Real-world outcome of crizotinib for anaplastic lymphoma kinase-positive lung cancer: Multicenter retrospective analysis in South Korea.

BACKGROUND: About 3%-5% of non-small cell lung cancer (NSCLC) presents positive anaplastic lymphoma kinase (ALK). Recently, several target agents have been approved as a treatment for ALK-positive NSCLC. This study aimed to analyze the real-world efficacy and outcome when administered crizotinib, the first approved target agent for ALK-positive NSCLC, according to first- or late-line treatment. METHODS: A total of 290 patients with ALK-positive advanced NSCLC who were treated with crizotinib in 15 institutions in South Korea from January 2009 to December 2018 were enrolled. RESULTS: The median age of patients was 57.0 years, and 50.3% were male. The median follow-up duration was 29.3 months. Among them, 113 patients received crizotinib as first-line therapy. The objective response rate (ORR) was 60.1% (57.0% for first-line recipients, 61.8% for second-/later-line). Median (95% CI) progression-free survival (PFS) was 13.7 (11.6-17.0) months. For first-line recipients, overall survival (OS) was 26.3 (17.6-35.0) months. No significant difference in ORR, PFS and OS, according to the setting of crizotinib initiation, was observed. In a multivariate Cox regression analysis, old age, male gender, initially metastatic, and number of metastatic organs were associated with poor PFS and OS. The most common adverse events were nausea and vomiting, and severe adverse event leading to dose adjustment was hepatotoxicity. CONCLUSIONS: ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials. Our findings could aid in the efficient management of ALK-positive lung cancer patients.

Association between ergonomic risk exposures and insomnia symptoms: a mediation analysis of the 5th Korean working conditions survey.

BACKGROUND: This study investigates the relationship between ergonomic risk exposures and insomnia symptoms, using data representative of Korea's general working population. METHODS: Data from the 5th Korean Working Conditions Survey were used for this study. The eligible population (employees) for the current study was 37,026. Insomnia symptoms were estimated using the minimal insomnia symptom scale (MISS) questionnaire. Logistic regression analysis was conducted to explore the association between ergonomic risks and insomnia symptoms. RESULTS: All the investigated ergonomic risks increased odd ratios (ORs) for insomnia symptoms: Tiring or painful positions (OR, 1.64; 95% CI, 1.43-1.88); lifting or moving heavy loads (OR, 2.33; 95% CI, 1.99-2.71); long periods of standing (OR, 1.47; 95% CI, 1.29-1.69); and repetitive hand or arm movements (OR, 1.46; 95% CI, 1.29-1.67). The mediated proportion of musculoskeletal pain was 7.4% (95% CI, 5.81-10.13), and the mediated proportion of feeling of exhaustion was 17.5% (95% CI, 5.81-10.13). CONCLUSIONS: This study provides evidence for the relationship between ergonomic risks and insomnia symptoms, for which musculoskeletal pains and the feeling of exhaustion may be potential mediators.

Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

BACKGROUND: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

Association between social jetlag and self-rated health: Evidence from Korean representative working population.

BACKGROUND: Social jetlag is a circadian misalignment that arises from a discrepancy between activity/sleep schedules on school/work days and free days. This study explored the correlation between social jetlag and self-rated health (SRH) in a representative sample of Korea. METHODS: This study included 8259 working population in the Korea National Health and Nutrition Examination Survey, 2016-2018. Social jetlag was calculated as the difference between the midpoint of sleep time on work day and work-free day. Five-point Likert scale of SRH was used to assess subjective health perception on general health conditions. Multiple logistic regression analysis was performed to calculate the odds ratios (ORs) and 95 % confidence interval (CI) for poor SRH in the 1-2 h or longer than 2 h social jetlag groups compared to that in the reference group (less than 1 h), after adjusting for age, sex, marital status, occupation, household income, and weekly working hours. RESULTS: The proportions of those with <1 h, 1-2 h, >2 h of social jetlag were 63.80 %, 25.67 %, and 10.53 %, respectively. The risk of poor SRH increased as social jetlag increased. Greater social jetlag was significantly associated with an increased likelihood of reporting poor SRH. The adjusted ORs for the groups with social jetlag between 1 and <2 h, and >2 h were 1.100 (95 % CI = 0.935-1.295), and 1.503 (95 % CI = 1.097-1.727), respectively. Moreover, the OR trend was statistically significant (p for trend = 0.008). CONCLUSION: This study found that social jetlag and poor SRH were significantly related in the Korean working population.

