• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.851-856
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• 2012

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

• 한국정보과학회논문지:소프트웨어및응용
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• 제33권8호
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• pp.681-691
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• 2006

유전자 데이타의 클러스터링은 방대한 유전자 정보를 발현 정도에 따라 비슷한 그룹으로 나누어 분석하는 방법으로 유전자의 기능을 분석하는데 사용되어 왔다. 클러스터링의 한 종류인 퍼지 클러스터링은 하나의 샘플이 소속정도에 따라 여러 그룹에 동시에 소속되도록 나누는 방법으로, 하나의 유전자 데이타는 여러가지 유전 정보를 가칠 수 있기 때문에 유전자 발현 데이타의 분석에 보다 적절한 방법이다. 그러나 보통 클러스터링 방법은 초기 값에 민감하고, 지역해에 빠질 수 있는 단점을 갖는다. 이런 단점을 해결하기 위해 본 논문에서는 진화 연산을 이용한 퍼지 클러스터링 방법을 제안한다. 이때, 적합도 평가를 위해서 모든 데이타에 대해 동일한 기준을 적용하는 베이지안 검증방법의 단점을 개선하여, 데이타의 특성 을 고려하여 결정된 적용적 ${\alpha}$-cut 기반 평가방법을 사용한다. SRBCT 데이타와 효모 세포주기 데이타를 이용해 실험을 하고 결과를 분석하여 제안하는 방법의 유용성을 확인하였다.

• Radiation Oncology Journal
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• 제33권3호
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• pp.207-216
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• 2015

Purpose: Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods: This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results: The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ${\geq}65$ years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion: SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

• 대한핵의학회지
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• 제37권3호
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• pp.178-189
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• 2003

목적: 다약제내성이 유발된 암세포에서 $^{99m}Tc-sestamibi$와 $^{99m}Tc-tetrofosmin$의 암세포 내 섭취정도를 비교하고 다약제내성 극복제로 잘 알려진 verapamil 과 cyclosporin A 처리에 의한 두 방사성 의약품의 암세포 내 섭취정도를 비교해 보았다. 재료 및 방법: Doxorubicin으로 다약제내성이 유발된 HCT15/CL02 대장암 세포와 doxorubicin과 vincristine으로 다약제내성을 유발시킨 K562(Adr)과 K562(Vcr) 백혈병 세포를 사용하였다. 다약제내성의 발현은 RT-PCR로 증명하였으며, verapamil은 1, 10, 50, 100, 200 ${\mu}M$의 농도로, cyclosporin A는 0.1, 10, 50, 100 ${\mu}M$의 농도로 각각 사용하였다. MIBI와 tetrofosmin의 암세포내 섭취는 $37^{\circ}C$에서 $1{\times}10^{6}cells/ml$ 농도의 단일세포 부유상태에서 1, 15, 30, 45, 60분 간격으로 배양하여 각 시간대별로 상층액과 침전물을 분리하여 각각의 방사능을 감마 계수기로 측정하였다. 결과: 다약제내성이 발현된 암세포에서는 모세포에 비하여 MIBI와 tetrofosmin의 섭취가 감소되었다. 두 방사성약품의 섭취정도는 HCT15/CL02세포와 K562(Adr)세포에서는 유의한 차이가 없었으나, K562(Vcr)세포에서는 MIBI가 tetrofosmin보다 다소 높았다. Verapamil과 cyclosporin A를 처리하였을 때 MIBI와 tetrofosmin의 섭취율은 기저치보다 모두 증가하였고, verapamil 에 의한 MIBI와 tetrofosmin의 섭취율(30분)을 기저치(30분)와 비교해 본 결과 HCT15/CL02 세포에서($100{\mu}M$)는 각각 11.9배와 6.8배, K562(Adr) 세포에서($50{\mu}M$)는 각각 14.3배와 8배, K562(Vcr) 세포에서($10{\mu}M$)는 각각 7배와 5.7배 증가하였다. Cyclosporin A에 의한 MIBI와 tetrofosmin의 섭취율(30분)을 기저치(30분)와 비교해 본 결과 HCT15/CL02세포에서($50{\mu}M$)는 각각 10배와 2.4배, K562(Adr)세포에서($50{\mu}M$)는 각각 44배와 13배, K562(Vcr)세포에서($10{\mu}M$)는 각각 18.8배와 11.8배 증가하여, MIBI의 섭취율이 tetrofosmin보다 1.2배에서 4배정도 높게 나타났다. 결론: 이러한 결과로 보아 MIBI와 tetrofosmin은 다약제내성의 발현을 평가할 수 있는 방사성의약품으로 판단되며, 다약제내성 극복제의 효능평가에는 MIBI가 tetrofosmin보다 더 우수할 것으로 사료되나, 세포추에 따른 차이가 있을 수 있으므로 보다 많은 세포주에서의 추가적인 연구가 필요할 것이다.

