• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1507-1513
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• 2015

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Journal of Chest Surgery
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• v.52 no.4
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• pp.195-204
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• 2019

Lobectomy is considered the standard strategy for early-stage non-small cell lung cancer (NSCLC). However, sublobar resection for NSCLC has recently received increased attention. The objective of this study was to compare 5-year survival, recurrence-free survival, postoperative mortality, and postoperative morbidities in patients who received segmentectomy versus those who received lobectomy through a meta-analysis. Sixteen studies were included and the combined hazard ratios or odds ratios were calculated. The results revealed that the 5-year survival rate after segmentectomy was comparable to that of lobectomy for stage IA NSCLC. However, segmentectomy for stage I NSCLC had lower rates of postoperative mortality and morbidities than lobectomy.

• Tuberculosis and Respiratory Diseases
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• v.86 no.1
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• pp.14-22
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• 2023

A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.

• Tuberculosis and Respiratory Diseases
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• v.87 no.1
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• pp.31-39
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• 2024

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.973-981
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• 1998

Background: About 30% to 40% of the patients with pathologic stage I non-small cell lung cancer (NSCLC) die within 5 years after complete resection. The identification of poor prognostic factors and the application of additional treatment are very important to improve the survival rate in resected stage I NSCLC. Materials and methods: Sixty-eight(68) patients who had been diagnosed postoperatively between Janury 1989 and December 1995 as having stage I non-small cell lung cancer according to the TNM classification were studied. The postoperative 5-year survival rate was calculated with the Kaplan-Meier method, and clinico- histopathologic factors including age, sex, operative method, type of tumor cell, T factor, grade of the differentiation in a squamous cell carcinoma, invasion of blood vessel and expression of the nm23-H1 protein were investigated and analyzed. Results: The median survival of the entire group of patients was 58$\pm$3 months, with a 5-year survival of 58.9%. In univariate analysis, invasion of blood vessel and poor differentiation of the tumor cell in a squamous cell carcinoma significantly worsened the survival. In multivariate analysis, invasion of blood vessel and grade of the differentiation of the tumor cells in a squamous cell carcinoma remained independent prognostic factors. High expression of the nm23-H1 protein was related to a high postoperative 5-year survival in comparision with low expression of the nm23-H1 pretein (73.0% vs 50.7%), but there was no statistical significance. Conclusions: These results highlight the negative prognostic value of poor differentiation of tumor cells in a squamous cell carcinoma and invasion of blood vessel in stage I non-small cell lung cancer. Also, further studies are necessary to be determined prognostic value of the T factor and expression of the nm23 protein in non-small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2089-2094
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• 2014

Background: Although many prognostic factors have been identified for lung cancers, new ones are needed to determine the course of the disease. Recently, a high neutrophil to lymphocyte ratio (NLR) prior to surgery or treatment has been shown to be an indicator of prognosis for cancer. The aim of this study was to investigate the value of NLR as a prognostic factor and the correlation between NLR and other probable clinical prognostic factors in non small cell lung cancer patients prior to treatment. Materials and Methods: Data of patients who were diagnosed with non-small cell lung cancer in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR was calculated before the application of any treatment. Results: A total of 299 patients, 270 (90%) males and 29 (10%) females, were included in the study. Age (p<0.001) stage (p<0.001), Eastern Cooperative Oncology Group performance status (p<0.001), weight loss (p<0.001), anemia (p<0.001), histopatology (p<0.001), NLR ${\geq}3$ (p=0.048), NLR ${\geq}4$ (p=0.025) and NLR ${\geq}5$ (p=0.018) were found to be the prognostic factors. Age, anemia, Eastern Cooperative Oncology Group performance status, the stage, NLR (${\geq}5$) were an independent prognostic factors. There was a positive correlation between NLR and the Eastern Cooperative Oncology Group performance status (0.23, p=0.001), the C reactive protein levels (r=0.36, p<0.001). Conclusions: Prior to treatment high NLR was found as an independent poor prognosis factor. Besides, NLR correlated with Eastern Cooperative Oncology Group performance status and the C reactive protein levels.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.639-643
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• 2013

Aim: Connexin 43 (Cx43) and E-cadherin are important biomarkers related with cancer. Their expression at protein and mRNA levels was here investigated in 50 primary lung carcinoma tissues and 20 samples of adjacent normal tissue of Chinese patients with non-small cell lung cancer (NSCLC). Methods: Protein and mRNA expression were evaluated by ABC immunohistochemistry and RT-PCR. Results: (1) The positive expression rates of Cx43 and E-cadherin protein were higher in the adjacent normal tissues than those in the primary lung carcinoma tissues; (2) the positive expression rates of Cx43 and E-cadherin protein decreased with NSCLC progression; (3) the expression of E-cadherin protein was not related with the pathological type of NSCLC; and (4) the relative quantity of the Cx43 or E-cadherin mRNA expression was correlated with the the histological type, clinical stage, cancer cell differentiation and the lymph node metastasis. Conclusion: The data suggested that the Cx43 and E-cadherin are reduced with NSCLC progression, and might be important biomarkers for judging the metastasis and prognosis.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.149-155
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• 2019

In metastatic non-small cell lung cancer (NSCLC), the role of radiotherapy (RT) has been limited to palliation to alleviate the symptoms. However, with the development of advanced RT techniques, recent advances in immuno-oncology therapy targeting programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) and targeted agents for epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation allowed new roles of RT in these patients. Within this metastatic population, there is a subset of patients with a limited number of sites of metastatic disease, termed as oligometastasis that can achieve long-term survival from aggressive local management. There is no consensus on the definition of oligometastasis; however, most clinical trials define oligometastasis as having 3 to 5 metastatic lesions. Recent phase II randomized clinical trials have shown that ablative RT, including stereotactic ablative body radiotherapy (SABR) and hypofractionated RT, to primary and metastatic sites improved progression-free survival (PFS) and overall survival (OS) in patients with oligometastatic NSCLC. The PEMBRO-RT study, a randomized phase II study comparing SABR prior to pembrolizumab therapy and pembrolizumab therapy alone, revealed that the addition of SABR improved the overall response, PFS, and OS in patients with advanced NSCLC. The efficacy of RT in oligometastatic lung cancer has only been studied in phase II studies; therefore, large-scale phase III studies are needed to confirm the benefit of local ablative RT in patients with oligometastatic NSCLC. Local intensified RT to primary and metastatic lesions is expected to become an important treatment paradigm in the near future in patients with metastatic lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3945-3948
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• 2013

Background: Lung cancer is the leading cause of cancer death, late diagnosis being the main obstacle to improving the outcomes with stage at diagnosis as an important prognostic factor. Relationships between ABO blood groups and risk of benign or malignant diseases have been observed and in this study, we aimed to investigate whether they might affect prognosis and response to chemoradiotherapy in patients with local advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eighty-one patients with non-metastatic local advanced NSCLC were included in the study. ABO blood groups were A in 45 (55.6%), B in 7 (8.6%), AB in 8 (9.9%), and O in 21 (25.9%) patients. The patients were also divided two groups according to blood group A (45 patients) and non-A (B, AB and O; 36 patients). Response to chemoradiotherapy was complete remission in 10 (12.3%), disease regression in 42 (51.9%), stable disease in 12 (14.8%), and disease progression in 17 (21.0%) patients. Results: There was no significant difference among ABO blood group categories or between patients with A blood group and those with non-A blood group in terms of responses to chemoradiotherapy (p>0.05). There were also no significant differences regarding overall and disease-free survival rates. Conclusion: The ABO blood group system has no significant effect on prognosis and response to chemoradiotherapy in patients with non-metastatic NSCLC.