• Korean Journal of Bronchoesophagology
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• v.17 no.1
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• pp.9-13
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• 2011

Endobronchial ultrasound (EBUS), which enables visualization of lesions beyond the bronchus, broadens the fields of bronchoscopy. Two types of ultrasound, radial and linear, are used for bronchoscopy. Radial EBUS is performed by inserting an ultrasound mini-probe through the working channel of a flexible bronchoscope. Evaluation of the depth of invasion of early endobronchial lung cancers using radial EBUS is useful in deciding endobronchial treatment. A central tumor limited to within the cartilaginous layer is a good indication for endobronchial photodynamic therapy. EBUS-guide sheath (GS) technique is a sampling method assisted by localization of peripheral lesions using EBUS. The diagnostic yield of EBUS-GS method is higher than that of conventional transbronchial biopsy. High diagnostic values of EBSU-GS method are reported even in small (${\leq}2cm$) peripheral tumors. Linear EBUS is used for endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). EBUS-TBNA has high diagnostic yields in mediastinal staging of lung cancer even in patients having radiologically early stage lung cancers with normal CT or PET findings in the mediastinum. EBUS is a valuable method in evaluating early endobronchial tumors and peripheral small lung cancers and as well as in mediastinal staging.

• Tuberculosis and Respiratory Diseases
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• v.67 no.4
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• pp.338-344
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• 2009

In photodynamic therapy, a chemical photosensitizer is activated by light of a specific wavelength., Photodynamic therapy has been combined with bronchoscopy in patients who are ineligible for surgical resection in order to treat patients with early central lung cancer. Here, we describe 3 patients with early central lung cancer who were treated effectively using photodynamic therapy. Our experience shows that this approach is a useful modality in the therapy of these types of tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4893-4898
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• 2016

Objective: To investigate the impact of a Croton tiglium extract on cellular proliferation and apoptosis in a non-small cell lung cancer cell line (A549) in vitro. Methods: A Croton tiglium seed methanol extract was prepare and assessed for effects on A549 cells regarding cellular proliferation, apoptotic rates, and expression of apoptosis related genes and proteins using real-time PCR and immunofluorescence. Results: The tested Croton tiglium extract inhibited A549 cell proliferation in a dose- and time-dependent manner, with significant elevation of apoptotic indexes at various concentrations after 24 h. In addition, rates in both early and late stages were higher in treated than untreated groups, the $100{\mu}g/ml$ dose causing the highest levels of apoptosis. RT-PCR showed that A549 cells treated with $100{\mu}g/ml$ Croton tiglium extract for 24 h has markedly higher Bax mRNA expression levels and obviously lower Bcl-2 expression levels than controls, equivalent results being observed for proteins by immunofluorescence. However, the mRNA expression levels of Fas and caspase-8 were not significantly altered. Conclusion: A Croton tiglium extract can inhibit proliferation of A549 cells and promote apoptosis though Bax/Bcl-2 pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7799-7803
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• 2014

Background: To determine the imprinting status of the IGF2 in Chinese patients with primary lung cancer and to analyze the clinical significance of the loss of imprinting (LOI) of IGF2. Materials and Methods: PCRRFLP and RT-PCR-RFLP were carried out to select heterozygous cases for the ApaI polymorphism within exon 9 of the IGF2 gene and further analyze IGF2 LOI in 64 lung cancer patients, respectively. Results: Of 64 lung cancer patients, 31 were heterozygous for IGF2. The positive rates of IGF2 LOI of lung cancer foci, matched paracancer tissues, and normal lung tissues were 77.4% (24/31), 61.3% (19/31), and 29.0% (9/31), respectively. The LOI differences for IGF2 among the three groups were statistically significant (${\chi}^2=15.267$, p=0.000), and the LOI frequency of IGF2 in normal lung tissue was significantly lower than that in lung cancer foci and paracancer tissues (${\chi}^2=14.577$, p=0.000; ${\chi}^2=6.513$, p=0.011). No statistical difference was observed between the lung tumor group and the matched paracancer group (${\chi}^2=1.897$, p=0.168). The prevalence of advanced clinical stages (${\chi}^2=2.379$; p=0.017) and lymph node metastasis (${\chi}^2=5.552$; p=0.018) was significantly higher for LOI-positive paracancer tissues than for LOI-negative paracancer tissues. Conclusions: IGF2 LOI is highly frequent in Chinese primary lung cancer patients, especially those with increased risk of lymph node metastasis and advanced clinical stages. IGF2 LOI may be an early epigenetic event in human lung carcinogenesis.

