dc.contributor.author | Stylianopoulos, T. | en |
dc.contributor.author | Jain, R. K. | en |
dc.creator | Stylianopoulos, T. | en |
dc.creator | Jain, R. K. | en |
dc.date.accessioned | 2019-05-06T12:24:40Z | |
dc.date.available | 2019-05-06T12:24:40Z | |
dc.date.issued | 2013 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/48859 | |
dc.description.abstract | Blood perfusion in tumors can be significantly lower than that in the surrounding normal tissue owing to the leakiness and/or compression of tumor blood vessels. Impaired perfusion reduces oxygen supply and results in a hypoxic microenvironment. Hypoxia promotes tumor progression and immunosuppression, and enhances the invasive and metastatic potential of cancer cells. Furthermore, poor perfusion lowers the delivery of systemically administered drugs. Therapeutic strategies to improve perfusion include reduction in vascular permeability by vascular normalization and vascular decompression by alleviating physical forces (solid stress) inside tumors. Both strategies have shown promise, but guidelines on how to use these strategies optimally are lacking. To this end, we developed a mathematical model to guide the optimal use of these strategies. The model accounts for vascular, transvascular, and interstitial fluid and drug transport as well as the diameter and permeability of tumor vessels. Model simulations reveal an optimal perfusion region when vessels are uncompressed, but not very leaky. Within this region, intratumoral distribution of drugs is optimized, particularly for drugs 10 nm in diameter or smaller and of low binding affinity. Therefore, treatments should modify vessel diameter and/or permeability such that perfusion is optimal. Vascular normalization is more effective for hyperpermeable but largely uncompressed vessels (e.g., glioblastomas), whereas solid stress alleviation is more beneficial for compressed but less-permeable vessels (e.g., pancreatic ductal adenocarcinomas). In the case of tumors with hyperpermeable and compressed vessels (e.g., subset of mammary carcinomas), the two strategies need to be combined for improved treatment outcomes. | en |
dc.language.iso | eng | en |
dc.source | Proceedings of the National Academy of Sciences of the United States of America | en |
dc.subject | 2':4 | |
dc.subject | Models | en |
dc.subject | Computer Simulation | en |
dc.subject | article | en |
dc.subject | doxorubicin | en |
dc.subject | human | en |
dc.subject | Neoplasms | en |
dc.subject | Humans | en |
dc.subject | controlled study | en |
dc.subject | cancer survival | en |
dc.subject | priority journal | en |
dc.subject | taxane derivative | en |
dc.subject | treatment outcome | en |
dc.subject | solid tumor | en |
dc.subject | breast carcinoma | en |
dc.subject | upregulation | en |
dc.subject | bevacizumab | en |
dc.subject | sunitinib | en |
dc.subject | Biological | en |
dc.subject | pancreas adenocarcinoma | en |
dc.subject | human cell | en |
dc.subject | ovary carcinoma | en |
dc.subject | regulatory mechanism | en |
dc.subject | nelfinavir | en |
dc.subject | surgical technique | en |
dc.subject | drug delivery system | en |
dc.subject | Drug Delivery Systems | en |
dc.subject | glioblastoma | en |
dc.subject | Biomechanical Phenomena | en |
dc.subject | Mathematical modeling | en |
dc.subject | Regional Blood Flow | en |
dc.subject | extracellular matrix | en |
dc.subject | losartan | en |
dc.subject | Tumor microenvironment | en |
dc.subject | monoclonal antibody DC101 | en |
dc.subject | blood vessel permeability | en |
dc.subject | vascular normalization | en |
dc.subject | cediranib | en |
dc.subject | saridegib | en |
dc.subject | tissue perfusion | en |
dc.subject | drug transport | en |
dc.subject | hydraulic conductivity | en |
dc.subject | 2 (4 hydroxyphenyl) 4 morpholinopyrido[3' | en |
dc.subject | 2 d]pyrimidine | en |
dc.subject | 5]furo[3 | en |
dc.subject | blood vessel diameter | en |
dc.subject | Capillary Permeability | en |
dc.subject | diphtheria toxin | en |
dc.subject | drug binding | en |
dc.subject | Mechanical forces | en |
dc.subject | neutralizing antibody | en |
dc.subject | procollagen proline 2 oxoglutarate 4 dioxygenase | en |
dc.subject | protein farnesyltransferase inhibitor | en |
dc.subject | protein tyrosine phosphatase | en |
dc.subject | semaxanib | en |
dc.subject | vasculotropin antibody | en |
dc.subject | Vessel decompression | en |
dc.subject | Vessel permeability | en |
dc.title | Combining two strategies to improve perfusion and drug delivery in solid tumors | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1073/pnas.1318415110 | |
dc.description.volume | 110 | |
dc.description.startingpage | 18632 | |
dc.description.endingpage | 18637 | |
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 | 18632-18637 | |
dc.gnosis.orcid | 0000-0002-3093-1696 | |