• Journal of Korean Traditional Oncology
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• v.17 no.1
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• pp.45-53
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• 2012

Objective : We introduce a case of non-small cell lung cancer patient treated with allergen removed Rhus verniciflua Stokes. Methods : This patient started Allergen-removed Rhus Verniciflua Stokes from Feb 2010 right after his firstline chemotherapy, and maintained his Oriental medicine regimen until now. Results : It shows 12.0 months of progression-free-survival since starting point of maintenance chemotherapy, and 9.3 months of overall-survival since progression disease after 2nd chemotherapy, compared with 6.3 months of its known overall survival. Conclusion : Allergen removed Rhus verniciflua Stokes prolonged overall survival and slowed disease progression of a non-small cell lung cancer patient.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.785-789
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• 2016

A key drug for treatment of EGFR mutation-positive non-small cell lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). While the dosage of many general anti-tumor drugs is adjusted according to the patient body surface area, one uniform dose of most TKIs is recommended regardless of body size. In many cases, dose reduction or drug cessation is necessary due to adverse effects. Disease control, however, is frequently still effective, even after dose reduction. In this study, we retrospectively reviewed the characteristics of 26 patients at Fukuoka University Hospital between January 2004 and January 2015 in whom the EGFR-TKI dose was reduced with respect to progression free survival and overall survival. There were 10 and 16 patients in the gefitinib group and the erlotinib group, respectively. The median progression-free survival in the gefitinib group and the erlotinib group was 22.4 months and 14.1 months, respectively, and the median overall survival was 30.5 months and 32.4 months, respectively. After stratification of patients by body surface area, the overall median progression-free survival was significantly more prolonged in the low body surface area (<1.45 m2) group (25.6 months) compared to the high body surface area (>1.45 m2) group (9.7 months) (p=0.0131). These results indicate that low-dose EGFR-TKI may sufficiently control disease without side effects in lung cancer patients with a small body size.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4583-4587
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• 2015

Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. Materials and Methods: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression-free survival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.121-126
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• 2009

Background: Pemetrexed has been prescribed newly as a second line chemotherapy in advanced non-small cell lung carcinoma (NSCLC). The aim of study was to determine the efficacy and toxicity of pemetrexed in advanced NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC were evaluated from June 2006 to December 2008. The patients had relapsed or progressed after prior chemotherapy treatment. They were treated with intravenous pemetrexed $500mg/m^2$ for 10 min on Day 1 of each 21-day cycle. Results: A total of 89 patients were eligible for analysis. The response rate and disease control rate were 11% and 66%. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (p=0.035) and disease control rate (p=0.009) than squamous cell carcinoma histology. The median survival time was 13 months and the median progression free survival time was 2.3 months. The median survival time of patients with ECOG PS 0~1 was 13.2 months, whereas median survival time was 11.6 months for patients with PS 2 (p=0.002). The median progression free survival time of patients with PS 0~1 were 3.8 months, but 2.1 months for patients with PS 2 (p=0.016). The median progression free survival time of smokers with non-squamous cell carcinoma was 3.4 months, which was significant (p=0.014). Grade 3~4 neutropenia were seen in 7.9% patients. Conclusion: Pemetrexed has efficacy in patients who had prior chemotherapy with advanced NSCLC and less hematologic toxicity.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• Genomics & Informatics
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• v.7 no.2
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• pp.122-130
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• 2009

A systems biology approach for the identification of perturbed molecular functions is required to understand the complex progressive disease such as breast cancer. In this study, we analyze the microarray data with Gene Ontology terms of molecular functions to select perturbed molecular functional modules in breast cancer tissues based on the definition of Gene ontology Functional Code. The Gene Ontology is three structured vocabularies describing genes and its products in terms of their associated biological processes, cellular components and molecular functions. The Gene Ontology is hierarchically classified as a directed acyclic graph. However, it is difficult to visualize Gene Ontology as a directed tree since a Gene Ontology term may have more than one parent by providing multiple paths from the root. Therefore, we applied the definition of Gene Ontology codes by defining one or more GO code(s) to each GO term to visualize the hierarchical classification of GO terms as a network. The selected molecular functions could be considered as perturbed molecular functional modules that putatively contributes to the progression of disease. We evaluated the method by analyzing microarray dataset of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Based on the integration approach, we selected several interesting perturbed molecular functions that are implicated in the progression of breast cancers. Moreover, these selected molecular functions include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting perturbed molecular functions that putatively play roles in the progression of diseases and provides an improved interpretability of GO terms based on the definition of Gene Ontology codes.

• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.384-392
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• 2018

Background: A very low protein diet (VLPD) with ketoacid analogs of essential amino acids (KA/EAA) administration can remarkably influence protein synthesis and metabolic disturbances of patients with advanced chronic kidney disease (CKD), and may also slow the decline in renal function. Methods: A retrospective cohort study was carried out to monitor renal progression and metabolic and nutritional status among 140 patients with CKD stage III or IV. One group (n = 70) was on a low protein diet (LPD) with 0.6 g of protein intake, and another group (n = 70) was on a VLPD with 0.3 g of protein and KA/EAA supplementation of 100 mg/kg/day for 12 months. Results: At 12-month follow-up, estimated glomerular filtration rate (GFR) significantly decreased from $41.6{\pm}10.2$ to $36.4{\pm}8.8mL/min/1.73m^2$ (P < 0.001) and urine protein increased from $0.6{\pm}0.5$ to $0.9{\pm}1.1g/day$ (P = 0.017) in the LPD group, but no significant changes in estimated GFR and urine protein were found in the VLPD plus KA/EAA group. A significant mean difference in rate of change in estimated GFR ($-5.2{\pm}3.6mL/min/1.73m^2$ per year; P < 0.001) was observed between the two groups. After Cox regression analysis, treatment with VLPD plus KA/EAA significantly protected against the incidence of declining GFR > 10% annually (adjusted hazard ratio, 0.42; 95% confidence interval, 0.23-0.79; P = 0.006) and significant correlations were found between using VLPD plus KA/EEA and increased GFR. Conclusion: VLPD supplementation with KA/EAA is associated with delayed renal progression while preserving the nutritional status in the patients with CKD. Co-administration of VLPD and KA/EAA may prove an effective alternative to conservative management of CKD.

• Journal of Korean society of Dental Hygiene
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• v.13 no.6
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• pp.1015-1021
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• 2013

Objectives : The purpose of the study is to find the association between obesity and periodontal disease by age in adults. Methods : The subjects were 5,728 adults in the first year of the Fifth National Health and Nutrition Examination Survey in 2010. The questionnaire included oral examinations, periodontal disease, and body mass index screenings. Chi-square test was performed to confirm the periodontal disease. Results : The impact of obesity and waist circumference on body mass index (BMI) showed high risk of periodontal diseases. The risk of periodontal disease according to BMI by age was closely related to obesity ranged form 35 to 59 yeard old. The increased waist circumference and those who were in 35 to 59 and over 60 years old had a significant association with the periodontal disease risk. Conclusions : Obesity and periodontal disease are closely related factors. Those aged from 35 to 59 are the high risk groups of potential obesity and periodontal disease. It is very important to control well-balanced nutrition and physical activity that can prevent the progression of periodontal disease.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1213-1224
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• 2021

Objective: To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. Materials and Methods: Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. Results: Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. Conclusion: CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.89-96
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• 2013

Atherosclerotic vascular dysfunction is a chronic inflammatory process that spreads from the fatty streak and foam cells through lesion progression. Therefore, its early diagnosis and prevention is unfeasible. Reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerotic vascular disease. Intracellular redox status is tightly regulated by oxidant and antioxidant systems. Imbalance in these systems causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, and leads to dysregulation. Paradoxically, large clinical trials have shown that non-specific ROS scavenging by antioxidant vitamins is ineffective or sometimes harmful. ROS production can be locally regulated by cellular antioxidant enzymes, such as superoxide dismutases, catalase, glutathione peroxidases and peroxiredoxins. Therapeutic approach targeting these antioxidant enzymes might prove beneficial for prevention of ROS-related atherosclerotic vascular disease. Conversely, the development of specific antioxidant enzyme-mimetics could contribute to the clinical effectiveness.