• 대한암한의학회지
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• 제14권1호
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• pp.45-52
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• 2009

Lung cancer is the most common primary tumor of brain metastasis. Metastasis to the brain is a frequent complication of non-small cell lung cancer (NSCLC) occuring in 12 ~ 18% of patient. The incidence of brain metastasis is rising because of longer survival of cancer patients as a result of the increase in early diagnosis of primary tumors and aggressive management, and improvements in imaging quality and accessibility such as widespread use of MRI. The most common symptoms are gradual onset of headache, focal weakness, and mental changes. Surgery, chemotherapy, radiotherapy and steroid therapy are treatment of NSCLC with brain metastasis. We report a patient with NSCLC metastasis to the brain. This patient underwent chemotherapy, radiotherapy and steroidtherapy. However, the patient requested oriental medical treatment for the patient's continuous headache and disease. We administered Banhabaekchulchoenma-tang gagambang with Allergen-removed Rhus Verniciflua Stokes(aRVS). The patient showed remarkable improvement in terms of frequency and severity of headache. Further study will be needed in order to determine the long-term effectiveness of oriental medical treatment on cancer patient with headache.

• Korean Journal of Radiology
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• 제22권4호
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• pp.584-595
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• 2021

Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

• 생명과학회지
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• 제18권10호
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• pp.1395-1399
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• 2008

우리는 최근에 PRC1 프로모터가 유방암 유전자치료를 위하여 전사 표적이 된 유전자의 발현을 조절할 수 있는 후보 프로모터임을 보고하였다. 우리는 본 실험에서 PRC1이 폐암유전자 치료에서도 적용이 가능한지 조사하였다. 특정 프로모터가 루시퍼라제 유전자와 연결된 플라스미드를 이용한 형질전환 assay에서 PRC1 프로모터는 정상폐세포주에서는 활성을 보이지 않으나 폐암세포주에선 약 30 배의 활성을 보였다. 이는 이미 암특이적인 발현으로 알려진 BIRC5 (survivin) 프로모터와 유사한 결과였다. 또한, 바이러스 벡터를 이용한 실험에서 PRC1은 CMV 프로모터에 비해 아데노부속바이러스에서 약 75%, 아데노바이러스에서 약 66%의활성을 보였다. 이와 대조적으로, PRC1 프로모터를 함유한 이 들 두 종류의 바이러스는 정상 폐세포에서는 20%정도의 낮은 활성을 보였다. 흥미롭게도, 인간 폐종양세포를 이식한 생쥐모델을 사용한 결과에서는 PRC1 프로모터가 CMV 프로모터와 비슷한 생체 활성을 보였다. 종합하면, 이상의 결과는 PRC1이 폐암 유전자치료를 위한 전사표적 유전자의 발현을 위한 프로모터로 사용 가능함을 암시한다.

• Molecules and Cells
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• 제25권1호
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• pp.99-104
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• 2008

Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many neuronal diseases, but the precise molecular mechanisms underlying their pathological activities are poorly understood. Here we report that TLR2 participates in the initiation of ganglioside-triggered inflammatory signaling responses. Using FACS analysis and immunofluorescence microscopy, we found that gangliosides rapidly enhanced the cell surface expression of TLR2 in microglia, while reducing that of TLR4. The ganglioside-dependent increase of TLR2 expression was also observed at the messenger and protein levels. We also showed that gangliosides stimulate the interaction of TLR2 with Myd88, an adaptor for TLRs, and obtained evidence that lipid raft formation is closely associated with the ganglioside-induced activation of TLR2 and subsequent inflammatory signaling. These results collectively suggest that TLR2 contributes to the ability of gangliosides to cause inflammatory conditions in the brain.

• Journal of Korean Neurosurgical Society
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• 제54권4호
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• pp.329-335
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• 2013

