1.Prognostic Significance of Fibrotic Focus and Tumor Infiltrating Lymphocytes in Breast Cancer According to Molecular Subtypes
Do Bin LEE ; Hoon Kyu OH ; Na-Rang LEE ; Sung Hwan PARK ; Young Ju JEONG
Journal of Breast Disease 2022;10(1):18-28
Purpose:
This study aimed to analyze the association between fibrotic focus (FF) and tumor-infiltrating lymphocytes (TILs) and to determine the prognostic significance of FF and TILs in the breast according to its molecular subtypes.
Methods:
The study included patients who underwent surgical treatment for breast cancer, for whom tissue samples were available. FF within the tumor and TILs in breast cancer tissues were evaluated. Clinicopathological characteristics were reviewed from medical records.
Results:
FF and TILs were present in 31.3% and 81.7% of the patients, respectively. FF and TILs showed a positive correlation. FF were significantly associated with tumor size, lymphovascular invasion, regional lymph node metastasis, and tumor stage. TILs were significantly associated with menopausal status, histologic grade, tubule formation, nuclear grade, mitosis, human epidermal growth factor receptor 2 (HER2) overexpression, molecular subtype of breast cancer, and the number of cluster of differentiation 8+ T cells. In TIL-positive cases, FF were significantly associated with tumor size, regional lymph node metastasis, extranodal extension, lymphovascular invasion, tumor stage, recurrence-free survival, and overall survival (OS). Based on HER2 overexpression status, TILs were significantly associated with tumor size, tumor necrosis, histologic grade, estrogen receptor status, and epidermal growth factor receptor expression in HER2-negative breast cancer. Further, in HER2-negative breast cancer, OS and recurrence-free survival were significantly associated with FF. The OS of FF-positive patients was significantly shorter than that of FF-negative patients.
Conclusion
Our study showed an association between FF and TIL levels in breast cancer, indicating that FF are associated with poor prognostic factors for breast cancer and poor OS, and that TILs are associated with HER2 overexpression. However, further studies are needed to elucidate the interactions between FF and TILs in breast cancer.
2.Meal skipping relates to food choice, understanding of nutrition labeling, and prevalence of obesity in Korean fifth grade children.
Hye Young KIM ; Na Rae LEE ; Jung Sug LEE ; Young Sun CHOI ; Tong Kyung KWAK ; Hae Rang CHUNG ; Sehyug KWON ; Youn Ju CHOI ; Soon Kyu LEE ; Myung Hee KANG
Nutrition Research and Practice 2012;6(4):328-333
This study was performed to investigate the differences in food choice, nutrition labeling perceptions, and prevalence of obesity due to meal skipping in Korean elementary school children. A national survey was performed in 2010 to collect data on food intake frequency, understanding of nutrition labeling, and body mass index from 2,335 fifth grade students in 118 elementary schools selected from 16 metropolitan local governments by stratified cluster sampling. The data were analyzed using the SAS 9.1 and SUDAAN 10.0 packages. Students who consumed three meals for 6-7 days during the past week were classified into the regular meal eating (RM) group (n = 1,476) and those who did not were placed into the meal skipping (MS) group (n = 859). The daily intake frequency of fruits, vegetables, kimchi, and milk was significantly lower in the MS group compared to that in the RM group (P < 0.001), whereas the daily intake frequency of soft drinks and instant noodles (ramyeon) was significantly higher in the MS group than that in the RM group (P < 0.05). The MS group demonstrated a significantly lower degree of understanding with regard to nutrition labeling and high calorie foods containing low nutritional value than that in the RM group. The distribution of obesity based on the percentile criteria using the Korean growth chart was different between the MS and RM groups. The MS group (8.97%) had a higher percentage of obese subjects than that in the RM group (5.38%). In conclusion, meal skipping was related to poor food choice, low perception of nutrition labeling, and a high prevalence of obesity in Korean fifth grade children.
Body Mass Index
;
Carbonated Beverages
;
Child
;
Eating
;
Food Labeling
;
Fruit
;
Growth Charts
;
Humans
;
Meals
;
Milk
;
Nutritive Value
;
Obesity
;
Phenothiazines
;
Prevalence
;
Vegetables
3.Characterization of the expression of cytokeratins 5, 8, and 14 in mouse thymic epithelial cells during thymus regeneration following acute thymic involution.
