• Journal of Korean Neurosurgical Society
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• v.38 no.2
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• pp.126-131
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• 2005

Objective : The choice of tumor antigen for dendritic cell[DC]-loading has still been an unresolved problem in the DC-based vaccine strategies against malignant gliomas that has not been found well-characterized tumor specific antigens. In this study, we compare tumor-specific T cell response induced by glioma apoptotic body[GAB]-pulsed DCs to response induced by glioma cell lysate-pulsed ones quantitatively. Methods : DCs generated in the presence of granulocyte macrophage-colony stimulating factor and interleukin[IL]-4 from peripheral blood mononuclear cells[PBMCs] of HLA-A2 positive healthy donors were cultured. Each GABs and glioma cell lysate generated from HLA-A2 positive T98G glioblastoma cells were co-incubated with DCs. $CD8^+$ T lymphocytes isolated from PBMCs of same donors were cultured in media containing IL-2 and either stimulated by GAB- or lysate-pulsed DCs three times at a weekly interval. The interferon[IFN]-${\gamma}$ concentrations of each cell culture supernate were measured by enzyme immunoassay technique. Cytolytic activity of the generated cytotoxic $CD8^+$ T cells either stimulated with GAB- or lysate-pulsed DCs was determined by a standard 4-h $^{51}Cr$-release assay. Results : IFN-${\gamma}$ production and cytolytic activity of effector T cells stimulated by GAB-pulsed DCs were significantly higher than those of T cells stimulated by lysate-pulsed ones. Conclusion : These results indicate the choice of antigen is a critical determinant in the induction of antitumor immunity against malignant glioma. Antigen preparations from GABs represent a promising alternative to glioma cell lysate in DC-based glioma vaccine strategies.

• Radiation Oncology Journal
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• v.29 no.3
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• pp.147-155
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• 2011

Purpose: This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). Materials and Methods: The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. Results: Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose $(BED)_3$ (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed <6 months after radiotherapy was associated with inferior overall survival rates compared to cases of RIBI that occurred ${\geq}6$ months (p = 0.085). Conclusion: Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5137-5142
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• 2012

UHRF2 is a member of the ubiquitin plant homeo domain RING finger family, which has been proven to be frequently up-regulated in colorectal cancer cells and play a role as an oncogene in breast cancer cells. However, the role of UHRF2 in glioma cells remains unclear. In this study, we performed real-time quantitative PCR on 32 pathologically confirmed glioma samples (grade I, 4 cases; grade II, 11 cases; grade III, 10 cases; and grade IV, 7 cases; according to the 2007 WHO classification system) and four glioma cell lines (A172, U251, U373, and U87). The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines. An in vitro assay was performed to investigate the functions of UHRF2. Using a lentivirus-based RNA interference (RNAi) approach, we down-regulated UHRF2 expression in the U251 glioma cell line. This down-regulation led to the inhibition of cell proliferation, an increase in cell apoptosis, and a change of cell cycle distribution, in which S stage cells decreased and G2/M stage cells increased. Our results suggest that UHRF2 may be closely related to tumorigenesis and the development of gliomas.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5225-5230
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• 2013

Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

• Molecules and Cells
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• v.38 no.11
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• pp.991-997
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• 2015

Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of ARE-scontaining mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4'-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3' untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.

• Journal of Korean Neurosurgical Society
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• v.29 no.4
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• pp.471-476
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• 2000

