Chronic obstructive pulmonary disease(COPD)is incurable chronic disease which kills 3.3 million each year worldwide.Number of global cases of COPD is steadily rising alongside with life expectancy,disproportionally hi...Chronic obstructive pulmonary disease(COPD)is incurable chronic disease which kills 3.3 million each year worldwide.Number of global cases of COPD is steadily rising alongside with life expectancy,disproportionally hitting middle-income countries like Russia and China,in such conditions,new approaches to the COPD management are desperately needed.DNA microarray technology is a powerful genomic tool that has the potential to uncover underlying COPD biological alteration and brings up revolutionized treatment option to clinicians.We executed systematic review studies of studies published in last 10 years regarding DNA microarray application in COPD management,with complacence to PRISMA criteria and using PubMed and Medline data bases as data source.Out of 920 identified papers,39 were included in the final analysis.We concluded that Genome-wide expression profiling using DNA microarray technology has great potential in enhancing COPD management.Current studied proofed this method is reliable and possesses many potential applications such as individual at risk of COPD development recognition,early diagnosis of disease,COPD phenotype identification,exacerbation prediction,personalized treatment optioning and prospect of oncogenesis evaluation in patients with COPD.Despite all the proofed benefits of this technology,researchers are still in the early stage of exploring it’s potential.Therefore,large clinical trials are still needed to set up standard for DNA microarray techniques usage implementation in COPD management guidelines,subsequently giving opportunity to clinicians for controlling or even eliminating COPD entirely.展开更多
目的 研究 DNA m icroarray的制备及其检测淋球菌耐喹诺酮类药物基因突变的准确性。方法 根据淋球菌药敏及测序结果分别对淋球菌 gyr A和 par C基因的序列设计特异引物和探针并制作 DNA m icroarray。对淋球菌临床拭子进行 PCR扩增并...目的 研究 DNA m icroarray的制备及其检测淋球菌耐喹诺酮类药物基因突变的准确性。方法 根据淋球菌药敏及测序结果分别对淋球菌 gyr A和 par C基因的序列设计特异引物和探针并制作 DNA m icroarray。对淋球菌临床拭子进行 PCR扩增并荧光标记包含 gyr A和 par C基因的目的 DNA片段 ,与芯片杂交 ,同时以测序法进行双盲淋球菌耐喹诺酮类药物基因突变的检测。结果 87份泌尿生殖道试子全部可用 DNA m icroarray检测出来 ,芯片检测结果与药敏结果符合率为 10 0 % ,与测序结果符合率为 97.7%。结论 用 DNA microarray来检测淋球菌 gyr A和 par C基因突变快速、特异性高和灵敏度高 。展开更多
AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We...AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.展开更多
AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parame...AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.METHODS:Purified gastric adenocarcinoma cells(GAC)and normal gastric epithelial cells(NGEC)were obtained from 15 patients with gastric cancer by laser capture microdissection.All of the peptide specimens were labeled as18O/16O after trypsin digestion.Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry(nanoRPLC-MS/MS).The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis.The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry(IHC).The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.RESULTS:A total of 78 differential proteins were identified.Western blotting revealed that ANXA1 expression was significantly upregulated in GAC(2.17/1,P<0.01).IHC results showed the correlations between ANXA1protein expression and the clinicopathological parameters,including invasive depth(T stage),lymph node metastasis(N stage),distant metastasis(M stage)and tumour-lymph node metastasis stage(P<0.01).However,the correlations between ANXA1 protein expression and the remaining clinicopathological parameters,including sex,age,histological differentiation and the size of tumour were not found(P>0.05).CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis,progression,invasion and metastasis of GAC.This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.展开更多
OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarrayand detect target genes for further study.METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 ...OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarrayand detect target genes for further study.METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 cases ofmoderate-differentiated pancreatic carcinoma were studied by means of cDNA microarray consisting of18 000 genes.RESULTS: 1484 and 1353 different expressed genes were observed in two cancer samples respectively.We identified 455 genes altered with the same tendency in both samples, including 102 up-regulated and353 down-regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and 52.0%genes respectively had an expression level in cancer that was 2-fold higher or lower than that in normalsamples. Tumor suppressor genes, growth factors and receptor genes, signal conduction genes,transcription factor genes were identified.CONCLUSIONS: cDNA microarray is an efficient and high-throughout method to investigate geneexpression profiles in pancreatic carcinoma. MBD1, EDG1 and gene hypermethylation mechanism wouldplay an important role in the pathogenesis of pancreatic carcinoma.展开更多
