美国揭示脑部基因与肾癌相关

来自佛罗里达梅奥诊所的研究者报告称，一个控制脑部生长和发育的基因与肾透明细胞癌生长显著相关。

比利时南部基因5型丙型肝炎病毒患者:流行病学特征和治疗应答

Data are scarce on patients infected with hepatitis C virus of genotype 5, due to the low prevalence of this genotype around the world. To better define the characteristics of these patients, we reviewed the files of 16 genotype 5 patients. Mean age was 38 ± 14. All patients were of European origin. Most of them (75% ) had been contaminated by transfusion within a short time period (between 1980 and 1991). There were no intravenous drug addicts. Seven patients received treatment. One patient did not respond to interferon (IFN) monotherapy. Of four patients treated with IFN and ribavirin, three became sustained viral responders. Two patients treated with pegylated IFN and ribavirin became sustained viral responders. In our region, genotype 5 patients seem to have been contaminated within a relatively short time period. Treatment with IFN or pegylated IFN and ribavirin gave a high rate (83% ) of sustained viral responses.

Survivin基因在肝门部胆管癌组织中的表达及其与nm23和PTEN相关性的研究

目的:探讨Survivin基因在肝门部胆管癌组织中的表达情况以及与nm23和PTEN基因表达的相关性。方法:应用免疫组织化学方法测定肝门部胆管癌及相应癌旁正常组织中Survivin、nm23和PTEN基因的表达,分析Survivin基因表达与肿瘤组织病理分级、淋巴结转移以及nm23和PTEN基因的相关性。结果:44例肝门部胆管癌组织中,Survivin基因阳性表达率63.6%,15例癌旁组织中Sur-vivin基因阳性表达率为6.67%,二者比较差异有统计学意义(P<0.05);Survivin基因表达与病理分级无关(P>0.05),与淋巴结转移无关(P>0.05);Survivin基因表达与PTEN及nm23的表达呈负相关(P<0.05)。结论:Survivin基因的高表达在肝门部胆管癌的发生、进展和转移过程中可能起重要作用;联合检测Survivin与PTEN及nm23基因表达可能有助于临床诊断及判断预后。

c-fos、bcl-2基因表达与肠型、弥漫型胃癌的关系

目的 :探讨c fos、bcl 2基因蛋白表达与肠型、弥漫型胃癌的发生的关系 ,为胃癌分型、早期诊断提供分子病理学依据。方法 :用免疫组织化学方法 ,检测 5 4例胃癌切除标本c fos、bcl 2基因蛋白的表达 ,所有结果均用EXCEL录入计算机、SAS统计软件包分析。结果 :在肠型胃癌中c fos、bcl 2基因蛋白表达高于弥漫型胃癌 (P <0 0 1) ;c fos、bcl 2蛋白表达淋巴结转移组高于非转移组 (c fos为 6 3.6 4%、5 4.5 5 %;bcl 2为 5 0 .0 0 %,2 7.2 7%) ,但无统计学意义 ;c fos、bcl 2在癌旁组织、异型增生组织和高分化腺癌中呈强阳性表达。结论 :c fos、bcl 2在肠型和弥漫型胃癌中的不同表达表明两型胃癌的发生机制有所不同 ,可为胃癌分型提供分子病理学依据 ;c fos、bcl 2基因蛋白表达变化发生在肿瘤细胞形态变化之前 ,可作为胃癌早期诊断的分子病理学指标。

基于融合特征与GA-SVM算法的脑疾病基因预测

单一生物数据网络提供的特征信息是十分受限的,针对这一问题,提出了一种基于半监督自编码器的多网络特征融合方法,丰富特征信息。此外,为解决在人为设置模型的超参数时,易出现模型性能较低、陷入局部最优等问题,进一步提出了利用遗传算法优化支持向量机(GA-SVM算法)模型的方法,提高脑部疾病基因的预测性能。构建来自不同数据源的相似性数据网络,利用重启随机游走算法从四个数据网络中提取特征,通过半监督自编码器进行处理及融合,在十折交叉验证的策略下使用GA-SVM算法模型预测脑部疾病基因,并与其他算法进行比较。实验结果表明,在PD数据集上的AUC和AUPR值分别为0.805、0.792,而在MDD数据集上的AUC和AUPR值分别为0.825、0.823,均优于已有的预测模型,有效证明了该方法能够提高脑部疾病基因的预测效果。