Eun Na LEE ; Jin Kyeong PARK ; Ja Rang LEE ; Sae Ock OH ; Sun Yong BAEK ; Bong Seon KIM ; Sik YOON
Anatomy & Cell Biology 2011;44(1):14-24
The thymus is a central lymphoid organ for T cell development. Thymic epithelial cells (TECs) constitute a major component of the thymic stroma, which provides a specialized microenvironment for survival, proliferation, and differentiation of immature T cells. In this study, subsets of TECs were examined immunohistochemically to investigate their cytokeratin (CK) expression patterns during thymus regeneration following thymic involution induced by cyclophosphamide treatment. The results demonstrated that both normal and regenerating mouse thymuses showed a similar CK expression pattern. The major medullary TECs (mTEC) subset, which is stellate in appearance, exhibited CK5 and CK14 staining, and the minor mTEC subset, which is globular in appearance, exhibited CK8 staining, whereas the vast majority of cortical TECs (cTECs) expressed CK8 during thymus regeneration. Remarkably, the levels of CK5 and CK14 expression were enhanced in mTECs, and CK8 expression was upregulated in cTECs during mouse thymus regeneration after cyclophosphamide-induced acute thymic involution. Of special interest, a relatively high number of CK5+CK8+ TEC progenitors occurred in the thymic cortex during thymus regeneration. Taken together, these findings shed more light on the role of CK5, CK8, and CK14 in the physiology of TECs during mouse thymus regeneration, and on the characterization of TEC progenitors for restoration of the epithelial network and for concomitant regeneration of the adult thymus.
Adult
;
Animals
;
Cyclophosphamide
;
Epithelial Cells
;
Humans
;
Keratins
;
Light
;
Mice
;
Regeneration
;
T-Lymphocytes
;
Thymus Gland
4.Development of Evaluation Indicators for a Children's Dietary Life Safety Index in Korea.
Hae Rang CHUNG ; Tong Kyung KWAK ; Young Sun CHOI ; Hye Young P KIM ; Jung Sug LEE ; Jung Hwa CHOI ; Na Young YI ; Sehyug KWON ; Youn Ju CHOI ; Soon Kyu LEE ; Myung Hee KANG
The Korean Journal of Nutrition 2011;44(1):49-60
This study was performed to develop a children's dietary life safety index required by the Special Act on Safety Management of Children's Dietary Life enacted in 2009. An analytical hierarchy process was used to obtain initial weights of dietary life safety evaluation indicators. The Delphi method was applied to develop the weights along with 98 food and nutrition professionals. Three representative policy indicators, nine strategy indicators, 11 main evaluation indicators, and 20 detailed evaluation indicators were selected for the children's dietary life safety assessment. Three policy indicators and nine strategy indicators were the following: children's food safety indicator (support level of children' safety, safety management level of children's favorite foods, and safety management level of institutional food service), children's nutrition safety indicator (management level of missing meals and obesity, nutrition management level of children's favorite foods, and nutrition management level of institutional food service), and children's perception and practice level indicator ("Dietary Life Law" perception level, perception, and practice level for dietary life safety management, perception, and practice level for nutrition management). Weights of 40%, 40%, and 20% were given for the three representative policy indicators. The relative importance of nine strategic indicators, which were determined by the Delphi method is as follows: For children's food safety, support level of children's safety, safety management level of children's favorite foods, and safety management level of institutional food service were given weights of 12%, 9%, and 19%, respectively. For children's nutrition safety, the missing meals and obesity management level, nutrition management level of children's favorite foods, and the nutrition management level of institutional food service were given weights of 13%, 11%, and 16%, respectively. The "Dietary Life Law" perception level, perception and practice level of dietary life safety management, and perception and practice level of nutrition management were given weights of 4%, 7%, and 9%, respectively.
Food Safety
;
Food Services
;
Korea
;
Meals
;
Obesity
;
Safety Management
;
Weights and Measures
5.Structure and Expression Analyses of SVA Elements in Relation to Functional Genes.
