ABSTRACT
Advancements in digital technology have led to increased usage of digital devices among teenagers. The coronavirus disease 2019 pandemic and the subsequent implementation of social distancing policies have further accelerated this change. Consequently, a new concept called the metaverse has emerged. The metaverse is a combination of a virtual reality universe that allows individuals to meet, socialize, work, play, entertain, and create. This review provides an overview of the concept and main features of the metaverse and examples of its utilization in the real world. It also explains the unique developmental characteristics of childhood and adolescence, as well as the possible negative influences of the metaverse on them, including addiction, antisocial behavior, cyberbullying, and identity confusion.This review summarizes several suggestions for future research because the metaverse is a relatively new concept.
ABSTRACT
Purpose@#In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs. @*Materials and Methods@#We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed. @*Results@#High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI. @*Conclusion@#High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.
ABSTRACT
Objective@#Menopause symptoms can vary in type, duration, and severity. The purpose of this study was to investigate the key factors predicting severe symptoms among Korean perimenopausal women with various demographic data, obstetric and psychiatric histories, and menopausal symptoms screening scale scores. @*Methods@#Data were collected from 1,060 women, and 4 latent classes were identified using latent profile analysis, with 6 major categories of menopausal complaints. Among the 4 classes, we selectively used data from the “all unimpaired” and “all impaired” groups. Menopause rating scale (MRS), sociodemographic, obstetric, and psychiatric factors were assessed, and hierarchical logistic regression analyses were conducted with the “all impaired” group as a dependent variable. @*Results@#Marital status and scores on the psychological and somatic subscales of the MRS were statistically related to being in the “all impaired” group. Otherwise, family history of menopausal symptoms, menarche age, and history of other psychiatric disorders were not statistically significant predictors of being in the “all impaired” group. @*Conclusion@#The psychological and somatic subscales of the MRS predict the severity of perimenopausal syndrome better than obstetric and psychiatric history do among Korean perimenopausal women. Psychological and somatic symptoms as well as genitourinary symptoms in menopausal patients should be closely evaluated.
ABSTRACT
Purpose@#Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. @*Materials and Methods@#We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. @*Results@#In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. @*Conclusion@#Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.
ABSTRACT
Purpose@#This study aimed to examine the changes in stress, occupational stress, and subjective health problems of novice female nurses within the first 18 months of work. @*Methods@#This was a longitudinal study conducted with a secondary data analysis based on the Shift Work Nurse’s Health and Turnover (SWNHT) study. The participants were 178 female novice nurses who participated in all 3 data collection activities (on the first day of orientation before ward placement [T0], 6 months after work [T1], and 18 months after work [T2]). The stress, occupational stress, 8 subjective health problems (upper musculoskeletal pain, leg/foot discomfort, depression, anxiety or emotional disorder, sleep disturbance, headache, gastrointestinal disorder, menstrual disorder, and others), and the greatest health problem during the study period were measured, respectively. Data were analyzed using SPSS 26.0 to obtain descriptive statistics. @*Results@#The subjective health of novice female nurses were found to be poor at T1 compared to T0 on both physical (upper musculoskeletal pain, leg/foot discomfort, and sleep disturbance) and psychological health problems (depression and stress). However, the psychological health problems of the participants were alleviated at T2 whereas; physical health problems persisted until T2. @*Conclusion@#Novice nurses had poor health problems 6 months after work. Sleep disturbance and musculoskeletal pain persisted although other health problems such as depression and stress were alleviated over the period. Strategies to prevent and manage different health problems of novice female nurses at different work duration are urgently needed.
ABSTRACT
Background@#Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates’ effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications. @*Methods@#Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records. @*Results@#We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44). @*Conclusion@#To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.
ABSTRACT
Purpose@#This study aimed to identify the changes in dietary behavior of shift work nurses and its influencing factors over time. @*Methods@#This was a secondary data analysis study based on the Shift Work Nurses’ Health and Turnover study. Data of 165 shift work nurses, who were followed for three-time points [before shift work (T0), after 6 months (T1), and after 18 months(T2) of shift work], were analyzed. Dietary behavior, level of stress, fatigue, depressive symptoms, and the amount of physical activity were measured. SPSS 28.0 was used to analyze the data to acquire descriptive statistics, repeated-measures ANOVA, and multiple linear regression with generalized estimating equations (GEE). @*Results@#Dietary behavior of shift work nurses was poorer at T1 and T2 as compared to T0. As a result of GEE, shift work duration, level of stress, fatigue, and depressive symptoms were found to have negative impacts on dietary behavior. @*Conclusion@#Dietary behavior deteriorated and remained poor over time since shift work began. Shift work, along with stress, fatigue, and depressive symptoms, were the factors influencing their dietary behavior. Thus, to improve shift work nurses’ dietary behavior, efforts to decrease stress, and alleviate fatigue and depressive symptoms are urgently required.
