• Radiation Oncology Journal
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• v.32 no.1
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• pp.43-47
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• 2014

Purpose: The degree of radiation-induced lung fibrosis (RILF) can be measured quantitatively by fibrosis volume (VF) on chest computed tomography (CT) scan. The purpose of this study was to investigate the interobserver and intraobserver variability in CT-based measurement of VF. Materials and Methods: We selected 10 non-small cell lung cancer patients developed with RILF after postoperative radiation therapy (PORT) and delineated VF on the follow-up chest CT scanned at more than 6 months after radiotherapy. Three radiation oncologists independently delineated VF to investigate the interobserver variability. Three times of delineation of VF was performed by two radiation oncologists for the analysis of intraobserver variability. We analysed the concordance index (CI) and inter/intra-class correlation coefficient (ICC). Results: The median CI was 0.61 (range, 0.44 to 0.68) for interobserver variability and the median CIs for intraobserver variability were 0.69 (range, 0.65 to 0.79) and 0.61(range, 0.55 to 0.65) by two observers. The ICC for interobserver variability was 0.974 (p < 0.001) and ICCs for intraobserver variability were 0.996 (p < 0.001) and 0.991 (p < 0.001), respectively. Conclusion: CT-based measurement of VF with patients who received PORT was a highly consistent and reproducible quantitative method between and within observers.

• Korean Journal of Radiology
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• v.23 no.3
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• pp.370-380
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• 2022

Objective: To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival after curative surgery and to identify prognostic factors for pIMA. Materials and Methods: From January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA. Results: The 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC (p = 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant (p = 0.11 and p = 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval [CI], 1.95-11.11), p < 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59-12.89), p = 0.005 for OS}. Conclusion: The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.

• Journal of Chest Surgery
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• v.31 no.3
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• pp.271-278
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• 1998

In order to access the value of computed tomography in mediastinal LN staging of NSCLCa, 581 LN stations of 77 patients were selected from 552 patients who were diagnosed as Lung Ca and operated in Seoul National University Hospital from 1992 to 1995. The selection criteria were as follows ; the patients 1) whose preoperative chest CTs were available; 2) underwent curative resection (lobectomy or more) with complete lymph node dissection; 3) whose final pathologic diagnosis were proven to be non-small cell lung cancer. We adopted Receiver Operating Characteristic curve method to determine a proper size criterion for diagnosing malignant mediastinal adenopathy. From curve analysis, we decided the size criterion of lymph node to 1 cm in their short axis. Using this size criterion, it's sensitivity was 43.9%, specificity was 87.4%, and accuracy was 83.1%. Eventhough we couldn't determine the precise size criterion for the adenoca, it seemed that shorter than 1 cm size criterion should be applied in that particular cell type. Lymph node stations associated with the tuberculosis or bronchiectasis tend to be overestimated in nodal staging and have relatively high false positive rate. The low sensitivity of CT scan suggest that radical and complete dissection or precise mediastinal lymph node evaluation through the surgical approach is mandatory.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.553-558
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• 2017

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.290-297
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• 2000

Background : Current non-invasive methods for evaluating the mediastinum by computed tomographic (CT) scan have limited sensitivity and specificity. The recently introduced PET was reported to be a more sensitive and specific method for the mediastinal staging of NSCLC (sensitivity : 76-100 %, specificity : 81-100%) than CT or MRI. We assessed the usefulness of PET in the mediastinal staging of NSCLC. Methods : We reviewed the medical records of NSCLC patients that had undertaken staging work-up by both CT and PET before thoracotomy between January 1997 and December 1998. A total of 23 patients were enrolled in the study (14 males and 7 females) with a mean age of 61$\pm$9 years. By comparing the clinical(CT and PET) and pathologic stagings, we evaluated the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET in thoracic nodal staging. Results : Sensitivity, specificity, positive predicted value and negative predicted value were 38%, 40%, 25% and 50% respectively for computed tomography, and 50%, 60%, 30% and 69% for PET. The accuracy of FDG-PET in our study was lower than that reported by previous other studies. Conclusion : The addition of FDG-PET to CT scanning has limited benefit for the thoracic nodal staging of NSCLC, but its value in our study was lower than that observed by others.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.35-44
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• 2008

