In addition, ZD led to large tumor size (Fig. 1c) and malignant progression of tongue/esophageal/forestomach tumors in ZD:Cox-2−/− and ZD:Cox-2+/− mice compared with ZD:WT mice (Fig. 1d), with statistical significance achieved for tongue SCC (ZD:Cox-2−/−vs. ZD:WT, 35.7% [5 of 14] vs. 0% [0 of 19], p < 0.01; ZD:Cox-2+/−vs. ZD:WT, 32.6% [15 of 46] vs. 0% [0 of 19], p < 0.01) (Fig. 1a, Supporting Information Table 1). This evidence concerns the gene PTGS2 and neoplasm.