Hwaseong, South Korea
Hwaseong, South Korea

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Shim H.J.,Yonsei University | Kim H.I.,Yonsei University | Kim H.I.,Shingyeong University | Lee S.-T.,Yonsei University
Oncology Letters | Year: 2017

Protein tyrosine kinase (PTK)6, also known as breast tumor kinase, is a non-receptor tyrosine kinase. It is closely associated with, but evolutionarily distinct from, the Src family members. PTK6 has a role in proliferation, migra-tion and invasion in various cancers, and therefore has been suggested as a potentially valuable therapeutic target. In an attempt to develop PTK6 inhibitors, chemicals known to inhibit various kinases were screened for their ability to inhibit PTK6. Pyrazolopyrimidine (PP)1, PP2 and a lymphocyte-specific protein tyrosine kinase inhibitor strongly inhibited the catalytic activity of PTK6 in vitro. These chemicals suppressed the phosphorylation of PTK6 substrate proteins, including signal transducer and activator of transcription 3, in human embry-onic kidney (HEK) 293 cells expressing hyperactive PTK6. They also expressed selectivity towards PTK6 over other PTK members in HEK 293 cells. PP1 and PP2 specifically inhibited the PTK6-dependent proliferation of human breast carcinoma T-47D cells. PP1 and PP2 were more selective for PTK6 than for Src family kinases, and may be useful for the treatment of PTK6-positive malignant diseases such as breast cancer. © 2017, Spandidos Publications. All rights reserved.


Kim J.-H.,Chosun University | Yoo S.-J.,Seonam University | Kwak D.-H.,Seonam University | Jung H.-J.,Shingyeong University | And 3 more authors.
Nanoscale Research Letters | Year: 2014

Alumina nanofibers were prepared by a technique that combined the sol-gel and electrospinning methods. The solution to be electrospun was prepared by mixing aluminum isopropoxide (AIP) in ethanol, which was then refluxed in the presence of an acid catalyst and polyvinylpyrolidone (PVP) in ethanol. The characterization results showed that alumina nanofibers with diameters in the range of 102 to 378 nm were successfully prepared. On the basis of the results of the XRD and FT-IR, the alumina nanofibers calcined at 1,100°C were identified as comprising the α-alumina phase, and a series of phase transitions such as boehmite → γ-alumina → α-alumina were observed from 500°C to 1,200°C. The pore size of the obtained γ-alumina nanofibers is approximately 8 nm, and it means that they are mesoporous materials. The kinetic study demonstrated that MO adsorption on alumina nanofibers can be seen that the pseudo-second-order kinetic model fits better than the pseudo-first-order kinetic model. © 2014 Kim et al.


Lee S.-J.,U.S. National Cancer Institute | Lee S.-J.,Shingyeong University | Tsang P.S.,U.S. National Cancer Institute | M Diaz T.,U.S. National Cancer Institute | And 2 more authors.
Laboratory Investigation | Year: 2010

In this study, we examine the effects of tissue inhibitor of metalloproteinases-2 (TIMP-2) on the phosphorylation status of specific phosphotyrosine residues on the vascular endothelial cell growth factor receptor-2 (VEGFR-2) cytoplasmic tail and examine the effects on associated downstream signaling pathways. To focus on metalloproteinase-independent mechanisms, we used the TIMP-2 analog known as AlaTIMP-2 that is deficient in matrix metalloproteinase-inhibitory activity. Our experiments are designed to compare the effects of VEGF-A stimulation with or without AlaTIMP-2 pretreatment, as well as basal responses in human microvascular endothelial cells. Our results show that AlaTIMP-2 selectively alters the phosphorylation pattern of VEGFR-2 after VEGF-A stimulation and disrupts the downstream activation of PLC-γ, Ca 2 flux, Akt, and eNOS, as well as decreasing cGMP levels. Moreover, we observed an AlaTIMP-2-induced reduction in cGMP levels typically elevated by exogenous NO donors implicating AlaTIMP-2 in the direct activation of an isobutylmethylxanthine (IBMX)-sensitive cGMP phosphodiesterase activity. TIMP-2 suppression of endothelial mitogenesis and angiogenesis involves at least two mechanisms, one mediated by protein tyrosine phosphatase inhibition of VEGFR-2 activation as well as downstream signaling and a second mechanism involving direct activation of an IBMX-sensitive phosphodiesterase activity. © 2010 USCAP, Inc All rights reserved.


