• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.482-489
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• 2017

Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3155-3158
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• 2013

Many published studies have concerned associations between the CYP1A2 -163 C>A polymorphism and risk of lung cancer, but the results have been inconsistent. Therefore, we performed a meta-analysis to obtain a more precise estimate. We searched the PubMed database up to March 1, 2013 for relevant cohort and case-control studies. Supplementary search was conducted manually by searching the references of the included studies and relevant meta-analyses. A meta-analysis was performed using RevMan 5.2 software for calculation of pooled odds ratios (ORs) and relevant 95% confidence intervals (CIs) after data extraction. Finally, seven case-control studies and one nested case-control study involving 1,675 lung cancer patients and 2,393 controls were included. The meta-analysis showed that there was no association of CYP1A2 -163 C>A polymorphism with risk of lung cancer overall [(OR=0.89, 95%CI= 0.74-1.07) for C vs. A; (OR=0.73, 95%CI= 0.50-1.07) for AA vs. CC ; (OR=0.82, 95%CI= 0.62-1.09) for AC vs. CC; (OR=0.79, 95%CI= 0.58-1.07) for (AC+AA) vs. CC; and (OR=0.87, 95%CI= 0.67-1.13) for AA vs. (CC+AC)]. Subgroup analysis indicated that there was an associationbetween CYP1A2 -163C>A polymorphism and lung cancer risk for population-based controls, a trend risk for SCCL (squamous cell carcinoma of lung) and Caucasians. These results suggested that -163 C>A polymorphism is likely to be associated with risk of lung cancer compared with population-based controls.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.310-317
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• 1992

Background: Angiotensin converting enzyme is a glycoprotein peptidyldipeptide hydrolase which cleaves the c-terminal dipeptides of several oligopeptides. It is a menbrane-bound protein mainly synthesized by the endothelial cells. Since the lung has the largest capillary bed of any organ in the body, it is here that ACE acts on circulating substrates like angiotensin I and bradykinin. It is well known that ACE correlates with disease activity in sarcoidosis and also there are reports that changes in serum ACE activity are found in many acute and chronic lung diseases. So we planned this study to see if serum ACE activity can act as a prognostic factor in lung cancer. Methods: Forty-one newly diagnosed lung cancer patients were included in the study group. There were 19 patients with squamous cell lung cancer, 13 with adenocarcinoma, and 9 with small cell carcinoma. Patients were excluded from the study if they had high blood pressure, heart disease, liver disease, renal disease, or other lung disease. Serum ACE activity was analyzed according to cell type, staging, mode of treatment, and clinical response to treatment. Results: 1) There was no difference in serum ACE activity between lung cancer patients and the control group. Also no difference in serum ACE activity was found according to cancer cell type or staging. 2) In patients who underwent curative resection of lung cancer, serum ACE activity was decreased significantly after the operation. 3) In patients who were diagnosed as non-small cell lung cancer and were treated with 4 cycles of anti-cancer chemotherapy without clinical improvement, changes in serum ACE activity were not seen after the treatment. 4) In patients diagnosed as small cell lung cancer treated with 4 cycles of anti-cancer chemotherapy with clinical improvement, changes in serum ACE activity were also not observed. Conclusion: Serum ACE activity was decreased after lung resection but had no relation to cell type, staging, or clinical response to treatment in lung cancer patients. Therefore, serum ACE activity is not suitable in predicting clinical outcome of lung cancer patients.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.354-362
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• 1994

Objectives and Methods : The presence of aneuploidy or high proliferative activity in cytologic specimens is considered as complementary for the diagnosis of malignancy. To evaluate the diagnostic usefulness of DNA ploidy and cell cycle analysis in lung cancer, we compared the diagnostic yielding rates of DNA ploidy test by brushing specimens using flow cytometry with bronchoscopic forceps biopsy and brushing cytology. Results : Of the seventy-six cases, 55 cases proved to have malignant diseases(squamous cell cancer: 27, adenocarcinoma: 7, large cell cancer: 1, undifferentiated: 4 and small cell cancer: 16). The incidence of aneuploidy in lung cancer patients was 32.7%(18/55), as opposed to no cases in benign disease. And the proportion of high proliferative activity(S+G2M>22%) in lung cancer patients was 42.9%(15/35), but none in benign diseases. In fifty-six of 75 cases(74.7%), cytology of brushing specimens and DNA analysis(either aneuploidy or high proliferative activity vs. diploidy and low proliferative activity) were in concordance. The sensitivity with only brushing cytology was 41.8%(23/55), but with the addition of DNA analysis, it was increased to 56.4%(31/55), without decreasing the specificity(100%). And there was a case whose clue for malignancy was absent except aneuploidy, and he was confirmed to have squamous cell cancer following open thoracotomy. There were no differences in the frequency of aneuploidy or high proliferative activity between histologic subtypes of bronchogenic malignancy. Conclusions : The diagnostic detection rate of lung cancer was improved with the addition of DNA ploidy and cell cycle analysis, and the presence of aneuploidy or high proliferative activity was a relatively specific indicator of malignant disease. It would be useful to test DNA ploidy and cell cycle analysis with brushing specimen for the diagnosis of bronchogenic malignancy particularly in patients whose biopsy specimen could not be obtainable.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.321-330
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• 1993

Purpose: A retrospective analysis was performed to evaluate the incidence of radiation induced lung damage after the radiation therapy for the patients with carcinoma of the lung. Method and Materials: Sixty-six patients with lung cancer (squamous cell carcinoma 27, adenocarcinoma 14, large cell carcinoma 2, small cell carcinoma 13, unknown 10) were treated with definitive, postoperative or palliative radiation therapy with or without chemotherapy between July 1987 and December 1991. There were 50 males and 16 females with median age of 63 years (range: 33~80 years). Total lung doses ranged from 500 to 6,660 cGy (median 3960 cGy) given in 2 to 38 fractions (median 20) over a range or 2 to 150 days (median in days) using 6 MV or 15 MV linear accelerator. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, $ED=D{\dot}N^{-0.377}{\dot}T^{-0.058}$ was used in which D was the lung dose in cGy, N was the number of fractions, and T was the overall treatment time in days. The range of ED was 370 to 1357. The endpoint was a visible increase in lung density within the irradiated volume on chest X-ray as observed independently by three diagnostic radiologists. Patients were grouped according to ED, treatment duration, treatment modality and age, and the percent incidence of pulmonary damage for each group was determined. Result: In 40 of 66 patients, radiation induced change was seen on chest radiographs between 11 days and 314 days after initiation of radiation therapy. The incidence of radiation pneumonitis was increased according to increased ED, which was statistically significant (p=0.001). Roentgenographic changes consistent with radiation pneumonitis were seen in $100\%$ of patients receiving radiotherapy after lobectomy or pneumonectomy, which was not statistically significant. In 32 patients who also received chemotherapy, there was no difference in the incidence of radiation induced change between the group with radiation alone and the group with radiation and chemotherapy, among the sequence of chemotherapy No correlation was seen between incidence of radiation pneumonitis and age or sex. Conclusions: The occurrence of radiation pneumonitis varies. The incidence of radiation pneumonitis depends on radiation total dose, nature of fractionation, duration of therapy, and modifying factors such as lobectomy or pneumonectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.731-736
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• 2014

Objective: To observe the short-term efficacy, long-term survival time and adverse responses with nedaplatin (NDP) or cisplatin (DDP) concomitant with other chemotherapy in treating non-small cell lung cancer. Materials and Methods: A retrospective, randomized, control study was conducted, in which 619 NSCLC patients in phases III and IV who were initially treated and re-treated were randomly divided into an NDP group (n=294) and a DDP group (n=325), the latter being regarded as controls. Chemotherapeutic protocols (CP/DP/GP/NP/TP) containing NDP or DDP were given to both groups. Patients in both groups were further divided to evaluate the clinical efficacies according to initial and re-treatment stage, pathological pattern, type of combined chemotherapeutic protocols, tumor stage and surgery. Results: The overall response rate (ORR) and disease control rate (DCR) in the NDP group were 48.6% and 95.2%, significantly higher than in the DDP group at 35.1% and 89.2%, respectively (P<0.01). In NSCLC patients with initial treatment, squamous carcinoma and phase III, there were significant differences in ORR and DCR between the groups (P<0.05), while ORR was significant in patients with adenocarcinoma, GP/TP and in phase IIIa (P<0.05). There was also a significant difference in DCR in patients in phase IIIb (P<0.05). According to the statistical analysis of survival time of all patients and of those in clinical phase III, the NDP group survived significantly longer than the DDP group (P<0.01). The rates of decreased hemoglobin and increased creatinine, nausea and vomiting in the NDP group were evidently lower than in DDP group (P<0.05). Conclusion: NDP concomitant with other chemotherapy is effective for treating NSCLC, with higher clinical efficacy than DDP concomitant with chemotherapy, with advantages in prolonging survival time and reducing toxic and adverse responses.

