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1.
Endocrinology and Metabolism ; : 568-577, 2023.
Article in English | WPRIM | ID: wpr-1000325

ABSTRACT

Background@#Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. @*Methods@#We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. @*Results@#The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. @*Conclusion@#CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

2.
Diabetes & Metabolism Journal ; : 846-858, 2023.
Article in English | WPRIM | ID: wpr-1000268

ABSTRACT

Background@#The effect of obesity on the development of type 2 diabetes mellitus (DM) in different age groups remains unclear. We assessed the impact of obesity on the development of DM for two age groups (40-year-old, middle age; 66-year-old, older adults) in the Korean population. @*Methods@#We analyzed Korean National Health Insurance Service data of 4,145,321 Korean adults with 40- and 66-year-old age without DM, between 2009 and 2014. Participants were followed up until 2017 or until the diagnosis of DM. We assessed the risk of DM based on the body mass index and waist circumference of the participants. Multiple confounding factors were adjusted. @*Results@#The median follow-up duration was 5.6 years. The association of general and abdominal obesity with the risk of DM development was stronger in the 40-year-old group (general obesity: hazard ratio [HR], 3.566, 95% confidence interval [CI], 3.512 to 3.622; abdominal obesity: HR, 3.231; 95% CI, 3.184 to 3.278) than in the 66-year-old group (general obesity: HR, 1.739; 95% CI, 1.719 to 1.759; abdominal obesity: HR, 1.799; 95% CI, 1.778 to 1.820). In the 66-year-old group, abdominal obesity had a stronger association with the development of DM as compared to general obesity. In the 40-year-old group, general obesity had a stronger association with the risk of DM development than abdominal obesity. @*Conclusion@#The influence of general and abdominal obesity on the development of DM differed according to age. In older adults, abdominal obesity had a stronger association with DM development than general obesity.

3.
Clinical and Experimental Reproductive Medicine ; : 213-222, 2023.
Article in English | WPRIM | ID: wpr-999887

ABSTRACT

Cryopreservation is an option for the preservation of pre- or post-pubertal female or male fertility. This technique not only is beneficial for human clinical applications, but also plays a crucial role in the breeding of livestock and endangered species. Unfortunately, frozen germ cells, including oocytes, sperm, embryos, and spermatogonial stem cells, are subject to cryoinjury. As a result, various cryoprotective agents and freezing techniques have been developed to mitigate this damage. Despite extensive research aimed at reducing apoptotic cell death during freezing, a low survival rate and impaired cell function are still observed after freeze-thawing. In recent decades, several cell death pathways other than apoptosis have been identified. However, the relationship between these pathways and cryoinjury is not yet fully understood, although necroptosis and autophagy appear to be linked to cryoinjury. Therefore, gaining a deeper understanding of the molecular mechanisms of cryoinjury could aid in the development of new strategies to enhance the effectiveness of the freezing of reproductive tissues. In this review, we focus on the pathways through which cryoinjury leads to cell death and propose novel approaches to enhance freezing efficacy based on signaling molecules.

4.
Brain Tumor Research and Treatment ; : 254-265, 2023.
Article in English | WPRIM | ID: wpr-999765

ABSTRACT

Background@#This study aims to elucidate clinical features, therapeutic strategies, and prognosis of pineal parenchymal tumors (PPT) by analyzing a 30-year dataset of a single institution. @*Methods@#We reviewed data from 43 patients diagnosed with PPT at Seoul National UniversityHospital between 1990 and 2020. We performed survival analyses and assessed prognostic factors. @*Results@#The cohort included 10 patients with pineocytoma (PC), 13 with pineal parenchymaltumor of intermediate differentiation (PPTID), and 20 with pineoblastoma (PB). Most patients presented with hydrocephalus at diagnosis. Most patients underwent an endoscopic third ventriculostomy and biopsy, with some undergoing additional resection after diagnosis confirmation. Radiotherapy was administered with a high prevalence of gamma knife radiosurgery for PC and PPTID, and craniospinal irradiation for PB. Chemotherapy was essential in the treatment of grade 3 PPTID and PB. The 5-year progression-free survival rates for PC, grade 2 PPTID, grade 3 PPTID, and PB were 100%, 83.3%, 0%, and 40%, respectively, and the 5-year overall survival rates were 100%, 100%, 40%, and 55%, respectively. High-grade tumor histology was associated with lower survival rates. Significant prognostic factors varied among tumor types, with World Health Organization (WHO) grade and leptomeningeal seeding (LMS) for PPTID, and the extent of resection and LMS for PB. Three patients experienced malignant transformations. @*Conclusion@#This study underscores the prognostic significance of WHO grades in PPT. It is nec-essary to provide specific treatment according to tumor grade. Grade 3 PPTID showed a poor prognosis. Potential LMS and malignant transformations necessitate aggressive multimodal treatment and close-interval screening.

5.
Blood Research ; : 46-51, 2023.
Article in English | WPRIM | ID: wpr-999712

ABSTRACT

Owing to donor-related issues, blood shortages and transfusion-related adverse reactions have become global issues of grave concern. In vitro manufactured red blood cells (RBCs) are promising substitutes for blood donation. In the United Kingdom, a clinical trial for allogeneic mini transfusion of cultured RBCs derived from primary hematopoietic stem cells has recently begun. However, current production quantities are limited and need improved before clinical use. New methods to enhance manufacturing efficiencies have been explored, including different cell sources, bioreactors, and 3-dimensional (3D) materials; however, further research is required. In this review, we discuss various cell sources for blood cell production, recent advances in bioreactor manufacturing processes, and the clinical applications of cultured blood.

6.
Annals of Surgical Treatment and Research ; : 252-263, 2023.
Article in English | WPRIM | ID: wpr-999453

ABSTRACT

In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750–800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG’s role, advantages, disadvantages, and potential clinical impact in colorectal surgery.

7.
Annals of Pediatric Endocrinology & Metabolism ; : 144-148, 2023.
Article in English | WPRIM | ID: wpr-999358

ABSTRACT

Thyroid hormone plays a vital role in regulating human metabolism. They affect the functions of major organs, such as the brain, liver, skeletal muscle, and heart. Hypothyroidism can lead to dilated cardiomyopathy and decreased heart function. In this report, we describe a case of a teenage boy who developed dilated cardiomyopathy due to hypothyroidism and was considered to undergo heart transplantation. Levothyroxine monotherapy was initiated but produced no improvement. Thereafter, a combination therapy of liothyronine and levothyroxine was administered, and heart function was gradually restored; he recovered completely after 6 months. Cardiac myocytes respond more specifically to liothyronine than to levothyroxine. Therefore, we suggest that liothyronine and levothyroxine combination therapy should be considered rather than levothyroxine monotherapy for hypothyroidism accompanied by heart disease.

8.
Tuberculosis and Respiratory Diseases ; : 133-141, 2023.
Article in English | WPRIM | ID: wpr-968833

ABSTRACT

Background@#The present study evaluated the association between participation in a rehabilitation program during a hospital stay and 1-year survival of patients requiring at least 21 days of mechanical ventilation (prolonged mechanical ventilation [PMV]) with various respiratory diseases as their main diagnoses that led to mechanical ventilation. @*Methods@#Retrospective data of 105 patients (71.4% male, mean age 70.1±11.3 years) who received PMV in the past 5 years were analyzed. Rehabilitation included physiotherapy, physical rehabilitation, and dysphagia treatment program that was individually provided by physiatrists. @*Results@#The main diagnosis leading to mechanical ventilation was pneumonia (n=101, 96.2%) and the 1-year survival rate was 33.3% (n=35). One-year survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score (20.2±5.8 vs. 24.2±7.5, p=0.006) and Sequential Organ Failure Assessment score (6.7±5.6 vs. 8.5±2.7, p=0.001) on the day of intubation than non-survivors. More survivors participated in a rehabilitation program during their hospital stays (88.6% vs. 57.1%, p=0.001). The rehabilitation program was an independent factor for 1-year survival based on the Cox proportional hazard model (hazard ratio, 3.513; 95% confidence interval, 1.785 to 6.930; p<0.001) in patients with APACHE II scores ≤23 (a cutoff value based on Youden’s index). @*Conclusion@#Our study showed that participation in a rehabilitation program during hospital stay was associated with an improvement of 1-year survival of PMV patients who had less severe illness on the day of intubation.

9.
The Korean Journal of Internal Medicine ; : 218-225, 2023.
Article in English | WPRIM | ID: wpr-968741

ABSTRACT

Background/Aims@#Despite the obvious benefits of adding immune checkpoint inhibitors to platinum-etoposide chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), real-world data remain scarce. @*Methods@#This retrospective study included 89 patients with ES-SCLC treated with platinum-etoposide chemotherapy alone (chemo-only group; n = 48) or in combination with atezolizumab (atezolizumab group; n = 41) and compared the survival outcomes between these two groups. @*Results@#Overall survival (OS) was significantly longer in the atezolizumab group than in the chemo-only group (15.2 months vs. 8.5 months; p = 0.047), whereas the median progression-free survival was almost the same (5.1 months vs. 5.0 months) in both groups (p = 0.754). Subsequent multivariate analysis revealed that thoracic radiation (hazard ratio [HR], 0.223; 95% confidence interval [CI], 0.092–0.537; p = 0.001) and atezolizumab administration (HR, 0.350; 95% CI, 0.184–0.668; p = 0.001) were favorable prognostic factors for OS. In the thoracic radiation subgroup, patients who received atezolizumab demonstrated favorable survival outcomes and no grade 3–4 adverse events (AEs). @*Conclusions@#The addition of atezolizumab to platinum-etoposide resulted in favorable outcomes in this real-world study. Thoracic radiation was associated with improved OS and acceptable AE risk in combination with immunotherapy in patients with ES-SCLC.

10.
Psychiatry Investigation ; : 9-17, 2023.
Article in English | WPRIM | ID: wpr-968555

ABSTRACT

Objective@#We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants. @*Methods@#A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13–24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups. @*Results@#At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group. @*Conclusion@#These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

11.
Osong Public Health and Research Perspectives ; (6): 5-14, 2023.
Article in English | WPRIM | ID: wpr-968438

ABSTRACT

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA’s COVID-19 vaccination data and the National Health Insurance Service’s claims data. The CoVaSC’s 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

12.
Korean Journal of Dermatology ; : 52-56, 2023.
Article in English | WPRIM | ID: wpr-968077

ABSTRACT

Congenital cutaneous candidiasis (CCC) is a rare disease caused by Candida spp. that occurs within the first six days of life. Its exact pathogenesis remains unclear; however, the suspected pathomechanisms include maternal vulvovaginal candidiasis and ascending infections. A preterm, 1,550-g male infant presented with generalized maculopapules and pustules on his whole body. The patient’s mother had undergone cervical cerclage at a gestational age (GA) of 29 weeks due to an incompetent internal os of the cervix. The pregnancy was terminated at GA 37-week because the mother developed chorioamnionitis. We performed a potassium hydroxide microscopic examination, skin biopsy, and fungal culture test on the baby. Microscopic examination of the skin scrapings revealed pseudohyphae with yeasts, and Candida albicans was identified in the culture test. Maternal placental biopsy revealed fungal organisms, and the baby was diagnosed with CCC due to an ascending infection. The skin lesions completely disappeared after intravenous liposomal amphotericin B treatment.

