Publications by authors named "Tae-Jin Yoon"

65 Publications

Performance of the BIG Score in Predicting Mortality in Normotensive Children With Trauma.

Pediatr Emerg Care 2020 Jun 16. Epub 2020 Jun 16.

From the Department of Emergency, Department of Trauma Surgery, Ajou University School of Medicine, Suwon, Korea.

Objectives: Children have a larger reserve for traumatic hemorrhagic shock, requiring a score that uses physiologic variables other than hypotension. Recently, the BIG score comprising admission base deficit, international normalized ratio, and the Glasgow Coma Scale has been reported to predict traumatic mortality. We aimed to validate the performance of the BIG score in mortality prediction of normotensive children with trauma.

Methods: We reviewed 1046 injured children (<18 years) who visited a Korean academic hospital from 2010 to 2018, excluding those with age-adjusted hypotension. In-hospital mortality, the BIG score and its predicted mortality, Revised Trauma Score, and Pediatric Trauma Score were calculated. We compared areas under the curve (AUCs) for in-hospital mortality of the 3 scores and did in-hospital and BIG-predicted mortalities.

Results: Of the 1046 children, 554 were enrolled with a 4.9% in-hospital mortality rate. The median BIG score was higher in the nonsurvivors (6.4 [interquartile range, 4.4-9.2] vs 20.1 [16.5-24.8]; P < 0.001). The AUC of the BIG score was 0.94 (95% confidence interval [CI], 0.92-0.96), which was higher than that of Pediatric Trauma Score (0.87 [95% CI, 0.84-0.90]; P < 0.001). The AUC of the BIG score tended to be higher than that of Revised Trauma Score without statistical significance (0.90 [95% CI, 0.87-0.92]; P = 0.130). We noted a parallel between in-hospital and BIG-predicted mortalities. The hemorrhage-related nonsurvivors showed higher median base deficit and BIG score than did the isolated traumatic brain injury-related ones.

Conclusions: The BIG score can predict mortality with excellent accuracy in normotensive children with trauma.
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http://dx.doi.org/10.1097/PEC.0000000000002122DOI Listing
June 2020

Sorafenib induces pigmentation via the regulation of β-catenin signalling pathway in melanoma cells.

Exp Dermatol 2020 May 11. Epub 2020 May 11.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Korea.

We conducted large-scale screening test on drugs that were already approved for other diseases to find pigmentation-modulating agents. Among drugs with potential for pigmentation control, we selected sorafenib and further investigated the effect on pigmentation using HM3KO melanoma cells. As a result of treating melanoma cells with sorafenib, pigmentation was promoted in terms of melanin content and tyrosinase activity. Sorafenib increased mRNA and protein levels of pigmentation-related genes such as MITF, tyrosinase and TRP1. To uncover the action mechanism, we investigated the effect of sorafenib on the intracellular signalling pathways. Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. In addition, sorafenib significantly increased the level of active β-catenin, together with activation of β-catenin signalling. Mechanistic study revealed that sorafenib decreased phosphorylation of serine 9 (S9) of GSK3β, while it increased phosphorylation of tyrosine 216 (Y216) of GSK3β. These results suggest that sorafenib activates the β-catenin signalling through the regulation of GSK3β phosphorylation, thereby affecting the pigmentation process.
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http://dx.doi.org/10.1111/exd.14112DOI Listing
May 2020

Nicotinamide N‑methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells.

Oncol Rep 2019 Nov 16;42(5):1805-1814. Epub 2019 Sep 16.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University and Hospital, Jinju 52727, Republic of Korea.

Cutaneous squamous cell carcinoma (cSCC) is a common malignancy initiated by keratinocytes of the epidermis, which are able to invade the dermis and its periphery. Although most patients with cSCC present with curable localized tumors, recurrence, metastasis and mortality occasionally occur. In the present study, nicotinamide N‑methyltransferase (NNMT) was identified as an upregulated protein in the SCC12 cell line, which has high invasive potential compared with the SCC13 cell line. The effects of NNMT knockdown on proliferation, migration and invasion were investigated using SCC cells. shRNA‑mediated downregulation of NNMT expression levels inhibited the proliferation and density‑dependent growth of SCC12 cells. In addition, the results of a cell motility assay showed that the migration and invasion of SCC cells were markedly decreased in NNMT‑knockdown cells. The assessment of epithelial‑mesenchymal transition (EMT)‑associated gene expression using PCR array analysis revealed that high NNMT expression levels were accompanied by high expression levels of EMT‑associated genes, and that NNMT knockdown effectively suppressed the expression of matrix metalloproteinase 9, osteopontin, versican core protein and zinc finger protein SNAI2 in SCC12 cells. These results revealed that the upregulation of NNMT induced cellular invasion via EMT‑related gene expression in SCC cells.
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http://dx.doi.org/10.3892/or.2019.7315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787961PMC
November 2019

Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells.

