SCI 발표논문
2016년 247편
- 72016
제1저자 박진균 · 교신저자 Francesco Boin
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Association of Acroosteolysis With Enhanced Osteoclastogenesis and Higher Blood Levels of Vascular Endothelial Growth Factor in Systemic Sclerosis.Arthritis Rheumatol. 2016;68(1):201-9.
PubMed IF 9.9 류마티스내과Abstract
OBJECTIVE Bone resorption of distal phalanges, or acroosteolysis (AO), can develop in patients with systemic sclerosis (SSc), causing pain and functional limitation. This study was undertaken to investigate whether AO may be associated with abnormal osteoclastogenesis in SSc patients and whether hypoxia may be involved in this process.
METHODS Peripheral blood mononuclear cells (PBMCs) obtained from 26 SSc patients (11 with AO and 15 without AO) and 14 healthy controls were cultured in the presence of RANKL and macrophage colony-stimulating factor for 9 days. Tartrate-resistant acid phosphatase-positive multinucleated giant cells (MGCs) containing 3 or more nuclei were counted as osteoclasts. Plasma levels and effects of vascular endothelial growth factor (VEGF) on osteoclast formation were evaluated.
RESULTS SSc patients with AO formed significantly more osteoclasts after 9 days than did patients without AO (mean ± SD 142.4 ± 67.0 versus 27.2 ± 17.6 MGCs/well; P < 0.001) or healthy controls (mean ± SD 18.7 ± 27.0 MGCs/well; P < 0.001). No significant difference in osteoclast formation was noted between the patients without AO and healthy controls. Plasma levels of VEGF were higher in SSc patients with AO compared to those without (mean ± SD 142.4 ± 69.6 pg/ml versus 88.1 ± 38.2 pg/ml; P < 0.005) or healthy controls (54.2 ± 24.6 pg/ml; P = 0.018). Priming with VEGF-A for 24 hours significantly increased osteoclast generation by 5.3 ± 1.9 fold (P = 0.0018). The radiographic extent of AO was associated with increased osteoclast formation (Spearman's ρ = 0.741, P = 0.01).
CONCLUSION Our findings indicate that increased osteoclast formation and higher VEGF levels may contribute to AO in SSc patients. Further studies are needed to elucidate whether targeting osteoclastogenesis may provide a specific therapeutic option for SSc-associated AO.
- 62016
제1저자 강미현 · 교신저자 김지현
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Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic Agents, in Colorectal Cancer Cells.Cancer Res Treat. 2016;48(1):355-64.
PubMed IF 4.2 혈액종양내과Abstract
PURPOSE HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in CRC cell lines.
MATERIALS AND METHODS The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index.
RESULTS The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50, 0.003 µM and 0.005 µM, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells.
CONCLUSION These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, singly or in combination with chemotherapeutic agents. The role of BMX expression as a marker of response to HM781-36B should be further explored.
- 52016
제1저자 김수정 · 교신저자 유철규
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Age-related annual decline of lung function in patients with COPD.Int J Chron Obstruct Pulmon Dis. 2016;11:51-60.
PubMed IF 4.1 호흡기내과Abstract
BACKGROUND According to the Fletcher-Peto curve, rate of decline in forced expiratory volume in 1-second (FEV1) accelerates as age increases. However, recent studies have not demonstrated that the rate of FEV1 decline accelerates with age among COPD patients. The objective of the study is to evaluate annual rate of FEV1 decline as age increases among COPD patients.
METHODS In this retrospective cohort study, we enrolled COPD patients who were followed up at two tertiary care university hospitals from January 2000 to August 2013. COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of <0.7. All participants had more than two spirometries, including BD response. Age groups were categorized as follows: below versus above median age or four quartiles.
