Indirubin is the ac ti ve ingredi ent of a traditional Chinese herbal medicine, Danggui Longhui Wan, used for t he t reatment of chronic myelocytic leukemia Here, we report that novel indirubin ,- 11‘ ivative‘ 5’ - nitro-indirubinoxime (5’ NIO) , has potent anti- proliferative activity on va rious human cancel‘ cells and oncogenic RK3E- ras rat kidney cells with ha lf- inhibi tory concentrati ons (1C50) ra nging from 1- 12 M, Treatment with indirubin derivative induced the activation 01' caspase 7 rollowed by apoptos is in RK3E- ras cells. lndirubin derivative showed strong anti-tumor activity in rat solid and oral tUll10r models , Direct inj ection of indirubin deri vative every other day for 10 days induced signifi cant inhi bition of tumor growth in Sprague-Dawley rats bearing RK3E- ras-induced tumors Histologically. t reatment with indiru bin de ri vative caused s ignifi cant inhi bit ion of tumor formation with increased apoptosis and decreased tumor cell prolife ration, These f indings provide the potent ial va lue of indirubin deri vative a s a novel candidate for ant i-tumor agents

Cherubi sm is a ra re autosoma l dominant inherited condi tion caused by mutations in the c-Abl-binding protein SH3BP2. 1t is characteri zecl by mul t iple cystic giant cell lesions of the jaw appearing in early childhood with stabi li zation and rcmi ssion after pubcr ty, In thc present study, genomic DNA was purified f rom a blood sample obtained from the patient a ncl pa rents a ncl used f'or di rect sequence analysis of the SH3BP2 gene, 1n addit ion, a sample of the lesion was used f0 1" hi stologic ancl immunoh is toche mical purposes, Histology revealed a proliferation of spindle s haped fibroblas t ic cells and irregu la ry dis persed multinucleated giant cell s , The multinucleated giant cells proved posit ive for CD68 and TRAP, Ge nomic DNA sequencing f'ou ncl a missense mutation Pro418Arg in exon 9 of the SH3BP2 gene of the patient and the mother, Theref'ore, the mul t inucleated giant cells are basically osteoclastic in nature, Additionally, as the PI'o418Arg mutation had been repol' ted as caus ing cherubism, it represents a mutational hotspot,