Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tasquinimod, a Quinoline-3-Carboxamide Anti-Angiogenic Agent, treated Prostate Cancer Cell Line in-vivo and in-vitro

ABSTRACT: The quinoline-3-carboxamide ABR-215050 (Tasquinimod (INN)), exhibits anti-tumor activity via inhibition of tumor angiogenesis in human and rodent tumors. To further explore the mode of action of ABR-215050, in vivo experiments with gene microarray analysis were performed using samples of LNCaP prostate tumors excised from nude mice exposed to ABR-215050 for 24h at 10 mg/kg(ad.lib.). The array data were validated by real-time PCR (sqRT-PCR), as well as by protein expression experiments. Among several significant differentially expressed gene after exposure to ABR-215050, were cytokine receptor CXCR4, cytochrome P450 1A1 (CYP1A1), thrombospondin-1 (THBS1) and Lysyloxidase preprotein (LOX). To further explore the mode of action of ABR-215050, in vitro experiments with gene microarray analysis were performed using LNCaP prostate tumor cells. The array data were validated by real-time PCR (sqRT-PCR), as well as by protein expression experiments. One of the most significant differentially expressed genes after exposure to ABR-215050, was thrombospondin-1 (THBS1).

ORGANISM(S): Homo sapiens

PROVIDER: GSE17031 | GEO | 2011/03/01

SECONDARY ACCESSION(S): PRJNA117795

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tasquinimod, a Quinoline-3-Carboxamide Anti-Angiogenic Agent, treated Prostate Cancer Cell Line in-vivo and in-vitro

Project description:The quinoline-3-carboxamide ABR-215050 (Tasquinimod (INN)), exhibits anti-tumor activity via inhibition of tumor angiogenesis in human and rodent tumors. To further explore the mode of action of ABR-215050, in vivo experiments with gene microarray analysis were performed using samples of LNCaP prostate tumors excised from nude mice exposed to ABR-215050 for 24h at 10 mg/kg(ad.lib.). The array data were validated by real-time PCR (sqRT-PCR), as well as by protein expression experiments. Among several significant differentially expressed gene after exposure to ABR-215050, were cytokine receptor CXCR4, cytochrome P450 1A1 (CYP1A1), thrombospondin-1 (THBS1) and Lysyloxidase preprotein (LOX). To further explore the mode of action of ABR-215050, in vitro experiments with gene microarray analysis were performed using LNCaP prostate tumor cells. The array data were validated by real-time PCR (sqRT-PCR), as well as by protein expression experiments. One of the most significant differentially expressed genes after exposure to ABR-215050, was thrombospondin-1 (THBS1). 2-color treatment vs. control microarray experiment comprising four biological replicates. Each biological replicate was hybridized with dye-swap; resulting in eight hybridizations for each dataset (in vitro and in vivo), for a total of 16 hybridizations.

2011-03-01 | E-GEOD-17031 | biostudies-arrayexpress

Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity II

Project description:This study defines the impact of in vivo thrombospondin-1 (THBS1) ablation on diaphram stromal cell profile, histology and contractile funciton in a mosue model of diet-induced obesity

2023-08-18 | GSE241168 | GEO

Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity

2023-08-16 | GSE241005 | GEO

O-fucosylation of Thrombospondin Type I Repeats on Thrombospondin 1 is dispensable for trafficking to Platelets

Project description:Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. THBS1’s diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. THBS1’s three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. It is unknown whether these modifications impact trafficking and/or function of THBS1 in vivo. The O-fucose is added by Protein O-fucosyltransferase 2 (POFUT2) and is sequentially extended to the disaccharide by β3glucosyltransferase (B3GLCT). The C-mannose is added by one or more of four C-mannosyltransferases. O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to platelet secretory granules, a major site of THBS1 expression. Additionally, we demonstrated that all three TSRs from platelet THBS1 were highly C-mannosylated, which has been shown to stabilize TSRs in vitro. Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide.

2023-02-02 | PXD037158 | Pride

Regulation of muscle mass by Thrombospondin-1

Project description:Loss of muscle mass is a pathological driver in both chronic illness and aging. We have discovered that skeletal muscle specific thrombospondin-1 (Thbs1) transgenic mice have profound muscle atrophy with age-dependent decreases in exercise capacity and premature lethality. Here, we compared the transcriptional profiles of skeletal muscle from control non-transgenic mice with those overexpressing Thbs1 in order to elucidate the transcriptional changes underlying the observed effects on skeletal muscle mass. The overall purpose was to identify new, effective targets to combat muscle atrophy and sarcopenia.

