However, in addition to VEGF, whether other pro-angiogenic factors, such as IL-6 et al., involved in REC8-mediated angiogenesis, whether REC8 regulated NF-κB activity in classical or non-classical pathway, and whether clinical trials with anti-angiogenic agents suppressed tumor angiogenesis in REC8-dependent manner, these unsolved issues remained to be addressed. The gene discussed is NFKB1; the disease is neoplasm.