• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.42-46
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• 2009

Lung cancer is one of the most prevalent cancers and it has the highest mortality of all forms of cancers. Although surgery, chemotherapy and radiotherapy are routinely used for the treatment of lung cancer treatment, little progress has been made in the treatment of this condition over the past 20 years. The histological subtype of squamous cell carcinoma (SCC) accounts for approximately 30% of all lung cancer patients. Spontaneous regression of non-small-cell lung cancer (NSCL) is an extremely rare phenomenon. Spontaneous regression of cancer (SR) is defined as a complete or partial, temporary or permanent disappearance of all or at least some the relevant parameters of soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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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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• v.45 no.2
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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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• v.40 no.2
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• pp.98-103
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• 1993

Background: Inactivation of retinoblastoma gene (Rb) has been observed in a variety of human cancers. Loss of heterozygosity (LOH) of Rb which is a common mode of allelic inactivation of Rb, has been known as a frequent genetic event in small cell lung cancer but it has been detected less frequently in non-small cell lung cancer. To define the role of Rb deletion in lung cancer, we investigated the genomic DNAs of 43 non-small cell lung cancers and 1 small cell lung cancer paired with normal lung tissues obtained by thoracotomy. Methods: The genomic DNAs were obtained by the digestion with proteinase K followed by phenol-chloroform extraction method. The genomic DNAs were digested by restriction endonuclease (EcoRI), separated by agarose gel electrophoresis, transferred to nylon membrane by Southern blot transfer and then hybridized with labelled Rb 1 probe which contains. 1.4 kb sized DNA sequence containing N-terminal portion of Rb. Results: In 26 squamous cell lung cancers, 16 cases were informative after EcoRI digestion and LOH of Rb was found in 10 cases (62.5%). In 17 adenocarcinomas of lung, 11 cases were informative and LOH of Rb was found in five cases (45.4%). The analysis of clinical parameters revealed no significant differences between the two groups with or without LOH of Rb in the aspects of age, sex, degree of differentiation, stage and smoking amount. Conclusions: These results suggest that Rb inactivation is also significantly involved in the molecular pathogenesis of non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.79 no.2
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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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• v.17 no.10
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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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• v.29 no.3
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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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.

• Journal of Korean Traditional Oncology
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• v.17 no.1
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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.

• CELLMED
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• v.3 no.1
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• pp.9.1-9.10
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• 2013

In traditional systems of medicine including homeopathy, the Condurango extract (Con) is often used to cure stomach cancer mainly, without having any scientific validation of its anti-cancer ability. Con has therefore been tested against non-small-cell lung cancer cells (NSCLC) A549 and NCI-H522 (H522) known to contain the KRAS mutation, making them resistant to most chemotherapeutic agents. As cancer cells generally defy cytotoxicity developed by chemopreventive agents and escape cell death, any drug showing the capability of preferentially killing cancer cells through apoptosis is worth consideration for judicious application. A549 and H522 cells were exposed to $0.35{\mu}g/{\mu}l$ and $0.25{\mu}g/{\mu}l$ of Con, respectively, for 48 h and analysed based on various protocols associated with apoptosis and DNA damage, such as MTT assay to determine cell viability, LDH assay, DNA fragmentation assay, comet assay, and microscopical examinations of DNA binding fluorescence stains like DAPI, Hoechst 33258 and acridine orange/ethidium bromide to determine the extent of DNA damage made in drug-treated and untreated cells and the results compared. Changes in mitochondrial membrane potential and the generation of reactive oxygen species were also documented through standard techniques. Con killed almost 50% of the cancer cells but spared normal cells significantly. Fluorescence studies revealed increased DNA nick formation and depolarized membrane potentials after drug treatment in both cell types. Caspase-3 expression levels confirmed the apoptosis-inducing potential of Con in both the NSCLC lines. Thus, overall results suggest considerable anticancer potential of Con against NSCLC in vitro, validating its use against lung cancer by practitioners of traditional medicine including homeopathy.