• Journal of Life Science
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• v.19 no.7
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• pp.871-877
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• 2009

We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.86-92
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• 2005

Goodpasture's syndrome is a disease that is characterized by hemoptysis, anemia, and glomerulonephritis with renal failure. Goodpasture reported a case of a young man who expired as a result of a pulmonary hemorrhage and glomerulonephritis at the recovery phase after an influenza infection in 1919. In 1958, Stanton et al. described a combined case of these two diseases as Goodpasture's syndrome. Since then, antiglomerular basement membrane antibody(anti-GBM Ab) has been confirmed to play an important role in the mechanism of this syndrome, and it was reported that this syndrome was an autoimmune disease. The triad of alveolar hemorrhage, glomerulonephritis and circulating anti-GBM Ab forms the basis of a diagnosis of Goodpasture's syndrome. When patients are affected by disease, the relief of symptoms can be accomplished by eliminating the anti-GBM Ab from the circulatory system through hemodialysis, plasmapheresis and immunoabsorption. However, the patients usually die from a massive pulmonary hemorrhage when the diagnosis or treatment is delayed. The incidence of Goodpasture's syndrome is common in the western world, but it is extremely rare in Korea with only five cases being reported. In three of these cases, pulmonary hemorrhage and renal failure was the initial manifestation. Therefore, hemodialysis or plasmapheresis were absolutely essential treatments. We report a case of Goodpasture's syndrome in Korea with a normal renal function.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.166-179
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• 2000

Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

• The Korean Journal of Nuclear Medicine
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• v.28 no.1
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• pp.124-132
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• 1994

Radioactive iodine has been widely used in patients with thyroid cancer combined with surgical treatment. However, due to individual variations in absorption and excretion and uptake by tumor tissue of radioactive iodine, there are differences in therapeutic effect and adverse effects even if the same doses are administrated. So this study compared the therapeutic effect and radiation hazard by measuring internal radiation dose. Of total 27 patients with well differentiated thyroid cancer who had been thyroidectomized, we administered radioactive iodine 100 mCi, 150 mCi, 200 mCi. According to BEL DOSIMETRY PROTO-COL, beta and gamma ray dose were estimated from a pelt of the logarithm of the percent of dose per liter of whole blood versus day, and percent dose retained versus day using somilogarithmic paper, respectively. 1) Physical dose to whole blood averaged $56.54{\pm}13.02$ rad in 100 mCi administered group, $76.83{\pm}19.97$ rad in 150 mCi administered group, $95.08{\pm}25.51$ rad in 200 mCi administered group and there has been a significant correlation among the groups. 2) Mean percent dose retained 48 hours later was 26.34%. 3) There was no significant correlation of physical dose between absence and presence of metastasis. 4) 17 of 19 patients who has been followed up with TSH and serum throglobulin, Thallium scan were successfully ablated by radioactive iodine. 5) Leukocyte, lymphocyte, neutrophil, platelet counts all deelined in 4.6 weeks and most of all were restored 3 months later. 6) There was no significant correlation between physical dosimetry and biologic dosimetry. Generally administered doses of radioactive iodine (100-200 mCi) to patients with thyroid cancer postoperatively had developed transient bone marrow suppression and minimal chromosomal aberration, but they were within safety dose to blood (200 rad). And there has been no significant differences in residual dose 48 hours later between Korean and western people.

• Journal of Oral Medicine and Pain
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• v.34 no.3
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• pp.261-276
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• 2009

Lactacystin, a microbial natural product synthesized by Streptomyces, has been commonly used as a selective proteasome inhibitor in many studies. Proteasome inhibitors is known to be preventing the proliferation of cancer cells in vivo as well as in vitro. Furthermore, proteasome inhibitors, as single or combined with other anticancer agents, are suggested as a new class of potential anticancer agents. This study was undertaken to examine in vitro effects of cytotoxicity and growth inhibition, and the molecular mechanism underlying induction of apoptosis in SCC25 human tongue sqaumous cell carcinoma cell line treated with lactacystin. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingiva fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay respectively. The hoechst staining, hemacolor staining and TUNEL staining were conducted to observe SCC25 cells undergoing apoptosis. SCC25 cells were treated with lactacystin, and Western blotting, immunocytochemistry, confocal microscopy, FAScan flow cytometry, MMP activity, and proteasome activity were performed. Lactacystin treatment of SCC25 cells resulted in a time- and does-dependent decrease of cell viability and a does-dependent inhibition of cell growth, and induced apoptotic cell death. Interestingly, lactacytin remarkably revealed cytotoxicity in SCC25 cells but not normal cells. And tested SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA contents, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, the up-regulation of Bax, and the activation of caspase-7, caspase-3, PARP, lamin A/C and DFF45 (ICAD). Flow cytometric analysis revealed that lactacystin resulted in G1 arrest in cell cycle progression which was associated with up-regulation in the protein expression of CDK inhibitors, $p21^{WAF1/CIP1}$ and $p27^{KIP1}$. We presented data indicating that lactacystin induces G1 cell cycle arrest and apoptois via proteasome, mitochondria and caspase pathway in SCC25 cells. Therefore our data provide the possibility that lactacystin could be as a novel therapeutic strategy for human tongue squamous cell carcinoma.

