• Biomolecules & Therapeutics
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• 제20권4호
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• pp.357-370
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• 2012

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5699-5703
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• 2013

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

• Journal of the Korean Data and Information Science Society
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• 제26권1호
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• pp.55-64
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• 2015

학습감각과 뇌 활동의 관계를 규명하기 위해 학습자의 학습감각 유형과 뇌의 분화성 및 통합성에 따른 뇌파 지표에 따라 상호관계성을 규명하였다. 학습자는 시각, 청각, 운동감각을 통해서 정보를 습득한다. 이러한 뇌에 반영되는 학습 감각은 다양한 학습감각의 조합으로 나타나는데 뇌의 분화성과 통합성에 관여하는 학습감각의 유형을 측정하기 위해서는 관련된 학습양식을 규명하는 것이 요구된다. 또한 학습감각에 포함된 자기 주도적 학습은 뇌의 기능에 연계된 문제 중심학습이 통합 뇌로 알려진 균형적인 뇌의 활용을 강조하는 것과 관련이 있다는 것을 보여주고 있다. 본 연구결과는 감각운동리듬 (SMR) 뇌파에서 효과적인 통합뇌 학습이 높은 청각학습과 시각학습에 밀접하게 관련되어 있다는 것을 보여주며 베타파에서는 효과적인 통합뇌 학습이 높은 운동감각과 시각 학습에 밀접하게 관련되어 있다는 것을 보여주었다.

• Radiation Oncology Journal
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• 제1권1호
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• pp.37-40
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• 1983

Whole brain irradiation is one mode in the treatment of brain cancer and brain metastasis, but it might cause brain injury such as brain necrosis. It has been studied whether the dose distribution could be a cause of brain injury. The dose distribution in whole brain irradiated by Co-60 beam has been measured by means of calibrated TLD chips inserted in the brain of Humanoid phantom. The following results were obtained. 1. Dose distribution on each transverse section of the brain was uniform. 2. On the midsagital plane of the brain, the dose was highest in upper portion and lowest in lower portion, varying 8 from 104% to 90%. 3. When the radiation field includes free space of 2cm or more width out of the head, the dose distribution in the whole brain is almost independent of the field width. 4. It is important to determine adequate shielding area and to set shielding block exactly in repetition of treatment.

• Journal of Radiation Protection and Research
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• 제38권4호
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• pp.166-171
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• 2013

While high-dose ionizing radiation results in long term cellular cytotoxicity, chronic low-dose (<0.2 Gy) of X- or ${\gamma}$-ray irradiation can be beneficial to living organisms by inducing radiation hormesis, stimulating immune function, and adaptive responses. During chronic low-dose-rate radiation (LDR) exposure, whole body of mice is exposed to radiation, however, it remains unclear if LDR causes changes in gene expression of the whole brain. Therefore, we aim to investigate expressed genes (EGs) and signaling pathways specifically regulated by LDR-irradiation ($^{137}Cs$, a cumulative dose of 1.7 Gy for total 100 days) in the whole brain. Using microarray analysis of whole brain RNA extracts harvested from ICR and AKR/J mice after LDR-irradiation, we discovered that two mice strains displayed distinct gene regulation patterns upon LDR-irradiation. In ICR mice, genes involved in ion transport, transition metal ion transport, and developmental cell growth were turned on while, in AKR/J mice, genes involved in sensory perception, cognition, olfactory transduction, G-protein coupled receptor pathways, inflammatory response, proteolysis, and base excision repair were found to be affected by LDR. We validated LDR-sensitive EGs by qPCR and confirmed specific upregulation of S100a7a, Olfr624, and Gm4868 genes in AKR/J mice whole brain. Therefore, our data provide the first report of genetic changes regulated by LDR in the mouse whole brain, which may affect several aspects of brain function.

• Interdisciplinary Bio Central
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• 제3권3호
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• pp.11.1-11.5
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• 2011

The MRI (magnetic resonance imaging) volumetric analysis of the brain was performed in 59 healthy elderly Koreans (aged 62-76 years; 34 male, 25 female) to investigate whether the previously reported significant correlations between body height and brain volumes in the young aged Koreans (20's) still exist in the old aged Koreans (60's and 70's). Unlike previously reported significant correlations in the young aged Koreans, neither the correlation between whole brain volume and body height in male nor the correlation between cerebellar volume and body height in female show any significance in the old aged Koreans. The significant correlation between body height and whole brain volume was still observed when both male and female data were combined (r=0.27, P<0.05), but the correlation coef-ficient and the level of significance markedly decreased from those of previously reported Korean youth data (r=0.67, P<0.01). Simple linear regression analysis shows decrease of explanatory power of height (measured in $r^2$) from 44% in the youth group to 7% in the old age group on the variance of whole brain volume. Multiple linear regression analysis shows that age and sex, rather than height, are major explanatory variables for whole brain volume in the old aged Koreans. The loss of correlations in the aged group is suspected to be mainly due to age related brain volume changes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.911-915
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• 2014

