We demonstrated that in vitro drug responses in patient-derived organoids (PDOs) are correlated to clinical responses to targeted therapies in individual patients with advanced lung adenocarcinoma and PDOs can be used to identify effective anti-cancer therapies for novel molecular targets. PDOs recapitulated progression-free survival and objective responses of NSCLC patients receiving clinically approved targeted agents. PDOs also predicted activity of therapeutic strategies under clinical investigation. YUO-071 harboring an EGFR exon 19 deletion and a BRAF G464A mutation and the matching patient responded to dabrafenib/trametinib combination therapy. YUO-004 and YUO-050 harboring an EGFR L747P mutation was sensitive to afatinib, consistent with the response in the matching patient of YUO-050. Furthermore, we utilized organoids to demonstrate preclinical efficacy of poziotinib against ERBB2 exon 20 insertions and pralsetinib against RET-fusions. Our findings suggest utility of PDOs in clinical decision making and development of therapeutic strategies.

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The aim of this study was to provide descriptive information on meal and snack patterns and to investigate snacks in relation to energy intake and food choice according to the meal patterns of employed people in Korea. 683 employed people (292 males, 391 females) were interviewed to collect one day dietary data by using 24-h dietary recall. A recorded day was divided into 3 meal and 3 snack periods by the respondent's criteria and the time of consumption. To analyze the eating pattern participants were divided as the more frequent snack eaters (MFSE) and the less frequent snack eaters (LFSE). They were also categorized into 6 groups according to the frequency of all eating occasions. The common meal pattern in nearly half of the subjects (47.6%) was composed of three meals plus one or two snacks per day. A trend of an increasing the number of snacks in between main meals emerges, although the conventional meal pattern is still retained in most employed Korean adults. Women, aged 30-39, and urban residents, had a higher number of being MFSE than LFSE. Increasing eating occasions was associated with higher energy, protein, and carbohydrate intakes, with the exception of fat intakes. 16.8% of the total daily energy intake came from snack consumption, while the 3 main meals contributed 83.2%. Energy and macronutrient intakes from snacks in the MFSE were significantly higher than the LFSE. Instant coffee was the most popular snack in the morning and afternoon, whereas heavy snacks and alcohol were more frequently consumed by both of the meal skipper groups (≤2M+2,3S and ≤2M+0,1S) in the evening. In conclusion, meal pattern is changing to reflect an increase of more snacks between the three main meals. Meal and snack patterns may be markers for the energy and macronutrient intakes of employed people in Korea.

The purpose of this study was to compare the beverage consumption by gender and season in elementary school children and to investigate the role of beverage consumption patterns on their daily nutrient intakes and BMIs. Beverage consumption and dietary energy intake in 160 elementary school students in the Gyeongnam area were measured by a beverage frequency and quantity questionnaire and three 24-hour dietary recalls during winter and summer. The number of drinking moments per month, the amounts of beverage per day, and the energy from beverage consumption were not different between winter and summer. In summer, the contribution of energy from sweetened beverage to the daily energy intake in girls accounted for 13.5% which was significantly higher compared to 7.7% in boys. In girls, the consumption of health beverage showed a significant correlation with various nutrient intakes in winter. Meanwhile, the sweetened beverage intake was negatively correlated with energy, protein, vitamin A and niacin intake in summer. Consumption of most of the beverages, including sweetened beverages, were not related with BMI in both sexes and both seasons, except functional drinks which were related with BMI in boys in winter.

This study aimed to improve the production of phycobiliproteins using TiO nanoparticles (NPs) in Synechocystis sp. PCC 6803. The growth characteristics of Synechocystis cells were not affected by TiO NPs treatment, but this treatment increased the chlorophyll content significantly by 62.2% (14.6 mg/L) compared to that of control (9.0 mg/L) on day 16. Phycocyanin production was increased by 33.8% (29.3 g/L) compared to that of control (21.9 g/L) on day 8. Allophycocyanin production was increased by 55.0% (6.2 g/L) compared to that of control (4.0 g/L) on day 8, and by 22.4% (16.4 g/L) compared to that of control (13.4 g/L) on day 16. Direct infusion mass spectrometry revealed that TiO NPs treatment significantly increased the levels of major thylakoid membranes of monogalactosyldiacylglycerols (18:2/18:3, 18:2/18:2, 18:1/18:2), phosphatidylglycerol (16:0/16:1), and sulfoquinovosyldiacylglycerols (16:0/16:1, 16:0:18:4) on day 8. These findings indicate that TiO NPs have potential for commercial applications in Synechocystis species or other microalgal strains.