• 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.19 no.1
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• pp.140-147
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• 1986

A clinical study was made on 72 cases of primary lung cancer operated in the department of thoracic & cardiovascular surgery, Kyungpook national university hospital from January 1975 to May 1985. The ratio of male to female was 13.4: I and mean age was 53. Histologically, squamous cell carcinoma comprised 72.2% of 72 operated cases. Before admission to our hospital, the erroneous diagnoses were made at local clinics on the 43 cases[59.7%] and a large percentage of them was diagnosed as pulmonary tuberculosis. And then, total of 56 cases received inadequate treatment or delayed the operation. For the location of the tumor, right to left ratio is 1.2:1 and the right upper lobe was most often involved [23.6%]. Operation was performed on the 72 cases and resection on the 59 cases[8.2%]. Postsurgical staging showed that stage III was found most frequently [59.4%] and T,N,M, was 28% of total cases. Two common surgical complications were bleeding in 7 and acute respiratory failure in 6 cases, and these 6 cases of acute respiratory failure were all died. On the basis of these experiences, we conclude that aggressive effort is needed for the early accurate diagnosis and adequate treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.660-668
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• 1999

Background: Lung cancer continues to increase and one half of all cases of lung cancer occur in patients age 65 years and older. However, it seems that lung cancer is less treatable in elderly patients because of co-morbid illness or poor tolerance of surgery and chemotherapy. The intention of this study is to seek an adequate treatment approach for lung cancer in the elderly through an understanding of its characteristics. Method: The clinical data of 207 patients who were diagnosed with histologically proven lung cancer at the department of internal medicine in Seoul Municipal Boramae Hospital between September 1994 and August 1998 were retrospectively analyzed according to their age groups; group I$\geq$65 years(n=122) and group II<65 years(n=85). Results: The peak incidence of age was 7th decade(36.2%) and male age 65 years and older were 42% of all patients. Although dyspnea was more common in group I(26%) than in group II(11%)(p=.0l), there were no significant difference in other symptoms, stage, and histologic type between two groups. Group I significantly had more patients with poor performance(ECOG 3&4) than group II(35.2% vs.12.9%, p=.000). The percentage of patients with non-small cell carcinoma received supportive care only was significantly higher in group I than in group I(74% vs. 35%, p=.000). However, survival of patients who had curative intent treatment was similar between two groups(median survival 11.3 mos vs. 23 mos, p>.05). The histologic subtype, stage and performance status were significant prognostic factors affecting survival, but age itself was not. Conclusion : Lung cancer is prevalent in the elderly and aggressive diagnosis and treatment should be considered in elderly patients with good performance status.

• Journal of Biomedical Engineering Research
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• v.44 no.5
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• pp.303-314
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• 2023

This study aimed to assess the practical feasibility of advanced deformable image registration (DIR) algorithms in radiotherapy by employing two distinct datasets. The first dataset included 14 4D lung CT scans and 31 head and neck CT scans. In the 4D lung CT dataset, we employed the DIR algorithm to register organs at risk and tumors based on respiratory phases. The second dataset comprised pre-, mid-, and post-treatment CT images of the head and neck region, along with organ at risk and tumor delineations. These images underwent registration using the DIR algorithm, and Dice similarity coefficients (DSCs) were compared. In the 4D lung CT dataset, registration accuracy was evaluated for the spinal cord, lung, lung nodules, esophagus, and tumors. The average DSCs for the non-learning-based SyN and NiftyReg algorithms were 0.92±0.07 and 0.88±0.09, respectively. Deep learning methods, namely Voxelmorph, Cyclemorph, and Transmorph, achieved average DSCs of 0.90±0.07, 0.91±0.04, and 0.89±0.05, respectively. For the head and neck CT dataset, the average DSCs for SyN and NiftyReg were 0.82±0.04 and 0.79±0.05, respectively, while Voxelmorph, Cyclemorph, and Transmorph showed average DSCs of 0.80±0.08, 0.78±0.11, and 0.78±0.09, respectively. Additionally, the deep learning DIR algorithms demonstrated faster transformation times compared to other models, including commercial and conventional mathematical algorithms (Voxelmorph: 0.36 sec/images, Cyclemorph: 0.3 sec/images, Transmorph: 5.1 sec/images, SyN: 140 sec/images, NiftyReg: 40.2 sec/images). In conclusion, this study highlights the varying clinical applicability of deep learning-based DIR methods in different anatomical regions. While challenges were encountered in head and neck CT registrations, 4D lung CT registrations exhibited favorable results, indicating the potential for clinical implementation. Further research and development in DIR algorithms tailored to specific anatomical regions are warranted to improve the overall clinical utility of these methods.