• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.363-368
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• 2018

Background: Vitiligo is a chronic autoimmune disease in which the destruction of melanocytes causes white spots on the affected skin. Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-signal transducer and activator of transcription pathway. The aim of the present study is to explore the possible role of JAK1 in the pathogenesis of vitiligo using immunohistochemical methods. Methods: The current study was conducted in a sample of 39 patients who presented with vitiligo and 22 healthy individuals who were age and sex matched as a control group. We used immunohistochemistry to evaluate JAK1 status (intensity and distribution) and assess the percentage of residual melanocytes using human melanoma black 45 (HMB45). Results: Intense and diffuse JAK1 expression was significantly more likely to indicate vitiliginous skin compared to normal skin (p<.001). Strong and diffuse JAK1 expression was associated with short disease duration, female sex, and lower percentage of melanocytes (detected by HMB45) (p<.05). Conclusions: JAK1 may be involved in the pathogenesis of vitiligo, as indicated by intense and diffuse expression compared to control and association with lower percentage of melanocytes detected by HMB45 immunostaining.

• Journal of Interdisciplinary Genomics
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• v.3 no.2
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• pp.41-46
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• 2021

Inherited platelet function disorders (IPFDs) are a disease group of heterogeneous bleeding disorders associated with congenital defects of platelet functions. Normal platelets essential role for primary hemostasis by adhesion, activation, secretion of granules, aggregation, and procoagulant activity of platelets. The accurate diagnosis of IPFDs is challenging due to unavailability of important testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. Among several IPFDs, Glanzmann thrombasthenia (GT) is a most representative IPFD and is relatively frequently found compare to the other types of rarer IPFDs. GT is an autosomal recessive disorder caused by mutations of ITGA2B or ITGB3. There are quantitative or qualitative defects of the GPIIb/IIIa complex in platelet, which is the binding receptor for fibrinogen, von Willbrand factor, and fibronectin in GT patients. Therefore, patients with GT have normal platelet count and normal platelet morphology, but they have severely decreased platelet aggregation. Thus, GT patients have a very severe hemorrhagic phenotypes that begins at a very early age and persists throughout life. In this article, the general contents about platelet functions and respective IPFDs, the overall contents of GT, and the current status of genetic diagnosis of GT in Korea will be reviewed.

• Journal of Neurocritical Care
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• v.7 no.2
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• pp.104-110
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• 2014

Background: Cefepime is a fourth-generation cephalosporin widely used for empiric treatment of severe infections. Neurotoxicity by cefepime have been reported due to γ-aminobutyric acid A receptor inhibition or other mechanisms. The aim of this study was to evaluate the risk factors for cefepime-induced neurotoxicity between group showing cefepime-induced neurotoxicity and group without neurotoxicity. Methods: From Jan 2005 to June 2010, a total of 2,461 patients (older than 20) who used cefepime were considered in this study. We compared patients who developed cefepime-induced neurotoxicity (patient group, n=21) to patients who had no cefepime-induced neurotoxicity (control group, n=31). We analyzed demographic, underlying diseases, and metabolic parameters before cefepime treatment and during cefepime treatment between the two groups. Statistical analysis was performed using SPSS 18 software. Results: Of the total 2461 patients, 21 (0.85%) were diagnosed with cefepime-induced neurotoxicity. Impaired glomerular filtration rate (GFR at 15-30 ml/min) before cefepime use were significantly (P<0.05) higher risk for developing cefepime-induced neurotoxicity in patient group compared to that in the control group. Age, sex, and other metabolic parameters except GFR before and during, usage of cefepime did not show any statistical difference between the two groups. Conclusion: The present study revealed that cefepime-induced neurotoxicity was prone to develop in patients with impaired renal function before cefepime usage.

• Anatomy and Cell Biology
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• v.56 no.1
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• pp.94-108
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• 2023

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.6.1-6.20
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• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.5
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• pp.749-756
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• 2014

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between $32^{\circ}C$ to $34^{\circ}C$ at day to $27^{\circ}C$ to $29^{\circ}C$ at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-$1{\beta}$, IL-6, interferon (IFN)-${\gamma}$, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5511-5515
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• 2012

Introduction: The nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-${\kappa}B$ /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. Materials and Methods: In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. Results: NF-${\kappa}B$/p65 was significantly associated with advanced stage, large tumor size (${\geq}5$ cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-${\kappa}B$/p65 expression was more frequent in patients with a high NPI ($NPI{\geq}5.4$, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p = 0.002). Conclusion: NF-${\kappa}B$/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-${\kappa}B$/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-${\kappa}B$ /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-${\kappa}B$ positive tumors need to be treated aggressively.

