Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2''-deoxy-5-fluorouridine (5-FdU) and 3''-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis. Overall design: Platinum-sensitive A2780 and platinum resistant-cells A2780cis were treated with 5-FdU-Ecyd for 6h and 12h, there are also 6h and 12h untreated controls, all groups are in triplicates
The conjugated antimetabolite 5-FdU-ECyd and its cellular and molecular effects on platinum-sensitive vs. -resistant ovarian cancer cells <i>in vitro</i>.
Cell line, Subject, Time
View SamplesTumor progression is associated with an immunosuppressive microenvironment that consists of several elements, such as regulatory T cells, type 2 macrophages and myeloid-derived suppressor cells. Here, we identify for the first time a BDCA1+CD14+ population of immunosuppressive cells that resides both in the blood and tumor of melanoma patients. We demonstrated that the presence of these cells in dendritic cell (DC)-based anti-tumor vaccines significantly suppresses CD4+ T cells in an antigen-specific manner. In an attempt to reveal the mechanism of this suppressive activity, we noticed that BDCA1+CD14+ cells express elevated levels of the check-point molecule PD-L1, which thereby hinders T cell proliferation. Importantly, although this suppressive BDCA1+CD14+ population expresses markers of both BDCA1+ DCs and monocytes, functional, transcriptome and proteome analyses clearly revealed that they comprise a unique population of cells that is exploited by tumors to evade immunity. Thus, targeting these cells may improve the efficacy of cancer immunotherapy. Overall design: mRNA profiles of BDCA1+ DCs, BDCA1+CD14+ cells and monocytes, isolated from 3 healthy volunteers, were generated by deep RNA sequencing using HiSeq 2000 System (TruSeq SBS KIT-HS V3,Illumina)
Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines.
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View SamplesWe used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen part
View SamplesWild-type and exo mutant (SALK_098602) were grown in parallel in three independent experiments in a greenhouse. 3 x 2 profiles were established.
The extracellular EXO protein mediates cell expansion in Arabidopsis leaves.
Age, Specimen part, Time
View SamplesJoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.
MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells.
Specimen part, Cell line
View SamplesIisomer-specific effects of conjugated linoleic (CLA) supplementation on gene expression with particular consideration of the PPAR 2 Pro12Ala SNP in human adipose tissue.
Isomer-specific effects of CLA on gene expression in human adipose tissue depending on PPARgamma2 P12A polymorphism: a double blind, randomized, controlled cross-over study.
Subject
View SamplesFolic acid supplements prior to and during gestation are recommended and necessary to prevent neural tube defects in developing embryos. But there are also studies suggesting possible adverse effects of high-dose folic acid supplementation. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects gene expression in the offspring generation. Overall design: Total RNA extracted from hippocampi of 6 control (CD) F1 mice and 5 FD F1 mice at the age of 14 weeks.
High-dose maternal folic acid supplementation before conception impairs reversal learning in offspring mice.
Sex, Age, Specimen part, Cell line, Subject
View SamplesThe protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Treatment
View SamplesmRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Age, Specimen part, Subject
View SamplesRPB1, the largest subunit of RNA polymerase II, contains a highly modifiable C-terminal domain (CTD) that consists of variations of a consensus heptad repeat sequence (Y1S2P3T4S5P6S7). The consensus CTD repeat motif and tandem organization represent the ancestral state of eukaryotic RPB1, but across eukaryotes CTDs show considerable diversity in repeat organization and sequence content. These differences may reflect lineage-specific CTD functions mediated by protein interactions. Mammalian CTDs contain eight non-consensus repeats with a lysine in the seventh position (K7). Posttranslational acetylation of these sites was recently shown to be required for proper polymerase pausing and regulation of two growth factor-regulated genes. To investigate the origins and function of RPB1 CTD acetylation (acRPB1), we computationally reconstructed the evolution of the CTD repeat sequence across eukaryotes and analyzed the evolution and function of genes dysregulated when acRPB1 is disrupted. Modeling the evolutionary dynamics of CTD repeat count and sequence content across diverse eukaryotes revealed an expansion of the CTD in the ancestors of Metazoa. The new CTD repeats introduced the potential for acRPB1 due to the appearance of distal repeats with lysine at position seven. This was followed by a further increase in the number of lysine-containing repeats in developmentally complex clades like Deuterostomia. Mouse genes enriched for acRPB1 occupancy at their promoters and genes with significant expression changes when acRPB1 is disrupted are enriched for several functions, such as growth factor response, gene regulation, cellular adhesion, and vascular development. Genes occupied and regulated by acRPB1 show significant enrichment for evolutionary origins in the early history of eukaryotes through early vertebrates. Our combined functional and evolutionary analyses show that RPB1 CTD acetylation was possible in the early history of animals, and that the K7 content of the CTD expanded in specific developmentally complex metazoan lineages. The functional analysis of genes regulated by acRPB1 highlight functions involved in the origin of and diversification of complex Metazoa. This suggests that acRPB1 may have played a role in the success of animals.
Evolution of lysine acetylation in the RNA polymerase II C-terminal domain.
Cell line
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