Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd-nivolumab and nivolumab-T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions: T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.
Bakhovuddin Azamov;Yeowon Kang;Chanhee Lee;Wan-Seog Shim;Kwang Min Lee;Parkyong Song
Journal of Life Science
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v.34
no.4
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pp.227-235
/
2024
Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.
Hye Kyung Choi;Eun Jeong Jo;Jee Eun Heo;Hyun Gi Kong;Seon-Woo Lee
Research in Plant Disease
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v.30
no.2
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pp.148-156
/
2024
Ralstonia pseudosolanacearum, a plant pathogenic bacterium that can survive for a long time in soil and water, causes lethal wilt in the Solanaceae family. Sigma S is a part of the RNA polymerase complex, which regulates gene expression during bacterial stress response or stationary phase. In this study, we investigated the role of sigma S in R. pseudosolanacearum under stress conditions using a rpoS-defective mutant strain of R. pseudosolanacearum and its wild-type strain. The phenotypes of rpoS-defective mutant were complemented by introducing the original rpoS gene. There were no differences observed in bacterial growth rate and exopolysaccharide production between the wild-type strain and the rpoS mutant. However, the wild-type strain responded more sensitively to nutrient deficiency compared to the mutant strain. Under the nutrient deficiency, the rpoS mutant maintained a high bacterial viability for a longer period, while the viability of the wild-type strain declined rapidly. Furthermore, a significant difference in pH was observed between the culture supernatant of the wild-type strain and the mutant strain. The pH of the culture supernatant for the wild-type strain decreased rapidly during bacterial growth, leading to medium acidification. The rapid decline in the wild-type strain's viability may be associated with medium acidification and bacterial sensitivity to acidity during transition to the stationary phase. Interestingly, the rpoS mutant strain cannot utilize acetic acid, D-alanine, D-trehalose, and L-histidine. These results suggest that sigma S of R. pseudosolanacearum regulates the production or utilization of organic acids and controls cell death during stationary phase under nutrient deficiency.
Young Min Ko;Geun-Hye Gang;Dae Ho Jung;Youn-Sig Kwak
Research in Plant Disease
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v.30
no.2
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pp.165-175
/
2024
The Korean fir tree (Abies koreana), an endemic species of South Korea, is experiencing a severe decline in population due to climate change. Studies on the conservation of Korean fir have been extensive, yet research regarding its correlation with rhizosphere bacterial communities remains scarce, warranting further investigation. In this study, metagenome amplicon sequencing targeting the 16S rRNA V4 region was conducted to examine the presence of specific bacterial communities in Korean fir and to investigate potential differences based on habitat types (rhizosphere of native or cultivated trees, soil of dead trees, and bulk soil) and seasonal variations (April, June, September, November). Here we show that although we could not identify specific taxa highly specifically with Korean fir, the rhizosphere bacterial community in native trees exhibited less variability in response to seasonal changes compared to that in bulk soils. Suggesting the establishment of relatively stable bacterial populations around the Korean fir natural habitat. Further research on other types of rhizosphere and/or microbes is necessary to investigate the distinct relationship of Korean fir with microbial communities.
Frailty is a clinical syndrome as an increased vulnerability to stressors, leading to a decrease in physiologic reserves and a decline in the ability to maintain a good homeostasis. This condition leads to an increased risk of hospitalization, disability and mortality. Frailty occurs due to various causes and requires a multidimensional approach. It is also important to detect and manage it early. Frailty is also deeply related to neuropsychiatric problems such as pain and depression. In evaluating frailty, it is desirable to comprehensively consider not only physical areas such as disease, nutrition, movement, and sensory functions, but also psychosocial areas, and representative scales include Fried's physical frailty phenotype and Rockwood's frailty index. Physical activity and appropriate protein intake are important for frailty management, and inappropriate drug use should be reduced and oral care, cognitive function, and falls should also be noted. Frailty and pain can affect each other, and pain can promote frailty. Evidence has been published that hormone and protein abnormalities, immune system activity and inflammatory response, and epigenetic mechanisms work in common in the field of frailty and pain. More extensive and high-quality research should be conducted in the future, and the quality of life will be improved if the results are applied to the suppression and treatment of old age and pain.