Kim S.H.,Kangwon National University | Cho Y.-R.,Dankook University | Kim H.-J.,Dankook University | Oh J.S.,Dankook University | And 8 more authors.
Blood | Year: 2012

In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A-induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3β1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2-mediated inhibition of vascular permeability involves an integrin α3β1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3β1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through "normalization" of vascular permeability in addition to previously described antiangiogenic effects. © 2012 by The American Society of Hematology.


Kim S.,Sungkyunkwan University | Kim C.-S.,National Academy of Agricultural Science | Lee J.,National Academy of Agricultural Science | Lee I.-Y.,National Academy of Agricultural Science | And 3 more authors.
Plant Systematics and Evolution | Year: 2014

The genus Setaria (tribe Paniceae, subfamily Panicoideae, family Poaceae) comprises approximately 125 species, including agriculturally important food crop (Setaria italica) and globally distributed weed species (S. viridis, S. faberi, S. verticillata, and S. pumila). As an ongoing attempt to determine phylogenetic relationships among species of Setaria in East Asia, we generated phylogeny of Setaria based on a total of 44 accessions representing all the species in Korea. We sequenced two nuclear loci (nrDNA ITS and kn1) and three chloroplast DNA non-coding regions (trnL-trnF, psbJ-petA, and trnQ-rps16) and conducted maximum parsimony, maximum likelihood and Bayesian Inference analyses. The results identified two groups of Setaria in Korea, i.e., S. glauca (=S. pumila) group and S. viridis–S. faberi complex (S. viridis, S. italica, S. faberi, and S. × pycnocoma) group. Only one representative perennial species (i.e., S. chondrachne) in Korea is sister to the S. viridis–S. faberi clade. A minimum of two independent origins of S. faberi, a putative allotetraploid, is suggested in this study, but the contribution from B genome (i.e., S. adhaerens) was not supported. The origin of tetraploid, perennial species of Setaria in Korea, S. chondrachne, is uncertain, but this study suggests possible autotetraploidy and close relationship of S. chondrachne with A genome type species in S. viridis–S. faberi clade. We also documented possible ancient gene flow between D genome (i.e., S. glauca var. dura) and A genome (e.g., S. viridis) in this study. © 2014, Springer-Verlag Wien.


PubMed | Shingyeong University and Gachon University
Type: Journal Article | Journal: Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis | Year: 2016

Bomarea, a member of the family Alstroemeriaceae, is distributed from Chile to Mexico and includes approximately 120 species. Recent molecular phylogenetic studies have clarified the monophyly of the family within the order Liliales and the sister relationship with the family Colchicaceae. At this time, five plastid genomes of Liliales have been analyzed at the familial level. To examine plastid genome variation at the generic level, we sequenced the plastid genome of Bomarea edulis, which is the most widely distributed species in the genus, and compared it with Alstroemeria aurea. The plastid genome sequence of B. edulis was 154,925bp in length with a similar structure as A. aurea, excluding the IR-LSC junction. Ycf68 and infA were pseudogenes caused by frameshift mutations, and the ycf15 gene was deleted, similar to A. aurea.


Kim H.I.,Shingyeong University | Lee H.-S.,Baylor College of Medicine | Kim T.H.,Shingyeong University | Lee J.-S.,University of Houston | And 2 more authors.
Oncotarget | Year: 2015

Tissue inhibitors of metalloproteinases (TIMPs) control extracellular matrix (ECM) homeostasis by inhibiting the activity of matrix metalloproteinases (MMPs), which are associated with ECM turnover. Recent studies have revealed that TIMPs are implicated in tumorigenesis in both MMP-dependent and MMP-independent manners. We examined a mechanism by which TIMP-2 stimulated lung adenocarcinoma cell proliferation, independent of MMP inhibition. The stimulation of growth by TIMP-2 in A549 cells required c-Src kinase activation. c-Src kinase activity, induced by TIMP-2, concomitantly increased FAK, phosphoinositide 3-kinase (PI3-kinase)/AKT, and ERK1/2 activation. Selective knockdown of integrin a3β1, known as a TIMP-2 receptor, did not significantly change TIMP-2 growth promoting activity. Furthermore, we showed that high TIMP-2 expression in lung adenocarcinomas is associated with a worse prognosis from multiple cohorts, especially for stage I lung adenocarcinoma. Through integrated analysis of The Cancer Genome Atlas data, TIMP-2 expression was significantly associated with the alteration of driving genes, c-Src activation, and PI3-kinase/AKT pathway activation. Taken together, our results demonstrate that TIMP-2 stimulates lung adenocarcinoma cell proliferation through c-Src, FAK, PI3-kinase/AKT, and ERK1/2 pathway activation in an MMP-independent manner.


