• Journal of Life Science
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• v.27 no.2
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• pp.149-154
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• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.481-488
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• 1999

Background: The routine application of the combined regimen of corticosteroid-antituberculosis therapy to the tuberculous pleurisy remains controversial. Steroid therapy to tuberculous pleurisy could be effective on the acceleration of absorption of pleural effusion and symptom improvement, but there has been debate about the effect of prednisolone on the prevention of pleural adhesion. So we studied the efficacy of combined regimen of prednisolone-antituberculosis therapy on the absorption of pleural effusion and prevention of pleural adhesion. Method: A prospective, randomized study was performed in 82 patients, 50 patients(non-steroid group) were treated with only antituberculosis regimen for 6 months and in 32 patients(steroid group) prednisolone(30mg/day) were administered in addition to antituberculosis regimen for one months and tapered for another month. The amount of pleural effusion was compared at the beginning of treatment, 2nd month, 6th month and final visit with chest X-ray findings which were graded from grade 0(complete absorption) to grade 6(near total haziness). Results: The amount of pleural effusion of steroid group at 2nd month, 6th month and final visit was lesser than that of non-steroid group(P<0.05). The incidence of the complete absorption of the pleural effusion was 3/32(9.4%) in steroid group, 1/50(2%) in non-steroid group at 2nd month after treatment; and 12/32(37.5%) in steroid group, 6/50(12%) in non-steroid group at 6th month after treatment(P<0.05). At final observation, the incidence of residual pleural thickening was 15/32(47%) in steroid group and 37/50(74%) in non-steroid group(P<0.05). No serious side effects were noted during the treatment with prednisolone. Conclusion: The administration of prednisolone in conjunction with antituberculosis chemotherapy improved the absorption of pleural effusion and decreased the residual pleural thickening.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.484-492
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• 2001

Background : Pulmonary tuberculosis with a remaining cavitary lesion is considered to be a problem with the course of treatment. In particular, re-treatment cases tend to respond poorly to current anti-tuberculosis agents. Therefore the factors that are related with the poor closure of a cavitary lesion in pulmonary tuberculosis during treatment were evaluated. Methods : A retrospective review of the medical records and chest X -ray films of 68 patients who had chemotherapy for the pulmonary tuberculosis with cavitary lesions was made. All the patients had been followed up for more than 12 months at National Masan Tuberculosis Hospital as of Aug. 2000. Results : The male to female ratio was 3.9:1.72.4% of the patients were between 20 to 50 years of age. 66.2% of the cavitary lesions on the chest X-ray films were confined to the upper lung fields : 36.8% in the right upper lung field and 29.4% in the left upper lung field. 82.4% of the cavities were less than 40 mm in their size, and 83.8% were less than 6 mm thick. The cavitary lesions were closed in 48 cases and remained in 20 cases during a follow-up period of more than 12 months. The factors that are thought to affect to the outcomes of the cavities were age, past medication history, the number of unused drugs, and the number of sensitive drugs. Conclusion : In the treatment courses of pulmonary tuberculosis with cavitary lesions, the following factors are associated with less desirable outcome:an age over 45, a past medication history of more than 2 courses of treatment, The number of unused drugs not exceeding average 6 and the number of sensitive drugs not exceeding average 7.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.315-323
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• 2000

Background : An immunochromatographic assay (ICT Diagnostics) which facilitates the diagnosis of tuberculosis(TB) by detecting serum antibodies mainly directed against specific 38KDa of Mycobacterium tuberculosis has come into the market. The test consists of a cardboard folding device containing nitrocellulose strip and absorbent pads. The whole procedure is completed within 15 min and does not require any additional equipment. The test has been reported to be sensitive and specific in diagnosing active TB. Thus the test had been evaluated with sera from TB patients and TB-free subjects. Method : Sera from patients with active pulmonary tuberculosis(40 sputum positives for Mycobacterium tuberculosis, 79 sputum negatives, and 3 extrapulmonary tuberculosis) were obtained from the Double-Cross Chest Clinic of the Korean National Tuberculosis Association (KNTA) in Seoul. The control group consisted of TB-free 68 subjects(21 children under 7 years old and 47 healthy staff members of KNTA). Results : Nine out of 68(13.2%) TB-free controls had positive antibody response. Total 106 of 122(86.9%) radiologically active patients had positive antibodies while 16 (13.1%) showed negative reaction. Antibody was detected in 38 of 40(95.0%) sputum positive patients and 68 of 82(82.9%) sputum negative patients who were under the antituberculosis chemotherapy. The sensitivity and specificity were all 87% and the positive predictive value was 92.2% while the negative predictive value was 78.7%, when the prevalence of TB in the sample was 64.2%. Our results clearly show that the detection of antibodies which mainly react with the 38KDa antigen of M. tuberculosis is not suitable as the first-line method of diagnosis but considered only as an adjunctive test to standard techniques of tuberculosis diagnosis. when considering its high false positivity.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.683-692
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• 1996

