• Journal of Life Science
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• v.23 no.12
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• pp.1532-1540
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• 2013

T-box transcription factor 2 (Tbr2) is a member of the T-box family of transcription factors and it plays an important role in brain development, progenitor cell proliferation, and the modulation of differentiation and function in immune cells, such as CD8+ T cells and natural killer cells. This study aims to elucidate the involvement of Tbr2 in the pathophysiological events following pilocarpine-induced status epilepticus in mice. Status epilepticus resulted in prominent neuronal cell death in discrete brain regions, such as CA3, the hilus, and the piriform cortex. Interestingly, when the immunoreactivity of Tbr2 was examined two days after status epilepticus, it was transiently increased in CA3 and in the piriform cortex. Tbr2-positive cells in CA3 and the piriform cortex were double-labeled with CD11b, a marker of microglia and a subset of white blood cells, such as monocytes, CD8+ T cells, and natural killer cells. Moreover, the double-labeled cells with Tbr2 and CD11b showed amoeboid morphology, and this data indicates that Tbr2-expressing cells may be reactive microglia or infiltrating white blood cells. Furthermore, clustered Tbr2-positive cells were observed in the platelet endothelial cell adhesion molecule-1 (PECAM-1)-positive blood vessels near the CA3 area, which suggests that Tbr2-positive cells may be infiltrating the white blood cells. Based on this data, this study is the first to indicate the involvement of Tbr2 in neuropathophysiology in status epilepticus.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.3
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• pp.1-19
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• 2017

Objectives: The object of this study is to observe the possible ameliorating effects of Nokyongdaebo-tang (NYDBT) on the experimental subacute hemorrhagic anemia (SHA) in rats. Methods: In the present study, SHA in rats was induced by exsanguinations from orbital plexus, and ameliorating effects of NYDBT was observed based on the changes of body and hematopoietic organ (spleen, liver and femur) weights, red blood cell (RBC) related hematological values, smear cytology, histopathological changes and immunohistochemistrical analysis of hematopoietic stem cells in the femur bone marrow, liver and spleen. In addition, the gastrointestinal motility and the surface mucosa thicknesses of remnant fecal pellets in the colon lumen, mucosa thicknesses and the mucous producing cell numbers in the colonic mucosa were analyzed to observe the digestive disorders, especially on the constipation, the major discomfort problems in iron supplement. Results: SHA related abnormal anemic signs were markedly and dose-dependently inhibited by oral administration of NYDBT 500, 250 and 125 mg/kg in a condition of this experiment. In addition, no meaningful changes on the gastrointestinal motilities and mucous component on the colon and remnant feces were noticed in all three different dosages of NYDBT treated rats as compared with intact vehicle and SHA control rats in this study. Conclusions: It, therefore, is expected that NYDBT will be promising as a novel alternative hematopoietic and therapeutic agent for anemia.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.45-55
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• 2008

Purpose: This study evaluates the association of estrogen receptor(ER), progesterone receptor(PR), Her-2, COX-2, and survivin with the clinicopathological features and outcomes in young Korean women with breast cancer using recently developed tissue microarray(TMA) technology. Materials and Methods: A cohort of 212 young patients with breast cancer diagnosed at the age of 45 years or younger from March 1994 to August 2005, were enrolled in this study. The age range of patients was $23{\sim}45$ years(median age, 39 years). The minimum and median follow-up periods were 24 months and 60 months, respectively. Serial sections of primary tumors were processed by the use of a TMA for immunohistochemical staining for five biomarkers. The correlation of these five biomarkers and the clinicopathological features and outcomes were analyzed by statistical methods. Results: The majority of the patients were stage T1(90 patients) or T2(101 patients), and 105 patients(49.5%) had an axillary node metastasis. The 5-year overall and relapse free survival rates for all of the patients were 90.4% and 82.3%, respectively, and 36 patients had a locoregional or distant metastasis as a first event. Positive expression of ER, PR, Her-2, COX-2, and survivin was determined in 38.2%, 45.3%, 25.9%, 41.5%, and 43.4%, of the tumor samples, respectively. Tumor stage, nodal status, age, as well as expression of ER, PR, and HER-2 status were significantly associated with the disease free survival rate. Tumor stage, nodal status, as well as expression of ER, PR, and HER-2 were significantly related with the overall survival rate. Expression of COX-2 and survivin were not single independent prognostic factors for the disease free and overall survival rate although co-expression of HER-2 and COX-2 had a tendency as a poor prognostic factor. By multivariate analysis, only T stage and lymph node status were significant prognostic factors, and ER status was a marginally significant prognostic factor(p=0.075). Conclusion: Expression of ER, PR and HER-2 were significant prognostic factors for the relapse free and overall survival rate. Expression of COX-2 and survivin were not prognostic factors for young women with breast cancer.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.176-181
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• 2008

