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1

A pooled analysis of thyroid cancer studies. V. Anthropometric factors  

Microsoft Academic Search

Objective: To assess the relation between anthropometric factors and thyroid cancer risk in a pooled analysis of individual data from 12 case–control studies conducted in the US, Japan, China and Europe.

Luigino Dal Maso; Carlo La Vecchia; Silvia Franceschi; Susan Preston-Martin; Elaine Ron; Fabio Levi; Wendy Mack; Steven D. Mark; Anne McTiernan; Laurence Kolonel; Kiyohiko Mabuchi; Fan Jin; Gun Wingren; Maria Rosaria Galanti; Arne Hallquist; Eystein Glattre; Eiliv Lund; Dimitrios Linos; Eva Negri

2000-01-01

2

Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis From the International Lung Cancer Consortium  

PubMed Central

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984–2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk. PMID:22986146

Brenner, Darren R.; Boffetta, Paolo; Duell, Eric J.; Bickeboller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E.; Yang, Ping; Wichmann, H.-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G.; Cote, Michele L.; Tj?nneland, Anne; Friis, S?ren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N.; Lazarus, Philip; Field, John K.; Raji, Olaide; McLaughlin, John R.; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S.; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J.; Hung, Rayjean J.

2012-01-01

3

A Pooled Analysis of Thyroid Cancer Incidence Following Radiotherapy for Childhood Cancer  

PubMed Central

Childhood cancer five-year survival now exceeds 70–80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9–14.9), 4.5 (1.4–17.8) and 3.2 (0.8–10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10–15-fold for 10–30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0–24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors. PMID:22857014

Veiga, Lene H. S.; Lubin, Jay H.; Anderson, Harald; de Vathaire, Florent; Tucker, Margaret; Bhatti, Parveen; Schneider, Arthur; Johansson, Robert; Inskip, Peter; Kleinerman, Ruth; Shore, Roy; Pottern, Linda; Holmberg, Erik; Hawkins, Michael M.; Adams, M. Jacob; Sadetzki, Siegal; Lundell, Marie; Sakata, Ritsu; Damber, Lena; Neta, Gila; Ron, Elaine

2012-01-01

4

Lung cancer risk among bricklayers in a pooled analysis of case-control studies.  

PubMed

Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p?cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos. PMID:24861979

Consonni, Dario; De Matteis, Sara; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel C H; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, H B As; Schüz, Joachim; Straif, Kurt

2015-01-15

5

Intake of Fruits and Vegetables and Risk of Pancreatic Cancer in a Pooled Analysis of 14 Cohort Studies  

PubMed Central

Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7?20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk. PMID:22875754

Koushik, Anita; Spiegelman, Donna; Albanes, Demetrius; Anderson, Kristin E.; Bernstein, Leslie; van den Brandt, Piet A.; Bergkvist, Leif; English, Dallas R.; Freudenheim, Jo L.; Fuchs, Charles S.; Genkinger, Jeanine M.; Giles, Graham G.; Goldbohm, R. Alexandra; Horn-Ross, Pamela L.; Mannisto, Satu; McCullough, Marjorie L.; Millen, Amy E.; Miller, Anthony B.; Robien, Kim; Rohan, Thomas E.; Schatzkin, Arthur; Shikany, James M.; Stolzenberg-Solomon, Rachael Z.; Willett, Walter C.; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

2012-01-01

6

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO)  

PubMed Central

Background: The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated. Methods: We performed a pooled analysis of six case–control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types. Results: A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68–0.97) and HRT ever users (OR=0.77; 95% CI: 0.66–0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61–0.94, and OR=0.66; 95% CI: 0.49–0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37–0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66–0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19–0.71) in HRT users. No interaction with smoking status or BMI was observed. Conclusion: Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women. PMID:24002594

Pesatori, A C; Carugno, M; Consonni, D; Hung, R J; Papadoupolos, A; Landi, M T; Brenner, H; Muller, H; Harris, C C; Duell, E J; Andrew, A S; McLaughlin, J R; Schwartz, A G; Wenzlaff, A S; Stucker, I

2013-01-01

7

Meta- and Pooled Analysis of GSTP1 Polymorphism and Lung Cancer: A HuGE-GSEC Review  

PubMed Central

Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A ? 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio?=?1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites. PMID:19240225

Chen, Wei; Smith, Daryn W.; Benhamou, Simone; Bouchardy, Christine; Butkiewicz, Dorota; Fong, Kwun M.; Gene, Manuel; Hirvonen, Ari; Kiyohara, Chikako; Larsen, Jill E.; Lin, Pinpin; Raaschou-Nielsen, Ole; Povey, Andrew C.; Reszka, Edyta; Risch, Angela; Schneider, Joachim; Schwartz, Ann G.; Sorensen, Mette; To-Figueras, Jordi; Tokudome, Shinkan; Pu, Yuepu; Yang, Ping; Wenzlaff, Angela S.; Wikman, Harriet; Taioli, Emanuela

2009-01-01

8

Fruits, vegetables and lung cancer: a pooled analysis of cohort studies.  

PubMed

Inverse associations between fruit and vegetable consumption and lung cancer risk have been consistently reported. However, identifying the specific fruits and vegetables associated with lung cancer is difficult because the food groups and foods evaluated have varied across studies. We analyzed fruit and vegetable groups using standardized exposure and covariate definitions in 8 prospective studies. We combined study-specific relative risks (RRs) using a random effects model. In the pooled database, 3,206 incident lung cancer cases occurred among 430,281 women and men followed for up to 6-16 years across studies. Controlling for smoking habits and other lung cancer risk factors, a 16-23% reduction in lung cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of consumption for total fruits (RR = 0.77; 95% CI = 0.67-0.87 for quintile 5; p-value, test for trend < 0.001) and for total fruits and vegetables (RR = 0.79; 95% CI = 0.69-0.90; p-value, test for trend = 0.001). For the same comparison, the association was weaker for total vegetable consumption (RR = 0.88; 95% CI = 0.78-1.00; p-value, test for trend = 0.12). Associations were similar between never, past, and current smokers. These results suggest that elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk, which is mostly attributable to fruit, not vegetable, intake. However, we cannot rule out the possibility that our results are due to residual confounding by smoking. The primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation. PMID:14601062

Smith-Warner, Stephanie A; Spiegelman, Donna; Yaun, Shiaw-Shyuan; Albanes, Demetrius; Beeson, W Lawrence; van den Brandt, Piet A; Feskanich, Diane; Folsom, Aaron R; Fraser, Gary E; Freudenheim, Jo L; Giovannucci, Edward; Goldbohm, R Alexandra; Graham, Saxon; Kushi, Lawrence H; Miller, Anthony B; Pietinen, Pirjo; Rohan, Thomas E; Speizer, Frank E; Willett, Walter C; Hunter, David J

2003-12-20

9

Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium  

PubMed Central

Background Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. Methods We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. Results This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height =0.91, 95% CI 0.86–0.95 for men; adjusted OR=0.86, 95% CI 0.79–0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Conclusions Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted. PMID:24271556

Leoncini, Emanuele; Ricciardi, Walter; Cadoni, Gabriella; Arzani, Dario; Petrelli, Livia; Paludetti, Gaetano; Brennan, Paul; Luce, Daniele; Stucker, Isabelle; Matsuo, Keitaro; Talamini, Renato; La Vecchia, Carlo; Olshan, Andrew F.; Winn, Deborah M.; Herrero, Rolando; Franceschi, Silvia; Castellsague, Xavier; Muscat, Joshua; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Maso, Luigino Dal; Kelsey, Karl; McClean, Michael; Vaughan, Thomas L; Lazarus, Philip; Purdue, Mark P.; Hayes, Richard B.; Chen, Chu; Schwartz, Stephen M.; Shangina, Oxana; Koifman, Sergio; Ahrens, Wolfgang; Matos, Elena; Lagiou, Pagona; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Fernandez, Leticia; Menezes, Ana; Agudo, Antonio; Daudt, Alexander W.; Richiardi, Lorenzo; Kjaerheim, Kristina; Mates, Dana; Betka, Jaroslav; Yu, Guo-Pei; Schantz, Stimson; Simonato, Lorenzo; Brenner, Hermann; Conway, David I; Macfarlane, Tatiana V.; Thomson, Peter; Fabianova, Eleonora; Znaor, Ariana; Rudnai, Peter; Healy, Claire; Boffetta, Paolo; Chuang, Shu-Chun; Lee, Yuan-Chin Amy; Hashibe, Mia; Boccia, Stefania

2014-01-01

10

Lung cancer risk among hairdressers: a pooled analysis of case-control studies conducted between 1985 and 2010.  

PubMed

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

Olsson, Ann C; Xu, Yiwen; Schüz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Marcus, Michael W; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Brüning, Thomas; Straif, Kurt

2013-11-01

11

Lung Cancer Risk Among Hairdressers: A Pooled Analysis of Case-Control Studies Conducted Between 1985 and 2010  

PubMed Central

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

Olsson, Ann C.; Xu, Yiwen; Schuz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stucker, Isabelle; Guida, Florence; Bruske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jockel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardon, Adonina; Zaridze, David; Marcus, Michael W.; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Bruning, Thomas; Straif, Kurt

2013-01-01

12

Thyroid cancer after exposure to external radiation: A pooled analysis of seven studies  

SciTech Connect

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (>10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10{sup 4} PY Gy (EAR/10{sup 4} PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. 56 refs., 5 figs., 8 tabs.