A Schwann cell has regenerative capabilities and is an important cell in the peripheral nervous system.This microarray study is part of a bioinformatics study that focuses mainly on Schwann cells. Microarray data prov...A Schwann cell has regenerative capabilities and is an important cell in the peripheral nervous system.This microarray study is part of a bioinformatics study that focuses mainly on Schwann cells. Microarray data provide information on differences between microarray-based and experiment-based gene expression analyses. According to microarray data, several genes exhibit increased expression(fold change) but they are weakly expressed in experimental studies(based on morphology, protein and mRNA levels). In contrast, some genes are weakly expressed in microarray data and highly expressed in experimental studies;such genes may represent future target genes in Schwann cell studies. These studies allow us to learn about additional genes that could be used to achieve targeted results from experimental studies. In the current big data study by retrieving more than 5000 scientific articles from PubMed or NCBI, Google Scholar, and Google, 1016(up-and downregulated) genes were determined to be related to Schwann cells. However,no experiment was performed in the laboratory; rather, the present study is part of a big data analysis. Our study will contribute to our understanding of Schwann cell biology by aiding in the identification of genes.Based on a comparative analysis of all microarray data, we conclude that the microarray could be a good tool for predicting the expression and intensity of different genes of interest in actual experiments.展开更多
BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-canc...BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.展开更多
BACKGROUND:The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis(SAP) patients have been proved.This study was designed to investigate the influence of dexamethasone on apoptosis of ...BACKGROUND:The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis(SAP) patients have been proved.This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS:Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group(45 rats in each group),and another 45 rats formed the sham operation group.Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3,6 and 12 hours after operation.Tissue microarray technology was applied to prepare pancreatic tissue sections.The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining,and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS:The model and treated groups did not differ in mortality at each time point.The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours.The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours.TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS:Apoptosis may be a protective response to pancreatic cell injury.The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy,efficiency and highly representative.展开更多
BACKGROUND: Acute-on-chronic liver failure(ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA(miRNA) profiles in ACLF patie...BACKGROUND: Acute-on-chronic liver failure(ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA(miRNA) profiles in ACLF patients may provide new clues to the pathogenesis and management of this syndrome. METHODS: Genome-wide microarray was performed to compare the different miRNA expression profiles in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF patient and an HBV asymptomatic carrier(AsC). The case-control miRNA profiles were compared and confirmed by quantitative reverse transcription-polymerase chain reaction in 104 ACLF patients and 96 AsCs. A combined computational prediction algorithm was used to predict the potential target genes. RESULTS: Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and 8.63-fold in ACLF patients compared with that in AsCs, respectively(P<0.001). CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes of hsa-let-7a. CONCLUSIONS: Our results showed that there is a close relationship between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR-16 and hsa-let-7a may contribute to the development of ACLF.展开更多
