• Journal of Korean Neurosurgical Society
• /
• v.30 no.5
• /
• pp.553-560
• /
• 2001

Objective : The objective of this study was to determine the photodynamic therapeutic response of U-87 human glioma cell in vitro as well as in the nude rat xenograft model using photofrin as photosensitizer. Material and Method : U-87 cells were cultured on 96-well culture plates, photofrin(Quadralogic Technologies Inc., Vancouver, Canada) was added into the cell culture medium at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$. 24 hour after drug treatment, cells were treated with optical(632nm) irradiation of $100mJ/cm^2$, $200mJ/cm^2$ and $400mJ/cm^2$. Photofrin(12.5mg/kg, i.p.) was administered to 28 nude rats containing intracerebral U-87 human glioma as well as 26 normal nude rats. 48 hours after administration, animals were treated with optical irradiation(632nm) of $35J/cm^2$, $140J/cm^2$ and $280J/cm^2$ to exposed tumor and normal brain. The photofrin concentration was measured in tumor and normal brain in a separate population of animals. Results : By MTT assay, there was 100% cytotoxicity at any dose of photofrin with optical irradiation of $200mJ/cm^2$ and $400mJ/cm^2$. But at the optical irradiation of $100mJ/cm^2$ cells were killed in dose dependent manner 28.5%, 49.1%, 54.4%, 78.2%, and 84.6% at concentration of $1{\mu}g/ml$, $2.5{\mu}g/ml$, $5{\mu}g/ml$, $10{\mu}g/ml$ and $20{\mu}g/ml$, respectively. Dose dependent PDT lesions in both tumor and normal brain were observed. In the tumor lesion, only superficial tissue damage was found with optical irradiation of $35J/cm^2$. However, in the optical irradiation group of $140J/cm^2$ and $280J/cm^2$ the volume of lesions was measured of $7.2mm^3$ and $14.0mm^3$ for treatment at $140J/cm^2$ and $280J/cm^2$, respectively. The U-87 bearing rats showed a photofrin concentration in tumor tissue of $6.53{\pm}2.16{\mu}g/g$, 23 times higher than that found in the contralateral hemisphere of $0.28{\pm}0.15{\mu}g/g$. Conclusion : Our data indicate that the U-87 human glioma in vitro and in the xenografted rats is responsive to PDT. At these doses, a reproducible injury can be delivered to human glioma in this model. Strategies to spare the normal brain collateral damage are being studied.

• 대한핵의학회:학술대회논문집
• /
• 1995.05a
• /
• pp.189-189
• /
• 1995

• Journal of Microbiology and Biotechnology
• /
• v.28 no.1
• /
• pp.165-174
• /
• 2018

Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma. However, a direct link between KSHV infection and glioblastoma is currently not known. In this study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV to establish an in vitro cell model for KSHV-infected glioblastoma cells and glioma stem-like cells in order to identify virologic outcomes that overlap with markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs were successfully established. Additionally, using these cell models, we found that KSHV infection modulates the proliferation of glioma stem-like cells.

• Environmental Analysis Health and Toxicology
• /
• v.30
• /
• pp.15.1-15.11
• /
• 2015

Objectives There has been a growing concern about the possible carcinogenic effects of the electromagnetic radiofrequency fields emitted from mobile phones. The purpose of this study was to investigate the association between mobile phone use and the development of gliomas in Korea. Methods Our study methods were based on the International Interphone study that aimed to evaluate possible adverse effects of mobile phone use. This study included 285 histologically-confirmed Korean patients 15 to 69 years of age, with gliomas diagnosed between 2002 and 2007 in 9 hospitals. The 285 individually matched controls were healthy individuals that had their medical check-up in the same hospitals. Unconditional logistic regression was used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for use of mobile phones. Results For the entire group, no significant relationship was investigated between gliomas and regular use of mobile phones, types of mobile phones, lifetime years of use, monthly service fee, and the other exposure indices. Analyses restricted to self-respondents showed similar results. For ipsilateral users, whose the body side for usual mobile phone use match the location of glioma, the aORs (95% CIs) for lifetime years of use and cumulative hours of use were 1.25 (0.55 to 2.88) and 1.77 (0.32 to 1.84), respectively. However, the contralateral users showed slightly lower risk than ipsilateral users. Conclusions Our results do not support the hypothesis that the use of mobile phones increases the risk of glioma; however, we found a non-significant increase in risk among ipsilateral users. These findings suggest further evaluation for glioma risk among longterm mobile phone users.

• Journal of Korean Neurosurgical Society
• /
• v.30 no.sup1
• /
• pp.13-19
• /
• 2001

Objective : We investigated the feasibility of a double suicide gene/prodrug therapy, involving direct introduction of the herpes simplex virus Type 1 thymidine kinase(TK) gene and the Escherichia coli cytosine deaminase(CD) gene, via a recombinant adenoviral vector and ganciclovir(GCV) and/or 5-fluorocytosine(5-FC) treatment, in C6 glioma cells. Methods : Efficient gene transfer and transduction of C6 glioma cells via a recombinant adenovirus were evaluated by infecting cells with adenovirus bearing the ${\beta}$-galactosidase gene and then staining cells with 5-bromo-4-chloro-3-indolyl-13-D-galactoside. CD/TK expression in cells infected with adenovirus bearing the CD/TK gene(ad-CD/TK) was examined by immunoblotting analysis. For in vitro cytotoxicity experiments, the cells were infected with ad-CD/TK or ad-${\Delta}E1$(as a control). After addition of a variety of concentrations of GCV and 5-FU, either separately or in combination, cell viability was determined by staining the cells with crystal violet solution 6 days after infection. Result : C6 glioma cells were efficiently transduced with recombinant adenoviral vector at multiplicities of infection of 200 or more. In vitro cytotoxicity of GCV and/or 5-FC, either alone or in combination, was exclusively observed in the cells transduced with ad-CD/TK. Obvious cytotoxicity(>50% inhibition) was observed in the presence of 5-FC at concentrations greater than 30ug/ml or GCV at concentrations greater than 0.3ug/ml at a multiplicity of infection of 100. Additionally, cytotoxicity in the presence of both GCV and 5-FC was greater than that after sinlge-prodrug treatments, indicating additive effects of the prodrug treatments. Conclusion : The administration of a double-suicide gene/prodrug therapy might have great potential in the treatment of brain tumors.