Biomed Res Int 2019 9;2019:3689517. Epub 2019 Jun 9.

Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.

Drug repurposing and/or repositioning is an alternative method to develop new treatment for certain diseases. Albendazole was originally developed as an anthelmintic medication, and it has been used to treat a variety of parasitic infestations. In this study, we investigated the antitumor effect of albendazole and putative action mechanism. Results showed that albendazole dramatically decreased the cell viability of SCC cell lines (SCC12 and SCC13 cells). Albendazole increased apoptosis-related signals, including cleaved caspase-3 and PARP-1 in a dose-dependent fashion. The mechanistic study showed that albendazole induced endoplasmic reticulum (ER) stress, evidenced by increase of CHOP, ATF-4, caspase-4, and caspase-12. Pretreatment with ER stress inhibitor 4-PBA attenuated albendazole-induced apoptosis of SCC cells. In addition, albendazole decreased the colony-forming ability of SCC cells, together with inhibition of Wnt/-catenin signaling. These results indicate that albendazole shows an antitumor effect via regulation of ER stress and cancer stemness, suggesting that albendazole could be repositioned for cutaneous SCC treatment.
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http://dx.doi.org/10.1155/2019/3689517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590486PMC
December 2019

Induction of pigmentation by a small molecule tyrosine kinase inhibitor nilotinib.

Biochem Biophys Res Commun 2018 09 28;503(4):2271-2276. Epub 2018 Jun 28.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, South Korea. Electronic address:

Skin color is determined by the melanin pigments that are produced in melanocytes then transferred to surrounding keratinocytes. Despite the growing number of commercial products claiming the pigmentation-regulatory effects, there is still a demand for the development of new materials that are safe and more efficacious. We tried to screen the pigmentation-regulatory materials using a commercially available drugs, and found that nilotinib could induce pigmentation in melanoma cells. When HM3KO melanoma cells were treated with nilotinib, melanin content was increased together with increase of tyrosinase activity. Nilotinib increased the expression of pigmentation-related genes such as MITF, tyrosinase and TRP1. Consistent with these results, the protein level for MITF, tyrosinase, and TRP1 was significantly increased by nilotinib. To delineate the action mechanism of nilotinib, we investigated the effects of nilotinib on intracellular signaling. As a result, nilotinib decreased the phosphorylation of AKT, while increased the phosphorylation of CREB. The pretreatment of PKA inhibitor H89 markedly blocked the nilotinib-induced phosphorylation of CREB. In accordance with, pretreatment of H89 significantly inhibited the nilotinib-induced pigmentation, indicating that nilotinib induces pigmentation via the activation of PKA signaling. Together, our data suggest that nilotinib can be developed for the treatment of hypopigmentary disorder such as vitiligo.
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http://dx.doi.org/10.1016/j.bbrc.2018.06.148DOI Listing
September 2018

Prevention of total thyroidectomy in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) based on combined interpretation of ultrasonographic and cytopathologic results.

Clin Endocrinol (Oxf) 2018 Jan 27;88(1):114-122. Epub 2017 Sep 27.

Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.

Objective: To explore the potential preoperative ultrasonography (US) and cytopathological features to avoid total thyroidectomy in NIFTP.

Context: Recently, it has been proposed that that noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) be classified as tumours, rather than cancer.

Patients: A total of 142 surgically proven follicular variant papillary thyroid carcinomas (FVPTCs; 45 NIFTP, 97 non-NIFTP; mean size: 20.4±11.0 mm, range: 10.0-65.0 mm) from 142 patients were included in this study.

Measurements: Three preoperative features of thyroid nodules (each US finding, US and Bethesda category) were compared in NIFTP and non-NIFTP groups. The preoperative decision-making process to avoid total thyroidectomy in NIFTP was evaluated based on combination of those features.