Real-world first-line afatinib for advanced EGFR mutation-positive non-small cell lung cancer in Korea: updated survival data.

Background: Data from clinical trials and real-world studies show that afatinib is effective in treating non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) gene. A previous analysis of patients enrolled in the Korean Academy of Tuberculosis and Respiratory Disease (KATRD) EGFR cohort showed that first-line afatinib was well tolerated and effectiveness results were encouraging. At the time of the previous analysis, survival data were not mature. Here we briefly present updated survival data from the cohort. Methods: The study was a retrospective, multicenter (15 sites) review of electronic records of Korean adult patients (aged >20 years) with advanced EGFR mutation-positive NSCLC who initiated first-line afatinib (N=421). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves. Results: Overall, median PFS was 20.2 months and median OS was 48.6 months. OS rates at 36 and 60 months were 60.1% and 42.3%, respectively. Presence vs. absence of baseline brain metastases was associated with significantly reduced median PFS (14.9 vs. 28.0 months; P<0.001) and median OS (32.2 vs. 65.6 months; P<0.001). The presence of common baseline EGFR mutations (Del19, L858R) was associated with significantly prolonged median OS (49.6 vs. 30.1 months; P=0.017). In patients stratified by the presence/absence of T790M EGFR mutation, the T790M mutation was associated with significantly reduced median PFS (P=0.0005) but there was no significant difference between groups in survival (P=0.263). There were no significant differences in PFS or OS for patients stratified by afatinib dose reduction or by age group (<70 vs. ≥70 years). Conclusions: Afatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years. The presence of baseline brain metastases and/or uncommon EGFR mutations were associated with reduced survival. In the absence of baseline brain metastases, median OS was more than 5 years.

Working hours and the regulations for night shift workers.

There are several types of shift work in Korea: rotating shift, 24-hour shift, day-night shift, fixed night work, and.so on. As a result of analyzing the 8th Korea National Health and Nutrition Examination Survey and the 6th Korean Working Condition Survey, Korean shift workers accounted for 11.6%-13.9% of wage workers. Weekly working hours of shift workers were 57.69 ± 1.73 (24-hours shift) and 49.97 ± 0.67 (fixed night shift), which were significantly longer than day workers. To prevent health consequences of night work, many countries regulate the working hours of night work not to exceed 7-9 hours a day. However, Korea does not regulate working hours for night work, and some occupations may work more hours than the prescribed overtime hours. To prevent health consequences and reduce working hours for Korean night shift workers, it is necessary to regulate the working hours of night shift workers by law.

Risk adjustment model for tuberculosis compared to non-tuberculosis mycobacterium or latent tuberculosis infection: Center for Personalized Precision Medicine of Tuberculosis (cPMTb) cohort database.

BACKGROUND: The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. METHODS: Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. RESULTS: Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. CONCLUSIONS: Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. TRIAL REGISTRATION: This study registered ClinicalTrials.gov NO. NCT05280886.

Development of algorithm for work intensity evaluation using excess overwork index of construction workers with real-time heart rate measurement device.

Background: The construction workers are vulnerable to fatigue due to high physical workload. This study aimed to investigate the relationship between overwork and heart rate in construction workers and propose a scheme to prevent overwork in advance. Methods: We measured the heart rates of construction workers at a construction site of a residential and commercial complex in Seoul from August to October 2021 and develop an index that monitors overwork in real-time. A total of 66 Korean workers participated in the study, wearing real-time heart rate monitoring equipment. The relative heart rate (RHR) was calculated using the minimum and maximum heart rates, and the maximum acceptable working time (MAWT) was estimated using RHR to calculate the workload. The overwork index (OI) was defined as the cumulative workload evaluated with the MAWT. An appropriate scenario line (PSL) was set as an index that can be compared to the OI to evaluate the degree of overwork in real-time. The excess overwork index (EOI) was evaluated in real-time during work performance using the difference between the OI and the PSL. The EOI value was used to perform receiver operating characteristic (ROC) curve analysis to find the optimal cut-off value for classification of overwork state. Results: Of the 60 participants analyzed, 28 (46.7%) were classified as the overwork group based on their RHR. ROC curve analysis showed that the EOI was a good predictor of overwork, with an area under the curve of 0.824. The optimal cut-off values ranged from 21.8% to 24.0% depending on the method used to determine the cut-off point. Conclusion: The EOI showed promising results as a predictive tool to assess overwork in real-time using heart rate monitoring and calculation through MAWT. Further research is needed to assess physical workload accurately and determine cut-off values across industries.

