胃癌组织中p27KIP1和MMP-9的表达及其临床意义

目的：探讨p^27KIP和MMP－9在胃癌中的表达其与临床病理参数之间的关系。方法：采用免疫组化S－P法检测56例胃癌中p^27KIP和MMP－9蛋白的表达。结果：p^27KIP和MMP－9蛋白在胃癌中的阳性率分别为46．4％和53．6％。p^27KIP蛋白的表达与肿瘤的分化程度、Lauren分型、淋巴结转移和浸润深度有关（P＜0．05），MMP－9的表达只与胃癌的Lauren分型、淋巴结转移和浸润深度有关（P＜0．05），而与分化程度无关（P＞0．05）。结论：p^27KIP蛋白低表达参与了胃癌的发展，MMP－9可能在胃癌的侵袭和转移中发挥作用。     

胃癌组织中腺苷酸激酶4和HIF-1α的表达及其临床意义

目的观察胃癌组织中腺苷酸激酶4(adenylate kinase 4, AK4)和低氧诱导因子1α(hypoxia-inducible factor-1α, HIF-1α)的表达,探讨AK4和HIF-1α在胃癌发生、发展过程中的作用及其相关性。方法采用免疫组化EnVision法检测79例胃癌及其癌旁正常组织中AK4和HIF-1α蛋白表达,分析两者表达与胃癌临床病理特征之间的关系以及两者表达的相关性。结果胃癌组织中AK4和HIF-1α的高表达率分别为73.4%和69.6%,明显高于癌旁正常组织(25.3%和16.5%)(P0.05)。AK4高表达与胃癌淋巴结转移、脉管侵犯和临床分期密切相关(P0.05),与患者性别、年龄、Lauren分型、分化程度及浸润深度无关(P0.05);HIF-1α高表达与肿瘤Lauren分型、淋巴结转移及临床分期有关(P0.05),与患者性别、年龄、分化程度、浸润深度和脉管侵犯等无关(P0.05)。胃癌组织中AK4和HIF-1α表达呈正相关(P0.05)。结论 AK4和HIF-1α协同作用参与了胃癌的发生、发展。AK4和HIF-1α联合检测可有助于预测胃癌的生物学行为。     

Fra-1在胃癌中的表达与意义

目的:检测Fra-1在人胃癌、癌旁组织中的表达情况以及与临床病理参数之间的关系,以探讨Fra-1在胃癌发生、发展中的作用.方法:采用免疫印记技术检测50例人胃癌组织和30例相应癌旁组织中Fra-1的表达情况.并结合临床病理资料,分析其临床意义.结果:50例胃癌组织标本中40例Fra-1阳性表达,阳性率80%;而30例癌旁组织中17例Fra-1阳性表达,阳性率56.67%.利用免疫印记技术测得胃癌、癌旁组织中Fra-1相对表达量分别为(0.735±0.374)和(0.099±0.092),Fra-1在胃癌组织中的相对表达量较癌旁组织高(P＜0.01).胃癌组织Fra-1的相对表达量与有无淋巴结转移、TNM分期相关(P＜0.05),而与患者性别、年龄、肿瘤大小及病理分级无关(P＞0.05).结论:Fra-1可能参与胃癌的形成,并在胃癌的发展、侵袭及转移中起重要作用.但其具体作用机制仍有待进一步深入研究.     

Rac1和Pak1在胃癌中的表达及意义

目的:探讨胃癌组织中Ras相关的C3肉毒素底物1(Ras related C3 botulinum toxinsubstrate 1,Racl)和p21蛋白活化激酶1(p21- activated kinase 1, Pak1)蛋白的表达特点及其与胃癌侵袭、转移的关系.方法:收集60例胃癌及20例癌旁正常组织标本,采用免疫组织化学方法检测Rac1和Pak1的蛋白表达水平.结果:在胃癌组织中Rac1和Pak1的表达阳性率均高于周围正常组织(P<0.05);Rac1和Pak1的表达呈正相关(r=0.383,P<0.01),它们的表达均与肿瘤分化程度、浸润深度、Lauren分型和有无淋巴结转移有关.结论:Rac1和Pak1的表达与胃癌浸润、转移密切相关,并有可能作为反映其生物学行为的一种新型标志物.     

