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: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.
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.
Project description:Comparison of the gene expression profiles with meningiomas of different grading. 24 primary meningioma cultures from surgical specimen were maintained to primary meningioma cultures.