Objective : Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer. Methods : From March 2001 to May 2011, 124 women with metastatic brain lesions originating from a primary breast cancer underwent GKRS at a tertiary medical center in Seoul, Korea. All patients had radiosurgery as a primary treatment or salvage therapy. We retrospectively reviewed their clinical outcomes and radiological responses. The end point of this study was the date of patient's death or the last follow-up examination. Results : In total, 106 patients (268 lesions) were available for follow-up imaging. The median follow-up time was 7.5 months. The mean treated tumor volume at the time of GKRS was 6273 $mm^3$ (range, 4.5-27745 mm3) and the median dose delivered to the tumor margin was 22 Gy (range, 20-25 Gy). Local recurrence was assessed in 86 patients (216 lesions) and found to have occurred in 36 patients (83 lesions, 38.6%) with a median time of 6 months (range, 4-16 months). A treated tumor volume >5000 $mm^3$ was significantly correlated with poor local tumor control through a multivariate analysis (hazard risk=7.091, p=0.01). Overall survival was 79.9%, 48.3%, and 15.3% at 6, 12, and 24 months, respectively. The median overall survival was 11 months after GKRS (range, 6 days-113 months). Multivariate analysis showed that the pre-GKRS Karnofsky performance status, leptomeningeal seeding prior to initial GKRS, and multiple metastatic lesions were significant prognostic factors for reduced overall survival (hazard risk=1.94, p=0.001, hazard risk=7.13, p<0.001, and hazard risk=1.46, p=0.046, respectively). Conclusion : GKRS has shown to be an effective and safe treatment modality for treating brain metastases of primary breast cancer. Most metastatic brain lesions initially respond to GKRS, though, many patients have further CNS progression in subsequent periods. Patients with poor Karnofsky performance status and multiple metastatic lesions are at risk of CNS progression and poor survival, and a more frequent and strict surveillance protocol is suggested in such high-risk groups.

• Journal of Korean Neurosurgical Society
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• 제30권9호
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• pp.1108-1114
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• 2001

Objective : Prognostic factors of metastatic brain tumors have been widely reported and their operative indications also have been extended gradually even to the poor grade patients. Authors intended to analyze the causative factors for the clinical outcome of metastatic brain tumors, especially with relevant to the poor prognosis by one year follow-up evaluation. Patients and Methods : The authors retrospectively studied the clinical characteristics of 46 cases(35 patients) with metastatic brain tumors among 466 cases(437 patients) which were operated on due to the brain tumor, during the period between January 1994 to June 1999. Statistical analysis was performed by using SPSS 8.0$^{(R)}$. A p-value of less than 0.05 was considered clinically significant. Result : Among the variable clinical factors in patients with metastatic brain tumors, Karnofsky Performance Scale (KPS) score of less than 70(16 patients), uncontrolled primary tumor(8 patients), and surgical resection without further adjuvant therapy(9 patients) showed statistically significant poor prognosis ; p value of 0.002, 0.032, and 0.001, respectively. Other tested variables, such as old age(greater than 65 years ; 10 patients), gender(male ; 20 patients), type of primary cancer(primary undefined ; 6 patients, lung cancer ; 15 patients), location(infratentorial ; 9 patients, sellar ; 5 patients), number of lesion(multiple ; 12 patients), and number of operation(multiple craniotomy ; 7 patients) were not related to the poor prognosis. Conclusions : The most common primary site of distant metastasis was lung. The poorer prognosis was highly correlated with various factors including low KPS score(<70), no postoperative adjuvant therapy, and uncontrolled primary tumors.

• 한국산학기술학회논문지
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• 제15권10호
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• pp.6187-6192
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• 2014

전이성 뇌종양의 증가에 따라 전뇌 방사선치료가 증가하게 되었다. 그리고 치료기법의 발전은 삶의 질 향상의 중요성을 증가시키게 되었다. 체적변조회전 전뇌조사는 용적별 선량을 차등시킬 수 있는 우수한 치료기법이다. 이에 두피선량 증가에 따른 탈모에 대하여 기존 전뇌조사와 체적변조회전 전뇌조사를 비교하고자 하였다. 두정부 인체모형을 이용하여 치료계획을 비교하였다. 뇌 실질의 경우 정합지수, 동질성지수, 범위의 질지수를 적용하였으며, 두피, 안구, 수정체, 경추의 경우 20%선량의 용적, 50%선량의 용적을 적용하여 비교하였다. 비교결과 뇌 실질은 기존 전뇌조사가 10%정도 우수하였지만, 두피, 안구, 수정체, 경추의 경우는 체적변조회전 전뇌조사가 1000%정도 우수하였다. 향후 체적변조회전 전뇌조사의 처방선량을 조정한다면 탈모를 방지하는 전이성 뇌종양 방사선치료로 선정될 것이다.

