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@#Abstract:Objective - ToinvestigatetheeffectofchrysotileasbestosongeneexpressioninhumanbronchialepithelialBEAS 2B Methods - cells. BEAS 2B cells were randomly divided into two groups. The cells in the chrysotile malignant transformation- groupweretreatedwith 20μg/cm²chrysotiletoestablishthechrysotileinducedmalignanttransformationBEAS 2Bcellmodel, andthecellsinthecontrolgroupweretreatedwiththesamevolumeofphosphatesaltbuffersolution.ThetotalRNAinthecells--wasextractedandthecDNAwassynthesizedbyreversetranscription.Cy5dCTPandCy3dCTPfluoresceinwereusedtolabel the two groups to prepare probes for chip scanning. LuxScan 3.0 image analysis software was used to analyze the fluorescence signal of labeled DNA, and the differentially expressed genes were screened. The Kyoto Encyclopedia of Genes and Genomes Results (KEGG) signaling pathway analysis and Gene Ontology (GO) enrichment analysis were carried out. There were 642 - - differentiallyexpressedgenes(193up regulatedand449down regulated)inchrysotilemalignanttransformationgroupcompared with the control group. The KEGG signaling pathway analysis and GO enrichment analysis showed that the differentially - expressed genes in the malignant transformed BEAS 2B cells induced by chrysotile asbestos were mainly involved in P53 - signaling pathway, histone H3 K9 methylation and methylenetetrahydrofolate reductase deficiency pathway, phosphoinositide binding protein 3 activated protein kinase B signaling pathway, nucleoside phosphate metabolism process and the expression Conclusion inhibitionofhistocompatibilitycomplexⅡantigenpresentation. Chrysotileasbestoscaninducethechangeofgene - - expression profile in BEAS 2B cells. The P53 signaling pathway, histone H3 K9 methylation and other related pathways are
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Biclustering is an increasingly used data mining technique for searching groups of co-expressed genes across the subset ofexperimental conditions from the gene-expression data. The group of co-expressed genes is present in the form of variouspatterns called a bicluster. A bicluster provides significant insights related to the functionality of genes and plays animportant role in various clinical applications such as drug discovery, biomarker discovery, gene network analysis, geneidentification, disease diagnosis, pathway analysis etc. This paper presents a novel unsupervised approach ‘COmprehensiveSearch for Column-Coherent Evolution Biclusters (COSCEB)’ for a comprehensive search of biologically significantcolumn-coherent evolution biclusters. The concept of column subspace extraction from each gene pair and LongestCommon Contiguous Subsequence (LCCS) is employed to identify significant biclusters. The experiments have beenperformed on both synthetic as well as real datasets. The performance of COSCEB is evaluated with the help of key issues.The issues are comprehensive search, Deep OPSM bicluster, bicluster types, bicluster accuracy, bicluster size, noise,overlapping, output nature, computational complexity and biologically significant biclusters. The performance of COSCEBis compared with six all-time famous biclustering algorithms SAMBA, OPSM, xMotif, Bimax, Deep OPSM- and UniBic.The result shows that the proposed approach performs effectively on most of the issues and extracts all possible biologicallysignificant column-coherent evolution biclusters which are far more than other biclustering algorithms. Along with theproposed approach, we have also presented the case study which shows the application of significant biclusters for hub geneidentification.
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Introducción Las plataformas genómicas han tomado gran relevancia como factores pronósticos y predictivos para definir tratamiento adyuvante en pacientes con cáncer de mama. Su uso permitiría discriminar un subgrupo de pacientes en quienes la indicación de quimioterapia podría ofrecer más morbilidad que verdadero beneficio. Objetivos Describir las características de las pacientes en quienes se utilizó la plataforma Oncotype DX® y evaluar el impacto del Score de Recurrencia (Recurrence Score) como herramienta de decisión para la indicación de adyuvancia. Material y método Se consideraron pacientes operadas entre 2013 y 2017 en el Hospital Italiano de Buenos Aires, Argentina, con diagnóstico de carcinoma invasor primario de mama de subtipo Luminal A o B, her2neu negativas. Se seleccionaron los casos en los que se solicitó Oncotype DX® y se describieron sus características clínicas e histológicas. Resultados Se utilizó Oncotype DX® en 47 pacientes con cáncer de mama invasor. En el 48,9% se obtuvo un Recurrence Score de riesgo bajo, en el 40,4% de riesgo intermedio y en el 10,6% de riesgo alto. En 22 casos (46,8%) consideramos que hubo un cambio de conducta en la indicación de adyuvancia. Conclusiones En nuestra experiencia, hemos visto que la plataforma genómica Oncotype DX® sería una herramienta útil para definir tratamiento adyuvante en tumores de tipo Luminal, her2neu negativo.