• Korean Journal of Bronchoesophagology
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• v.17 no.1
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• pp.5-8
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• 2011

The proliferation of new technologies has significantly enhanced the diagnostic capabilities of flexible bronchoscopy compared with traditional methods. Narrow band imaging (NBI), an optical technique in which filtered light enhances superficial neoplasms based on their neoangiogenic patterns, was developed to screen for central intraepithelial moderate or severe dysplasia, carcinoma in situ (CIS), and microinvasive neoplasia in patients at risk for lung cancer. Because angiogenesis occurs preferentially in dysplastic and neoplastic lesions, NBI may identify early dysplastic lesions better than white light bronchoscopy (WLB) currently in use. NBI bronchoscopy can be used not only to detect precancerous lesions, but also to screen for cancerous lesions. We prospectively evaluated 101 patients with suspected lung cancer between July 2009 and June 2010. All were previously scheduled for flexible bronchoscopy CT scans. Abnormal NBI was defined by Shibuya's descriptors (tortuous, dotted, or spiral and screw patterns). Biopsies of 132 lesions in 92 patients showed that 78 lesions (59.1%) were malignant and 54 (40.9%) were benign. The diagnostic sensitivity of bronchoscopy in detecting malignancy was 96.2% (75/78). When assorted by lesion pattern, the sensitivity and specificity of NBI bronchoscopy in detecting malignancies were 69.2% (54/78) and 96.3% (52/54), respectively, for the spiral and screw pattern and 14.1% (11/78) and 96.3% (52/54), respectively, for the dotted pattern. Unexpectedly, additional cancerous lesions were detected in five patients (2 dotted and 3 spiral and screw). As a screening tool for malignant lesions, NBI bronchoscopy should assess combinations of all three lesion. The dotted and spiral and screw patterns may be helpful in determining which lesions should be biopsied. NBI bronchoscopy may be useful not only for the diagnosis of early-stage lung cancer but also for more accurate local staging of lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.507-510
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• 2013

Background: More and more research indicate that the immediately early response gene 3 (IER3) is involved inmany biological provesses, such as apoptosis and immunoreaction, as well as viral infection, tumorigenesis and tumour progression. Methods: Here we describe the construction of an eukaryotic expression vector containing IER3 gene and its expression in A549 cells as assessed through fluorescence microscopyand Western-blotting. Results: Fluorescence detection displayed that GFP in cytoplasm was high during 48 and 72 hours post-transfection. In addition, Western blotting showed significant increase in IER3 gene expression in the transfected cells compared with controls. Conclusion: The recombinate plasmid expression vector was constructed successfully, which may provide a basis for further exploration of function of IER3 in lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10937-10941
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• 2015