2024-04-18 | GSE245663 | GEO

Long noncoding RNA as putative biomarkers for protstate cancer detection [Set 2]

Project description:To identify which lncRNAs are differentially expressed in prostate cancer, the total RNA from prostate cancer cell lines (PC3, LNCaP), normal epithelial prostatic cells and the pool of 10 prostate tumor tissues and 10 adjacent normal prostate tissues were screened using SurePrint G3 human lncRNA microarrays (Agilent). The SurePrint G3 Human Gene array contains 16,472 lincRNAs and 34,127 mRNA genes. Gene expression in prostate cell lines and pooled tissue samples was measured. Three independent experiments (biological replicates) for cell lines (epithelial cells, PC3 and LNCap) and two independent experiments (technical replicates) for pooled prostate tissues (tumor and adjacent normal) samples were performed.

2014-10-17 | E-GEOD-55909 | biostudies-arrayexpress

secretome of human chondrocytes and adipose mesenchymal stem cells

Project description:Objective: Assuming that mesenchymal stem cells adapt to the osteoarthritic joint environment to exert a chondroprotective effect, we aimed at investigating the molecular response set up by MSCs after priming by OA chondrocytes in cocultures. Design: We used primary human OA chondrocytes and adipose stem cells (ASCs) in mono- and cocultures and performed a high throughput secretome analysis. Among secreted proteins differentially induced in cocultures, we identified thrombospondin-1 (THBS1) as a potential candidate that could be involved in the chondroprotective effect of ASCs. Results: Secretome analysis revealed significant induction of THBS1in ASCs/chondrocytes cocultures at the mRNA and protein levels. Interestingly, we showed that THBS1 was up-regulated at late stages of MSC chondrogenic differentiation while recombinant THBS1 exerted a prochondrogenic effect on MSC. However, down-regulation of THBS1 in ASCs did not revert OA chondrocyte phenotype by decreasing hypertrophic and inflammatory markers. Nevertheless, down-regulation of THBS1 in ASCs reduced their immunosuppressive activity while recombinant THBS1 exerted an anti-inflammatory role on T lymphocytes. THBS1 function was evaluated in vivo in the collagenase-induced OA (CIOA) model by comparing ASCs expressing siTHBS1 and control ASCs. The OA protective effect of ASCs was reversed when THBS1 was down-regulated in ASCs indicating that THBS1 plays a role in the therapeutic effect of ASCs Conclusions: Our data gather some evidence that THBS1 exerts a pro-chondrogenic and anti-inflammatory function in vitro, which could partially explain a chondroprotective effect of ASCs in OA.

2018-10-22 | PXD008146 | Pride

RNA-seq profiling identifies Androgen Receptor-regulated genes in prostate cancer cells

Project description:The goal of this analysis is to profile AR-regulated genes, especially non-coding RNAs in three androgen sensitive prostate cancer cell lines, MDA-PCA-2B, LNCaP and VCaP. The two cell lines were serum-starved first, followed by dihydrotestosterone (DHT) stimulation or treated with Enzalutamide (AR inhibitor) without starvation. Transcriptome profiling was generated by RNA-sequencing from polyA-selected RNA. These experiments are followed by knock-down experiments of AR and ARlnc1 in MDA-PCA-2B, and also Enzalutamide (anti-androgen) treatment of LNCaP cells.

2018-02-21 | GSE110903 | GEO

VPC-13822 - A Novel Nonsteroidal Drug for the Treatment of Castration Resistant Prostate Cancer by Blocking the Binding Function-3 of the Human Androgen Receptor.

Project description:Inhibition of the alternative target site Binding Function-3 (BF3) of the androgen receptor (AR) with small molecules may represent a novel and viable option for treating castration-resistant disease. In vitro transcription assays and microsome stability experiments were used to characterize the latest and most optimized AR BF3 inhibitor compound VPC-13789 to determine its anti-AR activity and pharmacokinetic properties. VPC-13789 selectively inhibited AR-mediated transcription with an IC50 value of 0.2 μM and effectively supressed the growth of androgen-stimulated LNCaP cell line with an IC50 of 0.32 μM while having no effect on AR-negative PC3 cells. We have further synthesized a pro-drug of VPC-13789 (VPC-13822) with improved solubility and bioavailability. The VPC-13822 pro-drug was evaluated for 4 weeks in mice xenograft LNCaP castration resistant model. When administered orally, VPC-13822 significantly reduced PSA production and tumor volume in this prostate cancer model. No signs of generic toxicity of the candidate compound were observed. Taken together, these results establish a novel class of orally available AR inhibitors with a completely distinct mode of action with a potential utility to treat drug-resistant forms of prostate cancer.

2022-04-05 | GSE147811 | GEO

BV02 perturbed proteome (prostate cancer models)

Project description:short term response of prostate cancer models LNCaP clone FGC and PC-3 to BV02 treatment.

2018-01-16 | MSV000081938 | MassIVE