GPR30阳性表达对子宫内膜癌患者预后的影响及其与雌、孕激素受体表达的相关性

目的 分析新型雌激素受体GPR30表达对子宫内膜癌患者预后的影响并探讨其与雌、孕激素表达的关系。方法 收集该院妇产科经病理确诊为子宫内膜癌的石蜡切片,采用免疫组化法检测GPR30、雌激素受体、孕激素受体表达,并分析其对子宫内膜癌的临床意义和分析三者间的关系。结果 GPR30阳性表达率与子宫内膜癌的FIGO分期、组织分级以及肌层浸润深度有关联(P＜0.05),与淋巴结转移无明显相关性(P＞0.05)。GPR30表达阳性率在子宫内膜癌中表达显著高于增殖期子宫内膜(P＜0.05),PR表达阳性率在子宫内膜癌与增殖期子宫内膜差异显著(P＜0.05),ER表达阳性率在两者间无差异(P＞0.05)。子宫内膜癌GPR30与ER阳性共表达率为61.2%(30/49),呈正相关(r=0.315,P=0.021);与 PR阳性共表达率为57.1%(28/49),呈正相关(r=0.303,P=0.027)。结论 GPR30阳性表达对子宫内膜癌的病理分期、组织分级以及肌层浸润深度相关,对子宫内膜癌预后产生重要作用;GPR30与ER、PR间存在共表达的交谈或调节作用。     

C-erB-2、ER、PR在子宫内膜癌中的表达及意义

目的 探讨雌激素受体(ER)、孕激素受体(PR)及第二人体表皮生长因子受体(C-erB-2)在子宫内膜癌中的表达及意义.方法 应用免疫组化SP法检测三者在30例正常子宫内膜、30例子宫内膜息肉及86例子宫内膜癌组织中的表达水平,分析其临床意义及相关性,并将其与子宫内膜癌手术病理分期、组织细胞学分化程度、肌层浸润深度、淋巴结转移等高危因素进行分析.结果 (1) C-erB-2、ER及PR在正常子宫内膜、子宫内膜息肉和子宫内膜癌中的阳性表达率组与组之间差异均有统计学意义(P＜0.05).(2) C-erB-2阳性表达与手术病理分期、组织细胞学分级及淋巴结转移相关(P＜0.05);ER阳性表达与手术病理分期、组织细胞学分级及肌层浸润相关(P＜0.05);PR与组织细胞学分级、肌层浸润及淋巴结转移相关(P＜0.05).(3)C-erB-2与ER的表达呈负相关(r=-0.247,P＜0.05),ER与PR的表达呈正相关(r=0.756,P＜0.05).结论 在子宫内膜癌中,C-erB-2、ER及PR 联合检测可作为早期诊断、指导内分泌治疗及判断预后的重要指标.     

子宫内膜癌ER、PR的表达及其临床意义

目的检测子宫内膜癌组织中雌激素受体（ER）、孕激素受体（PR）阳性表达率并探讨其临床意义。方法应用免疫组化技术对47例子宫内膜癌组织进行ER、PR检测,结合临床及病理指标进行分析。结果ER、PR在47例子宫内膜癌的阳性表达率分别为57.4%和61.7%,ER、PR的双阳性、双阴性分别为48.9%和29.8%。ER、PR在子宫内膜癌的阳性表达率与组织学分级密切相关,随组织学分级的增高,其阳性表达率逐渐降低,有统计学意义（P〈0.05）。ER、PR的表达与肌层浸润、子宫外病灶有关,差异有统计学意义（P〈0.05）。结论ER、PR均反应了子宫内膜癌的生物学行为,是一个可以综合反映病程、病情和病变性质的客观指标,其测定对估计患者预后,指导临床选择激素治疗具有重要意义。     

子宫内膜癌雌孕激素受体检测的临床意义

目的:检测子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)表达的阳性率并探讨其与预后的关系。方法:用免疫组化法对32例子宫内膜癌标本进行ER、PR的检测。结果:子宫内膜癌组织中ER、PR的阳性率分别为53.1%、50.0%。ER、PR的阳性表达率与癌组织的细胞分化程度有关,随着子宫内膜癌组织学分级的增高,ER、PR阳性率表达率逐渐降低,ER的表达还与肌层浸润深度有关。结论:ER、PR均反应了子宫内膜癌的生物学行为,其测定对预测临床预后、指导临床选择内分泌治疗具有重要意义。     

