E-cadherin、MMP-9及TIMP-1表达与大肠癌生物学行为及预后的关系

目的 探讨E-钙粘素(E-cadhefin)、基质金属蛋白酶-9(MMP-9)及其抑制剂(TIMP-1)表达与大肠癌生物学行为及预后的关系.方法 采用免疫组化染色法检测54例大肠癌组织标本中E.钙粘素、MMP-9及TIMP-1的表达情况,经结肠镜活检的大肠腺瘤组织标本15例作为正常对照.结果 E-cadherin的表达率在大肠腺瘤中为86.7%,显著高于大肠癌中55.6%的表达率,两者存在显著性差异(P<0.05).E-cadherin的表达与大肠癌的大体类型有关,且随着大肠癌分化程度的降低而减少.与浸润深度、淋巴结转移呈负相关(P<0.05).其表达率越高,患者的预后越好.大肠癌MMP-9和TIMP-1蛋白表达存在显著正相关(r=0.374,P<0.01).MMP-9的表达率在大肠腺瘤中为33.3%,显著低于大肠癌中的70.4%(P<0.05).其表达与大肠癌的浸润深度、Dukes分期、淋巴结转移及生存期均密切相关(P均<0.05).TIMP-1的表达在大肠腺瘤及大肠癌组织中没有显著性差异(P>0.05),但其表达与大肠癌组织学类型、分化程度、淋巴结转移密切相关,对预后无显著性影响(P>0.05).结论 E.钙粘素、MMP-9及TIMP-1对大肠癌生物学行为均有明显影响.E-钙粘素的正常表达将显著降低大肠癌的浸润和转移能力.MMP-9蛋白阳性表达促进大肠癌浸润和转移,患者预后欠佳.E-钙粘素、MMP-9和TIMP-1的检测可以成为临床判断大肠癌的生物学行为及预后的重要参考指标.     

转录调节因子Ets-1及MMPs在结直肠癌组织中的表达及意义

目的 探讨转录调节因子Ets-1、基质金属蛋白酶(MMPs)在结直肠癌组织中的表达及临床意义.方法 应用免疫组化法检测转录调节因子Ets-1、MMP-1、MMP-3在结直肠癌、大肠腺瘤及腺瘤伴异型增生组织中的表达.结果 Ets-1、MMP-1与MMP-3蛋白在大肠腺瘤、大肠腺瘤伴腺上皮异型增生及大肠癌组织中的阳性表达率依次递增.Ets-1、MMP-1、MMP-3高表达与1、3、5 a生存率呈负相关.Ets-1与MMP-1、MMP-3的表达呈正相关.结论 Ets-1、MMP1、MMP3在大肠癌的发生、发展、浸润及转移中发挥重要作用,与大肠癌患者的预后有关.     

大肠腺瘤及癌组织HIF-1α的表达与凋亡增生的关系

目的:研究缺氧诱导因子1-α(HIF-1α)在大肠肿瘤中的表达及其与凋亡、增生的关系,探讨HIF-1α在大肠癌发生发展中的作用. 方法:运用免疫组化的方法检测HIF-1α,Bcl-2,Bax, PCNA在正常大肠组织13例,大肠腺瘤26例,大肠癌50例中的表达. 结果:正常大肠组织HIF-1α均为阴性表达,腺瘤及癌组织中HIF-1α阳性表达率为30.8%和64%,大肠癌HIF-1α表达率显著高于腺瘤(x2=8.546,P<0.01).大肠癌HIF-1α表达与浸润,淋巴结转移,Dukes分期相关(x2=6.339, P<0.05;x2=9.091,P<0.01;x2=10.72,P<0.05).HIF- 1α表达与肿瘤大小、分化程度无关(P>0.05).Bcl-2在3 组中阳性表达率为15.4%,50.0%和76.0%,三者间表达率差别有显著意义(P<0.05).Bax在3组中阳性表达率为76.9%,65.4%和58.0%,三者间表达率无显著性差异(P>0.05).Bcl-2,Bax表达与肿瘤大小,分化,Dukes 分期无关(P>0.05).正常大肠组织PCNA表达均为低增生活性,腺瘤及癌中PCNA高增生活性者26.9%和56.0%, 癌组织PCNA高增生活性表达显著高于腺瘤(x2=5.073, P<0.05).大肠癌增生程度与浸润及Dukes分期相关(x2=6336, P<0.05;x2=11.219,P<0.01).腺瘤及大肠癌HIF-1α表达与Bcl-2,PCNA增生程度呈正相关(r=0.5,r=0.535, P<0.05;r=0.457,r=0.426,P<0.01),与Bax表达无关. 结论:HIF-1α抑制大肠肿瘤凋亡,促进增生,与肿瘤浸润转移密切相关,在大肠癌发生发展中发挥重要作用.     