• Radiation Oncology Journal
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• 제34권4호
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• pp.280-289
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• 2016

Purpose: Early hypopharyngeal squamous cell carcinoma (HPSCC) is a rarely diagnosed disease, for which the optimal treatment has not been defined yet. We assessed patterns of failure and outcomes in early HPSCC treated with various therapeutic approaches to identify its optimal treatment. Materials and Methods: Thirty-six patients with stage I (n = 10) and II (n = 26) treated between January 1992 and March 2014 were reviewed. Patients received definitive radiotherapy (RT) (R group, n = 10), surgery only (S group, n = 19), or postoperative RT (PORT group, n = 7). All patients in both the R and PORT groups received elective bilateral neck irradiation. In the S group, 7 patients had ipsilateral and 8 had bilateral dissection, while 4 patients had no elective dissection. Results: At a median follow-up of 48 months, the 5-year locoregional control (LRC) rate was 65%. Six patients had local failure, 1 regional failure (RF), 3 combined locoregional failures, and 2 distant failures. There was no difference in 5-year LRC among the R, S, and PORT groups (p = 0.17). The presence with a pyriform sinus apex extension was a prognosticator related to LRC (p = 0.01) in the multivariate analysis. Patients with a bilaterally treated neck showed a trend toward a lower RF rate (p = 0.08). Conclusion: This study shows that patients with early stage HPSCC involving the pyriform sinus apex might need a tailored approach to improve LRC. Additionally, our study confirms elective neck treatment might have an efficacious role in regional control.

• Restorative Dentistry and Endodontics
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• 제41권3호
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• pp.189-195
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• 2016

Objectives: A variety of root canal sealers were recently launched to the market. This study evaluated physicochemical properties, biocompatibility, and sealing ability of a newly launched resin-based sealer (Dia-Proseal, Diadent) compared to the existing root canal sealers (AHplus, Dentsply DeTrey and ADseal, Metabiomed). Materials and Methods: The physicochemical properties of the tested sealers including pH, solubility, dimensional change, and radiopacity were evaluated. Biocompatibility was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For microleakage test, single-rooted teeth were instrumented, and obturated with gutta-percha and one of the sealers (n = 10). After immersion in 1% methylene blue solution for 2 weeks, the specimens were split longitudinally. Then, the maximum length of staining was measured. Statistical analysis was performed by one-way analysis of variance followed by Tukey test (p = 0.05). Results: Dia-Proseal showed the highest pH value among the tested sealers (p < 0.05). ADseal showed higher dimensional change compared to AHplus and Dia-Proseal (p < 0.05). The solubility values of AHplus and Dia-Proseal were similar, whereas ADseal had the lowest solubility value (p < 0.05). The flow values of sealer in increasing order were AHplus, DiaProseal, and ADseal (p < 0.05). The radiopacity of AHplus was higher than those of ADseal and Dia-Proseal (p < 0.05). The cell viability of the tested materials was statistically similar throughout the experimental period. There were no significant differences in microleakage values among the tested samples. Conclusions: The present study indicates that Dia-Proseal has acceptable physicochemical properties, biocompatibility, and sealing ability.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9171-9176
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• 2014