Objective: The present study aimed to investigate circular RNA(circRNA) expression in uveal melanoma(UM).Methods: First,we used microarray to compare the expression profiles of circRNA in five UM samples and five norm...Objective: The present study aimed to investigate circular RNA(circRNA) expression in uveal melanoma(UM).Methods: First,we used microarray to compare the expression profiles of circRNA in five UM samples and five normal uvea tissues.Next,bioinformatics analyses,including gene ontology(GO) analysis and pathway analysis,were applied to study these differentially expressed circRNAs to predict pathogenic pathways that may be involved.Quantitative real-time polymerase chain reaction(qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circRNA expression profiles obtained from the microarray data.Finally,we analyzed the interaction between validated circRNAs and their potential cancer-associated miRNA targets.Results: In total,50,579 circRNAs [fold change(FC) ≥2.0; P<0.05],including 20,654 up-regulated and 29,925 down-regulated circRNAs,were identified as differentially expressed between UM tissues and normal uvea tissues.We used qRT-PCR to verify seven dysregulated circRNAs indicated by the microarray data,including hsa_circ_0119873,hsa_circ_0128533,hsa_circ_0047924,hsa_circ_0103232,hsa-circRNA10628-6,hsa_circ_0032148 and hsa_circ_0133460,which may be promising candidates to study future molecular mechanisms.Conclusions: This study explored,for the first time,the abnormal expression of circRNAs in UM and described the expression profile of circRNAs,providing a new potential target for the mechanism of UM and future treatment of UM.展开更多
AIM: To investigate the expression pattern of plasma long noncoding RNAs(lnc RNAs) in Chrohn's disease(CD) patients.METHODS: Microarray screening and q RT-PCR verification of lnc RNAs and m RNAs were performed in ...AIM: To investigate the expression pattern of plasma long noncoding RNAs(lnc RNAs) in Chrohn's disease(CD) patients.METHODS: Microarray screening and q RT-PCR verification of lnc RNAs and m RNAs were performed in CD and control subjects, followed by hierarchy c l u s t e r i n g, G O a n d K E G G p a t h w a y a n a l y s e s. Significantly dysregulated lnc RNAs were categorized into subgroups of antisense lnc RNAs, enhancer lnc RNAs and linc RNAs. To predict the regulatory effect of lnc RNAs on m RNAs, a CNC network analysis was performed and cross linked with significantly changed lnc RNAs. The overlapping lnc RNAs were randomly selected and verified by q RT-PCR in a larger cohort. RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lnc RNAs as well as 1020 up-regulated and 953 down-regulated m RNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lnc RNAs, whereas TBC1D17 and CCL3L3 had the highest foldchange of the up- and down-regulated m RNAs. Six(SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 m RNAs and 8(NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lnc RNAs showed the same change trends on the microarray and q RT-PCR results with statistical significance. Based on the q RT-PCR verified m RNAs, 1358 potential lnc RNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network. CONCLUSION: The plasma lnc RNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lnc RNA-m RNA pathway exploration.展开更多
The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on eluc...The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.展开更多
AIM: To investigate the microRNA(miRNA) expression profile in gastrointestinal stromal tumor(GIST) tissues that could serve as a novel diagnostic biomarker for GIST detection.METHODS: We performed a quantitative real-...AIM: To investigate the microRNA(miRNA) expression profile in gastrointestinal stromal tumor(GIST) tissues that could serve as a novel diagnostic biomarker for GIST detection.METHODS: We performed a quantitative real-time quantitative reverse transcriptase polymerase chain reaction assay to analyze the expression of 1888 miRNAs in a sample set that included 54 GIST tissue samples.RESULTS: We found that dysregulation of several miRNAs may be related to the malignant potential of GISTs. Six of these miRNAs, hsa-let-7c, miR-218,miR-488#, miR-4683, miR-34c-5p and miR-4773, were selected as the final list of biomarkers to separate the malignant GISTs(M group) from the benign GISTs(B group). In addition, MiR-29b-2#, hsa-let-7c, miR-891 b, miR-218, miR-204, miR-204-3p, miR-628-5p,miR-744, miR-29c#, miR-625 and miR-196 a were used to distinguish between the borderline(BO group) and M groups. There were 11 common miRNAs selected to separate the benign and borderline(BB) group from the M group, including hsa-let-7c, miR-218, miR-628-5p,miR-204-3p, miR-204, miR-891 b, miR-488#, miR-145,miR-891 a, miR-34c-5p and miR-196 a.CONCLUSION: The identified miRNAs appear tobe novel biomarkers to distinguish malignant from benign GISTs, which may be helpful to understand the mechanisms of GIST oncogenesis and progression,and to further elucidate the characteristics of GIST subtypes.展开更多
Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new op...Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.展开更多
AIM To investigated the association between the tumor cells' expression of E-cadherin and the numbers of several types of inflammatory cells infiltrating into the invasive portion of gallbladder cancer(GBC).METHOD...AIM To investigated the association between the tumor cells' expression of E-cadherin and the numbers of several types of inflammatory cells infiltrating into the invasive portion of gallbladder cancer(GBC).METHODS We analyzed 50 GBC cases for which a sufficient amount of tumor tissues for tissue microarray(TMA) had been saved. Three tissue cores(3.0 mm) of invasive lesion from each case were used for the TMA. The 4-μm cut sections on slides were immunostained using primary antibodies including E-cadherin for cancer cells, leukocyte common antigen for leukocyte, myeloperoxidase for neutrophils, CD3 for T cells, CD4 for helper T cells, CD8 for killer T cells, CD20 for B cells and CD68 for macrophages. The immunostained slides were digitally analyzed by imaging analysis software.RESULTS A significant inverse correlation between the number of infiltrating CD8^+ cells at invasive areas and the expression of E-cadherin by cancer cells was observed(P = 0.0001), although the degree of this correlation was relatively weak(R = 0.32). The number of CD8^+ cells and the cancer cells' E-cadherin expression were also significantly correlated with tumor differentiation(welldifferentiated vs poorly differentiated)(P = 0.0467 and P = 0.0294, respectively). Inverse correlation of T-stageand the number of CD8^+ cell infiltration was observed with statistical significance in comparison of T2 and T3 cases(P = 0.0324).CONCLUSION Our findings indicate an inverse correlation of CD8^+ T cell infiltration and cancer cells' E-cadherin expression at invasive areas of GBC. Further analyses are essential to test these findings.展开更多
A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors...A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a basis for potential treatments of peripheral nerve injury.The study was approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital,China(approval number:2016-x9-07)in September 2016.展开更多
Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for s...Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for selection of the multidrug resistant (MDR) cell lines. Methods: We used cDNA microarrays containing 12,720 sequences of known genes, expressed sequence tags and unknown clones to monitor gene expression profiles in MDR KB cells. Results: Preliminary data analysis showed that 18 genes were up-regulated and 18 genes were down-regulated by comparison of expression patterns between KB 3-1 and MDR KB-V1 cells. Furthermore, the highly over-expressed CGA, CLU genes in MDR KB-V1 cell were verified with conventional Northern blot analysis. These genes contain information predictive of drug resistance of cancer cells. Conclusion: Our study demonstrates that genome-wide gene expression profiling by using cDNA microarray technique is a valuable approach in obtaining molecular mechanism of drug resistance in cancer cells.展开更多
文摘Chronic obstructive pulmonary disease(COPD)is incurable chronic disease which kills 3.3 million each year worldwide.Number of global cases of COPD is steadily rising alongside with life expectancy,disproportionally hitting middle-income countries like Russia and China,in such conditions,new approaches to the COPD management are desperately needed.DNA microarray technology is a powerful genomic tool that has the potential to uncover underlying COPD biological alteration and brings up revolutionized treatment option to clinicians.We executed systematic review studies of studies published in last 10 years regarding DNA microarray application in COPD management,with complacence to PRISMA criteria and using PubMed and Medline data bases as data source.Out of 920 identified papers,39 were included in the final analysis.We concluded that Genome-wide expression profiling using DNA microarray technology has great potential in enhancing COPD management.Current studied proofed this method is reliable and possesses many potential applications such as individual at risk of COPD development recognition,early diagnosis of disease,COPD phenotype identification,exacerbation prediction,personalized treatment optioning and prospect of oncogenesis evaluation in patients with COPD.Despite all the proofed benefits of this technology,researchers are still in the early stage of exploring it’s potential.Therefore,large clinical trials are still needed to set up standard for DNA microarray techniques usage implementation in COPD management guidelines,subsequently giving opportunity to clinicians for controlling or even eliminating COPD entirely.
文摘目的 研究 DNA m icroarray的制备及其检测淋球菌耐喹诺酮类药物基因突变的准确性。方法 根据淋球菌药敏及测序结果分别对淋球菌 gyr A和 par C基因的序列设计特异引物和探针并制作 DNA m icroarray。对淋球菌临床拭子进行 PCR扩增并荧光标记包含 gyr A和 par C基因的目的 DNA片段 ,与芯片杂交 ,同时以测序法进行双盲淋球菌耐喹诺酮类药物基因突变的检测。结果 87份泌尿生殖道试子全部可用 DNA m icroarray检测出来 ,芯片检测结果与药敏结果符合率为 10 0 % ,与测序结果符合率为 97.7%。结论 用 DNA microarray来检测淋球菌 gyr A和 par C基因突变快速、特异性高和灵敏度高 。
文摘AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.