Results: In each US finding, there was only significantly less macrocalcification in the NIFTP group than in the non-NIFTP group (8.8% [4/45] vs 32.0% [31/97], P = .006). In US category, all of the NIFTP nodules were a low or intermediate suspicion (100% [45/45]). In Bethesda category, 26.7% [12/45] of the NIFTP was diagnosed as either suspicious malignancy or malignant, which increased the risk of a total thyroidectomy. In our study, a total thyroidectomy might be avoided in all of the NIFTP cases if lobectomy was selected for the nodules classified as a low or intermediate suspicion in US, despite being classified as a suspicious malignancy or malignant by cytopathology.

Conclusions: Combining the US and cytopathological results could sensitively reduce total thyroidectomy in cases of NIFTP.
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http://dx.doi.org/10.1111/cen.13473DOI Listing
January 2018

Procyanidins from seeds induce apoptotic and autophagic cell death via generation of reactive oxygen species in squamous cell carcinoma cells.

Oncol Lett 2017 Aug 19;14(2):1925-1932. Epub 2017 Jun 19.

Department of Dermatology, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongsangnam-do 52727, Republic of Korea.

Procyanidins can inhibit cell proliferation and tumorigenesis and induce apoptosis in human skin, breast and prostate carcinoma cell lines. Squamous cell carcinoma (SCC) of the skin is a common form of keratinocytic or non-melanoma skin cancer and is a deadly disease with a poor prognosis due to the ineffectiveness of therapy. The present study aimed to determine whether grape seed proanthocyanidin (GSP) may regulate different modes of cell death in the human SCC12 cell line. The present study found that the treatment of SCC12 cells with GSP inhibited proliferation in a dose-dependent manner and reduced the motility and invasiveness of SCC12 cells through suppression of matrix metalloproteinase-2/9 expression. GSP treatment also resulted in induction of apoptosis and autophagy via generation of reactive oxygen species. The inhibition of autophagy by 3-methyladenine decreased GSP-induced cell death, which suggested that GSP-induced autophagy can promote cell death. The results of the present study suggested that autophagy functions as a death mechanism in SCC and provided a rationale for the use of GSP in combination with autophagy activators for treating cancers such as SCC.
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http://dx.doi.org/10.3892/ol.2017.6422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530194PMC
August 2017

Inhibitory effect of 5-iodotubercidin on pigmentation.

Biochem Biophys Res Commun 2017 09 4;490(4):1282-1286. Epub 2017 Jul 4.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Republic of Korea. Electronic address:

Melanin pigments are the primary contributors for the skin color. They are produced in melanocytes and then transferred to keratinocytes, eventually giving various colors on skin surface. Although many depigmenting and/or skin-lightening agents have been developed, there is still a growing demand on materials for reducing pigmentation. We attempted to find materials for depigmentation and/or skin-lightening using the small molecule compounds commercially available, and found that 5-iodotubercidin had inhibitory potential on pigmentation. When HM3KO melanoma cells were treated with 5-iodotubercidin, pigmentation was dramatically reduced. The 5-iodotubercidin decreased the protein level for pigmentation-related molecules such as MITF, tyrosinase, and TRP1. In addition, 5-iodotubercidin decreased the phosphorylation of CREB, while increased the phosphorylation of AKT and ERK. These data suggest that 5-iodotubercidin inhibits melanogenesis via the regulation of intracellular signaling related with pigmentation. Finally, 5-iodotubercidin markedly inhibited the melanogenesis of zebrafish embryos, an in vivo evaluation model for pigmentation. Together, these data suggest that 5-iodotubercidin can be developed as a depigmenting and/or skin-lightening agent.
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http://dx.doi.org/10.1016/j.bbrc.2017.07.008DOI Listing
September 2017

Inhibition of collagen production by ICG-001, a small molecule inhibitor for Wnt/β-catenin signaling, in skin fibroblasts.

J Dermatol Sci 2017 Apr 6;86(1):76-78. Epub 2017 Jan 6.

Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2017.01.005DOI Listing
April 2017

Inhibition of collagen synthesis by IWR-1 in normal and keloid-derived skin fibroblasts.

Life Sci 2017 Mar 7;173:86-93. Epub 2016 Dec 7.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Republic of Korea. Electronic address:

Aims: Keloid is a benign tumor that is characterized by the hyperproliferation of dermal fibroblasts and excessive deposition of extracellular matrix (ECM) especially the collagen. Aberrant activation of Wnt/β-catenin signaling is implicated in the pathogenesis of keloid. In this study, we investigated the effects of IWR-1, a small molecule inhibitor for Wnt/β-catenin signaling via the inhibition of tankyrase, on production of collagen and matrix metalloproteinase (MMP) in dermal fibroblasts.

