1.Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway
Eunae KIM ; Hark Kyun KIM ; Jae Hoon SUL ; Jeongmi LEE ; Seung Hyun BAEK ; Yoonsuk CHO ; Jihoon HAN ; Junsik KIM ; Sunyoung PARK ; Jae Hyung PARK ; Yong Woo CHO ; Dong-Gyu JO
Biomolecules & Therapeutics 2024;32(4):432-441
Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.
2.Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer
Sujin PARK ; Junsik KIM ; Woncheol JANG ; Kyoung-Mee KIM ; Kee-Taek JANG
Journal of Pathology and Translational Medicine 2023;57(2):113-122
Background:
Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression.
Methods:
We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually.
Results:
The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression.
Conclusions
This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.
3.Exploring the Health and Social Needs of Community Residents Using an Online Community Care Platform: Linkage to the International Classification of Functioning, Disability, and Health
Myounghwa PARK ; Linh Khanh BUI ; Miri JEONG ; Eun Jeong CHOI ; Nayoung LEE ; Minjung KWAK ; Jahyeon KIM ; Jinju KIM ; Jihye JUNG ; Ouckyong SHIN ; Junsik NA ; Huynjeong GUK
Healthcare Informatics Research 2022;28(3):198-209
Objectives:
This study aimed to analyze the outcomes of the Comprehensive Health and Social Need Assessment (CHSNA) system, which identifies community residents’ health and social needs, and to link these needs with the International Classification of Functioning, Disability, and Health (ICF).
Methods:
Adult community residents in a metropolitan city in Korea were recruited. They were asked to assess their health and social needs via the CHSNA system, which was integrated into an online community-care platform. Three assessment steps (basic health assessment, needs for activities of daily living, and in-depth health assessment) associated with five ICF components were used to evaluate physical health impairment, difficulties in activities and participation, and environmental problems. The final list of health and social needs was systematically linked to the domains and categories of the ICF. Only data from participants who completed all three assessment steps were included.
Results:
Wide ranges of impairments and difficulties regarding the daily living activities, physical health, and environmental status of the community were recorded from 190 people who completed assessments of their health and social needs by the CHSNA system. These participants reported various health and social needs for their community life; common needs corresponded to the ICF components of body functions and activities/participation.
Conclusions
The ICF may be suitable for determining the health-related problems and needs of the general population. Possible improvements to the present system include providing support for completing all assessment steps and developing an ICF core set for an enhanced understanding of health and social needs.
4.A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive, recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial
Junsik PARK ; Myong Cheol LIM ; Jae-Kwan LEE ; Dae Hoon JEONG ; Se Ik KIM ; Min Chul CHOI ; Byoung-Gie KIM ; Jung-Yun LEE
Journal of Gynecologic Oncology 2022;33(2):e12-
Background:
Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi.
Methods
The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023.
5.Comparison of the Prognostic Outcome between High-Grade Ovarian Sertoli-Leydig Cell Tumors (SLCTs) and Low-Grade SLCTs
Kyung Jin EOH ; Junsik PARK ; Hye Min KIM ; Maria LEE ; Young Tae KIM
Yonsei Medical Journal 2021;62(4):366-369
The purpose of the current study was to compare prognostic outcomes between patients with high-grade ovarian Sertoli-Leydig cell tumors (SLCTs) and those with other low-grade SLCTs. We retrospectively reviewed medical records for 24 patients pathologically diagnosed with SLCTs between 2006 to 2019 at two institutions. The patients were grouped according to pathological grade: SLCT was classified as grade 1, well differentiated; grade 2, intermediated differentiated; or grade 3, poorly differentiated (Meyer’s classification). Statistical analysis was performed to compare survival outcomes according to pathological grade. The median patient age was 42.5 years (range 16–75). Eighteen patients (75%) were International Federation of Gynecology and Obstetrics stage I, and none were diagnosed in stage IV. Nine patients (37.5%) were grade 3, and 15 patients (63.5%) were grades 1–2. When comparing clinical baseline characteristics of the grade 1–2 group with those of the grade 3 group, only serum CA125 level at diagnosis was significantly higher in the grade 3 group (38.34 vs. 382.29, p=0.002). Five patients experienced recurrence of grade 3 disease, while no recurrence was reported in grade 1–2 disease. Four of the five recurrent patients died. In result, grade 3 ovarian SLCT showed significantly poorer prognosis than grade 1–2 disease (overall survival, hazard ratio=14.25, 95% confidence interval= 1.881–108.0; log-rank p=0.010). Our findings were consistent with the concept that patients with stage I/grade 1–2 tumors have a good prognosis without adjuvant chemotherapy. Since grade 3 ovarian SLCT appears to be relatively more fatal than grade 1 or 2, patients with grade 3 SLCT might require more aggressive surgical intervention and post-treatment surveillance.
