Glucose Uptake and Intracellular pH in a Mouse Model of Ductal Carcinoma In situ (DCIS) Suggests Metabolic Heterogeneity.

Mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast carcinoma remain unclear. Previously we showed that the transition to invasiveness in the mammary intraepithelial neoplastic outgrowth (MINO) model of DCIS does not correlate with its serial acquisition of genetic mutations. We hypothesized instead that progression to invasiveness depends on a change in the microenvironment and that precancer cells might create a more tumor-permissive microenvironment secondary to changes in glucose uptake and metabolism.

Na/H exchange inhibition protects newborn heart from ischemia/reperfusion injury by limiting Na+-dependent Ca2+ overload.

The results of the Guardian/Expedition trials demonstrate the need for more precisely controlled studies to inhibit Na/H exchange (NHE1) during ischemia/reperfusion. This is because overwhelming evidence is consistent with the hypothesis that myocardial ischemic injury results in part from increases in intracellular Na (Nai) mediated by NHE1 that in turn promote Na/Ca exchanger-mediated increases in intracellular Ca ([Ca]i) and Ca-dependent cell damage. We used a more potent and specific NHE1 inhibitor HOE 694 (HOE) to test whether inhibition of NHE1 during ischemia limits increases in Nai and [Ca]i in newborns.