Transcriptional profiling of medulloblastoma in children

2003 ◽  
Vol 99 (3) ◽  
pp. 534-541 ◽  
Author(s):  
Paul C. Park ◽  
Michael D. Taylor ◽  
Todd G. Mainprize ◽  
Laurence E. Becker ◽  
Michael Ho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
High Mobility Group Protein ◽  
Content Type ◽  
Expression Levels ◽  
Histone Deacetylase 2 ◽  
New Genes ◽  
Fine Print

Object. Although medulloblastoma is the most common malignant brain tumor found in children, little is known about its molecular pathogenesis. The authors have attempted to compare patterns of gene expression in medulloblastoma samples with those in the healthy cerebellum. Methods. The authors used complementary (c)DNA microarray analysis to compare the expression of genes in samples of medulloblastoma and normal cerebellum. The expression levels of a subset of genes were then verified by immunohistochemical analysis. Six genes were identified that were expressed at a much higher level in at least five of six medulloblastomas: ezrin, cyclin D2, high mobility group protein 2, MAPRE1, histone deacetylase 2, and ornithine decarboxylase 1. A number of potentially important genes whose expression was much lower in medulloblastomas than in control cerebellum were also identified: tenascin R, TRK-B, FGF receptor, and death receptor 3. The expression levels of a subset of the identified genes were confirmed by immunohistochemical analysis, which was performed on fetal cerebellum and medulloblastoma samples. Conclusions. The authors demonstrate that cDNA microarray analysis is an effective method of increasing understanding of the molecular biology of medulloblastomas found in children. A comparison between gene expression patterns in medulloblastoma and those observed in healthy cerebellum may provide clues as to the origin of these tumors and may lead to the identification of new genes or pathways to be targeted for future therapies.

Interleukin-6 overexpression as a marker of malignancy in human gliomas

2001 ◽  
Vol 94 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Christine Rolhion ◽  
Frédérique Penault-Llorca ◽  
Jean-Louis Kémény ◽  
Jean-Jacques Lemaire ◽  
Christiane Jullien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interleukin 6 ◽  
Vascular Endothelial Cells ◽  
Immunohistochemical Analysis ◽  
Vascular Endothelial ◽  
Content Type ◽  
Major Interest ◽  
Polymerase Chain ◽  
The Relationship ◽  
Fine Print

Object. Glioblastomas multiforme (GBMs) grow rapidly and are highly resistant to treatment compared with other glioma types and grades. Consequently, it is of major interest to identify markers of aggressiveness in these tumors that could represent new therapeutic targets. Interleukin (IL)—6 is frequently produced in gliomas and, given its manifold properties, could be considered as a candidate marker. Expression of IL-6 may be involved in cell growth, resistance to chemotherapy and radiotherapy (via an antiapoptotic pathway), and angiogenesis. This study was conducted to test this hypotheses and to evaluate the suitability of IL-6 as a target in the treatment of GBMs. Methods. The authors studied the relationship between the level of IL-6 gene expression as assessed using semiquantitative reverse transcription—polymerase chain reaction and by determining various histological types and grades in a series of 59 gliomas. It was found that GBMs displayed a significantly higher level of IL-6 expression than other types of glioma (p < 0.001). Immunohistochemical analysis revealed that IL-6 was produced mainly by malignant cells and a few vascular endothelial cells. Conclusions. It can be inferred from these findings that IL-6 gene expression is related to glioma aggressiveness and that IL-6 may play a central role in GBM behavior. Interleukin-6, therefore, could be considered as a new potential target in the treatment of GBMs.

scholarly journals Involvement of an ATP-Dependent Protease, PA0779/AsrA, in Inducing Heat Shock in Response to Tobramycin in Pseudomonas aeruginosa

2011 ◽  
Vol 55 (5) ◽  
pp. 1874-1882 ◽  
Author(s):  
Kristen N. Kindrachuk ◽  
Lucía Fernández ◽  
Manjeet Bains ◽  
Robert E. W. Hancock
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Heat Shock ◽  
Microarray Analysis ◽  
Prolonged Exposure ◽  
Short Term ◽  
Heat Shock Genes ◽  
Content Type ◽  
Expression Levels ◽  
Subinhibitory Concentrations

