Kimura et al[121] experimentally found that dihydroxycoumarin (aescinate or vuloxetine) inhibited M2 macrophage differentiation in tumor-associated macrophages and/or CyclinD1, CDK4, MMP-2, TGF-β1 and VEGF production in OS LM8 cells (in vitro) and tumor-bearing mouse models of high metastasis carrying LM8 cells (in vivo) through the TGF-β1 signaling pathway. The gene discussed is CDK4; the disease is neoplasm.