ABSTRACT
Background@#Smartphone use patterns may predict daily life efficacy and performance improvements in sports. Additionally, personal characteristics may be associated with smartphone overuse. @*Methods@#We investigated the correlation between the temperament and character inventory (TCI) and academic performance using smartphone log data. We hypothesized that the elite and general groups, divided based on academic performance, differed according to the TCI and downloadable smartphone apps (applications). Additionally, we hypothesized a correlation between smartphone app usage patterns and TCI. A total of 151 students provided smartphone log data of the previous four weeks. They also completed the TCI and provided academic records of the previous year. @*Results@#The first and second most frequently used apps by both groups of students were social networking and entertainment, respectively. Elite students scored higher on novelty seeking, reward dependence, persistence, self-directedness, and self-transcendence than general students. In all participants, the usage time of serious apps was correlated with the scores for novelty seeking (r = 0.32, P < 0.007), reward dependence (r = 0.32, P < 0.007), and self-transcendence (r = 0.35, P < 0.006). In the elite group, the usage time of serious apps was correlated with the scores for novelty seeking (r = 0.45, P < 0.001), reward dependence (r = 0.39, P = 0.022), and self-transcendence (r = 0.35, P = 0.031). In the general group, the usage time of serious apps was correlated only with self-transcendence (r = 0.32, P < 0.007). @*Conclusion@#High usage time of serious apps can help sports majors to excel academically. Particularly among sports majors, serious apps are related to activity, the desire for rewards and recognition, and the tendency to transcend themselves.
ABSTRACT
In a 3-year-old Samoyed, aortic bulging was found on radiography during a general check-up. On echocardiography, turbulent flow was found in left ventricular outflow tract (LVOT) with high velocity (6.1 m/s). A linear structure was attached to the interventricular septum and connected to the chordae tendineae reaching the papillary muscle. A part of the structure moved during cardiac cycle, similar to mitral motion. This dog was diagnosed with LVOT obstruction caused by accessory mitral valve tissue (AMVT). This is the first report of AMVT in veterinary medicine. AMVT should be considered as a possible cause of LVOT obstruction in dogs.
ABSTRACT
Background@#Education on internet games for parents and internet game literacy are needed to prevent problematic internet game playing in Korea. We created an 18-item Internet Game Literacy Scale (IGLS). It is a valuable tool for assessing the positive and negative aspects of internet game play. We aimed to determine the validity of the IGLS and the cut-off for the tendency for internet gameplay. @*Methods@#An online research company gathered data from 300 participants. Factor analysis, including Cronbach's α and consistency coefficient, exploratory factor analysis, and confirmatory factor analysis were conducted to verify the 18 items of the IGLS. Additionally, a K-means cluster analysis was performed to determine the cut-off values for positive and negative IGLS scores. @*Results@#The 18 items of the IGLS were proven to be reliable, as evidenced by a high Cronbach's alpha (α = 0.892). The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.903, and Bartlett's test of sphericity was good (χ2 = 1,623.314, P 0.4. In the analysis of the validity of the 18-item IGLS with confirmatory factor analysis (CFA) (maximum likelihood estimation, with an oblique method), the fit indices of the standard three-factor model reached acceptable standards. The cut-off point of the total score between the low positive and average positive groups was 23, and the cut-off point of the total score between the average positive and high positive groups was 30. The cut-off point of the total score between the low negative and the average negative groups was 24. The cut-off point of the total score between the average negative group and the high negative group was 32. @*Conclusion@#The study assessed the reliability and validity of the IGLS and suggested a cut-off for low, average, and high Internet game literacy degree with 300 Korean adults aged 21–49 years. The current results suggest that the IGLS has good internal consistency and a proper cut-off for positive and negative internet game literacy degrees.
ABSTRACT
The Korea National Health and Nutrition Examination Survey (KNHANES) was initiated in 1998 to provide evidence for the development and evaluation of health policies and programs. The Korea Disease Control and Prevention Agency is responsible for the KNHANES and has conducted it as a series of surveys. Over the past 20 years, efforts to produce accurate, timely, and nationwide health statistics have been refined by establishing a continuous annual survey system with full-time field staff, incrementally expanding survey components, collaborating with relevant academic societies for quality control, and revising the survey methods. Additionally, the utility of the collected data was increased by linking the KNHANES data with related data from other government agencies or institutions and making the overall data publicly available on the official website of KNHANES (https://knhanes.kdca.go.kr). Additional long-term plans are being developed, including plans to continue producing nationwide health indicators and invigorating the utilization of the KNHANES data.
