• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.441-449
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• 2018

Objective : Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. Methods : We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. Results : In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM $NGF-{\beta}$, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. Conclusion : These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6327-6330
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• 2015

Background: Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1.4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. Materials and Methods: We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Results: Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p = 0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. Conclusions: The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p = 0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.

• Journal of Korean Neurosurgical Society
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• v.64 no.6
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• pp.864-872
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• 2021

Objective : The aim of our study is to investigate the cytotoxic, antioxidant, and antimicrobial effects of newly synthesized boron compounds in U87MG glioblastoma cell treatment. Methods : We synthesized boron glycine monoester (BGM) and boron glycine diester (BGD) structures containing boron atoms and determined their cytotoxic activities on glioblastoma by the MTT method. The inhibitory concentration 50 (IC₅₀) value was calculated with GraphPad Prism 5.0 program. The IC₅₀ values were administered 48 hours on U87MG glioblastoma cell. Catalase (CAT), acid phosphatase (ACP) and alkaline phosphatase (ALP) enzyme activity, malondialdehyde (MDA), total glutathione (GSH), and total protein levels were detected using spectrophotometric methods. We determined the antimicrobial activities of BGM and BGD with the disc diffusion method. Results : After 48 hours of BGM and BGD application to U87MG glioblastoma cells, we found the IC₅₀ value as 6.6 mM and 26 mM, respectively. CAT and ACP enzyme activities were decreased in BGM and BGD groups. MDA which is a metabolite of lipid peroxidation was increased in both boron compounds groups. GSH level was reduced especially in BGD group. BGM and BGD have been found to be antimicrobial effects. Conclusion : Boron compounds, especially the BGM, can provide a new therapeutic approach for the treatment of glioblastoma with their anticancer, antioxidant, and antimicrobial effects.

• Molecules and Cells
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• v.43 no.6
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• pp.539-550
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• 2020

Glioblastoma multiforme (GBM) is a fatal malignant tumor that is characterized by diffusive growth of tumor cells into the surrounding brain parenchyma. However, the diffusive nature of GBM and its relationship with the tumor microenvironment (TME) is still unknown. Here, we investigated the interactions of GBM with the surrounding microenvironment in orthotopic xenograft animal models using two human glioma cell lines, U87 and LN229. The GBM cells in our model showed different features on the aspects of cell growth rate during their development, dispersive nature of glioma tumor cells along blood vessels, and invasion into the brain parenchyma. Our results indicated that these differences in the two models are in part due to differences in the expression of CXCR4 and STAT3, both of which play an important role in tumor progression. In addition, the GBM shows considerable accumulation of resident microglia and peripheral macrophages, but polarizes differently into tumor-supporting cells. These results suggest that the intrinsic factors of GBM and their interaction with the TME determine the diffusive nature and probably the responsiveness to non-cancer cells in the TME.

• BMB Reports
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• v.28 no.1
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• pp.33-39
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• 1995

The Gelatinases (typeIV collagenases) are metalloproteinases that may play an important role in tumor invasion and metastasis. Progelatinase A was purified from a conditioned medium of T98G human glioblastoma cells. TIMP-2 complexed progelatinase A and free progelatinase A were separated by heparin affinity HPLC. The final product was homogeneous on SDS-PAGE, with a molecular weight of 64,000 daltons without reduction. TIMP-2 and free progelatinase A were separated from TIMP-2 complexed progelatinase A by reverse-phase HPLC in the presence of trifluoroacetic acid. TIMP-2 complexed progelatinase A was resistant to activation by p-aminophenyl mercuric acetate (APMA), and showed less than 20% of the activity of the TIMP-2 free active enzyme. TIMP-2 free progelatinase A was easily activated to the mature form with a molecular weight of 57,000 daltons by APMA and showed high activity compared to the TIMP-2 complexed enzyme.