Real-world analysis of first-line afatinib in patients with EGFR-mutant non-small cell lung cancer and brain metastasis: survival and prognostic factors.

Background: Overall survival (OS) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs) is poor. We aimed to identify prognostic factors and ascertain treatment outcomes of first-line afatinib for patients with epidermal growth factor receptor (EGFR)-mutant NSCLC with BM in a real-world setting. Methods: This retrospective observational study reviewed electronic records of patients with EGFR-mutant NSCLC who received first-line afatinib treatment between October 2014 and October 2019 in 16 hospitals across South Korea. The Kaplan-Meier method estimated time on treatment (TOT) and OS; multivariate analyses were performed using Cox proportional hazards (PH) models. Results: Among 703 patients who received first-line afatinib, 262 (37.3%) had baseline BM. Of 441 patients without baseline BM, 92 (20.9%) developed central nervous system (CNS) failure. Compared with patients without CNS failure, those with CNS failure during afatinib treatment were younger (P=0.012), had a higher Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P<0.001), increased metastatic site involvement (P<0.001), advanced stage disease (P<0.001), with liver metastasis (P=0.008) and/or bone metastasis (P<0.001) at baseline. Cumulative incidence of CNS failure in years 1, 2 and 3 was 10.1%, 21.5% and 30.0%, respectively. In multivariate analysis, cumulative incidence was significantly higher in patients with ECOG PS ≥2 (P<0.001), uncommon EGFR mutations (P=0.001), and no baseline pleural metastasis (P=0.017). Median TOT was 16.0 months (95% CI: 14.8-17.2) and, in patients with CNS failure, without CNS failure, and with baseline BM was 12.2, 18.9, and 14.1 months, respectively (P<0.001). Median OS was 52.9 months (95% CI: 45.4-60.3) and, in patients with CNS failure, without CNS failure, and with baseline BM was 29.1, 67.3 and 48.5 months, respectively (P<0.001). Conclusions: First-line afatinib in the real-world setting showed clinically meaningful effectiveness in patients with EGFR-mutant NSCLC and BM. CNS failure was a poor prognostic factor for TOT and OS correlating with younger age, poor ECOG PS, higher metastatic number, advanced disease stage, uncommon EGFR mutations, and baseline liver and/or bone metastases.

Recommendation of pharmacokinetics/pharmacodynamics target of ethambutol to suppress tuberculosis resistance: A population pharmacokinetics study on a large prospective cohort.

BACKGROUND: The ability of ethambutol (EMB) to suppress bacterial resistance has been demonstrated in a time-dependent manner. Through the development of a population pharmacokinetics (PK) model, this study aimed to suggest the PK/pharmacodynamics (PD) target and identify the significant covariates that influence interindividual variability (IIV) in the PK of EMB. METHODS: In total, 837 patients from 20 medical centres across Korea were enrolled in this study. The non-linear mixed-effect method was used to establish and validate the population PK model. RESULTS: A two-compartment model with transit compartment absorption was sufficient to describe the PK of EMB. Body weight and renal function were identified as significant covariates that affect IIV of the apparent clearance (CL/F) of EMB. Patients with moderate renal function showed 35% and 55% lower CL/F (CL/F 89.9 L/h) compared with those with mild and normal renal function, respectively. All the renal function groups with simulated doses ranging from 800 to 1200 mg achieved area under the curve over minimum inhibitory concentration (MIC) >119, and maintained T>MIC for >23 h for MIC of 0.5 µg/mL. Based on our simulation result, it is suggested that doses of 800, 1000, and 1200 mg should obtain the T>MIC target of 4, 6, and 8 h, respectively. This model was validated internally and externally. CONCLUSION: This study provides insight into the PK/PD indexes of EMB for three different renal function groups and T>MIC targets for different doses. The results could be used to provide optimal-dose suggestions for EMB.

Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non-Small Cell Lung Cancer: Updated Analysis of the RESET Study.

PURPOSE: This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non-small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). MATERIALS AND METHODS: In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. RESULTS: The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). CONCLUSION: This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Social jetlag and risk of depression: Results from the Korea National Health and Nutrition Examination Survey.