Ron, E.; Lubin, J.H.; Pottern, L.M.; Tucker, M.A.; Boice, J.D. Jr. [National Institutes of Health, Bethesda, MD (United States); Shore, R.E. [New York University Medical Center, NY (United States); Mabuchi, Kiyohiko [Radiation Effects Research Foundation, Hiroshima (Japan); Modan, B. [Chaim Sheba Medical Center, Tel Hashomer (Israel); Schneider, A.B. [Univ. of Illinois, Chicago, IL (United States)

1995-03-01

13

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis  

PubMed Central

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case–control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3? variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case–control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01–1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62–1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer. PMID:18219286

Pearce, C L; Wu, A H; Gayther, S A; Bale, A E; Beck, P A; Beesley, J; Chanock, S; Cramer, D W; DiCioccio, R; Edwards, R; Fredericksen, Z S; Garcia-Closas, M; Goode, E L; Green, A C; Hartmann, L C; Hogdall, E; Kjaer, S K; Lissowska, J; McGuire, V; Modugno, F; Moysich, K; Ness, R B; Ramus, S J; Risch, H A; Sellers, T A; Song, H; Stram, D O; Terry, K L; Webb, P M; Whiteman, D C; Whittemore, A S; Zheng, W; Pharoah, P D P; Chenevix-Trench, G; Pike, M C; Schildkraut, J; Berchuck, A

2008-01-01

14

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).  

PubMed

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

2014-10-15

15

Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium  

PubMed Central

Background and Methods Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analyzed. Unconditional logistic regression models and generalized estimating equations were used to estimate odds ratios and 95% confidence intervals. Results Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in risk of lung cancer, after adjustment for smoking and other potential confounders(95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (OR=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions The increased risk among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those associated with cigarette smoking. While the role of genetic variation in the etiology of lung cancer remains to be fully characterized, family history assessment is immediately available and those with a positive history represent a higher risk group. PMID:22436981

Cote, Michele L.; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G.; Christiani, David C.; Spitz, Margaret R.; Muscat, Joshua E.; Rennert, Gad; Aben, Katja K.; Andrew, Angeline S.; Bencko, Vladimir; Bickeboller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J.; Fabianova, Eleonora; Field, John K.; Foretova, Lenka; Friis, S?ren; Harris, Curtis C.; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A.; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Marchand, Loic Le; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I.; McLaughlin, John R.; Morgenstern, Hal; Mueller, Heiko; Orlow, Irene; Park, Bernard J.; Pinchev, Mila; Raji, Olaide Y.; Rennert, Hedy S.; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Teare, M. Dawn; Tj?nnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F.M.; Wichmann, Erich; Wiencke, John K.; Woll, Penella J.; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J.; Hung, Rayjean J.

2012-01-01

16

Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer  

Microsoft Academic Search

Esophageal cancer has been associated with tobacco and alcohol consumption, gastric reflux, exposure to nitrosamines from food or other environmental sources, and diets lacking folate. Susceptibility to esophageal cancer may be modified by functional polymorphisms in genes along the folate metabolic pathway, such as methylenetetrahydrofolate reductase (MTHFR). The C677T polymorphism is the most common functional variant, leading to a reduction

S. M. Langevin; D. Lin; K. Matsuo; C. M. Gao; T. Takezaki; R. Z. Stolzenberg-Solomon; M. Vasavi; Q. Hasan; E. Taioli

2009-01-01

17

Welding and Lung Cancer in a Pooled Analysis of Case-Control Studies  

PubMed Central

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer. PMID:24052544

Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H.-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; ‘t Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

2013-01-01

18

Active Smoking and Breast Cancer Incidence: Pooled Analysis of Cohort Data - Mia Gaudet, Ph.D.  

Cancer.gov

October 30, 2014 10:00 AM - 11:00 AM Shady Grove Room 2E 908 + Add to Outlook Calendar NOTE NEW TIME:  10:00 to 11:00 AM Speaker: Mia Gaudet, Ph.D.Director, Genetic EpidemiologyAmerican Cancer Society, Inc. Host: Shelia Hoar Zahm, Sc.D., Scientific

19

Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis.  

PubMed

The 70-gene signature (MammaPrint™) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6 % (95 % CI 9.7-15.8) at 10 years, compared to 6.1 % (95 % CI 4.1-8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95 % CI 1.02-2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95 % CI 0.682-0.782) to 0.741 (95 % CI 0.693-0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature. PMID:25414025

Drukker, C A; Elias, S G; Nijenhuis, M V; Wesseling, J; Bartelink, H; Elkhuizen, P; Fowble, B; Whitworth, P W; Patel, R R; de Snoo, F A; van 't Veer, L J; Beitsch, P D; Rutgers, E J Th

2014-12-01

20

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium.  

PubMed

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.59-0.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC. PMID:22173631

Li, Qian; Chuang, Shu-Chun; Eluf-Neto, Jose; Menezes, Ana; Matos, Elena; Koifman, Sergio; Wünsch-Filho, Victor; Fernandez, Leticia; Daudt, Alexander W; Curado, Maria Paula; Winn, Deborah M; Franceschi, Silvia; Herrero, Rolando; Castellsague, Xavier; Morgenstern, Hal; Zhang, Zuo-Feng; Lazarus, Philip; Muscat, Joshua; McClean, Michael; Kelsey, Karl T; Hayes, Richard B; Purdue, Mark P; Schwartz, Stephen M; Chen, Chu; Benhamou, Simone; Olshan, Andrew F; Yu, Guopei; Schantz, Stimson; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia

2012-10-01

21

Alcohol, tobacco, diet and the risk of oral cancer: a pooled analysis of three case-control studies  

Microsoft Academic Search

This combined analysis of data from three large case—control studies of oral cancer confirms the important effect of tobacco in the aetiology of the disease. The studies have been conducted in the United States, Italy and China and results for risks associated with tobacco smoking were generally consistent across centres, while those for alcohol were not; increased risks amongst alcohol

G. J. Macfarlane; T. Zheng; J. R. Marshall; P. Boffetta; S. Niu; J. Brasure; F. Merletti; P. Boyle

1995-01-01

22

Risk of selected gastrointestinal toxicities in breast cancer patients treated with regimens containing lapatinib; a pooled analysis of randomized controlled studies.  

PubMed

We performed a pooled analysis of randomized controlled studies evaluating selected gastrointestinal adverse events associated with lapatinib use in breast cancer patients. Eligible studies included randomized Phase II and III trials of patients with breast cancer on lapatinib; describing events of diarrhea, nausea, vomiting and stomatitis. Our search strategy yielded 390 potentially relevant citations on lapatinib from Pubmed/Medline and other databases. After exclusion of ineligible studies, a total of 19 clinical trials were considered eligible for the analysis. The relative risk (RR) of all-grade diarrhea, nausea, vomiting and stomatitis were 3.09 (95% CI: 2.14-4.43; p < 0.00001), 1.24 (95% CI: 1.07- 1.43; p < 0.005), 1.35 (95% CI: 1.22-1.49; p = 0.0001), 1.96 (95% CI: 1.07-2.67; p = 0.02); respectively. Exploratory subgroup analysis showed no effect of disease stage on the RR of the relevant adverse events. While, The RR of high-grade diarrhea, nausea, vomiting and stomatitis were 6.63 (95% CI: 2.94-14.96; p < 0.00001), 1.37 (95% CI: 0.91-2.06; p = 0.13), 1.80 (95% CI: 1.21-2.68; p = 0.004), 2.44 (95% CI: 1.41-4.22 p < 0.001); respectively. Our pooled analysis has demonstrated that regimens containing lapatinib are associated with a significantly increased risk of high-grade diarrhea, vomiting and stomatitis in patients with breast cancer. Clinicians should be aware of these risks and perform regular clinical monitoring. PMID:25119858

Abdel-Rahman, Omar; Fouad, Mona

2014-10-01

23

EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data  

PubMed Central

Introduction Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC). The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs) were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group), and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8%) and 75.7% (95% CI: 70.3%–80.5%), respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%); a similar trend was observed for the DCR (94.6% vs 71.3%). The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9) and 11.9 months (95% CI, 7.7–16.2), respectively, with longer PFS (12.3 months vs 5.9 months) and OS (16.2 months vs 10.3 months) in the EGFR mutation group than in the unselected group. Conclusion This pooled analysis strongly suggests that EGFR-TKIs are an effective treatment for NSCLC patients with brain metastases, particularly in those patients harboring EGFR mutations. Larger prospective randomized clinical trials are warranted to confirm our conclusion and identify the most appropriate treatment model.

Fan, Yun; Xu, Xiaoling; Xie, Conghua

2014-01-01

24

Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case-control studies.  

PubMed

Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection practices and DBPs occurrence between both continents, specific risk estimates for bladder cancer in relation to DBPs exposure for European populations were needed. We conducted a pooled and a two-stage random-effect meta-analyses of three European case-control studies from France, Finland, and Spain (5467 individuals: 2381 cases and 3086 controls). Individual exposure to THMs was calculated combining information on residential history, estimates of the average total THMs (TTHM) level in tap water at the successive residences and personal water consumption. A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 ?g/l (OR = 1.47 (1.05; 2.05)) when compared to men exposed to levels ? 5 ?g/l. The linear trend of the exposure-risk association was significant (p = 0.01). Risks increased significantly for exposure levels above 25 ?g/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion. There was no evidence of a differential exposure-response relation for TTHM and bladder cancer in Europe and North America. Consequently, a global exposure-risk relation based on 4351 cases and 7055 controls is now available. PMID:21389011

Costet, N; Villanueva, C M; Jaakkola, J J K; Kogevinas, M; Cantor, K P; King, W D; Lynch, C F; Nieuwenhuijsen, M J; Cordier, S

2011-05-01

25

Stage-specific analysis of plasma protein profiles in ovarian cancer: Difference in-gel electrophoresis analysis of pooled clinical samples  

PubMed Central

Introduction: Ovarian cancer is the leading cause of death from gynecological cancer. Non-specific symptoms early in disease and the lack of specific biomarkers hinder early diagnosis. Multi-marker blood screening tests have shown promise for improving identification of early stage disease; however, available tests lack sensitivity, and specificity. Materials and Methods: In this study, pooled deeply-depleted plasma from women with Stage 1, 2 or 3 ovarian cancer and healthy controls were used to compare the 2-dimensional gel electrophoresis (2-DE) protein profiles and identify potential novel markers of ovarian cancer progression. Results/Discussion: Stage-specific variation in biomarker expression was observed. For example, apolipoprotein A1 expression is relatively low in control and Stage 1, but shows a substantial increase in Stage 2 and 3, thus, potential of utility for disease confirmation rather than early detection. A better marker for early stage disease was tropomyosin 4 (TPM4). The expression of TPM4 increased by 2-fold in Stage 2 before returning to “normal” levels in Stage 3 disease. Multiple isoforms were also identified for some proteins and in some cases, displayed stage-specific expression. An interesting example was fibrinogen alpha, for which 8 isoforms were identified. Four displayed a moderate increase at Stage 1 and a substantial increase for Stages 2 and 3 while the other 4 showed only moderate increases. Conclusion: Herein is provided an improved summary of blood protein profiles for women with ovarian cancer stratified by stage. PMID:23858298

Bailey, Mark J.; Shield-Artin, Kristy L.; Oliva, Karen; Ayhan, Mustafa; Reisman, Simone; Rice, Gregory E.

