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Induction of ZCCHC6 expression in peripheral blood mononuclear cells by HNSCC secretions

GENE 2020年 754卷 144880-144880页

作者： Arayataweegool, Areeya Srisuttee, Ratakorn Bin-Alee, Fardeela Mahattanasakul, Patnarin Tangjaturonrasme, Napadon Kerekhanjanarong, Virachai Mutirangura, Apiwat Kitkumthorn, Nakarin Chulalongkorn Univ Fac Med Ctr Excellence Mol Genet Canc & Human Dis Dept Anat Bangkok 10330 Thailand King Mongkuts Inst Technol Ladkrabang Fac Med Bangkok 10520 Thailand Chulalongkorn Univ Fac Med Program Med Sci Bangkok 10330 Thailand Chulalongkorn Univ Fac Med Dept Otolaryngol Head & Neck Surg Bangkok 10330 Thailand Thai Red Cross Soc King Chulalongkorn Mem Hosp Dept Otolaryngol Head & Neck Surg Bangkok 10330 Thailand Mahidol Univ Fac Dent Dept Oral Biol Payathai Rd Bangkok 10400 Thailand

Cancer secretion can change the properties of adjacent cells, including peripheral blood mononuclear cells (PBMCs). We investigated whether such secretion influences messenger RNA expression in PBMCs of patients with head and neck squamous cell carcinoma (HNSCC). In the present study, co-culture model of normal PBMCs and HNSCC cell lines were established. The PBMCs were subsequently subjected to RNA sequencing for transcriptome analysis. Furthermore, expression data from the Gene expression Omnibus repository, platform GPL4133, series GSE39400, were gathered to analyze, afterward identify zinc finger CysCysHisCys (CCHC)-type domain-containing protein 6 (ZCCHC6) as the main gene involved in HNSCC. This gene was then validated by a quantitative real-time polymerase chain reaction. The results showed that ZCCHC6 was expressed at significantly higher levels in the patients with HNSCC than in the healthy controls, and the sensitivity and specificity of these findings for diagnostic purposes were 100.00% and 70.83%, respectively. In summary, our findings demonstrated that the secretion of HNSCC cells could cause the alterations in messenger RNA expression by PBMCs. The ZCCHC6 expression level may apply in HNSCC screening.

关键词： Head and neck squamous cell carcinoma (HNSCC) Peripheral blood mononuclear cells (PBMCs) RNA sequencing expression array ZCCHC6 expression

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Female-specific risk of Alzheimer's disease is associated with tau phosphorylation processes: A transcriptome-wide interaction analysis

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NEUROBIOLOGY OF AGING 2020年 96卷 104-108页

作者： Caceres, Alejandro Gonzalez, Juan R. Inst Salud Global Barcelona ISGlobal Div Noncommunicable Dis Barcelona Spain Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE Madrid Spain Univ Autonoma Barcelona Dept Math Barcelona Spain

The levels of tau phosphorylation differ between sexes in Alzheimer's disease (AD). Transcriptome-wide associations of sex by disease interaction could indicate whether specific genes underlie sex differences in tau pathology;however, no such study has been reported yet. We report the first analysis of the effect of the interaction between disease status and sex on differential gene expression, meta-analyzing transcriptomic data from the 3 largest publicly available case-control studies (N = 785) in the brain to date. A total of 128 genes, significantly associated with sex-AD interactions, were enriched in phosphoproteins (false discovery rate (FDR) = 0.001). High and consistent associations were found for the overexpressions of NCL (FDR = 0.002), whose phosphorylated protein generates an epitope against neurofibrillary tangles and KIF2A (FDR = 0.005), a microtubule-associated motor protein gene. Transcriptome-wide interaction analyses suggest sex-modulated tau phosphorylation, at sites like Thr231, Ser199, or Ser202 that could increase the risk of women to AD and indicate sex-specific strategies for intervention and prevention. (C) 2020 Elsevier Inc. All rights reserved.

