dc.contributor.author | Polydorou, C. | en |
dc.contributor.author | Mpekris, F. | en |
dc.contributor.author | Papageorgis, P. | en |
dc.contributor.author | Voutouri, C. | en |
dc.contributor.author | Stylianopoulos, T. | en |
dc.creator | Polydorou, C. | en |
dc.creator | Mpekris, F. | en |
dc.creator | Papageorgis, P. | en |
dc.creator | Voutouri, C. | en |
dc.creator | Stylianopoulos, T. | en |
dc.date.accessioned | 2019-05-06T12:24:23Z | |
dc.date.available | 2019-05-06T12:24:23Z | |
dc.date.issued | 2017 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/48736 | |
dc.description.abstract | Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization. Using two orthotopic mammary tumor models we demonstrate that Pirfenidone reduces collagen and hyaluronan levels and, as a result, significantly increases blood vessel functionality and perfusion and improves the antitumor efficacy of doxorubicin. Reduction of extracellular matrix components were mediated via TGFβ signaling pathway inhibition due to downregulation of TGFβ1, COL1A1, COL3A1, HAS2, HAS3 expression levels. Our findings provide evidence that repurposing Pirfenidone could be used as a promising strategy to enhance drug delivery to solid tumors by normalizing the tumor microenvironment. | en |
dc.language.iso | eng | en |
dc.source | Oncotarget | en |
dc.subject | cancer chemotherapy | en |
dc.subject | doxorubicin | en |
dc.subject | human | en |
dc.subject | controlled study | en |
dc.subject | female | en |
dc.subject | cancer combination chemotherapy | en |
dc.subject | drug efficacy | en |
dc.subject | monotherapy | en |
dc.subject | antineoplastic activity | en |
dc.subject | tumor microenvironment | en |
dc.subject | dose response | en |
dc.subject | protein expression | en |
dc.subject | unclassified drug | en |
dc.subject | Breast cancer | en |
dc.subject | down regulation | en |
dc.subject | gene expression regulation | en |
dc.subject | nonhuman | en |
dc.subject | signal transduction | en |
dc.subject | transforming growth factor beta | en |
dc.subject | Article | en |
dc.subject | drug mechanism | en |
dc.subject | drug potentiation | en |
dc.subject | human cell | en |
dc.subject | animal cell | en |
dc.subject | animal experiment | en |
dc.subject | animal model | en |
dc.subject | animal tissue | en |
dc.subject | mouse | en |
dc.subject | drug dose comparison | en |
dc.subject | transforming growth factor beta1 | en |
dc.subject | collagen | en |
dc.subject | collagen type 1 | en |
dc.subject | Drug delivery | en |
dc.subject | Biomechanics | en |
dc.subject | extracellular matrix | en |
dc.subject | hyaluronic acid | en |
dc.subject | breast cancer cell line | en |
dc.subject | Vessel compression | en |
dc.subject | tissue perfusion | en |
dc.subject | Tumor perfusion | en |
dc.subject | drug repositioning | en |
dc.subject | 4T1 cell line | en |
dc.subject | blood vessel function | en |
dc.subject | cancer model | en |
dc.subject | collagen type 3 | en |
dc.subject | drug tissue level | en |
dc.subject | hyaluronan synthase 2 | en |
dc.subject | hyaluronan synthase 3 | en |
dc.subject | MCF10CA1a cell line | en |
dc.subject | pirfenidone | en |
dc.subject | synthetase | en |
dc.title | Pirfenidone normalizes the tumor microenvironment to improve chemotherapy | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.18632/oncotarget.15534 | |
dc.description.volume | 8 | |
dc.description.startingpage | 24506 | |
dc.description.endingpage | 24517 | |
dc.author.faculty | Πολυτεχνική Σχολή / Faculty of Engineering | |
dc.author.department | Τμήμα Μηχανικών Μηχανολογίας και Κατασκευαστικής / Department of Mechanical and Manufacturing Engineering | |
dc.type.uhtype | Article | en |
dc.contributor.orcid | Stylianopoulos, T. [0000-0002-3093-1696] | |
dc.description.totalnumpages | 24506-24517 | |
dc.gnosis.orcid | 0000-0002-3093-1696 | |