Similar Datasets
Project description:The microtubule-stabilising drug paclitaxel has activity in relapsed ovarian cancer. However, resistance frequently develops. Oncolytic adenoviruses are a novel cancer therapy, and replicate selectively within and lyse malignant cells, leading to productive infection of neighbouring cells. We found increased efficacy of adenoviruses of multiple subtypes in paclitaxel-resistant ovarian cancer cells. There was increased expression of a key adenovirus receptor, CAR (coxsackie adenovirus receptor), due to increased transcription that resulted from histone modification. Moreover, CAR transcription increased in intraperitoneal xenografts with acquired paclitaxel resistance and in tumours from patients with paclitaxel-resistant ovarian cancer. Finally, we identified dysregulated cell cycle control as a second mechanism of increased adenovirus efficacy in paclitaxel-resistant ovarian cancer and that inhibition of CDK4/6 using PD-0332991 was able both to reverse paclitaxel resistance and reduce adenovirus efficacy. Thus, paclitaxel resistance increases oncolytic adenovirus efficacy via at least two separate mechanisms. Parental SKOV3 and paclitaxel-resistant SKOV3-TR cells were analysed in duplicate
2015-12-10 | E-GEOD-54772 | biostudies-arrayexpress
Project description:The goals of this study are to compare the transcriptome differences between SKOV3 and rhCCL20-treated SKOV3 cells and identify the defferential expressed genes regulated by rhCCL20 in SKOV3 cells. We treated SKOV3 cells with 5% trehalose (control group) and rhCCL20 protein dissolved in 5% trehalose (experimental group) in vitro. The cells were collected 24 hours after treatment and used for RNA-sequencing.
2020-11-20 | GSE161799 | GEO
Project description:Transcriptomic analysis of tumor tissues isolated from animals bearing F9 teratocarcinoma. 129Sv mice were challenged with F9 tumor cells and, when tumors were palpable, mice were treated with EDA CAR-T s (a mixture of 1×107 CD4+ and 2×106 CD8+ CAR-T cells)or left untreated. 14 days after adoptive transfer, RNA was isolated from tumors for their transcriptomic analysis.
2022-08-10 | GSE204887 | GEO
Project description:Molecular mechanisms of anti-cancer activities of BG-P1600-TAT were explored employing genome-wide expression profiling experiments. Human neuroblastoma cell line SK-N-FI and primary cells SKNAS were treated with 30µM of the BG-P1600-TAT for 48 hours, harvested, and total RNA was immediately isolated from three biological replicates of control (vehicle-treated) and BG-P1600-TAT-treated cells. Gene expression profiling experiments identified 14-gene BG-P1600-TAT molecular interference signature captured most biologically important significantly enriched records reflecting the putative molecular mechanisms of anti-cancer activities of the BG-P1600-TAT. In BG-P1600-TAT treated SK-N-FI cells, 753 differentially expressed genes (DEGs) were identified compared to control vehicle-treated cells. Among 753 DEGs, 427 genes were down-regulated and 326 genes were up-regulated. In SKNAS cells, BG-P1600-TAT showed a significant effects on signal transduction pathways activated during cellular responses to IL-1alpha, TNF-alpha, EGF, TGF, PDGF, and AR. Further BG-P1600-TAT also showed a significant effect on multiprotein complexes of potential biological and therapeutic significance, including several complexes engaged during apoptosis (BCL-2 family protein complex; Survivin complex; BAX complex; Caspase complex), angiogenesis (VEGF-A complex; Thrombospondin complex), and cell adhesion (Galectin complex; Integrin alpha/beta complexes).
2021-09-06 | GSE183482 | GEO
Project description:The majority of patients treated with currently approved adoptive T-cell therapies (ACT) and, specifically, chimeric antigen receptor (CAR) T cells will eventually fail treatment. Furthermore, ACT has not been successful against solid cancers and several hematological malignancies, including T-cell lymphomas which have extremely poor prognosis. One of the main barriers to the effective activity of adoptively transferred T cells is their inhibition when they reach the tumor bed. In this study, we discover that CD5 inhibits CAR T activation and that the knockout (KO) of CD5 using CRISPR-Cas9 enhances the anti-tumor effect of CAR and TCR T cells in multiple hematological and solid cancer models. As a consequence, CD5 KO T cells display increased in vivo expansion and persistence. Despite this increased activity, no clear increased toxicity was observed in preclinical models. These findings support the development of CD5 KO adoptive T-cell therapies in early-phase clinical trials for relapsed and refractory cancer.
2024-07-18 | GSE248590 | GEO
Project description:Next Generation Sequencing of Transcriptomes in SKOV3 and rhCCL20-treated SKOV3 cells
| PRJNA679482 | ENA
Project description:The majority of patients treated with currently approved adoptive T-cell therapies (ACT) and, specifically, chimeric antigen receptor (CAR) T cells will eventually fail treatment. Furthermore, ACT has not been successful against solid cancers and several hematological malignancies, including T-cell lymphomas which have extremely poor prognosis. One of the main barriers to the effective activity of adoptively transferred T cells is their inhibition when they reach the tumor bed. In this study, we discover that CD5 inhibits CAR T activation and that the knockout (KO) of CD5 using CRISPR-Cas9 enhances the anti-tumor effect of CAR and TCR T cells in multiple hematological and solid cancer models. As a consequence, CD5 KO T cells display increased in vivo expansion and persistence. Despite this increased activity, no clear increased toxicity was observed in preclinical models. These findings support the development of CD5 KO adoptive T-cell therapies in early-phase clinical trials for relapsed and refractory cancer.
2024-07-18 | GSE237805 | GEO
Project description:Alpha-particle emitters have recently been explored as valuable therapeutic radionuclides. Yet, toxicity to healthy organs and cancer radioresistance limit the efficacy of targeted alpha-particle therapy (TAT). Identification of the radiation-activated mechanisms, which drive cancer cell survival, provides opportunities to develop new points for therapeutic interference to improve the efficacy and safety of TAT. Quantitative phosphoproteomics and matching proteomics followed were employed to identify alterations in the signaling networks in response to TAT with actinium-225 labeled minigastrin analogue 225Ac-PP-F11N in A431 cells, which overexpress cholecystokinin B receptor (CCKBR).
2023-06-02 | PXD039033 | Pride
Project description:CAR T-cell therapy has led to tremendous successes in the treatment of B-cell malignancies. However, 30%-50% of treated patients relapse – often with reduced target antigen expression. We report that anti-CD19 CAR T-cells cause a rapid reduction of CD19 expression within hours in CAR-T exposed CD19+ B-ALL cells. Initially, anti-CD19 CAR T-cells cause CD19 clusters at the T-cell – leukemia cell interface followed by CD19 internalization and decreased CD19 surface expression. Subsequently, CD19 expression is repressed by transcriptional rewiring. Using single-cell RNA-seq and single-cell ATAC-seq we demonstrate that a subset of CD19low cells that are refractory to CAR T-cell killing employ transcriptional programs of physiological B-cell activation and germinal center reaction in order to sustain decreased CD19 expression. Inhibiting B-cell activation programs with the BTK inhibitor ibrutinib increased the cytotoxic efficacy of anti-CD19 CAR T-cells without effecting CAR T-cell viability. These results demonstrate transcriptional plasticity as an underlying mechanism of CAR T-resistance and highlight the importance of combining CAR T-cell therapy with targeted therapies that aim to overcome this plasticity.
2022-06-09 | GSE176418 | GEO