2013-01-01

26

The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case-control studies  

PubMed Central

Background The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located in exon 26, 1236C > T in exon 12 and 2677G > T/A in exon 21 were the most extensively studied and were identified functionally important and ethnically diverse mapping to the gene region. Considering the potential influence of altering MDR1 activity, it is plausible that MDR1 polymorphisms might play a role in the development of cancer. Although the effects of MDR1 polymorphisms on susceptibility to human cancer have been investigated in many studies, the results still remain conflicting. Methods To resolve these conflicts, we performed a quantitative synthesis of the association between these three polymorphisms and cancer risk, including 52 studies (15789 cases and 20274 controls) for 3435C > T polymorphism, 10 studies (2101 cases and 2842 controls) for 1236C > T polymorphism and 18 studies (3585 cases and 4351 controls) for 2677G > T/A polymorphism. Results The stratified analyses for 3435C > T polymorphism, individuals with T-allele in 3435C > T had significantly higher ALL risks (TT versus CC: OR =1.286, 95% CI =1.123-1.474); significantly elevated risks were observed among Caucasian populations (TT versus CC: OR =1.276, 95% CI =1.112-1.464). When restricting the analysis to the source of controls, we found that HB (hospital-based) genetic models had higher risks (TT versus CC: OR =1.307, 95% CI =1.046-1.632), as well as in PB (population-based) genetic models (TT versus CC: OR =1.294, 95% CI =1.079-1.55). The T/A-allele frequency of 2677G > T/A polymorphism was associated with higher risk of cancer (TT + TA + AA vs. GG: OR =1.348, 95% CI =1.031-1.762), significantly elevated risks were observed among Asian populations (TT + TA + AA vs. GG: OR =1.642, 95% CI =1.340-2.012), and elevated risks could be associated with PB models (TT + TA + AA vs. GG: OR =1.641, 95% CI =1.018-2.646). Conclusions Our meta-analysis suggested that 3435C > T polymorphism and 2677G > T/A polymorphism were associated with cancer risk when all studies were pooled together, while 1236C > T polymorphism not. PMID:23687985

2013-01-01

27

Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials  

SciTech Connect

Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recorded for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.

Weiss, Christian, E-mail: christian.weiss@kgu.d [Departments of Radiation Therapy and Oncology, Goethe University, Frankfurt am Main (Germany); Arnold, Dirk [Departments of Haematology and Oncology, Martin-Luther University Halle-Wittenberg (Germany); Dellas, Kathrin [Department of Radiation Oncology, Martin-Luther University Halle-Wittenberg (Germany); Liersch, Torsten [Departments of General and Visceral Surgery, Georg-August University, Goettingen (Germany); Hipp, Matthias [Department of Radiation Oncology, University of Regensburg, Regensburg (Germany); Fietkau, Rainer; Sauer, Rolf [Department of Radiation Oncology, Friedrich-Alexander University, Erlangen (Germany); Hinke, Axel [WiSP, Research Institute Pharma GmbH, Langenfeld (Germany); Roedel, Claus [Departments of Radiation Therapy and Oncology, Goethe University, Frankfurt am Main (Germany)

2010-10-01

28

Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees  

PubMed Central

Background Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann–Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. Results The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence… Conclusions The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence. PMID:23506640

2013-01-01

29

Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies  

PubMed Central

Summary Background Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk. Methods Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0·05 was considered significant. Findings IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1·28 (95% CI 1·14–1·44; p<0·0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest fifth were 1·38 (95% CI 1·14–1·68) for oestrogen-receptor-positive tumours and 0·80 (0·57–1·13) for oestrogen-receptor-negative tumours (p for heterogeneity=0·007). Interpretation Circulating IGF1 is positively associated with breast-cancer risk. The association is not substantially modified by IGFBP3, and does not differ markedly by menopausal status, but seems to be confined to oestrogen-receptor-positive tumours. Funding Cancer Research UK. PMID:20472501

2010-01-01

30

Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls.  

PubMed

Genital powder use has been associated with risk of epithelial ovarian cancer in some, but not all, epidemiologic investigations, possibly reflecting the carcinogenic effects of talc particles found in most of these products. Whether risk increases with number of genital powder applications and for all histologic types of ovarian cancer also remains uncertain. Therefore, we estimated the association between self-reported genital powder use and epithelial ovarian cancer risk in eight population-based case-control studies. Individual data from each study were collected and harmonized. Lifetime number of genital powder applications was estimated from duration and frequency of use. Pooled ORs were calculated using conditional logistic regression matched on study and age and adjusted for potential confounders. Subtype-specific risks were estimated according to tumor behavior and histology. 8,525 cases and 9,859 controls were included in the analyses. Genital powder use was associated with a modest increased risk of epithelial ovarian cancer [OR, 1.24; 95% confidence interval (CI), 1.15-1.33] relative to women who never used powder. Risk was elevated for invasive serous (OR, 1.20; 95% CI, 1.09-1.32), endometrioid (OR, 1.22; 95% CI, 1.04-1.43), and clear cell (OR, 1.24; 95% CI, 1.01-1.52) tumors, and for borderline serous tumors (OR, 1.46; 95% CI, 1.24-1.72). Among genital powder users, we observed no significant trend (P = 0.17) in risk with increasing number of lifetime applications (assessed in quartiles). We noted no increase in risk among women who only reported nongenital powder use. In summary, genital powder use is a modifiable exposure associated with small-to-moderate increases in risk of most histologic subtypes of epithelial ovarian cancer. PMID:23761272

Terry, Kathryn L; Karageorgi, Stalo; Shvetsov, Yurii B; Merritt, Melissa A; Lurie, Galina; Thompson, Pamela J; Carney, Michael E; Weber, Rachel Palmieri; Akushevich, Lucy; Lo-Ciganic, Wei-Hsuan; Cushing-Haugen, Kara; Sieh, Weiva; Moysich, Kirsten; Doherty, Jennifer A; Nagle, Christina M; Berchuck, Andrew; Pearce, Celeste L; Pike, Malcolm; Ness, Roberta B; Webb, Penelope M; Rossing, Mary Anne; Schildkraut, Joellen; Risch, Harvey; Goodman, Marc T

2013-08-01

31

Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts  

PubMed Central

Background There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts. Methods The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education. Results In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR]?=?0.68, 95% CI 0.52–0.89) and cancer (HR?=?0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity. Conclusions Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women. PMID:24086292

Stamatakis, Emmanuel; Chau, Josephine Y.; Pedisic, Zeljko; Bauman, Adrian; Macniven, Rona; Coombs, Ngaire; Hamer, Mark

2013-01-01

32

Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium  

PubMed Central

Background Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. Methods We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcohol intake to estimate odds ratios (OR) and 95% confidence intervals (CI) according to frequencies of average daily intakes of beer, wine, liquor and total alcohol. Results Total alcohol intake was not associated with all OC: consumption of >3 drinks per day compared to none, OR=0.92, 95% CI=0.76-1.10, P trend=0.27. Among beverage types, a statistically non-significant decreased risk was observed among women who consumed >8?oz/d of wine compared to none (OR=0.83, 95% CI=0.68-1.01, P trend=0.08). This association was more apparent among women with clear cell OC (OR, 0.43; 95% CI, 0.22-0.83; P trend=0.02), although based on only 10 cases and not statistically different from the other histologic types (P value for statistical heterogeneity between histologic types = 0.09). Statistical heterogeneity of the alcohol- and wine-OC associations was seen among three European studies, but not among eight North American studies. No statistically significant associations were observed in separate analyses evaluating risk with borderline tumors of serous or mucinous histology. Smoking status did not significantly modify any of the associations. Conclusions We found no evidence that recent moderate alcohol drinking is associated with increased risk for overall OC, or that variation in risk is associated strongly with specific histologic types. Understanding modifiable causes of these elusive and deadly cancers remains a priority for the research community. PMID:23339562

2013-01-01

33

Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project.  

PubMed

Vitamin supplement use after breast cancer diagnosis is common, but little is known about long-term effects on recurrence and survival. We examined postdiagnosis supplement use and risk of death or recurrence in the After Breast Cancer Pooling Project, a consortium of four cohorts of 12,019 breast cancer survivors from the United States and China. Post-treatment supplement use (vitamins A, B, C, D, E, and multivitamins) was assessed 1-5 years postdiagnosis. Associations with risk of recurrence, breast cancer-specific mortality, or total mortality were analyzed in Cox proportional hazards models separately by cohort. Individual cohort results were combined using random effects meta-analysis. Interactions with smoking, treatment, and hormonal status were examined. In multivariate models, vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95 % CI 0.79-0.99), and vitamin C with decreased risk of death (RR: 0.81; 95 % CI 0.72-0.92). However, when supplements were mutually adjusted, all associations were attenuated. There were no statistically significant associations with breast cancer mortality. The use of antioxidant supplements (multivitamins, vitamin C, or E) was not associated with recurrence, but was associated with a 16 % decreased risk of death (95 % CI 0.72-0.99). In addition, vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (p-interaction = 0.01). In this large consortium of breast cancer survivors, post-treatment use of vitamin supplements was not associated with increased risk of recurrence or death. Post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine. Stratification by ER status and considering antioxidants as a group may be more clinically relevant when evaluating associations with cancer risk and mortality. PMID:23660948

Poole, Elizabeth M; Shu, XiaoOu; Caan, Bette J; Flatt, Shirley W; Holmes, Michelle D; Lu, Wei; Kwan, Marilyn L; Nechuta, Sarah J; Pierce, John P; Chen, Wendy Y

2013-06-01

34

Hydrocarbon pool and vapor fire data analysis  

SciTech Connect

The flame geometry and thermal radiation data from a series of large scale experiments involving liquefied petroleum gas (LPG) and gasoline spills on water were analyzed. The experiments were conducted at the Naval Weapons Center, China Lake, California. Two types of fires have been studied; namely, pool fires and vapor fires. The spill quantity varied from 4 m/sup 3/ to approximately 6 m/sup 3/. The LPG pool fire flame height to diameter ratio were between 3.5 and 4.5. The gasoline flame height was about 2. The flame emissive powers for LPG pool fires ranged from 78 kW/m/sup 2/ to 115 kW/m/sup 2/. The average surface emissive power for gasoline pool fire was 40 kW/m/sup 2/. The LPG vapor fire emissive power ranged from 159 to 269 kW/m/sup 2/. 63 figures, 13 tables.