认识人类配对盒基因Pax6,一个控制眼和大脑发育的关键基因

人类配对盒基因6（Pax6）是控制眼和大脑发育的关键基因。Pax6基因突变或表达水平改变导致一系列的眼部疾病。作为转录因子，Pax6在胚胎发育早期多个不同组织原基表达，单独或与其他转录因子共同作用，直接或间接调控不同下游基因的表达来调控眼、大脑、垂体、鼻及胰脏的发育。Pax6存在4种异构体，其功能受多种翻译后修饰的调控。全面认识Pax6的结构与功能及其与各种疾病的关系有助于眼科医师研究其突变或表达改变而引起的相关眼病的病理机制，为相关疾病的防治提供新的思路。

Relation between the Expression of K-ras in Hep-2 Cells and Development of Laryngeal Carcinoma~*

Objective： To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods： The expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and human pancreatic carcinoma cell lines （MIAPaCa-2） was detected by using RT-PCR. Results： The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion： The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines （Hep-2） is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.

Stable transfection of extrinsic Smac gene enhances apoptosis-inducing effects of chemotherapeutic drugs on gastric cancer cells

AIM: To explore the feasibility of enhancing apoptosis-inducing effects of chemotherapeutic drugs on human gastric cancer cells by stable transfection of extrinsic Smac gene. METHODS: After Smac gene was transferred into gastric cancer cell line MKN-45, subclone cells were obtained by persistent G_(418) selection. Cellular Smac gene expression was determined by RT-PCR and Western blotting. After treatment with mitomycin (MMC) as an apoptotic inducer, in vitro cell growth activities were investigated by trypan blue-staining method and MTT colorimetry. Cell apoptosis and its rates were determined by electronic microscopy, annexin V-FTTC and propidium iodide staining flow cytometry. Cellular caspase-3 protein expression and its activities were assayed by Western blotting and colorimetry. RESULTS: When compared with MKN-45 cells, the selected subclone cell line MKN-45/Smac had significantly higher Smac mRNA (3.12±0.21 vs 0.82±0.14, t=7.52, P＜0.01) and protein levels (4.02±0.24 vs0.98±0.11, t=8.32, P＜0.01). After treatment with 10 μg/mL MMC for 6-24 h, growth inhibition rate of MKN-45/Smac (15.8±1.2-54.8±2.9%) was significantly higher than that of MKN-45 (5.8±0.4-24.0±1.5%, t=6.42, P＜0.01). Partial MKN-45/Smac cancer cells presented characteristic morphological changes of apoptosis under the electronic microscope with an apoptosis rate of 36.4±2.1%, which was significantly higher than that of MKN-45 (15.2±0.8%, t=9.25, P＜0.01). Compared with MKN-45, caspase-3 expression levels in MKN-45/Smac were improved significantly (3.39±0.42 vs0.96±0.14, t=8.63, P＜0.01), while its activities were 3.25 times as many as those of MKN-45 (0.364±0.010 vs0.112±0.007, t=6.34, P＜0.01). CONCLUSION: Stable transfection of extrinsic Smac gene and its over-expression in gastric cancer cell line can significantly enhance cellular caspase-3 expression and activities, ameliorate apoptosis-inducing effects of mitomycin C on cancer cells, which is a novel strategy to improve chemotherapeutic effects on gastric cancer.

Mesenteric Ischemia:An unusual presentation of fistula between superior mesenteric artery and common hepatic artery

Chronic mesenteric ischemia is an uncommon condition associated with a high morbidity and mortality.We reported a 36-year old women with postprandial abdominal pain due to chronic mesenteric ischemia caused by a fistula between superior mesenteric and common hepatic artery.

