• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5551-5556
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• 2012

Cytological examination is widely used as a diagnostic tool because of the ease of collecting cells from the involved area. However, the diagnostic yield of cytological examination is unsatisfactory; the reasons include sampling error, poorly prepared samples, small numbers of malignant cells, and low grades of cellular atypia. In this study, we focused on the high infectivity of adenovirus towards epithelial cells and applied the luciferase-expressing adenoviral vector to a new cancer cell detection tool. In addition, adenoviral infectivity was enhanced by modifying viral fiber proteins. The sensitivity of the diagnostic tool was tested using the NCI-H1299 lung cancer cell line, and validated in body fluid samples from cancer patients with a variety of etiology. Results showed that the adenovirus efficiently transfected NCI-H1299 with high sensitivity. Only 10 cancer cells were sufficient for detection of luciferase signals. In body fluid samples, the adenovirus confirmed the diagnosis for malignant and benign cancer, but not in non-epithelial cell derived samples. This study provides proof-of-concept for a more reliable and sensitive diagnostic tool for epithelium-derived cancer.

• Journal of Chest Surgery
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• v.57 no.1
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• pp.44-52
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• 2024

Background: Visceral pleural invasion (VPI) is a poor prognostic factor that contributes to the upstaging of early lung cancers. However, the preoperative assessment of VPI presents challenges. This study was conducted to examine intraoperative pleural carcinoembryonic antigen (pCEA) level and maximum standardized uptake value (SUVmax) as predictive markers of VPI in patients with clinical T1N0M0 lung adenocarcinoma. Methods: A retrospective review was conducted of the medical records of 613 patients who underwent intraoperative pCEA sampling and lung resection for non-small cell lung cancer. Of these, 390 individuals with clinical stage I adenocarcinoma and tumors ≤30 mm were included. Based on computed tomography findings, these patients were divided into pleural contact (n=186) and non-pleural contact (n=204) groups. A receiver operating characteristic (ROC) curve was constructed to analyze the association between pCEA and SUVmax in relation to VPI. Additionally, logistic regression analysis was performed to evaluate risk factors for VPI in each group. Results: ROC curve analysis revealed that pCEA level greater than 2.565 ng/mL (area under the curve [AUC]=0.751) and SUVmax above 4.25 (AUC=0.801) were highly predictive of VPI in patients exhibiting pleural contact. Based on multivariable analysis, pCEA (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.14-7.87; p=0.026) and SUVmax (OR, 5.25; 95% CI, 1.90-14.50; p=0.001) were significant risk factors for VPI in the pleural contact group. Conclusion: In patients with clinical stage I lung adenocarcinoma exhibiting pleural contact, pCEA and SUVmax are potential predictive indicators of VPI. These markers may be helpful in planning for lung cancer surgery.

• Tuberculosis and Respiratory Diseases
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• v.66 no.5
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• pp.380-384
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• 2009

Drug-induced subacute cutaneous lupus erythematosus (SCLE) is associated with use of the following classes of medications: anti-hypertensives, anti-cholesterolemia, anti-psychotics, and anti-inflammatory drugs. Docetaxel is an anti-neoplastic agent, which is widely used for treatment of non-small cell lung cancer. Few cases of docetaxel-induced SCLE have been reported in the medical literature. Here, we report the case of a 58-year-old female patient who developed drug-induced SCLE after administration of docetaxel. After 4 cycles of chemotherapy with docetaxel and cisplatin, erythematous skin eruptions developed on the patient's face. Skin biopsies of the eruptions were remarkable for interfacing dermatitis with basement membrane thickening. Immunofluorescent study revealed characteristic features of SCLE, including granular deposition of IgM, C3, and apoptotic bodies along the basement membrane. The skin eruptions resolved gradually after cessation of drug and with the use of topical corticosteroids.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.216-223
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• 2001

