• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.475-484
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• 2002

Background : Unresectable non-small cell lung cancer has a poor response to chemotherapy and has an unfortunate prognosis. More effective and less toxic cytotoxic agents are needed to improve the outcome of these patients. The efficacy and safety of vinorelbine monotherapy in these advanced lung cancer patients was evaluanted. Materials and Methods : Sixteen patients with non-small cell lung cancer in stage III or IV, who received vinorelbine alone as an initial anticancer chemotherapy from June 1996 to December 2000 were enrolled in this study. Vinorelbine was given intravenously at a dose 30mg/$m^2$ every week. Results : A mong the sixteen patients, six had a partial response(38%) and the median survival was 16 weeks. The median response duration was 27 weeks (95% CI 6-47), and the time to progression was 16 weeks(95% CI 6-26). Among a total of 112 cycles, neutropenia(WHO grade 3 or 4) and anemia(grade 3) occurred in 9% and 3%, respectively. Only 1 patient required hospitalization for neutropenic fever. Non-hematologic toxicity was minor and was easily controlled. Conclusion : Vinorelbine monotherapy was well tolerated, and moderately effective in patients with advanced non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.344-351
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• 2005

Background : Both gemcitabine and vinorelbine are effective anticancer drugs with mild toxicity on non-small cell lung cancer, and monotherapy of these drugs are effective as a second-line chemotherapy. The aim of this trial was to assess the response and toxicity of a combination of gemcitabine and vinorelbine in patients of previously treated for non-small cell lung cancer. Materials and Methods : 24 patients, initial stage III A/B,IV and previously treated with platinium and taxane based regimens, were enrolled from June 2000 to March 2004. The regimens consisted of vinorelbine $25mg/m^2$ followed by an infusion of gemcitabine $1000mg/m^2$ on day 1 and day 8 every three weeks. This course was repeated more than twice. Results : Twenty-four patients were analyzed for the response, survival rate, and toxicities. The overall response was 17% with a complete remission rate of 4%. The median time-to progression (TTP) was 3.1 months (95%, CI 1-10months), and the survival time was 8.2 months (95%, CI 1-23 months). The grade 3/4 toxicities encountered were neutropenia (12.5%), anemia (0%), thrombocytopenia (0%). Non-hematological 3/4 toxicities were not observed. Conclusion : A combination of gemcitabine and vinorelbine in patients previously treated for non-small cell lung cancer provides a relatively good response rate, and a low toxicity profile. However, further study will be needed to confirm its effectiveness.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.161-166
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• 2014

Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1233-1239
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• 2014

Background: The incidence of brain metastases (BM) varies in patients with non-small cell lung cancer (NSCLC), calls into question the value of prophylactic cranial irradiation (PCI). It is possible that clinicopathologic characteristics are associated with the development of BM, but these have yet to be identified in detail. Thus, we conducted the present meta-analysis on risk factors for BM and the value of PCI in patients with NSCLC. Methods: Eligible data were extracted and the risk factors for BM and the value of PCI in patients with NSCLC were analyzed by calculating the pooled odds ratio (OR). Heterogeneity was detected using Q and I-squared statistics, and publication bias was tested by funnel plots and Egger's test. Results: Six randomized controlled trials with a focus on the value of PCI and 13 eligible studies with a focus on risk factors for BM were included. PCI significantly reduced the incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.34, 95% confidence interval = 0.37-0.59). Compared with non-squamous cell carcinoma, squamous cell carcinoma was associated with a low incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.47, 95% confidence interval =0.34-0.65). The funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis. Conclusions: This meta-analysis provides statistical evidence that compared with non-squamous cell carcinoma, squamous cell carcinoma can be used as a predictor for BM in patients with NSCLC, and PCI might reduce the incidence of BM in patients with NSCLC, but does not provide a survival benefit.

• Radiation Oncology Journal
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• v.32 no.2
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• pp.70-76
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• 2014

Purpose: To review the results of postoperative radiation therapy (PORT) for residual non-small cell lung cancer (NSCLC) following surgical resection and evaluate multiple clinicopathologic prognostic factors. Materials and Methods: A total of 58 patients, who completed scheduled PORT for positive resection margin, among 658 patients treated with PORT from January 2001 to November 2011 were retrospectively analyzed. Radiation therapy was started at 4 to 6 weeks after surgery. Chemotherapy was also administered to 35 patients, either sequentially or concurrently with PORT. Results: The median age of patients was 63 years (range, 40 to 82 years). The postoperative pathological stage I NSCLC was diagnosed in 10 (17.2%), stage II in 18 (31.0%), and stage III in 30 patients (51.7%). Squamous cell carcinoma was identified in 43, adenocarcinoma in 10, large cell in 1, others in 4 patients. Microscopic residual disease (R1) was diagnosed in 55 patients (94.8%), and the remaining three patients were diagnosed with gross residual disease (R2). The median dose of PORT was 59.4 Gy (range, 50.0 to 64.8 Gy). Chemotherapy was administered to 35 patients (60%), and the median follow-up time was 22.0 months (range, 6.0 to 84.0 months). The 3-year locoregional relapse-free survival and distant metastasis-free survival rates were 82.1% and 52.9%, respectively. The median overall survival was 23.8 months (range, 6.0 to 84.1 months), and the 3-year overall survival rate was 58.2%. Chemotherapy did not influence the failure pattern or survival outcome. Conclusion: PORT is an effective modality for improving local tumor control in incompletely resected NSCLC patients. Major failure pattern was distant metastasis despite chemotherapy.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.10-15
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• 2010