13.
Journal of Korean Neurosurgical Society ; : 162-171, 2023.
Article in English | WPRIM | ID: wpr-967513

ABSTRACT

Objective@#: The goal of this study was to analyze the clinical outcomes of endoscopic third ventriculostomy (ETV) and endoscopic septostomy when shunt malfunction occurs in a patient who has previously undergone placement of a ventriculoperitoneal shunt. @*Methods@#: From 2001 to 2020 at Seoul National University Children's Hospital, patients who underwent ETV or endoscopic septostomy for shunt malfunction were retrospectively analyzed. Initial diagnosis (etiology of hydrocephalus), age at first shunt insertion, age at endoscopic procedure, magnetic resonance or computed tomography image, subsequent shunting data, and follow-up period were included. @*Results@#: Thirty-six patients were included in this retrospective study. Twenty-nine patients, 18 males and 11 females, with shunt malfunction underwent ETV. At the time of shunting, the age ranged from 1 day to 15.4 years (mean, 2.4 years). The mean age at the time of ETV was 13.1 years (range, 0.7 to 29.6 years). Nineteen patients remained shunt revision free. The 5-year shunt revisionfree survival rate was 69% (95% confidence interval [CI], 0.54–0.88). Seven patients, three males and four females, with shunt malfunction underwent endoscopic septostomy. At the time of shunting, the age ranged from 0.2 to 12 years (mean, 3.9 years). The mean age at the time of endoscopic septostomy was 11.9 years (range, 0.5 to 29.5 years). Four patients remained free of shunt revision or addition. The 5-year shunt revision-free survival rate was 57% (95% CI, 0.3–1.0). There were no complications associated with the endoscopic procedures. @*Conclusion@#: The results of our study demonstrate that ETV or endoscopic septostomy can be effective and safe in patients with shunt malfunction.

14.
Journal of Korean Medical Science ; : e87-2023.
Article in English | WPRIM | ID: wpr-967469

ABSTRACT

National cohort data collected during the coronavirus disease 2019 (COVID-19) delta and omicron periods in Korea revealed a lower risk of severe infection in recipients of three doses of the COVID-19 vaccine (adjusted odds ratio [aOR], 0.05–0.08). The risk of death was reduced during the omicron period compared to the delta period (aOR, 0.75; 95% confidence interval, 0.67–0.84).

15.
Journal of Korean Medical Science ; : e17-2023.
Article in English | WPRIM | ID: wpr-967452

ABSTRACT

This study aims to explore the impact of distributional changes in coronavirus disease 2019 (COVID-19) infection fear with sex differences. A quota sampling strategy was followed and 483 Korean adults were surveyed in a community sample. Self-report questionnaires were used to assess COVID-19 infection fear, depressive symptoms, and general characteristics.Quantile regression was used to explore the regression relationship of COVID-19 infection fear and an individual’s sex. There was a significant difference in COVID-19 infection fear (P= 0.001) and depression (P = 0.008) between the sexes - male and female. The differences between sexes at the 20th and 30th percentiles were significant (β = 2.04, P = 0.006; β = 1.5, P = 0.004, respectively). The results demonstrate that sex significantly predicts COVID-19 infection fear and women had significantly greater fear than men in the mild-level of COVID-19 infection fear.

16.
Endocrinology and Metabolism ; : 10-24, 2023.
Article in English | WPRIM | ID: wpr-966831

ABSTRACT

The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

17.
Diabetes & Metabolism Journal ; : 45-58, 2023.
Article in English | WPRIM | ID: wpr-966774

ABSTRACT

Background@#There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. @*Methods@#Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. @*Results@#The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. @*Conclusion@#For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

18.
Diabetes & Metabolism Journal ; : 59-71, 2023.
Article in English | WPRIM | ID: wpr-966773

ABSTRACT

Background@#To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline. @*Methods@#We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018. @*Results@#The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08–1.33), 1.27 (1.15–1.42), 1.39 (1.23–1.56), 1.69 (1.45–1.96), and 1.84 (1.49– 2.27) in very high-risk group, and 1.07 (1.02–1.13), 1.16 (1.10–1.21), 1.29 (1.22–1.36), 1.45 (1.36–1.55), and 1.73 (1.58–1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130–159, 160–189, and ≥190 mg/dL were 1.15 (1.11–1.20), 1.28 (1.22– 1.34), and 1.45 (1.36–1.54) in moderate-risk group and 1.07 (1.02–1.13), 1.20 (1.13–1.26), and 1.47 (1.37–1.57) in low-risk group. @*Conclusion@#We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

19.
Clinical Psychopharmacology and Neuroscience ; : 188-196, 2023.
Article in English | WPRIM | ID: wpr-966683

ABSTRACT

Objective@#The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). @*Methods@#A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. @*Results@#The internal consistency (Cronbach’s alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = −0.771), WHOQOL-BREF (r = −0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). @*Conclusion@#The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

20.
Biomolecules & Therapeutics ; : 219-226, 2023.
Article in English | WPRIM | ID: wpr-966416

ABSTRACT

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

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