• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7559-7562
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• 2014

Currently the most important prognostic factor in lung cancer is the stage. In the current lung TNM classification system, N category is defined exclusively by anatomic nodal location though, in other type of tumours, number of lymph nodes is confirmed to be a fundamental prognostic factor. Therefore we evaluated the number of mediastinal lymph nodes as a prognostic factor in locally advanced NSCLC after multimodality treatment, observing a significant effect of the number of lymph nodes in terms of OS (p<0.01) and DFS (p<0.001): patients with a low number of positive mediastinal nodes have a better prognosis.

• Journal of Chest Surgery
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• v.48 no.4
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• pp.252-257
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• 2015

Background: Lobectomy is the generally accepted standard treatment for early-stage non-small cell lung cancer (NSCLC). However, especially in elderly patients, it is often necessary to perform pneumonectomy in order to maximize the likelihood of curative treatment, although pneumonectomy is a challenging procedure. Methods: We analysed patients who were clinically diagnosed with stage I NSCLC and underwent pneumonectomy with curative intent from 2004 to 2011. The patients were divided into an elderly group (${\geq}70$ years) and a younger group (<70 years). We retrospectively analysed the outcomes of these groups of patients in order to characterize the role of pneumonectomy as a treatment for elderly patients with clinical stage I NSCLC. Results: Thirty patients younger than 70 years of age (younger group) and fourteen patients 70 years of age or older (elderly group) who underwent pneumonectomy were enrolled in the present study. The median follow-up period was 35 months (range, 0 to 125 months). The perioperative mortality rate (within 90 days after the operation) was 7.1% in the elderly group and 6.7% in the younger group (p=0.73). No significant differences between the two groups were observed regarding the occurrence of pneumonia, acute respiratory distress syndrome, cardiac arrhythmia, bronchopleural fistula, and vocal cord paralysis. The overall five-year survival rate was 79.4% in the younger group and 35.7% in the elderly group, which was a significant difference (p=0.018). The five-year disease-free survival rate was 66.7% in the younger group and 35.7% in the elderly group, but this difference was not statistically significant (p=0.23). Conclusion: Although elderly patients with early stage lung cancer showed a worse long-term survival rate after pneumonectomy than younger patients, the outcomes of elderly patients were similar to those of younger patients in terms of perioperative mortality and postoperative complications. Patients should not be denied pneumonectomy solely due to old age.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.160-170
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• 2006

Background : The aberrant promoter hypermethylation of p16INK4a, as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of $p16^{INK4a}$ promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation. Methods : Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16INK4amethylation was determined using methylation-specific polymerase chain reaction. Results : $p16^{INK4a}$ methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum. Conclusions : There was a higher level of $p16^{INK4a}$ methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that $p16^{INK4a}$ promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5473-5476
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• 2013

Background: In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. Materials and Methods: Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. Results: A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). Conclusions: Molecular methods have been changing rapidly in today's world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods.

• Journal of Life Science
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• v.29 no.12
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• pp.1305-1313
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• 2019

Licochalcone (LC), isolated from the roots of Glycyrrhiza inflata has multiple pharmacological effects including anti-inflammatory and anti-tumor activities. To date, Licochalcone C (LCC) has induced apoptosis and inhibited cell proliferation in oral and bladder cancer cells, but lung cancer has not yet been studied. In addition, no study reported LCC-induced autophagy in cancer until now. The present study was designed to investigate the effect of LCC on gefitinib-sensitive and -resistant lung cancer cells and elucidate the mechanism of its action. The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay data showed that LCC significantly inhibited cell viability in non-small cell lung cancer (NSCLC) HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) cell lines. Interestingly, Annexin V/7-aminoactinomycin D double staining and cell cycle analysis showed an apoptosis rate within about 20% at the highest concentration of LCC. LCC induced G2/M arrest by reducing the expression of the cell cycle G2/M related proteins cyclin B1 and cdc2 in NSCLC cell lines. Treatment of LCC also induced autophagy by increasing the expression of the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) and the protein autophagy-related gene 5 involved in the autophagy process. In addition, LCC increased the production of reactive oxygen species (ROS), and the cell viability was partially restored by treatment with the ROS inhibitor N-acetyl-L-cysteine. In western blotting analysis, the expression of cdc2 was increased and LC3 was decreased by the simultaneous treatment of NAC and LCC. These results indicate that LCC may contribute to anti-tumor effects by inducing ROS-dependent G2/M arrest and autophagy in NSCLC. In conclusion, LCC treatment may be useful as a potential therapeutic agent against NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.120-128
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• 2005

Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6311-6318
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• 2012

Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.445-449
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• 2011

Non small cell lung cancer (NSCLC) frequently metastasizes to brain, bone, liver, and adrenal glands. While an autopsy of NSCLC reveals some cases of metastasis to the kidney, clinical detection of renal metastases is extremely rare. Furthermore, metastases to the kidney usually present as multifocal or bilateral lesions and solitary renal metastases are usually suspected to be renal cell carcinoma. We now report a case of asymptomatic solitary renal metastasis from a primary squamous cell carcinoma, which was detected by routine surveillance with abdominal CT after curative surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3997-4002
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• 2015

Background: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. Results: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ${\geq}3.24$) and PNI (<49.5 or ${\geq}49.5$). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). Conclusions: NLR (${\geq}3.24$) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4153-4158
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• 2014

Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III ${\beta}$-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin-based first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.