BACKGROUND: Social jetlag, which is the mismatch between endogenous rhythm and social timing, is prevalent among the working population. Social jetlag may result in mood changes; however, evidence of relationship between social jetlag and depressive disorders has not been fully verified. Hence, this study aimed to investigate the association between social jetlag and depressive symptoms in a representative working population of South Korea. METHODS: This study included 5447 Korean employees in the Korea National Health and Nutrition Examination Survey. Social jetlag was calculated as the difference between the midpoint of sleep time on weekdays and free days. Depressive symptoms were assessed using Patient Health Questionnaire-9. Multiple logistic regression was used to estimate the odds ratio after adjusting for confounding factors. Moreover, social jetlag and continuous depression scores were evaluated using linear regression and generalized additive models. RESULTS: The proportion of the participants who had >2 h of social jetlag was 10.26 %. Depressive symptoms increased as social jetlag increased. Multiple logistic regression analysis showed that the adjusted OR (95 % confidence interval) for 1 to 2 h of social jetlag was 1.355 (0.891-2.059) and for >2 h was 1.859 (1.084-3.187), which <1 h was reference. LIMITATIONS: This study used a cross-sectional design and measurements were based on self-reported scales. CONCLUSION: This study found that social jetlag and depressive symptoms were significantly related in the Korean working population.

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation-Positive Non-Small Cell Lung Cancer.

PURPOSE: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation-positive non-small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. MATERIALS AND METHODS: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. RESULTS: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. CONCLUSION: Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation-positive in Korean patients with no new safety signals.

Association between sleep quality and type of shift work in Korean firefighters.

Background: Shift work that interferes with normal sleep patterns, is known to be a cause of sleep disturbance and has been studied through various occupational groups. However, it is not known which shift type is better for sleep health. Methods: This study included 568 firefighters. Sleep quality was evaluated using Pittsburgh Sleep Quality Index. Sleep quality was categorized into 2 groups; good quality (≤ 5 points) and poor quality (≥ 6 points). Demographic variables, depression, anxiety, type of shift, and job were collected by self-reported questionnaires. The χ2 test, t-test, and multiple logistic regression analysis were used to evaluate the effect of shift type on the sleep quality of firefighters. Results: Three hundred thirty-seven firefighters (59.3%) have poor sleep quality. Compared to day workers, the odds ratios (ORs) of poor sleep quality were 2.169 (95% confidence interval: 1.137-4.134) in 6-day cycle, 2.161 (1.150-4.062) in 9-day cycle, 1.805 (1.087-2.997) in 21-day cycle, and 1.485 (0.718-3.069) in 3-day cycle. The ORs of poor sleep quality were 1.697(1.021-2.823) in fire suppression and 2.325 (1.213-4.455) in emergency medical service compared to administration. Conclusions: All shift work type except for the 3-day cycle was associated with poor sleep quality compared to day work.

Anti­inflammatory effects of Nypa fruticans Wurmb via NF­κB and MAPK signaling pathways in macrophages.

The inflammatory defense response of macrophages is a natural protective reaction in the immune system. Antioxidant and anti-inflammatory activities are closely related. In addition, the cell signaling pathway regulating inflammation is associated with MAPK and NF-κB signaling pathway phosphorylation. The present study aimed to evaluate whether the ethyl acetate fraction from N. fruticans (ENF) has a modulatory role in the MAPK signaling pathway and inhibition of the IκB/NF-κB signaling pathways, including translocation of NF-κB p65. Antioxidant and anti-inflammatory activities are closely related. In addition, the cell signaling pathway regulating inflammation is associated with MAPK and NF-κB signaling pathway phosphorylation. The results revealed that ENF exhibited antioxidant capacity, attenuated the cytokine levels and blocked nitric oxide production. ENF downregulated cyclooxygenase-2 and inducible nitric oxide synthase expression. We hypothesized that ENF treatment alleviated the various proinflammatory mediators via IκB phosphorylation and transcription of NF-κB compared with the untreated control. In conclusion, the present study demonstrated that the inhibitory effect of ENF treatment was attributed to the inhibition of MAPK and Akt/IκB/NF-κB signaling pathways.

Nypa fruticans Wurmb inhibits melanogenesis in isobutylmethylxanthine­treated melanoma via the PI3K/AKT/mTOR/CREB and MAPK signaling pathways.