ABSTRACTThe adaptive resistance ofPseudomonas aeruginosato aminoglycosides is known to occur during chronic lung infections in cystic fibrosis patients in response to nonlethal concentrations of aminoglycosides. Not only is it difficult to achieve high levels of drug throughout the dehydrated mucus in the lung, but also steep oxygen gradients exist across the mucus layer, further reducing the bactericidal activity of aminoglycosides. In this study, microarray analysis was utilized to examine the gene responses ofP. aeruginosato lethal, inhibitory, and subinhibitory concentrations of tobramycin under aerobic and anaerobic conditions. While prolonged exposure to subinhibitory concentrations of tobramycin caused increased levels of expression predominantly of the efflux pump genesmexXY, the greatest increases in gene expression levels in response to lethal concentrations of tobramycin involved a number of heat shock genes and the PA0779 gene (renamed hereasrA), encoding an alternate Lon protease. Microarray analysis of anasrA::luxCDABEtransposon mutant revealed that the induction of heat shock genes in response to tobramycin in this mutant was significantly decreased compared to that in the parent strain. The level of expression ofasrAwas induced from an arabinose-inducible promoter to 35-fold greater than wild-type expression levels in the absence of tobramycin, and this overexpression alone caused an increased expression of the heat shock genes, as determined by quantitative PCR (qPCR). This overexpression ofasrAconferred short-term protection against lethal levels (4 μg/ml) of tobramycin but did not affect the tobramycin MIC. The RpoH heat shock sigma factor was found to be involved in the regulation ofasrAin response to both heat shock and tobramycin at the posttranscriptional level. The results of this work suggest that the tobramycin concentration has a significant impact on the gene expression ofP. aeruginosa, with lethal concentrations resulting in immediate adaptations conferring short-term protection, such as the induction of the heat shock response, and with subinhibitory concentrations leading to more sustainable long-term protection mechanisms, such as increased efflux.

scholarly journals Use of the Chinchilla Model for Nasopharyngeal Colonization To Study Gene Expression by Moraxella catarrhalis

2011 ◽  
Vol 80 (3) ◽  
pp. 982-995 ◽  
Author(s):  
Todd C. Hoopman ◽  
Wei Liu ◽  
Stephanie N. Joslin ◽  
Christine Pybus ◽  
Jennifer L. Sedillo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Moraxella Catarrhalis ◽  
Expression Patterns ◽  
Surface Proteins ◽  
Content Type ◽  
Dna Microarray Analysis ◽  
Study Gene Expression

Young adult chinchillas were atraumatically inoculated withMoraxella catarrhalisvia the nasal route. Detailed histopathologic examination of nasopharyngeal tissues isolated from theseM. catarrhalis-infected animals revealed the presence of significant inflammation within the epithelium. Absence of similar histopathologic findings in sham-inoculated animals confirmed thatM. catarrhaliswas exposed to significant host-derived factors in this environment. Twenty-four hours after inoculation, viableM. catarrhalisorganisms were recovered from the nasal cavity and nasopharynx of the animals in numbers sufficient for DNA microarray analysis. More than 100M. catarrhalisgenes were upregulatedin vivo, including open reading frames (ORFs) encoding proteins that are involved in a truncated denitrification pathway or in the oxidative stress response, as well as several putative transcriptional regulators. Additionally, 200M. catarrhalisgenes were found to be downregulated when this bacterium was introduced into the nasopharynx. These downregulated genes included ORFs encoding several well-characterizedM. catarrhalissurface proteins including Hag, McaP, and MchA1. Real-time reverse transcriptase PCR (RT-PCR) was utilized as a stringent control to validate the results ofin vivogene expression patterns as measured by DNA microarray analysis. Inactivation of one of the genes (MC ORF 1550) that was upregulatedin vivoresulted in a decrease in the ability ofM. catarrhalisto survive in the chinchilla nasopharynx over a 3-day period. This is the first evaluation of global transcriptome expression byM. catarrhaliscellsin vivo.

scholarly journals The Potential of 2-aza-8-Oxohypoxanthine as a Cosmetic Ingredient

