• Journal of Korean Neurosurgical Society
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• v.52 no.4
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• pp.334-338
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• 2012

Objective : We compared the survival time between patients with multiple gamma knife radiosurgery (GKRS) and patients with a single GKRS plus whole brain radiation therapy (WBRT), in patients with multiple metachronous brain metastases from lung cancer. Methods : From May 2006 to July 2010, we analyzed 31 patients out of 112 patients who showed multiple metachronous brain metastases. 20 out of 31 patients underwent multiple GKRS (group A) and 11 patients underwent a single GKRS plus WBRT (group B). We compared the survival time between group A and B. Kaplan-Meier method and Cox proportional hazards were used to analyze relationship between survival and 1) the number of lesions in each patient, 2) the average volume of lesions in each patient, 3) the number of repeated GKRS, and 4) the interval of development of new lesions, respectively. Results : Median survival time was 18 months (range 6-50 months) in group A and 6 months (range 3-18 months) in group B. Only the average volume of individual lesion (over 10 cc) was negatively related with survival time according to Kaplan-Meier method. Cox-proportional hazard ratio of each variable was 1.1559 for the number of lesions, 1.0005 for the average volume of lesions, 0.0894 for the numbers of repeated GKRS, and 0.5970 for the interval of development of new lesions. Conclusion : This study showed extended survival time in group A compared with group B. Our result supports that multiple GKRS is of value in extending the survival time in patients with multiple metachronous brain metastases, and that the number of the lesions and the frequency of development of new lesions are not an obstacle in treating patients with GKRS.

• The Journal of Korean Society for Radiation Therapy
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• v.28 no.2
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• pp.139-148
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• 2016

Purpose : Range Compensator used for proton therapy compensates the proton beam dose which delivers to the normal tissues according to the Target's Distal Margin dose. We are going to check the improvement of dose on the target part by comparing the dose of PTV and OAR according to applying in different method of Smooth Thickness of Range Compensator which is used in brain tumor therapy. Materials and Methods : For 10 brain tumor patients taking proton therapy in National Cancer Center, Apply Smooth Thickness applied in Range Compensator in order from one to five by using Compensator Editor of Eclipse Proton Planning System(Version 10.0, Varian, USA). The therapy plan algorithm used Proton Convolution Superposition(version 8.1.20 or 10.0.28), and we compared Dmax, Dmin, Homogeneity Index, Conformity Index and OAR dose around tumor by applying Smooth Thickness in phase. Results : When Smooth Thickness was applied from one to five, the Dmax of PTV was decreased max 4.3%, minimum at 0.8 and average of 1.81%. Dmin increased max 1.8%, min 1.8% and average. Difference between max dose and minimum dose decreased at max 5.9% min 1.4% and average 2.6%. Homogeneity Index decreased average of 0.018 and Conformity Index didn't had a meaningful change. OAR dose decreased in Brain Stem at max 1.6%, min 0.1% and average 0.6% and in Optic Chiasm max 1.3%, min 0.3%, and average 0.5%. However, patient C and patient E had an increase each 0.3% and 0.6%. Additionally, in Rt. Optic Nerve, there was a decrease at max 1.5%, min 0.3%, and average 0.8%, however, patient B had 0.1% increase. In Lt. Optic Nerve, there was a decrease at max 1.8%, min 0.3%, and average 0.7%, however, patient H had 0.4 increase. Conclusion : As Smooth Thickness of Range Compensator which is used as the proton treatment for brain tumor patients is applied in stages, the resolution of Compensator increased and as a result the most optimized amount of proton beam dose can be delivered. This is considered to be able to irradiate the equal amount at PTV and reduce the unnecessary dose applied at OAR to reduce the side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.463-466
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• 2016

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor. Epileptic seizure is one of the most common symptoms in patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is often used as an anti-epileptic drug in patients with brain neoplasms due to its effectiveness and low toxicity profile. Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. The use of VPA in patients with GBM has thus recently receiving more attention. In this article, we review the role of VPA in radiation therapy for GBM, focusing on the clinical evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1995-1997
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• 2012

Background: Brain metastasis from cholangiocarcinoma (CCA) is a rare but fatal event. To the best of our knowledge, only few cases have been reported. Herein, we report the incident rate and a first case series of brain metastases from CCA. Methods: Between January 2006 and December 2010 5,164 patients were treated at Srinagarind hospital, Khon Kaen University; of those, 8 patients developed brain metastasis. Here we reviewed clinical data and survival times. Results: The incident rate of brain metastases from CCA was 0.15%. The median age of the patients was 60 years. Tumor subtypes were intrahepatic in 6 and hilar in 2 patients. All suffered from symptoms related to brain metastasis. Three patients were treated with whole-brain radiation therapy (WBRT), one of whom also underwent surgery. The median survival after the diagnosis of brain metastasis was 9.5 weeks (1-28 weeks). The longest survival observed in a patient in RPA class I with two brain lesions and received WBRT. Conclusion: This is a first case series of brain metastases from CCA with the incident rate of 0.15%. It is rare and associated with short survival time.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.438-447
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• 2023

Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.