Introduction Over the past decade, gene expression assays have become relevant prognostic factors for guiding clinical decision-making in patients with breast cancer. Their use allows to discriminate which patients are most likely to benefit from chemotherapy in the adjuvant setting, avoiding unnecessary toxicity. Objectives To describe the clinical and pathologic characteristics of patients in whom Oncotype DX® was used as a prognostic factor and assess the impact of the Recurrence Score on clinical decision-making. Materials and method Patients who underwent surgery at the Hospital Italiano de Buenos Aires, Argentina, between 2013 and 2017 for Estrogen-Receptor positive (er+), her2neu negative primary breast cancer were considered eligible. We evaluated the cases in which Oncotype DX® was ordered and described the clinical and pathologic characteristics, as well as whether Recurrence Score (rs) modified the prescription of adjuvant therapy. Results Oncotype DX® was performed in 47 patients. The distribution of patients according to rs was as follows: low risk rs 48,9%, intermediate risk 40,4% and high risk 10,6%. We considered that adjuvant therapy decision was modified after rs in 22 patients (46,8%). Conclusions Oncotype DX® and its resulting Recurrence Score appear to be a clinically useful tool for decision-making in the adjuvant setting for patients with er+, her2neu negative breast cancer.
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Humans , Female , Breast Neoplasms , Recurrence , Therapeutics , Genomics , Drug Therapy , GenesABSTRACT
A Síndrome Mielodisplásica (SMD) é um grupo de doenças clonais das células progenitorashematopoiéticas, caracterizadas por citopenia(s) periférica(s), displasia de uma ou mais linhagenscelulares mielóides e aumento do risco de desenvolvimento de leucemia mielóide aguda. A SMD éconsiderada uma doença de pessoas idosas, pois aproximadamente 80% dos pacientes possuemmais de 60 anos ao diagnóstico. As causas da SMD são conhecidas em apenas 15% dos casos. Emrelação aos fatores ambientais como desencadeadores da SMD, podem ser incluídos o uso dequimioterapia prévia, especialmente de agentes alquilantes e análogos da purina, radioterapia etabagismo. A patogênese da SMD envolve danos no DNA nas células tronco hematopoéticasacometido provavelmente pelos danos de fita dupla (DSB) no DNA tendo o processo de junções porextremidades não-homólogas (JENH) e recombinação homóloga como principais mecanismos dereparo necessários para garantir a estabilidade genômica das células-tronco. Este estudo de coortepropôs avaliar o nível de expressão do mRNA dos genes atuantes no mecanismo de reparo emdanos de fita dupla no DNA (BRCA1, BRCA2 e RAD51, atuantes no mecanismo de RecombinaçãoHomóloga; o XRCC5, XRCC6 e LIG4 relacionados ao mecanismo de Junções por Extremidadesnão-Homólogas e, por fim, o ATM) associando os achados moleculares com suas variantespolimórficas (rs4793191, rs9567623, rs1801320, rs3835, rs2267437, rs1805388 e rs228593,respectivamente) e com variáveis clínicas e sócio-demográficas de pacientes portadores deSíndrome Mielodisplásica...
The myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorderscharacterized by cytopenia (s) peripheral (s), dysplasia of one or more myeloid cell lineages andincreased risk of acute myeloid leukemia development. MDS is considered a disease of elderlypeople, since approximately 80% of patients are over 60 years of diagnosis. The causes of MDS areknown only in 15% of cases. With respect to environmental factors such as MDS triggers may beincluded the use of prior chemotherapy, especially alkylating agents and purine analogs, radiationtherapy and smoking. The pathogenesis of MDS involves DNA damage in hematopoietic stem cellsaffected probably by double-stranded damage (DSB) in the DNA and the case of joints by nonhomologousends (NHEJ) and homologous recombination main repair mechanisms necessary toensure stability genomics of stem cells. This cohort study aimed to assess the level of expression ofmRNA of the genes active in the repair mechanism of double-stranded DNA damage (BRCA1,BRCA2 and RAD51, operating in HR mechanism, the XRCC5, XRCC6 and LIG4 related mechanismfor NHEJ and, finally, the ATM) linking the molecular findings with their polymorphic variants(rs4793191, rs9567623, rs1801320, rs3835, rs2267437, rs1805388 and rs228593, respectively) andwith clinical and socio-demographic of patients of Myelodysplastic Syndromes...
