Publications by authors named "Ji Young Song"

98 Publications

Production of IL-31 in CD45ROCLAH4R T Cells in Atopic Dermatitis.

J Clin Med 2021 May 4;10(9). Epub 2021 May 4.

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea.

IL-31 is involved in pruritus in atopic dermatitis (AD) and the pathogenesis of AD. However, the mechanism of IL-31 production is not fully understood. We sought to investigate the association between CD45ROCLAH4R T cells and IL-31 production. Immunofluorescence studies were performed retrospectively on punch-biopsy specimens from five people with AD and three healthy controls. In addition, blood samples were collected prospectively from eight patients with AD and eight healthy controls for sorting CD45ROCLAH4R T cells. There was no overlap of patients between the biopsy group and the blood sampling group. Sorted cells were stimulated with 4-methylhistamine (4MH), and the level of IL-31 was measured by an enzyme-linked immunosorbent assay. Immunofluorescence showed co-localization of H4R and IL-31 in lesional AD skin but not in normal skin of healthy controls. The proportion of CLAH4R T cells among CD3CD45RO lymphocytes was 18.3 ± 6.2% in patients with AD and 11.2 ± 7.6% in healthy controls. In the AD group, production of IL-31 by CD45ROCLAH4R T cells increased from 32.4 ± 13.3 pg/mL to 47.5 ± 18.7 pg/mL by 4MH stimulation after 24 h ( < 0.001). However, in the control group, production of IL-31 was 20.1 ± 10.6 pg/mL without and 22.1 ± 9.3 pg/mL with 4MH stimulation ( > 0.05). According to our study, CD45ROCLAH4R T cells are an important source of IL-31 in AD, and may be a target for treatment of IL-31-induced pruritus.
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http://dx.doi.org/10.3390/jcm10091976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124489PMC
May 2021

Implant complications in bruxism patients.

Authors:
Ji-Young Song

J Korean Assoc Oral Maxillofac Surg 2021 Apr;47(2):149-150

Department of Dentistry, School of Medicine, Jeju National University, Jeju, Korea.

Bruxism is defined as a parafunctional activity during sleep or while awake that includes locking and grinding of teeth and clenching. It generates excessive occlusal force that may lead to implant failure. Therefore, diagnosis of bruxism and providing specific protocols such as occlusal splint and/or injection of botulinum toxin before implant installation are important to prevent increases the risk of implant failure in bruxism patients.
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http://dx.doi.org/10.5125/jkaoms.2021.47.2.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084741PMC
April 2021

Type 2 human papillomavirus E7 attenuates E-cadherin expression in human keratinocytes.

J Microbiol 2021 Jun 29;59(6):616-625. Epub 2021 Mar 29.

Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, 34054, Republic of Korea.

Human papillomaviruses (HPVs) are known to utilize the down-regulation of epithelial (E)-cadherin, a major component of adherens junctions of keratinocytes, to evade host immune surveillance in high-risk group. However, the effects of HPV on the function of E-cadherin in low-risk groups remain unknown. We investigated whether type 2 HPV (HPV-2) E7 could induce alterations in E-cadherin expression in transiently transfected keratinocytes and cell lines expressing HPV-2 E7. To examine the expression pattern of E-cadherin in cutaneous warts and normal skin samples, immunohistochemical analysis was performed. Quantitative real-time polymerase chain reactions, luciferase assays, western blot, immunocytochemistry, and electron microscopy were used to evaluate the mRNA and protein expression levels of E-cadherin in normal human epidermal keratinocytes transfected with HPV-2 E7 plasmid DNA or E7-specific siRNA and in E7-expressing cell lines. E-cadherin expression levels in HPV-2 positive cutaneous warts were significantly decreased compared to those in normal skin (p < 0.05). Similarly, the mRNA and protein expression levels of E-cadherin in E7 transiently transfected cells were significantly decreased compared to those in empty vector-transfected cells. The decreases were restored by transfection with E7-specific siRNA (p < 0.05). Likewise, cell lines expressing E7 showed a decreased expression of E-cadherin. When the cells were cultured in low attachment plates, cell-to-cell aggregation was inhibited. Taken together, our data suggest that HPV-2 E7, the causative agent of cutaneous warts, could mediate the transcriptional repression of E-cadherin.
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http://dx.doi.org/10.1007/s12275-021-0690-yDOI Listing
June 2021

Epigallocatechin-3-gallate Can Prevent Type 2 Human Papillomavirus from Suppressing Interferon-Stimulated Genes.

Int J Mol Sci 2021 Feb 28;22(5). Epub 2021 Feb 28.

Program of Immunology & Microbiology, Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea.

Human papillomavirus (HPV) in high-risk groups is known to suppress the type I interferon (IFN) signaling pathway leading to the transcription of interferon-stimulated genes (ISGs), which have many antiviral functions. However, the effects of HPV on the action of various ISGs in low-risk groups are not fully understood. We aimed to investigate whether antiviral ISGs are expressed in transfected keratinocytes with type 2 HPV (HPV-2) . The mRNA and protein expressions of ISGs and type I IFN signaling pathway components were evaluated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and/or immunohistochemistry. Compared with normal skin, mRNA expression of all ISGs in HPV-2 positive cutaneous warts was significantly decreased ( < 0.05). In comparison with empty vector transfection, transfection significantly down-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly up-regulated by siRNA transfection ( < 0.05). Interestingly, epigallocatechin-3-gallate (EGCG) pretreatment up-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly down-regulated by transfection ( < 0.05). Our results demonstrate that EGCG is a potential candidate for cutaneous wart prevention.
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http://dx.doi.org/10.3390/ijms22052418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957673PMC
February 2021

TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis.