Objective : p16/INK4a, a kind of tumor suppressor genes, encodes a specific inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. This prevents the association of CDK4 with cyclin D1, and subsequently inhibits phosphorylation of retinoblastoma tumor suppressor protein(pRb), thus preventing exit from the G1 phase. According to previous reports, over 50% of glioma tissue and 80% of glioma cell lines have been demonstrated inactivation of p16/INK4a gene. The purpose of this study was to determine whether recombinant adenovirus-p16 virus is a suitable candidate for gene replacement therapy in cases of glioma. Methods : Three human glioma cell lines(U251MG, U87MG and U373MG) that express mutant p16 protein were used. Replication-deficient adenovirus was utilized as an expression vector to transfer exogenous p16 cDNA into the cells ; control cells were infected with the Ad-${\beta}$-gal expressing ${\beta}$-galactosidase. To monitor gene transfer and the expression of exogenous genes, we used Western Blotting analysis. Flow cytometry studies of cellular DNA content were performed to determine the cell cycle phenotype of the glioma cells before and after treatment. Results : We showed here that restoration of p16/INK4a expression in p16 negative U87MG, U251MG and partially deleted U373MG by Ad-CMV-p16 induced growth suppression in vitro. Flow cytometric study revealed that Ad-CMV-p16 infected U87MG cells were arrested during the G0-G1 phase of the cell cycle. Expression of p16 transferred by Ad-CMV-p16 in glioma cells was highly efficient and maintained for more than seven days. Conclusions : Our results suggest that Ad-CMV-p16 gene therapy strategy is potentially useful and warrants further clinical investigation for the treatment of gliomas.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.751-757
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• 2022

Objective : Tumours of the brain are a rare occurrence accounting for approximately 2% of all neoplasms in adults. Few studies have been done in Nigeria on the profile of brain tumours. The aim of this study is to determine the profile of brain tumours in general and determine the change in Kanofsky Performance Score (KPS) after treatment. Methods : This is a prospective hospital-based study in Kaduna. All consecutive patients over 18 years of age with diagnosis of brain tumours from January 2016 to December 2019 were included in the study. Demographic and clinical data was collected using a proforma during the study. Patients who received treatment were followed up for 12 months. The primary outcome data was the difference in the quality of life as measured by KPS at the point of first contact and at 1-month after treatment and at 12-month follow up. Data obtained was analysed with SPSS version 25.0 for Windows. Descriptive statistics was done to determine the profile. Paired t-test at 95% confidence interval was done to check for significant correlation between the mean KPS. Results : A total of 39 consecutive patients were included in the study. There was a slight male preponderance with a M : F of 1.17 : 1. Meningioma and metastasis were more common in females while gliomas and pituitary tumours were more common in males. The mean age of patients was 49.8 years and standard deviation of 11.8 years. Pituitary tumours were the most common tumours. The most common location of the tumour was frontal lobe followed by the pituitary gland. The mean duration of symptoms before neurosurgical consultation was 38 weeks. The most common presenting symptoms of patient with brain tumour was headache. The quality of life improve compare to the baseline in 81% of patient at discharge and at 1 year follow up. The overall mortality rate was 25.6%. Conclusion : The most common brain tumour in our study is pituitary tumour. Most patients present late. The most common presenting symptoms is headache. There is significant improvement in the KPS of patients following treatment. The overall mortality rate at 1-year post treatment is 25.6%.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.241-247
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• 1993

Between July 1988 and December 1992, we treated 45 patients who had deep seated inoperable or residual and/or recurrent intracranial tumors using LINAC based stereotactic radiosurgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Treated intracranial tumors included pituitary tumors (n=15), acoustic neurinomas (n=8), meningiomas (n=7), gliomas (n=6), craniopharyngiomas (n=4), pinealomas (n=3), hemangioblastomas (n=2), and solitary metastatic tumor from lung cancer (n=1). The dimension of treatment field varied from 0.23 to 42.88 $cm^3\;(mean;\;7.26\;cm^3)$. The maximum tumor doses ranging from 5 to 35.5 Gy (mean; 29.9 Gy) were given, and depended on patients' age, target volume, location of lesion and previous history of irradiation. There were 22 male and 23 female patients. The age was varied from 5 to 74 years of age (a median age; 43 years). The mean duration of follow-up was 35 months (2~55 months). To date, 18 $(39.1\%)$ of 46 intracranial tumors treated with SRS showed absent or decrease of the tumor by serial follow-up CT and/or MRI and 16 $(34.8\%)$ were stationary, e.g. growth arrest. From the view point of the clinical aspects, 34 $(73.9\%)$ of 46 tumors were considered improved status, that is, alive with no evidence of active tumor and 8 $(17.4\%)$ of them were stable, alive with disease but no deterioration as compared with before SRS. Although there showed slight increase of the tumor in size according to follow-up imagings of 4 cases (pituitary tumor 1, acoustic neurinomas 2, pinealoma 1), they still represented clinically stable status. Clinically, two $(4.4\%)$ Patients who were anaplastic astrocytoma (n=1) and metastatic brain tumor (n=1) were worsened following SRS treatment. So far, no serious complications were found after treatment. The minor degree headache which could be relieved by steroid or analgesics and transient focal hair loss were observed in a few cases. There should be meticulous long term follow-up inall cases.