Background: Although most of the patients with tuberculous pleural effusions completely reabsorbed their effusions and became asymptomatic within 2 to 4 months, later surgical procedures such as decortication is needed in some patients because of dyspnea caused by pleural loculations and thickening despite anti-tuberculous chemotherapy. It is obligatory to secure adequate drainage to prevent the development of complications. But, the best methods for treating loculated tuberculous pleural effusions remain debatable. Recent several reports revealed that intrapleural instillation of fibrinolytic agents is an effective adjunct in the management of complicated empyema and may reduce the need of surgery. Purpose : The effects of catheterization with intrapleural urokinase instillation were prospectively evaluated in the patients with septated tuberculous pleural effusion, and compared with other therapeutic effects of different modalities of therapy such as repeated thoracentesis and small-bored catheterization. Methods : Forty-eight patients diagnosed with tuberculous pleurisy were randomly separated into three groups; control group(n=13), catheter group(n=12), urokinase group(n=22). In urokinase group, dose of 100.000U urokinase was instilled into the pleural cavity via a percutaneous drainage catheter for complete drainage or total dose of 700,000U of urokinase. After two hours clamping, the catheter was opened and intermittently irrigated. The early and late effectiveness of therapies was assessed by radiographically and by measuring the volume of fluid drained from the catheter. Results : There was statistically significantly better result in the urokinase group in respect of frequency of catheterization, frequency of catheter obstruction and the duration of catheterization in early effectiveness(p < 0.05). There were no difference in radiologic improvement of follow-up in later phase chest X-ray between urokinase group and catheter group in later phase(p > 0.05). But there were more failure rates in control group especially honeycomb septa in pleural effusion sonographically than former two groups. And there were no complications of urokinase such as fever or hemorrhage. Conclusion : In the treatment of septated tuberculous pleurisy, there were better results in urokinase than those of catheterization alone in early effectiveness. And there was no difference in radiographic improvement between urokinase group and catheter group. Intrapleural instillation of urokinase is an effective and safe mode of treatment for septated tuberculous pleural effusions and alleviates the need for thoracotomy.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.693-700
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• 1996

Background : Antituberculous therapy is set a short-term therpy used isoniazid(INH), rifampin(RFP), ethambutol(EMB), pyrazinamide(PZA) from 1970s' and treatment rate has been very improved. But drug interruption or irregular medication due to side effects and resistance of drug are serious problem to retreatment cases, specially. Ofloxasine(OFX), developed from Quinolone at 1980's is effective not only other respiratory infectious disease but also pulmonary tube rculosis. And this is useful drug instead of injection agents for retreatment patients who have side effects to other drugs, lived far distance from medical clinics. So, we will evaluate theffectiveness as four oral drugs involving OFX. Method : A retrospective study was made through the regular follow up of smear positive cases,who treated by four drug, namely, prothionamide (PTA) cycloserine(CS), OFX, paraminosalicylic acid(pAS). Results: 1) Out of 66case with positive sputum AFB smear, 42(64%)cases achieved the negative conversion. 2) Considering the negative conversion in all group, 34 case (52%) of sputum conversion occured within first 6 months, on the extent of diease was minimal, moderate, far advanced pulmonary tuberculosis, sputum AFB smear negative response to treatment was 100%, 78%, 46% respectively. 3) The roentgenological improvement occured in 38(58%), extent of diease was minimal, moderately, far advanced pulmonary tuberculosis, Roentgenological improvement to retreatment was 75%, 64%, 46%. 4) When the drnation of patients illness was less than 1 year, 1 to 3 years, 3 10 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 100%, 88%, 80%, 52 %. 5) On side effects, major problems are gastrointestinal troubles, mild liver function abnormality, psychotic problemes, and skin problem(urticaria, itching sensation). Conclusion : The duration & extents of patients illness was shorter & minimal, sputum AFB smear negative response rate was better. Radiologic response is better as shorter duration and minimal extent of diease. But, as diease is longer duration & far advanced, sputum negative conversion & Roentgenological improvement is poor and limited. The adverse reaction was mainly observed gastrointestinal troubles(indigestion, abdominal pain, nausea, vomiting, diarrhea) and are well controled by symptomatic management in most patients, as regard to tolerance to the secondary drugs.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.488-498
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• 2003