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Humans , Gene Expression , DNAABSTRACT
KLF9(Kruppel-likefactor9)isthetranscriptionfactorthatcanbindGC-richsitesthrough three C2H2-type zinc fingers and can regulate diverse biological processes,including cell proliferation,apopto-sis and the development of the organ.KLF9 is downregulated in some tumor specimens and tumorous cell lines relative to the normal samples and cell lines and plays an important role in the growth of cancer cells.Similar with the other KLF numbers,KLF9 could affect the development of tumors,especially for the endocrine-related cancers through multiple signaling pathways and interventions with other proteins.
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Objective To explore the association of expression of apoptosis-associated gene BAK and cFLIP with the biological behaviors in endometriosis. Methods The expression of BAK and cFLIP protein gene in eutopic and ectopic tissue samples from 40 cases with pathologically confirmed ovarian endometriosis and 40 cases with pathologically confirmed normal endometrium was detected by immunohistochemical method. Results ①The expression of BAK and cFLIP protein gene was found in three groups of different endometrial tissue. ②The expression of BAK protein gene was increased gradually in ectopic endometrial , eutopic endometrium and normal tissue and there was significantly difference between every two groups ,while cFLIP was contrary expressed (P 0.05). ④The expression of BAK protein gene in severe group (Ⅲ-Ⅳ period) is lower than mild group both in eutopic or ectopic endometrial tissues,while cFLIP was contrary expressed (P < 0.05). ⑤The expression of BAK and cFLIP was negatively correlated with each other in ectopic endometrium (r=-0.389,P< 0.05). Conclusion BAK and cFLIP was negatively expressed in EMS, which may take a part in the endometrial apoptosis and disorderly proliferation. BAK and cFLIP may play an important role in the the diagnosis and treatment of endometriosis.
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Even though the molecular mechanisms underlying the Down syndrome (DS) phenotypes remain obscure, the characterization of the genes and conserved non-genic sequences of HSA21 together with large-scale gene expression studies in DS tissues are enhancing our understanding of this complex disorder. Also, mouse models of DS provide invaluable tools to correlate genes or chromosome segments to specific phenotypes. Here we discuss the possible contribution of HSA21 genes to DS and data from global gene expression studies of trisomic samples.
Embora os mecanismos moleculares que causam a síndrome de Down (SD) não sejam totalmente conhecidos, a caracterização de genes e seqüências não gênicas conservadas do HSA21 e os estudos de expressão em grande escala em amostras de pacientes com SD estão aumentando o entendimento da síndrome. Por outro lado, os modelos murinos da SD provêm ferramentas valiosas para correlacionar genes ou segmentos cromossômicos a características fenotípicas específicas. Nesta revisão, são discutidas as possíveis contribuições dos genes do HSA21 à SD e os dados de estudos de expressão gênica global de amostras trissômicas.
Subject(s)
Animals , Humans , Mice , /genetics , Down Syndrome/genetics , Gene Expression Profiling , Disease Models, Animal , PhenotypeABSTRACT
Objective To investigate the signaling mechanisms underlying synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae(NTHi)and epidermal growth factor (EGF).Methods The expression of MUC5AC was measured by real-time quantitative polymerase chain reaction(PCR)and Luciferase assay.Western blot was performed to examine the synergistic induction of phosphorylation of P38,extracellular signal-regulated kinase(ERK)and P21-activated kinase(PAK)4 or the effect of dominant negative mutant of PAK4 on the synerglstic induction of phosphorvlation of P38 mitogen-activated protein kinase(P38MAPK)and ERK in HM3 cells treated with NTHi and EGF.Luciferase asgay was also performed to examine the effect of P38,ERK inhibitors or dominant negative mutants of P38MAPK and ERK on synergistic enhancement of NTHi-induced MUC5AC up-regulation by EGF at transcriptional level.Real-time quantitative PCR was performed to examine the effect of PAK4 siRNA on synergistic induction of NTHi-induced MUC5AC up-regulation by EGF.ResuIts NTHi induced MUC5AC mucin expression at both mRNA and transcriptional levels.Synergistic induction of phosFIhorylation of P38MAPK,ERK and PAK4 were observed in HM3 cells treated with NTHi and EGF.Either SB203580,a specific inhibitor for P38MAPK or PD98059,a specific inhibitor for ERK inhibited synergistic induction of MUC5AC at transcription level.Furthmore, overexpressing dominant negative mutant of P38MAPK and ERK also inhibited synergistic induction of MUC5AC at transcription level. PAK4 siRNA inhibited the synergistic induction of MUC5AC by NTHi and EGF. Overexpressing dominant negative mutant of PAK4 also reduccd synergistic induction of phosphorylation of P38 and ERK. Conclusion Synergistic induction of MUC5AC mucin by NTHi is up-regulated by EGF via PAK4-dependent P38MAPK and ERK pathways.
