1.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
2.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
3.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
4.Mitochondrial quality control and its emerging role in the pathogenesis of diabetic kidney disease
Jihyun BAEK ; Yu Ho LEE ; Hye Yun JEONG ; So-Young LEE
Kidney Research and Clinical Practice 2023;42(5):546-560
Most eukaryotic cells have mitochondrial networks that can change in shape, distribution, and size depending on cellular metabolic demands and environments. Mitochondrial quality control is critical for various mitochondrial functions including energy production, redox homeostasis, intracellular calcium handling, cell differentiation, proliferation, and cell death. Quality control mechanisms within mitochondria consist of antioxidant defenses, protein quality control, DNA damage repair systems, mitochondrial fusion and fission, mitophagy, and mitochondrial biogenesis. Defects in mitochondrial quality control and disruption of mitochondrial homeostasis are common characteristics of various kidney cell types under hyperglycemic conditions. Such defects contribute to diabetes-induced pathologies in renal tubular cells, podocytes, endothelial cells, and immune cells. In this review, we focus on the roles of mitochondrial quality control in diabetic kidney disease pathogenesis and discuss current research evidence and future directions.
5.Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12
Yun-Gyoo LEE ; Hyun CHANG ; Bhumsuk KEAM ; Sang Hoon CHUN ; Jihyun PARK ; Keon Uk PARK ; Seong Hoon SHIN ; Ho Jung AN ; Kyoung Eun LEE ; Keun-Wook LEE ; Hye Ryun KIM ; Sung-Bae KIM ; Myung-Ju AHN ; In Gyu HWANG
Cancer Research and Treatment 2021;53(3):671-677
Purpose:
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods:
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results:
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.
6.Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12
Yun-Gyoo LEE ; Hyun CHANG ; Bhumsuk KEAM ; Sang Hoon CHUN ; Jihyun PARK ; Keon Uk PARK ; Seong Hoon SHIN ; Ho Jung AN ; Kyoung Eun LEE ; Keun-Wook LEE ; Hye Ryun KIM ; Sung-Bae KIM ; Myung-Ju AHN ; In Gyu HWANG
Cancer Research and Treatment 2021;53(3):671-677
Purpose:
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods:
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results:
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.
7.γ-Linolenic Acid versus α-Lipoic Acid for Treating PainfulDiabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, NoninferiorityTrial
Jong Chul WON ; Hyuk-Sang KWON ; Seong-Su MOON ; Sung Wan CHUN ; Chong Hwa KIM ; Ie Byung PARK ; In Joo KIM ; Jihyun LEE ; Bong Yun CHA ; Tae Sun PARK
Diabetes & Metabolism Journal 2020;44(4):542-554
This study was a multicenter, parallel-group, double-blind, double-dummy, randomized,noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid(GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). This study included 100 T2DM patients between 20 and 75 years of age who had painfulDPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for12 weeks. The primary outcome measures were mean changes in pain intensities as measuredby the visual analogue scale (VAS) and the total symptom scores (TSS). Of the 100 subjects who initially participated in the study, 73 completed the 12-weektreatment period. Per-protocol analyses revealed significant decreases in the mean VASand TSS scores compared to baseline in both groups, but there were no significantdifferences between the groups. The treatment difference for the VAS (95% confidenceinterval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and theupper bound of the 95% CI did not exceed the predefined noninferiority margin(δ1=0.51). For the TSS, the treatment difference was −0.05(−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferioritymargin (δ2=0.054). There were no serious adverse events associatedwith the treatments. GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducingpain intensity measured by the VAS over 12 weeks.