6.A Single-Center, Retrospective Study of Bevacizumab-Containing Neoadjuvant Chemotherapy followed by Interval Debulking Surgery for Ovarian Cancer
Junsik PARK ; Kyung Jin EOH ; Eun Ji NAM ; Sunghoon KIM ; Sang Wun KIM ; Young Tae KIM ; Jung Yun LEE
Yonsei Medical Journal 2020;61(4):284-290
PURPOSE: We evaluated whether adding bevacizumab to current platinum-based chemotherapy could improve clinical outcomes without affecting safety.MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with pathologically confirmed ovarian cancer who received neoadjuvant chemotherapy (NAC) at Yonsei Cancer Hospital. We divided the patients into groups based on the use of bevacizumab for NAC (CP group: carboplatin+paclitaxel vs. BCP group: bevacizumab+carboplatin+paclitaxel) and compared patient characteristics, responses to NAC, and surgical and survival outcomes between the two groups. Overall, 88 patients in the CP group and 16 patients in the BCP group received NAC. The primary endpoint was survival outcomes. Complete resection rate after interval debulking surgery (IDS), cancer antigen 125 (CA-125) normalization after NAC, and chemotherapy response score were secondary endpoints.RESULTS: After NAC treatment, all patients underwent IDS. There were no significant differences in adverse events during NAC or postoperative complications between the two groups (p=0.293 and p=0.485, respectively). There were also no significant differences in CA-125 normalization after NAC (42.0% vs. 43.8%, p=0.899) or complete resection rate after IDS (47.7% vs. 56.3%, p=0.530). However, although the BCP group did not show longer overall survival (OS) (log-rank p=0.854), they had significantly longer progression-free survival (PFS) than the CP group (log-rank p=0.048).CONCLUSION: Bevacizumab-containing NAC might be safe and provide longer PFS than chemotherapy alone in patients with advanced ovarian cancer. However, further study is necessary to investigate the impact of bevacizumab-containing NAC on OS.
7.Clinical Factors Associated with Videofluoroscopic Swallowing Study Findings in Stroke Patients.
Jong Min LEE ; Junsik KIM ; Seock Hee HAN ; Jin Ho PARK ; Jung Hwan KIM
Journal of the Korean Dysphagia Society 2019;9(1):16-25
OBJECTIVE: To examine the clinical factors and brain lesion locations related to the patterns of dysphagia in stroke patients in a rehabilitation hospital. METHODS: The medical records of 116 stroke patients who underwent a videofluoroscopic swallowing study (VFSS) between January 2010 and January 2015 in a rehabilitation hospital were reviewed retrospectively. The swallowing-related parameters were assessed using a VFSS. The brain lesion locations were classified as the cortex, basal ganglia, thalamus, midbrain, pons, medulla, cerebellum, and others (subarachnoid or intraventricular hemorrhage). The ambulation ability was assessed using functional ambulation categories (FACs). The independence in the activities of daily living and the degree of cognitive impairment were assessed using the Korean versions of the modified Barthel index (K-MBI) and Mini-Mental State Examination (K-MMSE), respectively. After adjusting for the potential confounding factors in multivariate analysis, the odds ratios and confidence intervals of the stroke brain lesions were calculated and the clinical factors for predicting the VFSS findings were determined. RESULTS: Among the 116 patients, 35 (27%) had an impaired oral stage and 58 (50%) had aspiration. The impaired oral stage was associated significantly with the onset time, basal ganglia stroke, dietary and fluid intake methods at the time of the VFSS, symptoms of dysphagia, FACs, K-MBI, and K-MMSE. Aspiration was correlated with a pontine stroke, methods of dietary and fluid intakes at the time of the VFSS, symptoms of dysphagia, FACs, and K-MBI. Multivariate analysis showed that the pontine stroke and methods of dietary and fluid intake at the time of VFSS predicted aspiration after adjusting for the potential confounding factors. In subgroup analysis of the diet type, the liquid and semisolid aspirations were correlated with the dietary and fluid intake methods and pontine stroke, respectively. CONCLUSION: Patients with a pons lesion stroke, who are on a modified diet (fluid thickening and tube feeding), have higher risks of aspiration. This provides evidence for precise clinical reasoning in this specific patient group.