Functional Inferences of Environmental Coccolithovirus Biodiversity

The cosmopolitan calcifying alga Emiliania huxleyi is one of the most abundant bloom forming coccolithophore species in the oceans and plays an important role in global biogeochemical cycling. Coccolithoviruses are a major cause of coccolithophore bloom termination and have been studied in laboratory, mesocosm and open ocean studies. However, little is known about the dynamic interactions between the host and its viruses, and less is known about the natural diversity and role of functionally important genes within natural coccolithovirus communities. Here, we investigate the temporal and spatial distribution of coccolithoviruses by the use of molecular fingerprinting techniques PCR, DGGE and genomie sequencing. The natural biodiversity of the virus genes encoding the major capsid protein （MCP） and serine palmitoyltransferase （SPT） were analysed in samples obtained from the Atlantic Meridional Transect （AMT）, the North Sea and the L4 site in the Westem Channel Observatory. We discovered nine new coccolithovirus genotypes across the AMT and L4 site, with the majority of MCP sequences observed at the deep chlorophyll maximum layer of the sampled sites on the transect. We also found four new SPT gene variations in the North Sea and at L4. Their translated fragments and the full protein sequence of SPT from laboratory strains EhV-86 and EhV-99B 1 were modelled and revealed that the theoretical fold differs among strains. Variation identified in the structural distance between the two domains of the SPT protein may have an impact on the catalytic capabilities of its active site. In summary, the combined use of ＇standard＇ markers （i.e. MCP）, in combination with metabolically relevant markers （i.e. SPT） are useful in the study of the phylogeny and functional biodiversity of coccolithoviruses, and can provide an interesting intracellular insight into the evolution of these viruses and their ability to infect and replicate within their algal hosts.

Enhancement of NH_4^+ Uptake by NO_3^- in Relation to Expression of Nitrate-Induced Genes in Rice (Oryza sativa) Roots

This study aimed to survey the expression of genes involved in rice N uptake and aasimilatory network and to understand the potential molecular mechanisms responsible for the NO3^-enhanced NH4^＋ uptake. By using quantitative real-time polymerase chain reaction （PCR）, the genes related to N nutrition, including ammonium transporters （AMTs） and ammonium assimilatory enzymes （GS and GOGAT）, were transcriptionally analyzed in rice plants grown in the absence and presence of NO4^- in the NH4^＋-containing medium. The results showed that NH4^＋ uptake by rice was enhanced by the NO3^- supply to the medium. At the same time and in parallel, the amount of transcripts of seven genes （OsAMT1;1, OsAMT1;2, OsAMT4;1, OsGLNP, OsGLU1, OsGLT1, and OsGLTP） was increased in rice roots, but the expression of two genes （OsGLN1;1 and OsGLN1;P） was decreased and that of OsAMT1;3 remained without change. Up- or downregulation of these genes involved in NH4^＋ uptake and assimilation correlated with the increase in NH4^＋ uptake in the presence of NO3^- in rice roots.

Gene expression profile of esophageal cancer in North East India by cDNA microarray analysis

AIM： To identify alterations in genes and molecular functional pathways in esophageal cancer in a high incidence region of India where there is a widespread use of tobacco and betel quid with fermented areca nuts. METHODS： Total RNA was isolated from tumor and matched normal tissue of 16 patients with esophageal squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method. The labeled probes were hybridized with human 10K cDNA chip and expression profiles were analyzed by Genespring GX V 7.3 （Silicon Genetics）. RESULTS： Nine hundred twenty three genes were differentially expressed. Of these, 611 genes were upregulated and 312 genes were downregulated. Using stringent criteria （P ≤ 0.05 and ≥ 1.5 fold change）, 127 differentially expressed genes （87 upregulated and 40 downregulated） were identified in tumor tissue. On the basis of Gene Ontology, four different molecular functional pathways （HAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity）were most significantly upregulated and six different molecular functional pathways （structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activity）were most significantly downregulated. CONCLUSION： Several genes that showed alterations in our study have also been reported from a high incidence area of esophageal cancer in China. This indicates that molecular profiles of esophageal cancer in these two different geographic locations are highly consistent.

Prognostic Value of Ki67 and VE6F Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred (recurrent group), 3 cases metastasized (metastatic group), 8 cases died (deceased group) and 24 cased survived (survival group) over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group (P<0.01). Overexpression of Ki67 was found in the recurrent group and in the metastatic group (P< 0.05). VEGF expression was higher in the recurrent group than in the non recurrent group (P<0.05). With Cox-regression of multivariate analysis, Ki67 (RR:3.236; P=0.001), the clinical T stage (RR: 1.382; P=0.029) and metastasis in lymph nodes (RR:0.316; P=0.033) were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocar-cinoma.

