• Journal of Gastric Cancer
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• v.7 no.4
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• pp.185-192
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• 2007

Purpose: RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer. In the present study, we examined the pattern of RUNX3 expression in gastric cancer cells from gastric cancer specimens and the impact of its alteration on clinical outcome. Materials and Methods: A total of 124 samples of both gastric cancer and normal tissue were obtained from 124 patients who underwent curative gastrectomy at the Seoul Medical Center from January 2001 to December 2005. RUNX3 expression was determined by immunohistochemical staining, and the results were analyzed. Statistical analysis wabased on clinicopathological findings and differences in survival rates. Results: The mean age of the patients was 61 years, and the male:female ratio was 1.9:1. The expression rate of RUNX3 was 59.7% (74/124). The expression rate was higher in differentiated gastric cancers (nucleus: 9.1%, cytoplasm: 57.6%) than in the undifferentiated types (nucleus: 5.2%, cytoplasm: 46.6%) (P=0.133). The 5-year survival rates according to RUNX3 expression determined from cancer tissue were 88.9% for the nucleus $\pm$ cytoplasm(+) group of patients, 76.1% for the cytoplasm only (+) group of patients, and 65.3% for the RUNX3 negative expression group of patients (P=0.626). Only UICC TNM staging showed statistical significance related to the survival rate, as determined by multivariate analysis. Conclusion: The RUNX3 expression rate was higher in differentiated gastric cancer than in the undifferentiated types without significance. Although RUNX3 expression predicted better survival, based on multivariate analysis, the finding was not statistically significant. More cases should be further evaluated.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.104-109
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• 1998

Purpose : The proliferative nuclear antigen Ki-67, present in all cell cycle phases except G0, is a useful marker for the detection of proliferative cells in vivo. MIB I has been found to recognize an antigen in formalin-fixed and wax-embedded material. The aim of this study was to assess the efficacy of MIB-1 expression as a marker of representing the status of mesangial cell proliferation in renal tissues. Methods : Immunohistochemical staining for Ki-67 Ag using monoclonal antibody MIB-1 (Immunotech,505) were performed in 41 renal tissuses which were obtained by percutaneous renal biopsy done between January 1994 and December 1996. Results : In both glomeruli and renal tubules, MIB-1 expression was observed only in 2 of 18 ($11.1\%$) cases of IgA nephropathy, in 2 of the 4 ($50\%$) cases of mebranoproliferative glomerulonephritis, in 4 of the 5 ($80\%$) cases of poststreptococcal glomerulonephritis. But MIB-1 expression was not detected in all cases of minimal lesion and membranous nephropathy. Renal tubules In another 7 cases of IgA nephropathy were MIB-1 positive. Conclusion : MIB-1 expression in renal tissues may relate to the cell proliferation in glomeruli and renal tubules. But the efficacy of MIB-1 expression as a marker of mesangial cell proliferation may reveal a limited value because of it's lower positive rate in IgA nephropathy.

• Journal of Chest Surgery
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• v.41 no.4
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• pp.447-456
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• 2008

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.487-494
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• 2008

Background: Chromosome 17p allele losses and mutations of p53 gene are the most common genetic abnormalities in lung cancer. The purposes of this study were to evaluate the factors associated with p53 protein overexpression and to evaluate its prognostic value in patients with pathologic stage I non-small cell lung cancer (NSCLC). Methods: This is a retrospective review for the patients who underwent surgical resection at Samsung Medical Center between Jan 2003 and Jun 2004. Immunohistochemical staining for p53 protein was performed on tumor tissues from patients with lung cancer. The p53 overexpression was evaluated in relation to age, sex, smoking history, histology and pathologic stage by univariate and multivariate analyses. The disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were analyzed using the Kaplan-Meier methods and the differences in DFS, DSS and OS were assessed by using the log-rank tests. Results: A total of 125 patients were included in the analysis and a median frequency of p53 expression in tumor tissue was 10%. The p53 overexpression (${\geq}10%$) was more common in squamous cell carcinoma (66%) than in adenocarcinoma (38%, p=0.002). The p53 overexpression was more common in pathologic stage IB (59%) than in IA (38%, p=0.002). Patients with p53-overexpressing tumor (27 years) smoked more years compared with those without it (20 years, p=0.032). Smoking history ${\geq}25$ pack-years was more common in patients with p53 overexpression (58%) than in those without it (38%, p=0.024). In the multivariate analysis, only histology was significantly associated with p53 overexpression. However, there were no significant differences of DFS, DSS and OS in relation to p53 status. Conclusion: The p53 overexpression was associated with histology, pathologic stage and smoking history in patients with pathologic stage I NSCLC. However, the p53 overexpression was not associated with patient's survival.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1378-1384
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• 2005

