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Date of Award

Spring 2005

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Valerie Kish

Abstract

Approximately 50% of all primary intracranial tumors are gliomas, the most malignant of which is glioblastoma multiforme (GBM) (Berens et al., 1990). Able to arise from any type of glial cell, including oligodendrocytes, ependymal cells or astrocytes, glioblastoma multiforme is characterized by wide areas of necrosis or cell death and disruption of the blood-brain barrier within the tumor (Rao, 2003). The invasive properties of these malignant cells consequently lead to a poor patient prognosis and a short mean survival time with a range of 17 weeks without treatment to 50 weeks with the use of chemotherapy (Rao, 2003)

The final stage of tumorigenesis is reached when tumor cells become resistant to various types of therapy and are able to migrate to different sites in the brain. The ability of tumor cells to progress to this ultimate stage is dependent upon their invasive capability as well as their increased survival rate by means of resistance to apoptosis, or programmed cell death (Jaattela, 1999). The invasive capability of tumor cells is related to the production of matrix metalloproteinase 2 (MMP2) which is activated by the binding ofp53 to the promoter region of the MMP2 gene (Bian 1997). Matrix metalloproteinases are a family of enzymes that degrade the matrix that surrounds the cells of the brain so that the cancer cells can proliferate and migrate throughout the tissue (Chang et al., 2001). Several proteins, including the family of heat shock proteins are believed to increase the tumor cell survival rate of and thus also contribute to the aggressiveness of cancer by protecting tumor cells from apoptosis or genetically programmed cell death. All cells synthesize heat shock proteins in response to environmental stresses such as elevated temperature and additionally most other apoptotic stimuli (Jaattela, 1999). Heat shock protein 27 (hsp27) is of particular interest in studying the aggressive nature of GBM because it confers apoptotic resistance against anticancer drugs thereby limiting the effectiveness of cancer therapy.

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