• Radiation Oncology Journal
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• v.16 no.3
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• pp.291-301
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• 1998

Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

• Journal of Chest Surgery
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• v.29 no.5
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• pp.542-547
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• 1996

All patients who underwent video-assisted thoracic surgery (VATS) for diagnostic purposes from Jan. 1992 to Aug. 1995 were reviewed. The total number of patients were 111 with 57 male and 54 female, and the mean age was 49 years (range 1 to 74). Multiple biopsies from more than one location were performed in 17 patients , pleural biopsies were performed In 49 patients, lung biopsies in 43 patients, mediastinal mass or Iymph node biopsies in 33 patients, and two pericardium biopsies and one dia- phragm biopsy, for a total of 128 biopsies. Seventeen pleural biopsy cases and one lung biopsy case underwent operation under local anesthesia , the rest were performed under general anesthesia. In patients who underwent lung biopsy, the mean age was 49.1 ye rs (range 22~ 73). The operating time was 40 to 170 minutes (mean 97), intravenous or intramuscular injection for pain control was required 0 to 22 times(mean 4.7), and chest tube was inserted from 1 to 26 days(mean 7). In all patients except two, a diagnosis was obtained from the biopsy and complication was encountered in one patient in whom intraoperative paroxysmal atrial tachycardia was detected. In 7 patients, a thorn- cotomy had to be done due to pleural adhesion or intraoperative bleeding, and 7 patients had postoperative complications associated with the chest tube. In the pleural biopsy group, the mean age was 49 years (range 17~ 74). The operating time was 25 to 80 minutes (mean 49), intravenous or intramuscular injection for pain control was needed 0 to 20 times (mean 3.6), and the chest tube was i.nserted for 0 to 67 days(mean 9.8). In all the patients, a diagnosis was possible. The chest tube was inserted for longer than 7 days in 11 patients. In the Iymph node biopsy roup, the mean age was 44.2 years (range 1 ~ 68). The operating time was )0 to 3)5 minutes(mean 105), pain control was required 0 to 15 times(mean 3.2), and a chest tube was kept in place for 1 to 36 days(mean 6.1). In one patient, a diagnosis was not possible and a chest tube was kept in place for longer than 7 days in 7 patients. In the multiple biopsy group, the mean age was 53.1 years(range 20~ 71). The operating time was 15 to 165 minutes(mean 85), and pain control was done from 0 to 17 times(mean 3.1). The chest tube was kept in place for 1 to 16 days (mean 7.9).

• Progress in Medical Physics
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• v.25 no.2
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• pp.110-115
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• 2014

To compare 2 beam arrangements, circumferential equally angles (EA) beams or partially angles (PA) beams for stereotactic body radiation therapy (SBRT) of primary lung cancer for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques with respect to target, ipsilateral lung, contralateral lung, and organs-at-risk (OAR) dose-volume metrics, as well as treatment delivery efficiency. Data from 12 patients, four treatment plans were generated per data sets ($IMRT_{EA}$, $IMRT_{PA}$, $VMAT_{EA}$, $VMAT_{PA}$). The prescribed dose (PD) was 60 Gy in 4 fractions to 95% of the planning target volume (PTV) for a 6-MV photon beam. When compared with the IMRT and VMAT treatment plan for 2 beams, conformity index, homogeneity index, high dose spillage, D2 cm (Dmax at a distance ${\geq}2cm$ beyond the PTV), R50 (ratio of volume circumscribed by the 50% isodose line and the PTV), resulted in similar. But Dmax of the Organ at risk (OAR), spinal cord, trachea, resulted in differ between four treatment plans. Especially $HDS_{location}$ showed big difference in 21.63% vs. 26.46%.

• Journal of Life Science
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• v.14 no.5
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• pp.800-808
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• 2004

Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.

• Progress in Medical Physics
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• v.25 no.4
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• pp.242-247
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• 2014

To see the discrepancies between the calculated and the delivered dose distribution of IMRT fields for respiratory-induced moving target according to the motion ranges. Four IMRT plans in which there are five fields, for lung and liver patients were selected. The gantry angles were set to $0^{\circ}$ for every field and recalculated using TPS (Eclipse Ver 8.1, Varian Medical Systems, Inc., USA). The ion-chamber array detector (MatriXX, IBA Dosimetry, Germany) was placed on the respiratory simulating platform and made it to move with ranges of 1, 2, and 3 cm, respectively. The IMRT fields were delivered to the detector with 30~70% gating windows. The comparison was performed by gamma index with tolerance of 3 mm and 3%. The average pass rate was 98.63% when there's no motion. When 1.0, 2.0, 3.0 cm motion ranges were simulated, the average pass rate were 98.59%, 97.82%, and 95.84%, respectively. Therefore, ITV margin should be increased or gating windows should be decreased for targets with large motion ranges.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.510-518
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• 2002

Background : Bronchial anthracofibrosis (BAF) is a dark black or brown pigmentation of multiple large bronchi associated with a fibrotic stenosis or obliteration that is incidentally found during a diagnostic bronchoscopy some reporters have suggested endobronchial tuberculosis or tuberculous lymphadenitis as a possible cause of BAF. However, some BAF patients do not have any medical history of tuberculosis. The aim of this study was to elucidate the clinical features of simple BAF patients, which were not associated with tuberculosis. Methods : We reviewed the patients' charts retrospectiely and interviewed all BAF patients who were followed up for 1 year or more. Among the 114 BAF patients, 43 patents (38 %) had no associated tuberculosis, cancer and pneumoconiosis. The clinical characteristics, radiological findings and associated pulmonary diseases of these patients were evaluated. Results : Most patients were non-smokers, old aged, housewifes who resided in a farming village. The common respiratory symptoms were dyspnea, cough and hemoptysis. The predominant X-ray findings were a multiple bronchial wall thickening(89%), bronchial narrowing or atelectasis (76%) and a mediastinal lymph node enlargement with/without calcification (78%). Pulmonary function test usually showed mild obstructive ventilatory abnormalities but no patient showed a restrictive ventilatory pattern and the patients were frequently affected with chronic bronchitis(51%), post-obstructive pneumonia(40%) and chronic asthma(4%). Conclusion : Because BAF is frequently associated with chronic bronchitis and obstructive pneumonia as well as tuberculosis, a careful clinical evaluation and accurate differential diagnosis is more essential than empirical anti-tuberculous medication.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.624-629
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• 2009

Background: Making the histologic diagnosis of small pulmonary nodules and ground glass opacity (GGO) lesions is difficult. CT-guided percutaneous needle biopsies often fail to provide enough specimen for making the diagnosis. Video-assisted thoracoscopic surgery (VATS) can be inefficient for treating non-palpable lesions. Preoperative localization of small intrapulmonary lesions provides a more obvious target to facilitate performing intraoperative. resection. We evaluated the efficacy of CT-guided localization with using a hook wire and this was followed by VATS for making the histologic diagnosis of small intrapulmonary nodules and GGO lesions. Material and Method: Eighteen patients (13 males) were included in this study from August 2005 to March 2008. 18 intrapulmonary lesions underwent preoperative localization by using a CT-guided a hook wire system prior to performing VATS resection for intrapulmonary lesions and GGO lesions. The clinical data such as the accuracy of localization, the rate of conversion-to-thoracotomy, the operation time, the postoperative complications and the histology of the pulmonary lesion were retrospectively collected. Result: Eighteen VATS resections were performed in 18 patients. Preoperative CT-guided localization with a hook-wire was successful in all the patients. Dislodgement of a hook wire was observed in one case. There was no conversion to thoracotomy, The median diameter of lesions was 8 mm (range: $3{\sim}15\;mm$). The median depth of the lesions from the pleural surfaces was 5.5 mm (range: $1{\sim}30\;mm$). The median interval between preoperative CT-guided with a hook-wire and VATS was 34.5 min (range: ($10{\sim}226$ min). The median operative time was 43.5.min (range: $26{\sim}83$ min). In two patients, clinically insignificant pneumothorax developed after CT-guided localization with a hook-wire and there were no other complications. Histological examinations confirmed 8 primary lung cancers, 3 cases of metastases, 3 cases of inflammation, 2 intrapulmonary lymph nodes and 2 other benign lesions. Conclusion: CT-guided localization with a hook-wire followed by VATS for treating small intrapulmonary nodules and GGO lesions provided a low conversion thoracotomy rate, a short operation time and few localization-related or postoperative complications. This procedure was efficient to confirm intrapulmonary lesions and GGO lesions.