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Significance of HPV Infection and Genic Mutation of APC and K-ras in Patients with Rectal Cancer

  • Sun, Zhen-Qiang;Wang, Hai-Jiang;Zhao, Ze-Liang;Wang, Qi-San;Fan, Chuan-Wen;Kureshi, Kureshi;Fang, Fa
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.121-126
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    • 2013
  • Background: Significance of HPV infection and genic mutation of APC and K-ras in rectal cancer has been investigated but not clarified. The objective of our study was to investigate these parameters in patients with rectal cancer to analyze correlations with biological behaviour, to determine relationships among the three, and also to demonstrate survival prognosis effects. Methods: From December 2007 to September 2008, 75 rectal cancer cases confirmed by histopathology in the Tumor Hospital of Xinjiang Medical University were enrolled. The control group consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm distant from the carcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras were detected by PCR and PCR-SSCP. All results were analyzed in relation to clinical pathological material, using chi-square and correlation analysis via SPSS.13 and Fisher's Exact Probability via STATA. 9.0. All 75 patients were followed up for survival analysis using Kaplan-Meier and Log-rank tests. Results: 55 out of 75 cases demonstrated gene HPV L1 while it was notdetected in normal rectal mucosa tissue. HPV infection was correlated with age and lymphatic metastasis (P<0.05) but not other characteristics, such as ethnicity, tumor size, histological type, tumor type, Duke's stage and infiltration depth. Some 43 cases exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation (45.3%). APC genic mutation was correlated with gender(P<0.05), but not age, histological type, infiltration depth, lymphatic metastasis and Duke's stage. In 55 cases of rectal cancer with HPV infection, there were 31 cases with genic mutation of APC (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases of rectal cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%), respectively, with no significant relation. Survival analysis showed no statistical significance for K-ras genic mutation, APC genic mutation or HPV infection (P>0.05). However, the survival time of the patients with HPV infection was a little shorter than in cases without HPV infection. Conclusions: Our results suggest that HPV infection might be an important factor to bring about malignant phenotype of rectal cancer and influence prognosis. Genic mutation of APC and K-ras might be common early molecular events of rectal cancer, but without prognostic effects on medium-term or early stage patients with rectal cancer.

Pattern of Asthma Management by Primary Physicians in Seoul (서울 지역 내과 개원의 천식 진료 양상)

  • Lee, Eui Kyung;Bae, Eun Young;Park, Eun Ja;Lee, Suk Hyang;Oh, Yeon-Mok;In, Kwang Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.2
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    • pp.165-174
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    • 2003
  • Background : Asthma is one of the most prevalent diseases in Korea. Although the guidelines of asthma management were reported in Korea, the present pattern of asthma management by primary physicians has not been studied. The purpose of this study is to elucidate the pattern of asthma management by primary physicians. Methods : In November 2002, 710 primary physicians specializing in internal medicine in Seoul, Korea were provided with two scenarios of asthmatic patients, one mild and the other severe. By mail or interview, the physicians were asked several questions about their present pattern of asthma management for the patients in each scenario. Results : Among 710 primary physicians, we obtained the answers from 325 physicians (response rate 46%). The most preferred prescription was oral theophylline. 71% and 81% of the physicians answered that they would prescribe oral theophylline for the mild and severe asthmatics, respectively. The next prescription preferred were mucolytics and oral ${\beta}_2$-agonist, in that order. However, 36% and 56% of the physicians answered that they would prescribe inhaled steroids for the mild and severe asthmatics, respectively. Among diagnostic tests, physicians preferred pulmonary function test to the rank next to chest radiography. Conclusion : The primary physicians in Seoul prefer oral bronchodilators to inhaled steroids in asthma management. More efforts should be made to reduce the difference between the present pattern of asthma management by primary physicians and the asthma guidelines.