Cosmetics ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 60
Author(s):  
Hisae Aoshima ◽  
Masayuki Ito ◽  
Rinta Ibuki ◽  
Hirokazu Kawagishi
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Cell Activation ◽  
Skin Barrier ◽  
Efficacy Evaluation ◽  
Activation Effect ◽  
Expression Levels ◽  
Dna Microarray Analysis

In this study, we verified the effects of 2-aza-8-oxohypoxanthine (AOH) on human epidermal cell proliferation by performing DNA microarray analysis. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, which measures mitochondrial respiration in normal human epidermal keratinocyte (NHEK) cells. Gene expression levels were determined by DNA microarray analysis of 177 genes involved in skin aging and disease. AOH showed a significant increase in cell viability at concentrations between 7.8 and 31.3 μg/mL and a significant decrease at concentrations above 250 μg/mL. DNA microarray analysis showed that AOH significantly increased the gene expression of CLDN1, DSC1, DSG1, and CDH1 (E-cadherin), which are involved in intercellular adhesion and skin barrier functioning. AOH also up-regulated the expression of KLK5, KLK7, and SPIMK5, which are proteases involved in stratum corneum detachment. Furthermore, AOH significantly stimulated the expression of KRT1, KRT10, TGM1, and IVL, which are considered general differentiation indicators, and that of SPRR1B, a cornified envelope component protein. AOH exerted a cell activation effect on human epidermal cells. Since AOH did not cause cytotoxicity, it was considered that the compound had no adverse effects on the skin. In addition, it was found that AOH stimulated the expression levels of genes involved in skin barrier functioning by DNA microarray analysis. Therefore, AOH has the potential for practical use as a cosmetic ingredient. This is the first report of efficacy evaluation tests performed for AOH.

scholarly journals Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e92547 ◽  
Author(s):  
Hidekane Yoshimura ◽  
Yutaka Takumi ◽  
Shin-ya Nishio ◽  
Nobuyoshi Suzuki ◽  
Yoh-ichiro Iwasa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Deafness Gene

scholarly journals Jonckheere–Terpstra–Kendall-based non-parametric analysis of temporal differential gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Hitoshi Iuchi ◽  
Michiaki Hamada
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Time Course ◽  
Time Series Data ◽  
Expression Patterns ◽  
Detection Methods ◽  
Series Data ◽  
Expression Levels ◽  
Over Time ◽  
Non Parametric

Abstract Time-course experiments using parallel sequencers have the potential to uncover gradual changes in cells over time that cannot be observed in a two-point comparison. An essential step in time-series data analysis is the identification of temporal differentially expressed genes (TEGs) under two conditions (e.g. control versus case). Model-based approaches, which are typical TEG detection methods, often set one parameter (e.g. degree or degree of freedom) for one dataset. This approach risks modeling of linearly increasing genes with higher-order functions, or fitting of cyclic gene expression with linear functions, thereby leading to false positives/negatives. Here, we present a Jonckheere–Terpstra–Kendall (JTK)-based non-parametric algorithm for TEG detection. Benchmarks, using simulation data, show that the JTK-based approach outperforms existing methods, especially in long time-series experiments. Additionally, application of JTK in the analysis of time-series RNA-seq data from seven tissue types, across developmental stages in mouse and rat, suggested that the wave pattern contributes to the TEG identification of JTK, not the difference in expression levels. This result suggests that JTK is a suitable algorithm when focusing on expression patterns over time rather than expression levels, such as comparisons between different species. These results show that JTK is an excellent candidate for TEG detection.

scholarly journals Activation of the JAK1 / STAT1 Signaling Pathway is Associated with Prdx6 Expression Levels in Human Epididymis Epithelial Cells

2021 ◽  
Author(s):  
Jianyuan Li ◽  
Hui Shi ◽  
Xiaoyu Liu ◽  
Yanwei Wang ◽  
Haiyan Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Expression Patterns ◽  
Digital Gene Expression ◽  
Protective Role ◽  
Expression Levels ◽  
Human Epididymis ◽  
Total Antioxidant ◽  
Stat1 Signaling

