Publications by authors named "Kang Hoon Lee"

72 Publications

Dermoscopic findings of genital keratotic lesions: Bowenoid papulosis, seborrheic keratosis, and condyloma acuminatum.

Photodiagnosis Photodyn Ther 2021 Jul 19;36:102448. Epub 2021 Jul 19.

Department of Dermatology, Kosin University College of Medicine, Busan, South Korea. Electronic address:

Dermatologists often encounter keratotic or warty lesions in the genital area. Establishing a clear diagnosis may seem challenging, particularly when the differential diagnosis includes bowenoid papulosis, seborrheic keratosis, and condyloma acuminatum. This study aimed to compare the dermoscopic features of bowenoid papulosis (BP), seborrheic keratosis, and condyloma acuminatum in the genital area. All lesions histopathologically confirmed underwent clinical assessment and dermoscopic observation. Dermoscopically, glomerular vessels were predominant in bowenoid papulosis, whereas seborrheic keratosis was the least vascular-patterned disease. Most cases of bowenoid papulosis presented mucosal pigmentation and classified as "flat". Seborrheic keratosis had a pigmented, cerebriform appearance. Condyloma acuminatum was characterised by a finger-like appearance, highly vascular-patterned features surrounded by whitish halos. Dermoscopic findings can be useful for differentiating the entity of genital keratotic lesions ahead of an invasive method. When dermoscopic features favor BP, different from genital warts, it should be removed completely but conservatively.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102448DOI Listing
July 2021

Clinical characteristics and long-term outcome of 223 patients with mycosis fungoides at a single tertiary center in Korea: A 29-year review.

J Am Acad Dermatol 2021 Jun 29. Epub 2021 Jun 29.

Department of Dermatology, Kosin University College of Medicine, Busan, Korea. Electronic address:

Background: Data regarding Asian patients with mycosis fungoides (MF) are limited.

Objective: We aimed to investigate the clinical profile and long-term outcomes of patients with MF in Korea.

Methods: A retrospective review of 223 patients with MF who were followed up for more than 6 months or died of MF within 6 months of diagnosis was performed.

Results: Approximately 96.4% and 3.6% of the patients had an early stage and advanced stage, respectively. The mean age at diagnosis was 44.8 years. The mean duration of symptoms before diagnosis was 47.0 months. Various subtypes were noted, including mycosis fungoides palmaris et plantaris (21.5%), folliculotropic (8.5%), pityriasis lichenoides-like (6.7%), ichthyosiform (4.0%), lichenoid purpura-like (2.7%), and hypopigmented (2.2%) MF. Juvenile patients accounted for 16.6%. The higher the skin T stage, the poorer the response to treatment. The 10-year overall survival was 96.8% in early-stage patients and 25.0% in advanced-stage patients. General prognosis was favorable, while recurrence and subtype switching were seen in 29.4% and 2.7% of patients, respectively.

Limitations: Our patients may not represent all Korean patients with MF.

Conclusion: MF in Korea has a high proportion of variants, a younger age at onset, and favorable prognosis. A high index of suspicion and skin biopsy are needed for early diagnosis.
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http://dx.doi.org/10.1016/j.jaad.2021.06.860DOI Listing
June 2021

METTL8 mRNA Methyltransferase Enhances Cancer Cell Migration via Direct Binding to ARID1A.

Int J Mol Sci 2021 May 21;22(11). Epub 2021 May 21.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

The association of RNA modification in cancer has recently been highlighted. Methyltransferase like 8 (METTL8) is an enzyme and its role in mRNA m3C modification has barely been studied. In this study, we found that METTL8 expression was significantly up-regulated in canine mammary tumor and investigated its functional roles in the tumor process, including cancer cell proliferation and migration. METTL8 expression was up-regulated in most human breast cancer cell lines tested and decreased by Yin Yang 1 (YY1) transcription factor knockdown, suggesting that YY1 is a regulating transcription factor. The knockdown of METTL8 attenuated tumor cell growth and strongly blocked tumor cell migration. AT-rich interactive domain-containing protein 1A (ARID1A) was identified as a candidate mRNA by METTL8. ARID1A mRNA binds to METTL8 protein. ARID1A mRNA expression was not changed by METTL8 knockdown, but ARID1A protein level was significantly increased. Collectively, our study indicates that METTL8 up-regulated by YY1 in breast cancer plays an important role in cancer cell migration through the mRNA modification of ARID1A, resulting in the attenuation of its translation.
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http://dx.doi.org/10.3390/ijms22115432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196784PMC
May 2021

Usefulness of dermoscopy in identifying amyloid purpura.

J Dermatol 2021 Jun 20;48(6):e260-e262. Epub 2021 Apr 20.

Department of Dermatology, Kosin University College of Medicine, Busan, South Korea.

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http://dx.doi.org/10.1111/1346-8138.15854DOI Listing
June 2021

The Experimental Process Design of Artificial Lightweight Aggregates Using an Orthogonal Array Table and Analysis by Machine Learning.

