Abstract

A bimodal pattern of hazard of Clinical evidence in a limited number of patients supports the concept that glioblastoma multiforme (GBM) is a thyroid hormone-dependent cancer. In vitro evidence indicates that Lthyroxine (T4), the principal secretory product of the thyroid gland, at physiological concentrations stimulates proliferation of glioma /GBM cancer cells via a poly-functional cell surface receptor for T4 on the extracellular domain of cancer cell plasma membrane integrin αvβ3. This action of T4 is blocked by nanoparticulate tetraiodothyroacetic acid (Nanotetrac, Nanodiamino-tetrac, NDAT). Tetrac in this NDAT formulation is covalently bound via a diaminopropane linker to a poly(lacticco-glycolic acid) (PLGA) nanoparticle. We have examined histopathologically the induction by NDAT of devascularization, of necrosis and apoptosis in U87MG human GBM cell xenografts in nude mice. Treatment regimen was 1 mg tetrac equivalent/kg body weight s.c. as NDAT daily X10 d, begun 2 d following tumor cell implantation when tumor volume estimates were 350 mm3.