We sequenced mRNA from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h. Overall design: Examination of mRNA levels from HCT116 p21-/- cells treated with Nutlin-3a, doxorubicin, or DMSO for 24 h using four replicates each.
Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cellulose-Derived Oligomers Act as Damage-Associated Molecular Patterns and Trigger Defense-Like Responses.
Specimen part, Treatment, Time
View SamplesPlants can perceive the presence of pathogens at the cell surface and plant damage-derived molecules via recognition of conserved microbial molecules, named pathogen- or microbe-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). Well-studied examples of PAMPs are chito-oligomers, breakdown products of fungal cell walls and insect exoskeletons. Pectin-derived oligogalacturonides (OGs) are well-characterized DAMPs. Both PAMPs nd DAMPs are capable of activating plant immunity, generating changes in gene expression that lead to increased production of defense compounds and proteins; thus, equipping the plant cell to defend itself.
Cellulose-Derived Oligomers Act as Damage-Associated Molecular Patterns and Trigger Defense-Like Responses.
Specimen part, Treatment, Time
View SamplesPlants can perceive the presence of pathogens at the cell surface and plant damage-derived molecules via recognition of conserved microbial molecules, named pathogen- or microbe-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). Well-studied examples of PAMPs are chito-oligomers, breakdown products of fungal cell walls and insect exoskeletons. Pectin-derived oligogalacturonides (OGs) are well-characterized DAMPs. Both PAMPs nd DAMPs are capable of activating plant immunity, generating changes in gene expression that lead to increased production of defense compounds and proteins; thus, equipping the plant cell to defend itself.
Cellulose-Derived Oligomers Act as Damage-Associated Molecular Patterns and Trigger Defense-Like Responses.
Specimen part, Treatment, Time
View SamplesmiR-155 has recently emerged as an important promoter of antitumor immunity through its functions in T lymphocytes. However, the impact of T cell expressed miR-155 on immune cell dynamics in solid tumors remains unclear. In the present study, we used single-cell RNA-sequencing to define the CD45+ immune cell populations within B16F10 murine melanoma tumors growing in either wild-type (WT) or miR-155 T cell conditional knockout (TCKO) mice at different timepoints. miR-155 was required for optimal T cell activation and reinforced the T cell response at the expense of infiltrating myeloid cells. Further, myeloid cells from tumors growing in TCKO mice were defined by an increase in wound healing genes and a decreased IFNg response gene signature. Finally, we found that miR-155 expression predicted a favorable outcome in human melanoma patients and was associated with a strong immune signature. Moreover, gene expression and histological analysis of the Cancer Genome Atlas (TCGA) data revealed that miR-155 expression also correlates with an immune-enriched subtype in 29 other human solid tumor types. Together, our study provides an unprecedented analysis of the cell types and gene expression signatures by immune cells within experimental melanoma tumors and elucidates miR-155's role in coordinating this dynamic response. Overall design: B16F10 murine melanoma cells expressing ovalbumin model antigen were injected subcutaneously (1e6) into wild-type (C57BL/6) and miR-155 T cell conditional knockout mice (n>4). 9 or 12 days after injection, tumors were pooled in each group, and DAPI(-)CD45(+) live tumor infiltrating immune cells were sorted via flow cytometry. Sorted immune cells were processed for single-cell RNA-sequencing via 10x platform.
MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers.
Specimen part, Cell line, Subject, Time
View Samples10 days old tumor spheroids were processed for RNA isolation using the Quiagen RNeasy Micro Kit and cDNA synthesis was done using the Ambion WT Expression Kit. Wt, HIF-1 k/d and HIF-2 k/d samples were compared to each other.
HIF-2alpha-dependent PAI-1 induction contributes to angiogenesis in hepatocellular carcinoma.