− Ginseng (Panax ginseng) is recognized as one of the most valuable medicinal herbs in Asia and it contains diverse phytochemicals that contribute to its pharmacological effects. Although lipids represent a major component of ginseng, ginseng lipids are still far from being fully explored. This review is focused on ginseng lipid components and methodologies of their analysis. The ginseng lipid compounds were categorized according to the structural features of each lipid class. This basic information on ginseng lipid components and the analysis methods will be applicable to authentification or quality control of ginseng products, and development of lipidbased pharmaceuticals and nutraceuticals from ginseng.

Rice (Oryza sativa L.) is a widely consumed food source, and its geographical origin has long been a subject of discussion. In our study, we collected 44 and 20 rice samples from different regions of the Republic of Korea and China, respectively, of which 35 and 29 samples were of white and brown rice, respectively. These samples were analyzed using nuclear magnetic resonance (NMR) spectroscopy, followed by analyses with various data normalization and scaling methods. Then, leave-one-out cross-validation (LOOCV) and external validation were employed to evaluate various machine learning algorithms. Total area normalization, with unit variance and Pareto scaling for white and brown rice samples, respectively, was determined as the best pre-processing method in orthogonal partial least squares–discriminant analysis. Among the various tested algorithms, support vector machine (SVM) was the best algorithm for predicting the geographical origin of white and brown rice, with an accuracy of 0.99 and 0.96, respectively. In external validation, the SVM-based prediction model for white and brown rice showed good performance, with an accuracy of 1.0. The results of this study suggest the potential application of machine learning techniques based on NMR data for the differentiation and prediction of diverse geographical origins of white and brown rice.

PURPOSE: Although EGFR exon20 insertion (ex20ins) mutations account for 4~12 % of EGFR mutant NSCLC patients, there is no effective and selectable anticancer drugs targeting ex20ins mutations so far due to various variant mutations in ex20ins mutations. Moreover, most EGFR ex20ins mutants show primary resistance to EGFR TKIs. JNJ-61186372 (JNJ-372), a bispecific antibody that targets the EGFR and cMet receptors, is currently being explored in a first-in-human study in patients with NSCLC. To better understand the mechanism of JNJ-372 activity in this patient population, we conducted preclinical studies exploring the activity of JNJ-372 in different EGFR ex20ins models. METHODS: To elucidate whether JNJ-372 has antitumor effect in EGFR ex20ins mutants via EGFR and c-MET inhibition, cell viability, western blot, cell cycle, colony formation assay, FACS analysis were performed in JNJ-372 treated BaF3 cells, PDCs, PDOs, and PDX expressing EGFR ex20ins mutation. For mouse tumor models, JNJ-372 was administered i.p. twice a week at 10 mg/kg or 30 mg/kg. Antibody dependent cellular cytotoxicity (ADCC) assay was assessed to figure out whether JNJ-372 had ADCC effects. Referenced patients with ex20ins disease were administered 1050 mg JNJ-372 i.v. weekly for the first 4-week cycle, then biweekly for each subsequent cycle RESULTS: JNJ-372 inhibited the growth of BaF3 cells, PDCs, and a PDO harboring a range of ex20ins, which were resistant to osimertinib and gefitinib. Mechanistic assays revealed the reduction of EGFR and cMet receptor levels and decreases in phospho-EGFR and c-Met, as well as inhibition of their downstream signaling pathways. Cleaved caspase-3 and BIMEL were upregulated at anti-proliferative doses, suggesting caspase-mediated cell death. JNJ-372 demonstrated corresponding antitumor activity in PDC and PDX models harboring different ex20ins; inhibition of signaling and engagement of the apoptotic pathway was confirmed in tumors of JNJ-372-treated mice. In PDCs with EGFR ex20ins mutation, we verified that JNJ-372 had a significant ADCC effect compared to EGFR antibody drug cetuximab. In the first-in-human trial, CT scans from two patients treated with JNJ-372 revealed reductions in tumor burden. A 58-year patient harboring H773delinsNPY showed -63% tumor reduction with progression-free survival of > 20 months and a 48-year patient harboring S768_D770dup showed -38.9% tumor reduction. CONCLUSION: JNJ-372 drives antitumor activity in preclinical models of EGFR ex20ins, which have no therapeutic options in clinic, by decreasing EGFR and cMet receptor levels, inhibiting downstream signaling cascades, activating apoptotic signaling as well as ADCC. These results provide a promising therapeutic option to patients with EGFR ex20ins mutations and an understanding of the activity of JNJ-372 being observed in the first-in-human study. Citation Format: Jiyeon Yun, Han Na Kang, Soo-Hwan Lee, Seo-Yoon Jeong, Chae Won Park, Jae-Hwan Kim, Kyoung-Ho Pyo, Ji Min Lee, Seok-Young Kim, Min Hee Hong, Hye Ryun Kim, Meena Thayu, Joshua Curtin, Roland Knoblauch, Matthew Lorenzi, Byoung Chul Cho. JNJ-61186372, an EGFR-cMet bispecific antibody, in EGFR Exon 20 insertion-driven advanced non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5199.