关键词： Alzheimer's disease Female risk Sexual dimorphism Gene expression Transcriptome expression array Tau Phosphorylation Neurofibrillary tangles NCL KIF2A Transcriptome-wide interaction analysis Differential expression

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Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients

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GENES CHROMOSOMES & CANCER 2019年第3期58卷 164-174页

作者： Garcia-Diez, Irene Hernandez-Munoz, Inmaculada Hernandez-Ruiz, Eugenia Nonell, Lara Puigdecanet, Eulalia Bodalo-Torruella, Marta Andrades, Evelyn Pujol, Ramon M. Toll, Agusti UAB Hosp del Mar Dept Dermatol Barcelona Spain Hosp del Mar Grp Inflammatory & Neoplast Dermatol Dis IMIM Med Res Inst Barcelona Spain UAB Hosp Univ Vall Hebron Dept Dermatol Barcelona Spain Hosp del Mar Microarray Anal Serv IMIM Med Res Inst Barcelona Spain

Although most cutaneous squamous cell carcinomas (cSCCs) develop from actinic keratoses (AKs), the key events in this evolution remain unclear. We have combined the results of different genomic and expression array platforms on matched concomitant samples of sun-exposed skin (SES), AK, and cSCC from 10 immunocompetent patients. Gene expression analysis and copy number alterations were assessed using GeneChip Human Gene 2.0 ST array (Affymetrix, Santa Clara, CA) and CytoScan HD Cytogenetics Solution (Affymetrix) platforms, respectively. Integration of transcriptome and genome results was evaluated using the DR-Integrator tool. Additional studies (qPCR, immunohistochemistry, and Western blot) were performed for selected genes. FOSL1 and BNC1 encode transcription factors whose expression was increased in cSCC in the expression array and the qPCR. By immunohistochemistry, FOSL1 showed an intense staining at the invasive front of cSCC samples and BNC1 expression varied from a nuclear (SES) to a cytoplasmic location (cSCC). Western blot analyses confirmed the enhancement of FOSL1 and BNC1. In addition, the smallest overlapping regions (SORIs) of genomic imbalance involving at least three of the samples were selected. One of the SORIs was a deletion in the p24.1 band of chromosome 3, shared by seven of the cSCCs. A strong correlation in the integration analysis was found for NEK10, a gene contained in the previously mentioned SORI. Loss of NEK10 expression in cSCC was confirmed by immunohistochemistry and Western blot analyses. In addition, functional studies in NEK10 depleted cells were performed. In conclusion, we identified FOSL1 and BNC1, which could act as tumor drivers, and NEK10, which could function as a tumor suppressor, to be differentially expressed during cSCC development.

关键词： actinic keratosis copy number alterations cutaneous squamous cell carcinoma expression array NEK10

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Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics

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PHYSIOLOGICAL GENOMICS 2019年第1期51卷 27-41页

作者： Levy, Hara Jia, Shuang Pan, Amy Zhang, Xi Kaldunski, Mary Nugent, Melodee L. Reske, Melissa Feliciano, Rachel A. Quintero, Diana Renda, Michael M. Woods, Katherine J. Murkowski, Kathy Johnson, Keven Verbsky, James Dasu, Trivikram Ideozu, Justin Eze McColley, Susanna Quasney, Michael W. Dahmer, Mary K. Avner, Ellis Farrell, Philip M. Cannon, Carolyn L. Jacob, Howard Simpson, Pippa M. Hessner, Martin J. Stanley Manne Childrens Res Inst Chicago Human Mol Genet Program Chicago IL USA Ann & Robert H Lurie Childrens Hosp Chicago Dept Pediat Div Pulm Med Chicago IL 60611 USA Northwestern Univ Feinberg Sch Med Chicago IL 60611 USA Med Coll Wisconsin Dept Pediat Div Endocrinol 8701 Watertown Plank Rd Milwaukee WI 53226 USA Med Coll Wisconsin Dept Pediat Max McGee Natl Res Ctr Juvenile Diabet 8701 Watertown Plank Rd Milwaukee WI 53226 USA Childrens Hosp Wisconsin Childrens Res Inst Milwaukee WI 53201 USA Med Coll Wisconsin Dept Pediat Div Quantitat Hlth Sci 8701 Watertown Plank Rd Milwaukee WI 53226 USA Med Coll Wisconsin Dept Pediat Div Pulmonol 8701 Watertown Plank Rd Milwaukee WI 53226 USA Med Coll Wisconsin Div Pediat Crit Care Med Milwaukee WI 53226 USA Med Coll Wisconsin Dept Pediat Div Rheumatol 8701 Watertown Plank Rd Milwaukee WI 53226 USA Univ Michigan Sch Med Div Pediat Crit Care Med Ann Arbor MI USA Med Coll Wisconsin Dept Pediat Div Nephrol 8701 Watertown Plank Rd Milwaukee WI 53226 USA Univ Wisconsin Sch Med & Publ Hlth Dept Pediat & Populat Hlth Sci Madison WI USA Baylor Coll Med Dept Pediat Div Pulm Med Houston TX 77030 USA Hudson Alpha Genom Med Inst Biotechnol Huntsville AL USA

Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and the development of inflammation and progression of lung disease are not fully understood, which limits our ability to predict an individual patient's clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status with plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients (n = 103) and unrelated, healthy controls (n = 31). Gene expression levels were measured with an Affymetrix microarray (GeneChip Human Genome U133 Plus 2.0). Peripheral blood samples from a subset of the CF patients (n = 40) were immunophenotyped by flow cytometry. and the data were compared with historical data for age-matched healthy controls (n = 351). Plasma samples from another subset of CF patients (n = 56) and healthy controls (n = 16) were analyzed by multiplex enzyme-linked immunosorbent assay (ELISA) for numerous cytokines and chemokines. Principal component analysis and hierarchical clustering of induced transcriptional data revealed disease-specific plasma-induced PBMC profiles. Among 1,094 differentially expressed probe sets. 51 genes were associated with pancreatic sufficient status, and 224 genes were associated with infection with Pseudomonas aeruginosa. The flow cytometry and ELISA data confirmed that various immune modulators are relevant contributors to the CF molecular signature. This study provides strong evidence for distinct molecular signatures among CF patients. An understanding of these molecular signatures may lead to unique molecular markers that will enable more personalized prognoses, individualized treatment plans, and rapid monitoring of treatment response.

关键词： cystic fibrosis expression array lung disease molecular signature RNA

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Precursor lesions of vulvar squamous cell carcinoma - histology and biomarkers: A systematic review

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CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2020年第0期147卷 102866-000页

作者： Dasgupta, Shatavisha Ewing-Graham, Patricia C. Swagemakers, Sigrid M. A. van der Spek, Peter J. van Doorn, Helena C. Hegt, Vincent Noordhoek Koljenovic, Senada van Kemenade, Folkert J. Erasmus MC Univ Med Ctr Rotterdam Dept Pathol Postbus 2040Be Bldg NL-3000 CA Rotterdam Netherlands Erasmus MC Univ Med Ctr Rotterdam Dept Bioinformat Rotterdam Netherlands Erasmus MC Canc Inst Dept Gynecol Oncol Rotterdam Netherlands

The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high grade squamous intraepithelial lesion (HSIL), and HPV-independent differentiated VIN (dVIN). Traditionally, histology and immunohistochemistry (IHC) have been the basis of diagnosis and classification of VIN. HSIL shows conspicuous histological atypia, and positivity on p16-IHC, whereas dVIN shows less obvious histological atypia, and overexpression or null-pattern on p53-IHC. For both types of VIN, other diagnostic immunohistochemical markers have also been evaluated. Molecular characterization of VIN has been attempted in few recent studies, and novel genotypic subtypes of HPV-independent VSCC and VIN have been identified. This systematic review appraises the VSCC precursors identified so far, focusing on histology and biomarkers (immunohistochemical and molecular). To gain further insights into the carcinogenesis and to identify additional potential biomarkers, gene expression omnibus (GEO) datasets on VSCC were analyzed;the results are presented.

关键词： Vulva Squamous cell carcinoma Vulvar intraepithelial neoplasia Precursor lesion Biomarker Immunohistochemistry Histology expression array Systematic review

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RNA-Seq and expression arrays: Selection Guidelines for Genome-Wide expression Profiling

RNA-Seq and Expression Arrays: Selection Guidelines for Geno...

