Research Of Tumorigenesis-related Genes,Anti-cancer Drugs And Cognitive Function Of Ordinary People

Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. Despite recent advances in neurosurgery, radiation therapy and chemotherapy to treat GBM, the prognosis of this cancer is extremely poor. In the present study, the role of Nestin in the tumorogenesis of glioma cells was investigated. The results showed that, in C6glioma cells, only Nestin positive cells would initiate tumors in SD rat brain. This suggested that Nestin might play an important role in the ability of tumor initiation of glioma cells.To further study the biological characters of GBM, A new human glioma cell line designated GBM-HSF was established. Stem cell related genes, Nestin、Klf4、 Oct4、Sox2、Nanog; neuronal markers β-tubulin III and Map2; and the metastasis related gene CD26were all positively transcribed in GBM-HSF cells. GBM-HSF cells grew and formed tumor spheres in conditioned cultured medium. Side population (SP) cells, which had a strong ability to efflux the fluorescent dye Hoechst33342, were also detected in the cell line. These results suggested the existence of cancer stem cells (CSC) in this cell line, which was demonstrated to be a good tool to research the biological characters of GBM.Then we focus on the effects of fluorocitrate (FC), melatonin and nicotinic acid (NA) on glioma cells were tested in order to find effective and specific drugs to GBM. All three drugs were shown to significantly inhibit proliferation and to induce apoptosis of glioma cells. FC suppressed the proliferation of G422glioma cells through inhibiting the tricarboxylic acid cycle of the cells; Melatonin significantly inhibit the growth of C6glioma cells and increase the mRNA levels of stem cell related genes Nestin、Bmi-1and Sox2; NA induced the apoptosis of U251cells, but not neurons, through disrupting intracellular calcium homeostasis. These results indicate that all three drugs might have therapeutic effects on GBM.NA was the most specific among the three drugs, because it had no effect on the survival of neurons. Furthermore, NA induced apoptosis of U251cells only under the acidic conditions. Importantly, the microenvironment of tumors is also acidic due to the high metabolic rate of cancer growth, which may provide a natural target condition for NA.In an additional study, cognitive functions were investigated in healthy controls. The modulation of irrelevant auditory stimuli by the brain during a visual working memory (WM) task was evaluated. Visual WM was found to affect the processing of irrelevant auditory stimuli. Visual WM load was also found to play an important role in this process. These results suggested that the brain could integrate information from different sensory channels in order to guide the execution of cognitive functions. These findings and methodology may have implications for GBM research as previous studies have identified gliomas to influence the cognitive functions.