a critical component of any programme to reduce maternal mortality. This paper also identifies the barriers to accessing EOC and proposes strategies to overcome them which could contribute to achieving Millennium Development Goal 5.