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| They also found that chronic Dll4 blockade was associated with the development of vascular neoplasms in rats in a dose-related manner. To be considered malignant, evidence is required to show that the tumours do not show involution on the discontinuation of Dll4 blockade and show aggressive local invasion and/or distant metastasis, which was not the case here. These observations were not reported in other species such as mice and monkeys, and a histopathological study of the natural history of these tumours, with continued therapy and on cessation of therapy, is critical to inform their behaviour. However, these findings will need to be taken into account in monitoring trials. |
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