Consistent with these data, while t

Consistent with these data, while these alterations were associated with areduction in glucose uptake (Fig. 3D), latent HR2 cells surviving severe ischemia demonstrated anincrease in conversion of glucose to lactate relative to alanine as compared to cells grown understandard conditions (Fig. 3E, 18). Indeed, latent HCC cells were dependent on this metabolicreprogramming as demonstrated by the necessity of LDH for survival. The chemical inhibition of LDH(LDHi, 2.5 μM) resulted in the near complete abrogation of lactate synthesis in HR2 cells grownunder standard and ischemic conditions (Fig 3F). However, while cells cultured under standardconditions with LDHi demonstrated persistent growth and viability, cells cultured under ischemicconditions with LDHi failed to maintain viability beyond 48 hours (Fig. 3G). Taken together, thesedata demonstrate that HCC cells surviving TAE-like ischemia cells undergo metabolicreprogramming of glycolysis to shunt glucose carbons away from anabolic processes and towardslactate. This suggests that metabolic imaging of pyruvate metabolism may provide the sensitivityrequired to detect this latent cell population (Fig. 3H).