大肠癌组织中PTEN和NDRG-1的表达及其相关性

目的探讨磷酸酯酶与张力蛋白同源物(PTEN)和分化相关基因(NDRG)-1在大肠癌中的表达及其相关性。方法应用免疫组织化学S-P法检测114例大肠癌组织及80例正常大肠组织中PTEN和NDRG-1的表达。结果大肠癌组织中PTEN蛋白表达显著低于正常大肠组织(P<0.01),与淋巴结转移及Dukes分期相关(P<0.05),而与大肠癌组织分化程度不相关(P>0.05)。NDRG-1在大肠癌中的表达显著低于正常大肠黏膜(P<0.01),与淋巴结转移及Dukes分期相关(P<0.05),而与大肠癌组织分化程度不相关(P>0.05)。PTEN在大肠癌中的表达与NDRG-1呈正相关(P<0.05)。结论 PTEN蛋白表达降低与大肠癌淋巴结转移及Dukes分期相关,且与NDRG-1呈正相关。抑癌基因PTEN和NDRG-1在大肠癌的发生发展过程中起重要作用。     

骨桥蛋白与缺氧诱导因子-1在大肠腺瘤及癌组织中的表达及意义

目的:探讨骨桥蛋白(OPN)及缺氧诱导因子-1α(HIF-1α)在大肠癌、大肠腺瘤及大肠正常组织中的表达程度及其与临床病理学之间的关系.方法:采用免疫组织化学SABC法检测50例大肠癌及24例大肠腺瘤、12例正常大肠组织病理标本OPN及HIF-1α的表达.结果:OPN及HIF-1α在正常组织中无表达,在大肠癌组织、腺瘤组织中为高表达.OPN的表达率在腺瘤组与肠癌组间比较差别无显著性.HIF-1α的表达率在腺瘤组与肠癌组间比较,差别有显著性(33.33%vs 62.00%,P<0.05).二者在肠癌组中的表达与肿瘤的浸润深度、淋巴结转移、Dukes分期呈正相关;与患者的性别、年龄、肿瘤的大小则无相关性.OPN与HIF-1α在大肠癌组织中的表达具有明显的相关性(r=0.700,P<0.01).结论:OPN及HIF-1α在大肠癌的浸润和转移中起重要作用;HIF-1α高表达的肿瘤组织具有较强的浸润与转移能力.     