RESULTS A total of 518 participants (94.2% male; median age, 67 years; range, 42-90 years) were included. Mean absolute and predictive values of post-BD FEV1 were 1.57±0.62 L and 52.53%±18.29%, respectively. Distribution of Global initiative for Chronic Obstructive Lung Disease groups did not show statistical differences between age groups categorized by two different criteria. After grouping the population by age quartiles, the rate of FEV1 decline was faster among older patients than younger ones whether expressed as absolute value (-10.60±5.57 mL/year, -15.84±6.01 mL/year, -18.63±5.53 mL/year, 32.94±6.01 mL/year, respectively; P=0.048) or predicted value (-0.34%±0.19%/year, -0.53%±0.21%/year, -0.62%±0.19%/year, -1.26%±0.21%/year, respectively, P=0.010).
CONCLUSION As suggested conceptually by the Fletcher-Peto curve, annual FEV1 decline among COPD patients is accelerated among older patients than younger ones.
- 42016
제1저자 오도연 · 교신저자 방영주
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Pertuzumab in gastrointestinal cancer.Expert Opin Biol Ther. 2016;16(2):243-53.
PubMed IF 4 혈액종양내과Abstract
INTRODUCTION Human epidermal growth factor receptor 2 (HER2) and HER3 are altered in multiple tumor types, including gastrointestinal cancer. The HER2/HER3 dimer is crucial for HER2-mediated signaling in HER2-positive tumors. HER2-targeting agents, including trastuzumab, lapatinib, trastuzumab emtansine, and pertuzumab, have been approved for the treatment of HER2-positive breast cancer, with trastuzumab also approved for the treatment of HER2-positive gastric cancer. Pertuzumab, a recombinant humanized immunoglobulin (Ig) G1 monoclonal antibody targeting HER-2, binds to the dimerization domain (extracellular domain II) of HER2, which leads to blocking of ligand-induced HER2 heterodimerization. It is under investigation in gastrointestinal cancers, including HER2-positive gastric cancer.
AREA COVERED In this review, the authors summarize the biology of HER2/HER3 and its alterations in gastrointestinal cancers. The authors focus specifically on the current status of development of pertuzumab in gastrointestinal cancers.
EXPERT OPINION The HER2/HER3 alteration in gastrointestinal cancers is quite interesting. In HER2-positive gastric cancer, the dual blockade of HER2 and HER3 using trastuzumab and pertuzumab is being tested in an international phase III trial, the JACOB study. This strategy may benefit HER2-positive gastric cancer patients more as in the case of HER2-positive breast cancer. In other gastrointestinal cancers, including biliary tract cancer, esophageal cancer, pancreatic cancer, and colorectal cancer, there is huge room for the development of pertuzumab.
- 32016
제1저자 이성우 · 교신저자 진호준
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Glomerular Hypertrophy Is a Risk Factor for Relapse in Minimal Change Disease Patients.Nephron. 2016;132(1):43-50.
PubMed IF 2.3 신장내과Abstract
BACKGROUND/AIMS Patients with minimal change disease (MCD) have a high relapse rate, which results in many complications. Identifying the risk factors for relapse is crucial, but little is known about these factors. Therefore, we performed the current study to determine the factors related to relapse in this patient population.
METHODS We retrospectively analyzed 51 adult patients with biopsy-proven primary MCD treated between 2003 and 2013. The demographic, physiologic, laboratory and therapeutic data were gathered from the electronic medical records database. Lesions of the glomerulus, tubulointerstitium and vasculature were analyzed for associations with relapse.
RESULTS During a median 50.9 months, 96.1% (49 of 51) of patients had achieved complete remission, and the rest ultimately achieved at least partial remission. A total of 56.9% (29 of 51) patients experienced at least 1 episode of relapse after the first remission. Patients with relapse had a higher rate of glomerular hypertrophy (GH; 34.5%) than those without relapse (9.1%; p < 0.05). After adjusting for confounders, GH was associated with increased odds of relapse (OR 15.992; 95% CI 1.537-166.362; p = 0.02). In a subgroup analysis according to median age, sex and tubulointerstitial (TI) lesions, the association between GH and relapse was evident only in men and in the group with TI lesions.
CONCLUSION GH is associated with relapse in adult patients with MCD, particularly in men and in those with TI lesions. Frequent monitoring and early intervention are needed in these groups. Future large prospective cohort studies are needed to confirm the study results.