雌激素受体、孕激素受体、p53蛋白、p16蛋白在子宫内膜癌组织中的表达及其临床意义

目的探讨雌激素受体(ER)、孕激素受体(PR)、p53蛋白(p53)、p16蛋白(p16)在子宫内膜癌组织中的表达及其临床意义。方法选取2017年1月至2021年5月于滁州市第一人民医院住院切除的子宫内膜癌组织57例作为研究组, 选取30例子宫内膜增生症患者的周围正常子宫内膜组织作为对照组。采用Envision法免疫组化染色, 观察ER、PR、p53、p16在子宫内膜组织中的表达及其与临床病理学特征间的关系。结果子宫内膜癌组ER、PR、p16的阳性表达率分别为70.2%、61.4%、38.6%, 均低于对照组的90.0%、86.7%、93.3%(χ2=4.36、5.98、24.09, 均P < 0.05);p53在子宫内膜癌组阳性表达率52.6%、明显高于对照组的13.3%(χ2=12.75, P < 0.001);有无淋巴结转移、肌层浸润程度、组织分级、病理分期等子宫内膜癌患者的ER、PR表达差异均有统计学意义(均P < 0.05);p53在病理分期、发病年龄、组织分级、肌层浸润程度、淋巴结转移中差异均无统计学意义(均P > 0.05);p16阳性表达率在子宫...     

子宫内膜癌组织雌、孕激素受体测定及其临床意义

目的探讨子宫内膜癌组织雌激素受体(ER)和孕激素受体(PR)与临床病理特征的关系。方法采用葡聚糖-活性炭吸附法(DCC法)对68例子宫内膜癌原发病灶组织进行ER、PR测定,同时采用免疫组化法对其中30例进行ER、PR检测。结果DCC法检测ER、PR的阳性率分别为79．4％和77．9％,免疫组化法均为86．7％。两种测定方法比较,ER与PR的总符合率分别为82．4％和95．7％。免疫组化法可在DCC法基础上进一步明确组织来源。ER、PR水平与组织学分级呈负相关。组织类型中腺癌(包括乳头状腺癌)与腺棘癌的ER、PR水平高于其他癌。ER水平与肥胖呈正相关。结论ER、PR水平与组织学分级、组织学类型均反映了子宫内膜癌的生物学行为,ER、PR的测定对估计预后和临床选择激素治疗具有重要意义。     

子宫内膜癌中Maspin、uPA、ER、PR的表达及临床意义

目的 探讨子宫内膜癌中Maspin蛋白、uPA蛋白及雌激素受体(ER)、孕激素受体(PR)间表达的相关性及临床意义.方法 对2004年6月至2014年6月病理科存档的蜡块,子宫内膜癌50例、不典型增生的子宫内膜50例及正常增殖期子宫内膜30例,采用免疫组化SP法,检测Maspin蛋白、uPA蛋白、ER、PR的表达情况,结合临床病理特征分析4种蛋白间表达的相关性.结果 Maspin蛋白、ER、PR在增殖期子宫内膜,不典型增生的子宫内膜,子宫内膜癌中阳性表达率逐渐降低,且组间比较有统计学意义(P＜0.05),而uPA的阳性表达率逐渐升高(P＜0.05).Maspin、uPA、ER、PR的阳性表达率在手术病理分期、肌层浸润深度及有无淋巴结转移组中的差异均有统计学意义(P＜0.05).Maspin和ER、PR的表达呈一致性,Maspin与uPA呈负相关(r=-0.341,P＜0.05),uPA和ER呈负相关(r=-0.293,P＜0.05).结论 ER、PR的减少,Maspin蛋白表达的缺失,伴随uPA蛋白表达上调,四者均参与了子宫内膜癌的发生、发展、浸润等过程,有可能成为判断子宫内膜癌治疗及预后的指标.     

