Non-small cell lung cancers (NSCLCs) harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as erlotinib and geffitinib. However, nearly all patients show relapse within 1 year after initial treatment.
Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells.
Cell line, Treatment
View SamplesComparison of 2 P. s. tritici-inoculated and mock-inoculated genotypes that differ for the Yr39 high-temperature adult-plant resistance phenotype over a time course (12, 24, 48h) ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Tristan Coram. The equivalent experiment is TA11 at PLEXdb.]
Transcriptome analysis of high-temperature adult-plant resistance conditioned by Yr39 during the wheat-Puccinia striiformis f. sp. tritici interaction.
Specimen part, Treatment, Time
View SamplesThe Affymetrix GeneChip Wheat Genome Array currently provides the most comprehensive coverage of the wheat genome for a microarray. In addition to using this resource for transcript expression studies and hybridization-based DNA marker discovery, we endeavored to use the GeneChip to discover the expression of natural antisense transcript (NAT) pairs. By using alternative target preparation schemes, both the sense- and antisense-strand derived transcripts were labeled and hybridized to the Wheat GeneChip. To enable maximum discovery, five different tissue types were selected for assay, and the wheat cultivar Chinese Spring was used considering that most of the GeneChip probe sequences were based on sequencing of this genome. [PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Tristan Coram. The equivalent experiment is TA21 at PLEXdb.]
Large-scale analysis of antisense transcription in wheat using the Affymetrix GeneChip Wheat Genome Array.
No sample metadata fields
View SamplesThe current study investigates the direct effects of in utero vinclozolin exposure on the developing rat testis transcriptome. Vinclozolin is a commonly used fungicide in agriculture and is an endocrine disruptor with anti-androgenic activity. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states that include spermatogenic cell defects, prostate disease, kidney disease, and tumor development. An investigation of the molecular actions of vinclozolin was initiated through an analysis of direct actions on the F1 generation embryonic testis development. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Interestingly, genes previously shown to be regulated during normal male sex determination were not altered by vinclozolin treatment. Categorization by major known functions of all 576 genes altered by in utero vinclozolin exposure demonstrates transcription, signaling, cytoskeletal and extra cellular matrix associated transcripts are highly represented. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin.
Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.
Sex, Specimen part
View SamplesThe possible benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. Little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy subjects considered Se sufficient. We evaluated the transcriptional response of the zebrafish (Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency.
Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Specimen part, Cell line, Treatment
View SamplesAcquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKC activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance.
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Cell line, Treatment
View SamplesAcquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKC activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance.
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Specimen part, Cell line, Treatment
View SamplesThe paraveinal mesophyll (PVM) of soybean leaves is a layer of laterally expanded cells sandwiched between the palisade and spongy mesophyll chlorenchyma. The vacuoles of PVM cells contain an abundance of a putative vegetative storage protein, VSP (, ). VSP is is constitutively produced, but is up-regulated during sink limitation experiments involving flower, fruit, or vegetative bud removal. Soybean vegetative lipoxygenases (Vlx), consisting of 5 isozymes (Vlx, A-D), have been identified as potential storage proteins because they accumulate to high levels with experimental sink limitation and have been co-localized with VSP to the vacuoles of PVM cells. We re-investigated the sub-cellular locations of these enzymes with TEM immuno-cytochemistry. We employed laser micro-dissection to compared RNA expression of PVM cells with mesophyll chlorenchyma cells, and we performed a micro-array analysis of soybean leaf samples representing a time-course, sink-limitation, experiment. We found that none of the Vlx isozymes co-localize with putative storage proteins in PVM vacuoles, and that our sink limitation experiment (typical of those used in the past) induced a strong up-regulation of stress response genes, simultaneous with the up-regulation of the Vlx isozymes. Our findings do not support a storage function for soybean Vlx.
Experimental sink removal induces stress responses, including shifts in amino acid and phenylpropanoid metabolism, in soybean leaves.
Specimen part, Disease
View SamplesDomesticated animal populations often show profound reductions in predator avoidance and fear-related behavior compared to wild populations. These reductions are remarkably consistent and have been observed in a diverse array of taxa including fish, birds, and mammals. Experiments conducted in common environments indicate that these behavioral differences have a genetic basis. In this study, we quantified differences in fear-related behavior between wild and domesticated zebrafish strains and used microarray analysis to identify genes that may be associated with this variation.
Brain transcriptome variation among behaviorally distinct strains of zebrafish (Danio rerio).
Sex, Specimen part
View Samples