Cancer Res Treat 2021 Jan 16;53(1):9-24. Epub 2020 Sep 16.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be 'some sort of problem.' Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2).

Materials And Methods: Modified Tukey's fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes.

Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines.

Conclusion: Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.
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http://dx.doi.org/10.4143/crt.2020.434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812009PMC
January 2021

[Opening Status of the Korea Midwifery Birthing Centers and Development of Midwifery Practice Guideline].

J Korean Acad Nurs 2020 Aug;50(4):583-598

College of Nursing, Korea University, Seoul, Korea.

Purpose: This study was to investigate the operational status of the midwifery birthing centers (MBCs) and midwives' job status (Phase 1) and to develop midwifery practice guidelines (MPG) (Phase 2) in Korea.

Methods: In the first phase, the subjects were 15 midwives who operated 11 of 14 MBCs that were opened as of August 2018. The questionnaire consisted of items to measure the operational status of the MBC and midwives' job status. In the second phase, the MPG was developed from literature review, interviews with five midwives opening their MBCs, surveys with 74 midwives, and a validity evaluation conducted by seven experts.

Results: The distribution of operating MBCs was five in Gyunggi-do, two each in Seoul and Incheon, one each in Busan, Chungcheongbuk-do, Gyeongsangbuk-do, Gyeongsangnam-do and Jeju-do. The mean age of midwives was 54.3 and all were female. In 2017, a total of 762 births including 81 homebirths were performed by midwives. The job performance was highest in the order of neonatal care 3.81, childbirth care 3.56, and postpartal care 3.53, respectively. The MPG included seven areas of prenatal care, childbirth care, postpartal care, neonatal care, primary health care, law/ethics, and administration, with 56 tasks and 166 task elements.

Conclusion: This study provides the valid basic data for the operational status of the MBC and the midwives' job status. The MPG describes the midwife's job and may be used as basic data for preparing policies for the development of midwifery practice in Korea.
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http://dx.doi.org/10.4040/jkan.20032DOI Listing
August 2020

Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes.

J Biol Chem 2020 05 17;295(19):6754-6766. Epub 2020 Mar 17.

Department of Biological Sciences, Chungnam National University, Daejeon 34134, Korea

The atypical trichromatic cyanobacterial phytochrome TP1 from ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of TP1 (here renamed TCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of sp. PCC7910, sp. PCC10023, and sp. PCC7513. Recombinant photosensory core modules of TCCP, TCCP, and TCCP exhibited violet-blue-absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15 bilin chromophores, but differ in the ionization state of the noncanonical "second" cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.
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http://dx.doi.org/10.1074/jbc.RA120.012950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212627PMC
May 2020

Amplification as a Predictive Biomarker in Response to Ceritinib in Small Cell Lung Cancer.

Mol Ther Oncolytics 2020 Mar 10;16:188-196. Epub 2020 Jan 10.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Small cell lung cancer (SCLC) is a fast-growing and malignant cancer that responds well to chemotherapy; however, the survival rate is less than 15% after 2 years of diagnosis. Therefore, novel therapeutic agents for treating SCLC patients need to be evaluated. This study aims to identify the therapeutic targets based on the comprehensive genomic profiling of SCLC patients. Among the molecular-profiled SCLC samples obtained using targeted sequencing, the array-based comparative genomic hybridization (array CGH) identified focal () amplification in the SCLC patients. amplification was confirmed in 5% of 73 SCLC patients. To determine whether amplification could act as a therapeutic target, we generated a patient-derived xenograft (PDX) model and subsequently screened 43 targeted agents using the PDX-derived cells (PDCs). Ceritinib significantly inhibited the cell growth and impaired the tumor sphere formation in IRS2-expressing PDCs. Its effects were confirmed in various assays and were further validated in the mouse xenograft models. In this study, we present that amplification and/or expression serve as preclinical implications for a novel therapeutic target in SCLC progression. Furthermore, we suggest that insulin-like growth factor-1 (IGF-1) receptor inhibitor-based therapy could be used for treating SCLC with amplification.
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http://dx.doi.org/10.1016/j.omto.2019.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029374PMC
March 2020

Peptide transporter2 (PTR2) enhances water uptake during early seed germination in Arabidopsis thaliana.

Plant Mol Biol 2020 Apr 29;102(6):615-624. Epub 2020 Jan 29.

Department of Biological Sciences, Chungnam National University, Daejeon, 34134, Republic of Korea.

Key Message: PTR2 in Arabidopsis thaliana is negatively regulated by ABI4 and plays a key role in water uptake by seeds, ensuring that imbibed seeds proceed to germination. Peptide transporters (PTRs) transport nitrogen-containing substrates in a proton-dependent manner. Among the six PTRs in Arabidopsis thaliana, the physiological role of the tonoplast-localized, seed embryo abundant PTR2 is unknown. In the present study, a molecular physiological analysis of PTR2 was conducted using ptr2 mutants and PTR2CO complementation lines. Compared with the wild type, the ptr2 mutant showed ca. 6 h delay in testa rupture and consequently endosperm rupture because of 17% lower water content and 10% higher free abscisic acid (ABA) content. Constitutive overexpression of the PTR2 gene under the control of the Cauliflower mosaic virus (CaMV) 35S promoter in ptr2 mutants rescued the mutant phenotypes. After cold stratification, a transient increase in ABA INSENSITIVE4 (ABI4) transcript levels during induction of testa rupture was followed by a similar increase in PTR2 transcript levels, which peaked prior to endosperm rupture. The PTR2 promoter region containing multiple CCAC motifs was recognized by ABI4 in electrophoretic mobility shift assays, and PTR2 expression was repressed by 67% in ABI4 overexpression lines compared with the wild type, suggesting that PTR2 is an immediate downstream target of ABI4. Taken together, the results suggest that ABI4-dependent temporal regulation of PTR2 expression may influence water status during seed germination to promote the post-germinative growth of imbibed seeds.
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http://dx.doi.org/10.1007/s11103-020-00967-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062858PMC
April 2020

Genomic Survey of Salt Acclimation-Related Genes in the Halophilic Cyanobacterium Euhalothece sp. Z-M001.

Sci Rep 2020 01 20;10(1):676. Epub 2020 Jan 20.

Department of Biological Sciences, Chungnam National University, Daejeon, 34134, Korea.

Like other halophilic cyanobacterial genomes, the de novo-assembled genome of Euhalothece sp. Z-M001 lacks genes encoding keto-carotenoid biosynthesis enzymes, despite the presence of genes encoding carotenoid-binding proteins (CBPs). Consistent with this, HPLC analysis of carotenoids identified β-carotene and zeaxanthin as the dominant carotenoids. CBPs coexpressed with the zeaxanthin biosynthesis gene increased the survival rates of Escherichia coli strains by preventing antibiotic-induced accumulation of reactive oxygen species (ROS). RNA-seq analysis of Euhalothece revealed that among various salt resistance-related genes, those encoding the Na transporting multiple resistance and pH adaptation (Mrp) systems, glycine betaine biosynthesis enzymes, exopolysaccharide metabolic enzymes, and CBPs were highly upregulated, suggesting their importance in hypersaline habitats. During the early phase of salt deprivation, the amounts of β-carotene and zeaxanthin showed a negative correlation with ROS content. Overall, we propose that in some halophilic cyanobacteria, β-carotene and zeaxanthin, rather than keto-carotenoids, serve as the major chromophores for CBPs, which in turn act as effective antioxidants.
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http://dx.doi.org/10.1038/s41598-020-57546-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971039PMC
January 2020

Increasing the dietary fiber contents in isomaltooligosaccharides by dextransucrase reaction with sucrose as a glucosyl donor.

Carbohydr Polym 2020 Feb 11;230:115607. Epub 2019 Nov 11.

Department of Food Science & Biotechnology, and Carbohydrate Bioproduct Research Center, Sejong University, Seoul 05006, Republic of Korea. Electronic address:

Isomaltooligosaccharides (IMOs) have been widely used as alternative sweeteners owing to their stabilities, low calorigenic, and prebiotic properties. The aim of this research was to improve the functionality of conventionally produced IMOs by increasing dietary fiber (DF) content with newly synthesized α-(1,6)-linkages through the dextransucrase reaction. To optimize the reaction conditions, various combinations of IMO and sucrose concentrations were applied as acceptor and donor molecules, respectively. Soluble DF content in the enzymatically-modified IMOs increased significantly with the initial substrate mixture of 10 % sucrose and 20 % IMOs; both DF and IMO contents increased to 35 % and 54 %, respectively. It was clearly suggested a simple dextransucrase-involved bioprocess could be applied to increase the DF content to the IMOs produced via a conventional process without scarifying the original IMO contents. Thus, it will be expected that the DF-enhanced IMO products are potentially applicable as functional ingredients as sugar substitutes in the food industry.
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http://dx.doi.org/10.1016/j.carbpol.2019.115607DOI Listing
February 2020

Effects of Eupatilin on Insulin-Like Growth Factor 1-Induced Lipogenesis and Inflammation of SZ95 Sebocytes.

Ann Dermatol 2019 Aug 1;31(4):479-482. Epub 2019 Jul 1.

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.5021/ad.2019.31.4.479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992769PMC
August 2019

Molecular changes in solitary fibrous tumor progression.

J Mol Med (Berl) 2019 10 18;97(10):1413-1425. Epub 2019 Jul 18.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.

