• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.188-192
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• 2014

We present a case of an unusual infectious complication of a ruptured mediastinal abscess after endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which led to malignant pleural effusion in a patient with stage IIIA non-small-cell lung cancer. EBUS-TBNA was performed in a 48-year-old previously healthy male, and a mediastinal abscess developed at 4 days post-procedure. Video-assisted thoracoscopic surgery was performed for debridement and drainage, and the intraoperative findings revealed a large volume pleural effusion that was not detected on the initial radiographic evaluation. Malignant cells were unexpectedly detected in the aspirated pleural fluid, which was possibly due to increased pleural permeability and transport of malignant cells originating in a ruptured subcarinal lymph node from the mediastinum to the pleural space. Hence, the patient was confirmed to have squamous cell lung carcinoma with malignant pleural effusion and his TNM staging was changed from stage IIIA to IV.

• Journal of Microbiology and Biotechnology
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• v.34 no.7
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• pp.1452-1463
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• 2024

Fungi generate different metabolites some of which are intrinsically bioactive and could therefore serve as templates for drug development. In the current study, six endophytic fungi namely Aspergillus flavus, Aspergillus tubigenesis, Aspergillus oryzae, Penicillium oxalicum, Aspergillus niger, and Aspergillus brasiliensis were isolated and identified from the medicinal plant, Silybum marianum. These endophytic fungi were identified through intra transcribed sequence (ITS) gene sequencing. The bioactive potentials of fungal extracts were investigated using several bioassays such as antibacterial activity by well-diffusion, MIC, MBC, anti-biofilm, antioxidant, and haemolysis. The Pseudomonas aeruginosa PAO1 was used to determine the antibiofilm activity. The ethyl acetate extract of Aspergillus flavus showed strong to moderate efficacy against Staphylococcus aureus, Escherichia coli, P. aeruginosa, and Bacillus spizizenii. Aspergillus flavus and Aspergillus brasiliensis exhibited significant antibiofilm activity with IC₅₀ at 4.02 and 3.63 mg/ml, while A. flavus exhibited maximum antioxidant activity of 50.8%. Based on HPLC, LC-MS, and NMR experiments kojic acid (1) and carbamic acid (methylene-4, 1-phenylene) bis-dimethyl ester (2) were identified from A. flavus. Kojic acid exhibited DPPH free radical scavenging activity with an IC₅₀ value of 99.3 ㎍/ml and moderate activity against ovarian teratocarcinoma (CH1), colon carcinoma (SW480), and non-small cell lung cancer (A549) cell lines. These findings suggest that endophytic fungi are able to produce promising bioactive compounds which deserve further investigation.

• Journal of Life Science
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• v.26 no.12
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• pp.1383-1391
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• 2016

Anti-estrogen drugs such as tamoxifen have been used for treating patients with ER-positive, early breast cancer. However, resistance to anti-estrogen treatment is inevitable in most patients. Breast cancer anti-estrogen resistance-3 (BCAR3) has been identified as the protein responsible for the induction of tamoxifen resistance in estrogen-dependent human breast cancer. We have previously reported that BCAR3 regulates the cell cycle progression and the signaling pathway of EGF and insulin leading to DNA synthesis. In this study, we investigated the functional role of BCAR3 in regulating c-Jun transcription in non-tumorigenic human breast epithelial MCF-12A cells. A transient transfection of BCAR3 increased both the mRNA and protein of c-Jun expression, and stable expression of BCAR3 increased c-Jun protein expression. The overexpression of BCAR3 directly activated the promoter of c-jun, AP-1, and SRE but not that of $NF-{\kappa}B$. Furthermore, single-cell microinjection of BCAR3 expression plasmid in the cell cycle-arrested MCF-12A cells induced c-Jun protein expression, and co-injection of dominant negative mutants of Ras, Rac, and Rho suppressed the transcriptional activity of c-Jun in the presence of BCAR3. Furthermore, stable expression of BCAR3 increased the proliferation of MCF-12A cells. The microinjection of inhibitory materials such as anti-BCAR3 antibody and siRNA BCAR3 inhibited EGF-induced c-Jun expression but did not affect IGF-1 induced upregulation of c-Jun. Taken together, we propose that BCAR3 plays a crucial role in c-Jun protein expression and cell proliferation and that small GTPases (e.g., Ras, Rac, and Rho) are required for the BCAR3-mediated activation of c-Jun expression.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.54-58
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• 2005

Background : To evaluate the role of estrogen and progesterone in the carcinogenesis of NSCLC, IHC studies for the expression of the receptors of estrogen and progesterone have been performed with inconsistent results. Recently the TMA method has been developed and has become recognized as a useful and rapid method for extensively analysing molecular markers at the gene and protein level. We have investigated their expressions in the tissue from NSCLC using the microarray method. Methods : The TMA construction was made with 70 formalinfixed, paraffin-embedded tissues of NSCLC. After heat-induced epitope retrieval, IHC staining on primary tissues of NSCLC was performed with the monoclonal antibodies, ER1D5 and PR1A6. Results : Our sample of 70 consisted of 74% men and 26% women. Of the patients, 49% were current smokers, 27% were non-smokers and 24% were former smokers. By histologic classification, 34 patients had squamous cell carcinoma, 24 had adenocarcinoma, 9 had adenosquamous cell carcinoma, and 3 had other carcinomas. No cancer cells were immunostained with these monoclonal antibodies in any primary tissues of NSCLC. Conclusions : No expression of neither of the two receptors was found in any of the lung cancer tissues. This suggests that adequate genetic variants for IHC staining need to be developed for NSCLC.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.95-106
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• 2012

Purpose: The objective of this study was to investigate the usefulness of an IMRT treatment plan according to whether there was a shell-type pseudo target during radiation therapy for patients in Stage III or IV of non-small cell lung cancer (NSCLC). Materials and Methods: After setting an IMRT (Intensity-Modulated Radiation Therapy, IMRT) plan for when there was a shell-type pseudo target (SPT) and when there was none (WSPT) with 22 patients in Stage III or IV of NSCLC, the investigator analyzed dose-volume histograms (DVHs) and made assessment with dosimetric comparisons such as homogeneity index (HI) inside the tumor target, conformity index (CI) of the tumor target, spinal cord maximum dose, Esophagus $V_{50%}$, mean lung dose (MLD), and $V_{40%}$, $V_{30%}$, $V_{20%}$, $V_{10%}$, $V_{5%}$. Results: The mean CI of WSPT and SPT was $1.22{\pm}0.04$ and $1.16{\pm}0.032$ ($.000^*$), respectively, and the mean HI of WSPT and SPT was $1.06{\pm}0.015$ and $1.07{\pm}0.014$ ($.000^*$), respectively. In SPT, the mean of each CI difference decreased by $-5.16{\pm}2.54%$, while HI increased by average $0.81{\pm}0.47%$. Esophagus $V_{50%}$ recorded $14.54{\pm}12.01%$ (WSPT) and $12.14{\pm}11.09%$ ($.000^*$, SPT) with the mean of SPT differences dropping by $-26.37{\pm}25.05%$. Mean spinal cord maximum dose was $3,898.44{\pm}1,075.0$ cGy (WSPT) and $3,810.8{\pm}1,134.9$ cGy ($.004^*$, SPT) with SPT dropping by average $-3.36{\pm}5.81%$. As for lung $V_{X%}$, the mean of $V_{5%}$ and $V_{10%}$ differences was $-1.62{\pm}2.29%$ ($.006^*$) and $-1.98{\pm}5.02%$ ($.005^*$), respectively with SPT making a decrease. The mean of V20%, V30%, and V40% differences was $-3.51{\pm}3.07%$ ($.000^*$), $-4.84{\pm}6.01%$ ($.000^*$), and $-6.16{\pm}8.46%$ ($.001^*$), respectively, with SPT making a decrease with statistical significance. In MLD assessment, SPT also dropped by average $-2.83{\pm}2.41%$ ($.000^*$). Those results show that SPT allows for mean 169 cGy (Max: 547 cGy, Min: 6.4 cGy) prescription dose. Conclusion: An IMRT treatment plan with SPT during radiation therapy for patients in Stage III or IV of NSCLC will help to reduce the risk of lung toxicity and radiation-induced pneumonia by cutting down radiation doses entering the normal lung, reduce the local control failure rate during radiation therapy due to increasing prescription doses to a certain degree, and increase treatment effects.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.253-260
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• 2003

