Martino, A.; Terracciano, R.; Milićević, B.; Milošević, M.; Simić, V.; Fallon, B.C.; Carcamo-Bahena, Y.; Royal, A.L.R.; Carcamo-Bahena, A.A.; Butler, E.B.; Willson, R.C.; Kojić, M.; Filgueira, C.S. An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors. Pharmaceutics2024, 16, 1009.
Martino, A.; Terracciano, R.; Milićević, B.; Milošević, M.; Simić, V.; Fallon, B.C.; Carcamo-Bahena, Y.; Royal, A.L.R.; Carcamo-Bahena, A.A.; Butler, E.B.; Willson, R.C.; Kojić, M.; Filgueira, C.S. An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors. Pharmaceutics 2024, 16, 1009.
Martino, A.; Terracciano, R.; Milićević, B.; Milošević, M.; Simić, V.; Fallon, B.C.; Carcamo-Bahena, Y.; Royal, A.L.R.; Carcamo-Bahena, A.A.; Butler, E.B.; Willson, R.C.; Kojić, M.; Filgueira, C.S. An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors. Pharmaceutics2024, 16, 1009.
Martino, A.; Terracciano, R.; Milićević, B.; Milošević, M.; Simić, V.; Fallon, B.C.; Carcamo-Bahena, Y.; Royal, A.L.R.; Carcamo-Bahena, A.A.; Butler, E.B.; Willson, R.C.; Kojić, M.; Filgueira, C.S. An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors. Pharmaceutics 2024, 16, 1009.
Abstract
Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity which occur across the tumor microenvironment (TME). The goal of this study is to get insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis Lung Carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains - capillary and extracellular space. Anisotropy in tumor structure causes nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.
Keywords
Lung Cancer; Solid Tumors; Perfusion; Vascularity; Finite Element Computational Model; Smeared Physical Fields; Kojic Transport Model
Subject
Biology and Life Sciences, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
