V-ATPase:结构、功能及其在肿瘤细胞中的作用

真核细胞膜及管泡细胞器膜上广泛分布一种与H^ 主动转运有关的蛋白——V-ATPase。V-ATPase的结构由跨膜的V0和细胞质内的V1两个亚单位组成,前者为H^ 提供通道,后者能分解ATP,为逆浓度梯度转运H^ 提供能量。V0和V1只有在聚合时,V-ATPase全酶才有功能。肿瘤细胞中V-ATPase的过度表达或过度活跃,遏制了由酵解增强乳酸聚集导致的细胞内酸化趋势,使细胞避免了凋亡的命运。而H^ 排至细胞外,改变蛋白水解酶的活性,使细胞外基质分解增强,细胞更有侵袭力。肿瘤细胞的V-ATPase可望成为抑制细胞增生、扩散的有效靶点。     

中国湖南人群GSTM1和GSTT1基因多态性与肺癌易感性关系的研究

应用病例-对照分析研究(对照组205例,肺癌病例组104例),抽提静脉血基因组DNA,采用PCR及多重PCR方法,检测谷胱甘肽转移酶GSTM1和GSTT1单独及联合缺失基因型的遗传多态性在中国湖南人群中肺癌患者和正常人群体中的分布,探讨这些多态性基因型与肺癌易感性的关系.结果显示GSTM1-/-基因型在湖南地区居民肺癌群体和正常对照人群中的频率分别为62.5%和46.3%(P<0.05);肺癌患者组GSTT1-/-基因型的频率(66.3%)显著高于正常对照组(42.4%)(P<0.05).GSTM1-/-和GSTT1-/-联合基因型在肺癌组和正常对照组中的频率分别为41.3%和22.4%(P<0.05).SPSS11.5软件统计学分析表明,这些基因型在肺癌患者组和正常对照组人群中的发生频率具有显著性差异.由此可知GSTM1基因缺失和GSTT1基因缺失分别与肺癌的易感性相关;GSTM1和GSTT1基因联合缺失与肺癌的发生和发展呈现显著正相关.     

Effect of Variability in Pharmacokinetic Parameters on the Derivation of Exposure Limits for Pharmaceutical Compounds

The purpose of this study was to investigate how variability in pharmacokinetic parameters influences the determination of occupational exposure limits (OEL) for pharmaceutical compounds in potentially susceptible subpopulations. A compartmental pharmacokinetic model for quinidine was applied to derive OELs based on target blood concentrations in humans but relied on pharmacokinetic parameters in subjects with cirrhosis rather than normal subjects. Quinidine was used as the sample compound as this was used in the development of the methodology. The intent was not to set an OEL for quinidine for a particular population but rather to use the methodology to investigate how factors, which may influence susceptibility, could be incorporated into the analysis. The model was used to simulate exposure concentrations that would result in levels below those that cause undesirable pharmacological effects taking into account variability in parameters through incorporation of Monte Carlo sampling. Results indicate that cirrhotic patients did not require additional protection from occupational exposure to quinidine. These results cannot be extrapolated to other compounds, as the effects of variability in pharmacokinetics on systemic exposure are compound specific. However, this methodology does provide a framework for addressing issues related to the contribution of pharmacokinetics to susceptibility from occupational exposure to pharmaceutical compounds.     

人参皂苷-Rh2诱导肿瘤细胞凋亡信号转导通路研究进展

人参皂苷-Rh2诱导肿瘤细胞凋亡机制复杂,且不同机制间相互联系。它主要通过调节细胞周期蛋白依赖性激酶复合物特异性信号传递引发细胞周期阻滞诱导细胞凋亡,或通过调控细胞信号转导通路,如ROS、Ca2+、PKC、JNK介导的线粒体信号通路和TRAIL-R1(DR4)介导的死亡受体信号通路等诱导肿瘤细胞凋亡。     

Mapping markers linked to porcine salmonellosis susceptibility

The goal of this study was to identify pig chromosomal regions associated with susceptibility to salmonellosis. Genomic DNA from pig reference populations with differences in susceptibility to Salmonella enterica serovar Choleraesuis as quantified by spleen and liver bacterial colonization at day 7 post-infection (dpi; Van Diemen et al. 2002 ) was used. These samples belonged to the offspring of a sire thought to be heterozygous for genes involved in susceptibility to salmonellosis. Amplified fragment length polymorphism (AFLP) markers were created and used to determine associations with spleen or bacterial counts at 7 dpi. To position linked markers, two mapping populations, the Roslin and Uppsala PiGMaP pedigrees were used to create an integrated map which included the AFLP markers associated with salmonellosis. Twenty-six AFLP markers located in 14 different chromosomal regions in the porcine genome were found to be significantly associated with susceptibility (Chi-square P  < 0.05). More than one linked marker was found on chromosomes 1, 7, 13, 14 and 18. It is likely that these regions contain genes involved in Salmonella susceptibility. Regions on chromosomes 1, 7 and 14 were significantly associated with Salmonella counts in the liver and regions on chromosomes 11, 13 and 18 with counts in spleen. The identification of these chromosomal regions highlights specific areas to search for candidate genes that may be involved in innate or adaptive immunity. Further investigation into these chromosomal regions would be useful to improve our understanding of host responses to infection with this widespread pathogen.     

