During this fiscal year, we reported that stathmin, a microtubule destabilizer required for the progression of cells through the cell cycle, is a 1p encoded protein that is relatively underexpressed in anaplastic oligodendrogliomas (AO) with 1p loss of heterozygosity (LOH). Examination of patient outcomes indicated that low tumor expression of stathmin is significantly associated with improved survival of AO patients and wih 1p LOH. Functional and biochemical studies revealed that reduced cellular stathmin levels can decrease the resistance of tumor cells to nitrosourea chemotherapies in particular. We plan to explore further the mechanisms by which stathmin levels and function can be decreased in order to devise therapeutic strategies to make tumor cells less resistant to chemotherapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS003100-04
Application #
7594741
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2007
Total Cost
$1,016,596
Indirect Cost
City
State
Country
United States
Zip Code
Jarboe, John S; Johnson, Kory R; Choi, Yong et al. (2007) Expression of interleukin-13 receptor alpha2 in glioblastoma multiforme: implications for targeted therapies. Cancer Res 67:7983-6
Ngo, Teri-T B; Peng, Tien; Liang, Xing-Jie et al. (2007) The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst 99:639-52
Lee, Jeongwu; Kotliarova, Svetlana; Kotliarov, Yuri et al. (2006) Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9:391-403
Akeju, Oluwaseun; Peng, Tien; Park, John K (2006) Short hairpin RNA loop design for the facilitation of sequence verification. Biotechniques 40:154, 156, 158
Purow, Benjamin W; Haque, Raqeeb M; Noel, Martha W et al. (2005) Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res 65:2353-63