Materials (Basel) 2020 Dec 7;13(23). Epub 2020 Dec 7.

Department Civil & Environmental Engineering, Hanyang University, Seoul 04763, Korea.

The purpose of this study is to experimentally design the drying, calcination, and sintering processes of artificial lightweight aggregates through the orthogonal array, to expand the data using the results, and to model the manufacturing process of lightweight aggregates through machine-learning techniques. The experimental design of the process consisted of L(36), which means that 3 × 6 data can be obtained in 18 experiments using an orthogonal array design. After the experiment, the data were expanded to 486 instances and trained by several machine-learning techniques such as linear regression, random forest, and support vector regression (SVR). We evaluated the predictive performance of machine-learning models by comparing predicted and actual values. As a result, the SVR showed the best performance for predicting measured values. This model also worked well for predictions of untested cases.
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http://dx.doi.org/10.3390/ma13235570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730768PMC
December 2020

Hypermethylation in Canine Mammary Tumors and Human Breast Cancer.

Int J Mol Sci 2020 Nov 18;21(22). Epub 2020 Nov 18.

Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 08826 Seoul, Korea.

Canine mammary tumors (CMT) constitute the most common tumor types found in female dogs. Understanding this cancer through extensive research is important not only for clinical veterinary applications, but also in the scope of comparative oncology. The use of DNA methylation as a biomarker has been noted for numerous cancers in the form of both tissue and liquid biopsies, yet the study of methylation in CMT has been limited. By analyzing our canine methyl-binding domain sequencing (MBD-seq) data, we identified intron regions of canine and as differentially methylated regions (DMGs) in CMT. Subsequently, we established quantitative methylation specific PCR (qMSP) of and to validate the target hypermethylation in CMT tissue, as well as cell free DNA (cfDNA) from CMT plasma. Both and were hypermethylated in CMT and highlighted as potential tissue biomarkers in CMT. additionally showed significant hypermethylation in the plasma cfDNA of CMT, indicating that it could be a potential liquid biopsy biomarker as well. A similar trend towards hypermethylation was indicated in HBC at a specific CpG of the target on the orthologous human region, which validates the comparative approach using aberrant methylation in CMT.
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http://dx.doi.org/10.3390/ijms21228697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698701PMC
November 2020

Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases.

Int J Mol Sci 2020 Nov 6;21(21). Epub 2020 Nov 6.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has been reported not only in various cell development processes but also in the development of diseases. Furthermore, the involvement of long non-coding RNAs (lncRNAs), which are regarded as important epigenetic regulators in gene expression, has also been reported in cholesterol homeostasis. It is thus necessary to summarize the research on lncRNAs related to cholesterol with increased interest. This review organized the role of lncRNAs according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process.
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http://dx.doi.org/10.3390/ijms21218337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664438PMC
November 2020

Epigenetic Mechanisms of LncRNAs Binding to Protein in Carcinogenesis.

Cancers (Basel) 2020 Oct 11;12(10). Epub 2020 Oct 11.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Epigenetic dysregulation is an important feature for cancer initiation and progression. Long non-coding RNAs (lncRNAs) are transcripts that stably present as RNA forms with no translated protein and have lengths larger than 200 nucleotides. LncRNA can epigenetically regulate either oncogenes or tumor suppressor genes. Nowadays, the combined research of lncRNA plus protein analysis is gaining more attention. LncRNA controls gene expression directly by binding to transcription factors of target genes and indirectly by complexing with other proteins to bind to target proteins and cause protein degradation, reduced protein stability, or interference with the binding of other proteins. Various studies have indicated that lncRNA contributes to cancer development by modulating genes epigenetically and studies have been done to determine which proteins are combined with lncRNA and contribute to cancer development. In this review, we look in depth at the epigenetic regulatory function of lncRNAs that are capable of complexing with other proteins in cancer development.
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http://dx.doi.org/10.3390/cancers12102925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599656PMC
October 2020

Alternative methylation of intron motifs is associated with cancer-related gene expression in both canine mammary tumor and human breast cancer.

Clin Epigenetics 2020 07 21;12(1):110. Epub 2020 Jul 21.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Gwanak-ro1, Gwanak-gu, Seoul, Korea.

Background: Canine mammary tumor (CMT) has long been considered as a good animal model for human breast cancer (HBC) due to their pathological and biological similarities. However, only a few aspects of the epigenome have been explored in both HBC and CMT. Moreover, DNA methylation studies have mainly been limited to the promoter regions of genes.

