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What is important,administration of DLL4 neutralizing antibody was probably responsible for rapid changes in mouse liver gene expression associated with proliferation and cell cycle regulation. Moreover, animals models such as mice, rats and cynomolgus monkeys exposed to anti-DLL4 antibody have developed strong changes in the liver tissue including profound sinusoidal dilation and centrilobular hepatocyte atrophy. It is thought that those changes were the effect of DLL4 inhibition through Notch1 receptor. Why? Because similar changes were detected when Notch1 signaling was suppressed by ¦Ã-secretase or drugs targeting Notch1 receptors |
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