基金Supported by National Natural Science Foundation of China,No.81001101Natural Science Foundation of Xinjiang Uygur Autonomous Region,China,No.2010211B20
文摘AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.METHODS:Purified gastric adenocarcinoma cells(GAC)and normal gastric epithelial cells(NGEC)were obtained from 15 patients with gastric cancer by laser capture microdissection.All of the peptide specimens were labeled as18O/16O after trypsin digestion.Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry(nanoRPLC-MS/MS).The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis.The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry(IHC).The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.RESULTS:A total of 78 differential proteins were identified.Western blotting revealed that ANXA1 expression was significantly upregulated in GAC(2.17/1,P<0.01).IHC results showed the correlations between ANXA1protein expression and the clinicopathological parameters,including invasive depth(T stage),lymph node metastasis(N stage),distant metastasis(M stage)and tumour-lymph node metastasis stage(P<0.01).However,the correlations between ANXA1 protein expression and the remaining clinicopathological parameters,including sex,age,histological differentiation and the size of tumour were not found(P>0.05).CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis,progression,invasion and metastasis of GAC.This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.
文摘OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarrayand detect target genes for further study.METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 cases ofmoderate-differentiated pancreatic carcinoma were studied by means of cDNA microarray consisting of18 000 genes.RESULTS: 1484 and 1353 different expressed genes were observed in two cancer samples respectively.We identified 455 genes altered with the same tendency in both samples, including 102 up-regulated and353 down-regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and 52.0%genes respectively had an expression level in cancer that was 2-fold higher or lower than that in normalsamples. Tumor suppressor genes, growth factors and receptor genes, signal conduction genes,transcription factor genes were identified.CONCLUSIONS: cDNA microarray is an efficient and high-throughout method to investigate geneexpression profiles in pancreatic carcinoma. MBD1, EDG1 and gene hypermethylation mechanism wouldplay an important role in the pathogenesis of pancreatic carcinoma.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(2018R1D1A1B07040282 to JJ)+1 种基金a grant from Kyung Hee University in 2018(KHU-20181065 to JJ)
文摘A Schwann cell has regenerative capabilities and is an important cell in the peripheral nervous system.This microarray study is part of a bioinformatics study that focuses mainly on Schwann cells. Microarray data provide information on differences between microarray-based and experiment-based gene expression analyses. According to microarray data, several genes exhibit increased expression(fold change) but they are weakly expressed in experimental studies(based on morphology, protein and mRNA levels). In contrast, some genes are weakly expressed in microarray data and highly expressed in experimental studies;such genes may represent future target genes in Schwann cell studies. These studies allow us to learn about additional genes that could be used to achieve targeted results from experimental studies. In the current big data study by retrieving more than 5000 scientific articles from PubMed or NCBI, Google Scholar, and Google, 1016(up-and downregulated) genes were determined to be related to Schwann cells. However,no experiment was performed in the laboratory; rather, the present study is part of a big data analysis. Our study will contribute to our understanding of Schwann cell biology by aiding in the identification of genes.Based on a comparative analysis of all microarray data, we conclude that the microarray could be a good tool for predicting the expression and intensity of different genes of interest in actual experiments.
基金The study was supported by a grant from the National 863 program (2002AA2Z2021).
文摘BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.
文摘BACKGROUND:The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis(SAP) patients have been proved.This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS:Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group(45 rats in each group),and another 45 rats formed the sham operation group.Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3,6 and 12 hours after operation.Tissue microarray technology was applied to prepare pancreatic tissue sections.The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining,and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS:The model and treated groups did not differ in mortality at each time point.The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours.The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours.TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS:Apoptosis may be a protective response to pancreatic cell injury.The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy,efficiency and highly representative.
文摘BACKGROUND: Acute-on-chronic liver failure(ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA(miRNA) profiles in ACLF patients may provide new clues to the pathogenesis and management of this syndrome. METHODS: Genome-wide microarray was performed to compare the different miRNA expression profiles in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF patient and an HBV asymptomatic carrier(AsC). The case-control miRNA profiles were compared and confirmed by quantitative reverse transcription-polymerase chain reaction in 104 ACLF patients and 96 AsCs. A combined computational prediction algorithm was used to predict the potential target genes. RESULTS: Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and 8.63-fold in ACLF patients compared with that in AsCs, respectively(P<0.001). CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes of hsa-let-7a. CONCLUSIONS: Our results showed that there is a close relationship between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR-16 and hsa-let-7a may contribute to the development of ACLF.
