• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4039-4044
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• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.

• Journal of Preventive Medicine and Public Health
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• v.47 no.1
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• pp.36-46
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• 2014

Objectives: To evaluate the association between fracture risk and levothyroxine use in elderly women with hypothyroidism, according to previous osteoporosis history. Methods: We conducted a cohort study from the Korean Health Insurance Review and Assessment Service claims database from January 2005 to June 2006. The study population comprised women aged ${\geq}65$ years who had been diagnosed with hypothyroidism and prescribed levothyroxine monotherapy. We excluded patients who met any of the following criteria: previous fracture history, hyperthyroidism, thyroid cancer, or pituitary disorder; low levothyroxine adherence; or a follow-up period <90 days. We categorized the daily levothyroxine doses into 4 groups: ${\leq}50{\mu}g/d$, 51 to $100{\mu}g/d$, 101 to $150{\mu}g/d$, and > $150{\mu}g/d$. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the Cox proportional hazard model, and subgroup analyses were performed according to the osteoporosis history and osteoporosis-specific drug prescription status. Results: Among 11 155 cohort participants, 35.6% had previous histories of osteoporosis. The adjusted HR of fracture for the > $150{\mu}g/d$ group, compared with the 51 to $100{\mu}g/d$ group, was 1.56 (95% CI, 1.03 to 2.37) in osteoporosis subgroup. In the highly probable osteoporosis subgroup, restricted to patients who were concurrently prescribed osteoporosis-specific drugs, the adjusted HR of fracture for the > $150{\mu}g/d$ group, compared with the 51 to 100 ${\mu}g/d$ group, was 1.93 (95% CI, 1.14 to 3.26). Conclusions: While further studies are needed, physicians should be concerned about potential levothyroxine overtreatment in elderly osteoporosis patients.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.24 no.4
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• pp.207-212
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• 2013

Objectives : We investigated the long-term tolerability of escitalopram in Korean adolescents. Methods : The subjects were 37 adolescents, who had been diagnosed with depressive disorder in accordance to DSM-IV. Clinical effectiveness was assessed by Clinical Global Impression-Improvement (CGI-I) scale at the final follow-up visit. Tolerability was assessed through a medical record of the reason for discontinuation of escitalopram and documented adverse events. Results : The mean duration of treatment was $78.1{\pm}89.5$ days, and the mean dosage was $10.0{\pm}4.4$mg/day. Out of the total 37 patients, two (5%) patients sustained use of escitalopram. Twelve patients (32.4%) discontinued use of escitalopram due to target symptom remission, and 23 patients (61.9%) due to insufficient efficacy. Six patients (16.2%) had at least one documented adverse event. However, no suicidal ideation or self-injurious behavior was reported. Significant differences in clinical symptom improvement efficacy were seen between the patients who were receiving escitalopram for less than 8 weeks (4.3%, 1/13) and those for more than 8 weeks (92.9%, 13/14). There was no significant difference between the tolerability of monotherapy compared to the concomitant use group. Conclusion : The results of this study suggest that long-term use of escitalopram may result in superior efficacy than shortterm use, and is tolerable in Korean adolescents with depression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.261-267
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• 2012

