SCI 발표논문

2020년 305편

52020

제1저자 정혜승 · 교신저자 Bornfeldt KE

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TNF-α induces acyl-CoA synthetase 3 to promote lipid droplet formation in human endothelial cells.
J Lipid Res. 2020;61(1):33-44.

Abstract
Chronic inflammation contributes to cardiovascular disease. Increased levels of the inflammatory cytokine, TNF-α, are often present in conditions associated with cardiovascular disease risk, and TNF-α induces a number of pro-atherogenic effects in macrovascular endothelial cells, including expression of adhesion molecules and chemokines, and lipoprotein uptake and transcytosis to the subendothelial tissue. However, little is known about the roles of acyl-CoA synthetases (ACSLs), enzymes that esterify free fatty acids into their acyl-CoA derivatives, or about the effects of TNF-α on ACSLs in endothelial cells. Therefore, we investigated the effects of TNF-α on ACSLs and downstream lipids in cultured human coronary artery endothelial cells and human umbilical vein endothelial cells. We demonstrated that TNF-α induces ACSL1, ACSL3, and ACSL5, but not ACSL4, in both cell types. TNF-α also increased oleoyl-CoA levels, consistent with the increased ACSL3 expression. RNA-sequencing demonstrated that knockdown of ACSL3 had no marked effects on the TNF-α transcriptome. Instead, ACSL3 was required for TNF-α-induced lipid droplet formation in cells exposed to oleic acid. These results demonstrate that increased acyl-CoA synthesis as a result of ACSL3 induction is part of the TNF-α response in human macrovascular endothelial cells.
PubMed IF 4.9 내분비대사내과
42020

제1저자 유신혜, 강서영 · 교신저자 오도연

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Predictive Role of Temporal Changes in Intratumoral Metabolic Heterogeneity During Palliative Chemotherapy in Patients with Advanced Pancreatic Cancer: A Prospective Cohort Study.
J Nucl Med. 2020;61(1):33-39.

Abstract
Metabolic intratumoral heterogeneity (ITH) is known to be related to cancer treatment outcome. However, information on the temporal changes in metabolic ITH during chemotherapy and the correlations between metabolic changes and treatment outcomes in patients with pancreatic cancer is sparse. We aimed to analyze the temporal changes in metabolic ITH and the predictive role of its changes in advanced pancreatic cancer patients who underwent palliative chemotherapy. Methods: We prospectively enrolled patients with unresectable locally advanced or metastatic pancreatic cancer before first-line palliative chemotherapy. ¹⁸F-FDG PET was performed at baseline and at the first response follow-up. SUVs, volumetric parameters, and textural features of the primary pancreatic tumor were analyzed. Relationships between the parameters at baseline and first follow-up were assessed, as well as changes in the parameters with treatment response, progression-free survival (PFS), and overall survival (OS). Results: Among 63 enrolled patients, the best objective response rate was 25.8% (95% confidence interval [CI], 14.6%-37.0%). The median PFS and OS were 7.1 mo (95% CI, 5.1-9.7 mo) and 10.1 mo (95% CI, 8.6-12.7 mo), respectively. Most parameters changed significantly during the first-line chemotherapy, in a way of reducing ITH. Metabolic ITH was more profoundly reduced in responders than in nonresponders. Multiple Cox regression analysis identified high baseline compacity (P = 0.023) and smaller decreases in SUV_peak (P = 0.007) and entropy gray-level cooccurrence matrix (P = 0.033) to be independently associated with poor PFS. Patients with a high carbohydrate antigen 19-9 (P = 0.042), high pretreatment SUV_peak (P = 0.008), and high coefficient of variance at first follow-up (P = 0.04) showed worse OS. Conclusion: Reduction in metabolic ITH during palliative chemotherapy in advanced pancreatic cancer patients is associated with treatment response and might be predictive of PFS and OS.
PubMed IF 9.6 혈액종양내과
32020

제1저자 임수 · 교신저자 임수

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Therapeutic efficacy and safety of initial triple combination of metformin, sitagliptin, and lobeglitazone in drug-naïve patients with type 2 diabetes: initial triple study.
BMJ Open Diabetes Res Care. 2020;8(1):8/1/e000807.

Abstract
OBJECTIVE To compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS Among drug-naïve patients with 9.0%-12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and β-cell function, and hypoglycemia.
RESULTS After 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to β-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group.
CONCLUSIONS Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of β-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.
PubMed IF 4.4 내분비대사내과
22020

제1저자 이동석 · 교신저자 서동완

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Long-term safety and efficacy of ethanol retention therapy via percutaneous approach and/or EUS guidance for symptomatic large hepatic cysts (with video).
Endosc Ultrasound. 2020;9(1):31-36.

Abstract
BACKGROUND AND OBJECTIVES Ethanol retention therapy (ERT) under EUS guidance or a percutaneous approach is a safe treatment for large symptomatic hepatic cysts. However, reports on the long-term outcomes after ERT are very rare. Therefore, we aimed to evaluate the long-term outcomes of ERT in symptomatic large hepatic cysts.
MATERIALS AND METHODS A total of 47 consecutive patients with large symptomatic hepatic cysts treated at the Asan Medical Center from April 2009 to October 2017 were analyzed. Thirty patients with right hepatic cysts were treated with ERT through a percutaneous approach, and 14 patients with left hepatic cysts were treated with ERT under EUS guidance. Three patients were treated with ERT using both methods.
RESULTS Of the 47 patients, 43 (91%) showed complete regression and four (9%) showed partial regression on abdominal computed tomography. Recurrence of the cysts was not observed during the follow-up surveillance of a median of 66 months.
CONCLUSIONS Percutaneous catheter drainage-guided ERT and EUS-guided ERT, based on their favorable long-term outcomes, may be considered as first-line treatments in patients with large symptomatic hepatic cysts.
PubMed IF 4.7 소화기내과
12020

제1저자 박현경 · 교신저자 오도연

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The prognostic role of soluble TGF-beta and its dynamics in unresectable pancreatic cancer treated with chemotherapy.
Cancer Med. 2020;9(1):43-51.

Abstract
OBJECTIVES Transforming growth factor-beta (TGF-β) is a multifunctional regulatory factor. Here we measured serum soluble TGF-β (sTGF-β) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients.
METHODS We prospectively enrolled 60 patients treated with FOLFIRINOX as the first-line palliative chemotherapy. We collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF-β using an enzyme-linked immunosorbent assay.
RESULTS The patients' median overall survival (OS) and progression-free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5-12.1) and 6.5 (95% CI, 4.9-8.1) months, respectively. Patients with low sTGF-β at diagnosis (<31.2 ng/mL) had better OS and PFS than patients with high sTGF-β, respectively, (OS, 13.7 vs 9.2 months; hazard ratio [HR], 2.602; P = .004; PFS, 9.0 vs 5.8 months; HR, 2.010; P = .034). At the time of disease progression, sTGF-β was increased compared with that of diagnosis (mean, 26.4 vs 23.9 ng/mL). In particular, sTGF-β was significantly increased at disease progression in patients with a partial response (mean, 25.7 vs 31.0 ng/mL; P = .049).
CONCLUSIONS Pretreatment sTGF-β levels can serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. Likewise, the dynamics of sTGF-β during chemotherapy have prognostic value.
PubMed IF 3.5 혈액종양내과

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