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Objective To investigate genes involved in the mechanisms underlying the progression of severe preeclampsia.Methods We conducted a muhiregional gene expression analysis using peripheral leucocytes from patients with preeclampsia and normal controls.Total RNA was extracted from peripheral blood of six severe preeclampsia and five normotensive pregnancies.We performed genome-wide expression profiling using Affymetrix HG_U133 plus 2.0 chips to screen out differentially expressed genes of 2 fold or more and q_value ＜ 5.4%.Using Gene Ontology we identified the function of differentially expressed genes after cluster analysis.Results Among the 47 000 genes that were screened in the microarray,140 genes were found to be differentially expressed between normal and preeclamptic pregnancies. Eighty six up-regulated candidate genes were mainly involved in cysteine metabolism urea cycle and metabolism of amiogroups,proteasome,TGF-beta signaling pathway, and the ratio of calponin2 (CNN2), matrix metallopeptidase 8 (MMP8),V-set and immunoglobulin domain containing 4 (VSIG4),proteasome 26S subunit ATPase 5 (PSMC5) was evidently increased in preeclampsia patients.Among 54 down-regulatedcandidates,natural killer cell mediated cytotoxicity,antigen processing and presentation,metabolism of xenobiotics by cytochrome P450 were the main pathways.KIR3DL2,AKR1C3,CHURC1 and SLC25A13 were obviously decreased in preeclampsia patients. Conclusions The gene expression of peripheral leucocytes in preeclampsia patients is significantly different from that of uncomplicated pregnancies.CNN2,MMP8,VSIG4,PSMC5,KIR3DL2,AKR1C3,CHURC1 and SLC25A13 may be involved in the molecular mechanisms underlying the progression of severe preeclampsia.
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Objective To observe the effect of inhaled nitric oxide(INO) on the nitric oxide synthase (NOS) in piglet suffered from severe meconium aspiration syndrome(MAS). Methods Severe MAS model of piglet was reproduced, the oxygenation effect and the activity of pulmonary NOS were measured, hybridization in situ of pulmonary slices was used to show the gene expression of inducible NOS(iNOS). Results INO therapy attenuated respiratory dysfunction in MAS, while discontinuation of INO induced “rebound pulmonary hypertension”. The activity of iNOS in MAS group is higher than that in control group (16.9?3.1) fmol/(mg Pro?min)vs (11.6?2.7) fmol/(mg Pro?min),( P
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Objective: To investigate the expression of Cyclin E in colorectal carcinoma and its significance.Methods: The Cyclin E expression and the cell proliferation(PI,SPF)in 30 cases of colorectal carcinomas (including tumors and normal tissues distant to the tumors)were respectively assayed with Flow Cytometry (FCM), and the relationships between the Cyclin E expressive rate and clinical pathologic features were compared. Correlaction between the Cyclin E expressive rate and the cell proliferation(PI, SPF) was analyzed too.Results: The Cyclin E positive rate and the cell proliferation in colorectal carcinoma were significantly higher than those of the distal normal tissues. As for the Cyclin E positive rate and the cell proliferation,no significant differences were found among the subgroups divided according to malignance, lymphatic metastasis and the site of tumor. There was a significant correlation between the Cyclin E positive rate and the cell proliferation.Conclusion: The Cyclin E overexpression plays an important role in the onset of colorectal carcinoma.The Cyclin E expressive rate is not consistent with the general clinical pathologic features,but with the cell proliferation. The Cyclin E expressive rate may be one of the potential prognostic indicators in coloretal carcinoma.
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Objective To study the expressions of neuroglobin gene in cellular tissues of human body.Methods Total 13 species tissue RNA, superscription RNA 2 ?g of every tissue was reversed into transcription cDNA and 1 ?l of cDNA was made into PCR template. Total RNA 2 ?g from every specimen equivalently were reversed into transcription cDNA. PCR products experienced agarose gel electrophoresis and electrophoresis and extraviolet-gelatum Image J was quantitatively analyzed. All data were indicated with ?s and treated with Oneway mono agent analysis of variance of stata statistical package,P
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Two Escherichia coli clones expressing Mycobacterium tuberculosis antigens were isolated from a gene-bank in the plasmid vector pBR 325. 'Western blot' analysis revealed the presence of a unique protein band of molecular weight 68,000 and 38,000, respectively in cellextracts from each clone. The 68,000 dalton antigen was found to be expressed on Escherichia coli outer surface. Plasmid DNA from a third clone could confer leucine independence on two different leu Β mutants of Escherichia coli but not on mutants in other leu genes, pointing to the possibility ofgenetic complementation. Thus, Mycobacterium tuberculosis DNA is capable of expression in Escherichia coli.