基金supported by Beijing Municipal Administration of Hospitals’ Ascent Plan(No.DFL20150201)the National Natural Science Foundation of China(No.81570891)+2 种基金Beijing Natural Science Foundation(No.7151003)Advanced Health Care Professionals Development Project of Beijing Municipal Health Bureau(No.2014-2-003)The Capital Health Research and Development of Special(No.2016-1-2051)
文摘Objective: The present study aimed to investigate circular RNA(circRNA) expression in uveal melanoma(UM).Methods: First,we used microarray to compare the expression profiles of circRNA in five UM samples and five normal uvea tissues.Next,bioinformatics analyses,including gene ontology(GO) analysis and pathway analysis,were applied to study these differentially expressed circRNAs to predict pathogenic pathways that may be involved.Quantitative real-time polymerase chain reaction(qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circRNA expression profiles obtained from the microarray data.Finally,we analyzed the interaction between validated circRNAs and their potential cancer-associated miRNA targets.Results: In total,50,579 circRNAs [fold change(FC) ≥2.0; P<0.05],including 20,654 up-regulated and 29,925 down-regulated circRNAs,were identified as differentially expressed between UM tissues and normal uvea tissues.We used qRT-PCR to verify seven dysregulated circRNAs indicated by the microarray data,including hsa_circ_0119873,hsa_circ_0128533,hsa_circ_0047924,hsa_circ_0103232,hsa-circRNA10628-6,hsa_circ_0032148 and hsa_circ_0133460,which may be promising candidates to study future molecular mechanisms.Conclusions: This study explored,for the first time,the abnormal expression of circRNAs in UM and described the expression profile of circRNAs,providing a new potential target for the mechanism of UM and future treatment of UM.
基金Supported by National Natural Science Foundation of China,No.81370008 and No.81000169Natural Science Foundation of Zhejiang Province,No.R2110159,No.LY15H030006 and No.LY16H030003Science Technology Project of Zhejiang Province,No.2014C33205
文摘AIM: To investigate the expression pattern of plasma long noncoding RNAs(lnc RNAs) in Chrohn's disease(CD) patients.METHODS: Microarray screening and q RT-PCR verification of lnc RNAs and m RNAs were performed in CD and control subjects, followed by hierarchy c l u s t e r i n g, G O a n d K E G G p a t h w a y a n a l y s e s. Significantly dysregulated lnc RNAs were categorized into subgroups of antisense lnc RNAs, enhancer lnc RNAs and linc RNAs. To predict the regulatory effect of lnc RNAs on m RNAs, a CNC network analysis was performed and cross linked with significantly changed lnc RNAs. The overlapping lnc RNAs were randomly selected and verified by q RT-PCR in a larger cohort. RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lnc RNAs as well as 1020 up-regulated and 953 down-regulated m RNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lnc RNAs, whereas TBC1D17 and CCL3L3 had the highest foldchange of the up- and down-regulated m RNAs. Six(SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 m RNAs and 8(NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lnc RNAs showed the same change trends on the microarray and q RT-PCR results with statistical significance. Based on the q RT-PCR verified m RNAs, 1358 potential lnc RNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network. CONCLUSION: The plasma lnc RNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lnc RNA-m RNA pathway exploration.
基金Part of studies cited in this review was in partsupported by Johns Hopkins Institutional ResearchGrant(Ye,SQ),a pilot project(Ye,SQ)in The Hop-kins DK Center for the Analysis of Gene Expres-sion(R24DK58757-01,NIDDK)and Dorothy WallisWagner Charitable Tru
文摘The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.
基金Supported by Grants from the Ministry of Health of the China,No.W2012RQ02Shanghai Science and Technology Committee,No.12nm0501402Shanghai Education Committee,No.120311
文摘AIM: To investigate the microRNA(miRNA) expression profile in gastrointestinal stromal tumor(GIST) tissues that could serve as a novel diagnostic biomarker for GIST detection.METHODS: We performed a quantitative real-time quantitative reverse transcriptase polymerase chain reaction assay to analyze the expression of 1888 miRNAs in a sample set that included 54 GIST tissue samples.RESULTS: We found that dysregulation of several miRNAs may be related to the malignant potential of GISTs. Six of these miRNAs, hsa-let-7c, miR-218,miR-488#, miR-4683, miR-34c-5p and miR-4773, were selected as the final list of biomarkers to separate the malignant GISTs(M group) from the benign GISTs(B group). In addition, MiR-29b-2#, hsa-let-7c, miR-891 b, miR-218, miR-204, miR-204-3p, miR-628-5p,miR-744, miR-29c#, miR-625 and miR-196 a were used to distinguish between the borderline(BO group) and M groups. There were 11 common miRNAs selected to separate the benign and borderline(BB) group from the M group, including hsa-let-7c, miR-218, miR-628-5p,miR-204-3p, miR-204, miR-891 b, miR-488#, miR-145,miR-891 a, miR-34c-5p and miR-196 a.CONCLUSION: The identified miRNAs appear tobe novel biomarkers to distinguish malignant from benign GISTs, which may be helpful to understand the mechanisms of GIST oncogenesis and progression,and to further elucidate the characteristics of GIST subtypes.
基金supported by the Natural Science Foundation of Shaanxi Province of China,No.2018JQ8029(to LG)
文摘Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury,which may affect the microenvironment of the damaged site.Microarray analysis provides a new opportunity for investigating diagnosis,treatment,and prognosis of spinal cord injury.However,differentially expressed genes are not consistent among studies,and many key genes and signaling pathways have not yet been accurately studied.GSE5296 was retrieved from the Gene Expression Omnibus DataSet.Differentially expressed genes were obtained using R/Bioconductor software(expression changed at least two-fold;P < 0.05).Database for Annotation,Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors.The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease.In total,this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5,4,and 24 hours,and 3,7,and 28 days after spinal cord injury.The number of downregulated genes was smaller than the number of upregulated genes at each time point.Database for Annotation,Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord.Additionally,expression levels of these inflammation-related genes were maintained for at least 28 days.Moreover,399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes.Among the 10 upregulated differentially expressed genes with the highest degrees of distribution,six genes were transcription factors.Among these transcription factors,ATF3 showed the greatest change.ATF3 was upregulated within 30 minutes,and its expression levels remained high at28 days after spinal cord injury.These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.
文摘AIM To investigated the association between the tumor cells' expression of E-cadherin and the numbers of several types of inflammatory cells infiltrating into the invasive portion of gallbladder cancer(GBC).METHODS We analyzed 50 GBC cases for which a sufficient amount of tumor tissues for tissue microarray(TMA) had been saved. Three tissue cores(3.0 mm) of invasive lesion from each case were used for the TMA. The 4-μm cut sections on slides were immunostained using primary antibodies including E-cadherin for cancer cells, leukocyte common antigen for leukocyte, myeloperoxidase for neutrophils, CD3 for T cells, CD4 for helper T cells, CD8 for killer T cells, CD20 for B cells and CD68 for macrophages. The immunostained slides were digitally analyzed by imaging analysis software.RESULTS A significant inverse correlation between the number of infiltrating CD8^+ cells at invasive areas and the expression of E-cadherin by cancer cells was observed(P = 0.0001), although the degree of this correlation was relatively weak(R = 0.32). The number of CD8^+ cells and the cancer cells' E-cadherin expression were also significantly correlated with tumor differentiation(welldifferentiated vs poorly differentiated)(P = 0.0467 and P = 0.0294, respectively). Inverse correlation of T-stageand the number of CD8^+ cell infiltration was observed with statistical significance in comparison of T2 and T3 cases(P = 0.0324).CONCLUSION Our findings indicate an inverse correlation of CD8^+ T cell infiltration and cancer cells' E-cadherin expression at invasive areas of GBC. Further analyses are essential to test these findings.
基金supported by the National Key Research&Development Program of China,No.2017YFA0104702(to AJS)the National Basic Research Program of China(973 Program),No.2014CB542201(to JP)
文摘A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a basis for potential treatments of peripheral nerve injury.The study was approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital,China(approval number:2016-x9-07)in September 2016.
基金This work is supported by the City University of Hong Kong through a Strategic Research Grant (CityU Project No. 7001113).
文摘Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for selection of the multidrug resistant (MDR) cell lines. Methods: We used cDNA microarrays containing 12,720 sequences of known genes, expressed sequence tags and unknown clones to monitor gene expression profiles in MDR KB cells. Results: Preliminary data analysis showed that 18 genes were up-regulated and 18 genes were down-regulated by comparison of expression patterns between KB 3-1 and MDR KB-V1 cells. Furthermore, the highly over-expressed CGA, CLU genes in MDR KB-V1 cell were verified with conventional Northern blot analysis. These genes contain information predictive of drug resistance of cancer cells. Conclusion: Our study demonstrates that genome-wide gene expression profiling by using cDNA microarray technique is a valuable approach in obtaining molecular mechanism of drug resistance in cancer cells.