Results: Genome-wide methylation analysis was performed in CMT and adjacent normal tissues and focused on the intron regions as potential targets for epigenetic regulation. As expected, many tumor suppressors and oncogenes were identified. Of note, most cancer-associated biological processes were enriched in differentially methylated genes (DMGs) that included intron DMRs (differentially methylated regions). Interestingly, two PAX motifs, PAX5 (tumor suppressive) and PAX6 (oncogenic), were frequently found in hyper- and hypomethylated intron DMRs, respectively. Hypermethylation at the PAX5 motifs in the intron regions of CDH5 and LRIG1 genes were found to be anti-correlated with gene expression, while CDH2 and ADAM19 genes harboring hypomethylated PAX6 motifs in their intron region were upregulated. These results were validated from the specimens originally MBD-sequenced as well as additional clinical samples. We also comparatively investigated the intron methylation and downstream gene expression of these genes using human breast invasive carcinoma (BRCA) datasets in TCGA (The Cancer Genome Atlas) public database. Regional alteration of methylation was conserved in the corresponding intron regions and, consequently, gene expression was also altered in HBC.

Conclusions: This study provides good evidence for the conservation of epigenetic regulation in CMT and HBC, and suggests that intronic methylation can be an important factor in better understanding gene regulation in both CMT and HBC.
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http://dx.doi.org/10.1186/s13148-020-00888-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374976PMC
July 2020

Analysis of opposing histone modifications H3K4me3 and H3K27me3 reveals candidate diagnostic biomarkers for TNBC and gene set prediction combination.

BMB Rep 2020 May;53(5):266-271

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great correlation with gene expression. A list of signature genes was defined as active (highly enriched H3K4me3), including NOVA1, NAT8L, and MMP16, and repressive genes (highly enriched H3K27me3), IRX2 and ADRB2, according to the distribution of these histone modifications on the promoter regions. To further enhance the investigation, potential candidates were also compared with other types of breast cancer to identify signs specific to TNBC. RNA-seq data was implemented to confirm and verify gene regulation governed by the histone modifications. Combinations of the biomarkers based on H3K4me3 and H3K27me3 showed the diagnostic value AUC 93.28% with P-value of 1.16e-226. The results of this study suggest that histone modification analysis of opposing histone modifications may be valuable toward developing biomarkers and targets for TNBC. [BMB Reports 2020; 53(5): 266-271].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262508PMC
May 2020

Transplantation of hMSCs Genome Edited with LEF1 Improves Cardio-Protective Effects in Myocardial Infarction.

Mol Ther Nucleic Acids 2020 Mar 18;19:1186-1197. Epub 2020 Jan 18.

Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea. Electronic address:

Stem cell-based therapy is one of the most attractive approaches to ischemic heart diseases, such as myocardial infarction (MI). We evaluated the cardio-protective effects of the human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) stably expressing lymphoid enhancer-binding factor 1 (LEF1; LEF1/hUCB-MSCs) in a rat model of MI. LEF1 overexpression in hUCB-MSCs promoted cell-proliferation and anti-apoptotic effects in hypoxic conditions. For the application of its therapeutic effects in vivo, the LEF1 gene was introduced into an adeno-associated virus integration site 1 (AAVS1) locus, known as a safe harbor site on chromosome 19 by CRISPR/Cas9-mediated gene integration in hUCB-MSCs. Transplantation of LEF1/hUCB-MSCs onto the infarction region in the rat model significantly improved overall survival. The cardio-protective effect of LEF1/hUCB-MSCs was proven by echocardiogram parameters, including greatly improved left-ventricle ejection fraction (EF) and fractional shortening (FS). Moreover, histology and immunohistochemistry successfully presented reduced MI region and fibrosis by LEF1/hUCB-MSCs. We found that these overall positive effects of LEF1/hUCB-MSCs are attributed by increased proliferation and survival of stem cells in oxidative stress conditions and by the secretion of various growth factors by LEF1. In conclusion, this study suggests that the stem cell-based therapy, conjugated with genome editing of transcription factor LEF1, which promotes cell survival, could be an effective therapeutic strategy for cardiovascular disease.
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http://dx.doi.org/10.1016/j.omtn.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019046PMC
March 2020

Somatic Mutation of (H1047R) Is a Common Driver Mutation Hotspot in Canine Mammary Tumors as Well as Human Breast Cancers.

Cancers (Basel) 2019 Dec 12;11(12). Epub 2019 Dec 12.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Breast cancer is one of the most frequently diagnosed cancers in both women and female dogs. Genome-wide association studies in human breast cancer (HBC) have identified hundreds of genetic variations and somatic driver mutations. However, only a handful of variants have been studied for rare HBC and their associations remain inconclusive. Spontaneous canine mammary tumor (CMT) is a great model for HBC, with clinical similarity. We thus performed whole-exome sequencing in 20 pairs of CMT and normal tissues in dogs. We newly found that was the most frequently mutated gene in CMT (45%). Furthermore, canine A3140G (H1047R), at what is known as the mutational hotspot of HBC, is also a hotspot in CMT. Targeted sequencing confirmed that 29% of CMTs had the same A3140G mutation. Integration of the transcriptome suggests that the (H1047R) induced cell metabolism and cell cycle via an increase of and a decrease of but had no effect on cell apoptosis. We identified additional significantly mutated genes, including and , which have not been reported in HBC. Our study recapitulated some known HBC-associated genes and human cancer signatures in CMT, and identified novel genes that may be relevant to HBC. This study may allow us to better understand both HBC and CMT and lend new insights into the development of biomarkers.
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http://dx.doi.org/10.3390/cancers11122006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966585PMC
December 2019

Author Correction: Methylation of LINE-1 in cell-free DNA serves as a liquid biopsy biomarker for human breast cancers and dog mammary tumors.