Survivin、MMP-9在大肠腺瘤癌变过程中的表达及其临床意义

目的研究存活素(Survivin)和MMP-9在大肠腺瘤癌变过程中的表达,探讨他们在大肠癌发生、发展、浸润和转移中的作用及其相互关系。方法用免疫组化SABC法和原位杂交技术检测59例大肠腺癌、35例大肠腺瘤(包括21例低度异型增生和14例高度异型增生)和12例癌旁正常大肠黏膜组织中Survivin蛋白、SurvivinmRNA和MMP-9的表达。结果在大肠腺瘤-癌序列演变过程中,Survivin蛋白、mRNA和MMP-9的表达率逐渐升高;正常大肠黏膜、低度异型增生腺瘤与高度异型增生腺瘤、大肠癌间Survivin、MMP-9表达有显著性差异(P<0.05),大肠癌和高度异型增生腺瘤的Survivin、MMP-9表达无显著性差异(P>0.05);SurvivinmRNA阳性强度均低于蛋白表达水平;大肠癌组织中,Survivin的表达与临床病理分型之间均无相关性(P>0.05);MMP-9的表达与浸润深度、Dukes分期、淋巴道转移之间有显著性差异(P<0.05);Survivin与MMP-9两者在大肠腺瘤癌变过程中的表达密切相关(r=0.573,P<0.01)。结论Survivin在大肠腺瘤至癌的演变阶段起重要作用;MMP-9在大肠癌浸润、转移过程中起重要作用;Survivin蛋白表达的调控可能发生在转录以后水平;Survivin与MMP-9存在协同作用或相互调节机制,共同促进肿瘤的发生、发展、浸润和转移。     

大肠癌组织转化生长因子-β1、缺氧诱导因子-1α和血管内皮生长因子的表达及其临床意义

目的探究大肠癌组织中转化生长因子(TGF)-β1、缺氧诱导因子(HIF)-1α和血管内皮生长因子(VEGF)的表达及其临床意义。方法随机选取2010年5月至2012年5月住院治疗的大肠癌患者的癌组织(大肠癌组)和癌旁组织(癌旁组)各102例,对比分析两组TGF-β1、HIF-1α和VEGF的表达情况及其与临床病理参数和预后的相关性。结果大肠癌组TGF-β1、HIF-1α和VEGF总表达阳性率均显著高于癌旁组(P0.05);不同TNM分期和浸润深度的TGF-β1表达阳性率差异显著(P0.05),不同TNM分期、分化程度、浸润深度、是否存在淋巴结转移和远处转移的HIF-1α和VEGF表达阳性率差异显著(P0.05);TGF-β1、HIF-1α均与VEGF表达呈正相关(r=0.231、0.462,P0.05);HIF-1α和VEGF表达与患者预后密切相关,且HIF-1α和VEGF阳性表达者的生存时间显著低于阴性者(P0.05)。结论大肠癌组织中TGF-β1、HIF-1α和VEGF的表达有所上升,且表达水平与肿瘤的临床病理参数以及后期预后密切相关,三者联合检测对判断肿瘤侵袭转移和预测预后有一定的临床指导意义。     

热休克蛋白90、缺氧诱导因子-1α在大肠癌中的表达及意义

目的观察热休克蛋白90(HSP90)、缺氧诱导因子(HIF)-1α在大肠癌发生发展过程中的表达及意义。方法运用免疫组织化学法检测HSP90,HIF-1α两者在大肠癌及正常组织中的表达情况。结果 HSP90、HIF-1α在正常大肠组织,大肠腺癌中的阳性率分别为:30%、63.0%;15.0%、71.7%。两者在正常组织和大肠腺癌中的表达差异均有统计学意义(P=0.013,P<0.001)。HSP90蛋白的表达与大肠癌组织的分化程度,Duke分期及是否有淋巴结转移有关(P<0.05),HIF-1α的表达与Duke分期及是否有淋巴结转移有关(P<0.05);通过相关性分析,两者具有明显相关性(P<0.01)。结论 HSP90,HIF-1α可能与大肠腺癌的发生、浸润及转移有关;两者的协同作用可能参与了大肠癌的发生发展。     

27例大肠癌组织中LIMD1表达特点

目的探讨LIMD1在大肠癌组织中的表达特点。方法采用免疫组织化学法检测27例大肠癌患者及癌旁正常大肠黏膜组织中LIMD1表达情况。结果大肠腺癌、黏液癌、未分化癌中LIMD1阳性表达率分别为87.50%、85.71%、100%,大肠癌组织中LIMD1阳性表达率显著高于癌旁正常大肠黏膜组织(χ2=5.11,P0.05);LIMD1表达与大肠癌临床分期(Dukes分期)呈正相关。结论 LIMD1可能参与大肠癌的发生及演进。     