Purpose: The adipocyte-derived cytokine leptin plays a major role in the control of stable body weight by suppressing food intake and increasing energy metabolism. Leptin regulates the cell proliferation of various epithelial cells and it may be involved in the promotion of cancer. Leptin and its receptor are highly expressed in gastric adenocarcinoma, but the association between the serum leptin level and the tissue expression of leptin is uncertain. We evaluated the serum leptin level and the expressions of leptin and leptin receptor in gastric cancer, and we explore the possible mechanism and role of leptin in the carcinogenesis of gastric cancer. Materials and Methods: 72 carcinomas that were curatively resected at our hospital from October 2005 to March 2007 were included in this study. By immunoassay and immunohistochemical staining, we evaluated the serum leptin level and the expressions of leptin and its receptor, and we analyzed their relationship together with the clinicopathological variables. Results: The serum leptin level was increased as the patient's BMI increased and it was decreased in H. pylori infected patients. The expression of leptin was increased as the TNM stage increased (P=0.014), and the expression of leptin receptor in the intestinal type gastric adenocarcinoma was higher than that in the diffuse type gastric adenocarcinoma (71.4% vs 28.6%, respectively, P=0.033). Conclusion: There was no significant correlation between the serum leptin level and expression of leptin in gastric cancer patients. The expression of leptin was associated with the TNM stage, but its role in the pathogenesis of gastric cancer has to be elucidated.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.447-455
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• 2006

Background: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. Method: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2, -9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. Results: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. Conclusions: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.788-798
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• 2009

Objective : This study was undertaken to investigate effects of Opuntia ficus-indica (OP)extract on an asthma murine model. Methods : The total number of cells and eosinophils in BALF and the infiltration of inflammatory cells into lung tissues were determined by hematoxylin and eosin staining. Results : The number of OVA-induced total cells and eosinophils, a phenomenon of asthma, were decreased by treatment of the animals with OP extract (200 mg/kg) (respectively, p < 0.001 and p<0.01). Furthermore, we showed that OP extract reduced the increased immune cell infiltration induced by ovalbumin (p < 0.01). The levels of interleukin (IL)-4 in BAL fluid were measured by enzyme-linked immunosorbent assay, because the eosinophilia is associated with a T helper (Th) 2 response including IL-4. The level of OVA-induced IL-4 was decreased by OP extract in BAL fluid (p < 0.05). We investigated whether OP extract reduced nitrite (NO) production on lipopolysaccharide (LPS)-stimulated RAW 264.7 sells, because asthma is an inflammatory disease. The level of LPS-induced NO production was decreased by OP extract (50, 100 and 200 mg/ml) on RAW 264.7 cells (respectively, p < 0.05, p<0.01 and p<0.05). Conclusions : Our results indicate that OP extract has an inhibitory effect on lung eosinophilia of asthma and suggest that OP extract is a therapeutic candidate in the treatment of inflammatory disease, including asthma.

• Ultrasonography
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• v.32 no.2
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• pp.132-142
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• 2013