ABSTRACT
OBJECTIVES@#This study aimed to examine the trends in health behaviors in Korean population using data from the Korea National Health and Nutrition Examination Survey (KNHANES). @*METHODS@#The subjects were 96,408 adults aged 19 years or older who participated in the first (1998) through seventh (2016-2018) KNHANES health interview. The prevalence of health behaviors (cigarette smoking, alcohol drinking, and physical activity) and annual percent change (APC) were estimated using SAS and the Joinpoint program. @*RESULTS@#The prevalence of current cigarette smoking in men decreased by 2.8%p (APC= -2.8, p< 0.001) annually over the 20-year period, and the prevalence of exposure to secondhand smoke at home substantially decreased compared to 2005 (APC= -8.8, p< 0.001). Compared to 2005, the prevalence of current alcohol drinking in women, but not men, increased (APC= 2.0, p< 0.001), and the prevalence of binge drinking decreased in men (APC= -0.7, p< 0.001) and increased in women (APC= 2.4, p< 0.001). The prevalence of aerobic physical activity decreased from 2014 in both gendersd (p< 0.001). The prevalence of healthy behaviors practice (non-smoking, alcohol abstinence, and aerobic physical activity) was down-trending (APC= -5.3, p< 0.001), especially among women (APC= -6.4, p< 0.001). @*CONCLUSIONS@#Over the past 20 years, smoking behaviors improved. However, drinking behavior was unchanged and physical activity indicators markedly decreased. More active programs are necessary for improving health behaviors, which are major risk factors linked to chronic diseases.
ABSTRACT
In a 3-year-old Samoyed, aortic bulging was found on radiography during a general check-up. On echocardiography, turbulent flow was found in left ventricular outflow tract (LVOT) with high velocity (6.1 m/s). A linear structure was attached to the interventricular septum and connected to the chordae tendineae reaching the papillary muscle. A part of the structure moved during cardiac cycle, similar to mitral motion. This dog was diagnosed with LVOT obstruction caused by accessory mitral valve tissue (AMVT). This is the first report of AMVT in veterinary medicine. AMVT should be considered as a possible cause of LVOT obstruction in dogs.
ABSTRACT
Background@#Education on internet games for parents and internet game literacy are needed to prevent problematic internet game playing in Korea. We created an 18-item Internet Game Literacy Scale (IGLS). It is a valuable tool for assessing the positive and negative aspects of internet game play. We aimed to determine the validity of the IGLS and the cut-off for the tendency for internet gameplay. @*Methods@#An online research company gathered data from 300 participants. Factor analysis, including Cronbach's α and consistency coefficient, exploratory factor analysis, and confirmatory factor analysis were conducted to verify the 18 items of the IGLS. Additionally, a K-means cluster analysis was performed to determine the cut-off values for positive and negative IGLS scores. @*Results@#The 18 items of the IGLS were proven to be reliable, as evidenced by a high Cronbach's alpha (α = 0.892). The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.903, and Bartlett's test of sphericity was good (χ2 = 1,623.314, P 0.4. In the analysis of the validity of the 18-item IGLS with confirmatory factor analysis (CFA) (maximum likelihood estimation, with an oblique method), the fit indices of the standard three-factor model reached acceptable standards. The cut-off point of the total score between the low positive and average positive groups was 23, and the cut-off point of the total score between the average positive and high positive groups was 30. The cut-off point of the total score between the low negative and the average negative groups was 24. The cut-off point of the total score between the average negative group and the high negative group was 32. @*Conclusion@#The study assessed the reliability and validity of the IGLS and suggested a cut-off for low, average, and high Internet game literacy degree with 300 Korean adults aged 21–49 years. The current results suggest that the IGLS has good internal consistency and a proper cut-off for positive and negative internet game literacy degrees.
ABSTRACT
AbstractThe demand for natural substances with anti-melanogenic activity is increasing due to the recent interest in skin whitening. Intensive investigation on the culture broth of Streptomyces sp. SCO-736, a marine bacterium from the Antarctica coast, has led to the isolation of a new natural product named antaroide (1). The chemical structure was established through the interpretation of MS, UV, and NMR spectroscopic data. Antaroide is a nine-membered macrolide with lactone and lactam moieties. To investigate its applicability in skin whitening cosmetics, its anti-melanogenic activity in B16F10 murine melanoma cells was examined. As a result, antaroide displayed strong inhibitory activities against melanin synthesis and also attenuated the dendrite formation induced by the α-melanocyte stimulating hormone (α-MSH). Antaroide suppressed the mRNA expression of the melanogenic enzymes such as tyrosinase, TRP-1 and TRP-2. This suggests that it may serve as a transcriptional regulator of melanogenesis. Collectively, the discovery of this novel natural nine-membered macrolide and its anti-melanogenic activity could give new insights for the development of skin whitening agents.