Pathogenesis of lung cancer is a complicated biological process including multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this study was to determine whether tobacco exposure plays a role in gene methylation. Methylation of the RAR-${\beta}$ gene were detected using methylation-specific polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and corresponding 105 controls. A significant statistical association was found in the detection rate of the promoter methylation of RAR-${\beta}$ gene between NSCLC and controls ($x^2$=166.01; p<0.01), and hypermethylation of the RAR-${\beta}$ gene was significantly associated with smoking status (p=0.038, p<0.05). No relationship was found between RAR-${\beta}$ gene methylation and pathologic staging including clinical stage, cell type, gender and drinking (p>0.05), and the methylation of RAR-${\beta}$ gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in I+II (70.8%). Similar results were obtained for methylation of the RAR-${\beta}$ gene between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%). These results showed that the frequency of methylation increased gradually with the development of clinical stage in smoking-associated lung cancer patients, and tobacco smoke may be play a potential role in RAR-${\beta}$ gene methylation in the early pathogenesis and process in lung cancer, particularly squamous cell carcinoma. Aberrant promoter methylation is considered to be a promising marker of previous carcinogen exposure and cancer risk.

• Molecules and Cells
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• v.43 no.10
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• pp.889-897
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• 2020

K-RAS is frequently mutated in human lung adenocarcinomas (ADCs), and the p53 pathway plays a central role in cellular defense against oncogenic K-RAS mutation. However, in mouse lung cancer models, oncogenic K-Ras mutation alone can induce ADCs without p53 mutation, and loss of p53 does not have a significant impact on early K-Ras-induced lung tumorigenesis. These results raise the question of how K-Ras-activated cells evade oncogene surveillance mechanisms and develop into lung ADCs. RUNX3 plays a key role at the restriction (R)-point, which governs multiple tumor suppressor pathways including the p14^ARF-p53 pathway. In this study, we found that K-Ras activation in a very limited number of cells, alone or in combination with p53 inactivation, failed to induce any pathologic lesions for up to 1 year. By contrast, when Runx3 was inactivated and K-Ras was activated by the same targeting method, lung ADCs and other tumors were rapidly induced. In a urethane-induced mouse lung tumor model that recapitulates the features of K-RAS-driven human lung tumors, Runx3 was inactivated in both adenomas (ADs) and ADCs, whereas K-Ras was activated only in ADCs. Together, these results demonstrate that the R-point-associated oncogene surveillance mechanism is abrogated by Runx3 inactivation in AD cells and these cells cannot defend against K-Ras activation, resulting in the transition from AD to ADC. Therefore, K-Ras-activated lung epithelial cells do not evade oncogene surveillance mechanisms; instead, they are selected if they occur in AD cells in which Runx3 has been inactivated.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7785-7788
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• 2015

Utilization of high energy photons (>10MV) with an optimal weight using a mixed energy technique is a practical way to generate a homogenous dose distribution while maintaining adequate target coverage in intact breast radiotherapy. This study represents a model for estimation of this optimal weight for day to day clinical usage. For this purpose, treatment planning computed tomography scans of thirty-three consecutive early stage breast cancer patients following breast conservation surgery were analyzed. After delineation of the breast clinical target volume (CTV) and placing opposed wedge paired isocenteric tangential portals, dosimeteric calculations were conducted and dose volume histograms (DVHs) were generated, first with pure 6MV photons and then these calculations were repeated ten times with incorporating 18MV photons (ten percent increase in weight per step) in each individual patient. For each calculation two indexes including maximum dose in the breast CTV ($D_{max}$) and the volume of CTV which covered with 95% Isodose line ($V_{CTV,95%IDL}$) were measured according to the DVH data and then normalized values were plotted in a graph. The optimal weight of 18MV photons was defined as the intersection point of $D_{max}$ and $V_{CTV,95%IDL}$ graphs. For creating a model to predict this optimal weight multiple linear regression analysis was used based on some of the breast and tangential field parameters. The best fitting model for prediction of 18MV photons optimal weight in breast radiotherapy using mixed energy technique, incorporated chest wall separation plus central lung distance (Adjusted R2=0.776). In conclusion, this study represents a model for the estimation of optimal beam weighting in breast radiotherapy using mixed photon energy technique for routine day to day clinical usage.

• Journal of Chest Surgery
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• v.39 no.2 s.259
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• pp.106-110
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• 2006

Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.