• Journal of Korean Neurosurgical Society
• /
• v.46 no.4
• /
• pp.413-416
• /
• 2009

Since the start of the antibiotic era, syphilis has become rare. However, in recent times, it has tended to be prevalent concomitantly with human immunodeficiency virus (HIV) infection and coinfection in North America and Europe. Now, such cases are expected to increase in elsewhere including Korea. A 40-year-old male patient visited hospital complaining of a headache for about one month. Brain computed tomography and magnetic resonance imaging, showed leptomeninged enhancing mass with edema an right porisylvian region, which was suspected to be glioma. Patient underwent a blood test and was diagnosed with syphilis and acquired immune deficiency syndrome. Partial cortical and subcortical resection were performed after small craniotomy. The dura was thick, adhered to the brain cortex, and was accompanied by hyperemic change of the cortex. The pathologic diagnosis was meningovascular syphilis (MS) in HIV infection. After the operation, the patient was treated with aqueous penicillin G. Thereafter, he had no neurological deficit except intermittent headache. At first, this case was suspected to be glioma, but it was eventually diagnosed as MS in HIV coinfection. At this point the case was judged to be worth reporting.

• Journal of Korean Neurosurgical Society
• /
• v.54 no.2
• /
• pp.125-127
• /
• 2013

Here, we report a rare case of an anaplastic astrocytoma masquerading as a hypertensive basal ganglia hemorrhage. A 69-year-old woman who had been under medical management for hypertension during the past 3 years suddenly developed right hemiparesis with dysarthria. Brain computed tomography (CT) scans with contrast and CT angiograms revealed an intracerebral hemorrhage (ICH) in the left basal ganglia, without an underlying lesion. She was treated conservatively, but underwent a ventriculoperitoneal shunt operation 3 months after the initial attack due to deteriorated mental status and chronic hydrocephalus. Three months later, her mental status deteriorated further. Magnetic resonance imaging (MRI) with gadolinium demonstrated an irregular enhanced mass in which the previous hemorrhage occurred. The final histological diagnosis which made by stereotactic biopsy was an anaplastic astrocytoma. In the present case, the diagnosis of a high grade glioma was delayed due to tumor bleeding mimicking hypertensive ICH. Thus, a careful review of neuroradiological images including MRI with a suspicion of tumor bleeding is needed even in the patients with past medical history of hypertension.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.5
• /
• pp.467-478
• /
• 2021

In this study, we aimed to synthesize PAMAMG3 derivatives (PAMAMG3-KRRR and PAMAMG3-HKRRR), using KRRR peptides as a nuclear localization signal and introduced histidine residues into the KRRR-grafted PAMAMG3 for delivering a therapeutic, carcinoma cell-selective apoptosis gene, apoptin into human primary glioma (GBL-14) cells and human dermal fibroblasts. We examined their cytotoxicity and gene expression using luciferase activity and enhanced green fluorescent protein PAMAMG3 derivatives in both cell lines. We treated cells with PAMAMG3 derivative/apoptin complexes and investigated their intracellular distribution using confocal microscopy. The PAMAMG3-KRRR and PAMAMG3-HKRRR dendrimers were found to escape from endolysosomes into the cytosol. The JC-1 assay, glutathione levels, and Annexin V staining results showed that apoptin triggered cell death in GBL-14 cells. Overall, these findings indicated that the PAMAMG3-HKRRR/apoptin complex is a potential candidate for an effective nonviral gene delivery system for brain tumor therapy in vitro.

• The Korean Journal of Nuclear Medicine
• /
• v.38 no.3
• /
• pp.268-271
• /
• 2004

A 43-year-old man was presented with persistent headache for two weeks. 72 weighted MR imaging showed high signal intensity with surrounding edema in the left frontal lobe. These findings were considered with intracranial tumor such as glioma or metastasis. Tc-99m tetrofosmin SPECT showed focal radiotracer accumulation in the left frontal lobe. The operative specimen contained cerebral infarction with organizing leptomeningeal hematoma by pathologist. Another 73-year-old man was hospitalized for chronic headache. Initial CT showed ill-defined hypodensity with mass effect in the right parietal lobe. Tc-99m tetrofosmin SPECT showed focal radiotracer uptake in the right parietal lobe. These findings were considered with low-grade glioma or infarction. Follow-up CT after 5 months showed slightly decreased in size of low density in the right parietal lobe, and cerebral infarction is more likely than others. Tc-99m tetrofosmin has been proposed as a cardiotracer of myocardial perfusion imaging and an oncotropic radiotracer. Tc-99m tetrofosmin SPECT image provides a better attractive alternative agent than T1-201 as a tumor-imaging agent, with characteristics such as high-energy flux, short half-life, favorable biodistribution, dosimetry and lower background radioactivity. We have keep in mind on the analysis of Tc-99m tetrofomin imaging when cerebral infarction is being differentiated from brain tumor.

• Toxicological Research
• /
• v.33 no.1
• /
• pp.63-69
• /
• 2017

Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers.