• Radiation Oncology Journal
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• v.20 no.4
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• pp.323-327
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• 2002

Purpose : To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy alone and define the optimal radiotherapeutic regimen for these patients. Materials and Methods : A retrospective review was peformed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 59 Gy. No patients were lost to follow-up. Results : The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and $21\%$, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and $25\%$, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was $43\%$. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented $78\%$ of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm $(0\%\;vs\;36\%)$. Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70 $(25\%\;vs\;26\%,\;p>0.05)$. Conclusion : Radiation therapy 리one is an effective and safe treatment for early stage non-small ceil lung cancer patients who are medically inoperable or refuse surgery. Also we believe that a higher radiation dose to the primary site could improve the local control rate, and ultimately the overall survival rate.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.413-421
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• 1999

Background: Ischemia reperfusion injury is known to contribute to the major causes of the early graft failure in lung transplantation. Triiodothyronine (T3) has been suggested to ameliorate ischemia reperfusion injury from both in vivo and in vitro experiments of various organs. Prospecting its beneficial effect for pulmonary allograft preservation, we made a new solution by adding T3 into the extracellular type dextran solution. Material and Method: Twelve adult mongrel dogs underwent left lung allotransplantation. Six donor dogs were flushed with the new solution(Group 1, n=6), and the remaining six were flushed with Euro-Collins solution to serve as controls(Group 2, n=6). Allografts were stored in each preservation solution for 20 hours at 4$^{\circ}C$. Left single lung transplantations were performed. The right pulmonary artery and the right main bronchus were clamped at 15 minutes after the reperfusion and maintained throughout the experiment to evaluate the transplanted left lung function. Result: Arterial carbon dioxide tension was better in group 1 than in group 2 throughout the experiment period and the difference was statistically significant at 2 hours after reperfusion(28.0${\pm}$3.0 mmHg and 53.1${\pm}$17.4 mmHg, p<0.05). The differences of arterial oxygen partial pressure, peak airway pressure and pulmonary vascular resistance showed no statistical significance. The malondialdehyde(MDA) level, measured from tissue obtained at 120 minutes after reperfusion showed no statistically significant difference. The tissue wet/dry ratio of group 1(649${\pm}$27 %) was significantly lower than that of group 2(686${\pm}$71 %, p<0.05). The microscopic examination revealed varying degrees of injury represented mainly by findings such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. These findings were less severe in group 1 than those in group 2. Conclusion: The new solution demonstrated superior allograft preservation after 20 hour ischemia compared to Euro-Collins solution in canine single left lung transplantation model, these results suggest that T3 might be a promising agent for pulmonary allograft preservation.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.134-141
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• 1998

Primary lung cancer has recently increased progressively in its incidence in Korea. It is clearly evident that surgical resection offers the best offortunity for cure of non-small cell carcinoma. This study was designed to analyse the clinical data of 100 primary non-small cell carcinoma patients who underwent lung resection surgery from January 1992 to July 1995 at the department of Thoracic and Cardiovascular Sugery, Kyungpook National University Hospital. There were 86 males and 14 females(6:1). In the age distribution, the peak incidence was recorded in the seventh decade(43%). The methods of tissue diagnosis were bronchoscopic biopsy in 53 patients(50.5%), percutaneous needle aspiration in 17 patients(16.2%), transbronchial lung biopsy in 11 patients(10.5%), mediastinoscopic biopsy in 2 patients (1.9%), sputum cytology in 2 patients(1.9%), and thoracotomy in 20 patients(19.0%). Fifty-five lobectomies, 22 pneumonectomies, 15 bilobectomies, 2 segmentectomies, 4 sleeve lobectomies, a sleeve pneumonectomy, and a wedge pneumonectomy were performed. Operative mortality occured in 4 cases(sepsis in 2 cases, respiratory failure in 1 case, and acute myocardiac infarction in 1 case). The histologic types of tumor were 67 squamous cell carcinomas, 26 adenocarcinomas, 6 large cell carcinomas, and an adenosquamous cell carcinoma. Eighteen patients with N2 mediastinal lymph node metastases had 8 squamous cell carcinomas(11.9%), 9 adenocarcinomas(34.6%), and a large cell carcinoma(16.7%). The primary tumors in these patients were in the right upper lobe in 4 patients, the right middle and lower lobe in 9 patients, the left upper lobe in 3 patients, and the left lower lobe in 2 patients. With regard to pathologic stages, 45 patients had stage I disease; 13 patients, stage II; 36 patients, stage IIIa; 5 patients, stage IIIb; and 1 patient, stage IV. The overall actuarial survival rate was 77.5% at 12 months, 56.1% at 24 months and 43.7% at 43 months. The actuarial survival rates at 43 months were 81.3% in Stage I, 20.8% in Stage II, 27.9% in Stage IIIa, 25.0% in Stage IIIb and 33.3% in Stage IV. These facts suggest that early detection and surgical resection are recommended for favorable postoperative survival in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.111-119
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• 1994

