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Association of Single Nucleotide Polymorphisms in the Prostaglandin-endoperoxide Synthase 2 (PTGS2) and Phospholipase A2 Group IIA (PLA2G2A) Genes with Susceptibility to Esophageal Squamous Cell Carcinoma

  • Liu, Fen;Wei, Wen-Qiang;Cormier, Robert T.;Zhang, Shu-Tian;Qiao, You-Lin;Li, Xin-Qing;Zhu, Sheng-Tao;Zhai, Yan-Chun;Peng, Xiao-Xia;Yan, Yu-Xiang;Wu, Li-Juan;He, Dian;He, Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1797-1802
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    • 2014
  • Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.

Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Increasing DNA Promoter Methylation

  • Zekri, Abd El-Rahman Nabawy;Nassar, Auhood Abdel-Monem;El-Rouby, Mahmoud Nour El-Din;Shousha, Hend Ibrahim;Barakat, Ahmed Barakat;El-Desouky, Eman Desouky;Zayed, Naglaa Ali;Ahmed, Ola Sayed;Youssef, Amira Salah El-Din;Kaseb, Ahmed Omar;El-Aziz, Ashraf Omar Abd;Bahnassy, Abeer Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6721-6726
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    • 2013
  • Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

Analysis of Image Distortion on Magnetic Resonance Diffusion Weighted Imaging

  • Cho, Ah Rang;Lee, Hae Kag;Yoo, Heung Joon;Park, Cheol-Soo
    • Journal of Magnetics
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    • v.20 no.4
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    • pp.381-386
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    • 2015
  • The purpose of this study is to improve diagnostic efficiency of clinical study by setting up guidelines for more precise examination with a comparative analysis of signal intensity and image distortion depending on the location of X axial of object when performing magnetic resonance diffusion weighted imaging (MR DWI) examination. We arranged the self-produced phantom with a 45 mm of interval from the core of 44 regent bottles that have a 16 mm of external diameter and 55 mm of height, and were placed in 4 rows and 11 columns in an acrylic box. We also filled up water and margarine to portrait the fat. We used 3T Skyra and 18 Channel Body array coil. We also obtained the coronal image with the direction of RL (right to left) by using scan slice thinkness 3 mm, slice gap: 0mm, field of view (FOV): $450{\times}450mm^2$, repetition time (TR): 5000 ms, echo time (TE): 73/118 ms, Matrix: $126{\times}126$, slice number: 15, scan time: 9 min 45sec, number of excitations (NEX): 3, phase encoding as a diffusion-weighted imaging parameter. In order to scan, we set b-value to $0s/mm^2$, $400s/mm^2$, and $1,400s/mm^2$, and obtained T2 fat saturation image. Then we did a comparative analysis on the differences between image distortion and signal intensity depending on the location of X axial based on iso-center of patient's table. We used "Image J" as a comparative analysis programme, and used SPSS v18.0 as a statistic programme. There was not much difference between image distortion and signal intensity on fat and water from T2 fat saturation image. But, the average value depends on the location of X axial was statistically significant (p < 0.05). From DWI image, when b-value was 0 and 400, there was no significant difference up to $2^{nd}$ columns right to left from the core of patient's table, however, there was a decline in signal intensity and image distortion from the $3^{rd}$ columns and they started to decrease rapidly at the $4^{th}$ columns. When b-value was 1,400, there was not much difference between the $1^{st}$ row right to left from the core of patient's table, however, image distortion started to appear from the $2^{nd}$ columns with no change in signal intensity, the signal was getting decreased from the $3^{rd}$ columns, and both signal intensity and image distortion started to get decreased rapidly. At this moment, the reagent bottles from outside out of 11 reagent bottles were not verified from the image, and only 9 reagent bottles were verified. However, it was not possible to verify anything from the $5^{th}$ columns. But, the average value depends on the location of X axial was statistically significant. On T2 FS image, there was a significant decline in image distortion and signal intensity over 180mm from the core of patient's table. On diffusion-weighted image, there was a significant decline in image distortion and signal intensity over 90 mm, and they became unverifiable over 180 mm. Therefore, we should make an image that has a diagnostic value from examinations that are hard to locate patient's position.

