• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1391-1396
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• 2014

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.

• Tuberculosis and Respiratory Diseases
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• 제66권1호
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• pp.42-46
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• 2009

폐암의 자연적 퇴화는 매우 드문 질환이다. 아직 그 기전은 불분명하다. 그러나 신체의 면역반응이 중요한 역할을 하는 것으로 알려져 있다. 이에 본 저자들은 폐의 편평 세포암 환자에서 항암치료 및 방사선 치료 등을 하지 않은 상태에서 자연적 퇴화가 발생한 증례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• 동의생리병리학회지
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• 제22권3호
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• pp.630-641
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• 2008

Gamisamgibopae-tang (GMSGBPT) is a traditional Korean medicine, which has been used for patients suffering from a lung disease in Oriental medicine. In the present study, we examined the biochemical mechanisms of apoptosis by GMSGBPT in NCI-H460 and A549 human non-small-cell lung cancer cell lines. It was found that GMSGBPT could inhibit the cell proliferation of A549 cells in a concentration-dependent manner, however GMSGBPT did not affect the cell proliferation of NCI-H460 cells. Apoptotic cell death in A549 cells were detected using DAPI staining and annexin V fluorescein methods. The induction of apoptotic cell death by GMSGBPT was connected with a down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression, and proteolytic activation of caspase-3 and caspase-9 in A549 cells. However, GMSGBPT did not affect the levels of pro-apoptotic Bax and Bad expression, and activity of caspase-8. GMSGBPT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}$-catenin, phospholipase C-1 (PLC${\gamma}$1) and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings suggest that GMSGBPT may be a potential chemotherapeutic agent for the control of human non-small-cell lung cancer cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of GMSGBPT.

• Journal of Chest Surgery
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• 제45권2호
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• pp.101-109
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• 2012

Background: A better understanding of the histopathology and molecular biology of lung cancer might improve our capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I non-small cell lung cancer. Materials and Methods: One hundred ten patients at the Kyungpook National University Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. Results: Univariate analysis showed that the T stage, differentiation, visceral pleural invasion, and survivin expression were significantly associated with recurrence. Multivariate analysis demonstrated that differentiation and survivin overexpression emerged as independent prognostic factors of recurrence. Conclusion: In resected stage I non-small cell lung cancer, poor differentiation and survivin overexpression have been identified as independent predictors of poor disease-free survival.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.98-103
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• 1993

연구배경 : Retinoblastoma 유전자(Rb)의 비활성화는 여러 종류의 암에서 관찰되어 왔다. Rb의 이형성의 소실(loss of heterozygosity)은 Rb의 비활성화의 가장 흔한 기전으로 소세포폐암에서는 거의 모든 예에서 관찰되나 비소세포폐암에서는 훨씬 낮은 빈도로 관찰된다고 알려져 있다. 이에 저자들은 개흉수술시 얻은 한국인의 비소세포폐암 및 정상폐조직의 DNA 에서 Rb의 변화를 관찰하였다. 방법: 폐암조직 및 정상폐조직에서 proteinase K에 의한 소화 및 phenol-chloroform 추출 방법으로 genomic DNA를 추출한 후 제한효소인 EcoRI으로 소화시키고 agarose gel 에서 전기영동분리시켰다. Southern blot 방법으로 DNA를 nylon 막에 흡착시킨 후 Rb 1 탐식자로 hybridization 시켜 stringent condition에서 세척하여 X-ray 필름에 적당기간 노출시켜 현상하였다. 결과 : 26예의 편평상피세포암중 16예에서 정상폐 DNA 에서 RFLP에 의한 Rb의 이형성이 관찰되었으며 이중 10예 (62.5%)의 폐암조직 DNA 에서 이형성의 소실이 관찰되었다. 17예의 폐선암중 11예의 정상폐 DNA 에서 RFLP에 의한 Rb의 이형성이 관찰되었으며 이중 5예 (45.4%)의 폐암 DNA 에서 이형성의 소실이 관찰되었다. Rb의 비활성화 유무에 따른 두 군 사이에 연령, 성별, 암의 병기, 암의 분화도 및 흡연력의 차이가 없었다. 결론: 이상의 결과로 Rb의 비활성화는 비소세포폐암의 발생기전에 중요한 역할을 하리라 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제79권2호
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• pp.85-90
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• 2016

Background: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. Methods: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. Results: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. Conclusion: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.

