• Korean Journal of Clinical Laboratory Science
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• v.43 no.2
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• pp.48-56
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• 2011

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor and is associated with a specific immunophenotype index. It is very important to identify the specific immunophenotype and the diagnosis for the treatment GIST patients. Ninety two cases of GIST analyzed in this study were immuno-stained for c-kit, DOG1, CD34, PKC-${\theta}$, PDGFR-${\alpha}$. The rate of positive staining and statistical significance were then compared. In addition, the GISTs were analyzed as followings: very low risk, low risk, intermediate risk and high risk according to tumor size and nuclear division, and later correlated with clinical parameters. The results of the GIST positive stainings were: DOG1 (95.7%), PKC-${\theta}$ (90.2%), PDGFR-${\alpha}$ (88.0%), c-kit (87.0%) and CD34 (71.7%). Only DOG1 staining showed a statistical significance of p<0.05. It was identified in the classification system of histologic risk that staining expression of DOG1, PKC-${\theta}$, PDGFR-${\alpha}$ were significantly increased as histologic risk increases (p<0.05). However, clinical parameters such as age and sex of patients have no correlations with the classification system of histologic risk (p>0.05). Therefore, in this study, the expression of DOG1 showed statistical significance and DOG1, PKC-${\theta}$, PDGFR-${\alpha}$ staining increased significantly as the histologic risk increases in histologic classification system. Taken together, the DOG1 staining should be very effective for the diagnosis of GIST patients.

• Journal of Veterinary Clinics
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• v.33 no.4
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• pp.187-193
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• 2016

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions. This study aims to show that the actions of growth factors associated with PDGFR-${\alpha}$, PDGFR-${\beta}$, VEGFR-2, c-KIT, and c-ABL, which are used in veterinary medicine, are expressed in canine intractable tumors. This study used archival cases of canine paraganglioma, gastrointestinal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. Tissues had been immunohistochemical analysis. The antibodies used were PDGFR-${\alpha}$, PDGFR-${\beta}$, c-kit, VEGFR-2, and c-Abl. PDGFR-${\alpha}$ was expressed only in HCC, and PDGFR-${\beta}$ was expressed in all tumors. VEGFR was also only expressed in HCC, and c-KIT has been expressed in HCC, paraganglioma, and small intestinal adenocarcinoma. c-Abl was expressed in all cancers, but was weakly expressed in paraganglioma, while more than moderately expressed in other tissues. In conclusion, this study investigated how TKIs used in human medicine can be applied to canine intractable tumors, through immunohistochemistry. The results indicate that there may be an application for TKIs in treating canine intractable tumors.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.504-518
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect of greater celandine on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells (HSC-T6) were treated with various concentrations of greater celandine extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, mRNA of the ${\alpha}SMA$, TIMP-1, TIMP-2, collagen I ${\alpha}$ 1, MMP-2, IL-6, TGF-${\beta}1$, PDGFr-${\beta}1$, Bcl-2, Bax, Bcl-xl, caspase-3, caspase-9 and the activities of SOD and catalase were measured by using MTT assay, BrdU assay, real-time PCR, superoxide dismutase assay and catalase assay. Results : The viability, proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited as the concentration increased, which indicates the herb has an inhibitory effect on fibrogenesis of the liver by regulating the fibrosis associated genes in transcription. Conclusions : These results suggest that greater celandine would be beneficial in the treatment of fibrotic patients as well as for patients with chronic hepatitis.

• Molecules and Cells
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• v.39 no.11
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• pp.790-796
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• 2016

Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed mesenchymal stem cell (MSC)-like characteristics including the expression of surface antigens and in vitro osteogenic and adipogenic differentiation potentials. Moreover, SHEDs were positive for NG2, ${\alpha}$-smooth muscle actin (SMA), platelet-derived growth factor receptor beta ($PDGFR{\beta}$), and CD146 as pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs were transplanted into immunodeficient mouse using Matrigel with or without human umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or HUVECs alone resulted in no formation of vessel-like structures with enough red blood cells. However, when SHEDs and HUVECs were transplanted together, extensive vessel-like structures were formed. The presence of murine erythrocytes within lumens suggested the formation of anastomoses between newly formed vessel-like structures in Matrigel plug and the host circulatory system. To understand underlying mechanisms of in vivo angiogenesis, the expression of angiogenic cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and HUVECs. SHEDs showed higher expression of1VEGF, SDF-$1{\alpha}$, and $PDGFR{\beta}$ than HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors, CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested reciprocal interactions between SHEDs and HUVECs and their involvement during in vivo angiogenesis. In conclusion, SHEDs could be a feasible source of perivascular cells for in vivo angiogenesis.

