• Journal of Korean Neurosurgical Society
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• 제58권5호
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• pp.426-431
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• 2015

Objective : The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. Methods : Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at $50mg/m^2/day$ until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). Results : The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was $22.7{\pm}24.1/mm^2$ (mean${\pm}$standard deviation), and this was lower than that of the initial tumor ($61.4{\pm}32.7/mm^2$) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. Conclusion : The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.

• Journal of Korean Neurosurgical Society
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• 제30권sup2호
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• pp.221-227
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• 2001

Objective : The therapeutic impact of tumor resection in glioblastomas is poorly defined and still questionable. Therefore, we conducted the current study to verify the role of tumor resection in the treatment of these highly malignant tumors. Methods : A retrospective study was performed(1990-1999) to compare the treatment results of surgical resection plus radiotherapy(130 patients) with those of stereotactic biopsy plus radiotherapy(19 patients) in glioblastomas. Only adult patients with supratentorial, de novo glioblastoma located in one lobe were included. Survival time/rate was analysed with Kaplan-Meier method, and prognostic variables were obtained from the univariate log-rank test and the multivariate Cox's proportional hazards model. Results : The resection group and the biopsy group did not differ in terms of age, gender, duration of symptoms, presenting symptoms, tumor location, tumor side, tumor size, and the frequency of midline shift. Patients in the biopsy group more often were found to have worse preoperative Karnofsky performance status(KPS)(p=0.001). On univariate analysis, age, KPS, and tumor side were associated with survival(p=0.0053, 0.0001, and 0.0331 respectively). Median survival time and 1-year survival rate were also statistically improved by tumor resection ; resection group - 13 months and 61.2%, and biopsy group - 8 months and 19.7%, respectively(p=0.0001). In patients with midline shift of the tumor, resection was highly effective comparing to biopsy(p=0.0001), but in patients without midline shift, external beam radiation alone was as effective as tumor resection(p=0.0605). Other prognostic variables did not affect survival. On multivariate analysis after variable selection, survival was independently associated with KPS(p=0.001), but not the surgical resection(p=0.2837). Even in biopsy group with midline shift of the tumor, survival rate was not different from that seen after tumor resection(p=0.3505). Conclusions : Radiotherapy alone was as effective as tumor resection plus radiotherapy in patients without midline shift of the tumor. Although there was not statistically significant, tumor resection looked like effective in patients with midline shift. For supratentorial, lobar glioblastoma patients without mass effect of the tumor, biopsy with radiotherapy is one of rational treatment strategies. We consider that tumor resection should be performed in patients with pretreatment midline shift.

• Radiation Oncology Journal
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• 제10권2호
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• pp.163-169
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• 1992

1980년 1월부터 1991년 6월까지 경희대학교 부속병원 치료방사선과에서 수술후 방사선치료를 받은 뇌의 악성 성상세포종과 교아세포종 환자 53명을 대상으로 후향적 분석을 실시하였다. 48명이 추적 가능하였으며 5년생존율은 악성 성상세포종이 $29.4\%$였고 교아세포종이 $2.8\%$였으며 중앙생존기간은 각각 27개월, 11개월이었다. 조직 분화도, 나이, 수행능력, 방사선량이 통계학적으로 유의하게 의미있는 예후인자로 나타났다. 종양절제 정도, 증상발현 기간, 종양의 위치에따라 생존율의 차이를 보였으나 통계적인 유의성은 없었다.

• Journal of Korean Neurosurgical Society
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• 제60권3호
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• pp.380-384
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• 2017

Glioblastoma multiforme (GBM) is located most frequently in the cerebral hemispheres. Glioblastoma presenting as an extraaxial mass of cerebellopontine angle (CPA) is very rare in adults. We report a rare case of GBM arising in the CPA. The patient was a 71-year-old female, who complained of progressive gait disturbance and poor memory. Initial magnetic resonance imaging (MRI) revealed a $1.4{\times}1.3cm$ mass in the left CPA, with broad base to the petrous bone, showing homogenous enhancement. Follow-up MRI showed a rapid increase in size of mass ($2.7{\times}2.2cm$) with a necrotic portion. A stereotactic biopsy was done under the guidance of navigation system, and the histopathologic diagnosis was GBM, World Heath Organization grade IV. Further surgical resection was not performed considering her general condition, and the patient underwent concurrent chemotherapy with radiation therapy. Although rare, the possibility of glioblastoma should be included in the differential diagnosis of atypical CPA tumor.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.971-977
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• 2015

