Treatment of TRAMP-C2-Ras tumors with IL-27 and IL-18 therapies
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ABSTRACT:
PROVIDER: PRJNA737453 | ENA |
REPOSITORIES: ENA
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Project description:Interleukin-27 (IL-27) can partially reduce tumor growth in several animal models, including pros-tate cancer. We describe our findings on the effects of IL-27 gene delivery on prostate cancer cells and how sequential therapy with IL-18 enhances the efficacy of IL-27. We applied IL-27 and IL-18 deliv-ery with the goal of reducing prostate tumor growth, first in cell culture and then in an immunocom-petent mouse model. The combination of IL-27 followed by IL-18 (2718) successfully reduced can-cer cell viability, with significant effects found for a particular combination sequence. Interestingly, when we compared the 2718 combination with a single cytokine targeted to IL-6R via an oligo-peptide (27pepL) recently developed by our group, we observed similar efficacy. This efficacy was further enhanced when 27pepL was sequenced with IL-18 (27pepL18)
2021-07-27 | GSE178142 | GEO
Project description:Gene expression profiling of TRAMP-C2, transgenic adenocarcinoma of mouse prostate, cell line. The experiment was done to see which genes were over- or underexpressed in the cell line. The results were combined with aCGH results of the same samples (experiment Gene copy number profiling of TRAMP-C2 cell line using aCGH) to see, whether the copy number status had any effect on gene expression.
2008-09-11 | E-MEXP-1610 | biostudies-arrayexpress
Project description:Chronic responses to direct Ras-targetted therapies
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Project description:Gene expression profiling of TRAMP-C2, transgenic adenocarcinoma of mouse prostate, cell line was done after treating the cells with DNA demethylating agent 5-aza-2'-deoxycytidine (5azadC; Sigma-Aldrich, St. Louis, MO) and histone deacetylase inhibitor trichostatin A (TSA; Sigma-Aldrich), both separately and in combination. These treatments relieve epigenetic modifications, and thus reveal potentially epigenetically silenced genes amongst the genes with increased expression after the treatments.
2008-09-12 | E-MEXP-1611 | biostudies-arrayexpress
Project description:Constitutively active RAS plays a central role in the development of skin cancer in the classical two stage skin carcinogenesis in mice and in a number of human cancers. Ras-mediated tumor formation is commonly associated with upregulation of cytokines and chemokines that mediate an inflammatory response considered relevant to oncogenesis. MyD88 is a crucial intermediate in the expression of multiple innate immune responders through signaling from the Toll-like/IL-1R family. We report that mice ablated for MyD88 or the IL-1R are resistant to topical skin carcinogenesis, and cultured MyD88-/- keratinocytes transduced with an oncogenic ras vector form only a few small tumors in orthotopic grafts. Initiated keratinocytes arising from oncogenic activation of ras are hyperproliferative but also resist signals for induced differentiation and upregulate a host of pro-inflammatory genes. Ras-transduced MyD88-/- keratinocytes are also hyperproliferative but the differentiation response is intact and pro-inflammatory genes are not upregulated. Using both genetic and pharmacological approaches, we find that in keratinocytes, the differentiation and immune regulation functions mediated by oncogenic ras require the establishment of an autocrine loop through IL-1α and its receptor leading to NF-κB activation. In the absence of MyD88 or IL-1R, this loop cannot be established. Further, blocking the IL-1a mediated NF-κB activation in ras-transduced wildtype keratinocytes corrects the defect in both differentiation response and proinflammatory gene expression. Collectively, these results demonstrate that ras activation converts normal keratinocytes to an initiated phenotype through a series of potentially reversible feedback signals that provide therapeutic opportunities through inhibition of IL-1 signaling. Gene expression comparison of wild type ras-transformed keratinocytes untreated (n=3) or treated (n=3) in vitro with the IL1R antagonist Anakinra.