ER与C-erbB-2在子宫内膜癌中的表达及意义

目的 分析雌激素受体(ER)、C-erbB-2在子宫内膜癌中的表达及意义.方法 通过应用免疫组化技术对47例子宫内膜癌组织中ER和C-erbB-2的表达水平进行检测分析,探讨其意义.结果 显示ER在正常子宫内膜组织中的表达率为100%,在子宫内膜癌组织中的阳性表达率为55.3%,差异有统计学意义(P＜0.05);不同临床分期、组织学分级的子宫内膜癌患者ER阳性表达率相比,差异有统计学意义(P＜0.05).C-erbB-2在子宫内膜癌组织中的阳性表达率为51.1%,与正常子宫内膜组织中的12.0%相比,差异有统计学意义(P＜0.05);不同临床分期、组织学分级的子宫内膜癌患者C-erbB-2阳性表达率相比,差异有统计学意义(P＜0.05).ER与C-erbB-2在子宫内膜癌组织中的表达有相关性(P＜0.05).结论 ER、C-erbB-2二者在子宫内膜癌的发生、发展中发挥重要作用,联合检测ER与C-erbB-2在子宫内膜癌中的表达,对子宫内膜癌的诊断、预后判断以及治疗有一定的指导意义.     

ER与C-erbB-2在子宫内膜癌中的表达及意义

目的分析雌激素受体(ER)、C-erbB-2在子宫内膜癌中的表达及意义。方法通过应用免疫组化技术对47例子宫内膜癌组织中ER和C-erbB-2的表达水平进行检测分析,探讨其意义。结果显示ER在正常子宫内膜组织中的表达率为100%,在子宫内膜癌组织中的阳性表达率为55.3%,差异有统计学意义(P<0.05);不同临床分期、组织学分级的子宫内膜癌患者ER阳性表达率相比,差异有统计学意义(P<0.05)。C-erbB-2在子宫内膜癌组织中的阳性表达率为51.1%,与正常子宫内膜组织中的12.0%相比,差异有统计学意义(P<0.05);不同临床分期、组织学分级的子宫内膜癌患者C-erbB-2阳性表达率相比,差异有统计学意义(P<0.05)。ER与C-erbB-2在子宫内膜癌组织中的表达有相关性(P<0.05)。结论 ER、C-erbB-2二者在子宫内膜癌的发生、发展中发挥重要作用,联合检测ER与C-erbB-2在子宫内膜癌中的表达,对子宫内膜癌的诊断、预后判断以及治疗有一定的指导意义。     

癌基因蛋白c-erbB-2在子宫内膜癌中的表达

目的 探讨子宫内膜癌中癌基因蛋白c—erbB—2、ER及PR的表达与临尿病理特点的关系。方法 应用免疫组化SP法检测28例子宫内膜癌中c—erbB—2、ER及阳的表达。结果 28例子宫内膜癌中c—erbB—2、ER及PR的阳性表达率分别为53．57％(15/28)、67．85％(19／28)和60．71％(17/28)。c-erbB-2与ER、PR表达呈负相关，与子宫内膜癌病理分级呈正相关。结论 子宫内膜癌中c—erbB-2、ER及PR的表达可作为估计子宫内膜癌预后的重要指标。     

Effect of nonpersistent pesticides on estrogen receptor,androgen receptor,and aryl hydrocarbon receptor

Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos‐methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC₅₀‐values of 3.7 and 9.0 μM, respectively) and had time‐dependent effects on endogenous ERα‐target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF‐7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos‐methyl were AhR‐agonists (EC₅₀s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos‐methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1201–1216, 2014.     

International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor

The nuclear receptors of the NR1H and NR1I subgroups include the constitutive androstane receptor, pregnane X receptor, farnesoid X receptors, liver X receptors, and vitamin D receptor. The newly emerging functions of these related receptors are under the control of metabolic pathways, including metabolism of xenobiotics, bile acids, cholesterol, and calcium. This review summarizes results of structural, pharmacologic, and genetic studies of these receptors.     

