MALT lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the NF-B pathway. Gastric MALT lymphomas harboring such translocation do not respond to H. pylori eradication, while those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 24 MALT lymphomas (15 translocation-positive, 9 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-B target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions showed that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-B target genes, particularly TLR6, CCR2, CD69 and BCL2, while translocation-negative cases were featured by active inflammatory and immune responses, such as IL8, CD86, CD28 and ICOS. Separate analyses of the genes differentially expressed between translocation-positive and negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10 mediated NF-B activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors.
Differential expression of NF-kappaB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism.
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View SamplesAffymetrix Mouse Genome 430 2.0 arrays were used to measure genome-wide gene expression levels. The results show that high-risk human papillomavirus oncogenes E6 and E7 reprogram the cervical cancer microenvironment independently of and synergistically with estrogen, a critical co-factor in cervical cancer development and maintenance.
Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen.
Specimen part, Treatment
View SamplesBortezomib-induced resistant MCL cell lines (HBL2 BR and JEKO BR) were generated by continuous cultured of corresponding parental cell lines (HBL2 PT and JEKO PT) with increasing bortezomib concentrations
Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation.
Specimen part, Cell line
View SamplesUsing RNA-Seq, we reported novel findings in the comparison of transcriptome profiles of isogenic HMDM and IPSDM during differentiation and polarization. First, IPSDM lost expression of pluripotency markers, had remarkably distinct gene expression profiles relative to precursor iPSCs, and had largely similar gene expression as HMDM. Second, macrophage polarization to M1 was associated with a dramatic change in the transcriptome; expression profiles of IPSDM- and HMDM-derived M1 lines were highly correlated with each other but much less so with their respective IPSDM and HMDM precursors. Third, M2-HMDM lines had limited difference in gene expression compared to their non-polarized precursors, likely due to the known M2-like phenotype of M-CSF differentiated macrophages and their similarity to the IL-4 derived M2 phenotype Finally, through RNA-Seq we identified many new genes modulated during polarization in both HMDM and IPSDM thus providing novel, and potentially regulatory, candidates that warrant further study. Overall design: iPS, IPSDM (including M1/M2) and HMDM (including M1/M2)cells were sequenced by Illumina HiSeq 2000 with poly-A selection
Functional analysis and transcriptomic profiling of iPSC-derived macrophages and their application in modeling Mendelian disease.
No sample metadata fields
View SamplesAnimal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel antibody transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von-Willebrand-factor A like domain 2) transfer showed clear variability among inbred mouse strains; i.e. severe cutaneous blistering and inflammation in C57Bl/6J, and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57Bl/6J or MRL/MpJ mice showed an impaired ROS release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune-complex activated neutrophils from either C57Bl/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA.
Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in Experimental Epidermolysis Bullosa Acquisita.
Disease
View SamplesBackground : The aim of this study is to improve our understanding of the mechanisms underlying the role of sepsis in the limb muscles of ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factor triggering AQM that is endotoxin-induced sepsis.
Role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model.
Sex, Specimen part, Disease
View SamplesResponse of JHCO9 and JHOC5 cells to infection with NT (control) lentivirus or one of two knockdown lentiviruses, SPINK1 KD or IL-6 KD.
Targeting an autocrine IL-6-SPINK1 signaling axis to suppress metastatic spread in ovarian clear cell carcinoma.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.
Specimen part, Treatment
View SamplesIn this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated -gal (SA--gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, Focal adhesion kinase and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies which rely on senescence induction by inhibiting Shp2 or controlling its target gene products may be useful in blocking breast cancer.
Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.
Specimen part, Treatment
View SamplesWe used an unbiased approach to identify differences in gene expression that may account for the high degree of interindividual variability in inflammatory responses to LPS in the normal human population. We measured LPS-induced cytokine production ex vivo in whole blood from 102 healthy human subjects and identified individuals who consistently showed either very high or very low responses to LPS. Comparison of gene expression profiles between the lpshigh and lpslow individuals revealed 80 genes that were differentially expressed in the presence of LPS and 21 genes that were differentially expressed in the absence of LPS (p < 0.005, ANOVA). Expression of a subset of these genes was confirmed using real-time RT-PCR. These data illustrate a novel approach to the identification of factors that determine interindividual variability in innate immune inflammatory responses.
Identification of high and low responders to lipopolysaccharide in normal subjects: an unbiased approach to identify modulators of innate immunity.
Sex, Specimen part
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