We previously reported that stathmin, a microtubule destabilizer required for the progression of cells through the cell cycle, also mediates the motility, migration, and invasion of malignant glioma cells. This was shown in experiments in which stathmin levels were experimentally increased or decreased with resulting changes in these cellular functions. We also demonstrated that nitrosoureas, DNA alkylating and protein carbamoylating drugs that inhibit stathmin and that are traditionally thought to inhibit only cell division, also inhibit motility, migration, and invasion. As invasion of surrounding brain by malignant glioma cells is one of the major causes of morbidity and mortality for patients with malignant glioma tumors, we have continued pursuing strategies to inhibit stathmin function in vivo, alone and in combination with nitrosourea therapy.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2009
Total Cost
$792,284
Indirect Cost
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State
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Zip Code
Khormaee, Sariah; Chen, Rongjun; Park, John K et al. (2010) The influence of aromatic side-chains on the aqueous properties of pH-sensitive poly(L-lysine iso-phthalamide) derivatives. J Biomater Sci Polym Ed 21:1573-88
Liang, Xing-Jie; Choi, Yong; Sackett, Dan L et al. (2008) Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells. Cancer Res 68:5267-72
Wu, Wells W; Wang, Guanghui; Liang, Xing-Jie et al. (2008) Covalent modification of stathmin by CCNU determined by FTMS analysis of modified proteins and tryptic peptides. Biochem Biophys Res Commun 367:7-13