• Journal of Korean Traditional Oncology
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• v.23 no.2
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• pp.11-25
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• 2018

Objective: The purpose of this study is to report the case of a patient with non-small cell lung cancer (NSCLC) with Programmed cell death protein 1 (PD-1) mutation treated by Integrative Medicine Therapy (IMT). Methods: A patient with metastatic NSCLC received pembrolizumab 200mg intravenously for every 3 weeks from July 2017. Repeat cycle every 3 weeks since July 2017. The patient has been treated with Integrative Medicine Therapy (IMT) since December 2016. The tumor size was measured by computed tomography (CT) and magnetic resonance imaging(MRI). Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Results: After combined treatment, the extent of proximal portion of primary tumor in the left lower lobe was decreased and disease status was stable radiologically. No evidence of newly developed metastatic lesions in the brain since May 2017. The patient did not experience any adverse event according to NCI-CTCAE ver. 5.0. Conclusion: This case study suggests that Integrative Medicine Therapy (IMT) may contribute to tumor response, in conjunction with Pembrolizumab on the treatment of patients with NSCLC.

• Korean Journal of Head & Neck Oncology
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• v.28 no.2
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• pp.143-145
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• 2012

Follicular thyroid cancer(FTC) accounts for about 10-15% of thyroid cancer. Distant metastasis is common, usually to lung, bone and brain. 71-years-old man visited neurosurgery outpatient department. He complained of recent 6kg weight loss, left upper extremity pain with weakness and back pain. The radiologic findings showed multiple bone metastasis including thoracic spine and left scapular resulting from FTC. There was a probable brain metastatic lesion on right temporal fossa. The core biopsy of thyroid and thoracic spine(T11) confirmed metastatic follicular carcinoma. Radioactive iodine therapy and radiotherapy was done following total thyroidectomy. We report a unique case of multiple bone metastasis from follicular carcinoma of thyroid with literature review.

• Journal of Korean Neurosurgical Society
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• v.58 no.3
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• pp.205-210
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• 2015

Objective : This study was aimed at optimizing the treatment of non-small-cell lung cancer (NSCLC) patients who are candidates for stereotactic radiosurgery (SRS) for brain metastases and harbor activating epithelial growth factor receptor (EGFR) mutations. Methods : We retrospectively reviewed the medical records from 2005 to 2010 of NSCLC patients with brain metastases harboring an activating EGFR mutation. Patients who received a combination therapy of SRS and EGFR-tyrosine kinase inhibitor (TKI) for brain metastases and those who received SRS without EGFR-TKI were compared. The primary endpoint was progression-free survival (PFS) of the brain metastases. Results : Thirty-one patients were eligible for enrolment in this study (SRS with TKI, 18; SRS without TKI, 13). Twenty-two patients (71.0%) were women and the median overall age was 56.0 years. PFS of brain lesions was not significantly prolonged in SRS with TKI treatment group than in SRS without TKI group (17.0 months vs. 9.0 months, p=0.45). Local tumor control rate was 83.3% in the combination therapy group, and 61.5% in the SRS monotherapy group (p=0.23). There were no severe adverse events related with treatment in both groups. Conclusions : Therapeutic outcome of concurrent SRS and TKI treatment was not superior to SRS monotherapy, however, there was no additive adverse events related with combined treatment.

• Journal of Korean Neurosurgical Society
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• v.61 no.5
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• pp.633-639
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• 2018

Objective : We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. Methods : A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. Results : After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. Conclusion : The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.

• Physical Therapy Rehabilitation Science
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• v.11 no.3
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• pp.304-310
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• 2022

Objective: Mild cognitive impairment (MCI) is a condition in which cognitive and executive functions are reduced, and older adults with MCI are ten times more likely to develop dementia than healthy older adults. Expression of brain-derived neurotrophic factor (BDNF) through aerobic exercise is associated with increased cognitive and executive functions. in this review, randomized controlled trials (RCTs) on the effects of aerobic exercise on BDNF in individuals with mild cognitive impairment are summarized and qualitatively and quantitatively analyzed to suggest the necessity of aerobic exercise. Design: a systematic review and meta-analysis. Methods: RCTs were searched for changes in BDNF through aerobic exercise using four international databases. Quality assessment and quantitative analysis were performed using RevMan 5.4. Quantitative analysis was quantified with a standardized mean difference (SMD) and presented as a random effect model. Results: Three RCTs evaluated BDNF in 123 patients with MCI. There was a significant improvement in the experimental group that performed aerobic exercise compared to the control group. The results analyzed using the random effects model were SMD = 0.48. Conclusions: In this review, we reported the effects and mechanisms of aerobic exercise in individuals with MCI. As a result of synthesizing RCTs that performed aerobic exercise, a significant increase in BDNF was confirmed.