Malignant glioblastoma multiforme (GBM) is the most malignant brain tumor and despite recent advances in diagnostics and treatment prognosis remains poor. In this retrospective study, we assessed the clinical and radiological parameters, as well as fluorescence in situ hybridization (FISH) of 1p19q deletion, in a series of cases. A total of 816 patients with GBM who received surgery and radiation between January 2010 and May 2014 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patient progression free survival (PFS) and overall survival (OS). Age at diagnosis, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 and MMP9 expression level and adjuvant chemotherapy were statistically significant factors (p<0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age ${\leq}50$ years, preoperative KPS score ${\geq}80$, KPS score change after operation ${\geq}0$, involvement of single frontal lobe, deep structure involvement, low Ki-67 and MMP9 expression and adjuvant chemotherapy were independent favorable factors (p<0.05) for patient clinical outcomes.

• Journal of Korean Neurosurgical Society
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• 제64권6호
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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.

• Journal of Korean Neurosurgical Society
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• 제44권6호
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• pp.405-408
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• 2008

GBM is the most common primary brain tumor, but intraventricular GBM is rare and only few cases have been reported in the literature. The authors report a case of 64-year-old man who had a remote history of previous periventricular intracerebral hemorrhage. Brain computed tomography (CT) and magnetic resonance (MR) imaging showed an intraventricular lesion with inhomogeneous enhancement, infiltrative borders and necrotic cyst, and obstructive hydrocephalus. The patient underwent surgical removal through transcortical route via the bottom of previous hemorrhage site and the final pathologic diagnosis was GBM. We present a rare case of an intraventricular GBM with detailed clinical course, radiological findings, and pathological findings, and the possible origin of this lesion is discussed.

• Journal of Ginseng Research
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• 제36권1호
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• pp.86-92
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• 2012

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.225-230
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• 2008

Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against ${\alpha}v$ integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin ${\alpha}v{\beta}3$. Since the ${\alpha}v$ subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

• Radiation Oncology Journal
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• 제20권3호
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• pp.199-205
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• 2002

목적 : 본 연구의 목적은 악성 성상세포종 및 교모세포종 환자들의 방사선 치료 시 가장 적절한 조사 영역을 알아 보고자 시행하였다. 대상 및 방법 : 1994년 1월부터 2000년 3월까지 악성 성상세포종 및 교모세포종으로 진단되어 수술 및 방사선 치료를 받은 후 MRI로 추적관찰이 시행된 환자 중 재발이 확인된 21 명을 대상으로 분석하였다. 원발 병소 바깥 경계에서부터 처음 재발이 확인된 병소까지의 거리를 측정하였다. 그 외에 종양의 크기, 부종의 정도, 수술 절제의 범위, 감마나이프를 이용한 정위방사선수술, 다발성 병변 등이 재발 양상에 미치는 영향에 대하여 분석을 하였다. 결과 : 총 21명 중 18명$(86\%)$이 2 cm 이내에서 재발을 하였다. 이들 중 1 cm 이내가 12명, $1\~2\;cm$ 사이의 재발이 6명이었다. 나머지 3명의 재발은 3 cm, 4 cm, 5 cm, 떨어져서 각각 재발을 하였다. 2 cm 이상 떨어져 재발한 3명은 모두 다발성 병변이 있는 환자였다. 종양의 크기, 부종의 범위, 수술 절제의 범위, 감마나이프 시행 유무에 따른 재발의 양상에 차이가 없었다. 다만 다발성 병변일 경우 더 멀리서 재발하는 경향을 보였다. 결론 : 악성 성상세포종 및 교모세포종에서 재발 양상은 원발 병소 준위의 2 cm 이내 재발이 주 재발 양상이었다. 방사선 조사영역의 넓이는 부종의 범위나, 병소의 크기, 감마 나이프 수술 등에 따라 더 넓힐 필요는 없는 것으로 판단된다. 그러나 다발성 병변의 경우에는 단일 병소보다 더 넓은 조사 범위가 필요할 것으로 생각된다.