FIG. 4.

Effect of bicarbonate on tumor microenvironment pH_e and survival of tumor-bearing animals. Microscopic pH_e gradients in tumors inoculated into the window chamber were measured by fluorescence ratio imaging of SNARF-1 pH probe. Representative pH_e images are shown for untreated (A) and bicarbonate-treated (B) mice. Red lines, region of interest of tumor. (C) Distributions of pH_e along radial lines for control and bicarbonate-treated tumors. “0” is centroid of tumor, and vertical line indicates tumor edge. (D) Effect of bicarbonate treatment on survival of female SCID mice bearing MDA-MB-231 breast tumors. Mice were started on drinking water (ad libitum) supplemented with 200 mM NaHCO₃ at day 6 postinjection of MDA-MB-231 cells. Data are plotted as a Kaplan–Meier survival curve, the difference in the survival curve for the bicarbonate versus control animals was tested using the log-rank test (p=0.027). Adapted from Robey et al. (60) with permission. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars