Chemo-manipulation of tumor blood vessels by a metal-based anticancer complex enhances antitumor therapy.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_7744A7B4DE63
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chemo-manipulation of tumor blood vessels by a metal-based anticancer complex enhances antitumor therapy.
Journal
Scientific reports
Author(s)
Riedel T., Cavin S., van den Bergh H., Krueger T., Liaudet L., Ris H.B., Dyson P.J., Perentes J.Y.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
06/07/2018
Peer-reviewed
Oui
Volume
8
Number
1
Pages
10263
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Human pleural mesothelioma is an incurable and chemoresistant cancer. Using a nude mouse xenograft model of human pleural mesothelioma, we show that RAPTA-T, a compound undergoing preclinical evaluation, enhances tumor vascular function by decreasing blood vessel tortuosity and dilation, while increasing the coverage of endothelial cells by pericytes and vessel perfusion within tumors. This in turn significantly reduces the interstitial fluid pressure and increases oxygenation in the tumor. Consequently, RAPTA-T pre-treatment followed by the application of cisplatin or liposomal cisplatin (Lipoplatin) leads to increased levels of the cytotoxin in the tumor and enhanced mesothelioma growth inhibition. We demonstrate that the vascular changes induced by RAPTA-T are related, in part, to the inhibition of poly-(ADP-ribose) polymerase 1 (PARP-1) which is associated to tumor vascular stabilization. These findings suggest novel therapeutic implications for RAPTA-T to create conditions for superior drug uptake and efficacy of approved cytotoxic anti-cancer drugs in malignant pleural mesothelioma and potentially other chemoresistant tumors.
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2018 10:47
Last modification date
20/08/2019 14:34
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