Solitary fibrous tumors (SFTs) are NAB2-STAT6 fusion-associated neoplasms. There are several subtypes of NAB2-STAT6 fusions, but their clinical significances are still unclear. Moreover, the mechanisms of malignant progression are also poorly understood. In this study, using 91 SFT cases, we examined whether fusion variants are associated with clinicopathological parameters and also investigated the molecular mechanism of malignant transformation using whole-exome sequencing. We detected variant 1b (NAB2ex4-STAT6ex2) in 51/91 (56%) cases and variants 2a/2b (NAB2ex6-STAT6ex16/17) in 17/91 (19%) cases. The NAB2-STAT6 fusion variant types were significantly associated with their primary site (P < 0.001). In addition, a TERT promoter mutation was detected in 7/73 (10%) cases, and it showed a significant association with malignant SFTs (P = 0.003). To identify molecular changes during malignant progression, we selected an index patient to obtain parallel tissue samples from the primary and metastatic tumors. In the metastatic tissue, 10 unique molecular alterations, including those in TP53 and APAF1, were detected. In vitro functional experiments showed that APAF1 depletion increased the tumor potency of cells expressing NAB2-STAT6 fusion protein under treatment with staurosporine. We found that TP53 immunopositivity (P = 0.006) and loss of APAF1 immunoreactivity (P < 0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of TP53 and APAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation. KEY MESSAGES: We firstly found that the TERT promoter mutation was strongly associated with malignant SFTs (P = 0.003) and the representative 1b (NAB2ex4-STAT6ex2) or 2a (NAB2ex6-STAT6ex16) fusion variants similarly contribute to tumorigenicity. We also found that TP53 immunopositivity (P = 0.006) and loss of APAF1 immunoreactivity (P < 0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of TP53 and APAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation.
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http://dx.doi.org/10.1007/s00109-019-01815-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746689PMC
October 2019

Umbilical cord-derived mesenchymal stem cell extracts ameliorate atopic dermatitis in mice by reducing the T cell responses.

Sci Rep 2019 04 29;9(1):6623. Epub 2019 Apr 29.

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Mesenchymal stem cells derived from Wharton's jelly of the umbilical cord (UC-MSCs) have immunomodulatory properties. The aim of this study was to explore whether extracts of MSCs (MSC-Ex) could augment the low therapeutic efficacy of the whole cells in an Aspergillus fumigatus (Af)-induced atopic dermatitis (AD) model. LPS- or TNF-α/IFN-γ-stimulated keratinocytes (HaCaT cells) were treated with MSC-Ex, and the Af-induced AD model was established in BALB/c mice. In HaCaT cells, MSC-Ex treatment significantly reduced the inflammatory cytokine (IL-6, IL-1β, IL-4, IL-5 and TNF-α), iNOS and NF-κB levels, and upregulated the anti-inflammatory cytokines (IL-10 and TGF-β1). In the AD mice, the MSC-Ex group showed greatly reduced dermatitis, and lower clinical symptom scores and IgE levels. The histological dermatitis scores were also markedly lower in the MSC-Ex-treated animals compared with the MSC-treated group. Decreased levels of IFN-γ (Th1) and IL-17 (Th17), IL-4 and IL-13 (Th2) were detected in T cells and the skin tissue from the MSC-Ex treated AD mice. The therapeutic capacity of MSC-Ex was preserved after lyophilization and reconstitution. MSC-Ex treatment reproducibly suppresses dermatitis and inhibits the induction of inflammatory cytokines in the skin of AD mice. MSC-Ex is therefore a potential new treatment agent for AD.
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http://dx.doi.org/10.1038/s41598-019-42964-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488580PMC
April 2019

Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in -Rearranged NSCLC.

Clin Cancer Res 2018 09 18;24(17):4162-4174. Epub 2018 May 18.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.

Anaplastic lymphoma kinase (-positive cancers are sensitive to small-molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. We screened -rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence hybridization and then conducted multiplex gene expression analysis. We also performed a clinicopathologic analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and lung cancer model studies were performed. Among patients with -rearranged NSCLC, integrin β3 () was one of the overexpressed genes in comparison with that in ALK-negative NSCLC ( = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages ( < 0.005; < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity and (both < 0.05). We discovered a positive correlation between ALK and integrin β3 expression levels in -rearranged NSCLC. Our findings suggest that high integrin β3 expression in -rearranged NSCLC is associated with tumor progression and a worse prognosis. This finding demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with -rearranged NSCLC. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-3492DOI Listing
September 2018

Porcine Bone Incorporated With 4-Hexylresorcinol Increases New Bone Formation by Suppression of the Nuclear Factor Kappa B Signaling Pathway.

J Craniofac Surg 2018 Oct;29(7):1983-1990

Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, Skeletal Diseases Genome Research Center, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Objective: The objectives of this study were to evaluate the suppression of the nuclear factor kappa B (NF-kB) pathway by 4-hexylresorcinol (4HR), which was activated by tumor necrosis factor-α (TNF-α) in osteoblasts, and new bone formation by 4HR-incorporated porcine bone in an animal model.

Study Design: For the confirmation of successful incorporation of 4HR into porcine bone, scanning electron microscopy (SEM) and Fourier transform-infrared (FT-IR) analysis were performed. High performance liquid chromatography was performed for the analysis of the 4HR release profile from porcine bone. MC 3T3-E1 cells were used for the analysis of the NF-kB signaling pathway activation by western blotting and real-time reverse transcriptase polymerase chain reaction. New bone formation and the analysis of marker protein expression were studied in a rat calvarial critical-sized defect model.

Results: Both SEM and FT-IR analysis demonstrated successful incorporation of 4HR into porcine bone. Approximately 30% of 4HR was steadily released from porcine bone for 18 days. 4HR suppressed the NF-kB signaling pathway, which was activated by TNF-α application in MC 3T3-E1 cells. Histological analysis revealed that porcine bone particles with incorporated 4HR showed significantly greater new bone formation than those without 4HR at 4 and 8 weeks after operation (P < 0.05). The expression intensities of alkaline phosphatase, osteoprotegerin, and osteocalcin were also higher in the 4HR-incorporated group.