- 22016
제1저자 최병용 · 교신저자 송영욱
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Prevalence and clinical impact of fibromyalgia in patients with primary Sjögren's syndrome.Clin Exp Rheumatol. 2016;34(2 Suppl 96):S9-13.
PubMed IF 3.2 류마티스내과Abstract
OBJECTIVES Clinical features of primary Sjögren's syndrome (pSS) overlap with those of fibromyalgia (FM). This cross-sectional study was conducted to investigate the prevalence of FM in pSS patients and to compare the clinical features of pSS patients with FM to those without FM.
METHODS One hundred pSS patients were consecutively assessed to identify the presence of FM according to the American College of Rheumatology (ACR) 2010 criteria. Clinical and laboratory data were collected from all patients. Additional assessments included EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). The severity of depression was measured by Hamilton depression rating scale 17-items (HAM-D scale).
RESULTS The prevalence of FM was 31.0% (31/100) in pSS. Widespread pain index and symptom severity scale were significantly correlated with ESSPRI (r=0.6542 and r=0.7173, both p<0.0001) and HAM-D scale (r=0.6734 and r=0.6471, both p<0.0001) in pSS. In multivariate analysis, ESSPRI and HAM-D scale were independently associated with increase of tender point count and symptom severity scale. ESSPRI was significantly higher in pSS patients with FM compared to those without FM (p<0.0001). The prevalence of FM in pSS patients with moderate-to-severe depression was significantly higher than those with mild depression or without depression (odds ratio= 10.62, p=0.0009). Serum 25-hydroxy vitamin D3 levels in pSS patients with FM were significantly (p=0.0072) decreased compared to those without FM.
CONCLUSIONS Our study showed that FM was prevalent in pSS. FM was associated with higher ESSPRI and more severe depression.
- 12016
제1저자 김효진 · 교신저자 오국환
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Baseline FGF23 is Associated with Cardiovascular Outcome in Incident PD Patients.Perit Dial Int. 2016;36(1):26-32.
PubMed IF 1.8 신장내과Abstract
UNLABELLED ♦
BACKGROUND Fibroblast growth factor 23 (FGF23) is a phosphate regulating protein. Several studies demonstrated that elevated FGF23 is independently associated with mortality for early-stage chronic kidney disease and incident hemodialysis (HD) patients. However, little is known about the significance of elevated FGF23 in peritoneal dialysis (PD) patients. Here, we analyzed the association of FGF23 with cardiovascular (CV) events, all-cause mortality, residual renal function (RRF), and CV parameters in PD patients. ♦
METHODS The present study is a single-center, retrospective study. Patients who started PD at Seoul National University Hospital between January 2005 and July 2011 and whose baseline serum samples were available were enrolled. C-terminal FGF23 was measured. Subjects were divided into 2 groups; lower 2 tertiles (FGF23 ≤ 119.0 RU/mL) and top tertile (FGF23 > 119.0 RU/mL). The primary outcome was time to fatal or non-fatal CV events. In the subgroup analysis, the associations of FGF23 with aortic stiffness or with vascular calcification were analyzed. ♦
RESULTS A total of 205 incident PD patients were analyzed. Mean duration of follow-up was 41.6 ± 20.0 months. The baseline median FGF23 level was 78.6 RU/mL (inter-quartile range [IQR], 34.1 - 155.0). At baseline, subjects in the higher FGF23 group were younger, and had a lower RRF, lower prevalence of diabetes mellitus (DM), and cerebrovascular disease. During follow-up, 22 of the 205 patients (10.7%) reached primary outcome. After adjustment for age, DM, pre-existing coronary artery disease, cerebrovascular disease, congestive heart failure, and left ventricular mass index, the higher FGF23 group exhibited significantly higher risk of primary outcome, compared with the lower group (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.05 - 6.12; p = 0.045). There were no significant differences in all-cause mortality and development of anuria between the 2 FGF23 groups. In the subgroup analysis, FGF23 groups were not associated with pulse wave velocity and abdominal aortic calcification score. ♦
CONCLUSION Elevated FGF23 is associated with higher risk of adverse CV outcome for incident PD patients.
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