• Environmental Mutagens and Carcinogens
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• v.25 no.3
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• pp.118-123
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• 2005

Nicotine has been implicated as a potential factor in the pathogenesis of human lung cancer, however its mechanism of action in the development of lung cancer remains largely unknown. To explore the role of nicotine in the development of lung cancer, we first investigated the effects of nicotine on the expression of tumor associated genes by treating Sprague-Dawley rats with nicotine (10 mg/kg) by gavage once daily for 10 days. We determined the expression of proteins and mRNAs of the ras, raf, myc, jun, fos oncogenes and p53, Rb tumor suppressor genes by Western and Northern blotting, respectively. We did not detect any changes on the levels of proteins and mRNAs of these tumor associated genes in the lung of Sprague-Dawley rats from 3 days to 12 weeks after the last treatment of nicotine, indicating that nicotine appears to have no effect on expression of these oncogenes and tumor suppressor genes at an early stage in multistage chemical carcinogenesis. In a second experiment, we investigated the possibility that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could be formed endogenously by treating with nicotine and sodium nitrite. We treated groups of Fischer 344 rats with nicotine ($60{\mu}mol/kg$) and sodium nitrite ($180{\mu}mol/kg$), nicotine, sodium nitrite and NNK (120 nmol/kg) alone by gavage once daily for 7 days, respectively and determined the 8-hydroxydeoxyguanosine (8-OHdG), as an indicator of NNK formation, in the lungs of rats 24 hours and 48 hours after the last treatment by HPLC/ECD method. We detect increased level of 8-OHdG in the lungs of rats treated with NNK, but in the case of nicotine plus sodium nitrite, nicotine and sodium nitrite alone we could not detected any changes of 8-OHdG, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4853-4858
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• 2015

Background: Colorectal cancer is the most common gastrointestinal cancer in Oman with an increasing incidence. We here report the presenting features, treatment outcomes and survival in a University hospital in Oman and compare our data with regional and international studies. Materials and Methods: Medical records of patients with colorectal cancer were reviewed retrospectively between June 2000 and December 2013 and were followed until June 2014. Results: A total of 162 patients were diagnosed with colorectal cancer. The majority were males (58.6%), with a median age of 56 years. Rectum was involved in 29.6% of patients, followed by ascending and sigmoid colon. The majority of patients had stage III (42.6%) and stage IV (32.7%) disease at presentation. K-Ras status was checked for 79 patients, and 41 (51.9%) featured the wild type. Median relapse free survival was 22 months. Median overall survival for all patients was 43 months. Observed 5 year overall survival (OS) for stages I, II and III was 100%, 60% and 60% respectively. On Log rank univariate analysis, age, BMI, diabetes, hypertension, metformin use, stage, clinical nodal status for rectal cancer, pathological T and nodal status, site of metastasis, surgical intervention, chemotherapy, radiotherapy, chemotherapy regimen, no of cycles of chemotherapy, response, RFS, site of recurrence and administration of $2^{nd}$ line chemotherapy were significant factors affecting OS. On Cox regression multivariate analysis none of the factors independently affected the OS. Conclusions: The majority of patients present with advanced disease and at young age. The survival rates are comparable to the published regional and international literature.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3691-3698
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• 2014

Background: Published studies on the association between the Ras Association Domain Family 1 isoform A (RASSF1A) Ala133Ser polymorphism and cancer susceptibility have yielded conflicting results. Thus, a meta-analysis was here performed to assess the possible association. Materials and Methods: All eligible case-control studies published up to November 2013 on the association between RASSF1A Ala133Ser polymorphism and cancer susceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Bothfixed-effect and random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) by using the Comprehensive Meta-Analysis software version 2.2. Results: A total of 10 studies including 4,572 cancer cases and 4,320 controls were included in the meta-analysis. Overall, significantly increased cancer risk was associated with the variant Ser133 when all studies were pooled (Ser vs Ala: OR=1.51, 95% CI=1.08-2.12, $P_{heterogeneity}{\leq}0.001$; Ser/Ser+Ala/Ser vs Ala/Ala: OR=1.55, 95% CI=1.08-2.22, $P_{heterogeneity}{\leq}0.001$). Moreover, in subgroup analyses by cancer types, a significant association between RASSF1A Ala133Ser polymorphism and lung cancer risk was found (Ser vs Ala: OR=2.27, 95% CI=1.29-4.02, $P_{heterogeneity}$=0.61; Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.42, 95% CI=1.33-4.42, $P_{heterogeneity}=0.75$). In addition, in subgroup analyses by ethnicity, it was found that the RASSF1A Ala133Ser polymorphism was associated with overall cancer risk in Asians (Ser vs Ala: OR=1.37, 95% CI=1.06-1.77, $P_{heterogeneity}=0.06$) and Caucasians (Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.21, 95% CI=1.01-4.82, $P_{heterogeneity}{\leq}0.001$). Conclusions: This meta-analysis suggests, for the first time, that RASSF1A Ala133Ser polymorphism may contribute to cancer susceptibility, especially for lung cancer. Besides, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are needed to confirm these findings.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6109-6114
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• 2013

Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (${\pm}2.87$) months (95%CI: 13.62-24.88) in the BB group and 13.20 (${\pm}2.37$) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3543-3549
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• 2015

Background: Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Materials and Methods: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Results: Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. Conclusions: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2689-2698
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• 2013

Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5917-5920
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• 2014

Background: This study aimed to explore the effects of ras association domain family 1 A (RASSF1A) on proliferation and apoptosis of human cervical cancer cell line Hela cells. Materials and Methods: RASSF1A was cloned into the pcDNA3.1(+) vector to generate pcDNA3.1(+)-RASSF1A plasmid for transfection into Hela cells. Changes in the proliferation and apoptosis of cultured Hela cells were examined by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium chloride assay and flow cytometry. A protein array was used to analyze the expression of apoptotic factors. Results: Plasmid pcDNA3.1(+)-RASSF1A was generated and transfected into Hela cells to stably express RASSF1A in Hela cells. RASSF1A transfection was effective in inhibiting the proliferation of Hela cells up to 52.4%, as compared to cells transfected with an empty plasmid. RASSF1A expression also successfully induced apoptosis in human cervical cells with an apoptosis rate of 20.5%. More importantly, protein array results showed that RASSF1 A transfection induced overexpression of p21 and caspase 8, while decreasing the expression of survivin in Hela cells. Conclusions: RASSF1A expression was effective in suppressing the proliferation and increasing apoptosis of Hela cells, and may be a potential therapy for cervical cancer in clinic.

• Proceedings of the Korea Water Resources Association Conference
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• 2011.05a
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• pp.212-216
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• 2011

현재 하천 건천화에 따른 수생태계 교란 및 수질악화 등의 근본적인 문제가 발생하고 있으며, 최근 정부의 저탄소 녹색성장기조에 따라 조성되고 있는 신도시, 소규모 및 대규모 택지개발사업의 경우는 환경 친화적인 단지조성 요구에 부응하기 위해 기존 도심하천의 복원 및 인공하천의 녹색성장을 고려한 친환경적 생태하천으로 조성하고자 하는 다양한 노력이 시도되고 있으나 안정적인 생태복원의 수원확보 방안을 마련하지 못해 실제 설계가 반영되지 못하고 있다. 또한, 조성하고자 하는 소하천 혹은 실개울 등의 수질보전 및 생태계 보호 등 하천이 본래의 기능을 유지할 수 있도록 생태하천유량을 확보하는 다양한 기술들이 개발되어 있지만, 공사 유형과 주변 환경에 적합한 생태하천유량 확보 방안을 선정할 수 있는 비구조적 대책마련이 부족한 실정이다. 이러한 실정과 문제점을 고려해 볼 때, 조성하고자 하는 도시 내 자연하천 및 인공하천 조성 등 수변환경을 고려한 단지조성에 맞는 생태하천유량 확보 방안 및 평가에 대한 연구가 단계적으로 이루어져야 할 것이다. 따라서 본 연구에서는 생태하천유량 확보와 하천수질 개선이 필요한 특정 지역 또는 다양한 유형의 공사 지구 내 하천이 정상적인 기능을 수행할 수 있도록 적용 가능한 생태하천유량 확보 방안들과 수리해석 모델인 HEC-RAS(River Analysis System), 생태하천유량 산정 모델인 PHABSIM(Physical HABitat SIMulation)을 연계한 물리서식처 평가 모듈을 개발하고, 이를 기초로 가중치부여매트릭스 평가(국토해양부, 2006) 기법을 적용한 최적의 생태하천유량 확보 방안과 수질개선 방안을 제시해 줄 수 있는 의사결정지원 시스템을 구축 하고자 한다. 본 연구에서 개발된 최적의 생태하천유량 확보 방안 도출을 위한 의사결정지원 시스템의 활용으로 필요유량은 물론, 기준을 만족하는 수질의 확보가 절실히 요구되는 중 소규모 하천에 실질적으로 적정수질의 생태하천유량을 확보함으로서 하천으로서의 역할을 위한 본 기능의 회복과 동시에 소하천, 도심하천 및 인공하천 등 중 소규모 수계의 수문순환을 정상화하여 하천의 지속 가능한 개발과 관리가 효율적으로 이루어지도록 하는데 이용될 수 있을 것으로 예상되어진다.