Purpose: The purpose of this study is to investigate the correlations of various kinetic parameters derived from the time intensity curve in a xenograft mouse model injected with a prostate cancer model (PC-3 and LNCaP) using an ultrasound contrast agent with histopathologic parameters. Materials and Methods: Twenty nude mice were injected with human prostate cancer cells (15 PC-3 and five LNCaP) on their hind limbs. A bolus of $500{\mu}L$ ($1{\times}10^8$ microbubbles) of second-generation US contrast agent (SonoVue) was injected into the retroorbital vein. The region of interest was drawn over the entire tumor. The time intensity curve was acquired and then fitted to a gamma variate function. The maximal intensity (A), time to peak (Tp), maximal wash-in rate (washin), washout rate (washout), area under the curve up to 50 sec ($AUC_{50}$), area under the ascending slope ($AUC_{in}$), and area under the descending slope ($AUC_{out}$) were derived from the parameters of the gamma variate fit. Immunohistochemical staining for VEGF and CD31 was performed. Tumor volume, the area percentage of VEGF stained in a field, and the count of CD31 (microvessel density, MVD) positive vessels showed correlation with the parameters from the time intensity curve. Results: No significant differences were observed between the kinetic and histopathological parameters from each group. MVD showed positive correlation with A (r=0.625, p=0.003), washin (r=0.462, p=0.040), $AUC_{50}$ (r=0.604, p=0.005), and $AUC_{out}$ (r=0.587, p=0.007). Positive correlations were also observed between tumor volume and $AUC_{50}$ (r=0.481, p=0.032), washin (r=0.662, p=0.001), and $AUC_{out}$ (r=0.547, p=0.012). Washout showed negative correlations with MVD (r=-0.454, p=0.044) and tumor volume (r=-0.464, p=0.039). The area percentage of VEGF did not show any correlation with calculated data from the curve. Conclusion: MVD showed correlations with several of the kinetic parameters. CEUS has the potential for prediction of tumor vascularity in a prostate cancer animal model.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.26-34
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• 2009

Purpose: The purpose of this study was to find out what clinicopathologic or immunohistochemical parameter that may affect FDG uptake of primary tumor in PET/CT scan of the gastric carcinoma patient. Materials and Methods: Eighty-nine patients with stomach cancer who underwent pre-operative FDG PET/CT scans were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The clinicopathologic results such as depth of invasion (T stage), tumor size, lymph node metastasis, tumor differentiation and Lauren's classification and immunohistochemical markers such as Ki-67 index, expression of p53, EGFR, Cathepsin D, c-erb-B2 and COX-2 were reviewed. Results: Nineteen out of 89 gastric carcinomas showed imperceptible FDG uptake on PET/CT images. In cases with perceptible FDG uptake in primary tumor, SUVmax was significantly higher in T2, T3 and T4 tumors than T1 tumors ($5.8{\pm}3.1$ vs. $3.7{\pm}2.1$, p=0.002). SUVmax of large tumors (above or equal to 3 cm) was also significantly higher than SUVmax of small ones (less than 3 cm) ($5.7{\pm}3.2$ vs. $3.7{\pm}2.0$, p=0.002). The intestinal types of gastric carcinomas according to Lauren showed higher FDG uptake compared to the non-intestinal types ($5.4{\pm}2.8$ vs. $3.7{\pm}1.3$, p=0.003). SUVmax between p53 positive group and negative group was significantly different ($6.0{\pm}2.8$ vs. $4.4{\pm}3.0$, p=0.035). No significant difference was found in presence of LN metastasis, tumor differentiation, Ki-67 index, and expression of EGFR, Cathepsin D, c-erb-B2 and COX-2. Conclusion: T stage of gastric carcinoma influenced the detectability of gastric cancer on FDG PET PET/CT scan. When gastric carcinoma was perceptible on PET/CT scan, T stage, size of primary tumor, Lauren's classification and p53 expression were related to degree of FDG uptake in primary tumor.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.557-564
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• 2009

Purpose: To evaluate the relationship between F-18 FDG uptake of tumor in PET/CT scan and pathological or immunohistochemial parameters of colorectal cancer. Materials and Methods: 147 colorectal cancer patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The pathologic results such as site, size, depth of invasion (T stage), growth pattern, differentiation of primary tumor, lymph node metastasis and Dukes-Astler & Coller stage and immunohistochemical markers such as expression of EGFR, MLH1, MSH2 and Ki-67 index were reviewed. Results: 146 out of 147 PET/CT scans with colorectal cancer showed perceptible focal FDG uptake. SUVmax showed mild positive linear correlation with size of primary tumor (r=0.277, p=0.001) and Ki-67 index (r=0.226, p=0.019). No significant difference in F-18 FDG uptake was found according to site, depth of invasion (T stage), growth pattern, differentiation of primary tumor, presence of lymph node metastasis, Dukes-Astler & Coller stage and expression of EGFR. Conclusion: The degree of F-18 FDG uptake in colorectal cancer was associated with the size and the degree of Ki-67 index of primary tumor. It could be thought that FDG uptake of primary tumor has a correlation with macroscopic and microscopic tumor growth.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1285-1295
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• 1997

Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.