• Journal of Korean Neurosurgical Society
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• v.30 no.2
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• pp.137-143
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• 2001

Objective : Telomerase, a ribonucleoprotein adds telomere repeats to the ends of telomeres to compensate for the progressive loss. A favorable prognosis associated with low or no telomerase activity in some tumors, and cells transfected with antisense human telomerase lost telomeric repeats and die. We studied about the relationship between telomerase activity and apoptosis in the human brain tumors. Material and Methods : Between July 1998 and December 1999, 62 patients with brain tumors underwent surgery and their surgical specimens were obtained. Telomerase activity was investigated by telomeric repeats amplification protocol(TRAP) assay. Apoptosis was also evaluated by DNA fragmentation analysis. Differences and correlation in data were analyzed using Mann-Whitney test and Wilcoxon-signed rank test. Results : Expression rate of telomerase activity and apoptosis were 80% and 30% in malignant gliomas, 33% and 0% in low grade gliomas, 63% and 38% in meningiomas, 67% and 33% in pituitary adenomas, 33% and 33% in metastatic tumors, 67% and 17% in acoustic neurinomas, 100% and 100% in pineoblastomas, 100% and 0% in the hemangioblastoma, respectively. There was no significant difference of telomerase activity and apoptosis between histological types. But a significant difference was noted in the expression of telomerase activity between malignant gliomas and low grade gliomas(p = 0.022). Brain tumors with telomerase activity expressed the lower rate of apoptosis. A significant correlation was also found between telomerase activity and absence of apoptosis in the human brain tumors(p = 0.005). Conclusions : Our data suggests that telomerase may protect from apoptosis of the human brain tumors and also may play an important role in the biological malignancy of the gliomas.

• Korean Journal of Pharmacognosy
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• v.27 no.4
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• pp.350-353
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• 1996

The effects of acid hydrolysis product of Panax ginseng and MeOH extract of Euphorbia humifusa on the growth of human brain tumor cells were evaluated using U-373 MG human astrocytoma and SK-N-MC human neuroblastoma cells as model cellular systems. These plant extracts induced cytotoxicity in both cells in a dose-dependent manner. These cytotoxic effects were significantly inhibited by GSH, an antioxidant, in both cells. BAPTA/AM, an intracellular $Ca^{2+}$ chelator, significantly blocked the cytotoxic effects of these extracts in U-373 cells, but enhanced these effects in SK-N-MC cells. These results suggest that the plant extracts may be a valuable choice for the studies on the treatment of human brain tumors.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.159-163
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• 1995

Previously, we have reported that methylene blue (MB) induces cytotoxicity in human brain tumor cells through the generation of free radicals. In this study the effect of deferoxamine (DFO), an iron chelator, on MB-induced cytotoxicity was investigated using SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cells as model cellular systems. The cytotoxic effect of MB was potentiated by DFO. The potentiation effect of DFO was significantly blocked by either stoichiometric amounts of ferric ion, various antioxidants, hydroxyl radical scavengers or intracellular $Ca^{2+}$ release blockers. These results suggest that hydroxyl radical and intracellular $Ca^{2+}$ may act as important mediators of the enhanced cytotoxicity by MB and DFO. These results further suggest that the combined treatment with MB and DFO may be useful for the therapeutical applications of human brain tumors.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.12-15
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• 2005

Objective : Cerebral edema develops in the brain tumors by loosening of the endothelial tight junction. Tight junction[TJ] proteins, such as occludin and claudin bind adjacent cells tightly. Authors examine the expression rate of occludin in human brain tumors to evaluate the effect of altered expression of occludin on cerebral edema. Methods : Seventy surgical specimens stored at $-70^{\circ}C$ were used. It included 14 astrocytic tumors, 27 meningiomas, 12 scwannomas, 7 pituitary adenomas, 6 hemangioblastomas. and 4 craniopharyngiomas. After protein extraction, expression of occludin was investigated by Western blot analysis. The tumors were classified according to World Health Organization[WHO] classification. Results : The expression rates of occludin in brain tumors were : glioma [8/14=57.1%]. meningioma [16/27=59.3%], schwannoma [10/12=83.3%], pituitary adenoma [6/7=85.7%], hemangioblastoma [6/6=100%], and craniopharyngioma [3/4=75.0%]. The expression rate in glioma and meningioma was lower than other brain tumors. In gliomas, high grade tumor [1/4=25.0%] exhibited lower expression rate of occludin than low grade one [7/10=70.0%]. Conclusion : These results suggest that the expression of occludin is different among the various kinds of brain tumors. In gliomas, its expression is correlated with the histological grade. It may indicate that occludin plays a role in the development of edema in the brain tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9805-9812
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• 2014

Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.

• Journal of Korean Neurosurgical Society
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• v.48 no.1
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• pp.20-30
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• 2010

Objective : We determined whether the expression of GRIM-19 is correlated with pathologic types and malignant grades in gliomas, and determined the function of GRIM-19 in human gliomas. Methods : Tumor tissues were isolated and frozen at $-80^{\circ}C$ just after surgery. The tissues consisted of normal brain tissue (4), astrocytomas (2), anaplastic astrocytomas (2), oligodendrogliomas (13), anaplastic oligodendrogliomas (11), and glioblastomas (16). To profile tumor-related genes, we applied RNA differential display using a $Genefishing^{TM}$ DEG kit, and validated the tumor-related genes by reverse transcription polymerase chain reaction (RT-PCR). A human glioblastoma cell line (U343MG-A) was used for the GRIM-19 functional studies. The morphologic and cytoskeletal changes were examined via light and confocal microscopy. The migratory and invasive abilities were investigated by the simple scratch technique and Matrigel assay. The antiproliferative activity was determined by thiazolyl blue Tetrazolium bromide (MTT) assay and FACS analysis. Results : Based on RT-PCR analysis, the expression of GRIM-19 was higher in astrocytic tumors than oligodendroglial tumors. The expression of GRIM-19 was higher in high-grade tumors than low-grade tumors or normal brain tissue; glioblastomas showed the highest expression. After transfection of GRIM-19 into U343MG-A, the morphology of the sense-transfection cells became larger and more spindly. The antisensetransfection cells became smaller and rounder compared with wild type U343MG-A. The MTT assay showed that the sense-transfection cells were more sensitive to the combination of interferon-$\beta$ and retinoic acid than U343MG-A cells or antisense-transfection cells; the antiproliferative activity was related to apoptosis. Conclusion : GRIM-19 may be one of the gene profiles which regulate cell death via apoptosis in human gliomas.