Population Size Estimation of the Kaloula borealis in the Daemyung Retarding Basin (대명유수지에 서식하는 맹꽁이 Kaloula borealis 개체군 크기 추정)

  • Choi, Seo-Young;Rho, Paikho
    • Korean Journal of Environment and Ecology
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    • v.30 no.4
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    • pp.684-693
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    • 2016
  • Daemyung retarding basin located near the confluence floodplain of the Nakdong and Kumho River is a large spawning site for the endangered Kaloula borealis, and needs for protecting the habitat of the endangered species are increasing. However, scientific studies are rarely conducted on the population characteristics and ecological knowledge on the species in the basin. This paper aims to estimate the population size and spatial distribution of the species that inhabited at the Daemyung retarding basin, using the capture-recapture method. Also, pitfall traps were installed in each habitat types classified with micro-topographic features, slope aspects, and vegetation communities to identify the spatial distribution characteristics of the Kaloula borealis of each habitat in the retarding basin. Field survey on the species was conducted from May 2013 to October 2014, showing that the species emerged in May, became more active during July and August and started to hibernate at the end of October. Using capture-recapture method, the first survey was carried out from July to August, 2014. Ninety-eight toads were captured, marked, and released back into the site. In the second survey, 68 toads including 5 marked toads of the previous survey were captured. Based on these two-sample surveys, around 535-2,131 individual toads are estimated to inhabit the Daemyung retarding basin. Fifty-seven pitfall traps were installed in four habitat types: mounded and vegetated flatland, lowland swamps, and slope areas of both the southern and western parts of the basin in order to delineate spatial abundance of the endangered Kaloula borealis during the rainy season when the species is actively spawning. Pitfall traps at the spatially explicit array indicated that the species gradually move to the slope areas near the Daemyung stream, showing high occurrence density of the Kaloula borealis compared to the lowland swamps after the spawning season. The emergence of Kaloula borealis in the lowland swamps appeared to be comparatively higher during the spawning season. However, after the spawning season the toads species rapidly moved into the neighboring land of relatively high elevation such as the slope area towards the Dalsung protected wetlands and Daemyung River. These results are closely related to the migration patterns that toads tend to return to the sheltering sites and/or hibernating grounds after the spawning season. Also, the Kaloula borealis moved to the nearest high-level vegetated areas as the lowland swamps of their spawning grounds deteriorated with the expansion of permanent ponds due to the rise in the groundwater level.

Development of a Method for Analyzing the Nicotine Content in Synthetic Flavoring Substances as Unauthorized E-cigarette Liquid by Using HPLC (전자담배 액상 충진제와 유사한 합성착향료 중 니코틴의 HPLC 분석법 개발)

  • Kim, Jae-Young;Lee, Sang-Mok;Chang, Moon-Ik;Cho, Yoon-Jae;Lee, Han-Jin;Chae, Young-Sik;Rhee, Gyu-Sik
    • Korean Journal of Food Science and Technology
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    • v.45 no.6
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    • pp.693-699
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    • 2013
  • A simple, sensitive, and specific method for quantifying the nicotine content of synthetic favoring substances (SFS) was developed using high performance liquid chromatography (HPLC) with a photo-diode array detector (PDA). Nicotine was extracted from SFS samples by using an acid-base liquid-liquid extraction method with dichloromethane and distilled water. The nicotine content was quantified by HPLC/PDA (261.9 nm) with a $C_{18}$ column under a gradient of 10% acetonitrile with 20 mM ammonium formate (ammonia solution adjusted to pH 8.7) to 100% acetonitrile. The calibration curve, analyzed from concentration standards between 0.1 to 2 mg/L, presented linearity with a correlation coefficient ($r^2$)>0.9999. The limit of quantitation (LOQ) of nicotine in SFS was 0.4 mg/kg, and the average recoveries ranged from 76.4% to 96.3%. The repeatability of measurements, expressed as the coefficient of variation (CV%), ranged from 1.74 to 5.12%. This newly developed method for nicotine quantification in SFS can be considered an analytical method with an acceptable level of sensitivity and repeatability.