Purpose : We evaluated retrospectively the outcomes of inoperable squamous cell lung cancer patients treated with radiotherapy to find out prognostic factors affecting survival. Materials and methods : Four hundred and eleven patients diagnosed as squamous cell lung cancer between November 1988 and December 1997 were the basis of this analyses. The planned dose to the gross tumor volume was ranged from 30 to 70.2 Gy. Chemotherapy was combined in 72 patients $(17.5\%)$ with the variable schedule and drug combination regimens. Follow-up period ranged from 1 to 113 months with the median of 8 months and survival status was identified in 381 patients $(92.7\%)$. Overall survival rate was calculated using the Kaplan-Meier method. Results : Age ranged from 23 years to 83 years with the median 63 years. The male to female ratio was about 16:1. For all 411 patients, the median overall survival was 8 months and the 1-year survival rate (YSR), 2-YSR, and 5-YSR were $35.6\%,\;12.6\%,\;and\;3.7\%$, respectively. The median and 5-YSR were 29 months and $33.3\%$ for Stage IA, 13 months and $6.3\%$ for Stage IIIA, and 9 months and $3.4\%$ for Stage IIIB, respectively(p=0.00). The median survival by treatment aim was 11 months in radical intent group and 5 months in palliative, respectively (p=0.00). Of 344 patients treated with radical intent, median survival of patients (N=247) who received planned radiotherapy completely was 12 months while that of patients (N=97) who did not was 5 months (p=0.0006). In the analyses of the various prognostic factors affecting to the survival outcomes in 247 patients who completed the planned radiotherapy, tumor location, supraclavicular LAP, SVC syndrome, pleural effusion, total lung atelectasis and hoarseness were statistically significant prognostic factors both in the univariate and multivariate analyses while the addition of chemotherapy was statistically significant only in multivariate analyses. The acute radiation esophagitis requiring analgesics was appeared in 49 patients $(11.9\%)$ and severe radiation esophagitis requiring hospitalization was shown in 2 patients $(0.5\%)$. The radiation pneumonitis requiring steroid medication was shown in 62 patients $(15.1\%)$ and severe pneumonitis requiring hospitalization was occurred in 2 patients $(0.5\%)$. During follow-up, 114 patients $(27.7\%)$ had progression of local disease with 10 months of median time to recur (range : $1\~87\;months$) and 49 patients $(11.9\%)$ had distant failure with 7 months of median value (range : $1\~52\;months$). Second malignancy before or after the diagnosis of lung cancer was appeared in 11 patients Conclusion : The conventional radiotherapy in the patients with locally advanced squamous cell lung cancer has given small survival advantage over supportive care and it is very important to select the patient group who can obtain the maximal benefit and to select the radiotherapy technique that would not compromise the life quality in these patients.

• Radiation Oncology Journal
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• v.32 no.4
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• pp.231-237
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• 2014

Purpose: To evaluate the predictive value of the early response of $^{18}F$-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). Materials and Methods: FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value ($SUV_{max}$), mean standardized uptake value ($SUV_{mean}$), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT. Results: One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of $SUV_{max}$ ($%{\Delta}SUV_{max}$) were larger in responder group than in non-responder group ($55.7%{\pm}15.6%$ vs. $23.1%{\pm}19.0%$, p = 0.01). The percent changes of $SUV_{mean}$ ($%{\Delta}SUV_{mean}$) were also larger in responder group than in non-responder group ($54.4%{\pm}15.9%$ vs. $22.3%{\pm}23.0%$, p = 0.01). The percent changes of MTV ($%{\Delta}MTV$) or TLG ($%{\Delta}TLG$) had no correlation with the tumor response after treatment. All the 7 patients (100%) with $%{\Delta}SUV_{max}{\geq}50%$ had PR, but only 2 out of 6 patients (33%) with $%{\Delta}SUV_{max}$ < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with $%{\Delta}SUV_{mean}{\geq}50%$ had PR, but only 3 out of 7 patients (43%) with $%{\Delta}SUV_{mean}$ < 50% had PR after CCRT (p = 0.026). Conclusion: The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.35-39
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• 1998