86株A群链球菌耐药性检测与分析

目的探讨A群链球菌对多种抗生素的耐药性,更好地指导临床用药。方法收集本院2005年度检出的39株和2006年度检出的47株A群链球菌的药物敏感试验结果,使用X^2检验比较A群链球菌耐药率。结果2006年度和上一年度相比A群链球菌对红霉素、克林霉素、阿齐霉素的耐药率增高显著（P〈0．05）,而对氯霉素、四环素的耐药性无明显改变（P〉0．05）,未发现耐万古霉素、青霉素、头孢吡肟、头孢噻肟的菌株。结论加强对A群链球菌耐药性检测及调查分析,对指导临床用药有重要意义。     

Distribution of HLA class Ⅰ and class Ⅱ haplotypes in Chinese Han population based on family segregation

HLA haplotype analysis has important application value in human population genetics, anthropological research and HLA matching transplantation. Based on HLA-A, -B, -C, -DRB1 and -DQB1 genotyping data from 663 families including 663 leukemia patients and 991 related donors, the allele frequency (AF) and haplotype frequency (HF) of two-, three- and five-locus haplotype distribution patterns in the Chinese Han population were determined by family segregation. A total of 38 alleles at A locus, 75 alleles at B locus, 35 alleles at C locus, 53 alleles at DRB1 locus and 22 alleles at DQB1 locus were discovered in this population. The frequencies of these alleles were basically consistent with those of previous reports except for some tiny differences. The study found 11 A-C, 15 C-B, 4 B-DRB1 and 11 DRB1-DQB1 two-locus haplotypes with a frequency over 2%. The number of A-C-B and A-B-DRB1 three-locus haplotype with a frequency over 1% were 11 and 3 respectively. The most common HLA-A-C-B-DRB1-DQB1 haplotype (HF>1%) were A*3001-C*0602-B*1302-DR*0701-DQ*0202 (4.30%), A*0207-C*0102-B*4601-DR*0901-DQ*0303 (3.07%), A*3303-C*0302-B*5801-DR*0301-DQ*0201 (1.49%) and A*1101-C*0102-B*4601-DR*0901-DQ*0303 (1.01%). The results are helpful for finding matching donors for hematopoietic stem cell transplant patients and also contribute to transplant immunology, HLA-related diseases, research of human genetics and other fields.     

Partial nucleotide sequences, and routine typing by polymerase chain reaction-restriction fragment length polymorphism, of the brown trout (Salmo trutta) lactate dehydrogenase, LDH-C1*90 and *100 alleles

The cDNA nucleotide sequences of the lactate dehydrogenase alleles LDH-C1*90 and *100 of brown trout (Salmo trutta) were found to differ at position 308 where an A is present in the *100 allele but a G is present in the *90 allele. This base substitution results in an amino acid change from aspartic acid at position 82 in the LDH-C1 100 allozyme to a glycine in the 90 allozyme. Since aspartic acid has a net negative charge whilst glycine is uncharged, this is consistent with the electrophoretic observation that the LDH-C1 100 allozyme has a more anodal mobility relative to the LDH-C1 90 allozyme. Based on alignment of the cDNA sequence with the mouse genomic sequence, a local primer set was designed, incorporating the variable position, and was found to give very good amplification with brown trout genomic DNA. Sequencing of this fragment confirmed the difference in both homozygous and heterozygous individuals. Digestion of the polymerase chain reaction products with BslI, a restriction enzyme specific for the site difference, gave one, two and three fragments for the two homozygotes and the heterozygote, respectively, following electrophoretic separation. This provides a DNA-based means of routine screening of the highly informative LDH-C1* polymorphism in brown trout population genetic studies. Primer sets presented could be used to sequence cDNA of other LDH* genes of brown trout and other species.     

胰腺实性假乳头状瘤临床分析(附2例小儿和6例成人病例)

目的:探讨胰腺实性假乳头状瘤(solid pseudopapillary tumor of pancreas,SPTP)的诊断和治疗方法.方法:回顾性分析上海市第一人民医院在2006年6月-2011年11月年收治的8例SPTP病人的临床表现和影像学检查、治疗的情况,其中小儿2例,成人6例.结果:有7例女性病人,1例男性病人,有腹痛或无特异性临床表现.所有病例均进行CT检查.肿瘤位于胰腺头部1例,胰腺颈部2例,位于胰体尾5例.1例行胰十二指肠切除术,2例行胰腺颈部节段性切除术,4例行胰体尾切除+脾切除术,1例行胰体尾切除术(保留脾脏),手术顺利,术后无并发症发生.随访时间4-56月,无复发和转移.结论:胰腺实性假乳头状瘤是一种较罕见的肿瘤,多发于年青女性.CT有助于该病的诊断.手术切除是该病的主要治疗手段,并可获得良好的预后.     

A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition

Tumor metastasis is not only a sign of disease severity but also a major factor causing treatment failure and cancer-related death. Therefore, studies on the molecular mechanisms of tumor metastasis are critical for the development of treatments and for the improvement of survival. The epithelial-mesenchymal transition (EMT) is an orderly, polygenic biological process that plays an important role in tumor cell invasion, metastasis and chemoresistance. The complex, multi-step process of EMT involves multiple regulatory mechanisms. Specifically, the PI3K/Akt signaling pathway can affect the EMT in a variety of ways to influence tumor aggressiveness. A better understanding of the regulatory mechanisms related to the EMT can provide a theoretical basis for the early prediction of tumor progression as well as targeted therapy.