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proposed a vascular normalization theory in which a judicious intensity of anti-angiogenic therapy could result in an equilibrium between anti-angiogenic and pro-angiogenic signals within the TMEvascular normalization statusand enable efficient delivery of oxygen, drugs, and anti-cancer immune cells into the tumor, rather than inducing excessive destruction of vessels and intratumoral hypoxia 35,36

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Therefore, our findings suggest that HG-induced hyperpermeability may be mainly mediated by the activation of PKC-Erk1/2-NOS axis in cultured hRECs