• 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.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.301-317
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• 2005

The number of patients with tongue carcinoma is increasing rapidly among young individuals in many parts of the world. Oral carcinoma progresses from hyperplastic lesion through dysplasia to invasive carcinoma and the concept of "field cancerization" with molecular alteration has been suggested for oral cavity carcinogenesis. Significant improvement in treatment and prognosis will depend on more detailed understanding of the multi-step process leading to cancer development. To induce tongue carcinoma in rat by 4-NQO, each drinking water was made to 10 ppm, 25 ppm, 50 ppm and control (only D.W. without 4-NQO). Specimens were classified into 4 groups such as control, I (mild & moderate dysplasia), II (severe dysplasia and carcinoma in situ), III (carcinoma). The mRNA expressions of Bcl-2 family were evaluated by RT-PCR technique. For anti-apoptotic Bcl-2 family, mRNA expression of Bcl-w was down-regulated in all stages of tongue carcinogenesis model. However, mRNA expression of Bcl-2 was up-regulated. For pro-apoptotic Bcl-2 family, all members were down-regulated in all stages of tongue carcinogenesis model except for Bad mRNA in group III. In terms of BH3 only protein, mRNA expressions of Bok and Mcl-1 were down regulated in all stages of specimen, but Bmf in group II and BBC3 in group III were up-regulated. Our current findings demonstrated the involvements of mRNA expression of Bcl-2 family in multi-step tongue carcinogensis. This highlights the necessity for continued efforts to discover suitable biomakers (Bcl-2 family) for early diagnosis of the disease, and to understand its pathogenesis as a first step in improving methods of treatment. The discovery of these potential biomarkers and molecular targets for cancer diagnostics and therapeutics has the potential to significantly change the clinical approach and outcome of the disease.

• Journal of radiological science and technology
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• v.21 no.1
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• pp.79-87
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• 1998

The total-bodies of 10 week-old Sprague-Dawley rats were irradiated with single doses 4.5 and 7.5 Gy, respectively. The effects on plasma and sciatic nerve platelet-derived growth factor(PDGF) concentrations and sciatic nerve PDGF ${\alpha}$ -and ${\beta}$ -receptors densities were examined up to 10 days post-treatment. There was no consistent significant variation in the plasma and sciatic nerve PDGF concentrations in time over the period of study between 4.5 and 7.5 Gy groups. Plasma PDGF concentrations were significantly reduced to 58% of control values between 5 and 10 days with 4.5 Gy and to 51% of control values as percentage of control values between 5 and 10 days with 7.5 Gy after irradiation, respectively(p<0.05). Sciatic nerve PDGF concentrations were increased to 118% of control values at 1 day with 4.5 Gy and to 130% of control values at 1 day with 7.5 Gy after irradiation, respectively(p>0.05). After irradiation, the levels of PDGF ${\alpha}$ -receptor protein density were reduced to 33% of control values at 2 days with 4.5 Gy and to 50% at 2 days with 7.5 Gy, while the levels of PDGF ${\beta}$-receptor protein density were reduced to maximally 26% of control values at 2 days with 4.5 Gy and to 27% at 2 days with 7.5 Gy, respectively, but both initial decreased levels of those were increased subsequently after 2 days following irradiation. These results suggest that the radiation-induced alteration of plasma and sciatic nerve PDGF concentrations, and sciatic nerve PDGF ${\alpha}$ -and ${\beta}$ -receptors densities may be involved in the pathogenesis of bone marrow stem cell and peripheral neuron damages.

• Journal of Life Science
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• v.21 no.8
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• pp.1134-1141
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• 2011

Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate ${\alpha}$-secretase-mediated A${\beta}$ production which was specifically observed in the brains of subjects with Alzheimer's disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of ${\gamma}$-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor $p75^{NTR}$ and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21may simultaneously induce the up-regulation of $p75^{NTR}$/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of ${\gamma}$-secretase activity.

• Journal of Life Science
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• v.21 no.9
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• pp.1346-1353
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• 2011

Sophora tonkinensis Gapnep has been used as a traditional herbal medicine in oriental regions since ancient times. In this study, the effect and mechanism of the MeOH extract of Sophora tonkinensis Gapnep (STME) on adipocite differentiation and adipogenesis in 3T3-L1 preadipocites were investigated. Treatment with STME in the concentration range of 0-200 ${\mu}g$/ml significantly inhibited the differentiation of 3T3-L1 preadipocites in a dose-dependent manner, as determined by a decrease in intracellular lipid droplets and lipid contents measured by Oil Red O staining. In association with the inhibitory effect of lipid accumulation, the expressions of the proteins concerned with adipogenesis in 3T3-L1 preadipocites were also investigated. Treatment with STME reduced the expressions of peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymine (CCAAT)/enhancer-binding proteins ${\alpha}$ and ${\beta}$ (C/EBP${\alpha}$ and C/EBP${\beta}$) and sterol regulatory element binding protein (SREBP), which are adipocyte specific markers. In flow cytometry analysis, the inhibitory effect of differentiation was caused by G1 arrest and following mitotic clonal expansion cease. Therefore, we also investigated the alteration of G1 phase arrest-related proteins. As a result, the expression of p21 protein was significantly increased, while the expressions of Cdk2, E2F-1 and phospho-Rb were reduced in a dose-dependent manner in STME treated 3T3-L1 cells. According to these results, STME might inhibit differentiation through G1 arrest in 3T3-L1 preadipocytes adipogenesis, and further studies, which are in progress, have to be completed to identify the active compounds.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.22-31
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• 2010