Sci Rep 2019 Nov 20;9(1):17459. Epub 2019 Nov 20.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, South Korea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-019-53895-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863920PMC
November 2019

Genome-Wide Methylation Profiling in Canine Mammary Tumor Reveals miRNA Candidates Associated with Human Breast Cancer.

Cancers (Basel) 2019 Sep 29;11(10). Epub 2019 Sep 29.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Genome-wide methylation profiling is used in breast cancer (BC) studies, because DNA methylation is a crucial epigenetic regulator of gene expression, involved in many diseases including BC. We investigated genome-wide methylation profiles in both canine mammary tumor (CMT) tissues and peripheral blood mononuclear cells (PBMCs) using reduced representation bisulfite sequencing (RRBS) and found unique CMT-enriched methylation signatures. A total of 2.2-4.2 million cytosine-phosphate-guanine (CpG) sites were analyzed in both CMT tissues and PBMCs, which included 40,000 and 28,000 differentially methylated regions (DMRs) associated with 341 and 247 promoters of differentially methylated genes (DMGs) in CMT tissues and PBMCs, respectively. Genes related to apoptosis and ion transmembrane transport were hypermethylated, but cell proliferation and oncogene were hypomethylated in tumor tissues. Gene ontology analysis using DMGs in PBMCs revealed significant methylation changes in the subset of immune cells and host defense system-related genes, especially chemokine signaling pathway-related genes. Moreover, a number of CMT tissue-enriched DMRs were identified from the promoter regions of various microRNAs (miRNAs), including cfa-mir-96 and cfa-mir-149, which were reported as cancer-associated miRNAs in humans. We also identified novel miRNAs associated with CMT which can be candidates for new miRNAs associated with human BC. This study may provide new insight for a better understanding of aberrant methylation associated with both human BC and CMT, as well as possible targets for methylation-based BC diagnostic markers.
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http://dx.doi.org/10.3390/cancers11101466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827104PMC
September 2019

Transposable element-mediated structural variation analysis in dog breeds using whole-genome sequencing.

Mamm Genome 2019 10 15;30(9-10):289-300. Epub 2019 Aug 15.

Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.

Naturally occurring diseases in dogs provide an important animal model for studying human disease including cancer, heart disease, and autoimmune disorders. Transposable elements (TEs) make up ~ 31% of the dog (Canis lupus familiaris) genome and are one of main drivers to cause genomic variations and alter gene expression patterns of the host genes, which could result in genetic diseases. To detect structural variations (SVs), we conducted whole-genome sequencing of three different breeds, including Maltese, Poodle, and Yorkshire Terrier. Genomic SVs were detected and visualized using BreakDancer program. We identified a total of 2328 deletion SV events in the three breeds compared with the dog reference genome of Boxer. The majority of the genetic variants were found to be TE insertion polymorphism (1229) and the others were TE-mediated deletion (489), non-TE-mediated deletion (542), simple repeat-mediated deletion (32), and other indel (36). Among the TE insertion polymorphism, 286 elements were full-length LINE-1s (L1s). In addition, the 49 SV candidates located in the genic regions were experimentally verified and their polymorphic rates within each breed were examined using PCR assay. Polymorphism analysis of the genomic variants revealed that some of the variants exist polymorphic in the three dog breeds, suggesting that their SV events recently occurred in the dog genome. The findings suggest that TEs have contributed to the genomic variations among the three dog breeds of Maltese, Poodle, and Yorkshire Terrier. In addition, the polymorphic events between the dog breeds indicate that TEs were recently retrotransposed in the dog genome.
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http://dx.doi.org/10.1007/s00335-019-09812-5DOI Listing
October 2019

Upregulation of Complement Factor H by SOCS-1/3⁻STAT4 in Lung Cancer.

Cancers (Basel) 2019 Apr 3;11(4). Epub 2019 Apr 3.

Department of Veterinary Biochemistry, The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Complement factor H (CFH) is a fluid phase regulator of complement proteins and functions to prevent complement attack and immune surveillance. CFH is known to inactivate therapeutic antibody-dependent complement-mediated cellular cytotoxicity. We found that CFH was highly expressed in human lung cancer cells and tissues. To investigate mechanisms of CFH upregulation, we searched for a CFH transcription factor and its regulatory factors. First, signal transducer and activator of transcription 4 (STAT4) expression patterns coincided with CFH expression patterns in lung cancer tissues. Knockdown of STAT4 led to decreased CFH secretion from lung cancer cells. STAT4 bound directly to the CFH promoter, as demonstrated by luciferase reporter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP) assay, suggesting that STAT4 is a transcription factor for CFH. In addition, a low level of suppressors of cytokine signaling (SOCS)-1/3, a Janus kinase (JAK) inhibitor, was observed in lung cancer cells and its transfection decreased CFH protein levels and promoter activity. Unexpectedly, the low level of SOCS-1/3 was not due to epigenetic silencing. Instead, differential methylation was found on the regulatory region of STAT4 between normal and lung cancer cells. In conclusion, our results demonstrated that CFH is upregulated by constitutive activation of STAT4, which is accounted for by SOCS silencing in lung cancer cells.
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http://dx.doi.org/10.3390/cancers11040471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520728PMC
April 2019

Concise approach for screening long non-coding RNAs functionally linked to human breast cancer associated genes.

