Notch blockade at the level of RBP-J (a downstream Notch-regulated transcription factor) in four types of cancer (lung carcinoma, hepatocellular carcinoma, osteogenic sarcoma, and melanoma) led to defective angiogenesis as evidenced by increased neovascularization and up-regulated hypoxia-inducible factor 1α (HIF1α), leading to hypoxia [48]. This evidence concerns the gene HIF1A and osteosarcoma.