子宫颈鳞状细胞癌中DLC-1和Cyclin D1的表达及其相关性分析

目的 观察肝癌缺失基因-1(deleted in liver cancer-1,DLC-1)和Cyclin D1在正常子宫颈组织、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及子宫颈鳞状细胞癌(cervical squamous cell carcinoma,CSCC)中的表达,并探讨二者与CSCC临床病理参数间的关系.方法 应用免疫组化SP法及逆转录-聚合酶链反应法(RT-PCR)检测DLC-1和Cyclin D1在正常子宫颈组织、CIN及CSCC中的表达,采用统计学软件SPSS 19.0对数据进行分析.结果 (1)DLC-1在正常子宫颈组织、CIN及CSCC中的阳性率依次降低,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,结合RT-PCR结果,差异具有统计学意义(P＜0.05);(2) Cyclin D1在正常子宫颈组织、CIN和CSCC中的阳性率依次升高,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,结合RT-PCR结果,差异具有统计学意义(P ＜0.05);(3) DLC-1和Cyclin D1在CSCC中的表达呈负相关(r=-0.526,P＜0.001).结论 DLC-1低表达和Cyclin D1高表达与CSCC的发生、发展和侵袭、转移相关,二者联合检测可作为CSCC诊断、治疗的重要判断指标.     

胃癌组织中BMAL1、GLI1的表达及意义

目的探讨BMAL1、GLI1蛋白在胃癌组织中的表达及临床意义。方法采用免疫组化EliVision两步法检测BMAL1、GLI1蛋白在胃癌及癌旁组织中的表达,分析两者表达与胃癌临床病理特征的关系及两者表达的相关性。结果与癌旁组织相比,BMAL1和GLI1蛋白在胃癌组织中的表达上调(P<0.01),阳性率分别为86.7%和83.3%。BMAL1过表达与胃癌淋巴结转移和TNM分期相关(P<0.05),GLI1过表达与胃癌浸润深度、淋巴结转移和TNM分期相关(P<0.05),两者在胃癌中的表达与其余临床病理特征均无关(P>0.05)。BMAL1和GLI1在胃癌中的表达呈正相关(r s=0.526,P<0.001)。结论BMAL1、GLI1与胃癌的发生、发展密切相关,在胃癌演进过程中两者可能起协同作用。     

胃癌中SPARC、TGFβ1和Ki-67的表达及意义

目的 探讨胃癌组织中SPARC和TGFβ1的表达及其与胃癌细胞增殖的关系.方法 用免疫组织化学方法检测80例胃癌组织和30例癌旁正常组织中SPARC、TGFβ1和Ki-67的表达.结果 (1)SPARC在胃癌中的阳性率高于正常胃黏膜(P=0.001)并主要表达于胃癌间质纤维母细胞的胞质,且与胃癌的分化程度、临床分期、Lauren分型及淋巴结转移相关有显著性(P<0.05);(2)胃癌中TGFβ1的阳性率和Ki-67标记指数均高于正常胃黏膜(P<0.001),且均与浸润深度、临床分期和淋巴结转移相关(P<0.05);(3)随着胃癌组织中SPARC的减少及TGFβ1的增多,Ki-67标记指数逐渐增大,且差异有显著性(P<0.05).结论 胃癌组织中SPARC抑制癌细胞的生长,而TGFβ1则促进癌细胞的生长,它们在胃癌的发生、发展中起着重要的作用.     