RECK,MMP-9及TGF-β1在胃癌组织中的表达及其相互关系

目的:研究RECK,MMP-9和TGF-β1在胃癌及正常胃组织中的表达,探讨其在胃癌的发生、发展、浸润和转移中的作用.方法:选择临床及病理资料齐全的存档胃腺癌蜡块标本54例,另取正常胃黏膜标本15例作对照.采用第二代通用型二步法监测系统(PV-9000)免疫组化方法检测RECK,MMP-9及TGF-β1在胃癌及正常胃组织中的表达.结果:RECK在胃癌组织中低表达(51.9%),并随肿瘤浸润深度的加深、淋巴转移的产生、远隔转移的发生、临床分期的提高、肿瘤病理分化程度的降低而降低(P<0.05).MMP-9在胃癌组织中高表达(75.9%),并随肿瘤浸润深度的加深、淋巴转移的产生、临床分期的提高、肿瘤病理分化程度的降低而增高(P<0.05).TGF-β1在胃癌组织中高表达(77.8%),并随淋巴转移的产生、临床分期的提高、肿瘤病理分化程度的降低而增高(P<0.05).胃癌组织中RECK与MMP-9、TGF-β1的表达呈负相关(r=-0.618,P<0.001;r=-0.620,P<0.001),MMP-9与TGF-β1的表达呈正相关(r=0.716,P<0.001).结论:胃癌组织中RECK低表达,MMP-9,TGF-β1高表达.RECK,MMP-9及TGF-β1可以作为评估胃癌发生浸润转移的重要指标.     

1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate

Abstract: The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.     

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands

Amodiaquine (AQ) is a 4‐aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short‐lived quinine‐imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar’s population regarding the appearance of adverse effects.     

Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1

Aims and background: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians.

Material and methods: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P?<?0.05 (compare 2, version 1.02).

Results: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P?=?0.0027, RR?=?18.27 (20.0061–915.28)).

Conclusion: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.     

Pandemic H1N1 influenza

The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.     

PD-1/PD-L1抑制途径与自身免疫性糖尿病

PD-1(CD279)是一种负性协同刺激分子,属于CD28超家族成员,呈诱导性表达于活化的T、B和自然杀伤细胞表面.PD-L1(B7-H1,CD274)和PD-L2(B7-DC,CD273)是PD-1的两个配体.PD-1和PD-L1相互作用可以使活化的自身反应性T细胞获得负性信号,抑制其对自身抗原持续的免疫应答.若PD...     

甲型H1N1与季节性H1N1流感病毒血凝素基因比较分析

目的分析泰安市2008～2009年度季节性流感与2009年度甲型H1N1流感病原学检测结果 ,比较季节性H1N1与甲型H1N1血凝素基因变异情况。方法选择国家级流感监测哨点医院以及暴发疫情的疫点,采集流感样病例的鼻咽拭子标本,通过RealtimePCR进行病毒检测,用MDCK细胞进行病毒分离,通过RT-PCR扩增血凝素HA1片段的基因并测序,利用生物信息学进行序列分析。结果 2008～2009年共检测鼻咽拭子标本283份,分离出流感病毒33株,分离阳性率为11.67%,其中季节性H1N1亚型31株。2009年5月1日～12月31日,检测鼻咽拭子标本996份,流感核酸检测阳性417份,阳性率为41.86%,其中甲型H1N1337份,季节性H1N1亚型1份。6株季节性H1N1病毒均在多个氨基酸位点上发生变异,与疫苗株A/Brisbane/59/2007(H1N1)比较,有11个位点发生了突变,其中5个位点位于抗原决定簇上;测序成功的6株甲型H1N1病毒在多个氨基酸位点发生变异,与疫苗株A/California/07/2009(H1N1)比较,有6个位点发生突变,其中1个位点位于抗原决定簇的B区。结论 2008～2009年度季节性H1N1为优势株,甲流暴发后,甲型H1N1成为绝对优势毒株。季节性H1N1分离株有多处氨基酸替换,抗原决定簇B区变异频繁;甲型H1N1病毒分离株的基因有变异,但关键位点第222位仍为D(天冬氨酸),与疫苗株相比抗原决定簇的关键位点变化不大。     

Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin

Abstract:  Administration of melatonin to rodents decreases the incidence of tumorigenesis initiated by benzo[ a ]pyrene or 7,12-dimethylbenz[ a ]anthracene, which requires bioactivation by cytochrome P450 enzymes, such as CYP1A1, CYP1A2 and CYP1B1, to produce carcinogenic metabolites. The present study tested the hypothesis that melatonin is a modulator of human CYP1 catalytic activity and gene expression. As a comparison, we also investigated the effect of melatonin on the catalytic activity of CYP2A6, which is also a procarcinogen-bioactivating enzyme. Melatonin (3–300 μ m ) decreased 7-ethoxyresorufin O -dealkylation catalyzed by human hepatic microsomes and recombinant CYP1A1, CYP1A2 and CYP1B1, whereas it did not affect coumarin 7-hydroxylation catalyzed by hepatic microsomes or recombinant CYP2A6. Melatonin inhibited CYP1 enzymes by mixed inhibition, with apparent K _i values (mean ± S.E.M.) of 59 ± 1 (CYP1A1), 12 ± 1 (CYP1A2), 14 ± 2 (CYP1B1) and 46 ± 8 μ m (hepatic microsomes). Additional experiments indicated that melatonin decreased benzo[ a ]pyrene hydroxylation catalyzed by hepatic microsomes and CYP1A2 but not by CYP1A1 or CYP1B1. Treatment of MCF-10A human mammary epithelial cells with melatonin (up to 300 μ m ) did not affect basal or benzo[ a ]pyrene-inducible CYP1A1 or CYP1B1 gene expression. Consistent with this finding, melatonin did not influence reporter activity in aryl hydrocarbon receptor-dependent pGudluc6.1-transfected MCF-10A cells treated with or without benzo[ a ]pyrene, as assessed in an in vitro cell-based luciferase reporter gene assay. Overall, melatonin is an in vitro inhibitor of human CYP1 catalytic activity, and it may be useful to develop potent analogues of melatonin as potential cancer chemopreventive agents that block CYP1-mediated chemical carcinogenesis.     

甲型H1N1流感合并肺炎的临床特点分析

目的通过对甲型H1N1流感合并肺炎的临床特点的分析。方法分析2009年月10月-2010年3月在我院入住的29例甲型H1N1流感合并肺炎患者的临床表现、实验室检查及胸部CT等资料。结果本组病例男性16例,女性13例。3例妊娠,13例合并有基础疾病。所有病例均有流感样前驱症状,呼吸道主要症状为发热、干咳少痰,严重者气短、呼吸困难、咯血。合并细菌感染时咯脓痰。肺部听诊无啰音或少啰音,合并哮喘时有哮鸣音,合并细菌感染时可有湿啰音。实验室检查65%白细胞不高或降低,41%心肌酶升高,58.6%存在低氧血症,35%呼吸衰竭。影像学表现多种多样：65.5%主要为单侧或双侧棉团样、团片样边界模糊高密度渗出影伴肺实变,其内见充气支气管征,病变沿支气管血管束分布。轻症及早期较局限,重症者及晚期病变融合呈双肺多发弥漫性改变。少数呈大叶及小叶性肺炎表现。预后大多良好,病死率6.9%。主要死亡原因为呼吸衰竭及大咯血。结论甲型H1N1流感合并肺炎是以甲型H1N1流感病毒肺炎为主要疾病的多种肺炎构成。甲型H1N1流感病毒肺炎临床表现具有流感病毒肺炎共性特点,其影像学表现有一定特征性。