Cell autonomy, receptor autonomy, and thermodynamics in nicotine receptor up-regulation

Chronic nicotine exposure, in smokers or in experimental rodents administered nicotine, produces elevated levels of nicotinic acetylcholine receptors in several brain regions. However, there are few data on up-regulation of receptors in specific neuronal subtypes. We tested whether functional up-regulation of nicotinic responses occurs in cultured GABAergic neurons of the ventral midbrain. Fura-2 measurements of nicotinic responses were made on ventral midbrain neurons from knock-in mice heterozygous for the alpha4-M2 domain Leu9'Ala mutation, which confers nicotine hypersensitivity. Chronic nicotine exposure at a concentration (10 nM for 3 days) that activates only the hypersensitive alpha4* (Leu9'Ala) receptors, but not wild-type receptors, resulted in significant potentiation of ACh (100 microM)-elicited responses. Experiments were also performed on midbrain neuronal cultures heterozygous for the alpha4* (Leu9'Ala) mutation as well as for a GFP protein fused to a GABA transporter that reliably reveals GABAergic neurons. In cultures chronically treated with 10nM nicotine, there was significantly increased alpha4* nicotinic-induced Ca(2+) influx elicited by low concentration of ACh (3 microM). Furthermore, chronic exposure to the competitive antagonist dihydro-beta-erythroidine, but not to the noncompetitive antagonist mecamylamine, induced up-regulation of ACh elicited nicotinic responses. These results suggest that occupation of alpha4* nicotinic receptor binding site(s), at the interface between two subunits, is sufficient to promote assembly and/or up-regulation of functional receptors in GABAergic neurons. Up-regulation in neurons is both "cell-autonomous", occurring at the cell itself, and "receptor autonomous", occurring at the receptor itself, and may be a thermodynamic necessity of ligand-protein interactions.     

Fmc，镰刀菌来源的多巴胺1受体抑制剂

应用以中枢神经系统为主的八个体外受体筛选系统,从15株真菌和12株放线菌中筛选出能产生具有与多巴胺1受体竞争性结合活性的镰刀菌Fusarium moniliflore;从其菌体中分离出活性成分Fmc。通过元素分析和质谱,确定其分子式为C10H13O2N。综合紫外光谱、红外光谱、^1H-NMR和^13C-NMR等图谱数据的解析,确定Fmc的结构与镰刀属真菌（Fusarium moniliflore)发酵液分离出来的夫西地酸（fusaric acid)一致,化学命名为：5－正丁基吡啶酸。但关于其作用于中枢神经系统多巴胺1受体的活性未见报道。     

Role of mPKCI, a novel mu-opioid receptor interactive protein, in receptor desensitization, phosphorylation, and morphine-induced analgesia

The human mu-opioid receptor (HmuOR) is a G-protein coupled receptor that mediates analgesia, euphoria and other important central and peripheral neurological functions. In this study, we found in a yeast two-hybrid screen that a protein kinase C-interacting protein (PKCI) specifically interacts with the C terminus of HmuOR. The interaction of PKCI with HmuOR was recapitulated in Chinese hamster ovary cells that express the full-length HmuOR and PKCI proteins. The affinity of HmuOR for an opioid ligand and its ability to mediate the activation of a G-protein were not altered by their interaction. However, the association of PKCI with HmuOR reduced agonist-induced inhibition of adenylyl cyclase and suppressed HmuOR desensitization partially at the G protein level and completely at the adenylyl cyclase level. Furthermore, PMA-induced, but not DAMGO-induced, HmuOR phosphorylation was partially inhibited by the coexpression of PKCI, suggesting that PKCI exerts a selective regulatory effect on HmuOR signaling. This effect was specific to the mu-opioid receptor because delta-opioid receptor desensitization was unaffected by PKCI. In addition, behavioral studies revealed that both basal and morphine-induced analgesia were significantly enhanced in the mutant mice that lacked expression of PKCI gene, and these mice developed a greater extent of tolerance to morphine analgesia. Taken together, these results suggest that PKCI functions as a negative regulator in HmuOR desensitization, phosphorylation, and in mediating morphine analgesia.