The Effect of CYP2D6/3A5 Genotypes on Plasma Concentrations of Haloperidol after Adjunctive Treatment of Aripiprazole

  • Shim, Joo-Cheol;Ahn, Jung-Mi;Jung, Do-Un;Kong, Bo-Geum;Kang, Jae-Wook;Liu, Kwang-Hyeon;Shin, Jae-Gook
    • Korean Journal of Biological Psychiatry
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    • v.18 no.2
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    • pp.95-100
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    • 2011
  • Objectives To evaluate the drug interactions between aripiprazole and haloperidol, authors investigated plasma concentrations of those drugs by genotypes. Method Fifty six patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders 4th edition diagnosis of schizophrenia were enrolled in this eight-week, double blind, placebo-controlled study. Twenty-eight patients received adjunctive aripiprazole treatment and twenty-eight patients received placebo while being maintained on haloperidol treatment. Aripiprazole was dosed at 15 mg/day for the first 4 weeks, and then 30 mg for the next 4 weeks. The haloperidol dose remained fixed throughout the study. Plasma concentrations of haloperidol and aripiprazole were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, week 1, 2, 4 and 8. $^*1$, $^*5$, and $^*10$ B alleles of CYP2D6 and $^*1$ and $^*3$ alleles of CYP3A5 were determined. The Student's T-test, Pearson's Chi-square test, Wilcoxon Rank Sum test and Logistic Regression analysis were used for data analysis. All tests were two-tailed and significance was defined as an alpha < 0.05. Results In the frequency of CYP2D6 genotype, $^*1/^*10$ B type was most frequent (36.5%) and $^*1/^*1$ (30.8%), $^*10B/^*10B$ (17.3%) types followed. In the frequency of CYP3A5 genotype, $^*3/^*3$ type was found in 63.5% of subjects, and $^*1/^*3$ type and $^*1/^*1$ were 30.8% and 5.8% respectively. The plasma levels of haloperidol and its metabolites did not demonstrate significant time effects and time-group interactions after adjunctive treatment of aripiprazole. The genotypes of CYP2D6 and 3A5 did not affect the plasma concentration of haloperidol in this trial. No serious adverse event was found after adding aripiprazole to haloperidol. Conclusion No significant drug interaction was found between haloperidol and aripiprazole. Genotypes of CYP2D6 and 3A5 did not affect the concentration of haloperidol after adding aripiprazole.

Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients

  • Sarojam, Santhi;Raveendran, Sureshkumar;Vijay, Sangeetha;Sreedharan, Jayadevan;Narayanan, Geetha;Sreedharan, Hariharan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3785-3792
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    • 2015
  • The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that plays a crucial role in the control of proliferation and differentiation of myeloid precursors. This gene was recognized as the target of genetic alterations and were associated with clinical complexity among AML. We here analyze the frequency and types of CEBPA mutations and polymorphisms in a de novo AML patients from South India and tried to find out associations of these variations with different clinical parameters and the prognostic significance in AML. Study was carried out in 248 de novo AML patients, cytogenetic analysis was performed from the bone marrow samples and was karyotyped. PCR-SSCP analysis and sequencing was performed for the detection of CEBPA gene variations. All the statistical analysis was performed using SPSS 17 (statistical package for social sciences) software. Pearson Chi-square test, Mann-Whitney U test, Kaplan-Meier survival analysis and log rank tests were performed. CEBPA mutations were detected in 18% and CEBPA polymorphisms were detected in 18.9% of AML cases studied. Most of the mutations occured at the C terminal region. Polymorphisms were detected in both N and C terminal region. with most common being, c.584_589dup ACCCGC and c.690G>T. A significant association was not observed for the mutation and polymorphism with respect to clinical and laboratory parameters. Survival advantage was observed for the mutated cases compared to non mutated cases, especially for the normal karyotype groups. Polymorphisms has no effect on the survival pattern of AML patients. CEBPA mutation and polymorphisms were observed with similar frequency and was identified in all the FAB subtypes as well as in cytogenetic risk groups in our study population, but CEBPA mutations alone confer a prognostic value for NK AML patients.