Specimen part, Cell line
View SamplesThe clinical impact of aberrant CEBPA promoter methylation (PM) in AML is controversial discussed. The aim of this study was to clarify the significance of aberrant CEBPA PM with regard to clinical features in a cohort of 572 de novo AML with wildtype CEBPA and normal karyotype. The distal promoter was methylated in 54/572 cases (9.41%) whereas proximal PM was never detected. Methylation of the core promoter was detected in only 8 of 326 cases (2.45%) and thus seems to be a rare event in AML. There was no correlation between CEBPA distal PM, age, sex, white blood cell (WBC) count or Hb levels at diagnosis. We also were not able to detect a significant correlation between the presence of CEBPA distal PM and molecular mutations such as FLT3-ITD, NPM1, AML1, MLL-PTD and IDH1. Solely the frequency of IDH2R140 mutations was significantly reduced in CEBPA distal PM positive compared to CEBPA distal PM negative cases (p=0.01). Furthermore, analysis of CEBPA mRNA expression level revealed no difference between CEBPA distal PM positive and CEBPA distal PM negative cases, suggesting that CEBPA distal PM has no influence on CEBPA expression. CEBPA distal PM did not show impact on overall survival (OS), event free survival (EFS) or incidence of relapse. Also when other mutations were taken into regard no prognostic impact of CEBPA distal PM could be shown. In contrast, a distinct expression profile of CEBPA distal PM positive cases compared to CEBPA mutated and CEBPA distal PM negative cases was observed. In addition, a significantly higher frequency of CEBPA distal PM was detected in RUNX1-RUNX1T1 positive AML compared to the CEBPA witdtype cases. We conclude that the presence of aberrant CEBPA PM has no clinical relevance and is therefore a negligible prognostic marker in de novo AML with normal karyotype.
Frequency and prognostic impact of CEBPA proximal, distal and core promoter methylation in normal karyotype AML: a study on 623 cases.
Disease
View SamplesThis series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue
Differential gene expression in pituitary adenomas by oligonucleotide array analysis.
No sample metadata fields
View SamplesBy WHO 2008, CEBPA-mutated AML became a provisional subentity, but it remains to be clarified how CEBPAmut AML with multilineage dysplasia (MLD; 50% dysplastic cells in 2-3 lineages) but no other MDS-related feature should be classified. We investigated 108 CEBPAmut AML (15.7-87.6 years) for the impact of MLD and genetic features. MLD-positive patients differed from MLD-negative only by lower mean WBC counts (p=0.004), but not by other blood values, biologic characteristics, cytogenetic risk profiles, or additional molecular markers (NPM1mut, FLT3-ITD/TKD, RUNX1, MLL-PTD, IDH1/2). Biallelic CEBPAmut differed from wild-type-cases by differential expression of 213 genes, but did not differ significantly between MLD-positive/-negative patients. Survival outcomes were improved for females and those <60 years, intermediate versus adverse karyotypes (p=0.021), and for biallelic versus monoallelic/homozygous CEBPAmut (p=0.060) in case of FLT3-ITD-negativity. In contrast, 2-year OS (MLD+: 56.5%; MLD-: 65.5%) and 2-year EFS (MLD+: 13.8 months; MLD-: 16.3 months) did not differ significantly between MLD-positive/-negative patients. By univariable Cox regression analysis, gender, age, WBC count and MRC-cytogenetic risk category only were prognostically relevant for OS, while MLD was irrelevant. Therefore, CEBPAmut AML patients should be characterized only according to mut-status, cytogenetic risk groups, or additional mutations, whereas dysplasia is not relevant for this subtype.
Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity.
Specimen part, Disease, Disease stage
View SamplesInterest focuses on genes encoding histone demethylases in hematologic malignancies, such as EZH2 (enhancer of zeste homolog 2). EZH2 mutations were recurrently observed in lymphomas and chronic myeloid malignancies, but data in acute leukemias are limited. We investigated 13 PICALM-MLLT10 (=CALM-AF10) rearranged acute leukemia predominantly of T-lineage (7 m/6 f; 653 years) by deep-sequencing for EZH2mut and identified 3 (23%) EZH2mut carriers: one splice site mutation in exon 14, while two patients had missense mutations in the D1 region of exon 5 which interacts with different DNA methyltransferase genes (but no DNMT3Amut was detected in the 13 PICALM-MLLT10-positive patients).
EZH2 mutations and their association with PICALM-MLLT10 positive acute leukaemia.
Specimen part, Disease, Disease stage
View Samples