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A Phase II Study of 5-Fluorouracil Administered as a One Hour Infusion in Combination With Calcium Leucovorin and Interferon Alpha-2A in Advanced Colorectal Cancer

ABSTRACT: This protocol will evaluate the activity of 5-Fluorouracil (FUra) given as a 1 hour infusion in combination with leucovorin (LV) and interferon IFN alpha-2a in patients with advanced, measurable colorectal cancer.

DISEASE(S): Solid Tumor,Colorectal Neoplasms

PROVIDER: 2001252 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Human tumor cell lines treated with interferon-alpha-2a

Project description:A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. Foser et al. 2006 have shown that costimulation with IFN-alpa and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. Gene induction by small concentration of interferon-alpha-2a (100 U/ml) was analyzed in human cancer cell lines with differences in sensitivity to IFN-alpha and TGF-beta. Among other antiproliferative genes we found upregulated IFITM3 gene expression levels and inducibility of this antiproliferative protein in interferon sensitive cell lines.

2010-05-16 | GSE21158 | GEO

Transcription profiling of human hepatitis C virus replicon cell line treated with interferon-alpha 2a in a time series

Project description:Temporal analysis of genes regulated by Interferon-alpha 2a in a HCV (Hepatitis C Virus) Replicon Cell line

2011-11-08 | E-MEXP-714 | biostudies-arrayexpress

MicroRNA expression profiling in human tumor cell lines treated with interferon-alpha-2a

Project description:MicroRNAs are positive and negative regulators of eukaryotic gene expression that modulate transcript abundance by specific binding to sequence motifs located prevalently in the 3’ untranslated regions (3’-UTR) of target messenger RNAs (mRNA). Interferon-alpha-2a (IFNα) induces a large set of protein-coding genes mediating anti-proliferative and antiviral responses. Here we use a global microarray-based microRNA detection platform to identify genes that are induced by IFNα in hepatoma- or melanoma-derived human tumor cell lines. Despite the enormous differences in expression levels between these models, we were able to identify microRNAs that are upregulated by IFNα in both lines, suggesting the possibility that interferon-regulated microRNAs (IRmiRs) are involved in the transcriptional repression of mRNA relevant to cytokine responses.

2009-07-28 | GSE16421 | GEO

Transcription Profiling of Human Aortic Endothelial Cells After Treatment with Interferon-Alpha

Project description:Systemic Lupus Erythematosus is associated with an increased risk of cardiovascular disease (CVD). Interferon-response genes have been associated with endothelial dysfunction in SLE patients. The aim of this study is to identify the effects of IFN-alpha on human endothelial cells in order to determine whether IFN-alpha can directly activate the endothelium.

2013-09-11 | E-MEXP-3746 | biostudies-arrayexpress

CRISPR screen for interferon-alpha inducible inhibitors of yellow fever virus replication

Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). A genome-wide CRISPR screen using IFN alpha-treated Huh7.5 cells was performed to determine which ISGs were required in order for host cells to suppress yellow fever virus (YFV) infection.

2018-10-25 | GSE121710 | GEO

Down-regulation of Interferon signature in systemic lupus erythematosus patients by active immunization with Interferon alpha-Kinoid

Project description:We performed a phase I/II, randomized, double-blind, placebo-controlled dose-escalation study to examine the safety, immunogenicity, and biological effects of active immunization with interferon alpha-Kinoid (IFN-K) in systemic lupus erythematosus (SLE) patients. Women 18-50 years of age with mild to moderate SLE were immunized with three (n=10) or four doses (n=9) of 30, 60, 120, 240 microgram IFN-K or saline. Anti-IFNalpha antibodies were detected in all IFN-K-immunized patients. Transcriptomic analysis separated patients at baseline into type I IFN signature-positive and -negative groups. IFN-K induced higher anti-IFNalpha titers in signature-positive than in signature-negative patients and, in signature-positive patients, reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNalpha antibody titers, and with baseline IFN score. IFN-K or placebo was administered at day 0, day 7, day 28 in all patients. Half the subjects received a fourth injection at day 84 (see treatment protocol)