Main Methods: We cultured human normal skin- and keloid-derived fibroblasts, then treated with IWR-1. The effects of IWR-1 on collagen and MMP production were determined by Western blot, ELISA and zymography.

Key Findings: IWR-1 significantly suppressed the proliferation and migration of both the normal and keloid fibroblasts. IWR-1 also inhibited the production and secretion of type I collagen from the fibroblasts. In addition, IWR-1 significantly increased the expression of MMPs, such as MMP-1, MMP-3 and MMP-13, along with the increase of gelatinase activity. These results suggest that inhibitory effect of IWR-1 on collagen production may be related with the increased MMP activity.

Significance: This study provides the possible action mechanism of IWR-1 on regulation of collagen expression, on which to base further investigation for preventing skin fibrotic diseases such as keloid.
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http://dx.doi.org/10.1016/j.lfs.2016.12.003DOI Listing
March 2017

Wnt/β-catenin signaling inhibitor ICG-001 enhances pigmentation of cultured melanoma cells.

J Dermatol Sci 2016 Nov 20;84(2):160-168. Epub 2016 Aug 20.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, South Korea. Electronic address:

Background: Wnt/β-catenin signaling is important in development and differentiation of melanocytes.

Objective: The object of this study was to evaluate the effects of several Wnt/β-catenin signaling inhibitors on pigmentation using melanoma cells.

Methods: Melanoma cells were treated with Wnt/β-catenin signaling inhibitors, and then melanin content and tyrosinase activity were checked.

Results: Although some inhibitors showed slight inhibition of pigmentation, we failed to observe potential inhibitory effect of those chemicals on pigmentation of HM3KO melanoma cells. Rather, one of powerful Wnt/β-catenin signaling inhibitors, ICG-001, increased the pigmentation of HM3KO melanoma cells. Pigmentation-enhancing effect of ICG-001 was reproducible in other melanoma cell line MNT-1. Consistent with these results. ICG-001 increased the expression of pigmentation-related genes, such as MITF, tyrosinase and TRP1. When ICG-001 was treated, the phosphorylation of CREB was significantly increased. In addition, ICG-001 treatment led to quick increase of intracellular cAMP level, suggesting that ICG-001 activated PKA signaling. The blockage of PKA signaling with pharmaceutical inhibitor H89 inhibited the ICG-001-induced pigmentation significantly.

Conclusions: These results suggest that PKA signaling is pivotal in pigmentation process itself, while the importance of Wnt/β-catenin signaling should be emphasized in the context of development and differentiation.
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http://dx.doi.org/10.1016/j.jdermsci.2016.08.013DOI Listing
November 2016

The inhibitory effect of A20 on the inflammatory reaction of epidermal keratinocytes.

Int J Mol Med 2016 Apr 3;37(4):1099-104. Epub 2016 Mar 3.

Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.

A20 is a negative regulator of nuclear factor κ-light‑chain-enhancer of activated B cells (NF-κB) signaling, and has been implicated in the pathogenesis of psoriasis through genome-wide association study (GWAS). In the present study, we investigated the putative role of A20 in epidermal keratinocytes. Immunohistochemical analysis showed that A20 was expressed in all layers of the epidermis, with an increasing pattern in the upper layers. In our model of calcium-induced keratinocyte differentiation, A20 expression was increased in a time-dependent manner. To investigate whether A20 affected keratinocyte differentiation, we overexpressed A20 in cultured keratinocytes. As a result, we noted that A20 overexpression did not affect keratinocyte differentiation, suggesting that A20 is not a direct modulator of keratinocyte differentiation. Interestingly, we found that A20 levels were decreased in psoriatic lesional skin compared to non-lesional areas. To investigate whether A20 played a role in the innate immune response of keratinocytes, we overexpressed A20 and then examined poly(I:C)-induced cytokine expression. We noted that A20 significantly inhibited poly(I:C)-induced cytokine production, and this effect was related to the inhibition of NF-κB signaling. These results suggest that the downregulation of A20 increased the susceptibility of keratinocytes to external stimuli, thus contributing to the development of psoriasis.
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http://dx.doi.org/10.3892/ijmm.2016.2514DOI Listing
April 2016

Identification of a possible susceptibility locus for UVB-induced skin tanning phenotype in Korean females using genomewide association study.

Exp Dermatol 2015 Dec 15;24(12):942-6. Epub 2015 Sep 15.

Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.

