This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Glufosfamide is a new cyotoxic agent in which isophophamide (IPM) is glycosidically linked to B-D-glucose. It has been shown in bone and soft tissue sarcomas that higher grade tumors express more glucose transporters (GLUT) and undergo enhanced glucose metabolism. Glucosides, such as glufosfamide have been shown to bind to GLUT which undergo endocytosis. This uptake mechanism, coupled with the elevated metablolic rate and up-regulated expression of transmembrane GLUT in most cancer cells, may contribute to the selective cytotoxicity of glufosfamide to tumor cells. It is hoped that glufosfamide will elicit response rates comparable to, or perhaps even better than those seen with ifosfamide and perhaps the lack of a toxic metabolite, acrolein which causes hemorrhagic cystitis, may result in improved safety profile for glufosfamide.
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