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotactic radiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a meta-analysis. Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inception up to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotactic radiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyses were performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patients were included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29, 95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologic radiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant difference existed in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that whole brain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brain metastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, as the samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4233-4235
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• 2016

Background: Whole brain radiotherapy (WBRT) and stereotactic radiosurgery were frequently used to palliate patients with brain metastases. It remains controversial which modality or combination of therapy is superior especially in the setting of limited number of brain metastases. The availability of newer medical therapy that improves survival highlighted the importance of reducing long term radiation toxicity associated with WBRT. In this study, we aim to demonstrate the hippocampal sparing technique with whole brain and integrated simultaneous boost Materials and Methods: Planning data from 10 patients with 1-5 brain metastases treated with SRS were identified. Based on the contouring guideline from RTOG atlas, we identified and contoured the hippocampus with 5mm isocentric expansion to form the hippocampal avoidance structure. The plan was to deliver hippocampal sparing whole brain radiotherapy (HSWBRT) of 30 Gy in 10 fractions and simultaneous boost to metastatic lesions of 30 Gy in 10 fractions each. Results: The PTV, hippocampus and hippocampal avoidance volumes ranges between 1.00 - 39.00 cc., 2.50 - 5.30 cc and 26.47 - 36.30 cc respectively. The mean hippocampus dose for the HSWBRT and HSWBRT and SIB plans was 8.06 Gy and 12.47 respectively. The max dose of optic nerve, optic chiasm and brainstem were kept below acceptable range of 37.5 Gy. Conclusions: The findings from this dosimetric study demonstrated the feasibility and safety of treating limited brain metastases with HSWBRT and SIB. It is possible to achieve the best of both worlds by combining HSWBRT and SIB to achieve maximal local intracranial control while maintaining as low a dose as possible to the hippocampus thereby preserving memory and quality of life.

• Molecules and Cells
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• 제22권1호
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• pp.119-125
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• 2006

The rat is an accepted model for studying human psychiatric/neurological disorders. We provide a protocol for total soluble protein extraction using trichloroacetic acid/acetone (TCA/A) from rat (female) whole brain, 10 brain regions and the pituitary gland, and show that two-dimensional gel electrophoresis (2-DGE) using precast immobilized pH (4-7) gradient (IPG) strip gels (13 cm) in the first dimension yields clean silver nitrate stained protein profiles. Though TCA/A precipitation may not be "ideal", the important choice here is the selection of an appropriate lysis buffer (LB) for solubilizing precipitated proteins. Our results reveal enrichment of protein spots by use of individual brain regions rather than whole brain, as well as the presence of differentially expressed spots in their proteomes. Thus individual brain regions provide improved protein coverage and are better suited for differential protein detection. Moreover, using a phosphoprotein-specific dye, ingel detection of phosphoproteins was demonstrated. Representative high-resolution silver nitrate stained proteome profiles of rat whole brain total soluble protein are presented. Shortcomings apart (failure to separate membrane proteins), gel-based proteomics remains a viable option, and 2-DGE is the method of choice for generating high-resolution proteome maps of rat brain and brain regions.

• 영재교육연구
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• 제21권2호
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• pp.255-268
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• 2011

21세기는 지식의 홍수 시대라 일컬어질 만큼 지식을 많이 아는 것보다 알고 있는 지식을 창의적으로 사용하는 능력에 대한 중요성이 더욱 커지고 있다. 또한 개인으로서의 문제 해결 능력에 더하여 효과적인 의사소통을 통한 팀 구성원 간의 문제 해결 능력이 요구되고 있으므로 영재성을 지닌 학습자들에게도 미래 사회에 적응할 수 있는 유능한 인재로 성장하도록 협동 학습을 통한 문제 해결 과정을 도입하여 이 같은 능력을 기를 수 있는 교육이 필요하다. 본 논문에서는 영재교육 프로그램에 참석한 42명의 중등 영재 학생들을 대상으로 전뇌(全腦: Whole Brain)이론을 바탕으로 학습자들을 그룹으로 나눈 뒤 협동 학습을 실시하였고 학습 동기의 사전 사후 변화를 분석하였으며 협동 학습 수업 과정 중 학생들의 상호작용을 분석하였다. 분석 결과 전뇌 이론에 기반을 둔 협동 학습은 학습의 정의적 요소 중 하나인 학습 동기 향상에 효과가 있었고, 상호작용 또한 활발하게 일어남을 관찰하였다. 따라서 영재들에게 있어서 전뇌 이론에 기반을 둔 집단 편성 방법이 학습의 정의적 영역인 학습 동기 향상과 상호작용 촉진 측면에 있어서 효과적임을 확인하였다.