Aim: P53, the most commonly mutated tumor suppressor gene in all types of human cancer, is involved in cell cycle arrest and control of apoptosis. Although p53 contains several polymorphic sites, the codon 72 polymorphism is by far more common. There are divergent reports but many studies suggest p53 pro/pro SNP may be associated with susceptibility to developing various cancers in different regions of the world. The present study aimed to find any correlation between H. pylori infection and progression of carcinogenesis, by studying apoptosis and the p53 gene in gastric biopsies from north Indian population. Materials and Methods: A total of 921 biopsies were collected and tested for prevalence of H. pylori by rapid urease test (RUT), imprint cytology and histology. Apoptosis was studied by the TUNEL method. Analysis of p53 gene polymorphism at codon 72 was accomplished by PCR using restriction enzyme BstU1. Observation: Out of 921 samples tested 56.7% (543) were H. pylori positive by the three techniques. The mean apoptotic index (AI) in the normal group was 2.12, while gastritis had the maximum 4.24 followed by gastric ulcer 2.28, gastropathy 2.22 and duodenal ulcer 2.08. Mean AI in cases with gastric cancer (1.72) was less than the normal group. The analysis of p53 72 SNP revealed that p53 (Arg/Arg), (Pro /Arg) variant are higher (40.59% & 33.66%) as compared to p53 pro/pro variant (25.74%) inthe healthy population. Conclusions: The North Indian population harbors Arg or Pro/Arg SNP that is capable of withstanding stress conditions; this may be the reason of low incidence of gastric disease in spite of high infection with H. pylori. There was no significant association with H. pylori infection and AI. However, there is increased apoptosis in gastritis which may occur independent of H. pylori or p53 polymorphism.

• Journal of Gastric Cancer
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• 제10권3호
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• pp.91-98
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• 2010

Purpose: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. Materials and Methods: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. Results: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. Conclusions: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.

• Journal of Chest Surgery
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• 제56권1호
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• pp.35-41
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• 2023

Background: We analyzed our experience with descending necrotizing mediastinitis (DNM) treatment and investigated the efficacy of video-assisted thoracoscopic surgery (VATS) for mediastinal drainage. Methods: This retrospective analysis included patients who underwent surgical drainage for DNM at our hospital from 2005 to 2020. We analyzed patients' baseline characteristics, surgical data, and perioperative outcomes and compared them according to the mediastinal drainage approach among patients with type II DNM. Results: Twenty-five patients (male-to-female ratio, 18:7) with a mean age of 54.0±12.9 years were enrolled in this study. The most common infection sources were pharyngeal infections (60%). Most patients had significantly increased white blood cell counts, elevated C-reactive protein levels, and decreased albumin levels on admission. The most common DNM type was type IIB (n=16, 64%), while 5 and 4 patients had types I and IIA, respectively. For mediastinal drainage, the transcervical approach was used in 15 patients and the transthoracic approach (VATS) in 10 patients. The mean length of hospital stay was 26.5±23.8 days, and the postoperative morbidity and in-hospital mortality rates were 24% and 12%, respectively. No statistically significant differences were found among patients with type II DNM between the transcervical and VATS groups. However, the VATS group showed shorter mean antibiotic therapy duration, drainage duration, and hospital stay length than the transcervical group. Conclusion: DNM manifested as severe infection requiring long-term inpatient treatment, with a mortality rate of 12%. Thus, active treatment with a multidisciplinary approach is crucial, and mediastinal drainage using VATS is considered relatively safe and effective.

• Tuberculosis and Respiratory Diseases
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• 제75권4호
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• pp.140-149
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• 2013

Background: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-${\beta}1$ initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. Methods: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. Results: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). Conclusion: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.