Position Uncertainty due to Multi-scattering in the Scintillator Array of Dual Collimation Camera (복합 집속 카메라의 섬광체배열에서 다중산란에 의한 위치 불확실성)

  • Lee, Won-Ho
    • Journal of radiological science and technology
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    • v.31 no.3
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    • pp.287-292
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    • 2008
  • Position information of radiation interactions in detection material is essential to reconstruct a radiation source image. With most position sensing techniques, the position information of a single interaction inside the detectors can be precisely obtained. Each interaction position of multi-scattering inside scintillators, however, can not be individually measured and only the average of the scattering positions can be obtained, which causes the uncertainty in the measured interaction position. In this paper, the position uncertainties due to the multi-scattering were calculated by Monte Carlo simulation. The simulation model was a 50 by 50 by 5 mm $LaCl_3$(Ce) scintillator(pixel size is 2 by 2 by 5mm) which was utilized for the dual collimation camera. The dual collimation camera uses the information from both photoelectric effect and Compton scattering, and therefore, position uncertainties for both partial and full energy deposition of radiation interactions are calculated. In the case of partial energy deposition(PED), the standard deviations of positions are less than $1{\sim}2mm$, which means the uncertainty caused by multi-scattering is not significant. Because the effect of the multi-scattering with PED is insignificant, the multi-scattering has little effect on the performance of Compton imaging of dual collimation camera. In the case of full energy deposition(FED), however, the standard deviation of the positions is about twice that of the pixel size of the 1stdetector, except for 122keV incident radiations. Therefore, the standard deviations caused by multi-scatterings should be considered in the design of the coded mask of the dual collimation camera to avoid artifact on the reconstructed image. The position uncertainties of the FEDs are much larger than those of the PEDs for all radiation energies and the ratio of PEDs to FEDs increases when the incident radiation energy increases. The position uncertainties of both PEDs and FEDs are dependent on the incident radiation energy.

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Verification of Non-Uniform Dose Distribution in Field-In-Field Technique for Breast Tangential Irradiation (유방암 절선조사 시 종속조사면 병합방법의 불균등한 선량분포 확인)

  • Park, Byung-Moon;Bae, Yong-Ki;Kang, Min-Young;Bang, Dong-Wan;Kim, Yon-Lae;Lee, Jeong-Woo
    • Journal of radiological science and technology
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    • v.33 no.3
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    • pp.277-282
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    • 2010
  • The study is to verify non-uniform dose distribution in Field-In-Field (FIF) technique using two-dimensional ionization chamber (MatriXX, Wellhofer Dosimetrie, Germany) for breast tangential irradiation. The MatriXX and an inverse planning system (Eclipse, ver 6.5, Varian, Palo Alto, USA) were used. Hybrid plans were made from the original twenty patients plans. To verify the non-uniform dose distribution in FIF technique, each portal prescribed doses (90 cGy) was delivered to the MatriXX. The measured doses on the MatriXX were compared to the planned doses. The quantitative analyses were done with a commercial analyzing tool (OmniPro IMRT, ver. 1.4, Wellhofer Dosimetrie, Germany). The delivered doses at the normalization points were different to average 1.6% between the calculated and the measured. In analysis of line profiles, there were some differences of 1.3-5.5% (Avg: 2.4%), 0.9-3.9% (Avg: 2.5%) in longitudinal and transverse planes respectively. For the gamma index (criteria: 3 mm, 3%) analyses, there were shown that 90.23-99.69% (avg: 95.11%, std: 2.81) for acceptable range ($\gamma$-index $\geq$ 1) through the twenty patients cases. In conclusion, through our study, we have confirmed the availability of the FIF technique by comparing the calculated with the measured using MatriXX. In the future, various clinical applications of the FIF techniques would be good trials for better treatment results.