Exp Mol Pathol 2019 06 3;108:89-96. Epub 2019 Apr 3.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, South Korea. Electronic address:

Cancer research studies using next-generation sequencing have revealed a number of genes of which aberrant expression is associated with various cancers. Recently, long non-coding RNA (lncRNA) has been highlighted due to its tissue-specific expression and cell cancerization functions, such as the regulation of key tumor suppressors. In this study, we suggest a very efficient approach to survey lncRNAs putatively associated with breast cancer. We targeted lncRNAs linked with breast cancer associated genes (BCAGs) and analyzed their expression pattern in human breast cancer cell lines. A total of 337 BCAGs were retrieved from literature review and the existence of 121 lncRNAs were identified from the 15 kb up- and downstream regions of the list of genes. Twenty lncRNAs' expression were detectable in human breast cancer cell lines with different expression patterns. Interestingly, the expression of three lncRNAs, two up-regulated (RAD51C v.4, LOC105371849) and one down-regulated (LOC102724064), were closely correlated with adjacent BCAGs (RAD51C, HEATR6 and BRMS1) in breast cancer cell lines. We thus demonstrated association between the lncRNA and its adjacent BCAG using LOC105371849-HEATR6, of which the function and regulation in breast cancer are still unknown. Knockdown of LOC105371849 by siRNA decreased the expression of HEATR6 mRNA in the MCF7 human breast cancer cell line. In conclusion, this study provides a better understanding about the biological roles of lncRNAs in breast cancer and may be useful in the investigation of proper targets for diagnostic and/or therapeutic breast cancer markers using public databases.
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http://dx.doi.org/10.1016/j.yexmp.2019.04.003DOI Listing
June 2019

Methylation of LINE-1 in cell-free DNA serves as a liquid biopsy biomarker for human breast cancers and dog mammary tumors.

Sci Rep 2019 01 17;9(1):175. Epub 2019 Jan 17.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul, South Korea.

Breast cancer (BC) is one of the most common cancers in both women and female dogs. Methylation changes of LINE-1 have been reported in human cancers. The aim of this study was to determine the hypomethylation of canine LINE-1 in liquid biopsies for canine mammary tumors (CMT) and to assess its diagnostic performance in human plasma. BC associated LINE-1 methylation was measured by methylation sensitive (HpaII) and insensitive (MspI) restriction enzyme digestion followed by real-time PCR using the cfDNA isolated from 300 µl of plasma. The relative level of methylated canine LINE-1 was less than 0.4 in the benign and malignant CMTs (0.29 ± 0.061 and 0.39 ± 0.066, respectively) when it was 0.92 ± 0.067 in the healthy controls. The area under the ROC curve (AUC) was significantly high in both benign and malignant tumors (0.97 and 0.93). Furthermore, this approach was also successfully implemented in a set of 26 human BCs with 10 healthy controls (AUC = 0.78). Altogether, our data suggest that the comparative approach using a dog model might be helpful to rapidly develop a new diagnostic biomarker and that the methylation of LINE-1 in cfDNA may be a good target as a diagnostic marker of both human BC and CMT.
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http://dx.doi.org/10.1038/s41598-018-36470-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336845PMC
January 2019

Comparison of additional minocycline versus iodopovidone pleurodesis during video-assisted thoracoscopic bleb resection for primary spontaneous pneumothorax: a propensity score-matched analysis.

J Thorac Dis 2018 Sep;10(9):5443-5448

Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.

Background: The optimal chemical agent for additional pleurodesis during video-assisted thoracoscopic surgery (VATS) bleb resection in primary spontaneous pneumothorax (PSP) remains controversial. We compared the efficacy and safety of iodopovidone with those of minocycline for additional chemical pleurodesis during VATS bleb resection.

Methods: Of 332 patients who underwent VATS bleb resection, 299 patients diagnosed with PSP were enrolled in this study. The patients were divided into two groups according to the chemical agents used for additional pleurodesis (iodopovidone versus minocycline). Propensity score matching was performed on the basis of the preoperative clinical parameters. Postoperative complications, chest tube indwelling time, postoperative hospital stay, and recurrence rate were compared between the two groups.

