• Tuberculosis and Respiratory Diseases
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• 제75권2호
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• pp.52-58
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• 2013

Background: More than half of cases for advanced non-small-cell lung cancer (NSCLC) occur in elderly patients with a median age at diagnosis of 70 years. The aim of our study was to examine the clinical features and prognostic factors contributing to mortality in elderly patients with advanced NSCLC. Methods: Following a retrospective review of clinical data, 122 patients aged 70 years and over with a histopathological diagnosis of locally advanced (stage IIIB, n=32) and metastatic (stage IV, n=90) NSCLC between 2005 and 2011 were enrolled. Results: The median age was 76 years (interquartile range, [IQR], 72-80 years), and 85 (70%) patients were male. Fifty-seven (46%) patients had never smoked, and 17 (19%) were in a malnourished state with a body mass index (BMI) of <$18.5kg/m^2$. The initial treatments included chemotherapy (40%) and radiotherapy (7%), but 57% of the patients received supportive care only. The 1-year survival rate was 32%, and the 3-year survival rate was 4%, with a median survival duration of 6.2 months (IQR, 2.5-15.3 months). Male gender (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p=0.005), low BMI (HR, 2.3; 95% CI, 1.3-3.9; p=0.004), and supportive care only (HR, 1.9; 95% CI, 1.2-2.9; p=0.007) were independent predictors of shorter survival based on a Cox proportional hazards model. Conclusion: Elderly patients with advanced NSCLC had a poor prognosis, particularly male patients, those with a low BMI, and those who received supportive care only.

• 생명과학회지
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• 제17권8호통권88호
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• pp.1115-1120
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• 2007

본 연구에서는 다섯 종류의 phytochemical (resveratrol, genistein, epicatechin gallate, diaIly disulfide, caffeic acid phenetyl ester)과 sulindac sulfide가 암 억제 단백질 p53을 유도할 수 있는지에 대해 연구하였다. 처리한 모든 phytochemical에 의해 p53 단백질의 발현이 강하게 유도된 반면, sulindac sulfide에 의해서는 p53 단백질이 유도되지 않았다. 처리한 phytochemical 중 포도껍질이나 와인에 많이 들어있는 resveratrol에 의해 p53 단백질이 농도의존적 혹은 처리시간 의존적으로 증가 발현되는 것을 확인하였다. 암 억제 단백질인 p53 하위 단계의 유전자들만 집적되어 있는 membrane microarray를 이용하여 실험을 수행한 결과, 25개의 유전자가 up-regulation 된 반면, 2개의 유전자가 down-regulation 되는 것을 확인하였다. Up-regulation 되는 유전자중 4개를 선택하여, RT-PCR을 수행한 결과 모두 membrane microarray 실험의 결과와 일치하였다. 게다가 p53 null인 HCT116 세포주를 이용한 RT-PCR을 통하여 TSP-1 유전자의 발현은 p53 의존적이지 않은 반면, MASPIN 유전자는 p53 의존적임을 확인하였다. 이러한 연구 결과는 resveratrol에 의한 화학적 암 예방법의 분자생물학적 기전을 이해하는데 도움을 줄 것으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4025-4030
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• 2012

Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat. Methods: Wistar males (weighing $257{\pm}28g$) were divided into six groups: (1) control+placebo (2) control+DOX $10mg.kg^{-1}$ (3) control+DOX $20mg.kg^{-1}$ (4) training+placebo (5) training+ DOX$10mg.kg^{-1}$ (6) training+DOX $20mg.kg^{-1}$. Cardiotoxicity was induced by DOX (10 and $20mg.kg^{-1}$). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to $39min.day^{-1}$ and 15 to $17m.min^{-1}$, 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX $10mg.kg^{-1}$ and DOX $20mg.kg^{-1}$, respectively. Result: DOX administration (10 and $20mg.kg^{-1}$) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with $10mg.kg^{-1}$ and $20mg.kg^{-1}$, a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX$10mg.kg^{-1}$ and DOX$20mg.kg^{-1}$ treatments in MDA levels only. Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up-regulation of antioxidants in heart tissue.

