Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration

Abstract

Tumor growth is dependent both on endothelial and tumor cells. The aim of this study was to investigate dynamically whether changes in tumor vasculature implicate tumor tissue degeneration during antiangiogenic therapies. In order to quantify intra-tumor vascularization and necrosis, we have used ultrasound technology. This study has identified essential parameters needed to quantify specifically and sensitively the number of microvessels and the extent of necrosis in xenografted human carcinomas during natural tumor evolution, using contrast-enhanced high-frequency ultrasonography with (HFCDUS) or without (HFUS) color Doppler. We showed that quantification of intra-tumor microvessels between HFCDUS and immunohistochemistry is correlated using an anti-CD31 antibody. Furthermore, quantification of tumor necrosis with HFUS was confirmed by histological examination of hematoxylin-eosin-saffraninstained sections over the observation period. Subsequently, for the assessment of novel angiogenic inhibitors, HFCDUS and HFUS were used to elucidate the underlying dynamics linking vessel inhibition and tumor eradication. We describe a novel application for HFCDUS/HFUS that constitutes an effective, convenient, and non-invasive method for clinical assessment of angiogenic inhibitors. In conclusion, we showed that tumor cells abruptly became necrotic following an antivascular therapy, whereas untreated tumors were protected from degeneration by a significant blood supply.

Imaging and targeted agents in gastrointestinal cancers: overview on perfusion- and diffusion-weighted magnetic resonance imaging and angiogenesis inhibitors

“…Especially when low b-values-in part influenced by microperfusion-are applied, an initial decrease of ADC can be expected due to the loss of intravascular perfusion and secondary ischemic swelling of the tumoral cells [6,47]. In our experience and similar to the results of a recent experimental study, the necrosis developed at 4 weeks after initiation of treatment detected by DW-MRI is able to reliably determine therapeutic efficacy by angiogenesis inhibitors [48].…”

Capecitabine combined with (-)-epigallocatechin-3-gallate inhibits angiogenesis and tumor growth in nude mice with gastric cancer xenografts

“…Recent advances in the knowledge of tumor angiogenesis have shed light on the pivotal role of VEGF (21), and VEGF is an important mediator of angiogenesis; it is a potent endothelial cell mitogen, morphogen and vascular permeability-inducing agent (22). MVD is accepted as a standard indicator of angiogenesis (23), and VEGF expression is strictly correlated with MVD (24). In the present study, MTD capecitabine and EGCG did not significantly change the expression levels of VEGF mRNA; instead, the VEGF mRNA expression in the LDM and combination groups decreased significantly.…”

Quantitative elasticity measurements reveal intratumoral changes in response to antiangiogenic therapy - preliminary results

“…Quantitative elasticity measurement curves depicted in Figure 2b show that both control and bevacizumab-treated tumors became stiffer (i.e., shear wave speeds increased) over the course of the study. The more pronounced change in the therapy group is likely due to increased concentrations of extracellular matrix (collagen) in response to dispersed cellularity and necrosis [15]. Alternatively, increased intratumoral elasticity measurements in the control (untreated) tumor group are attributed to increased intratumoral pressures, a known consequence of increased vascular permeability and fluid leakage [4].…”