• Title, Summary, Keyword: whole brain

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Whole Brain Radiation-Induced Cognitive Impairment: Pathophysiological Mechanisms and Therapeutic Targets

  • Lee, Yong-Woo;Cho, Hyung-Joon;Lee, Won-Hee;Sonntag, William E.
    • Biomolecules & Therapeutics
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    • v.20 no.4
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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.

Clinical Observation of Whole Brain Radiotherapy Concomitant with Targeted Therapy for Brain Metastasis in Non-small Cell Lung Cancer Patients with Chemotherapy Failure

  • Cai, Yong;Wang, Ji-Ying;Liu, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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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.

Brain laterality and whole brain EEG on the learning senses (학습감각에 대한 뇌의 분화성과 통합성 뇌파연구)

  • Kwon, Hyungkyu
    • Journal of the Korean Data and Information Science Society
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    • v.26 no.1
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    • pp.55-64
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    • 2015
  • The present study identified the brain based learning activities on the individual learning senses by using the brain laterality and the whole brain index. Students receive the information through the visual, auditory, and kinesthetic senses by Politano and Paquin's (2000) classification. These learning senses are reflected on brain by the various combinations of senses for learning. Measuring the types of the learning senses involving in brain laterality and whole brain is required to figure out the related learning styles. Self-directed learning involved in the learning senses shows the problem-based learning associated to the brain function by emphasizing the balanced brain utilization which is known as whole brain. These research results showed the successful whole brain learning is closely associated with elevated auditory learning and elevated visual learning in sensorimotor brainwave rhythm (SMR) while it shows the close association with elevated kinesthetic and elevated visual learning in beta brainwave rhythm.

Dose Distribution in the Brain in Radiotherapy of Whole Brain (전뇌조사시(全腦照射時) 뇌(腦)에 있어서의 선량분포(線量分布))

  • Kang, Wee Saing;Ha, Sung Whan;Park, Charn Il
    • Radiation Oncology Journal
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    • v.1 no.1
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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.

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IDENTIFICATION OF GENES EXPRESSED IN LOW-DOSE-RATE γ-IRRADIATED MOUSE WHOLE BRAIN

  • Bong, Jin Jong;Kang, Yu Mi;Choi, Seung Jin;Kim, Dong-Kwon;Lee, Kyung Mi;Kim, Hee Sun
    • Journal of Radiation Protection and Research
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    • v.38 no.4
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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.

Body Height Effect on Brain Volumes in Youth Decreases in Old Age in Koreans

  • Koh, In-Song
    • Interdisciplinary Bio Central
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    • v.3 no.3
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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.

Whole Brain Radiotherapy Combined with Stereotactic Radiotherapy Versus Stereotactic Radiotherapy Alone for Brain Metastases: a Meta-analysis

  • Duan, Lei;Zeng, Rong;Yang, Ke-Hu;Tian, Jin-Hui;Wu, Xiao-Lu;Dai, Qiang;Niu, Xiao-Dong;Ma, Di-Wa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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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.

Hippocampal Sparing Whole Brain Radiotherapy and Integrated Simultaneous Boost vs Stereotactic Radiosurgery Boost: A Comparative Dosimetric Planning Study

  • Cheah, Soon Keat;Matthews, Thomas;Teh, Bin Sing
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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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.

New Protein Extraction/Solubilization Protocol for Gel-based Proteomics of Rat (Female) Whole Brain and Brain Regions

  • Hirano, Misato;Rakwal, Randeep;Shibato, Junko;Agrawal, Ganesh Kumar;Jwa, Nam-Soo;Iwahashi, Hitoshi;Masuo, Yoshinori
    • Molecules and Cells
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    • v.22 no.1
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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.

Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

  • Lee, Seung-Heon;Lee, Kyu-Chan;Choi, Jin-Ho;Kim, Hye-Young;Lee, Seok-Ho;Sung, Ki-Hoon;Kim, Yun-Mi
    • Radiation Oncology Journal
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    • v.30 no.2
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    • pp.53-61
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    • 2012
  • Purpose: To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Materials and Methods: Nine patients with multiple (${\geq}4$) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. Results: The median biologically effective dose to metastatic tumors was 68.1 $Gy_{10}$ and 67.2 $Gy_{10}$ and the median brain volume irradiated more than 100 $Gy_3$ were 1.9% (24 $cm^3$) and 0.8% (13 $cm^3$) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. Conclusion: RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.