Conclusion: The application of 4HR suppressed the NF-kB signaling pathway in osteoblasts and 4HR-containing porcine bone particles promoted new bone formation in a rat calvarial defect model.
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http://dx.doi.org/10.1097/SCS.0000000000004517DOI Listing
October 2018

Psychological Risk Factors for Posttraumatic Stress Disorder in Workers After Toxic Chemical Spill in Gumi, South Korea.

Workplace Health Saf 2018 Aug 13;66(8):393-402. Epub 2018 Feb 13.

2 Dongguk University Ilsan Hospital.

The extent and severity of the psychological effects following chemical release disasters have not been widely reported. The aim of this study was to examine the prevalence of hydrogen fluoride (HF)-related posttraumatic stress disorder (PTSD) and to identify associated psychological risk factors. On September 2012, an estimated 8 to 12 tons of HF gas, which dissolves in air moisture to form droplets of corrosive hydrofluoric acid, escaped from an industrial complex in Gumi, South Korea. Ten months later, structured questionnaires that included items from the Impacts of Event Scale (revised Korean version) as well as questions about demographic and psychological risk factors related to PTSD were distributed to workers in the affected area. The prevalence rate of PTSD was 5.7%. The odds of PTSD in non-alcohol-dependent workers (odds ratio [OR] = 3.10, 95% confidence interval [CI] = [1.27, 7.60]) was significantly higher than in alcohol-independent workers. The OR for PTSD in workers with anxiety (OR = 7.63, 95% CI = [2.10, 27.71) was significantly higher than the OR workers without anxiety. The odds of PTSD in workers with high perceived stress scale (PSS) scores (OR = 8.72, 95 % CI = [2.29, 33.16]) was significantly higher than for workers with low PSS. Alcohol dependence, psychiatric symptoms at the time of the event, anxiety, and high PSS were associated with HF-related PTSD. Long-term employee assistance programs are needed to assist occupational health nurses and clinicians to reduce PTSD after industrial disasters.
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http://dx.doi.org/10.1177/2165079917750168DOI Listing
August 2018

Engrailed 1 overexpression as a potential prognostic marker in quintuple-negative breast cancer.

Cancer Biol Ther 2018 04 13;19(4):335-345. Epub 2018 Feb 13.

a Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by poor patient prognosis and for which no targeted therapies are currently available. TNBC can be further categorized as either basal-like (BLBC) or quintuple-negative breast cancer (QNBC). In the present study, we aimed to identify novel molecular therapeutic targets for TNBC by analyzing the mRNA expression of TNBC-related genes in publicly available microarray data sets. We found that Engrailed 1 (EN1) was significantly overexpressed in TNBC. Using breast cancer cell lines, we found that EN1 was more highly expressed in TNBC than in other breast cancer subtypes. EN1 expression was analyzed in 199 TNBC paraffin-embedded tissue samples by immunohistochemistry. EN1 protein expression was positively associated with reduced overall survival (OS) rate in patients with QNBC, but not those with BLBC. The importance of EN1 expression in QNBC cell viability and tumorigenicity was evaluated using the QNBC cell lines, HCC38 and HCC1395. Based on our data, EN1 may promote the proliferation, migration, and multinucleation of QNBC cells, likely via the transcriptional activation of HDAC8, UTP11L, and ZIC3. We also demonstrated that actinomycin D effectively inhibits EN1 activity in QNBC cells. The results of the present study suggest that EN1 activity is highly clinically relevant to the survival prognosis of patients with QNBC and EN1 is a promising potential therapeutic target for future QNBC treatment.
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http://dx.doi.org/10.1080/15384047.2018.1423913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902237PMC
April 2018

Injury-related hospital admission of female firefighters in South Korea.

Int J Occup Saf Ergon 2019 Dec 5;25(4):575-582. Epub 2018 Feb 5.

c Department of Occupational and Environmental Medicine, Dongguk University Ilsan Hospital , Republic of Korea.

. The main objective of this study was to ascertain whether injury-related hospital admission in all South Korea female firefighters is greater than that in the general population. . To perform this comparison, the standardized admission ratios (SARs) and their 95% confidence intervals (CIs) were calculated by person-years and mortality computation software. . Compared to the general population, the SARs for overall injury (SAR = 1.57, 95% CI [1.24, 1.96]) and for injury to the lower back (SAR = 2.78, 95% CI [1.81, 4.07]) in the female firefighters were significantly higher. The SARs for injury to the knee (SAR = 2.48, 95% CI [1.18, 4.55]) in emergency medical services (EMS) workers were significantly higher than those in the general population. . Our study shows that the SARs of overall injury and injury to the lower back in female firefighters and knee injury in the EMS were significantly higher than those in the general population. Further studies are needed to protect the lower back of firefighters and the knees of EMS.
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http://dx.doi.org/10.1080/10803548.2017.1411666DOI Listing
December 2019

Unforeseen clonal evolution of tumor cell population in recurrent and metastatic dermatofibrosarcoma protuberans.

PLoS One 2017 4;12(10):e0185826. Epub 2017 Oct 4.

Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy, Seoul National University, Seoul, Korea.

Dermatofibrosarcoma protuberans (DFSP) is a very rare soft tissue sarcoma, generally of low-grade malignancy. DFSP is locally aggressive with a high recurrence rate, but metastasis occurs rarely. To investigate the mechanism of metastasis in DFSP, we analyzed the whole exome sequencing data of serial tumor samples obtained from a patient who had a 10-year history of recurrent and metastatic DFSP. Tracking various genomic alterations, namely somatic mutations, copy number variations, and chromosomal rearrangements, we observed a dramatic change in tumor cell population during the occurrence of metastasis in this DFSP case. The new subclone that emerged in metastatic DFSP harbored a completely different set of somatic mutations and new focal amplifications, which had not been observed in the primary clone before metastasis. The COL1A1-PDGFB fusion, characteristic of DFSP, was found in all of the serial samples. Moreover, the break position on the fusion gene was identical in all samples. Based on these observations, we suggest a clonal evolution model to explain the mechanism underlying metastasis in DFSP and identified several candidate target genes responsible for metastatic DFSP by utilizing The Cancer Genome Atlas database. This is the first study to observe clonal evolution in metastatic DFSP and provide insight for a possible therapeutic strategy for imatinib-resistant or metastatic DFSP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185826PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627939PMC
November 2017

Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages.

Sci Rep 2017 08 25;7(1):9412. Epub 2017 Aug 25.

Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Human umbilical cord mesenchymal stem cells (hUC-MSCs), originating in Wharton's jelly, are multipotent stem cells that home to damaged tissues and can modulate the immune system. We examined whether administering extracts of MSCs (MSC-Ex) instead of MSCs could augment the beneficial effects of MSC therapy by overcoming the low homing efficiency of MSCs systemically administered in inflammatory bowel diseases (IBD). Dextran sodium sulfate-induced colitis model was established in C57BL/6 mice, and MSC-Ex was administered intraperitoneally. MSC-Ex reduced colitis, disease activity index (DAI), and histological colitis scores, and increased the body weight. Treatment with MSC-Ex completely blocked the induction of inflammatory cytokines, which were strongly detected in mice with colitis. MSC-Ex shifted the macrophage functional phenotype from M1 to M2 by decreasing the levels of MCP1, CXCL9, and iNOS, but increasing the levels of IL-10, LIGHT, CCL1, and Arg-1. MSC-Ex recovered the destruction of the epithelial barrier in the differentiated Caco-2 cells in vitro. Treatment with MSC-Ex was more potent than that with MSC in reducing DAI, the histological score, and nitrite levels. These data strongly support that MSC-Ex treatment can be a potent approach to overcome severe refractory IBD.
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http://dx.doi.org/10.1038/s41598-017-09827-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573412PMC
August 2017

Precision medicine approaches to lung adenocarcinoma with concomitant MET and HER2 amplification.

BMC Cancer 2017 Aug 10;17(1):535. Epub 2017 Aug 10.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

Background: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models.

Methods: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations. PDX cells were obtained from PDXs and subsequently screened in vitro with 17 targeted agents.

Results: PDX tumors recapitulated the histopathologic and genetic features of the patient tumors. Among the samples from lung cancer patients that were molecularly-profiled, copy number analysis identified unique focal MET amplification in one sample, 033 T, without RTK/RAS/RAF oncogene mutations. Although HER2 amplification in 033 T was not detected in the cancer panel, the selection of HER2-amplified clones was found in PDXs and PDX cells. Additionally, MET and HER2 overexpression were found in patient tumors, PDXs, and PDX cells. Crizotinib or EGFR tyrosine kinase inhibitor treatments significantly inhibited cell growth and impaired tumor sphere formation in 033 T PDX cells.

Conclusions: We established PDX cell models using surgical samples from lung cancer patients, and investigated their preclinical and clinical implications for personalized targeted therapy. Additionally, we suggest that MET and EGFR inhibitor-based therapy can be used to treat MET and HER2-overexpressing lung cancers, without receptor tyrosine kinase /RAS/RAF pathway alterations.
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http://dx.doi.org/10.1186/s12885-017-3525-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557466PMC
August 2017

Prevalence and Microbiological Characteristics of qacA/B-Positive Methicillin-Resistant Staphylococcus aureus Isolates in a Surgical Intensive Care Unit.

Microb Drug Resist 2018 Apr 11;24(3):283-289. Epub 2017 Aug 11.

1 Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine , Jinju, Republic of Korea.