• Proceedings of the Korea Water Resources Association Conference
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• 2011.05a
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• pp.31-31
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• 2011

해마다 반복되는 수해를 대비하여 배수펌프장을 설치하고, 취수보를 철거하는 방법으로 수해예방시스템을 고도화 시키고 있지만, 증가하는 홍수량에 대한 대비책으로는 역부족이다. 따라서, 홍수 피해에 대한 선제적 대응방안으로 강변저류지를 설치하여 상습 침수구역에 대한 대비가 진행되고 있다. 강변저류지 설치를 통해 유역의 홍수량을 분담하고 인접지역의 침수피해를 예방하는 역할을 기대할 수 있다. 국내에서도 영월군의 상습침수구역에 대한 대비책 중 하나로 국토해양부 및 강원도가 함께 영월강변저류지 조성공사를 추진하고 있다. 영월군은 지난 2002년과 2003년에 태풍 '루사'와 '매미'로 인해 심각한 피해를 입었으며, 2006년 집중호우시에도 현재 저류지 예정지역인 방절리 일대와 영월읍 시가지, 북쌍리 등이 대규모로 침수피해를 입은 바 있다. 해당 저류지의 총 넓이는 68만 8천 $m^2$로 물 290만 $m^3$을 가두어 둘 수 있는 규모이다. 하지만, 영월 강변저류지의 저류용량이 290만 $m^3$에 불과해 홍수예방 효과가 미흡하다는 지적이 잇따르고 있다. 따라서, 적절한 수문운영을 통해 홍수저감량과 저류효과를 증대시키는 홍수예방 방안을 제안하고자 한다. 본 연구에서는 유전알고리즘의 적용을 통하여 강변저류지에 설치된 수문의 운영 방법을 개선함으로써 홍수저감량을 최대화하고자 하였다. 수리 수문학적 모형인 HEC-RAS, HEC-I 모형을 연계 운용하여 평창강 유역을 대상으로 수문분석, 홍수유출량 분석, 하류 하천의 홍수영향 분석 결과를 도출하였다. 강변저류지 설치로 인하여 저류지 직하류부를 기준으로 약 $131\;m^3/s$의 첨두홍수량 저감 효과가 발생하는 것으로 검토되었지만, 본 연구에서 제안된 최적화 기법이 적용된 수문운영 방법을 병행하여 운영한다면 추가적으로 $24\;m^3/s$를 저감하는 효과를 얻을 수 있다. 효율적으로 저류지를 운영하여 홍수피해를 사전에 방지하고 나아가 다른 저류지 유역에도 본 연구를 적용하여 홍수피해를 줄이고 합리적으로 용수를 이용하는데 기여할 수 있을 것으로 사료된다.

• Proceedings of the Korea Water Resources Association Conference
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• 2011.05a
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• pp.297-301
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• 2011

최근에는 전 지구적으로 이상기후 현상이 빈번히 발생하고 있으며 이로 인해 과거와는 달리 예측하기 어려운 집중호우와 돌발강우에 따른 피해가 증가하고 있는 추세이다. 이러한 이상 강우현상에 의해 하천 및 주변의 내 외수의 수위 상승을 야기하며, 이로인해 제내지의 침수 위험성이 그 어느 때보다 높은 실정이다. 특히, 내수침수의 경우는 외수에 따른 범람보다는 내수배제 불량에 따른 침수 빈도와 범위가 증가되고 있는 상황이며, 이에 대한 대비가 절실히 요구되고 있다. 주기적으로 반복되는 내수침수에 의한 국민의 재산과 인명피해를 최소화하기 위해서는 침수피해 위험도가 높은 지역을 파악 관리하여야 하며, 지역의 주민에게도 지역의 특성을 주지시켜야 한다. 이와 함께 침수 발생시 피해 최소화를 위한 피난 경로와 피난 장소 등을 상세히 제공하여 신속한 재난 대처와 함께 인명과 재산의 피해를 최소화하여야 한다. 침수예상지도는 태풍이나 집중호우에 의한 침수 발생시 제방의 월류 및 붕괴, 내수배제 불량 등으로 인한 예상 침수지역을 강우빈도별로 나타내고, 침수면적과 깊이를 표현한 지도로서 방재형 국토관리의 정책결정과 침수 피해에 대한 대민 홍보의 수단으로 활용되고 있다. 국내에서도 홍수에 의한 피해가 나날이 커지고 국토의 개발에 따른 자연 재해가 많아짐에 따라 홍수에 의한 피해를 최소화하기 위한 노력의 일환으로 침수예상지도의 제작 및 관리 시스템의 필요성이 증대되고 있다. 본 연구에서는 지석천 유역의 태풍 및 집중호우에 의한 과거 침수실적을 조사하여 침수실적도를 작성하 였으며, 내 배수 불량에 따른 홍수빈도, 강우빈도별 침수예상도를 작성하였다. 이를 위해 현재 보편적으로 이용되고 있는 1차원 수리 수문 모델인 미 공병단의 HEC-HMS, HEC-RAS 모델과 내 배수 영향 검토를 위해 한국농어촌공사에서 개발된 GATE 프로그램을 이용하였다. 이렇게 계산된 연구 대상지역의 침수심과 침수면적을 GIS를 이용하여 침수예상도를 작성하였다.