Prognosis and Management for Gallbladder Cancer with Hepatic Invasion: Long-term Results of 139 Patients from a Single Center in China

  • Qu, Kai;Chang, Hu-Lin;Liu, Si-Nan;Liu, Chang;Xu, Xin-Sen;Wang, Rui-Tao;Zhou, Lei;Tian, Feng;Wei, Ji-Chao;Tai, Ming-Hui;Meng, Fan-Di
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.1015-1018
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    • 2012
  • Objective: To improve the diagnosis of primary gallbladder carcinoma (GBC) with/without hepatic metastases by analyzing our experience of different GBC treatment in our patients. Methods: A retrospective study was carried out to analyze the clinical data of the 139 patients with GBC who underwent hepatic resection in our unit from January 2003 to December 2007. Patients were divided into two groups according to whether they demonstrated hepatic invasion. Tumor presentation, surgical modes, and prognosis of each patient were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the survival rates of those patients undergoing different surgical procedures. Results: Of the 139 patients, 46 were men and 93 were women with the male to female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age of $62.8{\pm}10.4$ years. There were 73 patients complicated with hepatic invasion (group A), and no hepatic invasion occurred in the other 66 patients (group B). Compared with the group B, the patients with hepatic invasion suffered lower differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and poorer prognosis (p=0.013). Radical resection were more frequently performed in group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000). Conclusion: GBC patients complicated with hepatic invasion had poorer prognosis than those without invasion in long-term follow-ups. Radical resection might result in a satisfied prognosis in patients without hepatic invasion, but appears less favorable than palliative resection in those who were complicated with hepatic invasion.

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

  • Xu, Jia-Li;Hu, Ling-Min;Huang, Ming-De;Zhao, Wan;Yin, Yong-Mei;Hu, Zhi-Bin;Ma, Hong-Xia;Shen, Hong-Bing;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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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.

Effect of a Worksite-based Dietary Intervention Program for the Management of Metabolic Syndrome (대사증후군 관리를 위한 직장기반 식생활 중재 프로그램의 효과)

  • Kim, Hye Jin;Choi, Injoo;Kim, Won Gyoung;Asano, Kana;Hong, Jeongmin;Cho, Young Min;Yoon, Jihyun
    • Korean Journal of Community Nutrition
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    • v.21 no.3
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    • pp.237-246
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    • 2016
  • Objectives: To investigate the effect of a worksite-based dietary intervention program for the management of metabolic syndrome (MS) among male employees. Methods: A dietary intervention program combining individual and environmental approach was implemented targeting white-collar employees at a worksite located in Seoul for 10 weeks. Out of 104 employees having agreed to participate in the program, those having three or more out of five components of MS and having two components, including a waist circumference component were classified into "the high risk group" (n=41) and received group nutrition education and individual nutrition counseling three times each. The rest of the study subjects were considered as "the low risk group" (n=63). The food environment at the worksite, where both the high and low risk groups were exposed, was changed to promote healthy eating. Physical data including MS components were collected and a questionnaire on dietary behaviors was administered before and after the intervention. The data from the high risk group (n=17) and the low risk group (n=20), excluding the subjects ineligible for or failed to complete the study (n=67), were analyzed. The difference before and after intervention was tested for significance by Wilcoxon signed-rank tests. Results: Weight, body mass index (BMI), waist circumference, blood pressure, HDL-cholesterol, and HbA1c and the healthy dietary practice score improved significantly after intervention in the high risk group. The median number of MS components decreased significantly from 3.0 to 1.0 in the high risk group. In the low risk group, only HbA1c significantly decreased. Conclusions: The 10-week worksite-based dietary intervention program combining individual and environmental approach was found to be effective for managing MS of male employees.

Proposal of stability standards for slopes reclaimed by soils mixed with stone dust (석분슬러지 혼합토 매립사면에 대한 안정성 기준 제안)

  • Song, Young-Suk;Kim, Kyeng-Su
    • The Journal of Engineering Geology
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    • v.17 no.3
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    • pp.425-434
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    • 2007
  • In this paper, the stability standards of slopes reclaimed by soils mixed with stone dust were proposed to manage the stone dust as recovery soils. First of all, the mixed ratio between stone dust and natural soil is classified into 5 groups, and a series of soil test was performed in each group. As the results of tests, the shear strength and the maximum dry unit weight were increased in decrease of the mixed ratio of stone dust. On the basis of the investigation to the safety factor standards of embankment slopes in and outside the country, a slope stability rank of slopes reclaimed by mixed soils were divided into 3 stages such as unstable stage, attention stage and stable stage. The slope angle, the slope height and the mixed ratio with stone dust were proposed by the result of stability analysis of slopes reclaimed by mixed soils. As the result of slope stability analysis, the slope angle of 1 : 1.8 at the reclaimed slope should be constructed in case of the slope height of 10 m. Also, the slope angle of 1 : 1.8 and the mixed ratio of stone dust less than 50% should be constructed in case of the slope height of 15 m. The analysis result of reclaimed slope constructed inside the quarry is similar to that of reclaimed slope constructed on the open ground in same conditions of the slope angle, the slope height and the mixed ratio with stone dust. The proposed stability standards of slopes reclaimed by soils mixed with stone dust can be used practically at the quarrying site.