Mudan, K.S.

1984-10-01

35

Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214  

SciTech Connect

Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.

Gondi, Vinai, E-mail: vgondi@chicagocancer.org [Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States) [Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States); University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States)] [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Bruner, Deborah W. [Nell Hodgson Woodfull School of Nursing, Emory University, Atlanta, Georgia (United States)] [Nell Hodgson Woodfull School of Nursing, Emory University, Atlanta, Georgia (United States); Meyers, Christina A. [University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gore, Elizabeth M. [Medical College of Wisconsin, Milwaukee, Wisconsin (United States)] [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wolfson, Aaron [University of Miami School of Medicine, Miami, Florida (United States)] [University of Miami School of Medicine, Miami, Florida (United States); Werner-Wasik, Maria [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States)] [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Sun, Alexander Y. [Princess Margaret Hospital, Toronto, ON (Canada)] [Princess Margaret Hospital, Toronto, ON (Canada); Choy, Hak [University of Texas Southwestern Moncreif Cancer Center, Fort Worth, Texas (United States)] [University of Texas Southwestern Moncreif Cancer Center, Fort Worth, Texas (United States); Movsas, Benjamin [Henry Ford Health System, Detroit, Michigan (United States)] [Henry Ford Health System, Detroit, Michigan (United States)

2013-07-15

36

IS URBAN LOGISTICS POOLING VIABLE? A MULTISTAKEHOLDER MULTICRITERIA ANALYSIS  

E-print Network

IS URBAN LOGISTICS POOLING VIABLE? A MULTISTAKEHOLDER MULTICRITERIA ANALYSIS Jesus Gonzalez. Urban consolidation and logistics sharing. III. Multi-stakeholder mutli-criteria methodology. A seems a good city logistics alternative to classical urban consolidation centres, but it is still

Boyer, Edmond

37

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials  

Microsoft Academic Search

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether\\u000a characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity\\u000a in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials\\u000a with uniform protocols. PCR was associated with

Gunter von Minckwitz; Michael Untch; Eveline Nüesch; Sibylle Loibl; Manfred Kaufmann; Sherko Kümmel; Peter A. Fasching; Wolfgang Eiermann; Jens-Uwe Blohmer; Serban Dan Costa; Keyur Mehta; Jörn Hilfrich; Christian Jackisch; Bernd Gerber; Andreas du Bois; Jens Huober; Claus Hanusch; Gottfried Konecny; Werner Fett; Elmar Stickeler; Nadia Harbeck; Volkmar Müller; Peter Jüni

2011-01-01

38

KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials  

SciTech Connect

Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.

Kim, Sun Young; Shim, Eun Kyung [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)] [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Yeo, Hyun Yang [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)] [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)] [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)] [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of) [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Tae Won [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)] [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jee Hyun [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of)] [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Im, Seock-Ah [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)] [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Kyung Hae [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)] [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chang, Hee Jin, E-mail: heejincmd@yahoo.com [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

2013-01-01

39

Urban logistics pooling viabililty analysis via a multicriteria multiactor method  

E-print Network

Urban logistics pooling viabililty analysis via a multicriteria multiactor method Jesus Gonzalez. In the last years, collaborative transportation seems a good city logistics alternative to classical urban consolidation centres, but it is still in a development stage. This paper proposes a framework for urban

Paris-Sud XI, Université de

40

A pooled analysis of magnetic fields and childhood leukaemia  

Microsoft Academic Search

Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24\\/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them

A Ahlbom; N Day; M Feychting; E Roman; J Skinner; J Dockerty; M Linet; M McBride; J Michaelis; J H Olsen; T Tynes; P K Verkasalo

2000-01-01

41

Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium  

Microsoft Academic Search

Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the

Mia Hashibe; Paul Brennan; Simone Benhamou; Xavier Castellsague; Chu Chen; Maria Paula Curado; Luigino Dal Maso; Alexander W. Daudt; Eleonora Fabianova; Victor Wünsch-Filho; Silvia Franceschi; Richard B. Hayes; Rolando Herrero; Sergio Koifman; Carlo La Vecchia; Philip Lazarus; Fabio Levi; Dana Mates; Elena Matos; Ana Menezes; Joshua Muscat; Jose Eluf-Neto; Andrew F. Olshan; Peter Rudnai; Stephen M. Schwartz; Elaine Smith; Erich M. Sturgis; Neonilia Szeszenia-Dabrowska; Renato Talamini; Qingyi Wei; Deborah M. Winn; David Zaridze; Witold Zatonski; Zuo-Feng Zhang; Julien Berthiller; Paolo Boffetta

42

Reciprocal regulation of autophagy and dNTP pools in human cancer cells.  

PubMed

Ribonucleotide reductase (RNR) plays a critical role in catalyzing the biosynthesis and maintaining the intracellular concentration of 4 deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools cause serious genotoxic consequences. Autophagy is the process by which cytoplasmic constituents are degraded in lysosomes to maintain cellular homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP pools is not well understood. Herein, we reported that starvation- or rapamycin-induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in human cancer cells. Furthermore, downregulation of the small subunit of RNR (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially induced autophagy. Conversely, cancer cells with abundant endogenous intracellular dNTPs or treated with dNTP precursors were less responsive to autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels are regulated through a negative feedback loop. Lastly, treatment with si-RRM2 caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in xenografted Tu212 tumors in vivo. Together, our results revealed a previously unrecognized reciprocal regulation between dNTP pools and autophagy in cancer cells. PMID:24905824

Chen, Wei; Zhang, Lisheng; Zhang, Keqiang; Zhou, Bingsen; Kuo, Mei-Ling; Hu, Shuya; Chen, Linling; Tang, Michelle; Chen, Yun-Ru; Yang, Lixin; Ann, David K; Yen, Yun

2014-07-01

43

Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts  

PubMed Central

Background Marine microorganisms are considered to be an important source of bioactive molecules against various diseases and have great potential to increase the number of lead molecules in clinical trials. Progress in novel microbial culturing techniques as well as greater accessibility to unique oceanic habitats has placed the marine environment as a new frontier in the field of natural product drug discovery. Methods A total of 24 microbial extracts from deep-sea brine pools in the Red Sea have been evaluated for their anticancer potential against three human cancer cell lines. Downstream analysis of these six most potent extracts was done using various biological assays, such as Caspase-3/7 activity, mitochondrial membrane potential (MMP), PARP-1 cleavage and expression of ?H2Ax, Caspase-8 and -9 using western blotting. Results In general, most of the microbial extracts were found to be cytotoxic against one or more cancer cell lines with cell line specific activities. Out of the 13 most active microbial extracts, six extracts were able to induce significantly higher apoptosis (>70%) in cancer cells. Mechanism level studies revealed that extracts from Chromohalobacter salexigens (P3-86A and P3-86B(2)) followed the sequence of events of apoptotic pathway involving MMP disruption, caspase-3/7 activity, caspase-8 cleavage, PARP-1 cleavage and Phosphatidylserine (PS) exposure, whereas another Chromohalobacter salexigens extract (K30) induced caspase-9 mediated apoptosis. The extracts from Halomonas meridiana (P3-37B), Chromohalobacter israelensis (K18) and Idiomarina loihiensis (P3-37C) were unable to induce any change in MMP in HeLa cancer cells, and thus suggested mitochondria-independent apoptosis induction. However, further detection of a PARP-1 cleavage product, and the observed changes in caspase-8 and -9 suggested the involvement of caspase-mediated apoptotic pathways. Conclusion Altogether, the study offers novel findings regarding the anticancer potential of several halophilic bacterial species inhabiting the Red Sea (at the depth of 1500–2500 m), which constitute valuable candidates for further isolation and characterization of bioactive molecules. PMID:24305113

2013-01-01

44

Identifying sexual orientation health disparities in adolescents: analysis of pooled data from the Youth Risk Behavior Survey, 2005 and 2007.  

