In vivo efficacy of a ROCK inhibitor, fasudil, in EBV⁺-DLBL mouse models. (A-B) The efficacy of a ROCK inhibitor, fasudil, in EBV⁺-DLBL mouse models with the RHPN2 I300M mutation (X102). Mice were treated with fasudil (50 mg/kg/day) or vehicle for 17 days (n = 5). Average tumor sizes for each group were plotted (A), and representative tumors after treatment are shown (B). Asterisks indicate statistically significant differences (*P < .05) between vehicle- and fasudil-treated groups. Scale bar, 10 mm. (C) Immunohistological analysis of fasudil-treated residual tumors in EBV⁺-DLBL PDX models. Microscopic examination (hematoxylin and eosin stain, 1.25×) showed decreased numbers of viable cells highlighted by Ki-67 labeling and increased necrosis with fibrosis. Fibrosis was determined by collagen staining. HE, hematoxylin and eosin stain. (D) The synergistic effect of fasudil and CHOP in EBV⁺-DLBL mouse models with the RHPN2 V73M mutation (X88). Mice were treated with fasudil (50 mg/kg/day), CHOP (cyclophosphamide, 30 mg/kg, day 1; hydroxydoxorubicin, 2.475 mg/kg, day 1; vincristine, 0.375 mg/kg, day 1; and prednisone, 0.15 mg/kg, day 1-5), or a combination of fasudil and CHOP for 17 days (n = 5), and average tumor sizes for each group were plotted.