2012-11-01 | E-GEOD-39088 | biostudies-arrayexpress

Gene expression profiling data from sooty mangabeys treated with interferon alpha

Project description:In contrast to pathogenic HIV and SIV infection of humans and macaques, SIV infection of sooty mangabeys (SMs) is typically non-pathogenic despite high virus replication. A key feature of primary SIV infection of SMs is a strong type I interferon (IFN-I) response, characterized by massive up-regulation of interferon-stimulated genes (ISG), followed by rapid resolution during the acute-to-chronic phase transition and establishment of an immune quiescent state that persists throughout the chronic infection. Based on these observations we hypothesized that low levels of IFN-I signaling may be instrumental in preventing chronic immune activation and disease progression in SIV-infected SMs. We used microarrays to characterize gene expression changes induced by IFNalpha treatment. To directly assess the effects of an experimentally-induced augmentation of IFN-I signaling in chronically SIV-infected SMs, we administered recombinant rhesus macaque IFNalpha2-IgFc (rmIFNα2) to eight naturally SIV-infected SMs weekly for 16 weeks and longitudinally monitored viral load, lymphocyte counts, immune activation, SIV-specific CD8+ T-cell responses, and gene expression profile. Administration of rmIFNα2 was bioactive in vivo with gene expression profiling revealing a strong upregulation of numerous ISGs in the blood of treated animals.

2012-07-09 | E-GEOD-35460 | biostudies-arrayexpress

Slc1a3-2A-CreERT2 knock-in mouse to study astrocyte gene expression and calcium signaling

Project description:RNA was obtained by applying a RiboTag procedure to RiboTag mice crossed with Slc1a3-2A-CreERT2 mice driving recombination in mouse brain astroglia.

2020-02-19 | GSE145484 | GEO

Label-free Proteomic Analysis of Exosomes Secreted from THP-1-Derived Macrophages in the Absence or Presence of Interferon-α

Project description:Exosomes are extracellular vesicles that function in intercellular communication. We have previously reported that exosomes play a role in the transmission of antiviral molecules during interferon-α (IFN-α)-mediated immune responses. In this study, the protein contents of THP-1-derived macrophages with or without interferon-α treatment and of the exosomes secreted from these cells were analyzed by the label-free LC-MS/MS quantitation technologies. A total number of 1845 and 1550 protein groups were identified in the THP-1 macrophages and the corresponding exosomes, respectively. Treating the cells with IFN-α resulted in the differential abundance of 110 proteins in cells and 260 proteins in exosomes (greater than 2.0-fold), among which 35 proteins were both up-regulated in the IFN-α treated cells and corresponding exosomes while 139 proteins were specifically up-regulated in exosomes but not in the donor cells. GO and KEGG analysis of the protein function categories suggested that IFN-α promoted the abundance of proteins involved in “defense response to virus” in both exosomes and cells, and proteins related to “RNA processing” only in exosomes. Functional analysis further indicated that exosomes from IFN-α-treated cells exhibited potent antiviral activity that restored the impaired antiviral response of IFN-α in hepatitis B virus-replicating hepatocytes. These results have deepened the understanding of the exosome-mediated transfer of IFN-α-induced antiviral molecules and may provide new basis for therapeutic strategies to control viral infection.

2018-12-17 | PXD009746 | Pride

Whole blood transcriptome alteration between pigs with extreme in vivo dsRNA-induced serum interferon-alpha production

Project description:The interferon (IFN) is a major effector of the innate immunity which mediates an adaptive immune response against broad spectrum pathogens. The aim of this work has been to investigate the differences of the virus mimic dsRNA (Poly I:C)-inducted in vivo transcriptomic alteration between pigs with high (HIGH) and low (LOW) serum interferon-alpha production. The pigs with extreme yield of induced interferon-alpha from a F2 resource population were selected for whole blood gene expression analysis using the porcine Affymetrix microarray

2011-12-23 | E-MEXP-3452 | biostudies-arrayexpress

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