Inference of Global HIV-1 Sequence Patterns and Preliminary FeatureAnalysis

The epidemiology of HIV-1 varies in different areas of the world, and it is possible that this complexity may leave unique footprints in the viral genome. Thus, we attempted to find significant patterns in global HIV-1 genome sequences. By applying the rule inference algorithm RIPPER (Repeated Incremental Pruning to Produce Error Reduction) to multiple sequence alignments of Env sequences from four classes of compiled datasets, we generated four sets of signature patterns. We found that these patterns were able to distinguish southeastern Asian from non- southeastern Asian sequences with 97.5% accuracy, Chinese from non-Chinese sequences with 98.3% accuracy, African from non-African sequences with 88.4% accuracy, and southern African from non-southern African sequences with 91.2% accuracy. These patterns showed different associations with subtypes and with amino acid positions. In addition, some signature patterns were characteristic of the geographic area from which the sample was taken. Amino acid features corresponding to the phylogenetic clustering of HIV-1 sequences were consistent with some of the deduced patterns. Using a combination of patterns inferred from subtypes B, C, and all subtypes chimeric with CRF01_AE worldwide, we found that signature patterns of subtype C were extremely common in some sampled countries (for example, Zambia in southern Africa), which may hint at the origin of this HIV-1 subtype and the need to pay special attention to this area of Africa. Signature patterns of subtype B sequences were associated with different countries. Even more, there are distinct patterns at single position 21 with glycine, leucine and isoleucine corresponding to subtype C, B and all possible recombination forms chimeric with CRF01_AE, which also indicate distinct geographic features. Our method widens the scope of inference of signature from geographic, genetic, and genomic viewpoints. These findings may provide a valuable reference for epidemiological research or vaccine design.

Effect of Cytokine on the Expression of Sodium Iodide Symporter Gene in Breast Cancer Cell

Objective: To investigate the effect of cytokines (TNF-α,IFN-γ and IL-6) on the expression of sodium-iodide symporter(NIS)gene in breast cancer cell(MCF-7). Methods:The breast cancer cell was cultureds with negative control culture or culture with different concentrations of cytokines for 72 h.NIS gene mRNA in breast cancer cells cultured was determined by reverse transcriptase-polymerase chain reaction(RT-PCR). Results:Expression of sodium-iodide symporter mRNA can be found decreasing along with increasing the concentration of cytokine dose-dependently. Conclusion: Cytokine may play a role in iodide-uptake modulating in breast cancer cells by their effect on NIS gene expression.

CHANGES OF ENDOTHELIN－1 GENE EXPRESSION IN RAT BRAINS DURING ISCHEMIA AND ISCHEMIC REPERFUSION

Objective. The experiment was designed to study the association of cerebral ischemia and reperfusion with endothelin- 1 (ET- 1) gene expression of rat brains and time-dependent changes of ET- 1 gene expression during cerebral ischemia.Materials and methods. Thirty- three male SD rats were divided into dot blot hybridization(n = 27) and in silu hybridization groups(n= 6). The focal cerebral ischemia and reperfusion models were made with suture embolism of middle cerebral artery. Dot blot hybridization groups were redivided into control and ischemic subgroups (ischemia for 0. 5 , 1 , 1. 5 , 3 , 6 , 12 , 24 , 48 and 72 h respectively). In situ hybridization groups were redivided into ischemia and reperfusion groups. After 24 h ischemia and 24 h reperfusion,ET1 gene expressions were investigated with in situ hybridization and the resuhs were analyzed with IBAS 2000 Image Analysis System.Results. Dot blot hybridization showed that ET-1 mRNA of cerebral cortex and caudate- putamen was increased at 6 h of ischemia and reached peak at 24 h (3. 9 and 3. 7 fold respectively) ,and at 72 h of ischemia it remained at high levels(3. 5 and 2. 1 fold respectively). In silu hybridization showed that the levels of ET- 1 mRNA of cerebral cortex and caudate-putamen were also markedly increased both in 24 h ischemia and 24 h reperfusion groups (P<0. 01 , P<0. 05 respectively) .Conclusions. ET-1 gene expression in focal ischemic brain tissue were markedly and progressively increased during cerebral ischemia and reperfusion and downregulation of ET- 1 gene expression may be a new approach to the treatment of ischemic cerebrovascular diseases.

ENDOGENOUS EXPRESSION AND HLA STABILIZATION ASSAY OF PLASMODIUM FALCIPARUM CTL EPITOPE MINIGENE IN HUMAN HLA- A2.1 AND HLA- B51 CELLS

To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. Methods. Synthesized oligonucleotides encoding for P.f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT- PCR and HLA stabilization assay. Results. Two mini- genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA- B51, SH6 which was restricted to HLA- A2.1, and TS, which had the two aforementioned mini- genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini- gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. Conclusion. A successful expression and presentation of multiple CTL epitope mini- gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope plasmodium falciparum DNA vaccine that could cover most of Chinese population.