Objectives: Minimal improvement in the long-term survival of head and neck cancer(HNC) patients has occurred despite a multitude of advances in the control of loco regional disease and a second primary malignancy(SPM) contribute to the continued poor prognosis for the HNC patients. This study was performed in order to identify the clinical characteristics of SPM in the HNC patients. Materials and Methods: The medical records of 354 patients of head and neck squamous cell carcinoma that were followed up after initial treatment during the period of 1987 through 1994 were reviewed. This study examines the medical records of 354 patients with squamous cell carcinoma of the head and neck, of whom 26 subsequently developed a second neoplasm. Results: The actuarial SPM rate was 7.3%, and median time to presentation for the SPM was 26.8 months. The SPM were more likely to occur in male patients who had oral cavity index tumors. Patient whose index tumor was small at diagnosis had a greater chance of developing a second tumor as did those with no cervical lymph node metastases to the neck. Initial treatment modality was not associated with an increased risk of developing a second tumor. The commonest sites for the SPM were the lung and other head and neck area. The 3-year survival for patients who developed a secondary tumor from the time of its diagnosis was 27.8%. Conclusion: The SPM in the head and neck cancer patients are not uncommon and early detection of the SPM will contribute to increase the long-term survival of HNC patients.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.195-201
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• 1988

Sixty patients with proven lung cancer were retrospectively studied to determine whether postoperative radiation therapy improves survival. Patterns of treatment failure and 5 year survival were assessed according to extent of tumor spread, histology, type of operation, positive resection margin and radiation dose. Of the 60 patients, excluding S patients who received incomplete treatment or poor pulmonary function,55 patients received postoperative radiation therapy following curative resection. The overall survival at 5 years was $39\%$. The hilar and mediastinal lymph node involvement had an influence on survival. The authors recommend that patients with resection. lung cancer involving the hilar and mediastinal lymph nodes may require postoperative radiotherapy to reduce the local recurrence and improve survival.

• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.72-77
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• 2004

Previously, we synthesized a novel Cyclin-dependent kinase inhibitor, MCS-5A. Also, we investigated the involvement of cell cycle regulatory events during MCS-5A-mediated apoptosis in HL-60(+p16/-p53) cells with up-regulation of p16 protein expression. In contrast, apoptosis was not observed in A549(-p16/+p53) cells. Therefore we propose that $p16^{INK4A}$ is a key enzyme for inducing apoptosis. In the present studies, we have explored the mechanism of $p16^{INK4A}$ -mediated cytotoxicity and the role of p16.sup INK4A/ overexpression in the induction of apoptosis in human tumor cells. The tumor suppressor gene $p16^{INK4A}$ is known as a cyclin-dependent kinase inhibitor (CKI) and cell cycle regulator. We expressed wild type $p16^{INK4A}$ in pcDNA3.1 vector and then transfected into non-small cell lung cancer (NSCLC) cell expressing different statue of p16$^{INK4A}$, p53 gene〔A549(-p16/+p53), H1299(-p16/-p53) and HeLa(+pl6/+p53) cell line〕. TUNEL assay (including propidium iodide staining following transfection of these cell line with pcDNA3.1-pl6) indicate that p16$^{INK4A}$-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating an induction of caspase 3 cleavage due to the transfection of A549, H1299 and HeLa cells with pcDNA3.1-pl6. These results suggest that p16$^{INK4A}$ has a new function of inducing apoptosis which is not related with the function of tumor suppressor gene p53.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.49-59
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• 2000

Backgrounds : Recent cytogenetic studies indicated that long of the long arm of chromosome 5 is a frequent event in small cell lung canær (SCLC), suggesting the presence of a tumor suppressor gene in its place. To map the precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 15 primary SCLCs. Methods : The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Nineteen polymorphic microsatellite markers located in the long arm of chromosome 5 were used in the microsatellite analysis. Results : We found that ten (66.7%) of 15 tumors exhibited LOH in at least one of tested microsatellite markers. Two (13%) of 10 tumors exhibiting LOH lost a larger area in chromosome 5q. LOH was observed in five common deleted regions at 5q. Among those areas, LOH between 5q34-qter and 5q35.2-35.3 was most frequent (75%). LOH was also observed in more than 50% of the tumors at four other regions, between 5q14-15 and 5q23-31, 5q31.1, 5q31.3-33.3, and 5q34-35. Three of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 2.5% (7 of 285) of the loci tested. Conclusion : Our data demonstrated that at least five tumor-suppressor loci exist in the long arm of chromosome 5 and that they may play an important role in small cell lung cancer tumorigenesis.