Dose Distribution and Image Quality in the Gantry Aperture for CT Examinations (전산화단층촬영 검사 시 Gantry Aperture 내의 선량분포와 영상의 질)

  • Cho, Pyong-Kon;Kim, You-Hyun;Choi, Jong-Hak;Lee, Ki-Yeol;Kim, Hyung-Cheol;Kim, Jang-Seob;Shin, Dong-Chul;Lee, Sung-Hyun;Lee, Jun-Hyub;Shin, Gwi-Soon
    • Journal of radiological science and technology
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    • v.32 no.4
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    • pp.453-460
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    • 2009
  • The purpose of this study was to determine the dose distribution and image quality according to slice thickness and BC(beam collimation) in the gantry aperture. CT scans were performed with a 64-slice MDCT(Brilliance 64, Philips, Cleveland, USA) scanner. To determine the dose distribution according to BC, a ionization chamber was placed at isocenter and 5, 10, 15, 20, 25 and 30 cm positions from the isocenter in the 12, 3, 6 and 9 o'clock directions. The dose distribution for phantom scan was also measured using CT head and body dose phantom with five holes at the center of the phantom and the positions of the 12, 3, 6 and 9 o'clock directions. The image noise measurement for different BCs was performed using an AAPM CT phantom. Water-filled block of the phantom was moved by 5 cm or 10 cm to the 12 o'clock direction, and the image noise was measured at the center of the phantom, and the points of 12, 3, 6 and 9 o'clock direction respectively. Some points were placed beyond the scan field of view (SFOV), so that measurement was not possible at that points. The results are as follows: The CTDIw showed a larger decrease as the source goes farther from the iso-center or the BC became wider. The CTDIw depends on the BC width more than the number of the channel of a detector array. The value of CTDIW decreased with increasing BC, but the value decreased 16.6~31.9% in the head phantom scan in air scan and 51.0~64.5% in the body phantom scan. The value of the noise was 3.9~5.9 in the head and 5.3~7.4 in the body except for BC of $2{\times}0.5\;mm$, regardless of the degree of deviation from the iso-center. When a subject was located within the SFOV, the position did not significantly affect image quality even if the subject was out of the center.

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Characteristics of Sea Water Intrusion Using Geostatistical Analysis of Geophysical Surveys at the Southeastern Coastal Area of Busan, Korea (지구물리 탐사자료의 지구통계학적 분석에 의한 부산 동남해안 지역의 해수침투 특성)

  • 심병완;정상용;김희준;성익환;김병우
    • Journal of Soil and Groundwater Environment
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    • v.7 no.3
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    • pp.3-17
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    • 2002
  • Data analysis of groundwater monitoring wells and geostatistical methods are used to identify the local characteristics of sea water intrusion and the range of sea water intrusion at the southeastern coastal area of Busan, Korea. Rainfall and groundwater level of two monitoring wells show a linear correlation because of the direct groundwater recharge by the precipitation. However, rainfall and electric conductivity have the inverse relationship because of the increase of groundwater. Electric conductivity rapidly increased at 24m depth and exceeded 20,000$\mu\textrm{s}$/cm near 26m depth in the monitoring wells. The variations of groundwater level and electric conductivity show that the interface between sea water and fresh water tends to move upward when groundwater level goes down. In the cross correlation analysis, groundwater level versus rainfall represents the largest cross correlation coefficient in 0 time lag but the cross correlation coefficient of electric conductivity versus rainfall is the largest when the time lag is 9 days. This suggests that the fluctuations of groundwater level respond to rainfall in a short time, but the interface between sea water and fresh water respond very slow to rainfall. Horizontal extents of sea water intrusion are estimated to 14 m from the east of Line 1, and 25 m from the southeast end of Line 2 in the inversion of dipole-dipole profiling data of two survey lines. The data of VES by the Schulumberger array in May and July show lognormal distributions. In the kriged apparent resistivity and earth resistivity distributions, the resistivities of July are increased comparing to those of May. This reflects that the concentration of sea water in aquifer is reduced due to the increased groundwater recharge from the rainfall in June and July. In analyzing the vertical and horizontal apparent resistivities and earth resistivity distributions, the geostatistical methods are very useful to identify the variations of earth resistivity distributions at the coastal area.

The Immunohistochemical Analysis for the Expression of Survivin, HSP, and Bcl-2 in Non-small Cell Lung Carcinoma (비소세포폐암에서 Survivin, HSP 및 Bcl-2 발현에 관한 면역조직화학적 분석)

  • Hong, Hyun-Ju;Hong, Seok-Gyun;Lee, Kye-Young;Kim, Woo-Ho;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.441-452
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    • 2002
  • Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.