Results: The median duration of follow-up was 14 months (range, 1-94 months). After propensity score matching, 94 patients from the iodopovidone group and 94 patients from the minocycline group were matched. The perioperative outcomes, including fever, prolonged air-leak, prolonged-effusion, postoperative bed-side pleurodesis, and rehospitalization because of complications, were not significantly different between the two groups. However, the amount of drainage during the first two postoperative days, duration of chest tube indwelling, and duration of hospitalization were significantly shorter in the minocycline group (P<0.001).

Conclusions: This study confirmed the safety of both minocycline and iodopovidone for additional pleurodesis. However, we carefully recommend minocycline over iodopovidone for pleurodesis because of faster postoperative recovery.
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http://dx.doi.org/10.21037/jtd.2018.09.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196187PMC
September 2018

Transcriptome Signatures of Canine Mammary Gland Tumors and Its Comparison to Human Breast Cancers.

Cancers (Basel) 2018 09 7;10(9). Epub 2018 Sep 7.

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Breast cancer (BC)/mammary gland carcinoma (MGC) is the most frequently diagnosed and leading cause of cancer-related mortality in both women and canines. To better understand both canine MGC and human BC-specific genes, we sequenced RNAs obtained from eight pairs of carcinomas and adjacent normal tissues in dogs. By comprehensive transcriptome analysis, 351 differentially expressed genes (DEGs) were identified in overall canine MGCs. Based on the DEGs, comparative analysis revealed correlation existing among the three histological subtypes of canine MGC (ductal, simple, and complex) and four molecular subtypes of human BC (HER2+, ER+, ER&HER2+, and TNBC). Eight DEGs shared by all three subtypes of canine MGCs had been previously reported as cancer-associated genes in human studies. Gene ontology and pathway analyses using the identified DEGs revealed that the biological processes of cell proliferation, adhesion, and inflammatory responses are enriched in up-regulated MGC DEGs. In contrast, fatty acid homeostasis and transcription regulation involved in cell fate commitment were down-regulated in MGC DEGs. Moreover, correlations are demonstrated between upstream promoter transcripts and DEGs. Canine MGC- and subtype-enriched gene expression allows us to better understand both human BC and canine MGC, yielding new insight into the development of biomarkers and targets for both diseases.
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http://dx.doi.org/10.3390/cancers10090317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162473PMC
September 2018

Histopathologic Finding of Perieschar Lesions in Tsutsugamushi Disease Shows Lymphocytic Vasculitis Mimicking Angiocentric Lymphoma.

Ann Dermatol 2018 Feb 26;30(1):29-35. Epub 2017 Dec 26.

Department of Dermatology, Kosin University College of Medicine, Busan, Korea.

Background: Tsutsugamushi disease is an acute, febrile, infectious disease caused by . Several studies investigating the histopathologic findings of eschars in tsutsugamushi disease reported leukocytoclastic vasculitis and neutrophil infiltration as the major findings. However, these findings may result from secondary changes following tissue necrosis. The histopathologic findings of perieschar lesions may be important to understand the primary changes associated with tsutsugamushi disease.

Objective: To investigate characteristic histopathologic features of perieschar lesions and suppose the mechanism of vascular pathophysiological changes associated with tsutsugamushi disease.

Methods: We analyzed histopathological slides of perieschar lesions in 12 patients diagnosed with tsutsugamushi disease.

Results: In the epidermis, exocytosis of mononuclear cells (75.0%) and basal vacuolar changes (66.7%) were frequent. In the dermis, perivascular, interstitial, and perineural mononuclear cell infiltration (100.0%, 83.3%, and 83.3%, respectively), as well as thrombosis (83.3%), atypical lymphocyte infiltration (91.7%), and mitotic figures (83.3%) were commonly seen. Lymphocytic vasculitis and mononuclear cell infiltration around eccrine glands were found in all cases, but eosinophil infiltration was only found in one patient (8.3%). However, the characteristic findings of eschar lesions, such as leukocytoclastic vasculitis and neutrophil infiltration, were not found in perieschar lesions.

Conclusion: The major histopathologic findings in the perieschar lesions of tsutsugamushi disease were lymphocytic vasculitis and atypical lymphocytic infiltration, mimicking lymphoma. Therefore, we suggest that this lesion should be added to the list of pseudolymphomas. To observe these characteristic histopathologic features, we also recommend that skin biopsies should be performed on perieschar lesions, not eschar lesions.
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http://dx.doi.org/10.5021/ad.2018.30.1.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762473PMC
February 2018

[Clinical Course of Percutaneous Endoscopic Gastrostomy: A Single-center Observational Study].

Korean J Gastroenterol 2018 01;71(1):24-30

Department of Internal Medicine and Ewha Medical Research Institute, Ewha Womans University College of Medicine, Seoul, Korea.

Background/aims: Percutaneous endoscopic gastrostomy (PEG) is a widely used method for long-term tube feeding. This study aimed to investigate the clinical characteristics and outcomes of patients who utilized long-term feeding tube via PEG.

Methods: The medical records of 137 patients who underwent PEG tube insertion at Ewha Womans University Mokdong Hospital between January 2002 and December 2013 were reviewed.