Background: Lung cancer is the most common cause of cancer mortality in Korea. The TNM stage at presentation in patients with non-small cell lung cancer (NSCLC) has the greatest impact on prognosis. Patients who undergo a complete resection for NSCLC are likely to develop recurrent and/or metastatic disease. There are several factors influencing the development of recurrence. We explored risk factors of recurrence in patients with stages I and II NSCLC, who had undergone curative resection. Methods: We reviewed patients who had complete surgical resection as definitive treatment for stage I or II. Patients followed up for more than 36 months. We evaluated several factors which might have relationship with recurrence, such as patient's demographic factors, TNM staging, pathologic finding, tumor markers and surgical technique. Results: A total of 75 patients were enrolled for analysis, of whom 58 were men and 17 were women with mean age of 61 (range, 37 to 76) years. The average size of tumors was 3.9 cm (0.7 to 10 cm). There were 64 patients with stage I NSCLC and 11 with stage II NSCLC. Among 64 patients with stage I NSCLC, 35 patients showed recurrences whereas 8 patients have recurred in stage II NSCLC. Grade of differentiation of tumor was closely related to the recurrence. Seventy-five percent of patients who had poor tumor differentiation experienced a recurrence. In contrast, 3 patients of twelve had recurrences, who revealed differentiation in their tissue (p<0.05). Conclusion: Tumor differentiation could be a predictive factor for tumor recurrence in patients who have undergone curative resection for stage I or II NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.689-692
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• 2015

Background: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. Materials and Methods: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. Results: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. Conclusions: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.460-469
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• 2017

Heat shock proteins (HSPs) are induced as a self-defense mechanism of cells when exposed to various external stresses, such as high fever, infection, free radicals, and heavy metals. They affect the prognosis in the process of tumor formation. HSP is classified into four families: HSP27, HSP60, HSP90, and HSP100, depending on molecular weight. Heat shock protein 90 (HSP90), a molecular chaperone, plays an important role in the cellular protection against various stressful stimuli and in the regulation of cell cycle progression and apoptosis. In the present study, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC), and the correlation of their expression levels with clinicopathologic factors and patient survival rates. The result of this study can be summarized as follows; $HSP90{\alpha}$ showed higher expression in patients with no lymphovascular invasion (p=0.014). $HSP90{\beta}$ showed a higher expression of squamous cell carcinoma (p=0.003), and an over expression of glucose-related protein (GRP94) was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed a significant association with the survival status in patients with NSCLC. This study also indicates that $HSP90{\alpha}$ might contribute more to the carcinogenesis of NSCLC than $HSP90{\beta}$, and GRP94 and isoform selectivity should be considered when HSP90 inhibitors are studied or utilized in the treatment of NSCLC.

• The Plant Pathology Journal
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• v.18 no.3
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• pp.115-120
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• 2002

Xanthomonas axonopodis pv. glycines, the causal agent of bacterial pustule of soybean, induces hypersensitive response (HR) in a non-host plant, hot pepper (Capsicum annuum). A wild-type strain (8ra) and its non-patho-genic mutant (8-13) of X. axonopodis pv. glycines were inoculated into the pepper leaf tissues and their subcellular responses to the bacterial infections were examined by electron microscopy. Intrastructural changes related to HR were found in the leaf tissues infected with 8ra from 8 h after inoculation, characterized by separation of plasmalemma from the cell wall, formation of small vacuoles and vesicles, formation of cell wall apposition, and cellular necrosis. No such responses were observed in the tissues infected with the mutant. In 8ra, the bacterial cells were attached to the cell walls, with the cell wall material dissolved into and appearing to encapsulate the bacterial cells. The bacterial cells later became entirely embedded in the cell wall material. On the other hand, in 8-13, the bacterial cells were usually not attached tightly to the plant cell wall, and no or poor encapsulation of the bacteria by the wall material occurred, although these were encircled by rather loose wall materials at the later stages.

• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.271-278
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• 2010

Background: Recent studies have demonstrated that the epidermal growth factor receptor (EGFR) genotype is the most important predictive marker to EGFR-tyrosine kinase inhibitors (TKIs) and first-line gefitinib treatment will be approved in the near future for use in non-small cell lung cancer (NSCLC) patients with the EGFR mutation. Direct sequencing is known to be the standard for detecting EGFR mutations; however, it has limited sensitivity. Peptide nucleic acids (PNA)-mediated PCR clamping method is a newly introduced method for analyzing EGFR mutations with increased sensitivity and stability. Methods: A total of 71 NSCLC patients were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. Sixty-nine patients were analyzed for clinicopathologic correlation with EGFR genotype; 2 patients with indeterminate results were excluded. In order to determine EGFR-TKI drug response, 57 patients (42 gefitinib, 15 erlotinib) were included in the analysis. Results: The EGFR mutation rate was 47.8%. Being female, a non-smoker, and having adenocarcinoma were favorable clinicopathologic factors, as expected. However, more than a few smokers (33.3%), male (28.1%), and patients with non-adenocarcinoma (28.6%) had the EGFR mutation. Having a combination of favorable clinicopathologic factors did not increase the EGFR mutation rate significantly. Drug response to EGFR-TKIs showed significant differences depending on the EGFR genotype; ORR was 14.3% for wild type vs 69.0% for mutant type; DCR is 28.6% for wild type vs 96.6% for mutant type. The median EGFR-TKI treatment duration is 7.6 months for mutant type group and 1.4 months for wild type group. Conclusion: EGFR genotype determined using the PNA-mediated PCR clamping method is significantly correlated with the clinical EGFR-TKI responses and PNA-mediated PCR.