Project description:We demonstrate that DSF/Cu treatment reduced meningioma cell viability and increased intracellular ER stress. We used microarrays to analyze the DSF/Cu regulated gene expression.
Project description:To further explore the mechanism of DSF/Cu in TNBC, we conducted transcriptome sequencing experiments in MDA-MB-231 cells in response to 24 h treatment with DSF/Cu (0.2 µM). RNA-seq data revealed that 874 genes were upregulated and 764 genes were downregulated in DSF/Cu treated cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that TNBC cells death induced by DSF/Cu wais related to MAPK signaling pathway, p53 signaling pathway, mitophagy signaling pathway and ferroptosis.
Project description:Dilsulfiram together with Copper shows efficacy against patient derived Brain Tumor Initiating Cells (BTICs) in vitro and sensitizes BTICs to the DNA damaging agent TMZ. In addition, preclinical assessment found that DSF/Cu potentiaties the efficicacy of TMZ in vivo and prolongs survival. We used microarrays to detail the global profile of gene expression underlying DSF/Cu treatment in vitro and in vivo in BTICs.
Project description:Some chemotherapeutic agents have been found to enhance the antitumor immunity by inducing immunogenic cell death (ICD). The combination of disulfiram (DSF) and copper (Cu) has demonstrated anti-tumor effects in a range of malignancies including hepatocellular carcinoma (HCC). However, the potential of DSF/Cu as an ICD inducer and whether it could enhance the efficacy of immune checkpoint blockade in HCC remains unknown. Here, we showed that DSF/Cu-treated HCC cells exhibited characteristics of ICD in vitro, such as calreticulin (CRT) exposure, ATP secretion, high mobility group box 1 (HMGB1) release. DSF/Cu treated HCC cells elicited significant immune memory in a vaccination assay. DSF/Cu treatment promoted dendritic cell activation and maturation. The combination of DSF/Cu and CD47 blockade further facilitated DC maturation and subsequently enhanced CD8+ T cell cytotoxicity. Mechanically, DSF/Cu promoted the nuclear accumulation and aggregation of nuclear protein localization protein 4 (NPL4) to inhibit the ubiquitin-proteasome system, thus induced endoplasmic reticulum (ER) stress. Inhibition of NPL4 induced ICD-associated damage-associated molecular patterns. Collectively, our findings demonstrated that DSF/Cu induced ICD-mediated immune activation in HCC and enhanced the efficacy of CD47 blockade.
Project description:To investigate the effects of DSF on Arabidopsis in Xcc infecction, we used 2 μM DSF pretreated the roos of Arabidopsis for 48h and then inoculated with Xcc, We then performed gene expression profiling analysis using data obtained from RNA-seq of pretreated/unpretreated at two time points (inoculated with Xcc or not)
Project description:To study the early events of priming response leading to changes in gene expression in Arabidopsis thaliana Col0 wild type plant on infiltration with the potent elicitor molecule Diffusible Signal Factor (DSF). In the present experimentation we have employed total RNA microarray expression profiling as a discovery platform to identify differentially expressing genes that are upregulated and down regulated in the various pathways involved in priming the defense responses by the elicitor molecule DSF on infiltration in the host plant Arabidopsis thaliana. This would help understand the possible defense pathways elicited by the elicitor molecule during interaction. The rosette leaves of Arabidopsis thaliana Col0 plants of 4 weeks old were infiltrated with 100uM DSF and the total RNA samples at 4hpi, 8hpi and 16hpi were extracted along with methanol treatment serving as a control in two biological replicates 1A and 2A. Further, these RNA samples were checked for the quality and subjected to microarray analysis. The differentially expressing candidate genes were identified specific to DSF treatment and were quantified by real-time PCR post DSF treatments.
Project description:We performed expression profiling of 24 meningioma and two dura controls analyzing 55000 transcripts including 18300 known genes. We compared expression in meningioma vs. dura, expression of low grade (WHO I) vs. higher-grade (WHO II and WHO IIII) tumors and expression of meningothelial and syncytial meningioma vs. fibroblastic meningioma. Gene expression was analysed in 24 meningioma including eight of each WHO grade and two dura controls analyzing 55000 transcripts including 18300 known genes.