食管鳞状细胞癌组织中B7-H3和CD44的表达及其临床意义

目的探讨食管鳞状细胞癌组织中B7-H3和CD44的表达及其临床意义。方法采用免疫组化SP法检测128例食管鳞状细胞癌组织和64例癌旁正常组织中B7-H3与CD44的表达,分析B7-H3、CD44表达与临床病理特征的关系及两者的相关性。结果 B7-H3和CD44在食管鳞状细胞癌组织中的阳性率均明显高于癌旁正常组织(P均0.05)。B7-H3高表达与肿瘤分化程度、浸润深度、pTNM分期及淋巴结转移密切相关(P0.05),与患者性别、年龄、肿块大小均无关(P0.05)。CD44高表达与肿瘤浸润深度、pTNM分期及淋巴结转移有关(P0.05),与患者性别、年龄、肿块大小、肿瘤分化程度均无关(P0.05)。B7-H3与CD44在食管鳞状细胞癌组织中的表达呈正相关(r=0.333,P0.05)。结论 B7-H3、CD44均与食管癌侵袭性及淋巴结转移关系密切,且两者表达呈正相关,提示B7-H3和CD44协同参与肿瘤的进展,促进肿瘤转移。     

幽门螺旋杆菌感染性胃癌组织中Cyclin D1、MMP-9的表达及意义

目的探讨幽门螺旋杆菌(helicobacter pylori,HP)感染性胃癌组织中Cyclin D1、MMP-9的表达及临床意义。方法收集重庆市肿瘤医院手术切除的胃癌组织104例,分为HP阳性组(n=56)和HP阴性组(n=48),另收集40例癌旁正常胃组织作为对照组。采用免疫组化SP法检测各组中Cyclin D1和MMP-9蛋白的表达,分析两者表达与胃癌临床病理特征、HP感染的关系及其对预后的影响。结果 HP阳性组Cyclin D1和MMP-9阳性率高于HP阴性组和对照组,差异有统计学意义(P 0. 017);临床分期Ⅲ+Ⅳ期、分化程度低、有淋巴结转移者的Cyclin D1和MMP-9阳性率明显高于临床分期Ⅰ+Ⅱ期、分化程度高、无淋巴结转移者(P 0. 05); Cyclin D1和MMP-9均与HP感染呈正相关(rs=0. 504,rs=0. 532,P均0. 05); HP阳性、Cyclin D1和MMP-9阳性者生存期均显著较短(P均0. 05)。结论 Cyclin D1和MMP-9在HP感染性胃癌组织中表达上调,与HP共同促进胃癌的发生、发展,影响预后。     

Wnt信号通路成员蛋白NKD1、β-catenin和Cyclin D1在结直肠腺癌中的表达及意义

目的观察NKD1、β-catenin和Cyclin D1蛋白在结直肠正常黏膜、腺瘤和腺癌组织中的表达,探讨NKD1、β-catenin和Cyclin D1在结直肠正常黏膜-腺瘤-腺癌这一癌变过程中的表达变化及临床意义。方法应用免疫组化SP法检测38例结直肠正常黏膜、70例腺瘤、128例腺癌组织中NKD1、β-catenin和Cyclin D1蛋白的表达。结果 NKD1在结直肠正常黏膜、腺瘤、腺癌组织中的阳性率依次降低(P0.05),其在轻度异型增生腺瘤组织中的阳性率高于重度异型增生腺瘤组织(P0.05);β-catenin异位表达率与Cyclin D1阳性率在结直肠正常黏膜、腺瘤、腺癌组织中均依次升高(P0.01),且Cyclin D1在重度异型增生腺瘤组织中的阳性率高于中度及轻度异型增生腺瘤(P0.05)。NKD1、β-catenin、Cyclin D1在结直肠腺癌组织中的表达均与癌分化程度、Duke分期、淋巴结转移有关(P0.05)。在结直肠腺癌组织中NKD1的阳性率和β-catenin异位表达率呈负相关(r_s=-0.645,P0.01)。在结直肠腺癌组织中β-catenin异位表达率和Cyclin D1阳性率呈正相关(r_s=0.618,P0.01)。结论 NKD1、β-catenin、Cyclin D1三者可能参与结直肠肿瘤的发生、发展,有望成为评价结直肠腺癌恶性程度及预后的指标。     

NDE1 and NDEL1: Multimerisation,alternate splicing and DISC1 interaction

Nuclear Distribution Factor E Homolog 1 (NDE1) and NDE-Like 1 (NDEL1) are highly homologous mammalian proteins. However, whereas NDEL1 is well studied, there is remarkably little known about NDE1. We demonstrate the presence of multiple isoforms of both NDE1 and NDEL1 in the brain, showing that NDE1 binds directly to multiple isoforms of Disrupted in Schizophrenia 1 (DISC1), and to itself. We also show that NDE1 can complex with NDEL1. Together these results predict a high degree of complexity of DISC1-mediated regulation of neuronal activity.     

HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients

Japanese MS patients and controls were examined for the distribution of HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 alleles using in vitro amplification of genomic DNA and probing with sequence-specific oligonucleotides. No significant difference in frequency of the examined alleles was observed among the two groups. This is in contrast to Norwegian MS patients, where an association to a combination of certain DQA1 and DQB1 alleles has previously been demonstrated.     

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.     

AhR途径,CYP1A1、CYP1B1,雌激素代谢及作用过程中的调节

多环芳烃和多卤化烃是环境中广泛分布的有害物质,可通过与细胞芳烃受体结合,从而影响外来化合物代谢酶系如细胞色素氧化酶P450 1A1、1B1的表达,并通过这些酶的催化作用调控雌激素的代谢及作用,进而部分决定了雌激素对机体的作用效应。上述复杂的过程可受到多种因素的影响。     

Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset

Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction involving auto-reactive T-cells, pro-inflammatory cytokines, reactive oxygen species (ROS) and loss of insulin. Monozygotic twin studies show a 20–60% concordance with T1D indicating there may be an environmental component to the disease. Glutathione (GSH) is the major endogenous antioxidant produced by the cell. GSH participates directly in the neutralization of free radicals and plays a role in the immune response. Glutathione-s-transferases (GSTs) conjugate GSH to free-radicals or xenobiotics. GST activity depletes GSH levels and may either detoxify or enhance the toxicity of a compound. Glutathione-s-transferase mu 1 (GSTM1) and glutathione-s-transferase theta 1 (GSTT1) have polymorphic homozygous deletion (null) genotypes resulting in complete absence of enzyme activity. GSTM1 and GSTT1 null genotypes in Caucasian populations have frequencies of approximately 40–60% and 15–20%, respectively. GST null genotypes have been associated with susceptibility to cancer and protection against chronic pancreatitis. The aim of this study was to investigate associations with GSTM1 and GSTT1 polymorphisms in a group T1D patients and control subjects 0–35 years old who participated in the Combined Swedish Childhood Diabetes Registry and Diabetes Incidence Study (1986–1988). Results show that the presence of the GSTM1 and not the null genotype (OR, 2.13 95% CI, 1.23–3.70, p-value, 0.007, Bonferroni corrected p-value, 0.035) may be a susceptibility factor in T1D 14–20 years old. These results suggest that the GSTM1 null genotype is associated with T1D protection and T1D age-at-onset and that susceptibility to T1D may involve GST conjugation.     

韩国人CYP450 1A1、CYP450 2E1和GSTM1、GSTT1、GSTP1基因座遗传多态性分析

目的 调查代谢相关的CYP4501A1、CYP4502E1和GSTM1、GSIT1、GSTP1基因座在韩国人群中的遗传多态性分布状况。方法 采用多重聚合酶链式反应、聚合酶链式反应-限制性片段长度多态性技术，分析300名韩国健康大学生的CYP1A1基因3′端限制性内切酶Msp Ⅰ位点、CYP2E1基因5′端转录调节区Pst Ⅰ位点和GSTM1、GSTT1缺失与存在、GSTP1基因第5外显子BsmA Ⅰ位点的基因型，计算基因型和基因频率。结果 CYP1A1基因型频率为ml／ml型39．7％、ml／m2型49．7％、m2／m2型10．7％，基因频率为ml 0．645、m2 0．355。CYP2E1基因型频率为cl／cl型66．7％、cl／c2型30％、c2／c2型3．3％，基因频率为C1 0．818、C2 0．182。GSTM1基因缺失型频率为53．3％。GSTT1基因缺失型频率为54．7％。GSTP1基因型频率为Ile／Ile型62％、Ile／Val型34．3％、VaL／Val型3．7％，基因频率为Ile 0．792、Val 0．208。基因分布符合Hardy-Weirtberg平衡定律。结论 韩国人CYP1A1、CYP2E1、GSTM1、GSTT1基因分布与我国人群较为相近，半数以上人缺乏GSTM1和GSTT1基因，纯合缺失型频率超过印度人的3倍。     