PubMed

We studied sexual orientation disparities in health outcomes among US adolescents by pooling multiple Youth Risk Behavior Survey (YRBS) data sets from 2005 and 2007 for 14 jurisdictions. Here we describe the methodology for pooling and analyzing these data sets. Sexual orientation-related items assessed sexual orientation identity, gender of sexual contacts, sexual attractions, and harassment regarding sexual orientation. Wording of items varied across jurisdictions, so we created parallel variables and composite sexual minority variables. We used a variety of statistical approaches to address issues with the analysis of pooled data and to meet the aims of individual articles, which focused on a range of health outcomes and behaviors related to cancer, substance use, sexual health, mental health, violence, and injury. PMID:24328640

Mustanski, Brian; Van Wagenen, Aimee; Birkett, Michelle; Eyster, Sandra; Corliss, Heather L

2014-02-01

45

Meta and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: A Huge-GSEC review  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640

Stefania Boccia; Rayjean Hung; Gualtiero Ricciardi; Francesco Gianfagna; Matthias P. A. Ebert; Jing-Yuan Fang; Chang-Ming Gao; T. Götze; Francesco Graziano; M. Lacasaña-Navarro; Dongxin Lin; L. López-Carrillo; You-Lin Qiao; Hongbing Shen; Rachael Stolzenberg-Solomon; Toshiro Takezaki; Yu-Rong Weng; Fang Fang Zhang; P. Tikka-Kleemola; Paolo Boffetta; Emanuela Taioli

2008-01-01

46

Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project  

PubMed Central

Background Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of post-diagnostic weight variation on survival, we examined the relationship by comorbid status and initial BMI. Methods The current analysis included 12,915 breast cancer patients diagnosed between 1990 and 2006 with Stage I–III tumors from four prospective cohorts in the US and China Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of five weight change categories (within <5% [reference]; 5–<10% and ?10% loss and gain) with mortality were estimated using Cox proportional hazards models. Results Mean weight change was 1.6 kg. 14.7% of women lost and 34.7% gained weight. Weight stability in the early years post-diagnosis was associated with the lowest overall mortality risk. Weight loss ?10% was related to a 40% increased risk of death (HR=1.41; 95% CI: 1.14, 1.75) in the US and over three times the risk of death (HR=3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by pre-diagnosis BMI, and in the US lower survival were seen for women who lost weight and had comorbid conditions. Weight gain ?10% was associated with a non-significant increased risk of death. Conclusions Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Impact Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history. PMID:22695738

Caan, Bette J.; Kwan, Marilyn L.; Shu, Xiao Ou; Pierce, John P.; Patterson, Ruth E.; Nechuta, Sarah J.; Poole, Elizabeth M.; Kroenke, Candyce H.; Weltzien, Erin K.; Flatt, Shirley W.; Quesenberry, Charles P.; Holmes, Michelle D.; Chen, Wendy Y.

2012-01-01

47

Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis  

Microsoft Academic Search

A meta-analysis was carried out to calculate a pooled estimate of relative risk of lung cancer following exposure to environmental tobacco smoke (ETS) and to determine whether there was any heterogeneity in the pooled estimates according to selected characteristics of the studies. A total of 35 case-control and five cohort studies providing quantitative estimates of the association between lung cancer

Lijie Zhong; Mark S Goldberg; Marie-Élise Parent; James A Hanley

2000-01-01

48

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies  

PubMed Central

Background For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields. PMID:22862891

2012-01-01

49

Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials.  

PubMed Central

OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. DESIGN: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. RESULTS: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. CONCLUSIONS: The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events. PMID:9251544

Hemminki, E.; McPherson, K.

1997-01-01

50

Spatio-temporal analysis of nucleate pool boiling: identication of nucleation sites using non-orthogonal  

E-print Network

Spatio-temporal analysis of nucleate pool boiling: identi®cation of nucleation sites using non techniques. These limitations are especially evident in nucleate boiling. This paper investigates the analysis of a sequence of temperature ®elds obtained from a pool nucleate boiling experiment. Spatio

Stevenson, Paul

51

Hydrocarbon pool and vapor fire data analysis. Final report  

SciTech Connect

The flame geometry and thermal radiation data from a series of large scale experiments involving liquefied petroleum gas (LPG) and gasoline spills on water were analyzed. The experiments were conducted at the Naval Weapons Center, China Lake, California. Two types of fires have been studied; namely, pool fires and vapor fires. The spill quantity varied from 4 m/sup 3/ to approximately 6 m/sup 3/. The LPG pool fire flame height to diameter ratio were between 3.5 and 4.5. The gasoline flame height was about 2. The flame emissive powers for LPG pool fires ranged from 78 kW/m/sup 2/ to 115 kW/m/sup 2/. The average surface emissive power for gasoline pool fire was 40 kW/m/sup 2/. The LPG vapor fire emissive power ranged from 159 to 269 kW/m/sup 2/. 63 figures, 13 tables.

Mudan, K.S.

1984-10-01

52

Structural analysis of a reflux pool-boiler solar receiver  

NASA Astrophysics Data System (ADS)

Coupled thermal-structural finite element calculations of a reflux pool-boiler solar receiver were performed to characterize the operating stresses and to address issues affecting the service life of the receiver. Analyses performed using shell elements provided information for receiver material selection and design optimization. Calculations based on linear elastic fracture mechanics principles were performed using continuum elements to assess the vulnerability of a seam-weld to fatigue crack growth. All calculations were performed using ABAQUS, a general purpose finite element code, and elements specifically formulated for coupled thermal-structural analysis. Two materials were evaluated: 316L SS and Haynes 230 alloys. The receiver response was simulated for a combination of structural and thermal loads that represent the startup and operating conditions of the receiver. For both materials, maximum stresses in the receiver developed shortly after startup due to uneven temperature distribution across the receiver surface. The largest effective stress was near yield in the 316L SS receiver and below 39 percent of yield in the Haynes 230 receiver. The calculations demonstrated that stress reductions of over 25 percent could be obtained by reducing the aft dome thickness to one closer to the absorber. The fatigue calculations demonstrated that the stress distribution near the seam-weld notch depends primarily on the structural load created by internal pressurization of the receiver rather than the thermal, indicating that the thermal loads can be neglected when assessing the stress intensity near the seam-weld notch. The stress intensity factor, computed using the J-integral method and crack opening-displacement field equations, was significantly below the fatigue threshold for most steels. The calculations indicated that the weld notch was always loaded in compression, a condition which is not conducive to fatigue crack growth.

Hoffman, E. L.; Stone, C. M.

1991-06-01

53

Structural analysis of a reflux pool-boiler solar receiver  

SciTech Connect

Coupled thermal-structural finite element calculations of a reflux pool-boiler solar receiver were performed to characterize the operating stresses and to address issues affecting the service life of the receiver. Analyses performed using shell elements provided information for receiver material selection and design optimization. Calculations based on linear elastic fracture mechanics principles were performed using continuum elements to assess the vulnerability of a seam-weld to fatigue crack growth. All calculations were performed using ABAQUS, a general purpose finite element code, and elements specifically formulated for coupled thermal-structural analysis. Two materials were evaluated: 316L SS and Haynes 230 alloys. The receiver response was simulated for a combination of structural and thermal loads that represent the startup and operating conditions of the receiver. For both materials, maximum stresses in the receiver developed shortly after startup due to uneven temperature distribution across the receiver surface. The largest effective stress was near yield in the 316L SS receiver and below 39 percent of yield in the Haynes 230 receiver. The calculations demonstrated that stress reductions of over 25 percent could be obtained by reducing the aft dome thickness to one closer to the absorber. The fatigue calculations demonstrated that the stress distribution near the seam-weld notch depends primarily on the structural load created by internal pressurization of the receiver rather than the thermal, indicating that the thermal loads can be neglected when assessing the stress intensity near the seam-weld notch. The stress intensity factor, computed using the J-integral method and crack opening-displacement field equations, was significantly below the fatigue threshold for most steels. The calculations indicated that the weld notch was always loaded in compression, a condition which is not conducive to fatigue crack growth. 15 refs., 30 figs., 3 tabs.

Hoffman, E.L.; Stone, C.M.

1991-06-01

54

Spatio-temporal analysis of nucleate pool boiling: identi cation of nucleation sites using  

E-print Network

Spatio-temporal analysis of nucleate pool boiling: identi#12;cation of nucleation sites using non are often limited by the available techniques. These limitations are especially evident in nucleate boiling boiling experiment. Spatio-temporal data for the wall temperature in pool nu- cleate boiling of water

McSharry, Patrick E.

55

Stability analysis of two-dimensional pool-boiling systems M. Speetjens  

E-print Network

Stability analysis of two-dimensional pool-boiling systems M. Speetjens , A. Reusken , S. Maier In this paper we consider a model for pool-boiling systems known from the liter- ature. This model involves only the temperature distribution within the heater and models the heat exchange with the boiling medium via

56

A Fixed Point Analysis of a Gene Pool GA with Mutation Alden H. Wright  

E-print Network

A Fixed Point Analysis of a Gene Pool GA with Mutation Alden H. Wright Computer Science University This paper analyzes a recombina- tion/mutation/selection genetic algorithm that uses gene pool recombination grant GR/R47394. repeated applications of crossover is a population in link- age equilibrium (also known

Wright, Alden H.

57

A Fixed Point Analysis of a Gene Pool GA with Mutation Alden H. Wright #  

E-print Network

A Fixed Point Analysis of a Gene Pool GA with Mutation Alden H. Wright # Computer Science This paper analyzes a recombina­ tion/mutation/selection genetic algorithm that uses gene pool recombination by EPSRC grant GR/R47394. repeated applications of crossover is a population in link­ age equilibrium (also

Wright, Alden H.

58

Pooled genomic indexing (PGI): mathematical analysis and experiment design  

E-print Network

are mapped onto homologous human sequence. 1 Introduction Pooled Genomic Indexing (PGI) is a novel method Human Genome Sequencing Center, Department of Molecular and Human Genetics Baylor College of Medicine 3 comparative BAC­based physical maps at a fraction (on the order of 1%) of the cost of full genome sequencing

Csürös, Miklós

59

Pooled genomic indexing (PGI): mathematical analysis and experiment design  

E-print Network

are mapped onto homologous human sequence. 1 Introduction Pooled Genomic Indexing (PGI) is a novel method Human Genome Sequencing Center, Department of Molecular and Human Genetics Baylor College of Medicine 3 comparative BAC-based physical maps at a fraction (on the order of 1%) of the cost of full genome sequencing

Milosavljevic, Aleksandar

60

Pooled genomic indexing (PGI): analysis and design of experiments  

E-print Network

rat BAC clones and 207 mouse BAC clones are mapped onto homologous human sequence. D´epartement d College of Medicine, Houston, TX 77030, USA. Human Genome Sequencing Center, Department of Molecular Milosavljevic July 29, 2004 Abstract Pooled Genomic Indexing (PGI) is a novel method for physical mapping

Csürös, Miklós

61

Monte Carlo Test Assembly for Item Pool Analysis and Extension  

ERIC Educational Resources Information Center

A new test assembly algorithm based on a Monte Carlo random search is presented in this article. A major advantage of the Monte Carlo test assembly over other approaches (integer programming or enumerative heuristics) is that it performs a uniform sampling from the item pool, which provides every feasible item combination (test) with an equal…

Belov, Dmitry I.; Armstrong, Ronald D.