A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain-containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P-value = 1.16 × 10(-4) ). To understand the functional consequences of this locus located in the non-coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV-induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV-induced tanning ability in individuals.
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http://dx.doi.org/10.1111/exd.12809DOI Listing
December 2015

Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation.

Biochem Biophys Res Commun 2015 Apr 10;459(4):673-8. Epub 2015 Mar 10.

Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea; Skin Med Company, Daejeon, Republic of Korea. Electronic address:

Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis.
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http://dx.doi.org/10.1016/j.bbrc.2015.03.001DOI Listing
April 2015

Gene expression profiling in melasma in Korean women.

Dermatology 2014 28;229(4):333-42. Epub 2014 Nov 28.

Department of Dermatology, College of Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.

Background: There has been a paucity of data about the difference in gene expression between melasma lesional skin and normal adjacent one.

Objective: Our aim was to identify novel genes involved in the pathogenesis of melasma.

Methods: We performed a microarray analysis and confirmed the results on quantitative real-time polymerase chain reaction (qRT-PCR) in Korean women with melasma.

Results: There were 334 genes whose degree of expression showed a significant difference between melasma lesional skin and normal adjacent one. Of these, five were confirmed on qRT-PCR. In melasma lesional skin, there were down-regulation of genes involved in the PPAR signaling pathway and up-regulation of genes involved in neuronal component and the functions of stratum corneum barrier.

Conclusion: This result suggests that the pathogenesis of melasma might be associated with novel genes involved in the above signaling pathway in Korean women.
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http://dx.doi.org/10.1159/000365080DOI Listing
September 2015

Evaluation of the microenvironmental heterogeneity in high-grade gliomas with IDH1/2 gene mutation using histogram analysis of diffusion-weighted imaging and dynamic-susceptibility contrast perfusion imaging.

J Neurooncol 2015 Jan 10;121(1):141-50. Epub 2014 Sep 10.

Department of Radiology, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul, 110-744, Korea.

The purpose of our study was to explore the difference between isocitrate dehydrogenase (IDH)-1/2 gene mutation-positive and -negative high-grade gliomas (HGGs) using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. We enrolled 52 patients with histopathologically confirmed HGGs with IDH1/2 (P) (n = 16) or IDH1/2 (N) (n = 36). Histogram parameters of ADC and nCBV maps were correlated with gene mutations by using the unpaired student's t test and multivariable stepwise logistic regression analysis. The mean ADC value was higher in the IDH1 (P) group than IDH1 (N) (1,282.8 vs. 1,159.6 mm(2)/s, P = .0113). In terms of the cumulative ADC histograms, the 10th and 50th percentile values were also higher in the IDH1 (P) than IDH1 (N) (P = .0104 and .0183, respectively). We observed a higher 90th percentile value (3.121 vs. 2.397, P = .0208) and a steeper slope between the 10th (C10) and 90th (C90) of cumulative nCBV histograms (0.03386 vs. 0.02425/%, P = .0067) in the IDH1 (N) group. Multivariate analysis showed that the mean ADC mean value (P = .0048), the C90 value (P = .0113), and the slope between C10 and C90 (P = .0049) were the significant variables in the differentiation of IDH1 (P) from IDH1 (N). In conclusion, histogram analysis of ADC and nCBV maps based on entire tumor volume can be a useful tool for distinguishing IDH1 (P) and IDH1 (N), and it predicts that IDH (P) tumors have a more heterogeneous microenvironment than IDH (N) ones.
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http://dx.doi.org/10.1007/s11060-014-1614-zDOI Listing
January 2015

Anti-graying effect of the extract of Pueraria thunbergiana via upregulation of cAMP/MITF-M signaling pathway.

J Dermatol Sci 2014 Aug 21;75(2):153-5. Epub 2014 May 21.

Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environmental Interface Biology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2014.05.003DOI Listing
August 2014

Nrf2 negatively regulates melanogenesis by modulating PI3K/Akt signaling.

PLoS One 2014 24;9(4):e96035. Epub 2014 Apr 24.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea.

