Abstract:
:Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced inflammatory effects. The aim of the present study was (1) to illustrate the inflammatory effects of doxorubicin in vitro and (2) to evaluate a possibly protective effect of monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the possible protection of monoHER, proliferating human umbilical cord vascular endothelial cells (HUVECs) were incubated with different concentrations of doxorubicin ranging from 12.5 to 600 nM with(out) 200 micro M monoHER. Resting (confluent) HUVECs were incubated with (0.5-25 micro M) doxorubicin with(out) monoHER (0.2-1.2 mM) and the viability of endothelial cells and their propensity to adhere to neutrophils were measured 24 h after treatment. The localisation of adhered neutrophils was determined with immunofluorescence microscopy. To further characterise the mechanism of doxorubicin-induced neutrophil adhesion, the expression of the HUVECs surface adhesion molecules was determined after doxorubicin treatment. Doxorubicin decreased the viability and proliferation capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs were much more sensitive to doxorubicin (IC(50)=60.0+/-20.8 nM) than resting cells (LC(50)=4.0+/-0.3 micro M). Doxorubicin also increased the adhesion of neutrophils reaching a plateau value at a doxorubicin concentration of > or =0.4 micro M (P=0.0113). The induced neutrophil adhesion was accompanied by overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not reverse the effect of doxorubicin on the proliferation of endothelial cells, it significantly protected resting HUVECs against the cytotoxic effect of doxorubicin (< or =25 micro M, P<0.0015). In addition, monoHER completely protected against the stimulatory effect of doxorubicin on neutrophil adhesion, and inhibited the doxorubin-induced expression of VCAM and E-selectin on the surface of treated HUVECs. This study illustrates that monoHER, which protects against doxorubicin's cardiotoxic effect, can also protect against doxorubicin-induced inflammatory effects. These data prompt further investigation about the possible link between doxorubicin-induced inflammatory effects and its cardiotoxicity in vivo.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Abou El Hassan MA,Verheul HM,Jorna AS,Schalkwijk C,van Bezu J,van der Vijgh WJ,Bast Adoi
10.1038/sj.bjc.6601022subject
Has Abstractpub_date
2003-07-21 00:00:00pages
357-62issue
2eissn
0007-0920issn
1532-1827pii
6601022journal_volume
89pub_type
杂志文章abstract:BACKGROUND:Several tyrosine kinase inhibitors (TKIs) can decrease docetaxel clearance in patients by an unknown mechanism. We hypothesised that these interactions are mediated by the hepatic uptake transporter OATP1B1. METHODS:The influence of 16 approved TKIs on transport was studied in vitro using HEK293 cells expre...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.811
更新日期:2014-02-18 00:00:00
abstract:BACKGROUND:Epithelial ovarian cancer (EOC) cells are prone to metastasise throughout the peritoneal cavity. The epithelial-to-mesenchymal transition (EMT) is a necessary step towards metastatic tumour progression. CA125/MUC16 mucin is a high-molecular-weight glycoprotein overexpressed in the majority of serous carcinom...
journal_title:British journal of cancer
pub_type: 杂志文章
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abstract::MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in...
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pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605901
更新日期:2010-10-12 00:00:00
abstract::It is known that interferon-gamma (IFN-gamma) is produced by activated T and NK lymphoid cells, mononuclear cells, and macrophage and dendritic cells. Our previous studies have shown that IFN-gamma-like immunoreactivity also appears in human adrenal cortical tumour and phaeochromocytoma. To investigate whether human t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603870
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.27
更新日期:1987-02-01 00:00:00
abstract:BACKGROUND:The clinical utility of machine-learning (ML) algorithms for breast cancer risk prediction and screening practices is unknown. We compared classification of lifetime breast cancer risk based on ML and the BOADICEA model. We explored the differences in risk classification and their clinical impact on screenin...
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.193
更新日期:2016-07-26 00:00:00
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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更新日期:1996-05-01 00:00:00
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doi:10.1038/sj.bjc.6606056
更新日期:2011-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1987-01-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1970.11
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601211
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pub_type: 杂志文章
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更新日期:2002-11-04 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,meta分析,评审
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更新日期:2014-03-18 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602363
更新日期:2005-02-14 00:00:00
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doi:10.1038/sj.bjc.6601766
更新日期:2004-05-04 00:00:00
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pub_type: 杂志文章
doi:10.1054/bjoc.2001.1929
更新日期:2001-08-03 00:00:00
abstract::This article was originally published under a standard license to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
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pub_type: 已发布勘误
doi:10.1038/s41416-019-0534-2
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