2005-01-01

62

Calculation Notes for Subsurface Leak Resulting in Pool, TWRS FSAR Accident Analysis  

SciTech Connect

This document includes the calculations performed to quantify the risk associated with the unmitigated and mitigated accident scenarios described in the TWRS FSAR for the accident analysis titled: Subsurface Leaks Resulting in Pool.

Hall, B.W.

1996-09-25

63

Calculation notes for surface leak resulting in pool, TWRS FSAR accident analysis  

SciTech Connect

This document includes the calculations performed to quantify the risk associated with the unmitigated and mitigated accident scenarios described in the TWRS FSAR for the accident analysis titled: Surface Leaks Resulting in Pool.

Hall, B.W.

1996-09-25

64

Consequence analysis of aqueous ammonia spills using an improved liquid pool evaporation model  

E-print Network

CONSEQUENCE ANALYSIS OF AQUEOUS AMMONIA SPILLS USING AN IMPROVED LIQUID POOL EVAPORATION MODEL A Thesis by VIJAY RAGHUNATHAN Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE December 2004 Major Subject: Chemical Engineering CONSEQUENCE ANALYSIS OF AQUEOUS AMMONIA SPILLS USING AN IMPROVED LIQUID POOL EVAPORATION MODEL A Thesis by VIJAY...

Raghunathan, Vijay

2005-02-17

65

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.  

PubMed

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

McCullough, Marjorie L; Weinstein, Stephanie J; Freedman, D Michal; Helzlsouer, Kathy; Flanders, W Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J; Hankinson, Susan E; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B; Horst, Ronald L; Shu, Xiao-Ou

2010-07-01

66

Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.  

PubMed

The GSTP1, GSTM1, and GSTT1 detoxification genes all have functional polymorphisms that are common in the general population. A single study of 320 BRCA1/2 carriers previously assessed their effect in BRCA1 or BRCA2 mutation carriers. This study showed no evidence for altered risk of breast cancer for individuals with the GSTT1 and GSTM1 deletion variants, but did report that the GSTP1 Ile105Val (rs1695) variant was associated with increased breast cancer risk in carriers. We investigated the association between these three GST polymorphisms and breast cancer risk using existing data from 718 women BRCA1 and BRCA2 mutation carriers from Australia, the UK, Canada, and the USA. Data were analyzed within a proportional hazards framework using Cox regression. There was no evidence to show that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, and there was no evidence for heterogeneity between sites. These results support the need for replication studies to confirm or refute hypothesis-generating studies. PMID:19921428

Spurdle, Amanda B; Fahey, Paul; Chen, Xiaoqing; McGuffog, Lesley; Easton, Douglas; Peock, Susan; Cook, Margaret; Simard, Jacques; Rebbeck, Tim R; Antoniou, Antonis C; Chenevix-Trench, Georgia

2010-07-01

67

76 FR 72923 - Pool Corporation; Analysis To Aid Public Comment  

Federal Register 2010, 2011, 2012, 2013

...competition. The attached Analysis to Aid Public Comment...days. The following Analysis to Aid Public Comment...inventories, formulas, patterns, devices, manufacturing...ftc/privacy.htm. Analysis of Agreement Containing...The Agreement is for settlement purposes only and...

2011-11-28

68

Pooled analysis of the association of PTGS2 rs5275 polymorphism and NSAID use with invasive ovarian carcinoma risk  

PubMed Central

Inflammation is postulated to play an important role in ovarian carcinogenesis. Prostaglandin endoperoxide synthase 2 (PTGS2) is responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation. We examined the association of the PTGS2 rs5275 polymorphism with the risk of invasive ovarian carcinoma and the joint effect of rs5275 and use of nonsteroidal antiinflammatory drugs (NSAIDs) on risk in a pooled analysis of two population-based studies, the Hawaii Ovarian Cancer Case-Control Study and the New England Case-Control Study, including 1025 women with invasive ovarian carcinoma and 1687 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. In the pooled analysis, the CC genotype was associated with a reduced risk of nonserous ovarian carcinoma (OR=0.66; CI: 0.44-0.98). In addition, the lowest risk was observed among carriers of the CC genotype who were users of nonaspirin NSAIDs (OR=0.43; CI:0.20-0.93) in all women combined. The association of PTGS2 rs5275 with nonserous ovarian carcinoma and possible effect modification by NSAID use needs further validation, preferably in the prospective studies. PMID:20559705

Lurie, Galina; Terry, Kathryn L; Wilkens, Lynne R.; Thompson, Pamela J.; McDuffie, Katharine E.; Carney, Michael E.; Palmieri, Rachel T.; Cramer, Daniel W.; Goodman, Marc T.

2010-01-01

69

RELAP5 Analysis of the Hybrid Loop-Pool Design for Sodium Cooled Fast Reactors  

SciTech Connect

An innovative hybrid loop-pool design for sodium cooled fast reactors (SFR-Hybrid) has been recently proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to improve economics and safety of SFRs. In the hybrid loop-pool design, primary loops are formed by connecting the reactor outlet plenum (hot pool), intermediate heat exchangers (IHX), primary pumps and the reactor inlet plenum with pipes. The primary loops are immersed in the cold pool (buffer pool). Passive safety systems -- modular Pool Reactor Auxiliary Cooling Systems (PRACS) – are added to transfer decay heat from the primary system to the buffer pool during loss of forced circulation (LOFC) transients. The primary systems and the buffer pool are thermally coupled by the PRACS, which is composed of PRACS heat exchangers (PHX), fluidic diodes and connecting pipes. Fluidic diodes are simple, passive devices that provide large flow resistance in one direction and small flow resistance in reverse direction. Direct reactor auxiliary cooling system (DRACS) heat exchangers (DHX) are immersed in the cold pool to transfer decay heat to the environment by natural circulation. To prove the design concepts, especially how the passive safety systems behave during transients such as LOFC with scram, a RELAP5-3D model for the hybrid loop-pool design was developed. The simulations were done for both steady-state and transient conditions. This paper presents the details of RELAP5-3D analysis as well as the calculated thermal response during LOFC with scram. The 250 MW thermal power conventional pool type design of GNEP’s Advanced Burner Test Reactor (ABTR) developed by Argonne National Laboratory was used as the reference reactor core and primary loop design. The reactor inlet temperature is 355 °C and the outlet temperature is 510 °C. The core design is the same as that for ABTR. The steady state buffer pool temperature is the same as the reactor inlet temperature. The peak cladding, hot pool, cold pool and reactor inlet temperatures were calculated during LOFC. The results indicate that there are two phases during LOFC transient – the initial thermal equilibration phase and the long term decay heat removal phase. The initial thermal equilibration phase occurs over a few hundred seconds, as the system adjusts from forced circulation to natural circulation flow. Subsequently, during long-term heat removal phase all temperatures evolve very slowly due to the large thermal inertia of the primary and buffer pool systems. The results clearly show that passive safety PRACS can effectively transfer decay heat from the primary system to the buffer pool by natural circulation. The DRACS system in turn can effectively transfer the decay heat to the environment.

Hongbin Zhang; Haihua Zhao; Cliff Davis

2008-06-01

70

Selective Genotyping and Pooled DNA Analysis: An Innovative Use of an Old Concept  

Microsoft Academic Search

Selective genotyping and pooled DNA analysis using material from the two tails of the phenotypic distribution of a population provide an effective alternative to analysis of the entire population for genetic mapping. Past applications of this approach have been confounded by the use of small total and tail population sizes and insufficient marker density, which results in a high probability

Yunbi Xu; Jiankang Wang; Jonathan Crouch

2008-01-01

71

Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer  

PubMed Central

Background Activating KRAS mutations are common in ovarian carcinomas of low histological grade, less advanced clinical stage and mucinous histological subtype, and form part of the distinct molecular alterations associated with type I tumors in the dualistic model of ovarian carcinogenesis. Here, we investigated the occurrence, clinicopathological correlates and prognostic significance of specific KRAS mutations in tumours from 153 epithelial ovarian cancer (EOC) cases from a pooled, prospective cohort. Methods KRAS codon 12,13 and 61 mutations were analysed by pyrosequencing in tumours from 163 incident EOC cases in the Malmö Diet and Cancer Study and Malmö Preventive Project. Associations of mutational status with clinicopathological and molecular characteristics were assessed by Pearson Chi Square test. Ovarian cancer-specific survival (OCSS) according to mutational status was explored by Kaplan-Meier analysis and Cox proportional hazards modelling. KRAS-mutation status was also analysed in 28 concomitantly sampled benign-appearing fallopian tubes. Results Seventeen (11.1%) EOC cases harboured mutations in the KRAS gene, all but one in codon 12, and one in codon 13. No KRAS mutations were found in codon 61 and all examined fallopian tubes were KRAS wild-type. KRAS mutation was significantly associated with lower grade (p?=?0.001), mucinous histological subtype (p?=?analysis revealed a significantly improved OCSS for patients with KRAS-mutated compared to KRAS wild-type tumours (p?=?0.015). These associations were confirmed in unadjusted Cox regression analysis (HR?=?2.51; 95% CI 1.17-5.42) but did not remain significant after adjustment for age, grade and clinical stage. The beneficial prognostic impact of KRAS mutation was ony evident in tumours of low-intermediate differentiation grade (p?=?0.023), and in a less advanced clinical stage (p?=?0.014). Moreover, KRAS mutation was associated with a significantly improved OCSS in the subgroup of endometroid carcinomas (p?=?0.012). Conclusions The results from this study confirm previously demonstrated associations of KRAS mutations with well-differentiated and mucinous ovarian carcinomas. Moreover, KRAS-mutated tumours had a significantly improved survival in unadjusted, but not adjusted, analysis. A finding that merits further study is the significant prognostic impact of KRAS mutation in endometroid carcinomas, potentially indicating that response to Ras/Raf/MEK/ERK-targeting therapies may differ by histological subtype. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1788330379100147 PMID:23800114

2013-01-01

72

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies  

PubMed Central

Background The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. Materials and methods Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case–control studies (1983–2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. Results Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled ORtrend = 0.88, 95% CI 0.81–0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04–1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65–1.16). Conclusions Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall. PMID:22786757

Kane, E. V.; Roman, E.; Becker, N.; Bernstein, L.; Boffetta, P.; Bracci, P. M.; Cerhan, J. R.; Chiu, B. C. -H.; Cocco, P.; Costas, L.; Foretova, L.; Holly, E. A.; La Vecchia, C.; Matsuo, K.; Maynadie, M.; Sanjose, S.; Spinelli, J. J.; Staines, A.; Talamini, R.; Wang, S. S.; Zhang, Y.; Zheng, T.; Kricker, A.