Purpose: No general consensus has been reached regarding the necessity of postoperative radiation therapy (PORT) and the optimal techniques of its application for patients with chest wall invasion (pT3cw) and node negative (NO) non-small cell lung cancer (NSCLC). We retrospectively analyzed the PT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. Materials and Methods: From Aug. 1994 till June 2000, 21 pT3cwN0 NSCLC patients received PORT at Samsung Medical Center; all of whom underwent curative on-bloc resection of the primary tumor plus the chest wall and regional lymph node dissection. PORT was typically stalled 3 to 4 weeks after operation using 6 or 10 MV X-rays from a linear accelerator. The radiation target volume was confined to the tumor bed plus the immediate adjacent tissue, and no regional lymphatics were included. The planned radiation dose was 54 Gy by conventional fractionation schedule. The survival rates were calculated and the failure patterns analyzed. Results: Overall survival, disease-free survival, loco-regional recurrence-free survival, and distant metastases-free survival rates at 5 years were 38.8$\%$, 45.5$\%$, 90.2$\%$, and 48.1$\%$, respectively. Eleven patients experienced treatment failure: six with distant metastases, three with intra-thoracic failures, and two with combined distant and intra-thoracic failures. Among the five patients with intra-thoracic failures, two had pleural seeding, two had in-field local failures, and only one had regional lymphatic failure in the mediastinum. No patients suffered from acute and late radiation side effects of RTOG grade 3 or higher. Conclusion: The strategy of adding PORT to surgery to improve the probability, not only of local control but also of survival, was justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. The incidence and the severity of the acute and late side effects of PORT were markedly reduced, which contributed to improving the patients' qualify of life both during and after PORT, without increasing the risk of regional failures by eliminating the regional lymphatics from the radiation target volume.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.642-649
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• 1999

Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Journal of Chest Surgery
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• v.37 no.3
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• pp.252-260
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• 2004

The purpose of study is to evaluate the clinical implication of malignant Pleural Lavage Cytology (PLC) in primary lung cancer. 315 patients were examined with pleural lavage cytology in Asan Medical Center between November 1998 and August 2002. The patients were chosen from primary lung cancer patients with no pleural effusion according to preoperative radiologic examination; no tumor invasion into the chest wall and no diffuse pleural adhesion in intraoperative findings, The pleural cavity and lung were washed with 100 $m\ell$ of warm normal saline. The 315 patients consisted of 237 men and 78 women. The incidence of malignant PLC was found in 28 patients (8.9%). For patients in early stages (I & II), survival rate was 93.9% in positive malignant PLC and 85.7% in negative malignant PLC. 31 patients (13.6%) had local or distant recurrences; 2-year recurrence-free rate was 90.1% in negative PLC and 87.5% in positive PLC. The survival and recurrence-free rate in each stage were not statistically associated with the result of PLC. Median follow-up was 16.4 months from the surgery. To access implication of malignant PLC in primary lung cancer, a long-term follow-up and further study are required.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.195-201
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• 1988

Sixty patients with proven lung cancer were retrospectively studied to determine whether postoperative radiation therapy improves survival. Patterns of treatment failure and 5 year survival were assessed according to extent of tumor spread, histology, type of operation, positive resection margin and radiation dose. Of the 60 patients, excluding S patients who received incomplete treatment or poor pulmonary function,55 patients received postoperative radiation therapy following curative resection. The overall survival at 5 years was $39\%$. The hilar and mediastinal lymph node involvement had an influence on survival. The authors recommend that patients with resection. lung cancer involving the hilar and mediastinal lymph nodes may require postoperative radiotherapy to reduce the local recurrence and improve survival.