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作者： Jessica Minnier Nathan D. Pennock Qiuchen Guo Pepper Schedin Christina A. Harrington

The development of genome-wide gene expression profiling technologies over the past two decades has produced great opportunity for researchers to explore the transcriptome and to better understand biological systems and their perturbation. In this chapter we provide an overview of microarray and massively parallel sequencing technologies and their application to gene expression analysis. We discuss factors that impact expression data generation and analysis that which should be considered in the application of these technology platforms. We further present the results of a simple illustration study to highlight performance similarities and differences in expression profiling of protein-coding mRNAs with each platform. Based on technical and analytical differences between the two platforms, reports in the literature comparing arrays and RNA-Seq for gene expression, and our own example study and experience, we provide recommendations for platform selection for gene expression studies. less

关键词： Massively Parallel Signature Sequencing Microarray RNA-seq Gene expression Profiling Gene expression Analysis Differential expression expression array

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Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia

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CLINICAL AND EXPERIMENTAL IMMUNOLOGY 2018年第2期191卷 240-251页

作者： Isaksson, H. S. Farkas, S. A. Muller, P. Gustafsson, D. Nilsson, T. K. Orebro Univ Orebro Univ Hosp Fac Med & Hlth Dept Lab Orebro Sweden Karolinska Inst Affymetrix Core Facil Novum BEA Huddinge Sweden Orebro Univ Fac Med & Hlth Orebro Univ Hosp Dept Pediat Orebro Sweden Umea Univ Dept Med Biosci Clin Chem Umea Sweden

A child, 2 years with the hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38 degrees C, thrombocythaemia of >700x10(9)/l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 20 array in blood on three occasions 3-5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis;a large number of interleukins, their receptors and activators, accounting for the febrile apathic state;and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

关键词： expression array fever hypercalprotectinaemia hyperzincaemia thrombocytaemia

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expression of microRNAs in tumors of the central nervous system in pediatric patients in M,xico

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CHILDS NERVOUS SYSTEM 2017年第12期33卷 2117-2128页

作者： Eguia-Aguilar, Pilar Gutierrez-Castillo, Lisette Perezpena-Diazconti, Mario Garcia-Chequer, Jeanette Garcia-Quintana, Jorge Chico-Ponce de Leon, Fernando Gordillo-Dominguez, Luis Torres-Garcia, Samuel Arenas-Huertero, Francisco Hosp Infantil Mexico Dr Federico Gomez Dept Patol Clin & Expt Mexico City DF Mexico Univ Simon Bolivar Fac Ciencia & Tecnol Mexico City DF Mexico Hosp Infantil Mexico Dr Federico Gomez Dept Neurocirugia Mexico City DF Mexico Hosp Infantil Mexico Dr Federico Gomez Lab Invest Patol Expt Inst Nacl Salud Dr Marquez 162 Mexico City 06720 DF Mexico

MicroRNAs were identified as molecules that participate in gene regulation;alterations in their expression characterize central nervous system (CNS). Information in pediatrics is scarce, so the objective of this work was to determine and then compare the patterns of expression of microRNAs in astrocytomas, ependymomas, and medulloblastomas, as well as in non-neoplastic brain. Low-density arrays were utilized to evaluate 756 microRNAs in three samples of each type of tumor and non-neoplastic brain. The relative expression was calculated in order to identify the three microRNAs whose expression was modified notably. This was verified using RT-qPCR in more number of tumor samples. The microRNAs selected for testing were miR-100-5p, miR-195-5p, and miR-770-5p. A higher expression of miR-100-5p was observed in the astrocytomas and ependymomas compared to the medulloblastomas: on average 3.8 times (p < 0.05). MiR-770-5p was expressed less in medulloblastomas compared to astrocytomas four times (p = 0.0162). MiR-195-5p had a low expression in medulloblastomas compared to non-neoplastic cerebellum (p = 0.049). In all three tumor types, expression of miR-770-5p was lower than in non-neoplastic brain (p < 0.001). These microRNAs may represent potential markers in these tumors.