2012-01-01

73

Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis  

PubMed Central

Background Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis. Methods and Findings We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21–90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1–3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6–2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3–4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5–24.9) was associated with a gain of 7.2 (95% CI: 6.5–7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report. Conclusions More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups. Please see later in the article for the Editors' Summary PMID:23139642

Moore, Steven C.; Patel, Alpa V.; Matthews, Charles E.; Berrington de Gonzalez, Amy; Park, Yikyung; Katki, Hormuzd A.; Linet, Martha S.; Weiderpass, Elisabete; Visvanathan, Kala; Helzlsouer, Kathy J.; Thun, Michael; Gapstur, Susan M.; Hartge, Patricia; Lee, I-Min

2012-01-01

74

Weight management using a meal replacement strategy: meta and pooling analysis from six studies  

Microsoft Academic Search

OBJECTIVE: Although used by millions of overweight and obese consumers, there has not been a systematic assessment on the safety and effectiveness of a meal replacement strategy for weight management. The aim of this study was to review, by use of a meta- and pooling analysis, the existing literature on the safety and effectiveness of a partial meal replacement (PMR)

S B Heymsfield; C A J van Mierlo; H C M van der Knaap; M Heo; H I Frier

2003-01-01

75

Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis  

PubMed Central

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. PMID:24016459

Glaser, Sally L.; Schupp, Clayton W.; Ekstrom Smedby, Karin; de Sanjose, Silvia; Kane, Eleanor; Melbye, Mads; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Becker, Nikolaus; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo; Cocco, Pierluigi; Glimelius, Ingrid; Clavel, Jacqueline; Hjalgrim, Henrik; Chang, Ellen T.

2013-01-01

76

Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis.  

PubMed

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. PMID:24016459

Monnereau, Alain; Glaser, Sally L; Schupp, Clayton W; Ekström Smedby, Karin; de Sanjosé, Silvia; Kane, Eleanor; Melbye, Mads; Forétova, Lenka; Maynadié, Marc; Staines, Anthony; Becker, Nikolaus; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo; Cocco, Pierluigi; Glimelius, Ingrid; Clavel, Jacqueline; Hjalgrim, Henrik; Chang, Ellen T

2013-11-14

77

Genetic linkage analysis using pooled DNA and infrared detection of tailed STRP primer patterns  

NASA Astrophysics Data System (ADS)

The mapping of a disease locus to a specific chromosomal region is an important step in the eventual isolation and analysis of a disease causing gene. Conventional mapping methods analyze large multiplex families and/or smaller nuclear families to find linkage between the disease and a chromosome marker that maps to a known chromosomal region. This analysis is time consuming and tedious, typically requiring the determination of 30,000 genotypes or more. For appropriate populations, we have instead utilized pooled DNA samples for gene mapping which greatly reduces the amount of time necessary for an initial chromosomal screen. This technique assumes a common founder for the disease locus of interest and searches for a region of a chromosome shared between affected individuals. Our analysis involves the PCR amplification of short tandem repeat polymorphisms (STRP) to detect these shared regions. In order to reduce the cost of genotyping, we have designed unlabeled tailed PCR primers which, when combined with a labeled universal primer, provides for an alternative to synthesizing custom labeled primers. The STRP pattern is visualized with an infrared fluorescence based automated DNA sequencer and the patterns quantitated by densitometric analysis of the allele pattern. Differences in the distribution of alleles between pools of affected and unaffected individuals, including a reduction in the number of alleles in the affected pool, indicate the sharing of a region of a chromosome. We have found this method effective for markers 10 - 15 cM away from the disease locus for a recessive genetic disease.

Oetting, William S.; Wildenberg, Scott C.; King, Richard A.

1996-04-01

78

Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium  

Microsoft Academic Search

Some autoimmune disorders are increas- ingly recognized as risk factors for non- Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self- reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence

Karin Ekstrom Smedby; Claire M. Vajdic; Michael Falster; Eric A. Engels; Otoniel Martõ ´ nez-Maza; Jennifer Turner; Henrik Hjalgrim; Paolo Vineis; Adele Seniori Costantini; Paige M. Bracci; Elizabeth A. Holly; John J. Spinelli; Tongzhang Zheng; Brian C.-H. Chiu; Marc Maynadie; Paul Brennan; Scott Davis; James R. Cerhan; Elizabeth C. Breen; Andrew E. Grulich; Wendy Cozen

2008-01-01

79

Efficacy and tolerability of fluvastatin extended-release delivery system: a pooled analysis  

Microsoft Academic Search

Background: At high doses, the pharmacokinetics of fluvastatin immediate-release (IR) are nonlinear, possibly due to saturation of hepatic uptake. Fluvastatin delivery to the liver in a slower but sustained fashion would be expected to avoid hepatic saturation without elevating systemic drug levels.Objective: This pooled analysis compared the efficacy and tolerability of extended-release (XL) 80-mg and IR 40-mg formulations of fluvastatin

Christie M. Ballantyne; Franco Pazzucconi; Xavier Pintó; John P. Reckless; Evan Stein; James McKenney; Michele Bortolini; Yann Tong Chiang

2001-01-01

80

Pooled analysis of recent studies on magnetic fields and childhood leukaemia  

PubMed Central

Background: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000. Methods: Seven studies with a total of 10?865 cases and 12?853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences. Results: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1–0.2??T, 0.2–0.3??T and ?0.3??T, compared with <0.1??T, were 1.07 (95% CI 0.81–1.41), 1.16 (0.69–1.93) and 1.44 (0.88–2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model. Conclusions: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic. PMID:20877339

Kheifets, L; Ahlbom, A; Crespi, C M; Draper, G; Hagihara, J; Lowenthal, R M; Mezei, G; Oksuzyan, S; Schuz, J; Swanson, J; Tittarelli, A; Vinceti, M; Wunsch Filho, V

2010-01-01

81

Population pharmacokinetics of intravenous artesunate: a pooled analysis of individual data from patients with severe malaria.  

PubMed

There are ~660,000 deaths from severe malaria each year. Intravenous artesunate (i.v. ARS) is the first-line treatment in adults and children. To optimize the dosing regimen of i.v. ARS, the largest pooled population pharmacokinetic study to date of the active metabolite dihydroartemisinin (DHA) was performed. The pooled dataset consisted of 71 adults and 195 children with severe malaria, with a mixture of sparse and rich sampling within the first 12?h after drug administration. A one-compartment model described the population pharmacokinetics of DHA adequately. Body weight had the greatest impact on DHA pharmacokinetics, resulting in lower DHA exposure for smaller children (6-10?kg) than adults. Post hoc estimates of DHA exposure were not significantly associated with parasitological outcomes. Comparable DHA exposure in smaller children and adults after i.v. ARS was achieved under a dose modification for intramuscular ARS proposed in a separate analysis of children. PMID:25372510

Zaloumis, S G; Tarning, J; Krishna, S; Price, R N; White, N J; Davis, T M E; McCaw, J M; Olliaro, P; Maude, R J; Kremsner, P; Dondorp, A; Gomes, M; Barnes, K; Simpson, J A

2014-01-01

82

Computer technology of genogeographic analysis of a gene pool: II. Statistical transformation of maps  

SciTech Connect

Transformations of computer maps of geographic distribution of gene frequencies using basic mathematical statistical procedures are considered. These transformations are designated as statistical transformation of maps. Two transformation groups are considered: of one map separately and of a group of maps. Transformations possess a value beyond their use as intermediate stages of more complicated cartographical analysis: the resulting maps carry entirely new information on the geography of genes or a gene pool. This article considers three examples of obtaining new genetic profiles using statistical transformation algorithms. These profiles are of: (1) heterozygosity (of HLA-A, B, C loci in northeastern Eurasia); (2) disease risk (Rh-incompatibility of mother and child with simultaneous registration of Rh and ABO blood groups in Eastern Europe); (3) genetic distances (from own mean ethnic values for Belarus and from mean Russian values for the gene pool of Eastern Europe). 15 refs., 9 figs., 1 tab.

Balanovskaya, E.V.; Nurbaev, S.D.; Rychkov, Yu.G. [Vavilov Institute of General Genetics, Moscow (Russian Federation)

1994-11-01

83

Analysis of closed-pool boilup using the TRANSIT-HYDRO code. [LMFBR  

SciTech Connect

The benign termination of the transition phase of a hypothetical LMFBR accident rests on the avoidance of highly energetic recriticalities prior to escape of bottled molten core materials from the active core region. In scenarios where molten fuel is trapped due to axial blockages, the maintenance of subcritical configurations until radial flow paths develop requires stable boil-up of the molten fuel/steel mixture. This paper describes the analysis of an experiment investigating the behavior of closed boiling pools using the two-fluid hydrodynamics module of TRANSIT-HYDRO, a deterministic transition-phase analysis code.

Graff, D.L.

1983-01-04

84

Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies.  