8.Dietary and health characteristics of the young-old and the old-old by food security status: analysis of data from the 6(th) (2013 ~ 2015) Korea National Health and Nutrition Examination Survey
Ajung BAE ; Jihyun YOON ; Soh Yoon YUN ; Kana ASANO
Journal of Nutrition and Health 2019;52(1):104-117
PURPOSE: This study examined dietary and health characteristics of the young-old and the old-old by food security status. METHODS: The study used data from the 6th (2013 ~ 2015) Korea National Health and Nutrition Examination Survey. The study subjects consisted of 3,948 subjects, of whom 2,445 were the young-old (aged 65 to 74 years) and 1,503 were the old-old (aged 75 years and over). Food security status was evaluated using an 18-item questionnaire. Energy intake, nutrient densities, and prevalence of insufficient nutrient intake were assessed. Food intake was evaluated in terms of the number of food group servings. Dietary behaviors and health status were also assessed. RESULTS: The prevalence of food insecurity among the young-old and the old-old was 10.0% and 11.6%, respectively. Among the young-old, the food insecure group had a significantly higher level of prevalence of insufficient intake for all the nutrients (protein, vitamin A, thiamin, riboflavin, niacin, vitamin C, calcium, phosphorous, and iron) assessed in this study compared with the food secure group. In case of the old-old, significant differences were found only for four nutrients (protein, riboflavin, niacin, and phosphorus) in the prevalence of insufficient nutrient intake between the food secure and the food insecure groups. Kinds of food groups with significantly different numbers of servings by food security status were dissimilar between the two age groups. In both the age groups, the food insecure group consumed a significantly lower number of servings in meat·fish·eggs·legumes and fruits than the food secure group; grains and vegetables intake in the young-old and oils·sweets intake in the old-old differed in the number of servings by food security status. Among the young-old, the prevalence of chewing difficulties in the food insecure group was significantly higher than that of the food secure group, while among the old-old, no significant differences were found by food security status. CONCLUSION: Dietary and health characteristics of the young-old and the old-old differed by food security status. Such differences were more apparent in the young-old than the old-old. Therefore, it is suggested that food and nutrition assistant programs should be designed with consideration of the differences.
Ascorbic Acid
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Calcium
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Diet
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Eating
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Energy Intake
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Food Supply
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Fruit
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Humans
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Korea
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Mastication
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Niacin
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Nutrition Surveys
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Prevalence
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Riboflavin
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Vegetables
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Vitamin A
9.The role of customer service manual on workplace emotional burden in nationwide cross sectional study
Sehyun YUN ; Sung Shil LIM ; Jihyun KIM ; Young Kwang KIM ; Jong Uk WON ; Jin Ha YOON
Annals of Occupational and Environmental Medicine 2019;31(1):5-
BACKGROUND: We aim to discuss the overall effect of customer service manual (CSM) on service industry workers using Korean Working Condition Survey. METHODS: Out of 50,007 total survey participants, 11,946 customer service workers were included in the current study (5613 men, 6333 women). Answers to survey questions were used to define the use of CSM, emotional burden, emotional dissonance, engaging angry customers and other covariates. Emotional burden included either depressive event or stress level. Odds ratio (OR) with 95% confidence interval (95% CI) of experiencing emotional burden was calculated by logistic regression model. Interaction effect between CSM and engaging angry customer on emotional burden was also estimated. RESULTS: Out of 11,946 subjects, total of 3279 (27.4%) have experienced emotional burden. OR (95% CI) of experiencing emotional burden was 1.40 (1.19–1.64) in men and 1.25 (1.09–1.44) in women. There was gender difference in interaction effect between the use of CSM and engaging angry customers. In men, OR (95% CI) was 3.16 (1.38–7.23) with additive effect when always engaging angry customers with CSM compared to rarely engaging without CSM, while in women OR (95% CI) was 8.85 (3.96–19.75) with synergistic effect. Moreover, the risk of depressive event increased only in women with OR (95% CI) 2.22 (1.42–3.48). CONCLUSIONS: Our current study highlighted association between emotional burden and CSM in both men and women service workers. Furthermore, women were affected more severely by CSM. The results from current study suggest that CSM should be changed appropriately to benefit workers.
Female
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Humans
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Logistic Models
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Male
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Mental Health
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Odds Ratio
10.Theracurmin Ameliorates Cognitive Dysfunctions in 5XFAD Mice by Improving Synaptic Function and Mitigating Oxidative Stress
Jihyun KIM ; Jaehoon KIM ; Zhouchi HUANG ; Nayeon GOO ; Ho Jung BAE ; Yongwoo JEONG ; Ho Jae PARK ; Mudan CAI ; Kyungnam CHO ; Seo Yun JUNG ; Soo Kyung BAE ; Jong Hoon RYU
Biomolecules & Therapeutics 2019;27(3):327-335
As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.
Aged
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Alzheimer Disease
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Animals
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Cognition
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Colloids
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Curcumin
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Glutathione
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Humans
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Malondialdehyde
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Mice
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Microglia
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Neurons
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Oxidative Stress
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Post-Synaptic Density
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Spatial Memory
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Superoxide Dismutase
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Synaptophysin

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