Yun Jeong KWON ; Yuri CHOI ; Jungwoo EO ; Yu Na NOH ; Jeong An GIM ; Yi Deun JUNG ; Ja Rang LEE ; Heui Soo KIM
Genomics & Informatics 2013;11(3):142-148
SINE-VNTR-Alu (SVA) elements are present in hominoid primates and are divided into 6 subfamilies (SVA-A to SVA-F) and active in the human population. Using a bioinformatic tool, 22 SVA element-associated genes are identified in the human genome. In an analysis of genomic structure, SVA elements are detected in the 5' untranslated region (UTR) of HGSNAT (SVA-B), MRGPRX3 (SVA-D), HYAL1 (SVA-F), TCHH (SVA-F), and ATXN2L (SVA-F) genes, while some elements are observed in the 3'UTR of SPICE1 (SVA-B), TDRKH (SVA-C), GOSR1 (SVA-D), BBS5 (SVA-D), NEK5 (SVA-D), ABHD2 (SVA-F), C1QTNF7 (SVA-F), ORC6L (SVA-F), TMEM69 (SVA-F), and CCDC137 (SVA-F) genes. They could contribute to exon extension or supplying poly A signals. LEPR (SVA-C), ALOX5 (SVA-D), PDS5B (SVA-D), and ABCA10 (SVA-F) genes also showed alternative transcripts by SVA exonization events. Dominant expression of HYAL1_SVA appeared in lung tissues, while HYAL1_noSVA showed ubiquitous expression in various human tissues. Expression of both transcripts (TDRKH_SVA and TDRKH_noSVA) of the TDRKH gene appeared to be ubiquitous. Taken together, these data suggest that SVA elements cause transcript isoforms that contribute to modulation of gene regulation in various human tissues.
3' Untranslated Regions
;
5' Untranslated Regions
;
Exons
;
Gene Expression Profiling
;
Genome, Human
;
Genomics
;
Humans
;
Lung
;
Organ Specificity
;
Poly A
;
Primates
;
Protein Isoforms
6.Evaluation of the association between pollen count and the outbreak of allergic disease.
Ha Na KANG ; Hey Suk YUN ; Young Jin CHOI ; Jae Won OH ; Ui Young MIN ; Yoon Sook HEO ; Young Seop LEE ; Mijin KIM ; Kyu Rang KIM ; Baek Jo KIM
Allergy, Asthma & Respiratory Disease 2016;4(6):415-422
PURPOSE: This study focused on the evaluation of the relation between pollen concentration and the outbreak of allergic disease (symptom index), and this outcome would be necessary to upgrade risk grade for the pollen forecasting system. METHODS: Airborne particles carrying allergens, such as pollen, were collected daily at the Seoul and Guri area by using 7-day Burkard samplers for 6 years. A total of 596 Subjects were recruited from Hanyang University Seoul Hospital (n=144 for spring, n=139 for autumn), and Hanyang University Guri Hospital (n=157 for spring, n=156 for autumn). Symptom index was evaluated and recorded by phone calling to study subjects daily or asking questionnaire when they visit outpatient clinic every week. Statistical analysis of data was performed by using correlation coefficients and regression models with time series graph. RESULTS: Two peak seasons of pollen concentration were May and September in Korea. In skin prick tests, the sensitization rate to ragweed pollen was gradually increased in children. In the same period, sensitization rates to airborne pollen, especially oak, birch for spring, and Japanese hop for autumn were increased annually. There was a significantly relationship between symptom index of allergic patients and allergic pollen concentrations in this study. Especially symptom index was significantly correlated to the concentration of oak pollen of day 1 in spring and to the concentration of Japanese hop pollen of day 0 in autumn. CONCLUSION: Sensitization rates to pollens increased annually. There is a significant relationship between allergy symptom index and pollen concentration. There remains to confirm the Korean own risk grade of pollen allergy.
Allergens
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Ambrosia
;
Ambulatory Care Facilities
;
Asian Continental Ancestry Group
;
Betula
;
Child
;
Forecasting
;
Humans
;
Hypersensitivity
;
Korea
;
Pollen*
;
Rhinitis, Allergic, Seasonal
;
Seasons
;
Seoul
;
Skin
7.Fasiglifam (TAK-875), a G Protein-Coupled Receptor 40 (GPR40) Agonist, May Induce Hepatotoxicity through Reactive Oxygen Species Generation in a GPR40-Dependent Manner.
