• Radiation Oncology Journal
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• v.24 no.4
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• pp.237-242
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• 2006

$\underline{Purpose}$: We evaluated retrospectively the outcome of locally advanced non-small cell lung cancer patients treated with definitive radiotherapy to find out prognostic factros affecting survival. $\underline{Materials\;and\;Methods}$: 216 cases of stage IIIB non-small cell lung cancer were with treated radiotherapy at our Hospital between 1991 to 2002 and reviewed retrospectively. Cases were classified by mode of treatment and response to treatment. Patients showing complete response or partial response to treatment were included in the "response group", while those showing stable or progressive cancer were included in the "non-response group". $\underline{Results}$: 30 patients completed the planned radiotherapy treatments and 39 patients completed combined treatments or chemoradiotherapy. Median survival was 4.6 months for patients treated with radiotherapy and 9.9 months for those undergoing combined radiotherapy and chemotherapy. Survival rates for the first year were 13.3% with radiotherapy and 35.9% with chemoradiotherapy. In the second year, 3.3% of the radiotherapy patients survived and 20.5% of the patients receiving chemoradiotherapy survived. By the third year, 15.4% of the patients receiving the combined treatments survived. None of the patients treated with radiotherapy alone lived to the third year, however. Overall survival was significantly different between the radiotherapy patients and the combined chemoradiotherapy patients (p<0.001). In the response group, median survival was 7.2 months with radiotherapy and 16.5 months with combined therapy. In the non-response group, median survival was 4.4 months with radiotherapy and 6.7 months with combined treatments. Severe acute complications (grade 3) occurred in 2 cases using radiotherapy, and in 7 cases using combined therapy. $\underline{Conclusion}$: When the patients with stage IIIB non-small cell lung cancer received chemoradiotherapy, treatment response rate and overall survival was greater than with radiation alone.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6761-6766
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• 2014

Background: CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta-analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. Materials and Methods: Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to estimate the effects. Results: A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95%CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95%CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95%CI=1.93-4.72, p<0.00001). Conclusions: Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.

• Journal of Chest Surgery
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• v.40 no.10
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• pp.680-684
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• 2007

Background: Complete surgical resection is the most effective treatment for stage IB non-small cell lung cancer (NSCLC). Recurrence accounts for the disappointing survival rates after resection. There has been renewed interest in adjuvant therapy after complete resection. Appropriate selection of effective adjuvant therapy will depend on the prognostic factors for recurrence. Material and Method: The study included 114 patients with completely resected stage IB NSCLC. The variables selected for the study were gender, age, the type of resection, cell type, the degree of differentiation, the tumor size and the presence of visceral pleura invasion. The Kaplan-Meier method was used to estimate the survival and disease-free survival rate. The results were compared using the log rank test. Multivariate analysis was performed by Cox's proportional hazard model. Two-sided p-valves < 0.05 were considered to be statistically significant. Result: The 3-year overall survival and the disease-free survival rates were 87.0% and 79.4%, respectively. The degree of differentiation showed a significant influence on disease-free survival according to the univariate analysis. According to the multivariate analysis, a poor grade of differentiation was a significant poor prognostic factor. Conclusion: These results demonstrate that poor differentiation may be a poor prognostic factor for patients with completely resected IB NSCLC. Therefore, the patients with a poor grade of differentiation may require adjuvant therapies.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.417-424
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• 2011

Background: Recent evidences have revealed metabolic functions of p53 in cancer cells; adaptation or survival to metabolic stress and metabolic shift toward oxidative phosphorylation. However, further studies in clinical setting are needed. We investigated whether p53 protein expression, as a surrogate marker for loss of p53 function, is associated with metabolic features of stage I non-small cell lung cancer (NSCLC), focusing on tumor necrosis and maximal standardized uptake value (SUVmax) on $^{18}F$-fluorodeoxyglucose positron emission tomography. Methods: Clinical information was obtained from retrospective review of medical records. p53 expression was assessed by immunohistochemical staining. Results: p53 protein expression was detected in 112 (46%) of 241 NSCLC cases included in this study. p53 expression was independently associated with the presence of necrosis (odds ratio [OR], 2.316; 95% confidence interval [CI], 1.215~4.416; p=0.011). Non-adenocarcinoma histology (OR, 8.049; 95% CI, 4.072~15.911; p<0.001) and poorly differentiation (OR, 6.474; 95% CI, 2.998~13.979; p<0.001) were also independently associated with the presence of necrosis. However, p53 expression was not a significant factor for SUVmax. Conclusion: p53 protein expression is independently associated with the presence of necrosis, but not SUVmax.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.144-150
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• 1999