Purpose : This study was performed to evaluate the relationship between glomerular basement membrane (GBM) alterations to epithelial cell (EpC) structure and renal function in Alport Syndrome (AS) patients. Methods : Fifteen patients diagnosed with AS (4-26yrs) were examined. The GBM in AS was categorized as : C1) normal, C2) minor alterations (widening of lamina rara interna or externa without lamina densa change), C3) nonspecific splitting of lamina densa, C4) basket-weaving pattern of lamina densa splitting. The length of each GBM portion along the epithelial side was measured on the systematically obtained electron microscopic photographs. Furthermore to obtain an objective assessment of the degree of glomerular EpC foot process change, the number of slit pores along $10\;{\mu}m$ of peripheral GBM in each category was obtained. Results : The percentage of normal GBM portion (C1) correlated inversely with daily protein excretion (g/day/$m^2$, P<0.05) and sum of the percentage of abnormal GBM portion (C2+C3+C4) had direct correlation with daily protein excretion (g/day/$m^2$, P<0.05). There were no significant relationships between the percentages of other categories of GBM alterations and creatinine clearance or protein excretion. There were no significant relationships between of creatinine clearance in relation to normal GBM(C1) portion as well as that in relation to sum of the percentage of abnormal GBM portion (C2+C3+C4). GBM abnormality did not correlate with age at biopsy. Conclusion : The extent of GBM structural abnormality is related to proteinuria in AS but the epithelial response is uniform even though the GBM ultrastructural lesions are not.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.41-55
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• 2004

Objective : To investigate the possible molecular mechanism (s) of melittin as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Methods : Growth inhibitory study, flow cytometry analysis, SDS-polyacrylamide gel electrophoresis and Western blot analysis, RT-PCR and in vitro caspases activity assay were performed. Results : Melittin treatment declined the cell viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Melittin treatment down-regulated the levels of Bcl-XS/L mRNA and protein expression of A549 cells, an anti-apoptotic gene, however, the those of Bax, a pro-apoptotic gene, were up-regulated. Melittin induced the proteolytic cleavage and activation of caspase-3 and caspase-9 protease in a dose-dependent manner without alteration of inhibitor of apoptosis proteins family and Akt expression. Western blot analysis and RT-PCR data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 were also remained unchanged. Conclusions : Taken together, these findings suggest that melittin-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and melittin may have therapeutic potential in human lung cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.8
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• pp.1237-1245
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• 2004

Agaricus blazei Murill is a medicinal mushroom native to Brazil. It used to be a source of antitumor and immunoactive compounds and considered a health food in many countries. In the present study, it was examined the effects of water extract of A. blazei (WEAB) on the growth of human lung carcinoma cell line A549 in order to investigate the anti-proliferative mechanism by WEAB. Treatment of A549 cells to WEAB resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner as measured by MTT assay and flow cytometric analysis. Flow cytometric analysis revealed that WEAB caused G2/M phase arrest of the cell cycle, which was associated with a down-regulation of cyclin A in both transcriptional and translational levels. WEAB treatment induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21, however, the levels of Cdk2, Cdc2, Wee1, Cdc25C and p53 expression were remained unchanged in WEAB treated cells. In addition, WEAB treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein without alteration of COX-l expression. Taken together, these findings suggest that WEAB may be a potential chemotherapeutic agent for the control of human lung carcinorma cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of WEAB. Once such compounds are identified, the mechanisms by which they exert their effects can begin to be characterized.

• Herbal Formula Science
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• v.25 no.4
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• pp.483-497
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• 2017

Background : Behavioral stress has been suggested as one of the significant factors that is able to disrupt physiological systems and cause depression as well as changes in various body systems. The stressful events can alter cognition, learning, memory and emotional responses, resulting in mental disorders such as depression and anxiety. Results : We used a restraint stress model to evaluate the alteration of behavior and stress-related blood parameter. The animals were randomly divided into two groups of five animals each group. Furthermore, we assessed the change of body weight to evaluate the locomotor activity as well as status of emotional and anxiety in mice. After 7 days of restraint stress, the body weight had significantly decreased in the restraint stress group compared with the control group. We also observed stress-associated behavioral alterations, as there was a significant decrease in open field and forced swim test, whereas the immobilization time was significantly increased in the stress group compared to the control group. We observed the morphological changes of neuronal death and microglia by immunohistochemistry and western blot. In our study restraint stress did not cause change in neuronal cell density in the frontal cortex and CA1 hippocampus region, but there was a trend for an increased COX-2 and iNOS protein expression and microglia (CD11b) in brain, which is restraint stress. Conclusion : Our study, there were significant alterations observed in the behavioral studies. We found that mice undergoing restraint stress changed behavior, confirming the increased expression of inflammatory factors in the brain.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.119-127
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• 2005

Purpose : Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, p-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. Methods : To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT-PCR. Results : We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. Conclusion : We suggest that high glucose with or without AGE suppresses the Production of P-cadherin at the transcriptional level and that these changes nay explain the functional changes of SD in diabetic conditions. (J Korean Soc Pediatr Nephrol 2005;9:119-127)