Purpose : We hypothesized dexrazoxane(DXR) and pentoxifylline(PTX) may prevent myocardial damage in adriamycin(ADR)-induced cardiomyopathic rat model. We also investigated their effects on the myocardial apoptosis and fibrosis in ADR induced cardiomyopathy. Methods : The six-week old female Spregue-Dawley rats were divided into control group(CNT, n=4), ADR group(n=6), ADR+DXR group(DXR, n=5), ADR+PTX group(PTX, n=6), ADR+DXR+PTX group(DXPT, n=5). ADR(5 mg/week, twice) was administrated intravenously to rats except CNT group to induce cardiomyopathy. The PTX(50 mg/kg/day) was administered daily from day-0 to Day-21. The DXR(100 mg/kg) was administered 30 minutes before each ADR injection. On day 21, the rats were sacrificed and the degree of histopathologic changes of hypercontraction band necrosis, cytoplasmic vacuolar change and fibrosis were scored. Immunohistochemical staining for Bcl-2 expression and RT-PCR for $TNF-{\alpha}$ and CTGF were performed. Results : Histopathological scores of myocardial damage were significantly higher in ADR rats than CNT rats(P<0.05), and significantly lower in DXPT rats than ADR rats(P<0.01). Myocardial fibrosis was prevented in both PTX rats and DXPT rats. The expression of Bcl-2 was weaker in ADR rats than that in CNT rats(P<0.05), and stronger in both DXR and DXPT rats than that in ADR rats (P<0.05). $TNF-{\alpha}$ concentration of ADR rats was not different from that of treated groups. Conclusion : DXR prevented myocyte apoptosis with increased Bcl-2 expression, and PTX prevented myocardial fibrosis in ADR induced cardiomyopathic rats. The combination therapy of DXR and PTX showed prevention of cardiomyopathy in ADR induced cardiomyopathy rat model.

• The korean journal of orthodontics
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• v.26 no.5 s.58
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• pp.581-590
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• 1996

Bone resorptiion was predominate in compression site, bone formation in tension site of periodontal ligament during tooth movement. The biologic response at compressiion site was different from tension site. Thus the CGHP immuno-positive nerve fiber will respond differently to mechanical force according to the area( compression or tension site). The purpose of this study was to investigate this response of CGRP immune-positive nerve fiber in the periodontal ligament according to the duration of applied force and the area (compression or tension site) during experimental tooth movement. The experimental animals were 7 week old male rat (approximately 200 gm). The orthodontic force was applied mesially to the right maxillary molar using the Ni-Ti coil spring during 12hours, 1, 3, 7, and 120days. Immunohistochemical staining using antibody against CGRP was performed after sacrifice. The results were as follows. The CGRP immune-positive nerve bundle showed reduced immunoreactivity and nerve fibers reduced in density after application of orthodontic force for 12 hours and 1day. The CGRP immune-positive nerve fibers showed many thin branches at the apical periodontal ligament after application of force for 3 days as compared with normal. The tension site in the apical periodontal ligament showed more branches than the compression site. In 7 day group, the CGRP immune-positive nerve fibers increased in terms of the number and had many thin branches in the apical periodontal ligament. The tension site had more branches than the compression site. In 12 day group, the CGRP immune-positive nerve fibers showed similar distribution to normal control at compression site of apical periodontal ligament, but the fibers at the tension site increased in number. The CGRP immuno-positive nerve fibers showed more increased at tension site than compression site after application of orthodontic force. Therefore it seems to have some relation to the bone remodeling besides the local inflammatory process.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.218-227
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• 2009

Purpose: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-$1\alpha$ expression and apoptosis. Materials and Methods: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-$1\alpha$, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. Results: At day 1, HIF-$1\alpha$ and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-$1\alpha$, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-$1\alpha$ expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Conclusion: Neutron irradiation showed a decrease in HIF-$1\alpha$, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-$1\alpha$ expression and subsequent apoptotic protein expressions.

• Journal of Chest Surgery
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• v.40 no.8
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• pp.529-535
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• 2007

Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.437-447
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• 2001

Background: TNF-alpha is related to the generation of lung fibrosis in patients with UIP. The precise mechanism leading to lung fibrosis by TNF-alpha is unknown. However, the activation of a transcription factor like AP-1(down stream of c-jun N-terminal kinase, JNK) by TNF-alpha may be related to the induction of fibrogenic cytokines like PDGF or IGF-I. Furthermore, JNK was reported to be activated in the radiation-induced lung fibrosis model. This study examined JNK activity in patients with UIP. Methods : The expression of phosphorous JNK(p-JNK), macrophage/monocyte specific markers, CD68, and cytokeratin was evaluated by immunohistochemical(IHC) staining of lung tissues from patients with UIP and lung cancer. An in vitro kinase assay was performed with alveolar macrophages obtained by a bronchol-avleolar lavage from patients with UIP and healthy persons as the control. Results : The IHC stain showed that p-JNK is expressed in the almost all of the alveolar macrophages and smooth muscle cells in patients with UIP. In case of the normal areas of the lung from patients with lung cancer, the alveolar macrophages showed little p-JNK expression. Interestingly, increased JNK activity was not found in the in vitro kinase assay of the alveolar macrophages obtained from both patients with UIP and healthy persons as the control. Furthermore, 10 ng/mL of TNF-alpha failed to increase the JNK activity of the alveolar macrophages in both patients with UIP and healthy people. Conclusion : The JNK was activated constitutionally in patients with UIP. However, the role of JNK in the pathogenesis of lung fibrosis needs to be clarified.