• 대한소아치과학회지
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• 제36권4호
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• pp.607-612
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• 2009

소아기의 악성 종양은 질병으로 인한 소아 사망의 가장 흔한 원인이다. 이에 대한 대표적인 치료 방법으로 항암 화학 요법과 방사선 요법의 단독 사용 혹은 이들의 병용을 들 수 있다. 그러나 이러한 치료 방법은 다양한 구강 내 합병증을 동반한다. 성인과 달리 소아 환자는 항암치료 시기에 일부 영구치가 활발한 발육단계에 있으므로 발육중인 치아에 치과적 합병증이 예상된다. 치과적 합병증의 정도는 화학약물의 종류, 용량 및 방사선 조사 빈도와 치료 당시 환자의 나이에 따라 달라진다. 본 증례들에서는 특정 영구치의 발육단계에 있는 만 1-4세경에 종양의 치료를 위해 항암 화학 요법과 방사선 치료를 받은 어린이 3명을 대상으로 치료 내용과 치아 발육 상황을 검토해 보았다. 이환된 치아의 수나 그 정도에 차이는 있으나, 각각의 환자에서 영구치 치배의 선천 결손, 왜소치, 치근 저형성 등 발육장애 관련 소견이 관찰되었다. 항암치료를 받은 병력이 있는 소아에 있어서 항암치료 이후에 나타날 수 있는 일반적인 구강 합병증 이외에 발육시기 동안 치아에 미치는 영향을 고려하여, 공간 문제를 포함하여 향후 발생 할 수 있는 다앙한 문제점 예방을 위한 장기적인 관찰과 관리가 필요할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5019-5024
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• 2015

Background: The purpose of this study was to assess the dosimetric and clinical feasibility of volumetric modulated arc based hypofractionated stereotactic radiotherapy (RapidArc) treatment for large acoustic schwannoma (AS >10cc). Materials and Methods: Ten AS patients were immobilized using BrainLab mask. They were subject to multimodality imaging (magnetic resonance and computed tomography) to contour target and organs at risk (brainstem and cochlea). Volumetric modulated arc therapy (VMAT) based stereotactic plans were optimized in Eclipse (V11) treatment planning system (TPS) using progressive resolution optimizer-III and final dose calculations were performed using analytical anisotropic algorithm with 1.5 mm grid resolution. All AS presented in this study were treated with VMAT based HSRT to a total dose of 25Gy in 5 fractions (5fractions/week). VMAT plan contains 2-4 non-coplanar arcs. Treatment planning was performed to achieve at least 99% of PTV volume (D99) receives 100% of prescription dose (25Gy), while dose to OAR's were kept below the tolerance limits. Dose-volume histograms (DVH) were analyzed to assess plan quality. Treatments were delivered using upgraded 6 MV un-flattened photon beam (FFF) from Clinac-iX machine. Extensive pretreatment quality assurance measurements were carried out to report on quality of delivery. Point dosimetry was performed using three different detectors, which includes CC13 ion-chamber, Exradin A14 ion-chamber and Exradin W1 plastic scintillator detector (PSD) which have measuring volume of $0.13cm^3$, $0.009cm^3$ and $0.002cm^3$ respectively. Results: Average PTV volume of AS was 11.3cc (${\pm}4.8$), and located in eloquent areas. VMAT plans provided complete PTV coverage with average conformity index of 1.06 (${\pm}0.05$). OAR's dose were kept below tolerance limit recommend by American Association of Physicist in Medicine task group-101(brainstem $V_{0.5cc}$ < 23Gy, cochlea maximum < 25Gy and Optic pathway <25Gy). PSD resulted in superior dosimetric accuracy compared with other two detectors (p=0.021 for PSD.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4583-4589
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• 2013

Objective: This study aimed to investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma (HB) and the factors affecting prognosis. Methods: A total of 35 children underwent multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. The patients were followed up every month. Results: Serum AFP levels in 33 out of 35 patients in this study were significantly increased (P = 0.0002). According to the statistical scatter plot, the values of serum AFP on the 25th, 50th, and 75th percentages were 1,210, 1,210 and 28,318 ng/dl, respectively. Of the 35 cases, 21 were stage IV. 18 cases were treated with systemic chemotherapy before surgery, and 3 cases with locally interventional chemotherapy before surgery. Statistical analysis showed that the preferred interventional treatment affected prognosis, and that there was a statistically significant difference (P = 0.024). Some 33 patients completed the follow-up, of which 17 were in complete remission (CR), 5 were in partial remission (PR), 1 became disease progressive (DP), and 10 died. The remission and overall survival rates were 66.7% (22/33) and 69.7% (23/33), respectively. Patients with the mixed HB phenotypes had worse prognoses than the epithelial phenotype (P < 0.001), and patients in stage IV had a lower survival rate than those in stage III (P < 0.001). Conclusion: Multimodality treatment can effectively improve remission rate and prolong the survival of children with advanced HB. In addition, alpha-fetoprotein (AFP), a tumor marker of liver malignant tumors, HB pathological classification, and staging are highly useful in predicting prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.925-928
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• 2014