Malignant melanoma is responsible for 3.0 and 1.7% of cases of tumor incidence and tumor-associated mortality, respectively, in the Caucasian population. Melanoma is a type of skin cancer that occurs when melanocytes mutate and divide uncontrollably. Nypa fruticans Wurmb (NF) is abundant in phytochemicals (polyphenols and flavonoids) and is traditionally used to treat diseases of the respiratory tract. The present study investigated the inhibitory effect of the ethyl acetate fraction of NF (ENF) on melanogenesis-related factors in isobutylmethylxanthine-treated B16F10 melanoma cells. Phenolics and flavonoids (caffeic acid, catechin, epicatechin and hirsutine) in ENF were analyzed via liquid chromatography-mass spectrometry. In addition, the main factors involved in melanogenesis were identified using immunoblotting, reverse transcription-polymerase chain reaction (RT-PCR), RT-quantitative PCR and immunofluorescence. ENF significantly suppressed the expression of tyrosinase (TYR) and TYR-related proteins 1 and 2 (TYRP-1/2), which are the main factors involved in melanogenesis. ENF also inhibited the expression of microphthalmia-associated transcription factor (MITF) by phosphorylating the related cell signaling proteins (protein kinase B, mammalian target of rapamycin, phosphoinositide 3-kinase and cAMP response element-binding protein). Furthermore, ENF inhibited the phosphorylation of extracellular signal-regulated kinase and thereby downregulated melanogenesis. In conclusion, ENF inhibited melanogenesis by suppressing MITF, which controls TYRP-1/2 and TYR. These results suggested that ENF may be a natural resource that can inhibit excessive melanin expression by regulating various melanogenesis pathways.

Beneficial role of Boehmeria nivea in health and phytochemical constituents.

The leaf and stem extracts of Boehmeria nivea (BN) collected from three different regions in Korea were screened for their antioxidant, neuroprotective, estrogenic, insulin secretion, and α-glucosidase inhibitory activity. We also examined whether BN extracts regulate cancer cell growth, inflammatory-related gene expression, and lipid accumulation in cellular system. Leaf extracts possessed greater antioxidant, anti-proliferative in cancer cells, neuroprotective, estrogenic activity, and inhibitory effect on pro-inflammatory gene expression than stem extracts. Leaf and stem extracts inhibited lipid accumulation in three T3-L1 adipocytes but did not affect glucose-stimulated insulin secretion in INS-1 cells. We isolated and identified the phytochemical constituents in the n-butanol and ethyl acetate fractions of BN leaves by combining silica gel column chromatography with mass spectrometry and 1 H- and 13 C-NMR analysis. The active compounds (caffeic acid, isoquercitrin, p-coumaric acid, and rutin) exhibited ABTS and DPPH radical scavenging activity, which may contribute to the biological activities of BN leaf extract. An analytical method was developed to quantify marker compounds for the discrimination of BN collected from different regions. Our results support the use of this analysis method for accurate identification and quantification of marker compounds in BN for the development of functional foods. PRACTICAL APPLICATIONS: Boehmeria nivea (BN) has been used as a raw material for the textile industry or traditional herbal medicine. The current study established the biological activities and active components of BN. Our results showed that BN leaf and stem extracts exhibit antioxidant, neuroprotective, and estrogenic activity. BN leaf extract also inhibited cancer cell growth, inflammatory mediators and cytokines production, and lipid accumulation in vitro. Moreover, the bioactive compounds, such as caffeic acid, isoquercitrin, p-coumaric acid, and rutin, exert ABTS and DPPH radical scavenging activities. Therefore, BN could potentially be a promising source of bioactive phytochemicals for the development of functional foods or drugs.

A phase II, multicenter study of lazertinib as consolidation therapy in patients with locally advanced, unresectable, EGFR mutation-positive non-small cell lung cancer (stage III) who have not progressed following definitive, platinum-based, chemoradiation therapy (PLATINUM trial).

INTRODUCTION: The PACIFIC study demonstrated that durvalumab consolidation therapy significantly improved progression-free survival (PFS) and overall survival (OS) in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). However, there was no clinical benefit in both PFS and OS in epidermal growth factor receptor (EGFR) mutation-positive patient groups in a post hoc exploratory analysis. Moreover, the clinical effects of immune checkpoint inhibitors (ICIs) in EGFR mutation-positive stage IV NSCLC were demonstrated to be poor. Personalized treatment according to the mutation status is also required in stage III NSCLC. Lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is newly developed and approved for use in Korea. METHODS: This prospective, open, single-arm, multicenter, phase II clinical trial aims to evaluate the efficacy and safety of lazertinib as a consolidative therapy after CCRT treatment in unresectable, EGFR mutation-positive NSCLC stage III patients. The primary endpoint of this study is PFS, and the secondary endpoints are OS, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety profiles. DISCUSSION: Our study may extend the indications for third-generation EGFR-TKIs to treat patients with stage III NSCLC. Moreover, using this drug to treat stage III NSCLC would emphasize the value of mutation analysis and personalized medicine.