• Korean Journal of Human Ecology
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• v.4 no.1
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• pp.36-45
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• 2001

This study was performed to determine the changes of maternal iron status during pregnancy cross sectionally, and to evaluate the appropriateness of the cut-off points of hemoglobin (Hb). hematocrit (Hct), serum transferrin receptor (sTfR) and sTfR : ferritin ratio for assessing iron deficiency status based on serum ferritin level (< 12${\mu}g$/L). Serum Hb concentrations in the first trimester were significantly higher (p < 0.05) than those in the second and third trimester. Serum levels of iron and ferritin in the third trimester were significantly lower (p < 0.05) than those in the first and second trimester. On the other hand, sTfR:ferritin ratios in the third trimester were significantly higher (p < 0.05) than those in the first and second trimester. sTfR concentrations did not change significantly during pregnancy. The appropriate cut-off points of Hb were 11.5g/dL for whole period of pregnancy. 12.0g/dL for 1st trimester. and 11.5g/dL for both 2nd and 3rd trimester. The good cut-off points of Hct were 34% for whole period of pregnancy. 36% for 1st trimester. and 34% for both 2nd and 3rd trimester The suitable cut-off points of TIBC were 400${\mu}g$/dL for whole period of pregnancy. 360${\mu}g$/dL for 1st trimester, and 400${\mu}g$/dL for both 2nd and 3rd trimester. Any cut-off point of sTfR could not be selected because of its low sensitivity and specificity. The proper cut-off point of sTfR : ferritin ratio was 600 or 650 for all the periods determined except the first trimester. In conclusion, there were no reliable cut-off levels of sTfR and those of sTfR : ferritin ratio showed low specificity. The cut-off values of Hb and Hct for assessing iron deficiency were slightly higher than the values used to evaluate anemia. Thus, if appropriate cut-off levels were applied, Hb. Hct, or TIBC might be useful indices for evaluating iron deficiency as well as anemia.

• The Korean Journal of Nuclear Medicine
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• v.39 no.3
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• pp.200-208
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• 2005

Purpose: Tc-99m labeled diethylenetriaminepentaacctic acid (DTPA)-coupled galactosylated human serum albumin (GSA) is a currently used imaging agent for asialoglycoprotein receptor (ASGPR) of the liver, but, it has several shortcomings. Recently a new ASGPR imaging agent, $^{99m}Tc$-lactosylated human serum albumin (LSA), with simple labeling procedure, high labeling efficiency, high stability was developed. In order to assess the feasibility of the $^{99m}Tc$-LSA as a ASGPR imaging radiopharmaceuticals, we performed biodistribution study of the tracer in liver injured mice model and the results were compared with histolgic data. Materals and Methods: To induce hepatic damage in ICR mice, diethylnitrosamine (DEN) ($60mg/kg/week{\times}5time$, low dose or $180mg/kg/week{\times}2times$, high dose) and thioacetamide (TAA) ($50mg/kg{\times}1time$) were administrated intraperitoneally. Degree of liver damage was evaluated by tissue hematoxilin-eosin stain, and expression of asialoglycoprotein receptor (ASGPR) was assessed by immunohistochemistry using ASGPR antibody. $^{99m}Tc$-LSA was intravenously administrated via tail vein in DEN or TAA treated mice, and biodistribution study of the tracer was also performed. Results: DEN treated mice showed ballooning of hepatocyte and inflammatory cell infiltration in low dose group and severe hapatocyte necrosis in high dose group, and low dose group showed higher ASGPR staining than control mice in immunohistochemical staining. TAA treated mice showed severe hepatic necrosis. $^{99m}Tc$-LSA Biodistribution study showed that mice with hepatic necrosis induced by high dose DEN or TAA revealed higher blood activity and lower liver activity than control mice, due to slow clearance of the tracer by the liver. The degree of liver uptake was inversely correlated with the degree of histologic liver damage. But low dose DEN treated mice with mild hepatic injury showed normal blood clearance and hepatic activity, partly due to overexpression of ASGPR in mice with mild degree hepatic injury. Conclusion: Liver uptake of $^{99m}Tc$-LSA was inversely correlated with degree of histologic hepatic injury in DEN and TAA treated mice. These results support that $^{99m}Tc$-LSA can be used to evaluate the liver status in liver disease patients.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.160-168
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• 2004

Background : The role of second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) is known to be limited. Recently, ZD1839, the small molecule epidermal growth factor receptor-tyrosine kinase inhibitor, has been developed and has shown anti-tumor activity in patients with solid malignant tumors including lung cancer. We evaluated the response rate and toxicities of ZD1839 in patients with advanced NSCLC which has progressed after previous chemotherapy. Patients and Methods : We examined 83 patients with advanced NSCLC treated with ZD1839 for more than 1 month in Korea Cancer Center Hospital during the period from January 2002 to September 2003. All the patients were enrolled in the international expanded access program (EAP) with ZD1839 by AstraZeneca. The administered dose of ZD1839 was 250 mg once daily. Chest radiography and laboratory tests were followed-up. We evaluated the response rate, median survival, and toxicity after treatment. Results : Median age of the patients was 59 years (range 33-76). The most predominant cell type was adenocarcinoma and the most stage of the patients was IV. ECOG performance status was as follows; grade 0-1 in 10, grade 2 in 42, and grade 3 in 31 patients. Partial response was achieved in 12 patients (14.5%). Median overall survival was 9.2 (range 1.3-21.6+) months and median time to progression was 3.1 (range 1-21.2+) months. The most common adverse effect of ZD1839 was skin eruption which developed in 25 patients (25.8%). Significantly higher response rate and survival was found in patients with adenocarcinoma or good performance status. Conclusion : ZD1839 showed modest activity and tolerable toxicity in the treatment for patients with NSCLC which has progressed after previous chemotherapy.