Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alleviating iatrogenic effects of paclitaxel-coated balloons via anti-inflammatory treatment

ABSTRACT: Background: Paclitaxel is touted as an essential medicine due to its extensive use as a chemotherapeutic for various cancers and an antiproliferative agent for restenosis. Due to recent concerns related to long-term mortality, paclitaxel (PTX)-based endovascular therapy is now surrounded by controversies. Objective: Examine the inflammatory mediators driven by the systemic administration of PTX and explore the means to suppress these effects. Methods: RNAseq analysis, cell and mouse models. Results: RNAseq analysis of primary human endothelial cells (ECs) treated with PTX demonstrated transcriptional perturbations of a set of pro-inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1) and CD137, which were validated in EC lysates. These perturbations were abrogated with dexamethasone, a prototypic anti-inflammatory compound. The media of ECs pre-treated with PTX showed a significant increase in MCP-1 levels, which were reverted to baseline levels with DEX treatment. A group of mice harvested at different time points after PTX injection were analyzed for immediate and delayed effects of PTX. A 3-fold increase in MCP-1 was noted in blood and aortic ECs after 12 hours of PTX treatment. Similar changes in CD137 and downstream mediators such as tissue factor, VCAM-1 and E-selectin were noted in aortic ECs. Conclusions: Our study shows that systemic PTX exposure upregulates atherothrombotic markers, and co-delivery of DEX can subdue the untoward toxic effects. Long-term studies are needed to probe the mechanisms driving systemic complications of PTX-based therapies and evaluate the clinical potential of DEX to mitigate risk.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217550 | GEO | 2023/03/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BCLIN25 / miRNA-125b axis regulates chemotherapeutic resistance and epithelial-mesenchymal transition

Project description:paclitaxel-resistant triple-negative breast cancer cell lines (MDA-MB-231/PTX）transfect BCLIN25-specific si-BCLIN25 to knockdown BCLIN25 and analysis differential paclitaxel-resistantlung adenocarcinoma cell lines（PC9/GR）transfect HUMT-specific shHUMT to knockdown HUMT1 and analysis differential

2021-07-06 | GSE179144 | GEO

Effects of Dihydrotanshinone I on proliferation and invasiveness of Paclitaxel-resistant anaplastic thyroid cancer cells

Project description:ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In the patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined-chemotherapy, which is often not fully effective for appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches of this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel, to investigate the characteristics of these cells by analyzing the profile of gene expression and comparing with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment results in a reduction of cell viability, and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro.

2021-07-10 | GSE179786 | GEO

c-Myc drives nab-paclitaxel resistance in pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel has been added to the arsenal of first line therapies, and the combination of gemcitabine and nab-paclitaxel has modestly prolonged median overall survival. However, patients almost invariably succumb to the disease, and little is known about the mechanisms underlying nab-paclitaxel (n-PTX) resistance. Using the conditionally reprogrammed (CR) cell approach, we established and verified continuously growing cell cultures from treatment-naive PDAC patients. To study the mechanisms of primary drug resistance, nab-paclitaxel-resistant (n-PTX-R) cells were generated from primary cultures and drug resistance was verified in vivo, both in zebrafish and in athymic nude mouse xenograft models. Molecular analyses identified the sustained induction of c-MYC in the nab-paclitaxel-resistant cells. Depletion of c-Myc restored nab-paclitaxel sensitivity, as did treatment with either the MEK inhibitor, trametinib, or a small molecule activator of protein phosphatase 2a (SMAP). Implications: The strategies we have devised, including the patient-derived primary cells and the unique drug resistant isogenic cells, are rapid and easily applied in vitro and in vivo platforms to better understand the mechanisms of drug resistance and for defining effective therapeutic options on a patient by patient basis

2019-05-31 | GSE131762 | GEO

miR-1061 and miR-591 are involved in paclitaxel-resistance and their regulation increases the sensitivity to paclitaxel

Project description:MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared to that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and real-time RT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays.