• Rapid Communication in Photoscience
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• 제1권2호
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• pp.55-55
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• 2012

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7569-7576
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• 2013

Background: The purpose of this article is to present preliminary results of simultaneous boost irradiation radiotherapy for locally advanced nasopharyngeal carcinoma (NPC). Methods: Fifty-eight patients who underwent simultaneous boost irradiation radiotherapy for NPC in Cancer Center of Sun Yat-sen University between September 2004 and December 2009 were eligible. Acute and late toxicities were scored weekly according to the Radiation Therapy Oncology Group (RTOG) acute and late radiation morbidity scoring schemes. An especial focus was on evidence of post-radiation brain injury. Also quality of life was analysed according to the EORTC (European Organisation for Research and Treatment of Cancer) recommendations. Discrete variables were compared by ${\chi}^2$ test. The Kaplan-Meier method was used to calculate the survival rates and generate survival curves. Results: A total of 58 patients with a mean follow-up time of 36 months completed clinical trials.Fifty-seven patients (98.3) achieved complete remission in the primary sites and cervical lymph nodes, with only one patient (1.7%) showing partial remission.The most frequently observed acute toxicities during the concurrent chemoradiotherapy were mucositis and leucopenia. Four patients (6.9%) had RTOG grade 3 mucositis, whereas four patients (6.9%) had grade 3 leucopenia. No patient had grade 4 acute toxicity. Three (5.17%) of the patients exhibited injury to the brain on routine MRI examination, with a median observation of 32 months (range, 25-42months). All of them were RTOG grade 0. The 3-year overall, regional-free and distant metastasis-free survival rates were 85%, 94% and 91%, respectively. Conclusion: Simultaneous boost irradiation radiotherapy is feasible in patients with locally advanced nasopharyngeal carcinoma. The results showed excellent local control and overall survival, with no significant increase the incidence of radiation brain injury or the extent of damage. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

• 대한방사선치료학회지
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• 제30권1_2호
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• pp.177-183
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• 2018

목 적 : 체적변조회전방사선치료(VMAT)는 종양의 모양에 맞게 균일하면서도 정밀한 방사선 조사를 하면서 동시에 정상조직의 방사선 손상위험을 줄이는 장점이 있어 뇌암, 두경부암 및 전립선암 등의 종양과 정상장기가 가까운 암의 치료에 사용되고 있다. 본 연구의 목적은 뇌암 및 두경부암 환자의 VMAT 방사선 치료 시 Jaw-Tracking technique(JTT)의 선량학적 유용성을 평가하고자 한다. 대상 및 방법 : 본원에서 VMAT 치료기법으로 방사선치료를 받은 뇌암 및 두경부암 환자 8명을 선택하였다. 환자의 종양 및 정상 장기의 윤곽그리기(contouring) 정보를 Velocity(Varian, USA)의 deformable registration을 이용하여 Rando phantom에 fusion하였다. Varian Eclipse(ver 15.5, Varian, USA)를 사용하여 Jaw-Tracking 사용 유무를 제외하고 환자 치료 시 사용한 beam parameter와 동일하게 치료계획을 진행하였다. 평가 지표로써 target과 OAR의 최대선량, 평균선량을 사용하여 비교하였고 치료계획 검증을 위해 Portal dosimetry를 시행하였다. 결 과 : JTT를 사용했을 경우는 Static-Jaw technique(SJT)을 사용하였을 경우보다 OAR의 상대 선량이 각각 평균선량은 5.24 %, 최대선량은 7.05 % 감소한 것으로 나타났다. 다양한 OAR에서 평균선량과 최대선량의 감소의 범위는 각각 0.01~3.16 Gy, 0.12~6.27 Gy로 나타났다. Target의 경우는 JTT의 경우가 SJT보다 GTV, CTV, PTV의 최대선량이 각각 0.17 %, 0.43 %, 0.37 % 감소하였으며, 평균선량은 0.24 %, 0.47 %, 0.47% 감소하였다. 감마분석은 3 %/3 mm, 통과율 95 % 이상을 통과 기준으로 설정하였고 JTT, SJT 통과율은 각각 $98{\pm}1.73%$, $97{\pm}1.83%$이었다. 실험에 적용된 모든 OAR의 선량을 비교해 보았을 때, JTT을 사용하였을 경우가 SJT보다 MLC 외에 추가적인 jaw 차폐로 인하여 선량이 유의미하게 줄어들었다는 것을 알 수 있었다. 결 론 : VMAT 치료계획을 이용한 방사선 치료시 뇌암, 두경부암과 같이 종양과 정상 장기가 인접한 경우와 MLC를 통한 누설선량을 증가시킬 수 있는 넓은 조사야 및 높은 에너지의 사용을 필요로 하는 방사선 치료 시 JTT를 적용함으로써 종양주변 정상조직의 피폭선량을 낮추고 이로 인해 PTV의 target coverage를 높일 수 있을 것이라 판단된다.