Circulatinglong non-coding RNA FEZF1-AS1 and AFAP1-AS1 serve as potential diagnostic biomarkers for gastric cancer

BackgroundGrowing evidence indicates that two long non-coding RNAs (lncRNAs), FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) and Actin filament associated protein 1 antisenseRNA1 (AFAP1-AS1), are highly expressed in different cancers, including gastric cancer (GC). However, the expression pattern and clinical utility of these two lncRNAs are still unknown.MethodsSerum expression levels of FEZF1-AS1 andAFAP1-AS1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). CEA and CA19-9 were detected by ARCHITET I2000 SR. Analyses were all performed using SPSS software version 20.0 (SPSS Inc., Chicago, USA). P < 0.05 was considered statistically significant.ResultsDetection of serum FEZF1-AS1 and AFAP1-AS1 showed both of them were up-regulated in GC patients compared with the normal controls (p < 0.0001), and high serum expression levels were correlated with tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis. Besides, the area under the ROC curve (AUC) demonstrated the two lncRNAs had higher diagnostic utility than CEA and CA19-9. Furthermore, when combined the two lncRNAs as a model, it yielded an AUC of 0.866, and the combination of the model, CEA and CA19-9 could observably improve diagnostic sensitivity to 95.5 %. What’s more, circulating FEZF1-AS1 and AFAP1-AS1 were significantly decreased after the GC patients underwent the operation (both p < 0.001).ConclusionOur study indicated that serum FEZF1-AS1 and AFAP1-AS1 had better sensitivity and efficiency for the diagnosis of GC and the combination of the two lncRNAs might be used as a potential prognostic indicator in GC.     

DLA-DRB1 and DLA-DQB1 histocompatibility typing by PCR-SSCP and sequencing

Abstract: The dog has been an important model for solid organ and hematopoietic stem cell transplantation for over 30 years. Fundamental to the continuing usage of the model is the development of molecular-based histocompatibility typing of donors and recipients. Previous histocompatibility typing methods used in the dog have not been precise enough to identify dog leukocyte antigen (DLA)-matched unrelated dogs. This study was undertaken to begin the process of identifying DLA-matched unrelated dogs. In this study polymerase chain reaction-single-stranded conformational polymorphism is used to separate alleles thereby allowing sequenced-based typing of the two most polymorphic class II genes described to date in the dog - DLA-DRB1 and DLA-DQB1.     

非小细胞肺癌中Notch1、HIF-1、VEGF蛋白及Notch1 mRNA的表达及意义

目的 探讨Notch1、HIF-1、VEGF蛋白及Notch1 mRNA在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织的表达及其临床病理学意义.方法 采用免疫组化SP法和原位杂交法分别检测65例NSCLC组织、15例正常支气管上皮组织中Notch1、HIF-1、VEGF蛋白及Notch1 mRNA的表达.结果 Notch1、HIF-1、VEGF蛋白及Notch1 mRNA在非小细胞肺癌中阳性表达率分别为81.5%(53/65)、96.9%(63/65)、93.8%(61/65)、73.8%(48/65),均明显高于正常支气管上皮组织阳性表达率(P<0.05);NSCLC中Notch1、HIF-1、VEGF蛋白及Notch1 mRNA的表达均与临床分期、淋巴结转移有关(P<0.05);Notch1、HIF-1与VEGF蛋白间均正相关;Notch1蛋白与Notch1 mRNA的表达呈正相关.结论Notch1、HIF-1、VEGF蛋白及Notch1 mRNA在NSCLC中均表达上调,提示在肺癌的发生、发展中可能起重要作用;检测NSCLC组织Notch1蛋白及mRNA可作为判断肿瘤侵袭与转移的重要指标.