Nrf2 plays a role in protection of cells against oxidative stress and xenobiotic damage by regulating cytoprotective genes. In this study, we investigated the effect of Nrf2 on melanogenesis in normal human melanocytes (NHMCs). When NHMCs were transduced with a recombinant adenovirus expressing Nrf2, melanin synthesis was significantly decreased. Consistent with this result, overexpression of Nrf2 decreased the expression of tyrosinase and tyrosinase-related protein 1. The inhibitory effect of Nrf2 was reversed by overexpression of Keap1, an intracellular regulator of Nrf2. Interestingly, Nrf2 overexpression resulted in marked activation of PI3K/Akt signaling. Conversely, inhibition of PI3K activity by treatment with wortmannin reversed the depigmentary effects of Nrf2. Taken together, these results strongly suggest that Nrf2 negatively regulates melanogenesis by modulating the PI3K/Akt signaling pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096035PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999113PMC
July 2015

Melanosome uptake is associated with the proliferation and differentiation of keratinocytes.

Arch Dermatol Res 2014 Jan 31;306(1):59-66. Epub 2013 Oct 31.

Department of Anatomy, School of Medicine, Chungnam National University, 266 Munhwa-ro, Daejeon, 301-747, Korea.

Melanosomes are synthesized in melanocytes and transferred to neighboring keratinocytes. However, the associations of melanosome uptake with the proliferation and differentiation of keratinocytes are not fully understood. We examined the associations of melanosome uptake with keratinocyte differentiation and proliferation. SV40T-transformed human epidermal keratinocytes (SV-HEKs) were treated with isolated melanosomes. The effects of melanosome uptake on the proliferation and differentiation of the keratinocytes were analyzed by Western blotting and flow cytometry. The relationship between melanosome uptake and keratinocyte differentiation status was verified by determining the melanin content in the cells. Melanosomes reduced the proliferation of SV-HEKs in a dose-dependent manner, but did not induce differentiation. Melanosome uptake was higher in differentiating keratinocytes compared to non-differentiating keratinocytes, and inhibited significantly by PAR-2 inhibitor. Melanosomes inhibit keratinocyte proliferation. Moreover, melanosome uptake is influenced by keratinocyte differentiation status, being highest in mid-stage differentiating keratinocytes in a PAR-2 dependent manner.
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http://dx.doi.org/10.1007/s00403-013-1422-xDOI Listing
January 2014

SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation.

J Dermatol Sci 2013 Dec 8;72(3):246-51. Epub 2013 Aug 8.

Department of Physiology, Institute of Health Sciences and Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea.

Background: The formation of dendrites by melanocytes is highly analogous to that process in neural cells. We previously reported that a C2 domain-containing protein, copine-1, is involved in the extension of dendrites by neural cells. However, the effect of C2 domain-containing proteins in dendrite formation by melanocytes has not yet been elucidated.

Objective: The aim of this study was to screen novel C2 domain-containing proteins related to dendrite outgrowth in melanocytes and to investigate their precise roles in melanocyte dendrite formation during differentiation.

Methods: We transduced mouse melan-a melanocytes with a recombinant adenovirus expressing a C2 domain library. Dendrite elongation, melanin content, tyrosinase activity and Western blot analyses were conducted to elucidate the possible underlying mechanisms of action in melanocytes.

Results: Sixteen sets of C2 domain-containing proteins were identified whose over-expression resulted in dendrite lengthening. Among those, we focused on the C2 domain of SYT14L (truncated mutant of SYT14L) in this study. Forced expression of full length SYT14L or the C2 domain of SYT14L induced a significant elongation of dendrite length accompanied by the induction of melanocyte differentiation-related markers, including melanin synthesis, tyrosinase catalytic activity and the expression of tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and TRP-2. In addition, over-expression of either the C2 domain or the full length form of SYT14L significantly increased the phosphorylation of ERK and CREB.

Conclusion: These results suggest that SYT14L, especially its C2 domain, may play an important role in regulating melanocyte differentiation through the modulation of ERK and (or) CREB signaling.
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http://dx.doi.org/10.1016/j.jdermsci.2013.07.010DOI Listing
December 2013

A genome-wide association study in Koreans identifies susceptibility loci for allergic nickel dermatitis.

Int Arch Allergy Immunol 2013 31;162(2):184-6. Epub 2013 Jul 31.

Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul,Korea.

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http://dx.doi.org/10.1159/000353235DOI Listing
December 2013

Differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide: comparison study of standard and high-b-value diffusion-weighted imaging.

Radiology 2013 Dec 28;269(3):831-40. Epub 2013 Oct 28.

From the Department of Radiology (H.H.C., S.H.C., I.R., S.C.K., J.A.Y., H.S., S.C.J., A.L.L., T.J.Y., J.H.K., C.H.S.), Department of Internal Medicine, Cancer Research Institute (T.M.K., S.H.L.), Department of Neurosurgery (C.K.P.), Department of Pathology (S.H.P.), and Department of Radiation Oncology, Cancer Research Institute (I.H.K.), Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea; and Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (S.H.C.).