Results: PEG was indicated most frequently for cerebrovascular accidents (66 patients, 48.2%), followed by head and neck cancer (20 patients, 14.6%), and Parkinson's disease (10 patients, 7.3%). The tubes were endoscopically inserted in 133 patients (97.1%); 4 patients (2.9%) underwent radiologic intervention. The tubes of 90 patients (65.7%) were exchanged at least once during the follow- up period. At the first exchange, 71 patients (78.9%) had their tubes exchanged by endoscopy, 24 patients (16.7%) by manually, and 4 patients (4.4%) by radiologic intervention. Of the 61 patients (44.5%) who had their tubes exchanged twice, 44 patients (72.1%) changed their tubes by endoscopic exchange, 13 patients (21.3%) by manually, and 4 patients (4.4%) via radiologic intervention. The mean time interval between the initial insertion and the first exchange was 9.83±6.19 months, and that between the initial insertion and the second exchange was 10.7±6.25 months. Of all the 137 patients, acute complications at initial insertion occurred in only 18 patients (13.1%), with insertion site infection (9 patients, 6.6%) being the most common acute complication.

Conclusions: PEG appears to be a safe procedure for providing long-term tube feeding. Our results may help to develop strategies for further management of subjects receiving feeding tubes via PEG.
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http://dx.doi.org/10.4166/kjg.2018.71.1.24DOI Listing
January 2018

Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients.

PLoS One 2017 5;12(10):e0186120. Epub 2017 Oct 5.

Departments of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.

Objectives: Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients.

Method: A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1-7 weeks after treatment), and period 2 (8-16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing.

Results: A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2.

Conclusions: About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186120PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628927PMC
November 2017

Highly Variable Genomic Landscape of Endogenous Retroviruses in the C57BL/6J Inbred Strain, Depending on Individual Mouse, Gender, Organ Type, and Organ Location.

Int J Genomics 2017 29;2017:3152410. Epub 2017 Aug 29.

Department of Surgery, University of California, Davis, Sacramento, CA, USA.

Transposable repetitive elements, named the "TREome," represent ~40% of the mouse genome. We postulate that the germ line genome undergoes temporal and spatial diversification into somatic genomes in conjunction with the TREome activity. C57BL/6J inbred mice were subjected to genomic landscape analyses using a TREome probe from murine leukemia virus-type endogenous retroviruses (MLV-ERVs). None shared the same MLV-ERV landscape within each comparison group: (1) sperm and 18 tissues from one mouse, (2) six brain compartments from two females, (3) spleen and thymus samples from four age groups, (4) three spatial tissue sets from two females, and (5) kidney and liver samples from three females and three males. Interestingly, males had more genomic MLV-ERV copies than females; moreover, only in the males, the kidneys had higher MLV-ERV copies than the livers. Perhaps, the mouse-, gender-, and tissue/cell-dependent MLV-ERV landscapes are linked to the individual-specific and dynamic phenotypes of the C57BL/6J inbred population.
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http://dx.doi.org/10.1155/2017/3152410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603323PMC
August 2017

Kerion celsi caused by Trichophyton erinacei from a hedgehog treated with terbinafine.

J Dermatol 2017 Sep 5;44(9):1070-1071. Epub 2016 Nov 5.

Department of Dermatology, Kosin University College of Medicine, Busan, Korea.

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http://dx.doi.org/10.1111/1346-8138.13647DOI Listing
September 2017

Comparison of clinical outcomes after endoscopic submucosal dissection and surgery in the treatment of early gastric cancer: A single-institute study.

Medicine (Baltimore) 2017 Jul;96(30):e7210

Department of Internal Medicine Surgery Pathology, Ewha Womans University College of Medicine, Seoul, Korea.

The feasibility of expanding the indications for endoscopic submucosal dissection to treat early gastric cancer based on long-term outcomes has shown conflicting results. This study aimed to investigate whether outcomes or adverse events associated with endoscopic submucosal dissection are comparable to those of surgery for early gastric cancer that including the absolute and expanded indications.Data of 159 early gastric cancers from 153 patients treated with endoscopic submucosal dissection or surgery between January 2004 and October 2014 were reviewed retrospectively. Early gastric cancers fulfilled the absolute or expanded indications with differentiated type adenocarcinoma were included.The endoscopic submucosal dissection and surgery group showed no significant difference in the incidence of residual disease (P = .48), local recurrence (P = .46), and metachronous cancer (P = .22). Kaplan-Meier analysis showed no significant difference in 2-year (97.6% versus [vs] 92.4%; P = .45) and 5-year (95.8% vs 95.6%; P = .26) overall survival rate between 2 groups. There was also no significant difference in 2-year (100% vs 94.1%; P = .98) and 5-year (100% vs 98.4%; P = .89) disease-free survival rate. Early and late adverse events also showed no significant differences.For the treatment of early gastric cancer fulfilled absolute and expanded indications, endoscopic submucosal dissection is not inferior modality regarding the clinical outcomes and safety, compared with surgery.
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http://dx.doi.org/10.1097/MD.0000000000007210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627802PMC
July 2017

The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis.