The Relationship Between Balance and Gait Outcome in Patients With Stroke (뇌졸중환자의 균형과 보행능력과의 관계)

  • Kim, Myoung-Jin;Yi, Chung-Hwi;Chung, Bo-In;Lee, Young-Hee
    • Physical Therapy Korea
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    • v.5 no.1
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    • pp.17-29
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    • 1998
  • The purpose of this study was to identify the relationship between sitting and standing balance in acute stroke patients and gait outcome, and to determine appropriate test times. The subjects of this study were 20 hemiplegic patients who had been hospitalized in Sangji University Oriental Medical Hospital from August 26, 1997 through November 3, 1997. Twenty patients with cerebral infarcts had sitting and standing balance assessed on the 5th day and 10th day of stroke onset. Gait outcome was assessed 5 weeks later using the MMAS (Modified Motor Assessment Scale) score. The data were analyzed by the Spearman's Rho test and Wilcoxon signed rank test. The results were as follows: 1) Correlation coefficients between sitting balance on the 5th day and 10th day after their stroke and gait outcome 5 weeks after their stroke were $r_s$=0.89 and $r_s$=0.83, respectively. All of the sitting balance data significantly correlated with gait outcome (p<0.05). 2) Correlation coefficients between standing balance on the 5th day and 10th day after their stroke and gait outcome 5 weeks after their stroke were $r_s$=0.82 and $r_s$=0.87, respectively. All of the standing balance data significant1y correlated with gait outcome (p<0.05). 3) The difference between sitting balance scores on the 5th day and 10th day after stroke onset were statistically significant (p<0.05). But the difference between standing balance scores on the 5th day and 10th day after stroke onset were not statistically significant (p>0.05). In conclusion, sitting and standing balance tests on the 5th day and 10th day after their stroke appear to be predictive of gait outcome. Also, the result of this study can provide reference for appropriate test times as an assessment of sitting and standing balance in stroke patients.

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Associations Between Body Fat Percentage and Fitness among Police Officers: A Statewide Study

  • Violanti, John M.;Ma, Claudia C.;Fekedulegn, Desta;Andrew, Michael E.;Gu, Ja K.;Hartley, Tara A.;Charles, Luenda E.;Burchfiel, Cecil M.
    • Safety and Health at Work
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    • v.8 no.1
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    • pp.36-41
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    • 2017
  • Background: Police work is generally sedentary although there may be situations that require physical endurance and strength, such as foot chases and arresting suspects. Factors such as excessive body fat can impede an officer's physical ability to deal with such occurrences. Our objective was to examine associations between officers' body fat percentage (BF%) and performance on a standardized fitness protocol. Methods: Data were obtained from fitness screening among 1,826 male and 115 female officers in a large US police agency. The screening consisted of a 2.4-km run, push-ups, sit-ups, and sit-and-reach test. Sex-specific body fat percentages were estimated from skinfold thickness measured using calipers. Linear regression models were used to examine unadjusted and adjusted mean scores of fitness tests across BF% tertiles. Results: The prevalence of overall fitness was 4.3 times greater in male officers and 3.6 times greater in female officers having the lowest BF% tertile compared with the highest tertile (30.3% vs 7.1% and 46.0% vs 12.8%, respectively). BF% was linearly and positively associated with the time of 2.4-km run (p < 0.001), and linearly and inversely associated with the number of push-ups (p < 0.001), sit-ups (p < 0.001), and the distance of sit-and-reach (p < 0.001) in men. Similar associations were observed in women with the exception of sit-and-reach (p = 0.122). Associations were independent of age, race/ethnicity, rank, and duty station. Conclusion: Overall, BF% was inversely associated with fitness levels in male and female officers. Future longitudinal studies should be initiated to explore the potentially causal relationship between BF% and fitness in law enforcement officers.