Objectives: The pulp is the center of the tooth containing nerves and blood vessels. The condition in which the pulp becomes inflamed due to caries or periodontitis is called pulpitis. Pulpitis is a difficult-to-treat disease and causes peripheral nerve tissue changes and severe pain; however, the relationship between neuronal activity and voltage-gated sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG) during pulpitis has not been well studied. In this study, we found that experimentally induced pulpitis activates Nav1.7 expression in the periphery, leading to neuronal overexpression in the TG. Thus, we sought to identify ways to regulate this process. Methods: Acute pulpitis was induced in rat maxillary molars by treating the pulp with allyl isothiocyanate (AITC). Three days later, in vivo optical imaging was used to record and compare neural activities in the TG. Western blotting was used to identify molecular changes in terms of the expression of extracellular signal-regulated kinase (ERK), c-Fos, transient receptor potential ankyrin 1 (TRPA1), and collapsin response mediator protein-2 (CRMP2) in the brain stem. Results: The results confirmed the neurological changes in the TGs of the pulpitis model, and histological and molecular biological evidence confirmed that increased Nav1.7 expression induced by pulpitis leads to pain. Furthermore, selective inhibition of Nav1.7 resulted in changes in neural activity, suggesting that pulpitis induces increased Nav1.7 expression, and that effective control of Nav1.7 could potentially reduce pain. Conclusions: The inhibition of overexpressed Nav1.7 channels may modulate nociceptive signal processing in the brain and effectively control pain associated with pulpitis.
So Yun Lim;Ji Yeun Kim;Soonju Park;Ji-Soo Kwon;Ji Young Park;Hye Hee Cha;Mi Hyun Suh;Hyun Jung Lee;Joon Seo Lim;Seongman Bae;Jiwon Jung;Nakyung Lee;Kideok Kim;David Shum;Youngmee Jee;Sung-Han Kim
IMMUNE NETWORK
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v.21
no.6
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pp.41.1-41.13
/
2021
Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.
Rudi Alberts;Sze Chun Chan;Qian-Fang Meng;Shan He;Lang Rao;Xindong Liu;Yongliang Zhang
IMMUNE NETWORK
/
v.22
no.3
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pp.22.1-22.25
/
2022
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.
Yoon-Soo Jang;Jae-Han Lee;Na-Rae Lee;Dong-Woo Kim;June-Hee Lee;Kyung-Jae Lee
Annals of Occupational and Environmental Medicine
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v.35
/
pp.50.1-50.11
/
2023
Background: The rise in telecommuting or non-face-to-face work owing to the coronavirus disease 2019 pandemic has fueled conversations regarding the "right to disconnect." Although evidence suggests that receiving work-related communications through telecommunication devices outside of work hours may lead to various symptoms and illnesses, limited research has been undertaken on these symptoms. This study therefore aims to investigate the correlation between receiving work communications through telecommunication devices after work hours and the occurrence of work-related headaches and eyestrain in full-time, non-shift white-collar workers. Methods: This study used data from the 6th Korean Working Conditions Survey. The frequency of using telecommunication devices for work purposes outside of working hours was divided into five categories: "Every day," "Several times a week," "Several times a month," "Rarely," and "Never." Work-related headaches and eyestrain were categorized based on a "yes" or "no" response to the survey questions. Descriptive statistics, χ2 tests, and multiple logistic regression analyses were performed using SPSS 27.0. Results: After adjusting for sex, age, income level, education, occupation, workplace size, work hours, and sleep disorders, the odds ratio (OR) of work-related headaches and eyestrain based on frequency of telecommunication device usage were as follows: "rarely" (OR: 1.292; 95% confidence interval [CI]: 1.111-1.503), "several times a month" (OR: 1.551; 95% CI: 1.249-1.926), "several times a week" (OR: 1.474; 95% CI: 1.217-1.784), and "every day" (OR: 1.548; 95% CI: 1.321-1.813). Conclusions: Employees who use telecommunication devices for work after regular hours are more susceptible to experiencing work-related headaches and eyestrain compared to those who do not. However, there is a dearth of research examining the physical and mental health impacts of using telecommunication devices for after-hours work. Furthermore, the existing preventative measures in Korea are insufficient. Consequently, it is imperative to develop effective measures and conduct additional research to address this issue.
Journal of the Society of Cosmetic Scientists of Korea
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v.50
no.1
/
pp.19-27
/
2024
This study is to propose Lagerstroemia indica flower as an anti-acne cosmetic material, and confirmed the sebum control, anti-inflammatory, and antioxidant effects using Lagerstroemia indica flower extract (LIFE) . As a result of evaluating the sebum control effectiveness, it was confirmed that LIFE inhibited the production of sebum excessively induced with palmitic acid up to 65%. Subsequently, it was confirmed that LIFE has an antibacterial effect and the ability to inhibit lipase activity against Cutibacterium acnes (C. acnes), which mainly appears in acne lesions, and can also reduce the inflammatory response caused by virulence factors secreted by C. acnes. It was also confirmed that LIFE inhibited the secretion of nitrogen monoxide (NO) and prostaglandin E2 (PGE2), which are inflammatory mediators induced by LPS in macrophages, by 75% and 54%, respectively, and that it also had a high DPPH radical scavenging ability similar to that of ascorbic acid. These results suggest that LIFE, a natural extract, can be used as an anti-acne material to relieve and treat acne, a complex disease, by controlling sebum production and having antibacterial and lipase activity inhibiting against C. acnes, and anti-inflammatory, antioxidant properties.
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