We identified LAMP3 as a key driver gene of anti-viral subnetwork genes in cervical cancer patients. Therefore we tested this prediction using an in vitro system. This is the first direct demonstration of LAMP3 regulatory role in interferon-dependent immune response.
Gene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer.
Disease, Cell line, Treatment, Time
View SamplesAutophagy plays important roles in malignant pathogenesis and drug resistance. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC). ROC-325 exhibited superior in vitro anticancer effects than the existing autophagy inhibitor hydroxychloroquine in 12 different tumor models with diverse genetic backgrounds. Focused studies of the mechanism of action and efficacy of ROC-325 in RCC cells showed that drug treatment induced hallmark characteristics of autophagy inhibition including accumulation of autophagosomes with undegraded cargo, lysosomal deacidification, p62 stabilization, and disruption of autophagic flux. Subsequent experiments showed that ROC-325 antagonized RCC growth and survival in an ATG5/7-dependent manner, induced apoptosis, and exhibited favorable selectivity. Oral administration of ROC-325 to mice bearing 786-0 RCC xenografts was well tolerated, significantly more effective at inhibiting tumor progression than HCQ, and inhibited autophagy in vivo.
Disruption of Autophagic Degradation with ROC-325 Antagonizes Renal Cell Carcinoma Pathogenesis.
Specimen part, Cell line
View SamplesWe used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo.
Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesTranscriptomic comparison of 5 cell types during lethal and non-lethal influenza infection and further use of these signatures in a top-down systems analysis investigating the relative pathogenic contributions of direct viral damage to lung epithelium vs. dysregulated immunity during lethal influenza infection.
A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection.
Sex, Specimen part
View SamplesGene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions in comparison to controls. The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells.
Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.
Specimen part
View SamplesMutations in PfCRT confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. However, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR).
Genome-wide compensatory changes accompany drug- selected mutations in the Plasmodium falciparum crt gene.
No sample metadata fields
View SamplesThe epidemic character of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), especially the geographically widespread clone USA300, is poorly understood. USA300 isolates carry a type IV staphylococcal chromosomal cassette mec (SCCmec) element conferring -lactam antibiotic class resistance and a putative pathogenicity island, ACME (arginine catabolic mobile element).
The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus.
No sample metadata fields
View SamplesCD4+ T cell differentiation into multiple T helper lineages is critical for optimal adaptive immune responses. This report identified a novel intrinsic mechanism by which PD-1 signaling imparted regulatory phenotype to FoxP3+ Th1 cells (denoted as Tbet+iTregPDL1 cells) and iTregs. Tbet+iTregPDL1 cells were capable of preventing inflammation in murine models of experimental colitis and experimental graft versus host disease. PDL-1 binding to PD-1 imparted regulatory function to Tbet+iTregPDL1 cells and iTregs by specifically downregulating an endolysosomal protease asparaginyl endopeptidase (AEP)
PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells.
Specimen part
View SamplesTo determine the effect of iBET762+, a bromodomain BET inhibitor, on the transcription of 20861 and 20863 cells. These cells are subclones of W12 cells, derived from cervical intraepithelial neoplastic lesion. 20861 contains integrated HPV16 DNA and 20863 contains extrachromosomal HPV16 DNA. iBET762+ decreases expression of the HPV16 E6 and E7 oncogenes in both cell lines and this is expected to have dramatic effects on the cellular transcriptome
Tandemly Integrated HPV16 Can Form a Brd4-Dependent Super-Enhancer-Like Element That Drives Transcription of Viral Oncogenes.
Sex, Specimen part, Cell line
View Samples