Background: Because of the common etiologic factor, such as smoking, lung cancer and chronic obstructive pulmonary disease are often present in the same patient. The preoperative prediction of remaining pulmonary function after the resectional surgery is very important to prevent serious complication and postoperative respiratory failure. $^{99m}Tc$-MAA perfusion scan has been used for the prediction of postoperative pulmonary function, but it may be inaccurate in case of large V/Q mismatching. We compared $^{99m}Tc$-DTPA radioaerosol inhalation scan with $^{99m}Tc$-MAA perfusion scan in predicting postoperative lung function. Method: Preoperative inhalation scan and/or perfusion scan were performed and pulmonary function test were performed preoperatively and 2 month after operation. We predicted the postoperative pulmonary functions using the following equations. Postpneurnonectomy $FEV_1$=Preop $FEV_1x%$ of total function of lung to remain Postlobectomy $FEV_1$=Preop $FEV_1{\times}$(% of total 1-function of affected lung${\times}$$\frac{Number\;of\;segments\;to\;be\;resected}{Number\;of\;segments\;of\;affected\;lung})$ Results: 1) The inhalation scan showed good correlations between measured and predicted $FEV_1$, FVC and $FEF_{25-75%}$. (correlation coefficiency; 0.94, 0.91, 0.87 respectively). 2) The perfusion scan also showed good correlations between measured and predicted $FEV_1$, FVC and $FEF_{25-75%}$. (correlation coefficiency; 0.86, 0.72, 0.87 respectively). 3) Among three parameters, $FEV_1$ showed the best correlations in the prediction by lung scans. 4) Comparison between inhalation scan and perfusion scan in predicting pulmonary function did not show any significant differneces except FVC. Conclusion: The inhalation scan and perfusion scan are very useful in the prediction of postoperative lung function and don't make a difference in the prediction of pulmonary function a1though the former showed a better correlation in FVC.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.93-97
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• 2009

Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

• Journal of Chest Surgery
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• v.42 no.6
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• pp.725-731
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• 2009

Background: Lobectomy and more extended anatomic resection are regarded as standard treatment for stage Ia non-small cell lung cancer, but approximately 15~40% of patients suffer from treatment failures such as cancer recurrence or death. The authors analyzed types and causes of treatment failures in surgically treated cases of stage Ia non small cell lung cancer. Material and Method: We retrospectively reviewed the medical records of 156 patients who had undergone complete resection for stage Ia NSCLC between Jan 1992 and Aug 2005. Patients were divided into two different treatment failure groups: cancer-related deaths and non-cancer-related deaths. Risk factors were analyzed in each group by the Kaplan-Meyer survival method and the Cox proportional hazard model. Result: Among the 156 patients, 93 were males; the mean age was 61. The median follow-up period was 33.8 months. The 5 year survival rate was 87.6%. Microscopic lympho-vascular permeation was reported in 10 patients. Recurrence was reported in 19 patients and 12 patients died due to recurrent lung cancer. Noncancer related deaths occurred in 16 patients. Risk factors for cancer recurrence and cancer related death were microscopic lympho-vascular permeation (HR=6.81, p=0.007, HR=7.81, p<0.001); for non-cancer related death, risk factors were pneumonectomy (HR=25.92, p=0.001) and postoperative cardiopulmonary complications (HR=29.67, p=0.002). Conclusion: After complete resection of stage Ia non small cell lung cancer patients, mortality includes not only cancer related deaths but also cancer unrelated deaths. Adjuvant chemotherapy is advised for patients who show microscopic lympho-vascular permeation, which is a risk factor for recurrence and for cancer related death. Patients who had pneumonectomy or who suffered from cardiac or respiratory complications need meticulous care in order to reduce comorbidity-induced death.