Purpose: The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer (GC) patients remains controversial, although most studies reported poor survival and reduced response to fluoropyrimidine were related to high TS in tumors. We carried out a systematic review of the literature with meta-analysis to estimate the predictive value of TS expression from published studies. Methods: We indentified 24 studies analysing the outcome data in gastric cancer stratified by TS expression. Effect measures of outcome were hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS), or the odds ratio (OR) for overall response rate (ORR). HRs and ORs from these eligible studies were pooled using random-effects meta-analysis. Results: Fifteen studies investigated outcomes in a total of 844 patients with advanced GC, and nine studies investigated outcomes in a total of 1,235 patients with localized GC undergoing adjuvant therapy. Meta-analysis of estimates showed high TS expression was significantly associated with poor OS in the advanced setting (HR: 1.43, 95%CI: 1.08 - 1.90), and poor EFS in the adjuvant setting (HR: 1.53, 95%CI: 1.01 - 2.32). Subgroup analysis demonstrated TS expression to haves even greater value in predicting OS, EFS and ORR in advanced GC patients treated with fluoropyrimidine monotherapy (HR for OS: 2.32, 95%CI: 1.53 - 3.50; HR for EFS: 1.76, 95%CI: 1.19 - 2.60; OR for ORR: 0.32, 95%CI: 0.11 - 0.95). Conclusion: High levels of TS expression were asssociated with a poorer OS for advanced GC patients compared with low levels. In the adjuvant setting, high TS expression was also associated with a worse EFS. Additional studies with consistent methodology are needed to define the precise predictive value of TS.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.2
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• pp.121-131
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• 2020

Purpose: To determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review. Methods: An electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation. Results: In total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83-97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67-91% and 61-85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy. Conclusion: This review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.697-702
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• 2016

Background: The Asia-Pacific Breast Initiatives (APBI) I and II registries were established to collect safety data for patients with early stage breast cancer receiving adjuvant docetaxel-based regimens in the Asia-Pacific region. Materials and Methods: Data from the two registries were combined to perform a safety analysis. Participants in the registry were women with early stage operable breast cancer with an intermediate or high risk of recurrence. These women received adjuvant chemotherapy that included docetaxel between 2006 and 2011. Adverse events (AEs) were recorded and analyzed. Results: Data were collected from 3,224 patients from 13 countries. The mean dose intensity of docetaxel was 24.1, 22.7, $25.1mg/m^2/week$ among patients receiving docetaxel-based monotherapy, combination therapy and sequential therapy, respectively. Granulocyte colony-stimulating factor (G-CSF) was given with docetaxel to 41.8% of women and 20.6% of women receiving prophylactic antibiotics. Adverse events were reported in 86% of patients (anthracycline-containing regimens vs. non-anthracycline regimens; 87% vs. 80%). The most common adverse events were alopecia, nausea, neutropenia, vomiting, and myalgia. Adverse events NCI CTCAE ${\geq}$Grade 3 were reported in 45.4% of patients. Serious adverse events were reported in 13% of patients, of which 2.5% led to study discontinuation. Forty-six deaths (1.4%) were reported, with no significant difference between regimens. Conclusions: The safety parameters of adjuvant docetaxel therapy used to treat sequential Asian women were comparable to those reported in clinical trials evaluating the role of adjuvant docetaxel. No unusual adverse events linked to Asia-Pacific region patients were observed.

• Korean Journal of Psychosomatic Medicine
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• v.14 no.1
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• pp.25-32
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• 2006

Objectives : Headache is a clinical symptom that more than 90% of all individuals experience during their life time. This article provides a current concept of tension-type and migraine headaches and summarizes the effects of biofeedback treatment and/or relaxation techniques. Methods : The following terms were used for Pubmed/Medline search : biofeedback, relaxation, physiological, behavioral, nonpharmacological, headache, tension-type headache, and migraine. A review of references from relevant literature was also conducted to collect reports not identified in the Pubmed/Medline search. Interviews with experts on biofeedback were also included in this review. Results : Headache is a psychophysiological symptom that can be treated by some behavioral interventions including biofeedback and relaxation. Literatures on biofeedback and/or relaxation have consistently reported significant therapeutic effects on headaches. Important factors that we have to consider, when we apply to headache patients with biofeedback and relaxation techniques, were also presented. Conclusion : The available evidence suggests that biofeedback and relaxation techniques are effective treatments for the patients with headaches and can be provided to the patients as monotherapy or combination therapy with medication.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.165-170
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• 2008

