How Combretastatin A-4 Phosphate Affects Tumor Blood Vessels
Author Information
Author(s): Parkins C S, Holder A L, Hill S A, Chaplin D J, Tozer G M
Primary Institution: Tumour Microcirculation Group, Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK
Hypothesis
Neutrophil action contributes to vascular injury by CA-4-P and that NO generation acts to protect the tumour vasculature against CA-4-P-induced injury.
Conclusion
Combretastatin A-4 phosphate reduces blood vessel function in tumors, but nitric oxide can protect against this damage.
Supporting Evidence
- The anti-vascular action of CA-4-P was quantified in two types of murine tumors.
- The SaS tumor showed ~10-fold greater resistance to vascular damage by CA-4-P compared to the CaNT tumor.
- Simultaneous administration of CA-4-P with a NOS inhibitor resulted in enhanced vascular damage.
- Administration of diethylamine NO conferred protection against vascular damage.
- Neutrophil infiltration into the tumors was significantly increased after CA-4-P treatment.
- MPO activity correlated with levels of vascular injury and cytotoxicity.
- The protective effect of NO may be mediated by limiting neutrophil infiltration.
Takeaway
This study shows that a drug can hurt blood vessels in tumors, but a natural substance called nitric oxide can help protect them.
Methodology
The study assessed the functional vascular volume in two types of murine tumors after treatment with CA-4-P and measured neutrophil infiltration using myeloperoxidase activity.
Participant Demographics
Murine tumors (breast adenocarcinoma CaNT and round cell sarcoma SaS).
Digital Object Identifier (DOI)
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