Background : Activation of the transcription factor NF-${\kappa}B$ has been shown to protect cells from tumor necrosis factor-alpha, chemotherapy, and radiation-induced apoptosis. NF-${\kappa}B$-dependent cIAP expression is a major antiapoptotic mechanism for that. NF-${\kappa}B$ activation and cIAP expression in A549 lung cancer cells which is relatively resistant to radiation-induced cell death were investigated for the mechanism of radioresistance. Materials and methods : We used A549 lung cancer cells and Clinac 1800C linear accelerator for radiation. Cell viability test was done by MTT assay. NF-${\kappa}B$ activation was tested by luciferase reporter gene assay, Western blot for $I{\kappa}B{\alpha}$ degradation, and electromobility shift assay. For blocking ${\kappa}B$, MG132 and transfection of $I{\kappa}B{\alpha}$-superrepressor plasmid construct were used. cIAP expression was analyzed by RT-PCR and cIAP2 promoter activity was performed using luciferase assay system. Results : MTT assay showed that cytotoxicity even 48 hr after radiation in A549 cells were less than 20%. Luciferas assay demonstrated weak NF-${\kappa}B$ activation of $1.6{\pm}0.2$ fold compared to PMA-induced $3.4{\pm}0.9$ fold. Radiation-induced $I{\kappa}B{\alpha}$ degradation was observed in Western blot and NF-${\kappa}B$ DNA binding was confirmed by EMSA. However, blocking NF-${\kappa}B$ using MG132 and $I{\kappa}B{\alpha}$-superrepressor transfection did not show any sensitizing effect for radiation-induced cell death. The result of RT-PCR for cIAP1 & 2 expression was negative induction while TNF-${\alpha}$ showed strong expression for cIAP1 & 2. The cIAP2 promoter activity also did not show any change compared to positive control with TNF-${\alpha}$. Conclusion : We conclude that activation of NF-${\kappa}B$ does not determine the intrinsic radiosensitivity of cancer cells, at least for the cell lines tested in this study.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.57-64
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• 2006

Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.5-10
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• 2007

Background: Korean national guidelines for examining contacts with active pulmonary tuberculosis (TB) are a tuberculin skin test (TST) and chest radiographs. The treatment of a latent TB infection as performed only in those younger than six years of age who test positive for TST. Although there is a high incidence of active TB in young Korean soldiers, the current national guidelines for controlling contacts with active TB in soldiers are insufficient. This study highlights the problems with the Korean guidelines for controlling a TB outbreak in a small military unit. Material and Methods: In December of 2005, there was a tuberculosis outbreak in a military unit with a total of 464 soldiers in Kyung Gi province. The chest radiographs were taken of all the soldiers, and TST were carried out on 408 candidates. Results: In the first screening of the chest radiographs, two active TB patients were detected. By August of 2006, four additional cases were detected, making a total of six cases after the outbreak. All the patients showed active pulmonary TB or TB pleuritis. When the results of TST in the close contacts and non-close contacts were compared, there was a significant difference in the absolute size of the induration($9.70{\pm}7.50mm$ vs. $6.26{\pm}7.02mm$, p<0.001) as well as the ratio of patients showing an induration > 10mm (50.0% vs. 32.0%, p<0.001) and 15mm (33.2% vs. 20.9%, p= 0.005). Conclusion: Although the national guidelines for managing a TB outbreak in a military unit were followed, there were continuous instances of new active TB cases. This highlights the need for new guidelines to prevent the spread of TB.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.124-129
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• 2004

Purpose : To evaluate the clinical findings, prognosis and treatment strategy of patients with neuroendocrine carcinoma of cervix. Materials and Methods: Thirteen patients with neuroendocrine carcinoma of cervix were included in this study, as confirmed histologically and immunohistochemically at the Dongsan Medical Center, Keimyung University, between May 1944 and October 2001. The mean age of patients was 56 years with a range of 32 to 78 years of age. According to the FIGO staging system, there were 5 patients with stage IB carcinoma, 5 patients with IIA, and 3 patients with stage IIB. Four patients underwent radical hysterectomy with pelvic lymphadenectomy, 3 of these patients also received postoperative radiotherapy, and one patient underwent extrafascial hysterectomy after radiotherapy. Primary radiotherapy was done in 9 patients, and 3 were irradiated postoperatively. Nine patients received chemotherapy, 7 received neoadjuvant and 2 received concurrent chemoradiotherapy. The radical purpose of radiotherapy consisted of external irradiation to the whole pelvis (4,500 $\~$5,400 cGy) and intracavitary irradiation (3,000 $\~$ 3,500 cGy). Results : The mean follow up duration was 36 months with a range of 3 to 104 months. The overall 5-year survival rate was 61.5$\%$ and the 5-year survival rates for stage IB, IIA, IIB were 60.0$\%$, 60.0$\%$, and 66.7$\%$ respectively (p=0.99). Eight patients are still alive without disease, and all of the 5 patients with recurrence are dead due to distant metastasis. Conclusion : Neuroendocrine carcinoma of cervix is highly aggressive, with early lymphatic dissemination and a high rate of distant recurrence. Therefore, an aggressive therapeutic strategy Is required to obtain pelvic and distant disease control. Multimodal therapy should be considered at the time of Initial diagnosis.