• Tuberculosis and Respiratory Diseases
• /
• v.70 no.4
• /
• pp.301-306
• /
• 2011

Background: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. Methods: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. Results: The pre chemotherapy values (Response group $41.36{\pm}1.72$ vs. Non-response group $41.33{\pm}1.54$, p=0.78) and post chemotherapy values (Response group $39.92{\pm}1.81$ vs. Non-response group $40.41{\pm}1.47$, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). Conclusion: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.99.2-99.2
• /
• 2003

One of the major limitations in using adenoviral vector for gene therapy is inefficient infection of host cells. The presence of coxsackievirus and adenovirus receptor (CAR) and ${\alpha}$-integrin on cell surfaces is required for efficient adenovirus infection. In this study, we investigated the effect of trichostatin A, a histone deacetylase inhibitor, on transfection efficiency after transduction of adenovirus mediated p16$\^$INK4a/ gene transfer. In our previous study, p16$\^$INK4a/ tumor suppressor gene transfer in the non-small cell lung cancer cells (A549 cells) by transduction of recombinant adenovirus (Ad5CMV-p16) resulted in significant inhibition of cancer cell proliferation. (omitted)

• Journal of Chest Surgery
• /
• v.31 no.12
• /
• pp.1200-1205
• /
• 1998

Background: Lung cancer formation is a multistage process involving activation of protooncogene and inactivation of tumor suppressor genes. We evaluate the significance of cyclin D1, p53, bcl-2 gene mutations in patients with curatively resected stage IIIA non-small cell lung cancer(NSCLC). Material and Method: One hundred consecutive cases of stage IIIA lung cancers from patients operated on curatvely between 1990 and 1995 for which adequate paraffin blocks and clinical history were available. Immunohistochemical studies were performed on the representative tissue sections from each case by the labelled streptovidin- biotin method. Sections for cyclin D1, p53, Bcl-2 immunostaining were pretreated in a microwave oven for 10 to 20 minutes in citrate buffer before immunostaining. The overnight incubation with NCL-cyclin D1-GM for cyclin D1, with clone DO-7 for p53, with clone 124 for bcl-2 was done. Mean follow-up was 24.1 months (range 2-84 months) after operation. Result: One hundred cases of lung cancers were composed of 56 cases of squamous cell carcinoma, 37 cases of adenocarcinoma, 5 cases of adenosquamous cell carcinoma, and 2 cases of large cell carcinoma. The 5-year survival was 32.1%. The positive expression rate of cyclin D1 was 35%, p53 was 56%, and bcl-2 was 17%. But there were no correlation between cyclin D1, p53, Bcl-2 protein expression and survival. Conclusion: These observation indicate that cyclin D1, p53, bcl-2 protein overexpression might be implicated in the oncogenesis of non-small cell lung carcinomas but they have no usefulness as a prognostic marker.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2871-2877
• /
• 2013

Objectives: To evaluate the safety, efficacy, and invasiveness of lobectomy by video-assisted thoracoscopic surgery (VATS) in the treatment of stage I/II non-small cell lung cancer (NSCLC). Methods: A total of 148 patients presenting with Stage I or II NSCLC were enrolled into our study, comprising 71 who underwent VATS and 77 patients undergoing conventional thoracotomic lobectomy, in combination with systematic lymph node resection. Results: It was found that VATS was superior to conventional thoracotomy in terms of the duration of surgery, intraoperative blood loss, frequency of the need to administer postoperative analgesia, thoracic intubation indwelling time, post-operative hospital stay, and survival rate (P<0.05). We saw no obvious difference in the number of resected lymph nodes with either approach. Conclusions: VATS lobectomy is a safe and reliable surgical approach for the treatment of Stage I/II NSCLC, characterized by significantly minimal invasiveness, rapid post-operative recovery, and markedly lower loss of blood.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.3
• /
• pp.761-766
• /
• 2012

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.1
• /
• pp.43-50
• /
• 2007

Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.11
• /
• pp.6305-6309
• /
• 2013

Background: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. Materials and Methods: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. Results: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down-regulate the expression of MMP-3, Twist and Snail. Conclusions: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes.

• Radiation Oncology Journal
• /
• v.35 no.2
• /
• pp.180-184
• /
• 2017

Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second $[FEV1]{\leq}1L$) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function ($FEV1{\leq}1L$).

• Tuberculosis and Respiratory Diseases
• /
• v.82 no.3
• /
• pp.211-216
• /
• 2019

Background: Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods: Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel $25mg/m^2$ on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion: Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

• Korean Journal of Clinical Pharmacy
• /
• v.18 no.2
• /
• pp.75-83
• /
• 2008

Purpose: Currently lung cancer ranks second in cancer for incidence rate and is a disease that ranks first for a death rate by cancerous growth because it is already advanced at the time of diagnosis. The purpose of this paper was to analyze the factors that affect the effectiveness of and rash occurrence by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) in patients with non-small cell lung cancer. Methods: A retrospective chart review of 100 patients, who took EGFR TKI (erlotinib, gefitinib) among patients who were diagnosed with non-small cell lung cancer in a Hospital in Korea between May 2005 and February 2008, was conducted. The drug effectiveness was evaluated by Response Evaluation Criteria In Solid Tumor. Results: EGFR mutation was the only factor associated with drug response (complete response and partial response). When stable disease was added to drug response as the evaluation parameter, ECOG and rash as well as EGFR mutation were found to be important factors. Survival, however, was not affected by EGFR mutation. The factors influenced on survival were older age (${\geq}65$), low ECOG ($1{\sim}2$), adenocarcinoma and rash. In the case of rash, group with EGFR mutation or low ECOG showed significantly higher chance of occurrence. There was no significant difference in rash occurrence between gefitinib and erlotinib groups. Conclusions: Based on the results, EGFR mutation positive and low ECOG ($1{\sim}2$) were significantly important factors for both effectiveness of EGFR TKI and rash occurrence. Also, rash itself was found to be an independently significant factor for the disease control and survival. Therefore, while administering EGFR TKI, patients who have the factors associated with rash occurrence should be closely monitored for effective and safe drug therapy.