• Journal of Acupuncture Research
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• v.30 no.5
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• pp.155-167
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• 2013

Objectives : This research was conducted to investigate the factors that affect the level of facial nerve damage. Methods : From October 2009 to September 2013, the total number of 581 patients of Bell's palsy and Ramsay-Hunt syndrome visited Facial Palsy Center in Kyung Hee University Hospital at Gangdong for Traditional Korean and Western combined medical treatment. Of these, 453 patients of peripheral facial nerve palsy were selected for the research. After reviewing the medical records that have details of age, gender, diagnosis(Bell's palsy and Ramsay-Hunt syndrome), onset, underlying diseases(DM, HTN), and HbAlc value, the analysis on the influence factors on the level of facial nerve damage was drew out. Results : The axonal loss rate of oris branch and nasal branch were significantly higher than the axonal loss rate of frontal branch and oculi branch. In addition, the frequency of becoming a major damaged branch was also high in the oris branch nasal branch. The factors by month, weather, smoking, and alcohol did not influence EMG axonal loss rate. Male rather than female and patient with Rasmay-Hut syndrome rather than Bell's palsy had a higher axonal loss rate in all branches. Of those, front of branch of male was remarkably higher than female. Patient with DM as P/H had high axonal loss rate in all branches. Patient with HTN as P/H had high axonal loss rate in all branches except for oris branches. Patients with DM and HTN group had significantly higher value from the average of axonal loss rate than patients who are only with HTN and without DM/HTN. DM alone group had significantly higher value than patients who are without DM/HTN. However, HTN alone was not significantly high. By analysing HbAlc of the patients who were hospitalised regardless DM, axonal loss rate was high in the order of DM group, preDM group, normal group. Nevertheless, only DM group showed higher axonal rate statistically than normal group. Considering DM and HbA1c value, the patients can be divided into 4 different groups of hkDM, lkDM, hfDM and nDM. By analysing those groups, the average damaged value of the groups with diagnosis followed by treatment(lkDM, hkDM) were higher than the average rate of hfDM and statistically higher than the rate of the nDM. Conclusions : The influential factors of increasing the level of EMG damage are male(only for the frontal branch), age above sixties, HTN, DM, and HbAlc value above 6.5. Besides, the negligible factors are month, season, diagnosis, alcohol, and smoking. Further research including clinical prognosis should be conducted.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.431-438
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• 2006

Purpose : Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. Methods : The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. Results : Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. Conclusion : From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.262-268
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• 2009

Purpose: We wanted to analyze the clinicopathologic characteristics of patients with gastric carcinoid tumor, which is a rare gastric tumor (less than 2% of all gastric tumors). Materials and Methods: We reviewed all the carcinoid patients who were treated from 1996 to 2006. The clinicopathologic characteristics, the treatment modalities and the survival rates were retrospectively analysed. Results: There were 8 type I patients and 10 type III patients, but there were no type II patients. The mean age of onset for type I was 47.75 years and that for type III was 57.90 years. More type III patients were female, but the gender ratio of type I patients was equal at a ratio of 1：1. There were 4 cases of solitary tumor, which were all T1 except for one case, and there was neither distant metastasis nor lymph node involvement for the type T1 cases. In the 13 patients who had no metastasis, 5 underwent endoscopic mucosal resection and 8 underwent surgery, and their combined 5 year survival rate was 92.3%. For the 5 cases who had metastastses, their mean survival was 22 months and especially, 3 of them underwent palliative surgery and their median survival were 24 months (95%, ${\pm}6.52$). Conclusion: Higher incidence of type III gastric carcinoid tumor and less multiplicity in type I gastric tumor were identified in our study compared with previous reports. For the type III cases, there were some noteable differences compared with the Western country's survival rate for the patients who underwent palliative surgery, so physicians must pay close attention to the definite clinicopathologic characteristics of gastric carcinoid patients.

• Journal of Nutrition and Health
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• v.47 no.1
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• pp.12-22
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• 2014

Purpose: This study was conducted to establish the production conditions through optimization of the production process of beverages using Aspergillus oryzae CF1001, and to analyze volatile compounds and antidiabetic activity. Methods: The optimum condition was selected using the response surface methodology (RSM), through a regression analysis with the following independent variables gelatinization temperature (GT, $X_1$), saccharogenic time (ST, $X_2$), and dependent variable; ${\Delta}E$ value (y). The condition with the lowest ${\Delta}E$ value occurred with combined 45 min ST and $50^{\circ}C$ GT. The volatile compounds were analyzed quantitatively by GC-MS. Results: Assessment of antidiabetic activity of saccharogenic mixed grain beverage (SMGB) was determined by measurement of ${\alpha}$-glucosidase inhibition activity, and glucose uptake activity and glucose metabolic protein expression by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. Results of volatile compounds analysis, 62 kinds of volatile compounds were detected in SMGB. Palmitic acid (9.534% ratio), benzaldehyde (8.948% ratio), benzyl ethyl ether (8.792% ratio), ethyl alcohol (8.35% ratio), and 2-amyl furan (4.826% ratio) were abundant in SMGB. We confirmed that ${\alpha}$-glucosidase inhibition activity, glucose uptake activity, and glucose-metabolic proteins were upregulated by SMGB treatment with concentration dependent manner. Conclusion: Saccharogenic mixed grain beverage (SMGB) showed potential antidiabetic activity. Further studies will be needed in order to improve the taste and functionality of SMGB.