2011-08-28 | E-GEOD-22777 | biostudies-arrayexpress
Project description:Constitutively active RAS plays a central role in the development of skin cancer in the classical two stage skin carcinogenesis in mice and in a number of human cancers. Ras-mediated tumor formation is commonly associated with upregulation of cytokines and chemokines that mediate an inflammatory response considered relevant to oncogenesis. MyD88 is a crucial intermediate in the expression of multiple innate immune responders through signaling from the Toll-like/IL-1R family. We report that mice ablated for MyD88 or the IL-1R are resistant to topical skin carcinogenesis, and cultured MyD88-/- keratinocytes transduced with an oncogenic ras vector form only a few small tumors in orthotopic grafts. Initiated keratinocytes arising from oncogenic activation of ras are hyperproliferative but also resist signals for induced differentiation and upregulate a host of pro-inflammatory genes. Ras-transduced MyD88-/- keratinocytes are also hyperproliferative but the differentiation response is intact and pro-inflammatory genes are not upregulated. Using both genetic and pharmacological approaches, we find that in keratinocytes, the differentiation and immune regulation functions mediated by oncogenic ras require the establishment of an autocrine loop through IL-1α and its receptor leading to NF-κB activation. In the absence of MyD88 or IL-1R, this loop cannot be established. Further, blocking the IL-1a mediated NF-κB activation in ras-transduced wildtype keratinocytes corrects the defect in both differentiation response and proinflammatory gene expression. Collectively, these results demonstrate that ras activation converts normal keratinocytes to an initiated phenotype through a series of potentially reversible feedback signals that provide therapeutic opportunities through inhibition of IL-1 signaling.
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Project description:To investigate the response of H358 lung cancer cells to long term treatment with a panel of direct Ras and Ras pathway inhibitors. H358 cells harbour a heterozygous G12C mutation of KRAS.
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Project description:We identified a novel subset of iNKT cells, C2 iNKT cells, that circulate in the periphery. Correspondingly, we characterized the tissue-resident iNKT cell subset, C1 iNKT cells. We also found the precursor of these two subsets of iNKT cells, C0 iNKT cells in thymus. The development and terminal maturation of C2 iNKT cells completely depended on the thymic epithelial IL-15 niche, whereas C1 iNKT cells were regulated also by local IL-15 niches in peripheral tissues. C2 iNKT cells expressed high levels of genes related to cytotoxicity and exhibited more NK cell-like features. Here we characterized the C2 iNKT cells, C1 iNKT cells, and C0 iNKT cells using RNA-seq. We also performed RNA-seq for CD4+ T cells, CD8+ T cells and NK cells as a comparison. To investigate the effect of CD4, we performed the RNA-seq for the CD4+ and CD4- C2 iNKT cells.
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Project description:IL-11 neutralising therapies for the treatment of nonalcoholic steatohepatitis
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Project description:During nuclear surveillance in yeast, the RNA exosome functions together with the TRAMP complexes. These include the DEAH-box RNA helicase Mtr4 together with an RNA-binding protein (Air1 or Air2) and a poly(A) polymerase (Trf4 or Trf5). To better determine how RNA substrates are targeted, we analyzed protein and RNA interactions for TRAMP components. Mass spectrometry identified three distinct TRAMP complexes formed in vivo. These complexes preferentially assemble on different classes of transcripts. Unexpectedly, on many substrates, including pre-rRNAs and pre-mRNAs, binding specificity was apparently conferred by Trf4 and Trf5. Clustering of mRNAs by TRAMP association showed coenrichment for mRNAs with functionally related products, supporting the significance of surveillance in regulating gene expression. We compared binding sites of TRAMP components with multiple nuclear RNA binding proteins, revealing preferential colocalization of subsets of factors. TRF5 deletion reduced Mtr4 recruitment and increased RNA abundance for mRNAs specifically showing high Trf5 binding.
2020-07-02 | PXD017114 | Pride