Purpose: To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm(2), respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide.

Materials And Methods: This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm(2), and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated.

Results: In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm(2) (ADC1000) and the ADC at b value of 3000 sec/mm(2) (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively.

Conclusion: The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.13122024DOI Listing
December 2013

protective effect of tetracycline against dermal toxicity induced by Jellyfish venom.

PLoS One 2013 11;8(3):e57658. Epub 2013 Mar 11.

College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.

Background: Previously, we have reported that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of metalloproteinases, which apparently linked to the venom toxicity. Further, it is also well known that there is a positive correlation between the inflammatory reaction of dermal tissues and their tissue metalloproteinase activity. Based on these, the use of metalloproteinase inhibitors appears to be a promising therapeutic alternative for the treatment of jellyfish envenomation.

Methodology And Principal Findings: Tetracycline (a metalloproteinase inhibitor) has been examined for its activity to reduce or prevent the dermal toxicity induced by Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom (NnV) using in vitro and in vivo models. HaCaT (human keratinocyte) and NIH3T3 (mouse fibroblast) incubated with NnV showed decreases in cell viability, which is associated with the inductions of metalloproteinase-2 and -9. This result suggests that the use of metalloproteinase inhibitors, such as tetracycline, may prevent the jellyfish venom-mediated local tissue damage. In vivo experiments showed that comparing with NnV-alone treatment, tetracycline pre-mixed NnV demonstrated a significantly reduced progression of dermal toxicity upon the inoculation onto rabbit skin.

Conclusions/significance: It is believed that there has been no previous report on the therapeutic agent of synthetic chemical origin for the treatment of jellyfish venom-induced dermonecrosis based on understanding its mechanism of action except the use of antivenom treatment. Furthermore, the current study, for the first time, has proposed a novel mechanism-based therapeutic intervention for skin damages caused by jellyfish stings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594245PMC
December 2013

Autologous fat transfer in a patient with lupus erythematosus profundus.

Case Rep Dermatol 2012 Sep 9;4(3):207-10. Epub 2012 Oct 9.

Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea.

Lupus erythematosus profundus, a form of chronic cutaneous lupus erythematosus, is a rare inflammatory disease involving in the lower dermis and subcutaneous tissues. It primarily affects the head, proximal upper arms, trunk, thighs, and presents as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions. We present a rare case of lupus erythematosus profundus treated with autologous fat transfer.
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http://dx.doi.org/10.1159/000343469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493019PMC
September 2012

Correlation of apparent diffusion coefficient values measured by diffusion MRI and MGMT promoter methylation semiquantitatively analyzed with MS-MLPA in patients with glioblastoma multiforme.

J Magn Reson Imaging 2013 Feb 28;37(2):351-8. Epub 2012 Sep 28.

Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.

Purpose: To retrospectively determine whether the apparent diffusion coefficient (ADC) values correlate with O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation semiquantitatively analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in patients with glioblastoma.

Materials And Methods: The study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Newly diagnosed patients with glioblastoma (n = 26) were analyzed with an ADC histogram approach based on enhancing solid portion. The methylation status of MGMT promoter was assessed by methylation-specific polymerase chain reaction (MSP) and by MS-MLPA. MS-MLPA is a semiquantitative method that determines the methylation ratio. The Ki-67 labeling index was also analyzed. The mean and 5th percentile ADC values were correlated with MGMT promoter methylation status and Ki-67 labeling index using a linear regression model. Progression-free survival (PFS) was also correlated with the ADC values using Kaplan-Meier survival analysis.

Results: The mean methylation ratio was 0.21 ± 0.20. By MSP, there were 5 methylated and 21 unmethylated tumors. The mean ADC revealed a positive relationship with MGMT promoter methylation ratio (P = 0.015) and was also significantly different according to MSP-determined methylation status (P = 0.011). Median PFS was significantly related with methylation ratio (P = 0.017) and MSP-derived methylation status (P = 0.025). A positive relationship was demonstrated between PFS and the mean ADC value (P = 0.001). The 5th percentile ADC values showed a significant negative relationship with Ki-67 labeling index (P = 0.036).

Conclusion: We found that ADC values were significantly correlated with PFS as well as with MGMT promoter methylation status. We believe that ADC values may merit further investigation as a noninvasive biomarker for predicting treatment response.
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http://dx.doi.org/10.1002/jmri.23838DOI Listing
February 2013

Induction of melanogenesis by rapamycin in human MNT-1 melanoma cells.