In the present study, we aimed to identify the synergistic effects of concurrent treatment of low concentrations of cilostazol and probucol to inhibit the oxidative stress with suppression of inflammatory markers in the cultured human coronary artery endothelial cells (HCAECs). Combination of cilostazol (0.3${\sim}3{\mu}$M) with probucol (0.03${\sim}0.3{\mu}$M) significantly suppressed TNF-${\alpha}$-stimulated NAD(P)H-dependent superoxide, lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production and TNF-${\alpha}$ release in comparison with probucol or cilostazol alone. The combination of cilostazol (0.3${\sim}3{\mu}$M) with probucol (0.1${\sim}0.3{\mu}$M) inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) more significantly than did the monotherapy with either probucol or cilostazol. In line with these results, combination therapy significantly suppressed monocyte adhesion to endothelial cells. Taken together, it is suggested that the synergistic effectiveness of the combination therapy with cilostazol and probucol may provide a beneficial therapeutic window in preventing atherosclerosis and protecting from cerebral ischemic injury.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.298-305
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• 2016

Background: This study is to investigate the prescription patterns and factors related to the number of medications treating chronic obstructive pulmonary disease (COPD) in patients under 65 years old according to GOLD guidelines. Methods: We retrospectively analyzed the medical records of patients aged 40-64 years with a diagnosis of COPD from January to March 2016. Patients were classified by combined assessment of COPD (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. We analyzed prescribed medications, treatment options and factors related to the numbers of COPD medications. Results: The total number of prescriptions were 251. About 35.5% of patients were classified as GOLD A, 34.2% as GOLD B, 17.1% as GOLD C and 13.2% as GOLD D. Inhaled bronchodilator was prescribed for 86.9% of patients and the most frequent COPD medication was long-acting muscarinic antagonist (LAMA) followed by inhaled corticosteroids/long acting beta agonist (ICS/LABA). The majority of low risk patients (GOLD A/B) were prescribed a monotherapy with LAMA or LABA. For high risk patients (GOLD C/D), combination treatment with ICS+LAMA+LABA was mostly prescribed. The 21.2% of patients in GOLD D received systemic corticosteroid. The average number of medications per prescription was 3.7, and this number increased with increasing COPD grade, COPD duration and lung function reduction ($FEV_1$, $FEV_1/FVC$). Conclusion: Generally high adherence to GOLD guideline recommendations was reported. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD is warranted.

• Korean Journal of Clinical Pharmacy
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• v.30 no.2
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• pp.102-112
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• 2020

Objective: To analyze the prescription patterns for the treatment of ulcerative colitis (UC) and to investigate factors co-occurring with systemic corticosteroid use. Methods: We used patient-level data from Korean National Health Insurance claims database to identify patients diagnosed with UC (ICD-10 code : K51) and their medications prescribed for UC between January 1 and Decemeber 31, 2017. We found that medications for UC treatment were 5-aminosalicylic acid (5-ASA), immunomodulators, biologics, and corticosteroids. We presented the prescription pattern according to the sex, age group, type of health insurance, site of UC, type of medical institution, and concomitant medication. To evaluate factors associated with prescription of systemic corticosteroids for UC, we used a multivariate logistic regression model to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs). Results: Of 1,469 UC patients, 74.5% used 5-ASA and 15.2% used systemic corticosteroids. 5-ASA constituted 77.5% of all prescriptions and systemic corticosteroids accounted for 13.1%. The most widely used therapy was 5-ASA monotherapy (54.8%), followed by a double therapy with 5-ASA and immunomodulators (8.2%) or 5-ASA and systemic corticosteroids (7.2%). Systemic corticosteroids were more likely to be prescribed with immunomodulators (aOR=1.88, 95% CI=1.54-2.28) and biologics (aOR=2.82, 95% CI=2.28-3.50) than without them. Conclusions: We found that 15.2% of UC patients were prescribed with a systemic corticosteroid, which is less than reported previously. Systemic corticosteroids were more likely to be prescribed with immunomodulators and biologics.