MinJeong KIM ; Gyo Jeong GU ; Yun Sook KOH ; Su Hyun LEE ; Yi Rang NA ; Seung Hyeok SEOK ; Kyung Min LIM
Biomolecules & Therapeutics 2018;26(6):599-607
Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration- (>50 μM) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to 500 μM. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at 25 μM. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.
Acetylcysteine
;
Cell Line
;
Cytoplasm
;
Fibroblasts
;
GTP-Binding Proteins
;
Hepatocytes
;
Humans
;
Hyperglycemia
;
Hypoglycemia
;
Larva
;
Liver
;
Mortality
;
Reactive Oxygen Species*
;
RNA, Small Interfering
;
Weight Gain
;
Zebrafish
8.Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice.
Sung Hoon PARK ; Seo Na CHANG ; Min Won BAEK ; Dong Jae KIM ; Yi Rang NA ; Seung Hyeok SEOK ; Byoung Hee LEE ; Kyung Sul KIM ; Jae Hak PARK
Laboratory Animal Research 2013;29(1):39-47
Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer.
Adenocarcinoma
;
Adipose Tissue, White
;
Animals
;
Humans
;
Leptin
;
Male
;
Mice
;
Nucleolus Organizer Region
;
Prostate
;
Prostatic Neoplasms
9.In vivo alternative testing with zebrafish in ecotoxicology.
Seung Hyeok SEOK ; Min Won BAEK ; Hui Young LEE ; Dong Jae KIM ; Yi Rang NA ; Kyoung Jin NOH ; Sung Hoon PARK ; Hyun Kyoung LEE ; Byoung Hee LEE ; Jae Hak PARK
Journal of Veterinary Science 2008;9(4):351-357
Although rodents have previously been used in ecotoxicological studies, they are expensive, time-consuming, and are limited by strict legal restrictions. The present study used a zebrafish (Danio rerio) model and generated data that was useful for extrapolating toxicant effects in this system to that of humans. Here we treated embryos of the naive-type as well as a transiently transfected zebrafish liver cell line carrying a plasmid (phAhREEGFP), for comparing toxicity levels with the well-known aryl hydrocarbon receptor (AhR)-binding toxicants: 3,3',4,4',5-pentachlorobiphenyl (PCB126), 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 3-methylcholanthrene. These toxicants induced a concentration-dependent increase in morphological disruption, indicating toxicity at early life-stages. The transient transgenic zebrafish liver cell line was sensitive enough to these toxicants to express the CYP1A1 regulated enhanced green fluorescent protein. The findings of this study demonstrated that the zebrafish in vivo model might allow for extremely rapid and reproducible toxicological profiling of early life-stage embryo development. We have also shown that the transient transgenic zebrafish liver cell line can be used for research on AhR mechanism studies.
Animals
;
Benz(a)Anthracenes/toxicity
;
Cell Line
;
Green Fluorescent Proteins
;
Hepatocytes/cytology/physiology
;
Larva/drug effects/growth & development
;
Lethal Dose 50
;
Polychlorinated Biphenyls/toxicity
;
Tetrachlorodibenzodioxin/toxicity
;
Water Pollutants, Chemical/*adverse effects
;
Zebrafish/*physiology
10.Production of specific antibodies against SARS-coronavirus nucleocapsid protein without cross reactivity with human coronaviruses 229E and OC43.
Hyun Kyoung LEE ; Byoung Hee LEE ; Seung Hyeok SEOK ; Min Won BAEK ; Hui Young LEE ; Dong Jae KIM ; Yi Rang NA ; Kyoung Jin NOH ; Sung Hoon PARK ; Dutta Noton KUMAR ; Hiroaki KARIWA ; Mina NAKAUCHI ; Suk Jin HEO ; Jae Hak PARK
Journal of Veterinary Science 2010;11(2):165-167
Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.
Antibodies, Viral/*immunology
;
Blotting, Western
;
Coronavirus 229E, Human/*immunology
;
Coronavirus OC43, Human/*immunology
;
Cross Reactions
;
Humans
;
Nucleocapsid Proteins/genetics/*immunology
;
Recombinant Proteins/immunology
;
SARS Virus/genetics/*immunology
;
Severe Acute Respiratory Syndrome/diagnosis/*immunology