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD=13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권1호
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• pp.69-75
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• 2006

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer among men in the developed world affecting the tongue, pharynx, larynx and oral cavity. HNSCC is thought to represent a multistep process whereby carcinogen exposure leads to genetic instability in the tissue and accumulation of specific genetic events, which result in dysregulation of proliferation, differentiation, and cell loss and the acquisition of invasive capacity. Despite therapeutic and diagnostic progress in oncology during the past decades, the prognosis of HNSCC remains poor. Thus it seems that finding a biological tumor markers which will increase the early diagnosis and treatment monitoring rates, is of paramount importance in respect to improving prognosis. In an effort to identify gene expression signatures that may serve as biomarkers, this study several genes were selected, such as H3,3A, S100A7, UCHL1, GSTP1, PAI-2, PLK, TGF${\beta}$1 and bFGF, and used 7 HNSCC cell lines that were established various anatomical sites, and also 17 other cancer cell lines were used for control group using real-time quantitative RT-PCR and immunocytochemical analysis with a monoclonal antibody. In this study, S100A7 showed a clearly restricted occurrence in tongue originated cell line, and GSTP1 expression level in the pharynx originated cell line was very increased, relative to corresponding other cell lines. These results suggest that S100A7 and GSTP1 genes' expression can occur during tongue and pharynx originated head and neck tumorigenesis and that genetic change is an important driving force in the carcinogenesis process. This data indicate that S100A7 and GSTP1 expression pattern in HNSCC reflect both diagnostic clue and biological marker. And this is provides a foundation for the development of site-specific diagnostic strategies and treatments for HNSCC.

• Journal of Hospice and Palliative Care
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• 제18권3호
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• pp.179-187
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• 2015

환자가 죽음에 임박했을 때 환자, 보호자, 의사 사이에서 심폐소생술에 대한 논의는 피할 수 없는 주제이다. 환자가 회복 불가능한 말기의 암환자인 경우에는 환자의 품위 있는 죽음을 고려하여 심폐소생술을 시행하지 않음(Do-not-resuscitate, DNR)을 결정하게 된다. 그러나 DNR에 대한 선택은 환자와 보호자의 심폐소생술과 DNR의 의미 및 그 결과에 대한 이해를 바탕으로 한다. DNR에 대하여 환자, 보호자, 의료진이 상담을 할 때는 환자의 질환이 더 이상 치료가 불가능하며, 심폐소생술이 환자의 생명을 연장시키는 것이 아니라 죽음의 과정을 연장시키는 것이며, 심폐소생술 이후에 삶의 질이 급격히 나빠질 수 있는 상황이라는 합의가 필요하다. 충분한 이해는 환자 또는 보호자가 품위 있는 죽음을 위한 DNR을 선택하도록 한다. 국내에서는 DNR 자체 보다는 이미 생명유지장치를 가지고 있는 환자에서의 생명유지장치의 제거에 대한 법적인 문제가 2차례 발생하면서 사회적으로 품위 있는 죽음에 대한 일반 대중의 관심이 이전보다 증가하였다. 환자와 의료진을 대상으로 한 설문에서는 DNR에 대한 인식과 의지가 80년대에 비해 2000년대 초반에 이르러 상당히 증가하였으나, 실제 의료 현장에서는 DNR의 결정에 있어 환자가 직접 관여를 하는 경우는 많지 않았고 DNR 작성 시점과 사망 시점과의 시간 간격이 1주 이내로 환자가 관여를 하거나 임종시기의 의료를 결정하기에는 너무 짧은 문제가 있었다. 이러한 문제는 조기 완화의료의 확산을 통하여 개선이 가능할 것으로 생각된다. 일부에서는 DNR이라는 용어보다는 자연적인 죽음을 허용함(Allow-Natural-Death)이라는 용어로 바꾸어서 설명하는 것이 이해를 돕고 선택의 갈등을 줄인다는 보고를 하여 DNR 논의와 결정에 있어서 적절한 시기 이외에도 환자와 보호자에게 많은 어려움이 있다는 것을 보여 주고 있다. DNR은 말기암환자에서 품위 있는 죽음을 위해 고려해야 하는 사항이며, 임상에서 DNR이 잘 시행되도록 임상적, 제도적 노력이 필요하다.

• Journal of Korean Neurosurgical Society
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• 제60권1호
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• pp.21-29
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• 2017

Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.