Background: Surgery has been considered the most effective and standard treatment modality in non-small cell lung cancer(NSCLC). However in stage IIIA lung cancer, the role of surgery is still controversial. To evaluate the role of surgery for stage IIIA NSCLC, we investigated the survival after surgery and the prognostic factors. Material and Method: We evaluated 158 consecutive cases of stage IIIA NSCLC patients operated on between 1990 and 1996. There were 130 male patients and 28 female patients, and the mean age was 58.5 years. All patients except one underwent lung resection beyond lobectomy and extended mediastinal dissection. Postoperative adjuvant therapy were undertaken in 145(94.8%) patients. All patients(153) were followed and the mean follow-up period was 21.4months. Result: Twenty nine cases of the postoperative complications developed in 25 patients (15.8%). There were 5 operative mortality cases(3.2%) and the main cause of death was acute respiratory distress syndrome (ARDS). Local or distant recurrences developed in 84 patients(54.9%). The 5-year survival of 153 patients was 29.6% and the median survival time was 18.0 months. The 5-year survival of non N2 disease group(36.8%) was better than that of N2 disease group(26.6%)(p=0.35) and the 5-year survival of squamous cell carcinoma (38.1%) was better than that of adenocarcinoma(25.7%)(p=0.39) however there were no significant differences. Regarding the postoperative adjuvant therapy, in combined therapy group(84 patients), radiotherapy group(37 patients) and chemotherapy group(24 patients), the 5-year survival were 31.3%, 32.4%, and 14.6% respectively. There was no difference of survival between radiotherapy and combined therapy group(p=0.31), however the survival of the combined therapy group was better than the chemotherapy group(p=0.005). The survival of the complete resection group(31.9%) was better than the incomplete resection group(16.6%) however there was no significant difference(p=0.19). Conclusion: These observations indicate that the good 5-year survival(29.6%) in patients with stage IIIA NSCLC result from the agressive surgical treatment including extensive mediastinal nodes dissection.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.984-991
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• 1998

Background: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. Methods: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed. first strand cDNAs were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. Results: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. Conclusion: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.489-496
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• 2003

To clarify the prognostic implication of the location and number of the metastatic mediastinal nodes in resected stage IIIA N2 non-small cell lung cancer. Material and Method: One hundred and seventy-four patients with resected non-small cell lung cancer who eventually proved to have pathologic stage IIIA N2 disease were studied. Patients who received preoperative induction therapy, non-curative operation or defined as operative mortality were excluded from this study. Result: In upper lobe tumors, there was no difference in 5-year survival according to the involvement of lower mediastinal nodes (32.3% vs 25.6%, p＝0.86). In lower lobe tumors, no difference was found in 5-year survival according to the involvement of upper mediastinal nodes (25.1% vs 14.1%, p＝0.33). There was no significant difference in 5-year survival between patients with or without metastatic subcarinal node (20.9% vs 25.6%, p＝0.364). In terms of the number of metastatic mediastinal nodes, 5-year survival was better in single station group (26.3%) than multiple station group (18.3%) (p＝0.048). In multiple station N2 group, the patients who received postoperative chemotherapy and radiation therapy had better 5-year survival (34.2%) (p＝0.01). Cox's proportional hazards model revealed that the age $\geq$60 (O.R: 1.682, p＝.006), multiple station N2 (O.R: 1.503. p＝0.021), pneumonectomy (O.R: 1.562, p＝0.018), postoperative chemotherapy and radiation therapy (O.R: 0.625, p＝0.012) were the factors affecting the postoperative survival. Conclusion: Multiple station N2 disease was the important prognostic factor for postoperative survival in resected stage IIIA N2 non-small cell lung cancer. Postoperative chemotherapy and radiotherapy were thought to improve the survival in case of multiple station N2 disease.

• Journal of Chest Surgery
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• v.57 no.5
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• pp.460-466
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• 2024

Background: Numerous studies have investigated methods of predicting postoperative pulmonary complications (PPCs) in lung cancer surgery, with chronic obstructive pulmonary disease (COPD) and low forced expiratory volume in 1 second (FEV₁) being recognized as risk factors. However, predicting complications in COPD patients with preserved FEV₁ poses challenges. This study considered various diffusing capacity of the lung for carbon monoxide (DL_CO) parameters as predictors of pulmonary complication risks in mild COPD patients undergoing lung resection. Methods: From January 2011 to December 2019, 2,798 patients undergoing segmentectomy or lobectomy for non-small cell lung cancer (NSCLC) were evaluated. Focusing on 709 mild COPD patients, excluding no COPD and moderate/severe cases, 3 models incorporating DL_CO, predicted postoperative DL_CO (ppoDL_CO), and DL_CO divided by the alveolar volume (DL_CO/VA) were created for logistic regression. The Akaike information criterion and Bayes information criterion were analyzed to assess model fit, with lower values considered more consistent with actual data. Results: Significantly higher proportions of men, current smokers, and patients who underwent an open approach were observed in the PPC group. In multivariable regression, male sex, an open approach, DL_CO <80%, ppoDL_CO <60%, and DL_CO/VA <80% significantly influenced PPC occurrence. The model using DL_CO/VA had the best fit. Conclusion: Different DL_CO parameters can predict PPCs in mild COPD patients after lung resection for NSCLC. The assessment of these factors using a multivariable logistic regression model suggested DL_CO/VA as the most valuable predictor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4623-4627
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• 2014

Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4279-4282
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• 2013

Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.