The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to or tolerance of this antiseptic. We examined the frequency and characteristics of qacA/B chlorhexidine tolerance genes among MRSA isolates in a surgical intensive care unit (ICU) where MRSA-colonized patients are decolonized by chlorhexidine bathing. The MRSA isolates were evaluated for chlorhexidine susceptibility, mupirocin resistance, molecular typing, agr functionality, and the heterogeneous vancomycin-intermediate S. aureus (hVISA) phenotype according to the presence of the qacA/B genes. Overall, 119 MRSA isolates were obtained from active surveillance cultures (93, 78.2%) and clinical cultures (26, 21.8%) between 2012 and 2014. Among these isolates, 39 (32.8%) carried the qacA/B genes, and 23 (19.3%) exhibited mupirocin resistance. Most qacA/B-positive isolates (36/39, 92.3%) were identified as ST5-SCCmecII (69.2%) and ST239-SCCmecIII (23.1%), which are common healthcare-associated (HA)-MRSA strains in Korea. Multivariate analysis found that qacA/B-positive MRSA isolates were associated with agr dysfunction (OR, 4.87; 95% CI, 1.71-13.87) and the hVISA phenotype (OR, 4.09; 95% CI, 1.48-11.34). In conclusion, our study showed that qacA/B carriage was common among MRSA isolates in an ICU where chlorhexidine is commonly used for decolonization. qacA/B carriage was significantly associated with agr dysfunction and the hVISA phenotype. These features may confer a selective advantage on HA-MRSA strains, including ST5-SCCmecII and ST239-SCCmecIII, in the ICU setting.
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http://dx.doi.org/10.1089/mdr.2017.0072DOI Listing
April 2018

Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer.

J Pathol 2017 11 28;243(3):307-319. Epub 2017 Sep 28.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Korea.

Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects ALK at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05). In vitro experiments revealed that EML4-ALK short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of them undergo a non-homologous end-joining repair to generate ALK fusions. We also discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK fusion partners showed different intracellular localization. With our findings that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the ALK molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.4950DOI Listing
November 2017

MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values.

J Thorac Oncol 2017 08 10;12(8):1233-1246. Epub 2017 May 10.

Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Introduction: Response to mesenchymal-epithelial transition (MET) inhibitors in NSCLC with mesenchymal-epithelial transition gene (MET) exon 14 skipping (METex14) has fueled molecular screening efforts and the search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping.

Methods: Among 795 East Asian patients who underwent a surgical procedure for NSCLC, we screened 45 patients with quintuple-negative (EGFR-negative/KRAS-negative/anaplastic lymphoma kinase gene [ALK]-negative/ROS1-negative/ret proto-oncogene [RET]-negative) lung adenocarcinomas by using reverse-transcriptase polymerase chain reaction and found 17 patients (37.8%) with METex14 skipping. We also investigated the effect of small interfering RNA (siRNA) targeting skipping junction in cells with METex14 skipping.

Results: The median age of the 17 patients was 73 years. The acinar subtype was predominant (52.9%), followed by the solid subtype (35.3%). MET immunohistochemistry demonstrated 100% sensitivity and 70.4% specificity. Multivariate analyses showed that patients with METex14 skipping had a higher recurrence rate than those with ALK fusion (versus METex14 skipping) (hazard ratio = 0.283, 95% confidence interval: 0.119-0.670) in stage I to IIIA disease; however, the differences in overall survival were not significant after adjustment for pathologic stage (p = 0.669). Meanwhile, siRNA decreased MET-driven signaling pathways in Hs746T cells, and combined treatment with siRNA and crizotinib inhibited cell proliferation in crizotinib-resistant H596 cells.

Conclusions: The prevalence of METex14 skipping was quite high in East Asian patients without other driver mutations in lung adenocarcinomas. METex14 skipping was associated with old age, the acinar or solid histologic subtype, and high MET immunohistochemical expression. The prognosis of patients with METex14 skipping was similar to that of patients with major driver mutations. siRNA targeting the junction of METex14 skipping could inhibit MET-driven signaling pathways in cells with METex14 skipping.
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http://dx.doi.org/10.1016/j.jtho.2017.04.031DOI Listing
August 2017

SHP2 is induced by the HBx-NF-κB pathway and contributes to fibrosis during human early hepatocellular carcinoma development.

Oncotarget 2017 Apr;8(16):27263-27276

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

The non-receptor tyrosine phosphatase SHP2 has scaffolding functions in signal transduction cascades downstream of growth receptors. A recent study suggested that SHP2 acts as a tumor suppressor during hepatocellular carcinoma (HCC) development. Herein we examined whether SHP2 links the HBx-NF-κB pathway to EGFR signaling during HCC development. The overexpression of HBx or NF-κB led to increased SHP2 expression via NF-κB binding to the Shp2 promoter. EGF treatment induced ERK activation as well as the rapid assembly of SHP2, EGFR, and Gab1. Upon LPS stimulation, NF-κB-SHP2-ERK activation and phosphorylated STAT3 levels exhibited a negative correlation in vitro. By contrast, in patients with HBV-associated HCC, NF-κB-SHP2-ERK and IL-6-JAK-STAT3 pathway activity levels were concomitantly higher in adjacent non-neoplastic tissues than in HCC tissues. The immunohistochemical analysis of 162 tissues of patients with HCC revealed that SHP2 levels were significantly higher in non-neoplastic background tissues than in corresponding HCC tissues and considerably increased in background liver tissues with advanced fibrosis (P < 0.001). SHP2 expression increased gradually from normal liver to chronic hepatitis, cirrhosis, and background liver with a dysplastic nodule, but was decreased or lost in dysplastic nodules and HCC. This is the first report to describe the existence of the HBx-NF-κB-SHP2 pathway, linking HBV infection to the EGFR-RAS-RAF-MAPK pathway in the liver. SHP2 depletion from the negative crosstalk between NF-κB and STAT3 accelerates HCC development.
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http://dx.doi.org/10.18632/oncotarget.15930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432333PMC
April 2017

Factors Related to Noncompliance in Screening and Tracking Mild Cognitive Impairment Patients in a Single Community.