• Journal of Biomedical Engineering Research
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• v.42 no.4
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• pp.159-166
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• 2021

In order to analyze cell images, accurate segmentation of each cell is indispensable. However, the reality is that accurate cell image segmentation is not easy due to various noises, dense cells, and inconsistent shape of cells. Therefore, in this paper, we propose an algorithm that combines marker-based watershed segmentation and ellipse fitting method for glioblastoma cell segmentation. In the proposed algorithm, in order to solve the over-segmentation problem of the existing watershed method, the marker-based watershed technique is primarily performed through "seeding using local minima". In addition, as a second process, the concave point search using ellipse fitting for final segmentation based on the connection line between the concave points has been performed. To evaluate the performance of the proposed algorithm, we compared three algorithms with other algorithms along with the calculation of segmentation accuracy, and we applied the algorithm to other cell image data to check the generalization and propose a solution.

• Journal of the Korean Society of Radiology
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• v.8 no.7
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• pp.389-395
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• 2014

The research was carried out to develop a animal model of malignant brain tumor for the researches in glioblastoma multiform (GBM) diagnosis and therapy. C6 cells were transplanted into the right striatum of SD rat using stereotactic instrument for the development. The developed animal model was verified by MRI and H&E stain assay of anatomicohistological examination. The MRI observations showed that the tumor developed at the injection site at the 7 days after glioblastoma inoculation. At 14 days post inoculation, the tumor grew to a large volume occupying almost a half of the right cerebral hemisphere. It was confirmed that the expression of excessive mitosis and pleomorphism in anatomicohistological examination. The developed animal model must be necessary and useful tool for the in vivo level research in the development of the new modality for the diagnosis and therapy of brain cancer.

• Journal of Korean Neurosurgical Society
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• v.52 no.5
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• pp.484-487
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• 2012

Glioblastoma multiforme (GBM) is the most common primary brain tumor and the most malignant astrocytoma in adults, with rare extra-cranial metastases, especially for subcutaneous metastases. It could be easily misdiagnosed as primary subcutaneous tumor. In this report, we describe a patient with pontine GBM who developed a subcutaneous swelling at the ipsilateral posterior cervical region 8 months after operation, and the pathological and immunocytochemical examination carry the same characteristics as the primary intracranial GBM cells, which defined it as subcutaneous metastasis. GBM with subcutaneous metastasis is extremely rare, and knowledge of a prior intracranial GBM, pathological examinations and immunocytochemical tests with markers typically expressed by GBM are of vital importance for the diagnosis of GBM metastasis. Surgical resection of subcutaneous swelling, followed by chemotherapy and radiotherapy, could be the best strategy of treatment for the patients with GBM subcutaneous metastasis.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.1-12
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• 2005

Objectives: Malignant gliomas are often treated with cisplatin (cis-diamminedichloroplatinum(II), CDDP) and radiation but results remain unsatisfactory. Since malignant glioma displays moderate resistance to conventional therapy, a new treatment modality is needed to improve the outcome of patients with these tumors. The aim of this study was to investigate the effects of the combined use of Jongjihwan(JJH) and cisplatin(CDDP) on cultured malignant glioma cells, A172. Methodss & Results: The combined use of cisplatin and Jeongjihwan had synergistic effects on Al72 cells during 24 hr-incubation, This treatment resulted in a decrease of cell viability, Which was revealed as apoptosis Characterized by activation of caspase-3 protease as well as cleavage of poly ADP-ribose polymerase (PARP) with change of mitochondria membrane potential transition. The expression of members of the Bcl-2 protein family was modulated during co-treatment with Jeongjihwan and cisplatin. Activation of caspase-3 and mitochondrial alterations were central to co-treatment with Jeongjihwan and cisplatin-induced apoptosis. Conclusions: We conclude that co-treatment with Jeongjihwan and cisplatin-induced activation of the mitochondrial pathway enables cell death. Also, we suggest the combined theory of JJH and cisplatin could be a useful method for glioblastoma.

• Molecules and Cells
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• v.40 no.7
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• pp.515-522
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• 2017

CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-$1{\beta}$ and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-$1{\beta}$ gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-$1{\beta}$ signaling pathway.