1.Cremastranone-Derived Homoisoflavanes Suppress the Growth of Breast Cancer Cells via Cell Cycle Arrest and Caspase-Independent Cell Death
Yeram CHOI ; Sangkyu PARK ; Seul LEE ; Ha-Eun SHIN ; Sangil KWON ; Jun-Kyu CHOI ; Myeong-Heon LEE ; Seung-Yong SEO ; Younghee LEE
Biomolecules & Therapeutics 2023;31(5):526-535
Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.
2.Leptomeningeal Metastasis in Gliomas : Clinical Characteristics and Risk Factors
Jeyul YANG ; Ji-Woong KWON ; Sang Hoon SHIN ; Heon YOO ; Kyu-Chang WANG ; Sang Heyon LEE ; Ho-Shin GWAK
Journal of Korean Neurosurgical Society 2023;66(4):465-475
Objective:
: Our objective is to analyze the occurrence, clinical course and risk factors for glioma patients with leptomeningeal metastasis (LM) according to different metastasis patterns and clinical variables.
Methods:
: We retrospectively reviewed data from 376 World Health Organization (WHO) grade II–IV adult glioma patients who were treated in the National Cancer Center from 2001 to 2020. Patients who underwent surgery at other institutions, those without initial images or those with pathologically unconfirmed cases were excluded. LM was diagnosed based on magnetic resonance imaging (MRI) findings or cerebrospinal fluid (CSF) cytology. The metastasis pattern was categorized as nodular or linear according to the enhancement pattern. Tumor proximity to the CSF space was classified as involved or separated, whereas location of the tumor was dichotomized as midline, for tumors residing in the thalamus, basal ganglia and brainstem, or lateral, for tumors residing in the cerebral and cerebellar hemispheres.
Results:
: A total of 138 patients were enrolled in the study. A total of 44 patients (38%) were diagnosed with LM during a median follow-up of 9 months (range, 0–60). Among the clinical variables, tumor proximity to CSF space, the location of the tumor and the WHO grade were significant factors for LM development in univariate analysis. In multivariate analysis, the midline location of the tumor and WHO grade IV gliomas were the most significant factor for LM development. The hazard ratio was 2.624 for midline located gliomas (95% confidence interval [CI], 1.384–4.974; p=0.003) and 3.008 for WHO grade IV gliomas (95% CI, 1.379–6.561; p=0.006).
Conclusion
: Midline location and histological grading are an important factor for LM in glioma patients. The proximity to the CSF circulation pathway is also an important factor for WHO grade IV glioma LM. Patients carrying high risks should be followed up more thoroughly.
3.Application of Ultrasonography for Safe Flap Elevation at the Learning Period of Transoral Thyroidectomy: A Technical Report
Dong Won LEE ; Jeong Kyu KIM ; Seung Heon SHIN ; Kyung TAE
Korean Journal of Otolaryngology - Head and Neck Surgery 2022;65(3):180-185
Transoral thyroidectomy using the vestibular approach has achieved excellent cosmetic outcomes without leaving any visible scars. However, concerns have been raised on how to prevent complications, such as skin perforation and anterior jugular vein injury, especially in the learning period. This is because working space is generally created via blind and blunt dissection using a blunt dilator through small vestibular incisions unfamiliar to beginners. Herein, we explain an intraoperative real-time ultrasound technique employed in transoral thyroidectomy to safely elevate a skin flap while avoiding any damage to the flap and anterior jugular vein in the learning period.
5.Data resource profile: the allergic disease database of the Korean National Health Insurance Service
Sunyong YOO ; Dong-Wook KIM ; Young-Eun KIM ; Jong Heon PARK ; Yeon-Yong KIM ; Kyu-dong CHO ; Mi-Ji GWON ; Jae-In SHIN ; Eun-Joo LEE
Epidemiology and Health 2021;43(1):e2021010-
Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients’ characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients’ behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https:/hiss.nhis.or.kr).
6.Risk Model Establishment of Endoscopic Sinus Surgery for Patients with Chronic Rhinosinusitis:a Multicenter Study in Korea
Jin-Young MIN ; Yong Min KIM ; Dae Woo KIM ; Jeong-Whun KIM ; Jin Kook KIM ; Ji-Hun MO ; Jae-Min SHIN ; Kyu-Sup CHO ; Sanggyu KWAK ; Seung-Heon SHIN
Journal of Korean Medical Science 2021;36(40):e264-
Background:
Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes.
