Ava Paskewicz
Research Mentor(s): Xing Fan
Mentor Department: Neurosurgery and Cell and Developmental Biology
Authors: Xing Fan, Ava Paskewicz, Anna Park, Kierra Kim
Session: Session 3 (11:00am – 11:50am)
Presentation Type: Poster 67
Abstract
Glioblastoma is the most common malignant brain tumor in adults. Only less than 5% of patients survive more than 2 years and new therapeutic strategies are desperately needed. The cancer stem cell hypothesis purports that only by removing cancer stem cells within a tumor can the cancer be cured. Although CD133 and side population have been used to isolate glioblastoma stem cells, recent data indicated that cancer stem cells also exist in CD133 negative and non-side population in some type of cancer, including glioblastoma, suggesting that additional markers are needed to isolate pure cancer stem cell population. Recent studies showed that glioblastoma primary cultures propagated as neurospheres more accurately replicate the infiltrating growth patterns seen in primary tumors and contain cancer stem cells. There has also been a finding that the NOTCH signaling pathway regulates normal stem cells in the brain, and that GBMs contain stem-like cells with higher NOTCH activity. However, through this study it was discovered that some cancer cells were resistant to the notch pathways. Therefore, the goal of this proposal is to identify which cancer cells are notch resistant and to identify the gene signature for these cancer stem cells in malignant brain tumors. In order to achieve this we will start with an alamar blue assay in order to find the concentration of notch preceptors that kills 50% of the cancer cells and create a growth curve of the data. Based on this result we will plate the cells again using this new concentration found through the alamar blue assay and wait a couple of days until the 50% of the cells are killed. The remaining 50% of the cells that are still alive would be classified as cells that are notch resistant. Then we will identify additional cancer stem cell signatures by screening a cohort of stemness genes by real-time RT-PCR in glioblastoma neurosphere lines and primary tumors. Our lab has yet to find any results, due to heavy training, but considering the procedures goes well we expect to find the cells that are resistant and run them through RNA sequencing and qPCR to find the genes which make these cells resistant.