2013-01-17 | GSE43598 | GEO

Transcriptional screening in MDA-231 cells treated with low-dose Paclitaxel for 24 and 48 hours

Project description:Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. Notably, a comprehensive understanding of paclitaxelâs effects requires insight into the dose-specific activities of paclitaxel and their influence on the cancer cells and host microenvironment. The aim of our study is to reveal the gene transcriptional changes in response to low-Paclitaxel (PTX) treatment in breast cancer cells. For genome-wide gene expression analysis, MDA-MB-231 cells (high-invasive breast cancer cell line) were treated with 5 ng/ml PTX for 24 and 48 hours respectively and then the cell lysates were prepared by TRIzol reagent. Then the total RNA in each group was extracted and the genome-wide gene expressing profile was detected through the Human One Array (HOA) Microarray system (Phalanx Biotech Group, Taiwan).

2016-06-01 | E-GEOD-82048 | biostudies-arrayexpress

KFTX paclitaxel (PTX)-resistant ovarian cancer cells, KFTXlow PTX-resistant ovarian cancer cells and KFlow PTX-sensitive ovarian cancer cells expression profilies

Project description:Oncolytic vaccinia virus (OVV) has demonstrated appropriate safety profiles for clinical development. Although OVV was designed to kill cancer cells efficiently, sensitivity to OVV varies in individual cancers. Here, we found that OVV was much more efficient in KFTX paclitaxel (PTX)-resistant ovarian cancer cells, compared to that in KFlow PTX-sensitive cells. Microarray analysis showed that urothelial carcinoma-associated 1 (UCA1) upregulation contributed to both enhanced PTX resistance and OVV spread.

2018-11-10 | GSE122358 | GEO

Transcriptional screening in MDA-231 cells treated with low-dose Paclitaxel for 24 and 48 hours

Project description:Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. Notably, a comprehensive understanding of paclitaxel’s effects requires insight into the dose-specific activities of paclitaxel and their influence on the cancer cells and host microenvironment. The aim of our study is to reveal the gene transcriptional changes in response to low-Paclitaxel (PTX) treatment in breast cancer cells.

2016-06-01 | GSE82048 | GEO

miR-1061 and miR-591 are involved in paclitaxel-resistance and their regulation increases the sensitivity to paclitaxel

2013-01-17 | E-GEOD-43598 | biostudies-arrayexpress

KFTX paclitaxel (PTX)-resistant ovarian cancer cells, KFTXlow PTX-resistant ovarian cancer cells and KFlow PTX-sensitive ovarian cancer cells expression profilies

Project description:KFTX paclitaxel (PTX)-resistant ovarian cancer cells, KFTXlow PTX-resistant ovarian cancer cells and KFlow PTX-sensitive ovarian cancer cells expression profilies

| PRJNA504767 | ENA

Human Toll-Like Receptors Pathway Array Data

Project description:Endothelial cell (EC) Toll-like receptor 2 (TLR2) activation upregulates the expression of inflammatory mediators and of TLR2 itself, and modulates important endothelial functions, including coagulation and permeability. We defined TLR2 signaling pathways in ECs, and tested the hypothesis that TLR2 signaling differs in ECs and monocytes. We found that ERK5, heretofore unrecognized as mediating TLR2 activation in any cell type, is a central mediator of TLR2-dependent inflammatory signaling in HUVEC, primary human lung microvascular ECs and human monocytes. Additionally, we observed that whereas MEK1 negatively regulates TLR2 signaling in EC, MEK1 promotes TLR2 signaling in monocytes. We also noted that activation of TLR2 led to the upregulation of intracellularly expressed TLR2 and inflammatory mediators via NF-κB, JNK and p38-MAPK. Finally, we found that p38-MAPK, JNK, ERK5 and NF-κB promote the attachment of human neutrophils to lung microvascular EC that were pretreated with TLR2 agonists. This study newly identifies ERK5 as a key regulator of TLR2 signaling in ECs and monocytes, and indicates that there are fundamental differences in TLR signaling pathways between EC and monocytes.

2011-11-04 | GSE33449 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data