Related Experiment Video
Updated: Jul 9, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Alterations in vascular architecture and permeability following OXi4503 treatment
Lie Sam Chan1, Cathy Malcontenti-Wilson, Vijayaragavan Muralidharan
1Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. l.chan11@pgrad.unimelb.edu.au
Abstract:
OXi4503 retards tumor growth in a dose-dependent manner and improves survival in a murine model of colorectal liver metastases. This agent causes extensive vascular shutdown by selectively altering the tubulin cytoskeleton within the endothelial cells of tumor vessels. The destruction of tumor vessels is incomplete, however, and tumor revascularization occurs after the treatment. This study evaluates the pattern of microcirculatory changes and alterations to the ultrastructural properties of the tumor vasculature that result from OXi4503 treatment. Male CBA mice were induced with liver metastases via an intrasplenic injection of a murine-derived colorectal cell line. After administering a single intraperitoneal dose of OXi4503, changes in tumor perfusion, microvascular architecture and permeability were assessed at various time points. One hour after a 100-mg/kg dose of OXi4503, a significant decrease in the percentage of tumor perfusion (63.96+/-1.98 in controls versus 43.77+/-2.71 in treated mice, P<0.001) was observed, which was still evident 5 days after the treatment. Substantial tumor microvascular damage and minimal normal liver injury were observed. Tumor vascular permeability was significantly elevated 45 min after the OXi4503 treatment (67.5+/-3.60 in controls versus 80.5+/-2.24 microg/g, P<0.05). The findings suggest that OXi4503 selectively targets tumor vessels and causes immediate microvascular destruction. Even at the maximum tolerated dose, however, residual patent tumor vessels were still present after treatment, implying incomplete tumor destruction. A combination of OXi4503 with other chemotherapeutic modalities might achieve complete tumor eradication and improve long-term survival.
Insights
OXi4503 effectively reduces tumor perfusion and causes microvascular damage in colorectal liver metastases. However, incomplete destruction necessitates combination therapy for complete tumor eradication and improved survival.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Colorectal liver metastases pose a significant clinical challenge.
- Tumor vascular shutdown is a therapeutic strategy.
- OXi4503 targets tumor vasculature.
Purpose of the Study:
- To evaluate microcirculatory and ultrastructural changes in tumor vasculature after OXi4503 treatment.
- To assess the efficacy and selectivity of OXi4503 in a murine colorectal liver metastasis model.
Main Methods:
- Induction of liver metastases in male CBA mice.
- Single intraperitoneal administration of OXi4503.
- Assessment of tumor perfusion, microvascular architecture, and permeability at various time points.
- Histopathological analysis of tumor and normal liver tissue.
Main Results:
- OXi4503 significantly decreased tumor perfusion by 63.96% vs 43.77% (P<0.001) at 1 hour, persisting for 5 days.
- Tumor vascular permeability increased significantly post-treatment (67.5 vs 80.5 microg/g, P<0.05).
- Substantial tumor microvascular damage occurred with minimal normal liver injury.
Conclusions:
- OXi4503 selectively targets and destroys tumor vessels, causing immediate microvascular shutdown.
- Incomplete tumor vessel destruction remains, suggesting potential for revascularization.
- Combination therapy with OXi4503 may enhance tumor eradication and long-term survival.
