三阴性乳腺癌中CK5/6和PTEN的表达及其临床病理意义

[摘要]　目的　探讨三阴性乳腺癌组织中CK5/6和PTEN的表达及其临床病理意义。　方法　　通过免疫组化方法检测68例三阴性乳腺癌组织和22例正常乳腺组织CK5/6和PTEN的表达,分析两者的表达水平与临床病理特征及预后的关系。　结果　CK5/6在三阴性乳腺癌组织阳性率为52.9%（36/68）,明显高于正常乳腺组织9.1%（2/22）（P<0.05）。PTEN在三阴性乳腺癌组织阳性率为55.9%（38/68）,明显低于正常乳腺组织90.9%（20/22）（P<0.05）。CK5/6和PTEN表达在肿瘤直径<5 cm和≥5 cm间,淋巴结转移数目<5个和≥5个间及是否远处转移间比较,差异均有显著性意义（P<0.05）。三阴性乳腺癌CK5/6阳性组及PTEN阴性组患者的生存时间显著短于CK5/6阴性组及PTEN阳性组（P<0.05）。　结论　　三阴性乳腺癌CK5/6表达和PTEN表达缺失与肿瘤大小、淋巴结转移数目及远处转移有关,CK5/6表达和PTEN表达缺失提示患者预后不良。     

蛋白激酶CK2α与食管癌发生发展及临床病理因素的相关性研究

目的 探讨蛋白激酶CK2α在食管癌发生发展中的作用及其与食管癌的临床分期、病理类型之间的关系.方法 采用免疫组织化学法检测该院收治的120例食管癌患者癌组织及癌旁组织中蛋白激酶CK2α蛋白的表达水平,采用实时定量聚合酶链反应(qRT-PCR)和Western blot技术对其中的19例患者的术后标本的蛋白和mRNA进行检测.比较癌组织和癌旁组织中的蛋白激酶CK2α蛋白和mRNA表达差异.结果 食管癌组织中的CK2α中阳性与强阳性表达率分别高于癌旁组织(P＜0.05).CK2α阳性表达情况在不同T分期、淋巴结转移间差异无统计学意义(P＞0.05),CK2α阳性表达分布在不同临床TNM分期间差异有统计学意义(P＞0.05).CK2α蛋白、CK2αmRNA在食管癌组织的表达均显著的高于癌旁组织(P＜0.05).结论 蛋白激酶CK2α与食管癌的发展有着一定的关系,可以作为临床上对食管癌病变程度的一种分子判定标准.     

Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat experimental hepatopulmonary syndrome

BACKGROUND & AIMS: Hepatic production and release of endothelin 1 plays a central role in experimental hepatopulmonary syndrome after common bile duct ligation by stimulating pulmonary endothelial nitric oxide production. In thioacetamide-induced nonbiliary cirrhosis, hepatic endothelin 1 production and release do not occur, and hepatopulmonary syndrome does not develop. However, the source and regulation of hepatic endothelin 1 after common bile duct ligation are not fully characterized. We evaluated the sources of hepatic endothelin 1 production after common bile duct ligation in relation to thioacetamide cirrhosis and assessed whether transforming growth factor beta1 regulates endothelin 1 production. METHODS: Hepatopulmonary syndrome and hepatic and plasma endothelin 1 levels were evaluated after common bile duct ligation or thioacetamide administration. Cellular sources of endothelin 1 were assessed by immunohistochemistry and laser capture microdissection of cholangiocytes. Transforming growth factor beta1 expression and signaling were assessed by using immunohistochemistry and Western blotting and by evaluating normal rat cholangiocytes. RESULTS: Hepatic and plasma endothelin 1 levels increased and hepatopulmonary syndrome developed only after common bile duct ligation. Hepatic endothelin 1 and transforming growth factor beta1 levels increased over a similar time frame, and cholangiocytes were a major source of each peptide. Transforming growth factor beta1 signaling in cholangiocytes in vivo was evident by increased phosphorylation and nuclear localization of Smad2, and hepatic endothelin 1 levels correlated directly with liver transforming growth factor beta1 and phosphorylated Smad2 levels. Transforming growth factor beta1 also stimulated endothelin 1 promoter activity, expression, and production in normal rat cholangiocytes. CONCLUSIONS: Cholangiocytes are a major source of hepatic endothelin 1 production during the development of hepatopulmonary syndrome after common bile duct ligation, but not in thioacetamide-induced cirrhosis. Transforming growth factor beta1 stimulates cholangiocyte endothelin 1 expression and production. Cholangiocyte-derived endothelin 1 may be an important endocrine mediator of experimental hepatopulmonary syndrome.     

