Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anti-cancer effect and gene modulation of ET-743 in human biliary tract carcinoma preclinical models

ABSTRACT: Transcriptional profiling of EGI-1 xenografts and patient derived xenografts CHC001 PDX after treatment with ET-743

ORGANISM(S): Homo sapiens

PROVIDER: GSE63043 | GEO | 2017/02/09

SECONDARY ACCESSION(S): PRJNA266509

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Anti-cancer effect and gene modulation of ET-743 in human biliary tract carcinoma preclinical models.

Project description:BACKGROUND:Standard chemotherapy in unresectable biliary tract carcinoma (BTC) patients is based on gemcitabine combined with platinum derivatives. However, primary or acquired resistance is inevitable and no second-line chemotherapy is demonstrated to be effective. Thus, there is an urgent need to identify new alternative (chemo)therapy approaches. METHODS:We evaluated the mechanism of action of ET-743 in preclinical models of BTC. Six BTC cell lines (TFK-1, EGI-1, TGBC1, WITT, KMCH, HuH28), two primary cell cultures derived from BTC patients, the EGI-1 and a new established BTC patient-derived xenografts, were used as preclinical models to investigate the anti-tumor activity of ET-743 in vitro and in vivo. Gene expression profiling was also analyzed upon ET-743 treatment in in vivo models. RESULTS:We found that ET-743 inhibited cell growth of BTC cell lines and primary cultures (IC50 ranging from 0.37 to 3.08 nM) preferentially inducing apoptosis and activation of the complex DNA damage-repair proteins (p-ATM, p-p53 and p-Histone H2A.x) in vitro. In EGI-1 and patient-derived xenografts, ET-743 induced tumor growth delay and reduction of vasculogenesis. In vivo ET-743 induced a deregulation of genes involved in cell adhesion, stress-related response, and in pathways involved in cholangiocarcinogenesis, such as the IL-6, Sonic Hedgehog and Wnt signaling pathways. CONCLUSIONS:These results suggest that ET-743 could represent an alternative chemotherapy for BTC treatment and encourage the development of clinical trials in BTC patients resistant to standard chemotherapy.

| S-EPMC4289395 | biostudies-literature

Gene and microRNA modulation upon ET-743 treatment in a human intrahepatic cholangiocarcinoma paired patient derived xenograft and cell line [gene expression]

Project description:Transcriptional profiling and microRNA profiling of paired PDX and derived cell line MT-CHC01 upon ET-743 treatement Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. ET-743 has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of ET-743 at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of ET-743 were explored in the in vitro model. In vitro, ET-743 inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes. In the PDX model, ET-743 affected ECM-receptor interaction, focal adhesion, complement and coagulation cascades, Hedgehog, MAPK, EGFR signaling via PIP3 pathway, and apoptosis. In MT-CHC01, 24 microRNAs were deregulated upon drug treatment. Only 5 microRNAs were perturbed by ET-743 in PDX; 2 up and 3 down-regulated. Among down- regulated genes, we selected SYK and LGALS1; their silencing caused a significantly reduction of migration, but did not affect proliferation in MT-CHC01 and WITT cells. In conclusion, we described that ET-743 affected genes and microRNAs involved in tumor progression and metastatic processes, reflecting data previously obtained at macroscopically level; in particular, we identified SYK and LGALS1 as new putative targets of ET-743.

2017-06-10 | GSE84918 | GEO

Gene and microRNA modulation upon ET-743 treatment in a human intrahepatic cholangiocarcinoma paired patient derived xenograft and cell line [miRNA expression]

2017-06-10 | GSE84938 | GEO

Expression data from human chondrosarcoma cells resistance to ET-743 and PM00104

Project description:ET-743 (trabectedin, Yondelis®) and PM00104 (Zalypsis®) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood. Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines.

2009-06-24 | GSE16748 | GEO

Transcription profiling of human chondrosarcoma cells resistant to ET-743 and PM00104

Project description:ET-743 (trabectedin, YondelisÂ®) and PM00104 (ZalypsisÂ®) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood. Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines. Experiment Overall Design: Three samples CS-1/ER, CS-1/PR and CS-1 were compared.

2009-07-05 | E-GEOD-16748 | biostudies-arrayexpress

Zea mays cultivar:RSQ-743

Project description:Zea mays RSQ-743 Transcriptome

| PRJNA493332 | ENA

Acinetobacter sp. WC-743

Project description:Acinetobacter sp. WC-743 Genome sequencing and assembly

| PRJNA53455 | ENA

Characterization of a large panel of patient-derived hepatocellular carcinoma xenograft tumor models for preclinical development

Project description:We have generated a collection of patient-derived xenograft (PDX) tumor models and characterized them at the molecular level to facilitate precision oncology. Surgically resected HCC specimens were subcutaneously implanted in immunodeficient mice. Resulting xenografts were serially implanted to establish transplantable PDX models, which were sequentially subject to whole exome sequencing (WES), gene expression array, genome-wide human single nucleotide polymorphism (SNP) array 6.0, and serum a–fetoprotein (AFP) detection assay. The feasibility as a preclinical model was validated by efficacy studies using a standard-of-care (SOC) and a targeted agent, respectively.

2014-03-13 | E-GEOD-55828 | biostudies-arrayexpress

Vibrio vulnificus strain:99-743

Project description:Vibrio vulnificus strain:99-743 Genome sequencing and assembly

| PRJNA299128 | ENA

Juglans ailanthifolia isolate:743-58*2

Project description:Juglans ailanthifolia isolate:743-58*2 Genome sequencing and assembly

| PRJNA1055594 | ENA