Ann Dermatol 2012 May 26;24(2):151-7. Epub 2012 Apr 26.

Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Korea.

Background: Melanogenesis is one of the characteristic parameters of differentiation in melanocytes and melanoma cells. Specific inhibitors of phosphatidylinositol 3-kinase (PI3K), such as wortmannin and LY294002, stimulate melanin production in mouse and in human melanoma cells, suggesting that PI3K and mammalian target of rapamycin (mTOR) might be involved in the regulation of melanogenesis.

Objective: The involvement of the mTOR pathway in regulating melanogenesis was examined using human MNT-1 melanoma cells, and the effects of the potent inhibitor of mTOR, rapamycin, in the presence or absence of α-melanocyte-stimulating hormone (α-MSH) were evaluated.

Methods: In cells treated with rapamycin, cell viability, melanin content, and tyrosinase (TYR) activity were measured and compared with untreated controls. Protein levels of TYR, tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) were also analyzed by Western blot.

Results: In rapamycin-treated cells, the melanin content increased concomitantly with an elevation in TYR activity, which plays a major role in melanogenesis. There was also an up-regulation of TYR, TYRP-1, and MITF proteins. Combined treatment with rapamycin or wortmannin and α-MSH increased melanogenesis more strongly than α-MSH alone.

Conclusion: Rapamycin-induced melanin formation may be mediated through the up-regulation of TYR protein and activity. Furthermore, rapamycin and wortmannin, inhibitors of mTOR and PI3K, respectively, have co-stimulatory effects with α-MSH in enhancing melanogenesis in melanocyte cells.
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http://dx.doi.org/10.5021/ad.2012.24.2.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346904PMC
May 2012

Long term results of right ventricular outflow tract reconstruction with homografts.

Korean J Thorac Cardiovasc Surg 2011 Apr 14;44(2):108-14. Epub 2011 Apr 14.

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

Background: Homograft cardiac valves and valved-conduits have been available in our institute since 1992. We sought to determine the long-term outcome after right ventricular outflow tract (RVOT) reconstruction using homografts, and risk factors for reoperation were analyzed.

Materials And Methods: We retrospectively reviewed 112 patients who had undergone repair using 116 homografts between 1992 and 2008. Median age and body weight at operation were 31.2 months and 12.2 kg, respectively. The diagnoses were pulmonary atresia or stenosis with ventricular septal defect (n=93), congenital aortic valve diseases (n=15), and truncus arteriosus (N=8). Mean follow-up duration was 79.2±14.8 months.

Results: There were 10 early and 4 late deaths. Overall survival rate was 89.6%, 88.7%, 86.1% at postoperative 1 year, 5 years and 10 years, respectively. Body weight at operation, cardiopulmonary bypass (CPB) time and aortic cross-clamping (ACC) time were identified as risk factors for death. Forty-three reoperations were performed in thirty-nine patients. Freedom from reoperation was 97.0%, 77.8%, 35.0% at postoperative 1 year, 5 years and 10 years respectively. Small-sized graft was identified as a risk factor for reoperation.

Conclusion: Although long-term survival after RVOT reconstruction with homografts was excellent, freedom from reoperation was unsatisfactory, especially in patients who had small grafts upon initial repair. Thus, alternative surgical strategies not using small grafts may need to be considered in this subset.
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http://dx.doi.org/10.5090/kjtcs.2011.44.2.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249285PMC
April 2011

Phototoxicity of oriental medicinal plants: measurement and possible applications.

Skinmed 2011 Sep-Oct;9(5):294-300; quiz 300

Department of Chemical Education, Gyeongsang National University, Jinju, Kyungnam, Korea.

Phototoxicity can be either harmful and induce adverse skin reactions or beneficial and be used therapeutically as in psoralen and UV-A or photodynamic therapy. Hundreds of medicinal plants are widely used in Asia and Western countries in oriental medicine, yet the phototoxicity of oriental medicinal plants is an understudied area. In this contribution, the authors discuss some methods used to measure the phototoxicity of plants and give an overview of the results of their previous and ongoing studies into the phototoxicity of medicinal plants. The authors argue that because they found that more than a quarter of oriental medicinal plants can be phototoxic, such research is helpful for dermatologists and that active phototoxic components extracted from oriental medicinal plants may be used therapeutically.
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December 2011