• Journal of Chest Surgery
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• v.30 no.8
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• pp.786-792
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• 1997

A clinical study of 71 cases of pulmonary tuberculosis that had had surgical resection during the period of 7 years and 6months from January 1989 to June 1996 in National Masan Tuberculosis Hospital. The results were as follows. 1. The ratio of male to female was 3.7:1 and in the age incidence the fourth decade was 22%, the third decade 15%. Although medical treatment was performed for more than 3 to 6 months, preoHeratively the conversion failure rate of positive sputum to negative state was 66.2%(47 cases). Of the failure cases, multiple-drug-resistant(MDR) patients were 41 cases(87.2%), 3. In MDR group, preoperatively conversion failure rate was 71.9%. 4. From the view of indica ion for lung resection on the radiographic finding, cavitary lesions were 43 cases(60.6%), destroyed lung lesions were 24 cases(33.8%). 5. The incidence of postoperative complication was 28.2%(20 cases). All cases were MDR 6. group and the most common of complication was tuberculosis spreading. In bilateral lesion, incidence of postoperative tuberculosis spreading was 25%(7 cases). Of the 7 cases, there was the cavitary lesion in 6 cases(86.7%). Total conversion rate of AFB positive sputum to negative state related to resectional sugery was 76.6% and in MDR group conversion rate of AFB positive sputum to negative state was 73.2% Conversion rate of MDR group with bilateral lesion was the lowest(60%). Conversion rate of drug-sensitivity group was 100% regardeless of lesions Slt to. In conclusion, despite of long-standing medical treatment, it is difficult to converse sputum-positive to negative state in multiple-drug resistance patients and that increases postoperative complications su h as tuberculosis relapse as a lack of appropriate drugs postoperatively. Postoperative conversion rate of sputum-positive to negative state was decreased in multiple-drug resistance patients. Because multiple-drug resistance patients have inireased due to several factors in Korea, it is important to prevent spreading of multiple-drug resistnce patients through the aggressive operative treatment. When the first medical therapy is fail or drug-resistance is found, operative treatment should be considered with the secondary medical therapy. The operation should be aggressively attempted even though at first medical treatment if indicated.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.427-438
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• 2020

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

• The Korean Journal of Nuclear Medicine
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• v.19 no.2
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• pp.43-50
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• 1985

With the improvement of hemodialysis, the course of the disease in patient with endstage renal disease has been clearly improved. Nevertheless, among several shortcomings to our present mode of renal replacement therapy, cardiovascular complications have been the leading cause of morbidity and mortality. Several factors such as anemia, arteriovenous shunting of blood, intermittent extracorporeal circulation and hypertension may be contributing. But little is known about the quantitative cardiac hemodynamic characteristics occurred during hemodialysis. The purpose of this study is to observe the sequential hemodynamic changes before, during and after the hemodialysis and to investigate reliable parameters in the detection of ventricular dysfunction. In the present study, equilibrium radionuclide cardiac angiography was performed and left and right ventricular volume indices, ejection phase indices of both ventricular, performance were measured in the 16 stable patients with chronic renal failure treated with maintenance hemodialysis sequentially i.e. before, during (early and late phase) and after the hemodialysis. The results obtained were as follows; 1) The indices of the left ventricular function were not changed during the hemodialysis but increased after the hemodialysis. 2) The indices of the right ventricular function(EF, SVI) were significantly decreased in the early phase (15, 30 minutes after starting extracorporeal circulation) but recovered after the hemodialysis. 3) The ratio of right ventricular to left ventricular ejection fraction was significantly decreased in the early phase and the lung volume indices were significantly increased at the same phase. As a conclusion, hemodialysis improves left ventricular function maybe due to increased contractility, and effects on the right ventricular function maybe due to the increased lung volume in the early phase of hemodialysis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10597-10601
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• 2015

Up-regulation of multidrug resistance-associated protein 1 (MRP1) is regarded as one of the main causes for multidrug resistance (MDR) of tumor cells, leading to failure of chemotherapy-based treatment for a multitude of cancers. However, whether silencing the overexpressed MRP1 is sufficient to reverse MDR has yet to be validated. This study demonstrated that RNAi-based knockdown of MRP1 reversed the increased efflux ability and MDR efficiently. Two different short haipin RNAs (shRNAs) targeting MRP1 were designed and inserted into pSilence-2.1-neo. The shRNA recombinant plasmids were transfected into cis-dichlorodiamineplatinum-resistant A549 lung (A549/DDP) cells, and then shRNA expressing cell clones were collected and maintained. Real time PCR and immunofluorescence staining for MRP1 revealed a high silent efficiency of these two shRNAs. Functionally, shRNA-expressing cells showed increased rhodamine 123 retention in A549/DDP cells, indicating reduced efflux ability of tumor cells in the absence of MRP1. Consistently, MRP1-silent cells exhibited decreased resistance to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and DDP, suggesting reversal of MDR in these tumor cells. Specifically, MRP1 knockdown increased the DDP-induced apoptosis of A549/DDP cells by increased trapping of their cell cycling in the G2 stage. Taken together, this study demonstrated that RNAi-based silencing of MRP1 is sufficient to reverse MDR in tumor cells, shedding light on possible novel clinical treatment of cancers.