Normalization of the vasculature for treatment of cancer and other diseases.
The pathophysiology of tumor angiogenesis, the molecular underpinnings and functional consequences of vascular normalization, and the implications for treatment of cancer and nonmalignant diseases are reviewed.
Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases.
Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer
It is shown that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients.
Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model.
Using a mathematical model to simulate IFP and IFV profiles in tumors, it is shown that antiangiogenic therapy can decrease IFP by decreasing the tumor size, vascular hydraulic permeability, and/or the surface area per unit tissue volume of tumor vessels.
Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy
- Yuhui Huang, Jianping Yuan, M. Poznansky
- Biology, MedicineProceedings of the National Academy of Sciences
- 8 October 2012
It is demonstrated that targeting tumor vasculature with lower vascular-normalizing doses, but not high antivascular/antiangiogenic doses, of an anti-VEGF receptor 2 (VEGFR2) antibody results in a more homogeneous distribution of functional tumor vessels.
Micro-Environmental Mechanical Stress Controls Tumor Spheroid Size and Morphology by Suppressing Proliferation and Inducing Apoptosis in Cancer Cells
A strong correlation between the peri-spheroid solid stress distribution and spheroid shape is found, a result of the suppression of cell proliferation and induction of apoptotic cell death in regions of high mechanical stress, suggesting how tumors grow in confined locations where the level of solid stress becomes high.
Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors
- T. Stylianopoulos, John D. Martin, R. Jain
- BiologyProceedings of the National Academy of Sciences
- 29 August 2012
This work shows that therapeutic depletion of carcinoma-associated fibroblasts with an inhibitor of the sonic hedgehog pathway reduces solid stress, decompresses blood and lymphatic vessels, and increases perfusion, and can serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.
Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging
This work introduces optical frequency domain imaging (OFDI) as an intravital microscopy that circumvents the technical limitations of multiphoton microscopy and provides unprecedented access to previously unexplored, crucial aspects of tissue biology.
Mechanical compression drives cancer cells toward invasive phenotype
The results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell–substrate adhesion.
Fluid forces control endothelial sprouting
It is found that fluid shear stress, such as exerted by flowing blood, attenuates EC sprouting in a nitric oxide-dependent manner and that interstitial flow,such as produced by extravasating plasma, directs endothelial morphogenesis and sprout formation.