• Biomedical Science Letters
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• v.27 no.2
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• pp.95-98
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• 2021

The S100 family proteins act as inducers of cancer cell apoptosis and inflammatory mediators. This study examined the pro-apoptotic mechanism caused by S100A8 and S100A9 in human FIP1L1-PDGFRα-positive eosinophilic leukemia cells. S100A8 and S100A9 elicited the death of EoL-1 cells in a time and dose-dependent manner. The activation of PDGFRα was suppressed by a decrease in PDGFRα after treatment with S100A8 and S100A9. Cycloheximide, a translation inhibitor, suppressed PDGFRα expression from 1 h to 5 h, and a co-treatment with S100A8 and S100A9 boosted the decrease in expression. The phosphorylation and expression of STAT5 decreased after treatment with S100A8 and S100A9 in EoL-1 and imatinib-resistant (EoL-1-IR) cells. S100A8 and S100A9 induced the chemotaxis of EoL-1 cells but did not affect the chemoattraction of EoL-1-IR. These findings indicate the cell death mechanism due to S100 family proteins and the development of leukemia therapy using S100A8 and S100A9.

• The Journal of Korean Medicine
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• v.35 no.4
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• pp.36-51
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• 2014

Objectives: cDNA microarray is an effective method to snapshot gene expression. Functional clustering of gene expressions can identify herbal medicine mechanisms. Much microarray data is available for various herbal medicines. This study compares regulated genes with herbal medicines to evaluate the nature of the drugs. Methods: Published microarray data were collected. Total RNAs were prepared from dissociated hippocampal dissociate cultures which were given hypoxic shock in the presence of each herbal medicine. Up- or downregulated genes higher than Global M value 0.5 were selected, clustered in functional groups, and compared with various herbal treatments. Results: 1. Akt2 was upregulated by Acorus gramineus SOLAND, Arisaema amurense var. serratum $N_{AKAI}$ and Coptis chinensis $F_{RANCH}$, and they belong to Araceae herb. 2. Nf-${\kappa}b1$, Cd5, $Gn{\gamma}7$ and Sgne1 were upregulated by Arisaema amurense var. serratum $N_{AKAI}$, Coptis chinensis $F_{RANCH}$ and Rheum coreanum $N_{AKAI}$. 3. Woohwangcheongsim-won, Sohaphyang-won and Scutellaria baicalensis $G_{EORGI}$ downregulated Scp2 and upregulated Tsc2. Woohwangcheongsim-won and Sohaphyang-won upregulated Hba1 and downregulated Myf6. 4. Sohaphyang-won and Scutellaria baicalensis $G_{EORGI}$ downregulated Slc12a1. 5. Woohwangcheongsim-won and Arisaema amurense var. serratum $N_{AKAI}$ upregulated $Rar{\alpha}$, Woohwangcheongsim-won and Coptis chinensis $F_{RANCH}$ downregulated Rab5a and $Pdgfr{\alpha}$, and Woohwangcheongsim-won and Rheum coreanum $N_{AKAI}$ upregulated $Plc{\gamma}1$ and downregulated Pla2g1b and Slc10a1. Conclusions: By clustering microarray, genes are commonly identified to be either up- or downregulated. These results will provide new information to understand the efficacy of herbal medicines and to classify them at the molecular level.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1389-1393
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• 2012

Objective: To discuss the significance of DOG1, CD117 and PDGFRA in the diagnosis of gastrointestinal stromal tumors (GISTs), and analyze their correlations with clinicopathological features and risk ranking. Method: DOG1, CD117 and PDGFRA were detected with IHC Envision ldpe-g-nvp in 63 GISTs and 43 cases of non-GISTs, and analyzed for relations with clinicopathological factors (gender, age, location, tumor size, mitotic phase, histology) and risk degree. Results: The positive expression rate of DOG1, CD117 and PDGFRA in GISTs was 84.1% (53/63), 90.5% (57/63), 53.2% (33/63), respectively. Among the 6 CD117 negative cases, all were DOG1 positive and 5 were PDGFRA positive. Rates in patients with non-GISTs was 11.6%, 16.3%, 6.98%, respectively. Expression of DOG1 and PDGFRA demonstrated no significant variation with gender, age, position, tumor size, mitotic phase, histology, and risk rank. However, CD117 was related with position and histology (P=0.008 and P=0.045), those in the mesentery having a higher positive rate than those derived from stomach, small intestine, colon and rectum (50.0% vs 94.7%, P=0.008). Furthermore CD117 was also highly expressed in spindle and epithele types. Conclusions: DOG1 had a good sensitivity and specificity as a kind of newly discovered marker, especially for KIT negative GISTs. However, DOG1, CD117 and PDGFRA cannot be used for assessing the rish of patients.