• BMB Reports
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• v.51 no.10
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• pp.481-483
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• 2018

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.151-158
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• 1994

Since Jan. 1992, authors have conducted a pilot study to treat malignant glioma with multiple daily fractionated(MDF) radiation therapy and this paper presents the outcome compared MDF to conventional factionated(CF) radiation therapy Between Sep. 1989 and Jan. 1993, forty three patients with high grade glioma of brain except brain stem glioma were treated: nineteen patients were treated with CF radiation therapy and 24 patients were treated with MDF radiation therapy. In CF radiation therapy, total dose was 6300cGy/35fx in 7 weeks, which 5040cGy was delivered to the initial target volume and 1260cGy to reduced target volume. And in MDF radiation therapy, total dose was 6400cGy/40fx in 4 weeks, which 3200cGy was delivered to the initial target volume as 160cGy 2 times daily 6hr apart. All patients had histologically confirmed anaplastic astrocytoma(AA) of glioblastoma multiforme (GBM) with stereotactic biopsy or craniotomy for subtotal or gross tumor resection. The range of follow-up was 7 months to 4 years with a median follow-up of 9 months. The Median survival from surgery was 9 months for all patients. The median survival was 9 months and 10 months for MDF group and CF group and 10 months and 9.5 months for glioblastoma multiforme and anaplastic astrocytoma, respectively. In 36 patients with follow-up CT scan or MRI scan, disease status was evaluated according to treatment groups, Four patients(GBM:3, AA:1) of 21 patients in MDF group, were alive with no evidence of disease, while none of patient was alive with no evidence of disease in CF group. The progression of disease had occurred in 20 patients, 11 patients and 9 patients in MDF group and CF group, respectively All of these patients showed in-field progression of disease, Four of 11 patients($27\%$) in MDF group showed the new leasion outside of the treatment field, while 5 of 9 patients($56\%$) in CF group. In our study the prognosis was not influenced by age, KPS, grade, extent of surgery and different fractional scheduled radiation therapy. Authors concluded that MDF regimen was well tolerated and shortened the treatment period from 7 weeks to 4 weeks without compromising results. We believe that further follow-up is needed to assess the role of MDF.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.249-258
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• 1993

Between March 1983 and December 1989, ninety-six patients with intracranial glioma were treated in the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. We retrospectively reviewed each case to evaluate variable factors influencing the treatment results and to develop an optimal therapy Policy. Median follow-up is 57 months (range: 31~133 months). Of the 96 patients, 60 $(63\%)$ were males and 36 $(37\%)$ were females. Ages ranged from 3 to 69 years (median 42 years). The most common presenting symtoms were headeche $(67\%)$ followed by cerebral motor and sensory discrepancy $(54\%),$ nausea and vomiting $(34\%),$ seizure $(19\%),$ mental change $(10\%)$ and memory and calculation impairment $(8\%).$ Eighty five $(88.5\%)$ patients all, except 11 $(11.5\%)$ brain stem lesions, were biopsy proven intracranial glioma. The distribution by histologic type was 64 astrocytomas $(75\%),$ 4 mixed oligoastrocytomas $(5\%),$ and 17 oligodendrogliomas $(20\%).$ Fourty nine patients $(58\%$ were grade I, II histology and 36 $(42\%)$ patients were grade III, IV histology. Of the 96 patients, 64 $(67\%)$ recieved postoperative RT and 32 $(33\%)$ were treated with primary radiotherapy. Gross total resection was peformed in 14 $(16\%)$ patients, subtotal resection En 29 $(34\%),$ partial resection in 21 $(25\%),$ and biopsy only in 21 $(25\%).$ Median survival time was 53 months (range 2~ 133 months), and 2- and, 5-year survival rate were $69\%,49\%$ respectively. 5-year survival rate by histologic grade was grade I, $70\%,$ grade II, $58\%,$ grade III, $28\%,$ and grade IV, $15\%.$ Multivariated analysis demonstrate that age at diagnosis (p=0.0121), Karnofsky performance Status (KPS) (p=0.0002), histologic grade (p=0.0001), postoperative radiation therapy (p=0.0278), surgical extent (p =0.024), cerebellar location of tumor (p=0.0095) were significant prognostic factors influencing on survival.

• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.1016-1023
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• 2002

Purpose : Brain tumors are the most common solid tumor in children. We retrospectively investigated the clinical characteristics of pediatric brain tumors, such as age, sex, tumor site and survival, as seen in a single institution over the last 15 years. We tried to evaluate the role of chemotherapy on the survival of some brain tumors. Methods : Three hundred fifty four children with primary brain tumor who were treated at Severance Hospital from Jan. 1985 to Sep. 2001 were enrolled. Results : Pediatric brain tumors were found most frequently in 10-15 years of age group(35.3%) and the ratio of male to female was 1.3 : 1. Supratentorial tumors(52%) were more frequent than infratentorial tumors(48%). Medulloblastoma/primitive neuroectodermal tumor(PNET) was the most common type(24.6%), followed by cerebellar astrocytoma(14.1%). Ten year survival rate of medulloblastoma, cerebellar astrocytoma and cerebral astrocytoma were 59.4%, 79.3% and 71%, respectively. The prognosis for brain stem glioma and glioblastoma multiforme were still grim with a 10 year survival rate of 12.7% and 13.3%, respectively. The addition of chemotherapy for high grade medulloblastoma led to an improved 10 year survival rate of 54.5%, compared with 40% without chemotherapy. Conclusion : The combined use of chemotherapy and radiation and surgery improved survival rate of pediatric brain tumors in our study. Chemotherapy for high grade medulloblastoma improved the 10 year survival rate. Further data analysis of the treatment modalities will lead to better comparisons.