• Asian Pacific Journal of Cancer Prevention
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• 제17권10호
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• pp.4693-4697
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• 2016

Aim: The objective of this study is to investigate prognostic factors affecting survival of patients undergoing concurrent or sequential chemoradiotherapy (CRT) for stage III non-small-cell lung cancer (NSCL). Methods and materials: We retrospectively reviewed the clinical records of 148 patients with advanced, inoperable stage III NSCLC, who were treated between 2007 and 2015. Results: The median survival was found to be 19 months and 3-year overall survival was 27%. Age (<65 vs ${\geq}65years$, p=0.026), stage (IIIA vs IIIB, p=0.033), dose of radiotherapy (RT) (<60 vs ${\geq}60Gy$, p=0.024) and treatment method (sequential chemotherapy+RT vs concurrent CRT, p=0.023) were found to be factors affecting survival in univariate analyses. Gender, histological subtype, weight loss during CRT, performance status, induction/consolidation chemotherapy and presence of comorbidities did not affect survival (p>0.050). Conclusion: Young age, stage IIIA, radiotherapy dose and concurrent chemoradiotherapy may positively affect survival in stage III NSCL cases.

• Radiation Oncology Journal
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• 제29권3호
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• pp.181-190
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• 2011

Purpose: Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. Materials and Methods: The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Results: Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ${\geq}2$ radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ${\geq}2$ radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), $V_{20}$, $V_{30}$, $V_{40}$, MLDipsi, $V_{20}$ipsi, $V_{30}$ipsi, and $V_{40}$ipsi were associated with grade ${\geq}2$ radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ${\geq}2$ radiation pneumonitis. Conclusion: Concurrent chemotherapy, MLD and $V_{30}$ were statistically significant predictors of grade ${\geq}2$ radiation pneumonitis in patients with stage III non-small cell lung cancer undergoing definitive radiotherapy. The cutoff values for MLD and $V_{30}$ were 16 Gy and 18%, respectively.

• 대한암한의학회지
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• 제17권1호
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• pp.9-16
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• 2012

Objective : The aim of this study is to evaluate the synergistic effects of Traditional Korean Medicine with Gefitinib chemotherapy on a non small cell lung cancer. Methods : A 61 year-old male patient diagnosed with left non small cell lung cancer stage IIIb (T2aN0M1a) was admitted to East-West Cancer Center (EWCC) on Apr. 2012. He received Gefitinib chemotherapy since 20th June. 2011. He suffered from many complication like as skin toxicities, peripheral neuropathy, lassitude, diarrhea and so on. He was treated with Traditional Korean Medicine consisted of herbal medicine, acupuncture, and moxibustion. The symptoms were measured by Common Terminology Criteria for Adverse Events (CTCAE version 3.0) and visual analogue scale (VAS). Performance status was measured by Eastern Cooperative Oncology Group (ECOG). Results : TKM consisting of acupuncture, moxibusion, herbal medicine significantly alleviated Gefitinib induced complication. Quality of life was also significantly improved. Conclusion : This case study suggests that TKM would beneficial to adverse effects such as skin toxicities, peripheral neuropathy, lassitude from gefitinib.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.5041-5045
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• 2016

Background: Patients with recurrent or progressive lung cancer experience a significant symptom burden, negatively affecting quality of life and reducing life expectancy. Thoracic re-irradiation can be used for palliative treatment to relieve symptoms or as a curative treatment. Methods: Using patient charts, we identified and reviewed 28 cases that had received palliative thoracic re-irradiation for recurrent lung cancer. Results: Before re-irradiation, 32% of patients had stage III non-small cell lung cancer and six had small cell lung cancer. The median interval between treatments was 18.7 months. Median follow-up was 31.2 months from the initial radiotherapy and 5 months after re-irradiation. A better performance status before re-irradiation (<80 vs >80, p=0.09) and a lower overlap 90% isodose (<70 vs >70, p=0.09) showed trends toward improved survival. Grade 1-2 toxicity from re-irradiation was recorded in 12/28 patients, and no grade 3 or 4 acute toxicity was encountered. Conclusion: The role of palliative treatment in survival is not clear but it can provide symptomatic relief in patients, with no high grade toxicity. Further studies with greater patient numbers and longer follow-up times should facilitate determination of the role of this treatment in toxicity and effects on survival.