ABSTRACT
The Korea National Health and Nutrition Examination Survey (KNHANES) was initiated in 1998 to provide evidence for the development and evaluation of health policies and programs. The Korea Disease Control and Prevention Agency is responsible for the KNHANES and has conducted it as a series of surveys. Over the past 20 years, efforts to produce accurate, timely, and nationwide health statistics have been refined by establishing a continuous annual survey system with full-time field staff, incrementally expanding survey components, collaborating with relevant academic societies for quality control, and revising the survey methods. Additionally, the utility of the collected data was increased by linking the KNHANES data with related data from other government agencies or institutions and making the overall data publicly available on the official website of KNHANES (https://knhanes.kdca.go.kr). Additional long-term plans are being developed, including plans to continue producing nationwide health indicators and invigorating the utilization of the KNHANES data.
ABSTRACT
OBJECTIVES@#This study aimed to examine the trends in health behaviors in Korean population using data from the Korea National Health and Nutrition Examination Survey (KNHANES). @*METHODS@#The subjects were 96,408 adults aged 19 years or older who participated in the first (1998) through seventh (2016-2018) KNHANES health interview. The prevalence of health behaviors (cigarette smoking, alcohol drinking, and physical activity) and annual percent change (APC) were estimated using SAS and the Joinpoint program. @*RESULTS@#The prevalence of current cigarette smoking in men decreased by 2.8%p (APC= -2.8, p< 0.001) annually over the 20-year period, and the prevalence of exposure to secondhand smoke at home substantially decreased compared to 2005 (APC= -8.8, p< 0.001). Compared to 2005, the prevalence of current alcohol drinking in women, but not men, increased (APC= 2.0, p< 0.001), and the prevalence of binge drinking decreased in men (APC= -0.7, p< 0.001) and increased in women (APC= 2.4, p< 0.001). The prevalence of aerobic physical activity decreased from 2014 in both gendersd (p< 0.001). The prevalence of healthy behaviors practice (non-smoking, alcohol abstinence, and aerobic physical activity) was down-trending (APC= -5.3, p< 0.001), especially among women (APC= -6.4, p< 0.001). @*CONCLUSIONS@#Over the past 20 years, smoking behaviors improved. However, drinking behavior was unchanged and physical activity indicators markedly decreased. More active programs are necessary for improving health behaviors, which are major risk factors linked to chronic diseases.
ABSTRACT
Objectives@#. Bone-anchored hearing device (BAHD) is contraindicated in patients younger than 5 years because their calvarial bones are not thick enough to be implanted site. However, it has not been studied in the Korean population. This study was not only to establish a safe guideline for depth of implant device in all age groups who undergo BAHD implant surgery, but also to investigate whether implantation of currently used BAHDs could be done safely in Korean children, especially those younger than 5. @*Methods@#. Two hundred eighty patients, who underwent high-resolution temporal bone computed tomography (TBCT) images between August 2010 and October 2018 were randomly enrolled in all ages. We retrospectively reviewed TBCT imaging to measure skull bone thickness at the recommended BAHD implant site. @*Results@#. The average skull bone thickness was 2.87 mm in patients younger than 5 years and 6.72 mm in patients older than 5 years, respectively, which conforms to the current guideline. The results indicate nearly 50% of calvarial bone thicknesses were less than 3 mm in patients under 5 years old, while 92.78% of the patients older than 5 years of age showed bone thickness greater than 4 mm. Of note, calvarial bone thickness was thicker than 3 mm in all patients who are older than 6 years. @*Conclusion@#. This study confirms that the currently approved BAHD implantation guideline is suitable in the Korean population. For safety, we suggest taking TBCTs prior to surgery, especially in pediatric patients. Besides, noninvasive applications are recommended for patients younger than 5.
ABSTRACT
PURPOSE: Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1. MATERIALS AND METHODS: We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines. RESULTS: We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor. CONCLUSION: Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Catalytic Domain , Cell Line , Cell Proliferation , In Vitro Techniques , Parents , Phosphotransferases , Polymerase Chain Reaction , Protein-Tyrosine Kinases , ErbB Receptors , RNA, MessengerABSTRACT
PURPOSE: The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer. MATERIALS AND METHODS: We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed. RESULTS: PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163). CONCLUSION: PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.