Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.
Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases.
Specimen part, Disease, Disease stage
View SamplesAlthough abscisic acid (ABA) and gibberellins (GAs) play pivotal roles in many physiological processes in plants, their interaction in the control of leaf growth remains elusive. In this study, genetic analyses of ABA and GA interplay in leaf growth were performed in Arabidopsis thaliana. The results indicate that for ABA and GA interaction, leaf growth of both the aba2/ga20ox1 and aba2/GA20OX1-OE plants exhibits partially additive effects but is similar to the aba2 mutant. Consistent with this result, transcriptome analysis suggests that a substantial proportion (45-65%) of the gene expression profile of aba2/ga20ox1 and aba2/GA20OX1-OE plants overlaps and shares a similar pattern to the aba2 mutant. Thus, these data support that ABA deficiency dominates leaf growth regardless of GA levels. Moreover, gene ontology (GO) analysis indicates gene enrichment in the categories of hormone response, developmental and metabolic processes, and cell wall organization in these three genotypes. Leaf developmental genes are also involved in ABA-GA interaction. Collectively, these data support that the genetic relationship of ABA and GA interaction involves multiple coordinated pathways rather than a simple linear pathway in the regulation of leaf growth.
Genetic analyses of the interaction between abscisic acid and gibberellins in the control of leaf development in Arabidopsis thaliana.
Specimen part
View SamplesBile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis.
Regulation of cholesterol and bile acid homeostasis by the cholesterol 7α-hydroxylase/steroid response element-binding protein 2/microRNA-33a axis in mice.
Sex, Age, Specimen part
View SamplesPompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Specimen part
View SamplesOur current study showed that the ABA and ethylene signal transduction pathways function in parallel and have antagonistic interaction during seed germination and early seedling growth. To further address the possible mechanism by which these two hormones crosstalk, microarray analysis was performed. By microarray analysis we found that an ACC oxidase (ACO) was significantly up-regulated in the aba2 mutant, whereas the 9-CIS-EPOXYCAROTENOID DIOXYGENASE (NCED3) gene in ein2, and both the ABSCISIC ACID INSENSITIVE1 (ABI1) and cytochrome P450, family 707, subfamily A, polypeptide 2 (CYP707A2) genes in etr1-1 were up- and down-regulated, respectively. These data further suggest that ABA and ethylene may control the hormonal biosynthesis, catabolism or signaling of each other to enhance their antagonistic effects upon seed germination and early seedling growth.
Antagonism between abscisic acid and ethylene in Arabidopsis acts in parallel with the reciprocal regulation of their metabolism and signaling pathways.
No sample metadata fields
View SamplesWe transformed Populus trichocarpa and generated transgenics with knockdown or overexpression of monolignol genes and transcription factors Overall design: RNAseq of xylem tissue of transgenic and wildtype Populus trichocarpa. 378 samples.
Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesDespite many studies over a decade, it still remains ambiguous as to the real biological effects induced by radiofrequency electromagnetic fields (RF EMF). Epidemiological studies indicates that long-term exposure to EMF could increase the risk of breast cancer. Some reports have showed that in vitro EMF exposures change cellular gene expression. In this study, we investigated global gene expression responses to RF EMF simulating the Global System for Mobile Communications (GSM) 1800 MHz signal in human breast cancer cell line MCF-7 using transcriptomic approaches.
Effects of global system for mobile communications 1800 MHz radiofrequency electromagnetic fields on gene and protein expression in MCF-7 cells.
Cell line
View SamplesParental MM6 cells, as an additional control, were treated with LPS and PMA. Genes affected by the treatments were identified.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesCyclin T1-dependent genes in PMA-activated MM6 cells.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
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