Purpose: To evaluate the incidence and prognostic factors of treatment-related pneumonitis in non-small-cell lung cancer(NSCLC) patients treated with intensity modulated radiation therapy(IMRT). Materials and Methods: One-hundred-five patients with NSCLC treated with IMRT between 1 August 2004 and 30 November 2006 were analyzed retrospectively. The mean age of patients was 62.9 years, and squamous carcinomas were confirmed in 81 patients(77%). Sixty-six patients(62.9%) were classified as stage III, and 59 patients had lesions in the right lung. Twenty-seven patients were treated with a dose of 3,060 cGy preoperatively, and 10 patients were given a dose of 5,040 cGy postoperatively. Sixty-eight patients received a dose of 7,020 cGy for curative intent. Sixty-eight patients were treated with the use of the CORVUS planning system and 37 patients were treated with the use of the ECLIPSE planning system. Results: Of 105 patients, 21 patients(20%) had abnormal radiological findings, but only seven patients(6.7%) required treatment for radiation pneumonitis. Six of the seven patients had other serious lesions, including a bronchioesophageal fistula(one patient), recurrence in the treatment field(two patients), brain metastasis(one patient) and lung-to-lung metastasis(two patients); all of these patients died within 19 months after radiation treatment. Sixteen patients(23.5%) that received planning with the CORVUS system had abnormal lung findings. Five patients(13.5%) had abnormal lung findings with the use of the ECLIPSE planning system. Other prognostic factors such as perioperative radiation therapy, a volume over 10% of the V20 volume in the right lung, were also statistically significant. Conclusion: This retrospective analysis suggests that IMRT could be a beneficial treatment modality for the reduction of radiation pneumonitis in NSCLC patients. However, the higher incidence of abnormal radiological findings in perioperative patients treated with relatively lower doses($3,060{\sim}5,040$ cGy) suggest the need for judicious treatment planning in preoperative or postoperative treatment.

• Journal of Microbiology and Biotechnology
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• v.27 no.1
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• pp.72-76
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• 2017

Detection of exon 19 deletion mutation in the epidermal growth factor receptor (EGFR) gene, which results in increased and sustained phosphorylation of EGFR, is important for diagnosis and treatment guidelines in non-small-cell lung cancer. Here, we have developed a simple and convenient detection system using the interaction between G-quadruplex and fluorophore thioflavin T (ThT) for discriminating EGFR exon 19 deletion mutant DNA from wild type without a label and quencher. In the presence of exon 19 deletion mutant DNA, the probe DNAs annealed to the target sequences were transformed into G-quadruplex structure. Subsequent intercalation of ThT into the G-quadruplex resulted in a light-up fluorescence signal, which reflects the amount of mutant DNA. Due to stark differences in fluorescence intensity between mutant and wild-type DNA, we suggest that the induced G-quadruplex structure in the probe DNA can report the presence of cancer-causing deletion mutant DNAs with high sensitivity.

• BMB Reports
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• v.50 no.3
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• pp.150-155
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• 2017

Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor ${\kappa}B$ (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs). Consistently, afatinib inhibited the expression of osteoclast marker genes, whereas, it upregulated the expression of negative modulator genes. The bone resorbing activity of osteoclasts was also abrogated by afatinib. In addition, afatinib significantly inhibited RANKL-mediated Akt/protein kinase B and c-Jun N-terminal kinase phosphorylation. These results suggest that afatinib substantially suppresses osteoclastogenesis by downregulating RANK signaling pathways, and thus may reduce osteolysis after bone metastasis.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.507-511
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• 2004

From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyfla-vanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 $\mu$M, whereas compounds 4,7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 $\mu$M respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 $\mu$M, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 $\mu$M respectively.