Nanoparticle-coupled topical methotrexate effectively inhibits inflammation and induces re-modeling in pre-clinical psoriasis
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PROVIDER: PRJNA520906 | ENA |
REPOSITORIES: ENA
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Project description:This project explores the efficacy of a novel skin-permeable MTX formulation, on murine and human xenotransplant models of psoriasis. Phenotypical and histological examinations of psoriatic tissue in these models have shown that the novel MTX can significantly suppress the inflammation. In order to understand the mechanistics of the new drug transcriptome of different treatment regimens (MTX-based, corticosteroid-based, and Vaseline control) will be compared to assess the pathological state of the skin.
2019-11-05 | GSE126066 | GEO
Project description:bulk sequencing outputs of Caco2 cells after exposure to permeability modifying and permeability rescuing agents. To identify the molecular drivers for methotrexate-induced barrier dysfunction, we conducted RNA sequencing on Caco2 spheroids treated with methotrexate and lactoferrin. Given our observation that barrier function was compromised as early as 4-6 hours after exposure to methotrexate, we isolated RNA from spheroids 4-hour post-treatment to capture the transcriptional events responsible for initiating the processes.
2020-01-10 | GSE140066 | GEO
Project description:Caco2 response to methotrexate, lactoferrin, and methotrexate-lactoferrin co-exposure
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Project description:The C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease. The efficacy of topical baricitinib at treating established alopecia in the C3H/HeJ grafted model was also assessed. Microarrays were performed on skin RNA at week 0 and week 12 after starting treatment in all models. Baricitinib was administered in topical form after disease establishement. Skin samples were taken at the start of treatment and after 12 weeks.
2015-05-01 | E-GEOD-61554 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE9947: Transcriptional analysis of Leishmania infantum methotrexate resistant strains using full-genome DNA microarrays GSE9948: Transcriptional analysis of Leishmania major methotrexate resistant strains using full-genome DNA microarrays Keywords: SuperSeries Refer to individual Series
2010-05-25 | E-GEOD-9949 | biostudies-arrayexpress
Project description:<p>Methotrexate plasma concentration is related to its clinical effects. To identify the genetic basis of interindividual variability in methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia (ALL), we performed a genome-wide analysis (GWAS) of 500,568 germline single-nucleotide polymorphisms (SNPs) in 434 children with ALL who received 3,014 courses of methotrexate at 2 to 5 g/m2. SNPs were validated in an independent cohort of 206 patients. Adjusting for age, race, sex, and methotrexate regimen, the most significant associations were with SNPs in the organic anion transporter polypeptide, <i>SLCO1B1</i> (rs11045879 (P = 1.7 x 10<sup>-10</sup>) and rs4149081 (P = 1.7 x 10<sup>-9</sup>) (Trevino et al, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19901119" target="_blank">19901119</a>). To test whether rare variants in <i>SLCO1B1</i> could alter its function, we genotyped <i>SLCO1B1</i> exons in a slightly larger group of 699 children with ALL who received methotrexate and identified 93 single nucleotide polymorphisms (SNPs). We found several common and rare non-synonymous (NS) SNPs associated with methotrexate clearance.</p> <p>NS SNPs predicted to be functionally damaging (common or rare) were more likely to be found among patients with the lowest adjusted methotrexate clearance (lowest 10%) than patients with high clearance (highest 10%). Four <i>SLCO1B1</i> haplotypes were associated with reduced methotrexate clearance and we verified that these haplotypes have lower function with in vitro transport assays. We were able to quantitatively account for a third of the population variability in clearance of methotrexate with clinical and genetic covariates. This data set includes the dependent variable of methotrexate clearance and all of the SNP data available from arrays, sequencing, and genotyping.</p>
| phs000426.v1.p1 | EGA
Project description:Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. Its potential, however, has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide di-(methyl fumarate) (IDMF), which was designed to have anti-psoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is non-irritating and non-sensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically up-regulated in psoriatic skin lesions but not those of other skin diseases. IDMF also down-regulated genes induced by IL-17A and TNF in keratinocytes, as well as predicted targets of NF-κB and the anti-differentiation ncRNA (ANCR). IDMF further stimulated transcription of oxidative stress response genes (NQO1, GPX2, GSR) with stronger Nrf2/ARE activation compared to DMF. Finally, IDMF reduced erythema and scaling while repressing expression of immune response genes in psoriasiform lesions elicited by topical application of imiquimod in mice. These data demonstrate that IDMF exbibits anti-psoriatic activity that is similar or improved compared to DMF, without the harsh skin-sensitizing effects that have prevented topical delivery of the parent molecule.
2021-08-22 | GSE175473 | GEO
Project description:Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. Its potential, however, has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide di-(methyl fumarate) (IDMF), which was designed to have anti-psoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is non-irritating and non-sensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically up-regulated in psoriatic skin lesions but not those of other skin diseases. IDMF also down-regulated genes induced by IL-17A and TNF in keratinocytes, as well as predicted targets of NF-κB and the anti-differentiation ncRNA (ANCR). IDMF further stimulated transcription of oxidative stress response genes (NQO1, GPX2, GSR) with stronger Nrf2/ARE activation compared to DMF. Finally, IDMF reduced erythema and scaling while repressing expression of immune response genes in psoriasiform lesions elicited by topical application of imiquimod in mice. These data demonstrate that IDMF exbibits anti-psoriatic activity that is similar or improved compared to DMF, without the harsh skin-sensitizing effects that have prevented topical delivery of the parent molecule.
2021-08-22 | GSE175471 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE11440: Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCa on resistance to methotrexate in human HT29 colon cancer cells; GSE16066: Networking of differentially expressed genes in CaCo2 human colon cancer cells resistant to methotrexate; GSE16070: Networking of differentially expressed genes in human MCF7 breast cancer cells resistant to methotrexate; GSE16080: Networking of differentially expressed genes in human MDA-MB-468 breast cancer cells resistant to methotrexate; GSE16082: Networking of differentially expressed genes in human MIA PaCa2 pancreatic cancer cells resistant to methotrexate; GSE16085: Networking of differentially expressed genes in human K562 erythtoblastic leukemia cells resistant to methotrexate; GSE16089: Networking of differentially expressed genes in human Saos-2 osteosarcoma cells resistant to methotrexate Experiment Overall Design: Refer to individual Series
2009-09-11 | E-GEOD-16648 | biostudies-arrayexpress