前列腺癌CK5^+CK8^+细胞的分选及其分子生物学特性

目的在人前列腺癌细胞系中分选CK5^+CK8^+细胞,了解其分子生物学特性。方法流式细胞术在人前列腺癌细胞系PC3和LNCaP中分选CK5^+CK8^+细胞,用实时荧光定量聚合酶链反应(RT-PCR)和蛋白质印迹法方法检测LNCaP细胞分选的CK5^+CK8^+细胞CK5、CK8、雄激素受体(AR)和前列腺特异抗原(PSA)的表达,细胞迁移实验检测CK5^+CK8^+细胞迁移能力,琼脂糖凝胶克隆形成实验检测CK5^+CK8^+细胞成瘤能力。采用t检验进行统计学分析。结果采用流式细胞术可以在PC3中分选出(21.3±4.6)%的CK5^+CK8^+细胞,在LNCaP中分选出(1.2±0.4)%的CK5^+CK8^+细胞。与非CK5^+CK8^+细胞相比,LNCaP中分选的CK5^+CK8^+细胞CK5 mRNA表达差异有统计学意义(t=10.435,P<0.001),CK8 mRNA表达差异无统计学意义(t=1.974,P=0.121),AR和PSA mRNA表达差异有统计学意义(t=4.317,3.232;P=0.016,0.037)。蛋白质印迹法检测得到类似结果。细胞培养7 d后,CK5^+CK8^+细胞和非CK5^+CK8^+细胞均可以在Transwell小室迁移生长,迁移细胞数分别为(60±7)个和(32±5)个,2者比较差异有统计学意义(t=6.031,P=0.004)。细胞培养14 d后,CK5^+CK8^+细胞和非CK5^+CK8^+细胞均可以在软琼脂糖凝胶中克隆性生长,阳性克隆数分别为(71±5)个和(27±3)个,差异有统计学意义(t=13.009,P<0.001)。结论人前列腺癌细胞系LNCaP和PC3都可以分选出CK5^+CK8^+细胞,LNCaP中CK5^+CK8^+细胞AR和PSA均有一定程度表达,迁移和成瘤能力增强。     

脑脊液CK、Aβ42、P-tau在阿尔茨海默病中的诊断价值

目的探究脑脊液CK、Aβ42、P-tau在阿尔茨海默病中的诊断价值。方法选取2018年5月至2020年5月本院收治的40例阿尔茨海默病患者(AD)为研究对象,另选取40例轻度认知障碍期患者(MCI),40例血管性痴呆患者(VD),40例健康体检人员为对照组。采用ELISA法测定四组脑脊液CK、Aβ42、P-tau水平;以受试者工作特征曲线(ROC曲线)评估三者诊断AD的价值。结果脑脊液CK、Aβ42、P-tau水平比较,AD组、VD组、MCI组CK及P-tau水平均显著高于健康对照组(P<0.05),AD组、VD组、MCI组Aβ42均显著低于健康对照组差异均有统计学意义(P<0.05)。AD组CK、P-tau水平显著高于VD组(P<0.05),Aβ42水平显著低于MCI组、VD组(P<0.05);VD组CK、P-tau水平显著高于MCI组(P<0.05)。ROC曲线分析结果显示,脑脊液CK、Aβ42、P-tau水平分别取3.045 U/L、155.63 ng/L、182.32 ng/mL时诊断效能最高,AUC分别为0.816、0.690、0.790(95%CI:0.709~0.923、0.572~0.808、0.678~0.902);三项联合诊断AD的AUC为0.887(95%CI:0.816~0.958),敏感度为0.950、特异度为0.725。结论脑脊液CK、Aβ42、P-tau对阿尔茨海默病有一定诊断价值,三项联合诊断价值更高。     

胃癌患者外周血CK20mRNA的表达及临床意义

采集55例胃癌、46例良性胃病及正常献血员50例，应用逆转录多聚酶链反应（RT－PCR）技术研究外周血CK20mRNA的表达。结果：46例良性胃病及正常献血员50例外周血CK20mRNA均呈阴性，55例胃癌中有35例外周血CK20mRNA表达阳性，I、Ⅱ期20例中有7例外周血CK20mRNA表达阳性，表达率低于Ⅲ、Ⅳ期（28／35）；低、未分化腺癌38例中，30例外周血CK20mRNA表达阳性，高于高、中分化腺癌（5／17）。认为PT－PCR检测外周血CK20mRNA敏感性和特异性较高，可作为胃癌患者术前评估的指标之一。     

A critical review of the diagnosis and management of Barrett's esophagus: the AGA Chicago Workshop

BACKGROUND & AIMS: The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues. METHODS: A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion. RESULTS: There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia. CONCLUSIONS: Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.     

腹腔灌洗液中CK20m RNA水平与结直肠癌不同术式的研究

目的探讨腹腔灌洗液中CK20m RNA的临床意义以及腹腔镜直肠癌根治术的临床应用价值。方法选择49例直肠癌手术患者,利用RT-PCR技术分别检测以上患者腹腔灌洗液中CK20m RNA表达,从而探究CK20m RNA的临床价值以及评价腹腔镜直肠癌根治术的临床实用性。结果 10例良性病变腹部手术组患者腹腔灌洗液中CK20m RNA无明显表达。39例结直肠癌患者腹腔灌洗液中可见CK20m RNA表达,术前、术中以及术后的总表达率为40.2%(47/117),且术前、术中以及术后CK20m RNA的表达率比较差异无显著性(P0.05)。17例开腹手术组和22例腹腔手术组术前、术中以及术后CK20m RNA阳性表达率的比较差异无显著性(P0.05)。结论腹腔镜结直肠癌根治术治疗结直肠癌安全有效,与开腹手术相比并不增加癌细胞局部种植的风险。