Abstract I. Background: Peroxiredoxin 6 (Prdx6) is widely expressed in mammalian tissues. Our previous study demonstrated that Prdx6 was expressed in human epididymis and spermatozoa, and the protective role of Prdx6 in human spermatozoa was also reported. In this study, we demonstrate the potential role and mechanism of Prdx6 in human epididymis epithelial cells (HEECs).II. Methods and Results: Western blotting was used to measure expression levels of key proteins in the JAK / STAT signaling pathway. Digital gene expression analysis (DGE) was used to identify gene expression patterns in control HECs and in HECs after Prdx6-RNA interference (P6-RNAi). The DGE analysis identified 589 up-regulated and 314 down-regulated genes (including Prdx6) in Prdx6-RNAi (P6-RNAi) HEECs. Thirteen significantly different pathways were identified between the two groups, with the majority different expressed genes belonging to the CCL, CXCL, IL, and IFIT families. In particular, the expression levels of IL6, IL6ST, and eighteen IFN related genes were significantly increased in the condition of the down-regulated expression of Prdx6. Compared to control HEECs, the expression levels of JAK1, STAT1, phosphorylated JAK1 and STAT1 were significantly increased, while the expression levels of SOCS3 was significantly decreased in P6-RNAi HEECs. The Malondialdehyde (MDA) level and total antioxidant capacity in P6-RNAi HEECs were significantly increased and decreased compared to that of control, respectively. III. Conclusions: We speculated that knockdown of Prdx6 resulted in higher levels of ROS in HEECs, which in turn, activated the JAK1 / STAT1 signaling pathway induced by IL-6 receptor and IFN.

Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study

2000 ◽  
Vol 92 (5) ◽  
pp. 804-811 ◽  
Author(s):  
Griffith R. Harsh ◽  
Thomas S. Deisboeck ◽  
David N. Louis ◽  
John Hilton ◽  
Michael Colvin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzymatic Activity ◽  
Thymidine Kinase ◽  
Tumor Cells ◽  
Malignant Gliomas ◽  
Retroviral Vectors ◽  
Content Type ◽  
Tumor Bed ◽  
Immunohistochemical Evidence ◽  
Fine Print

Object. The gene therapy paradigm of intratumoral activation of ganciclovir (GCV) following transduction of tumor cells by retroviral vectors bearing the thymidine kinase (tk) gene has produced dramatic remissions of malignant gliomas in animal models. In human trials, although the technique has been deemed safe, little antitumor effect has been demonstrated. To evaluate the basis of this inefficacy in human gliomas, the authors conducted a gene-marking trial involving neuropathological and biochemical studies of treated tumor specimens.Methods. Five patients with malignant recurrent gliomas underwent stereotactic biopsy sampling and intratumoral implantation procedures with three aliquots of 106 vector-producing cells (VPCs) in columns. After 5 days, the tumor was resected and the tumor bed reimplanted with VPCs, and a course of GCV was given. Patients received clinical and radiological follow up for 6 months. Tumor specimens were analyzed neuropathologically and for tk gene expression by anti-TK immunohistochemistry and TK enzymatic activity.Four patients tolerated the treatment well but experienced tumor progression. The other developed an abscess after the second operation and died. Increased TK enzymatic activity was demonstrated in the one tumor specimen analyzed. Immunohistochemical evidence of tk gene expression was limited to VPCs. Transduction of tumor cells was not seen. Viable tumor cells were seen near VPCs containing TK. The lymphocytic immune response was mild.Conclusions. Except for the risk of infection inherent in reoperation, this tk—GCV paradigm was both feasible and safe. Pathological studies indicated that limited dissemination of VPCs and vector from the infusion site and failure to transduce tumor cells with the tk gene are major barriers to efficacy.

scholarly journals Host Gene Regulation by Transposable Elements: The New, the Old and the Ugly

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1089 ◽  
Author(s):  
Rocio Enriquez-Gasca ◽  
Poppy A. Gould ◽  
Helen M. Rowe
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transposable Elements ◽  
Essential Gene ◽  
Expression Patterns ◽  
Genetic Material ◽  
Endogenous Retroviruses ◽  
Host Gene ◽  
New Genes ◽  
Host Genes

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.

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