• Genomics & Informatics
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• v.3 no.3
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• pp.86-93
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• 2005

Human brain EST data provide important clues for our understanding of the molecular biology associated with the function of the normal brain and the molecular pathophysiology with brain disorders. To systematically and efficiently study the function and disorders of the human brain, 45,773 human brain ESTs were collected from 27 human brain cDNA libraries, which were constructed from normal brains and brain disorders such as brain tumors, Parkinson's disease (PO) and epilepsy. An analysis of 45,773 human brain ESTs using our EST analysis pipeline resulted in 38,396 high-quality ESTs and 35,906 ESTs, which were coalesced into 8,246 unique gene clusters, showing a significant similarity to known genes in the human RefSeq, human mRNAs and UniGene database. In addition, among 8,246 gene clusters, 4,287 genes ($52\%$) were found to contain full-length cONA clones. To facilitate the extraction of useful information in collected these human brain ESTs, we developed a user-friendly interface system, the Korea Brain Unigene Database (KBUD). The KBUD web interface allows access to our human brain data through three major search modes, the BioCarta pathway, keywords and BLAST searches. Each result when viewed in KBUD offers comprehensive information concerning the analyzed human brain ESTs provided by our data as well as data linked to various other publiC databases. The user-friendly developed KBUD, the first world-wide web interface for human brain EST data with ESTs of human brain disorders as well as normal brains, will be a helpful system for developing a better understanding of the underlying mechanisms of the normal brain well as brain disorders. The KBUD system is freely accessible at http://kugi.kribb.re.kr/KU/cgi -bin/brain. pI.

• Journal of Korean Neurosurgical Society
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• v.40 no.1
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• pp.1-5
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• 2006

Objective : Survivin is an inhibitor of apoptosis protein[IAP], which inhibits apoptosis through a pathway distinct from the Bcl-2 family members. Overexpression of survivin and Bcl-2 have been commonly reported in human neoplasms. The authors investigate whether there is a synergistic effect on the anti-apoptosis rate of primary brain tumors "in situ" based on the co-expression of survivin and Bcl-2. Methods : One hundred and two brain tumor patients who had been resected were included in this study. Survivin tin and Bcl-2 were detected by Western blotting analysis, while apoptosis was examined by DNA fragmentation analysis. An anti-apoptotic rate was assessed in these brain tumor samples based on the expression of survivin and Bcl-2 or co-expression of both. Results : Survivin and Bcl-2 were expressed in 57[55.9%] and 53[52.0%] of 102 brain tumor samples studied respectively, and co-expressed in 31[30.4%]. The percentage of astrocytic and meningeal tumors expressing survivin was significantly correlated with histological grades; however, Bcl-2 was not correlated [p=0.106]. The anti-apoptotic rate in primary brain tumors with survivin, Bcl-2, and both was detected in 49[86.0%] of 57 samples, 42[79.9%] of 53 samples, and 27[87.1%] of 31 samples, respectively. Their difference in the frequency of anti-apoptosis was not significant. Conclusion : Survivin or Bcl-2 is involved in the anti-apoptosis. However, it suggests that co-expression of survivin and Bcl-2, together, have no synergistic effect on the anti-apoptotic properties of the primary brain tumors.

• Journal of Korean Neurosurgical Society
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• v.43 no.4
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• pp.190-193
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• 2008

Objective : Cancer-testis (CT) genes are considered promising candidates for immunotherapeutic approaches. The aim of this study was to investigate which CT genes should be targeted in immunotherapy for brain tumors. Methods : We investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4, and HOMTES-85) using reverse-transcription polymerase chain reaction in 26 meningiomas and 32 other various brain tumor specimens, obtained from the patients during tumor surgery from 2000 to 2005. Results : The most frequently expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%) meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2 (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6. Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1 (2/6 or 33%). Conclusion : The data presented here suggest that MAGE-E1 and SOX-6 genes are expressed in a high percentage of human central nervous system tumors, which implies the CT genes could be the potential targets of immunotherapy for human central nervous system tumors.

• Journal of Korean Biological Nursing Science
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• v.7 no.1
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• pp.47-56
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• 2005

nm23-H1 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. However, its role with respect to the invasive behavior of central nervous system tumors has scarcely been addressed Because cell motility and invasion plays an essential role in metastatic dissemination, we have studied whether motile human glioma cell(U87MG) transfected with nm23-H1 complementary DNA have any alterations in their ability to migrate and invade. There was no significant changes in the shape and size of the cells following nm23-H1 transfection. The role of nm23-H1 in glioma migration and invasion have been evaluated by in vitro simple scratch technique and brain slice invasion model Basal migration ability of nm23-H1 transfectants cell(U87MG-pEGFP-nm23) were lesser than U87MG. Accordingly, U87MG-pEGFP-nm23 didn't migrate away apparently from the tumors implanted site comparing U87MG in brain slice invasion model. These results suggest that nm23-H1 may play an important role in suppressing the human glioma migration and invasion.