关键词： Epigenetic Astrocytomas Ependymomas Medulloblastomas expression array

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Effect of Extremely Low Frequency Magnetic Fields on Cell Proliferation and Gene expression

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BIOELECTROMAGNETICS 2015年第7期36卷 506-516页

作者： Lee, Hyung Chul Hong, Mi-Na Jung, Seung Hee Kim, Bong Cho Suh, Young Ju Ko, Young-Gyu Lee, Yun-Sil Lee, Byeong-Yoon Cho, Yeun-Gyu Myung, Sung-Ho Lee, Jae-Seon Inha Univ Coll Med Dept Biomed Sci Inchon 400712 South Korea Korea Inst Radiol & Med Sci Res Ctr Radio Senescence Seoul South Korea Korea Univ Sch Life Sci & Biotechnol Seoul South Korea Ewha Womans Univ Coll Pharm Seoul South Korea Ewha Womans Univ Div Life Sci & Pharmaceut Seoul South Korea Korea Electrotechnol Res Inst Smart Grid Res Div Changwon Si South Korea

Owing to concerns regarding possible effects of extremely low frequency magnetic fields (ELF-MF) on human health, many studies have been conducted to elucidate whether ELF-MF can induce modifications in biological processes. Despite this, controversies regarding effects of ELF-MF are still rife. In this study, we investigated biological effects of ELF-MF on MCF10A, MCF7, Jurkat, and NIH3T3 cell lines. ELF-MF with a magnetic flux density of 1 mT at 60 Hz was employed to stimulate cells for 4 or 16 h, after which the effects of ELF-MF on cell proliferation, cell death, cell viability, and DNA synthesis rates were assessed. Whereas Jurkat and NIH3T3 cells showed no consistent variation in cell number, cell viability, and DNA synthesis rate, MCF10A and MCF7 cells showed consistent and significant decreases in cell number, cell viability, and DNA synthesis rates. However, there was no effect of ELF-MF on cell death in any of tested cell lines. Next, to investigate the effect of ELF-MF on gene expression, we exposed MCF7 cells to 2 mT at 60 Hz for 16 h and examined transcriptional responses by using gene expression array. We found a gene, PMAIP1, that exhibited statistically significant variation using two-fold cut-off criteria and certified its expression change by using semi-quantitative and quantitative reverse transcription polymerase chain reaction. From these results, we concluded that ELF-MF could induce the delay of cell cycle progression in MCF7 and MCF10A cells in a cell context-specific manner and could up-regulate PMAIP1 in MCF7 cells. (C) 2015 Wiley Periodicals, Inc.

关键词： ELF-MF cell number cell viability DNA synthesis rate expression array

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Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells

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BMC CANCER 2014年第1期14卷 1-13页

作者： Leithner, Katharina Wohlkoenig, Christoph Stacher, Elvira Lindenmann, Joerg Hofmann, Nicole A. Galle, Birgit Guelly, Christian Quehenberger, Franz Stiegler, Philipp Smolle-Juettner, Freyja-Maria Philipsen, Sjaak Popper, Helmut H. Hrzenjak, Andelko Olschewski, Andrea Olschewski, Horst Med Univ Graz Dept Internal Med Div Pulmonol A-8036 Graz Austria Med Univ Graz Inst Pathol A-8036 Graz Austria Med Univ Graz Dept Surg Div Thorac & Hyperbar Surg A-8036 Graz Austria Med Univ Graz Stem Cell Res Unit A-8010 Graz Austria Med Univ Graz Inst Mol Biol & Biochem A-8010 Graz Austria Med Univ Graz Med Res Ctr Core Facil Mol Biol A-8010 Graz Austria Med Univ Graz Inst Med Informat Stat & Documentat A-8036 Graz Austria Med Univ Graz Dept Surg Div Transplant Surg A-8036 Graz Austria Erasmus Univ Med Ctr Dept Cell Biol NL-3000 CA Rotterdam Netherlands Med Univ Graz Univ Clin Anesthesiol & Intens Care Med A-8036 Graz Austria Ludwig Boltzmann Inst Lung Vasc Res A-8010 Graz Austria

Background: Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo. Methods: Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays. Results: Apoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets. Conclusions: The novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under

关键词： Hypoxia Tumor expression array Prognosis

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