Psychiatry Investig 2017 Mar 6;14(2):111-117. Epub 2017 Mar 6.

Department of Psychiatry, Kyung Hee University Hospital, Seoul, Republic of Korea.; Dongdaemun-gu Center for Dementia, Seoul, Republic of Korea.

Objective: We assessed the cumulative conversion rates (CCR) from minor cognitive impairment (MCI) to dementia among individuals who failed to participate in annual screening for dementia. Additionally, we analyzed the reasons for failing to receive follow-up screening in order to develop better strategies for improving follow-up screening rates.

Methods: We contacted MCI patients who had not visited the Dongdaemun-gu Center for Dementia for annual screening during the year following their registration. We compared the CCR from MCI to dementia in the following two groups: subjects registered as having MCI in the Dongdaemun-gu Center for Dementia database and subjects who failed to revisit the center, but who participated in a screening test for dementia after being contacted. The latter participants completed a questionnaire asking reasons for not previously visiting for follow-up screening.

Results: The final diagnoses of the 188 subjects who revisited the center only after contact were 19.1% normal, 64.9% MCI and 16.0% dementia. The final diagnoses of the 449 subjects in the Dongdaemun-gu Center for Dementia database were 25.6% normal, 46.1% MCI and 28.3% dementia. The CCR of the revisit-after-contact group was much lower than anticipated. The leading cause for noncompliance was "no need for tests" at 28.2%, followed by "other reasons" at 23.9%, and "I forgot the appointment date" at 19.7%.

Conclusion: Considering the low dementia detection rate of the group who revisited only after contact and the reasons they gave for noncompliance, there appears to be a need for ongoing outreach and education regarding the course and prognosis of MCI.
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http://dx.doi.org/10.4306/pi.2017.14.2.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355007PMC
March 2017

Prevalence of Mutations in Discoidin Domain-Containing Receptor Tyrosine Kinase 2 (DDR2) in Squamous Cell Lung Cancers in Korean Patients.

Cancer Res Treat 2017 Oct 25;49(4):1065-1076. Epub 2017 Jan 25.

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea.

Purpose: The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer.

Materials And Methods: We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2 mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2 mutants were confirmed by in vitro assays.

Results: We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied. One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant-bearing cells.

Conclusion: Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2 mutations were located in a kinase domain and induced an increase in cell proliferation rate.
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http://dx.doi.org/10.4143/crt.2016.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654160PMC
October 2017

Hydrophobic Residues near the Bilin Chromophore-Binding Pocket Modulate Spectral Tuning of Insert-Cys Subfamily Cyanobacteriochromes.

Sci Rep 2017 01 17;7:40576. Epub 2017 Jan 17.

Department of Biological Sciences, Chungnam National University, Daejeon 34134 Korea.

Cyanobacteriochromes (CBCRs) are a subfamily of phytochrome photoreceptors found exclusively in photosynthetic cyanobacteria. Four CBCRs containing a second Cys in the insert region (insert-Cys) have been identified from the nonheterocystous cyanobacterium Microcoleus B353 (Mbr3854g4 and Mbl3738g2) and the nitrogen fixing, heterocystous cyanobacterium Nostoc punctiforme (NpF2164g3 and NpR1597g2). These insert-Cys CBCRs can sense light in the near-UV to orange range, but key residues responsible for tuning their colour sensitivity have not been reported. In the present study, near-UV/Green (UG) photosensors Mbr3854g4 (UG1) and Mbl3738g2 (UG2) were chosen for further spectroscopic analysis of their spectral sensitivity and tuning. Consistent with most dual-Cys CBCRs, both UGs formed a second thioether linkage to the phycocyanobilin (PCB) chromophore via the insert-Cys. This bond is subject to breakage and relinkage during forward and reverse photoconversions. Variations in residues equivalent to Phe that are in close contact with the PCB chromophore D-ring in canonical red/green CBCRs are responsible for tuning the light absorption peaks of both dark and photoproducts. This is the first time these key residues that govern light absorption in insert-Cys family CBCRs have been identified and characterised.
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http://dx.doi.org/10.1038/srep40576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240096PMC
January 2017

Adenoid cystic carcinoma of the sublingual gland: A case report.

Authors:
Ji-Young Song

Imaging Sci Dent 2016 Dec 20;46(4):291-296. Epub 2016 Dec 20.

Department of Oral and Maxillofacial Surgery, School of Medicine, Jeju National University, Jeju, Korea.

Adenoid cystic carcinoma (ACC) of the sublingual gland is an extremely rare neoplasm. The clinicopathological characteristics of ACC are slow-growing swelling with or without ulceration, perineural spread, local recurrence, and distant metastasis. This report describes a 58-year-old male who had a slowly growing swelling without ulceration on the right side of the mouth floor that had been present for 1 month. In a radiological examination, the mass showed multilocular cystic features and no bony or tongue muscle invasion. No enlarged cervical lymph nodes were detected. Excisional biopsy and histological analysis showed that the lesion was ACC. In addition to reporting a rare case of ACC, this report also discusses the differential diagnosis and treatment of ACC with a review of the relevant literature.
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http://dx.doi.org/10.5624/isd.2016.46.4.291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192029PMC
December 2016
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