Prospects for Antiangiogenic Therapies Based upon VEGF Inhibition

2001 ◽  
pp. 282-298 ◽  
Author(s):  
Pascal Furet ◽  
Paul W. Manley
Keyword(s):  
Antiangiogenic Therapies ◽  
Vegf Inhibition

scholarly journals Hsps70 and 90 protect the heart of hyperthyroid rats via nitric oxide production and VEGF inhibition of apoptosis

2021 ◽  
pp. 100097
Author(s):  
Ajayi Ayodeji Folorunsho ◽  
Lateef Olubodun Micheal ◽  
Adebayo Oluwadunsi Iyanuoluwa ◽  
Adebayo Emmanuel Tayo
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Vegf Inhibition

scholarly journals TMIC-24. COLONY STIMULATING FACTOR 1 INHIBITION DECREASES TUMOR GROWTH AND MACROPHAGE INFILTRATION, AND INCREASES NEUTROPHIL INFILTRATION IN XENOGRAFT MICE MODELS OF GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi252-vi252
Author(s):  
Sabbir Khan ◽  
Yuji Piao ◽  
Sandeep Mittal ◽  
Kain McGee ◽  
Soon Park ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mouse Models ◽  
Myeloid Cell ◽  
Neutrophil Infiltration ◽  
Macrophage Infiltration ◽  
Colony Stimulating Factor ◽  
Vegf Inhibitors ◽  
Mesenchymal Transition ◽  
Vegf Inhibition ◽  
Stimulating Factor

Abstract Glioblastoma (GBM) is the most common, highly aggressive and lethal primary brain tumor in adults, and has a median overall survival ranging from 12 to 15 months. Several human cancers including glioma are infiltrated with numerous immune cell types which play a critical role in tumor growth, invasion and resistance to treatment. Previous studies, including our group, have shown that resistance to anti-VEGF therapy is associated with myeloid cell infiltration and mesenchymal transition in GBM. Notably, most glioma patients have shown increase in CD68+ cells due to overproduction of colony stimulating factor 1 (CSF-1) by tumor cells, a growth factor for macrophages. Therefore, we hypothesized that CSF-1 inhibition may reduce macrophage and/or myeloid cell infiltration in glioma, thereby increasing animal survival as monotherapy or in combination with VEGF inhibitors in xenograft GBM mouse models. We tested two CSF-1R inhibitors (AZD 7507 and JNJ-28312141) alone and in combination with VEGF inhibition to prevent macrophage infiltration in xenograft GBM mouse models. CSF-1R and VEGF inhibitors reduced macrophage infiltration (F4/80 staining), tumor volume, and mesenchymal transition (YKL-40 staining), and there was a marginal survival benefit in this model. Interestingly, despite significant reduction in tumor macrophages, we observed a significant increase in neutrophil infiltration and hypoxia (HIF1α staining), particularly in the combinatorial treated. Considering these observations, we further evaluated tumor-associated neutrophil (TAN) infiltration in GBM patient tumors by fluorescence-activated cell sorting (FACS). FACS-isolated TANs were identified as CD11b+/CD15+/CD66b+ triple positive. Our results shown that the infiltrating TAN population vary from 0.5 to 5% in GBM patient tumors. Detailed characterization of TAN population and polarization in patient tumors are ongoing. Our findings revealed that CSF-1 and VEGF inhibition reduced macrophage infiltration and tumor growth, but significantly increased TAN infiltration which will likely hamper the potential therapeutic benefit of anti-CSF1-directed inhibitors.

VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature

2006 ◽  
Vol 290 (2) ◽  
pp. H560-H576 ◽  
Author(s):  
Tomomi Kamba ◽  
Betty Y. Y. Tam ◽  
Hiroya Hashizume ◽  
Amy Haskell ◽  
Barbara Sennino ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Kinase Inhibitor ◽  
Normal Function ◽  
Epididymal Adipose Tissue ◽  
Vegf Receptor ◽  
Adult Mice ◽  
Fenestrated Capillaries ◽  
Transmission Electron ◽  
Vegf Inhibition ◽  
Dose Dependent

Unlike during development, blood vessels in the adult are generally thought not to require VEGF for normal function. However, VEGF is a survival factor for many tumor vessels, and there are clues that some normal blood vessels may also depend on VEGF. In this study, we sought to identify which, if any, vascular beds in adult mice depend on VEGF for survival. Mice were treated with a small-molecule VEGF receptor (VEGFR) tyrosine kinase inhibitor or soluble VEGFRs for 1–3 wk. Blood vessels were assessed using immunohistochemistry or scanning or transmission electron microscopy. In a study of 17 normal organs after VEGF inhibition, we found significant capillary regression in pancreatic islets, thyroid, adrenal cortex, pituitary, choroid plexus, small-intestinal villi, and epididymal adipose tissue. The amount of regression was dose dependent and varied from organ to organ, with a maximum of 68% in thyroid, but was less in normal organs than in tumors in RIP-Tag2-transgenic mice or in Lewis lung carcinoma. VEGF-dependent capillaries were fenestrated, expressed high levels of both VEGFR-2 and VEGFR-3, and had normal pericyte coverage. Surviving capillaries in affected organs had fewer fenestrations and less VEGFR expression. All mice appeared healthy, but distinct physiological changes, including more efficient blood glucose handling, accompanied some regimens of VEGF inhibition. Strikingly, most capillaries in the thyroid grew back within 2 wk after cessation of treatment for 1 wk. Our findings of VEGF dependency of normal fenestrated capillaries and rapid regrowth after regression demonstrate the plasticity of the adult microvasculature.

scholarly journals Dll4 Blockade Potentiates the Anti-Tumor Effects of VEGF Inhibition in Renal Cell Carcinoma Patient-Derived Xenografts

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112371 ◽  
Author(s):  
Kiersten Marie Miles ◽  
Mukund Seshadri ◽  
Eric Ciamporcero ◽  
Remi Adelaiye ◽  
Bryan Gillard ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Renal Cell Carcinoma Patient ◽  
Carcinoma Patient ◽  
Vegf Inhibition
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