J Mammary Gland Biol Neoplasia 2017 Sep 29;22(3):159-170. Epub 2017 Jun 29.

Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.

Smoking cigarettes is one of the most concerning issues that leads to tobacco-related cancers and can even result in death. Therefore, these issues should be addressed with a great sense of urgency with low-cost and simple approaches. Over the past several years, the scientific community has attempted to find solutions to overcome this issue. Thus, a large number of excellent studies have been reported in this field, and summarizing these results and providing important roadmaps for future studies is currently of great importance. Finding an outstanding solution to address aforementioned issue would be of great value to the community and to the social. Tobacco contains thousands of chemicals, and sixty-nine compounds have been established as human carcinogens; specifically, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the strongest carcinogen among the tobacco-specific nitrosamines. Tobacco carcinogens are also linked to mammary gland pathogenesis and increased risk of developing many cancers, including breast cancer, the most common cancer in women worldwide. This mini-review summarizes the role of NNK and the mechanisms of its receptor, nicotine acetylcholine receptor (nAChR), signaling in breast cancer based on publications identified using the keywords "secondhand smoke (SHS)", "Nitrosamines" and "breast cancer". Furthermore, this review considers the risk of NNK to the public in an effort to reduce exposure to SHS in women and their chances of developing breast cancer.
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http://dx.doi.org/10.1007/s10911-017-9381-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579148PMC
September 2017

Degos-Like Lesions Associated with Systemic Lupus Erythematosus.

Ann Dermatol 2017 Apr 24;29(2):215-218. Epub 2017 Mar 24.

Department of Dermatology, Kosin University College of Medicine, Busan, Korea.

Degos disease, also referred to as malignant atrophic papulosis, was first described in 1941 by Köhlmeier and was independently described by Degos in 1942. Degos disease is characterized by diffuse, papular skin eruptions with porcelain-white centers and slightly raised erythematous telangiectatic rims associated with bowel infarction. Although the etiology of Degos disease is unknown, autoimmune diseases, coagulation disorders, and vasculitis have all been considered as underlying pathogenic mechanisms. Approximately 15% of Degos disease have a benign course limited to the skin and no history of gastrointestinal or central nervous system (CNS) involvement. A 29-year-old female with history of systemic lupus erythematosus (SLE) presented with a 2-year history of asymptomatic lesions on the dorsum of all fingers and both knees. The patient had only skin lesions and no gastrointestinal or CNS vasculitis symptoms. Her skin lesions were umbilicated, atrophic porcelain-white lesions with a rim of erythema. On the basis of clinical, histologic, and laboratory findings, a diagnosis of Degos-like lesions associated with SLE was made. The patient had been treated for SLE for 7 years. Her treatment regimen was maintained over a 2 month follow-up period, and the skin lesions improved slightly with no development of new lesions.
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http://dx.doi.org/10.5021/ad.2017.29.2.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383749PMC
April 2017

The Therapeutic Efficacy of Tonsil-derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-induced Acute Murine Colitis Model.

Korean J Gastroenterol 2017 Feb;69(2):119-128

Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea.

Background/aims: Mesenchymal stem cells (MSCs) are multipotent progenitor cells currently under investigation for its efficacy as the treatment for inflammatory bowel disease. In this study, we evaluated the efficacy of tonsil-derived mesenchymal stem cells (T-MSCs) as a novel source of mesenchymal stem cells and traced their localization in a murine model of acute colitis induced by dextran sulfate sodium (DSS).

Methods: C57BL/6 mice were randomly assigned to the following three groups: the normal control group, DSS colitis group (DSS+phosphate buffered saline), and T-MSC group (DSS+T-MSCs, 1×10). The severity of colitis was assessed by determining the severity of symptoms of colitis, colon length, histopathologic grade, and levels of inflammatory cytokines. T-MSCs labeled with PKH26 were traced .

Results: The T-MSC group, compared with the DSS colitis group, showed a significantly lower disease activity index (11.3±1.5 vs. 8.3±1.9, p=0.015) at sacrifice and less reduction of body weight (-17.1±5.0% vs. -8.1±6.9%, p=0.049). In the T-MSC group, the histologic colitis score was significantly decreased compared with the DSS colitis group (22.6±3.8 vs. 17.0±3.4, p=0.039). IL-6 and IL-1β, the pro-inflammatory cytokines, were also significantly reduced after a treatment with T-MSCs. tracking revealed no PKH26-labelled T-MSCs in the colonic tissue of mice with acute colitis.

Conclusions: In the acute colitis model, we demonstrated that the administration of T-MSCs ameliorates inflammatory symptoms and histology. Moreover, the anti-inflammatory activities of T-MSCs were independent of gut homing.
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http://dx.doi.org/10.4166/kjg.2017.69.2.119DOI Listing
February 2017
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