Methods:
Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and LundMackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes.
Results:
In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [−0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) − 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed.
Conclusion
Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.
7.Data resource profile: the allergic disease database of the Korean National Health Insurance Service
Sunyong YOO ; Dong-Wook KIM ; Young-Eun KIM ; Jong Heon PARK ; Yeon-Yong KIM ; Kyu-dong CHO ; Mi-Ji GWON ; Jae-In SHIN ; Eun-Joo LEE
Epidemiology and Health 2021;43(1):e2021010-
Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients’ characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients’ behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https:/hiss.nhis.or.kr).
8.Risk Model Establishment of Endoscopic Sinus Surgery for Patients with Chronic Rhinosinusitis:a Multicenter Study in Korea
Jin-Young MIN ; Yong Min KIM ; Dae Woo KIM ; Jeong-Whun KIM ; Jin Kook KIM ; Ji-Hun MO ; Jae-Min SHIN ; Kyu-Sup CHO ; Sanggyu KWAK ; Seung-Heon SHIN
Journal of Korean Medical Science 2021;36(40):e264-
Background:
Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes.
Methods:
Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and LundMackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes.
Results:
In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [−0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) − 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed.
Conclusion
Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.
9.Phylogenetic Characteristics of Echinococcus granulosus Sensu Lato in Uzbekistan
Hye-Jin KIM ; Tai-Soon YONG ; Myeong Heon SHIN ; Kyu-Jae LEE ; Gab-Man PARK ; Uktamjon SUVONKULOV ; Dmitriy KOVALENKO ; Hak Sun YU
The Korean Journal of Parasitology 2020;58(2):205-210
Echinococcosis occurs mainly in areas with heavy livestock farming, such as Central Asia, America, and Australia. Echinococcus granulosus sensu lato (s.l.) infection causes echinococcosis in intermediate hosts, such as sheep, cattle, goats, camels, and horses. Numerous cases of echinococcosis occur in Uzbekistan as stock farming is a primary industry. Epidemiological and genetic studies of E. granulosus s.l. are very important for mitigating its impact on public health and the economy; however, there are no such studies on E. granulosus s.l. in Uzbekistan. In the present study, to determine which genotypes exist and are transmitted, we isolated Echinococcus sp. from definitive hosts (one isolate each from jackal and dog) and intermediate hosts (52 isolates from humans and 6 isolates from sheep) in Uzbekistan and analyzed the isolates by sequencing 2 mitochondrial DNA components (cox1 and nad1). The results showed that all of isolates except one belonged to the E. granulosus sensu stricto (s.s.) G1 and G3 genotypes. Phylogenetic analysis based on cox1 sequences showed that 42 isolates from humans, 6 isolates from sheep, and one isolate from jackal were the G1 genotype, whereas the remaining 8 isolates from human and the one isolate from dog were the G3 genotype. These results suggest that the G1 and G3 genotypes of E. granulosus s.s. are predominant in Uzbekistan, and both wild animals and domestic animals are important for maintaining their life cycle. Only one isolate from human sample was confirmed to be E. eqiinus (G4 genotype), which is known to be for the first time.
10.Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Ji Eun JUN ; In Kyung JEONG ; Jae Myung YU ; Sung Rae KIM ; In Kye LEE ; Kyung Ah HAN ; Sung Hee CHOI ; Soo Kyung KIM ; Hyeong Kyu PARK ; Ji Oh MOK ; Yong ho LEE ; Hyuk Sang KWON ; So Hun KIM ; Ho Cheol KANG ; Sang Ah LEE ; Chang Beom LEE ; Kyung Mook CHOI ; Sung Ho HER ; Won Yong SHIN ; Mi Seung SHIN ; Hyo Suk AHN ; Seung Ho KANG ; Jin Man CHO ; Sang Ho JO ; Tae Joon CHA ; Seok Yeon KIM ; Kyung Heon WON ; Dong Bin KIM ; Jae Hyuk LEE ; Moon Kyu LEE
Diabetes & Metabolism Journal 2020;44(1):78-90
BACKGROUND:
Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.
METHODS:
This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.
RESULTS:
After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.
CONCLUSION
The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

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