• Progress in Medical Physics
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• v.13 no.3
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• pp.120-128
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• 2002

To investigate differences between the metabolic ratios of normal controls and brain tumors such as astrocytomas and glioblastoma multiforme (GM) by proton MR spectroscopy (MRS) at 37 high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxel technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67$\pm$018 and 1.16$\pm$0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (P=0.005). Cho/Cr ratio of glioblastoma multiforme was significantly higher than that of astrocytomas (P=0.001). Lactate was observed in all tumor cases. The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. This results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.

• The Korean Journal of Nuclear Medicine Technology
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• v.28 no.1
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• pp.41-47
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• 2024

Purpose: ¹⁸F-FET, a radiopharmaceutical based on a Tyrosine amino acid derivative using the Sodium-Potassium Pump-independent Transporter (System L) for non-invasive evaluation of primary, recurrent, and metastatic brain tumors, exhibits distinct characteristics. Unlike the widely absorbed ¹⁸F-FDG in both tumor and normal brain tissues, ¹⁸F-FET demonstrates specific uptake only in tumor tissue while almost negligible uptake in normal brain tissue. This study aims to compare and evaluate the usefulness of ¹⁸F-FDG and ¹⁸F-FET Brain PET/CT quantitative analysis in brain tumor diagnosis. Materials and Methods: In 46 patients diagnosed with brain gliomas (High Grade: 34, Low Grade: 12), Brain PET/CT scans were performed at 40 minutes after ¹⁸F-FDG injection and at 20 minutes (early) and 80 minutes (delay) after ¹⁸F-FET injection. SUV_max and SUV_peak of tumor areas corresponding to MRI images were measured in each scan, and the SUV_max-to-SUV_peak ratio, an indicator of tumor prognosis, was calculated. Differences in SUV_max, SUV_peak, and SUV_max-to-SUV_peak ratio between ¹⁸F-FDG and ¹⁸F-FET early/delay scans were statistically verified using SPSS (ver.28) package program. Results: SUV_max values were 3.72±1.36 for ¹⁸F-FDG, 4.59±1.55 for ¹⁸F-FET early, and 4.12±1.36 for ¹⁸F-FET delay scans. The highest SUV_max was observed in ¹⁸F-FET early scans, particularly in HG tumors (4.85±1.44), showing a slightly more significant difference (P<0.0001). SUV_peak values were 3.33±1.13 for ¹⁸F-FDG, 3.04±1.11 for ¹⁸F-FET early, and 2.80±0.96 for ¹⁸F-FET delay scans. The highest SUV_peak was in ¹⁸F-FDG scans, while the lowest was in ¹⁸F-FET delay scans, with a more significant difference in HG tumors (P<0.001). SUV_max-to-SUV_peak ratio values were 1.11±0.09 for ¹⁸F-FDG, 1.54±0.22 for ¹⁸F-FET early, and 1.48±0.17 for ¹⁸F-FET delay scans. This ratio was higher in ¹⁸F-FET scans for both HG and LG tumors (P<0.0001), but there was no statistically significant difference between ¹⁸F-FET early and delay scans. Conclusion: This study confirms the usefulness of early and delay scans in ¹⁸F-FET Brain PET/CT examinations, particularly demonstrating the changes in objective quantitative metrics such as SUV_max, SUV_peak, and introducing the SUV_max-to-SUV_peak ratio as a new evaluation metric based on the degree of tumor malignancy. This is expected to further contributions to the quantitative analysis of Brain PET/CT images.