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This large size can impede diffusion within the dense tumor extracellular matrix, frequently restricting accumulation to perivascular regions and preventing penetration into hypoxic, acidic tumor cores, a limitation that contributes to heterogeneous therapeutic responses [221]

However, when there is a depletion of NO, may be due to depletion of L-arginine, a substrate of NO, or BH 4 , a co-factor in NO production, eNOS switches to an uncoupled state from a coupled state

They break down oxygen, fats and carbohydrates and convert them to make ATP, the energy molecule

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