Activities of Daily Living
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Aspirations (Psychology)
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Basal Ganglia
;
Brain
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Cerebellum
;
Cognition Disorders
;
Deglutition Disorders
;
Deglutition*
;
Diet
;
Humans
;
Medical Records
;
Mesencephalon
;
Multivariate Analysis
;
Odds Ratio
;
Oral Stage
;
Pons
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Rehabilitation
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Retrospective Studies
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Stroke*
;
Thalamus
;
Walking
8.ICT-Based Comprehensive Health and Social-Needs Assessment System for Supporting Person-Centered Community Care
Myonghwa PARK ; Eun Jeong CHOI ; Miri JEONG ; Nayoung LEE ; Minjung KWAK ; Mihyun LEE ; Eun Chung LIM ; Haesung NAM ; Dongil KIM ; Hanwool KU ; Bong Seok YANG ; Junsik NA ; Joong Shik JANG ; Ji Young KIM ; Wonpyo LEE
Healthcare Informatics Research 2019;25(4):338-343
OBJECTIVES: This study developed an information and communication technology (ICT)-based comprehensive health and social-needs assessment (CHSNA) system based on the International Classification of Functioning, Disability, and Health (ICF) with the aim of enhancing person-centered community care for community residents and supporting healthcare professionals and social workers who provide healthcare and social services in the community. METHODS: Items related to a CHSNA tool were developed and mapped with ICF codes. Experts validated the CHSNA system design and process using the Delphi method, and a pilot test of the initial version of the system was conducted. RESULTS: The following three steps of CHSNA were embedded in the system, which had a user-friendly screen and images: basic health assessment, life and activity assessment, and in-depth health assessment. The assessment results for the community residents were presented with visualized health profiles, including images, graphs, and an ICF model. CONCLUSIONS: The developed CHSNA system can be used by healthcare professionals, social workers, and community residents to evaluate the reasoning underlying health and social needs, to facilitate the identification of more appropriate healthcare plans, and to guide community residents to receive the best healthcare services. A CHSNA system can improve the implementation of standardized terminology utilizing the ICF and the accuracy of needs assessments of community residents.
Classification
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Community Health Services
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Decision Support Techniques
;
Delivery of Health Care
;
Methods
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Needs Assessment
;
Patient-Centered Care
;
Social Work
;
Social Workers
9.How to use immune checkpoint inhibitor in ovarian cancer?
Junsik PARK ; Jung Yun LEE ; Sunghoon KIM
Journal of Gynecologic Oncology 2019;30(5):e105-
No abstract available.
Ovarian Neoplasms
10.Effectiveness of the Trauma Team-Staffed Helicopter Emergency Medical Service
Tea youn KIM ; Sang Ah LEE ; Eun Cheol PARK ; Yo HUH ; Kyoungwon JUNG ; Junsik KWON ; Jonghwan MOON ; Jiyoung KIM ; Juryang KIM ; Kyungjin HWANG ; Seong Keun YUN ; John Cook Jong LEE
Health Policy and Management 2018;28(4):411-422
BACKGROUND: Whether there is a difference in outcomes for trauma patients transferring to the helicopter emergency medical service (HEMS) according to their previous team composition is controversial. The purpose of this study is to evaluate the effectiveness of trauma team-staffed-HEMS (TTS-HEMS) when transferring to a trauma center. METHODS: A retrospective comparison was conducted on patients transported to a trauma center over a 6-year period by the TTS-HEMS and paramedic-staffed-HEMS (119-HEMS). Inclusion criteria were blunt trauma with age ≥15 years. Patient outcomes were compared with the Trauma and Injury Severity Score (TRISS) (30-day mortality) and the Cox proportional hazard ratio of mortality (in hospital). RESULTS: There were 321 patients of TTS-HEMS and 92 patients of 119-HEMS. The TTS-HEMS group had a higher Injury Severity Score and longer transport time but a significantly shorter time to emergency surgery. The prehospital data showed that the trauma team performed more aggressive interventions during transport. An additional 7.6 lives were saved per 100 TTS-HEMS deployments. However, the TRISS results in the 119-HEMS group were not significant. In addition, after adjusting for confounders, the hazard ratio of mortality in the 119-HEMS group was 2.83 times higher than that in the TTS-HEMS group. CONCLUSION: HEMS was likely to improve the survival rate of injured patients when physicians were involved in TTS-HEMS. Survival benefits in the TTS-HEMS group appeared to be related to the fact that the trauma team performed both more aggressive prehospital resuscitation and clinical decision making during transportation.
Aircraft
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Clinical Decision-Making
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Emergencies
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Emergency Medical Services
;
Humans
;
Injury Severity Score
;
Mortality
;
Resuscitation
;
Retrospective Studies
;
Survival Rate
;
Transportation
;
Trauma Centers

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