PubMed | Yonsei University, Shingyeong University, University of Houston and Baylor College of Medicine
Type: Journal Article | Journal: Oncotarget | Year: 2016

Tissue inhibitors of metalloproteinases (TIMPs) control extracellular matrix (ECM) homeostasis by inhibiting the activity of matrix metalloproteinases (MMPs), which are associated with ECM turnover. Recent studies have revealed that TIMPs are implicated in tumorigenesis in both MMP-dependent and MMP-independent manners. We examined a mechanism by which TIMP-2 stimulated lung adenocarcinoma cell proliferation, independent of MMP inhibition. The stimulation of growth by TIMP-2 in A549 cells required c-Src kinase activation. c-Src kinase activity, induced by TIMP-2, concomitantly increased FAK, phosphoinositide 3-kinase (PI3-kinase)/AKT, and ERK1/2 activation. Selective knockdown of integrin 31, known as a TIMP-2 receptor, did not significantly change TIMP-2 growth promoting activity. Furthermore, we showed that high TIMP-2 expression in lung adenocarcinomas is associated with a worse prognosis from multiple cohorts, especially for stage I lung adenocarcinoma. Through integrated analysis of The Cancer Genome Atlas data, TIMP-2 expression was significantly associated with the alteration of driving genes, c-Src activation, and PI3-kinase/AKT pathway activation. Taken together, our results demonstrate that TIMP-2 stimulates lung adenocarcinoma cell proliferation through c-Src, FAK, PI3-kinase/AKT, and ERK1/2 pathway activation in an MMP-independent manner.


Jang J.-M.,Chonbuk National University | Park J.-I.,Chonbuk National University | Oh K.-Y.,Maeumsarang Hospital | Lee K.-H.,Maeumsarang Hospital | And 5 more authors.
Psychiatry Research | Year: 2014

The objective of this cross-sectional study was to investigate the relationships of anger, self-esteem, and depression with suicidal ideation. A survey was conducted in a wide range of community areas across Jeollabuk-do Province, Korea. A total of 2964 subjects (mean age=44.4. yr) participated in this study. Hierarchical regression was used to investigate predictors of suicidal ideation in terms of their sociodemographic characteristics, depression, self-esteem, and anger. Hierarchical regression analyses revealed that anger and self-esteem were significantly associated with suicidal ideation regardless of age and after controlling for depression. Moderation analysis showed that the impact of anger on suicidal ideation was significantly greater among females than males in adolescents, but not in other age groups. Additionally, there were some differences in sociodemographic predictors of suicidal ideation among age groups. Predictors included gender and family harmony in adolescents, marital status and family harmony in middle-aged individuals, and economic status and family harmony in elderly individuals. Our results revealed that anger and self-esteem play important roles in suicidal ideation beyond the effect of depression. Development and implementation of preventive strategies, including management of anger and self-esteem, could possibly reduce suicidal ideation and subsequent suicide attempts. © 2014 Elsevier Ireland Ltd.


Park J.-I.,Chonbuk National University | Han M.-I.,Maeumsarang Hospital | Kim M.S.,Jeonju University | Yoon M.-S.,Chonbuk National University | And 3 more authors.
International Journal of Geriatric Psychiatry | Year: 2014

Objectives Despite the importance of tending to older individuals who are vulnerable to suicide, little is known about suicidal ideation in the portion of this population receiving home-care services in Asian countries. The objective of this cross-sectional study was to examine predictors of suicidal ideation in older individuals using home-care service. Method Participants were randomly selected from the individuals 50 years old and over using home-care services across Jeollabuk-do Province, Korea. A total of 697 subjects participated in this study. Each participant completed the short version of the Geriatric Depression Scale, the Scale for Suicidal Ideation, the Multidimensional Scale of Perceived Social Support, and the World Health Organization Disability Assessment Schedule II. Results Hierarchical regression analyses revealed that depression, perceived social support, and disability were significant predictors of suicidal ideation, whereas the roles of subjective health status and fish consumption remained ambiguous in this regard. In terms of social support, we also found that less perceived social support from family members was related to higher levels of suicidal ideation. The associations between various categories of disability and suicidal ideation disappeared after controlling for depression. Our investigation of the mediating effect of depression on the relationship between disability and suicidal ideation revealed that depression was either a complete (disability related to cognition, self-care, getting along with others, and life activities) or partial (disability related to participation) mediator. Conclusions Preventive strategies focusing on depression, social support, and disability should be emphasized during encounters with older people receiving home-care services. © 2013 John Wiley & Sons, Ltd.

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