PubMed

The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors. PMID:25253172

Salmen, Jessica; Neugebauer, Julia; Fasching, Peter A; Haeberle, Lothar; Huober, Jens; Wöckel, Achim; Rauh, Claudia; Schuetz, Florian; Weissenbacher, Tobias; Kost, Bernd; Stickeler, Elmar; Klar, Maximilian; Orlowska-Volk, Marzenna; Windfuhr-Blum, Marisa; Heil, Joerg; Rom, Joachim; Sohn, Christof; Fehm, Tanja; Mohrmann, Svjetlana; Loehberg, Christian R; Hein, Alexander; Schulz-Wendtland, Ruediger; Hartkopf, Andreas D; Brucker, Sara Y; Wallwiener, Diethelm; Friese, Klaus; Hartmann, Arndt; Beckmann, Matthias W; Janni, Wolfgang; Rack, Brigitte

2014-11-01

85

Sample distillation/graphitization system for carbon pool analysis by accelerator mass spectrometry (AMS)  

NASA Astrophysics Data System (ADS)

A facility at the Naval Research Laboratory (NRL), Washington, DC, has been developed to extract, trap, cryogenically distill and graphitize carbon from a suite of organic and inorganic carbon pools for analysis by accelerator mass spectrometry (AMS). The system was developed to investigate carbon pools associated with the formation and stability of methane hydrates. However, since the carbon compounds found in hydrate fields are ubiquitous in aquatic ecosystems, this apparatus is applicable to a number of oceanographic and environmental sample types. Targeted pools are dissolved methane, dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), solid organic matrices (e.g., seston, tissue and sediments), biomarkers and short chained (C 1-C 5) hydrocarbons from methane hydrates. In most instances, the extraction, distillation and graphitization events are continuous within the system, thus, minimizing the possibility of fractionation or contamination during sample processing. A variety of methods are employed to extract carbon compounds and convert them to CO 2 for graphitization. Dissolved methane and DIC from the same sample are sparged and cryogenically separated before the methane is oxidized in a high temperature oxygen stream. DOC is oxidized to CO 2 by 1200 W ultraviolet photo-oxidation lamp, and solids oxidized in sealed, evacuated tubes. Hydrocarbons liberated from the disassociation of gas hydrates are cryogenically separated with a cryogenic temperature control unit, and biomarkers separated and concentrated by preparative capillary gas chromatography (PCGC). With this system, up to 20 samples, standards or blanks can be processed per day.

Pohlman, J. W.; Knies, D. L.; Grabowski, K. S.; DeTurck, T. M.; Treacy, D. J.; Coffin, R. B.

2000-10-01

86

A pooling-LiNGAM algorithm for effective connectivity analysis of fMRI data  

PubMed Central

The Independent Component Analysis (ICA)—linear non-Gaussian acyclic model (LiNGAM), an algorithm that can be used to estimate the causal relationship among non-Gaussian distributed data, has the potential value to detect the effective connectivity of human brain areas. Under the assumptions that (a): the data generating process is linear, (b) there are no unobserved confounders, and (c) data have non-Gaussian distributions, LiNGAM can be used to discover the complete causal structure of data. Previous studies reveal that the algorithm could perform well when the data points being analyzed is relatively long. However, there are too few data points in most neuroimaging recordings, especially functional magnetic resonance imaging (fMRI), to allow the algorithm to converge. Smith's study speculates a method by pooling data points across subjects may be useful to address this issue (Smith et al., 2011). Thus, this study focus on validating Smith's proposal of pooling data points across subjects for the use of LiNGAM, and this method is named as pooling-LiNGAM (pLiNGAM). Using both simulated and real fMRI data, our current study demonstrates the feasibility and efficiency of the pLiNGAM on the effective connectivity estimation. PMID:25339895

Xu, Lele; Fan, Tingting; Wu, Xia; Chen, KeWei; Guo, Xiaojuan; Zhang, Jiacai; Yao, Li

2014-01-01

87

A Pooled Analysis of Extremely Low-Frequency Magnetic Fields and Childhood Brain Tumors  

PubMed Central

Pooled analyses may provide etiologic insight about associations between exposure and disease. In contrast to childhood leukemia, no pooled analyses of childhood brain tumors and exposure to extremely low-frequency magnetic fields (ELF-MFs) have been conducted. The authors carried out a pooled analysis based on primary data (1960–2001) from 10 studies of ELF-MF exposure and childhood brain tumors to assess whether the combined results, adjusted for potential confounding, indicated an association. The odds ratios for childhood brain tumors in ELF-MF exposure categories of 0.1–<0.2 ?T, 0.2–<0.4 ?T, and ?0.4 ?T were 0.95 (95% confidence interval: 0.65, 1.41), 0.70 (95% CI: 0.40, 1.22), and 1.14 (95% CI: 0.61, 2.13), respectively, in comparison with exposure of <0.1 ?T. Other analyses employing alternate cutpoints, further adjustment for confounders, exclusion of particular studies, stratification by type of measurement or type of residence, and a nonparametric estimate of the exposure-response relation did not reveal consistent evidence of increased childhood brain tumor risk associated with ELF-MF exposure. These results provide little evidence for an association between ELF-MF exposure and childhood brain tumors. PMID:20696650

Kheifets, L.; Ahlbom, A.; Crespi, C. M.; Feychting, M.; Johansen, C.; Monroe, J.; Murphy, M. F. G.; Oksuzyan, S.; Preston-Martin, S.; Roman, E.; Saito, T.; Savitz, D.; Schuz, J.; Simpson, J.; Swanson, J.; Tynes, T.; Verkasalo, P.; Mezei, G.

2010-01-01

88

The Cancer Genome Atlas completes detailed ovarian cancer analysis:  

Cancer.gov

An analysis of genomic changes in ovarian cancer has provided the most comprehensive and integrated view of cancer genes for any cancer type to date. Ovarian serous adenocarcinoma tumors from 500 patients were examined by The Cancer Genome Atlas (TCGA) Research Network. TCGA researchers completed whole-exome sequencing, which examines the protein-coding regions of the genome, on an unprecedented 316 tumors.

89

A Pooled Analysis of Body Mass Index and Mortality among African Americans  

PubMed Central

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995–2009; Adventist Health Study 2, 2002–2008; Black Women's Health Study, 1995–2009; Cancer Prevention Study II, 1982–2008; Multiethnic Cohort Study, 1993–2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993–2009; Southern Community Cohort Study, 2002–2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30–104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25–27.4, 27.5–29.9, 30–34.9, 35–39.9, 40–49.9, and 50–60 kg/m2 were 1.02 (0.92–1.12), 1.06 (0.95–1.18), 1.32 (1.18–1.47), 1.54 (1.29–1.83), 1.93 (1.46–2.56), and 1.93 (0.80–4.69), respectively among men and 1.06 (0.99–1.15), 1.15 (1.06–1.25), 1.24 (1.15–1.34), 1.58 (1.43–1.74), 1.80 (1.60–2.02), and 2.31 (1.74–3.07) respectively among women (reference category 22.5–24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans. PMID:25401742

Cohen, Sarah S.; Park, Yikyung; Signorello, Lisa B.; Patel, Alpa V.; Boggs, Deborah A.; Kolonel, Laurence N.; Kitahara, Cari M.; Knutsen, Synnove F.; Gillanders, Elizabeth; Monroe, Kristine R.; de Gonzalez, Amy Berrington; Bethea, Traci N.; Black, Amanda; Fraser, Gary; Gapstur, Susan; Hartge, Patricia; Matthews, Charles E.; Park, Song-Yi; Purdue, Mark P.; Singh, Pramil; Harvey, Chinonye; Blot, William J.; Palmer, Julie R.

2014-01-01

90

Integrative prescreening in analysis of multiple cancer genomic studies  

PubMed Central

Background In high throughput cancer genomic studies, results from the analysis of single datasets often suffer from a lack of reproducibility because of small sample sizes. Integrative analysis can effectively pool and analyze multiple datasets and provides a cost effective way to improve reproducibility. In integrative analysis, simultaneously analyzing all genes profiled may incur high computational cost. A computationally affordable remedy is prescreening, which fits marginal models, can be conducted in a parallel manner, and has low computational cost. Results An integrative prescreening approach is developed for the analysis of multiple cancer genomic datasets. Simulation shows that the proposed integrative prescreening has better performance than alternatives, particularly including prescreening with individual datasets, an intensity approach and meta-analysis. We also analyze multiple microarray gene profiling studies on liver and pancreatic cancers using the proposed approach. Conclusions The proposed integrative prescreening provides an effective way to reduce the dimensionality in cancer genomic studies. It can be coupled with existing analysis methods to identify cancer markers. PMID:22799431

2012-01-01

91

Annual Energy Consumption Analysis and Energy Optimization of a Solar-Assisted Heating Swimming Pool  

E-print Network

This paper is concerned with the energy efficiency calculations and optimization for an indoor solar-assisted heating swimming pool in GuangZhou. The heating energy requirements for maintaining the pool constant temperature were investigated, which...

Zuo, Z.; Hu, W.; Meng, O.

2006-01-01

92

Inference of synergy/antagonism between anticancer drugs from the pooled analysis of clinical trials  

PubMed Central

Background Drug interactions can have a significant impact on the response to combinatorial therapy for anticancer treatment. In some instances these interactions can be anticipated based on pre-clinical models. However, the anticipation of drug interactions in the clinical context is in general a challenging task. Methods Here we propose the pooled analysis of clinical trials as a mean to investigate drug interactions in anticancer therapy. To this end we collected 1,163 Phase II clinical trials with response data on over 53,745 subjects. Results We provide statistical definitions of drugs resulting in clinical synergy and antagonism and identify drug combinations in each group. We also quantify the possibility of inferring interactions between three or more drugs from parameters characterizing the action of single and two-drugs combinations. Conclusions Our analysis provides a statistical methodology to track the performance of drug combinations in anticancer therapy and to quantify drug interactions in the clinical context. PMID:23758906

2013-01-01

93

Efficacy of topical treatments for cutaneous warts: a meta-analysis and pooled analysis of randomized controlled trials.  

PubMed

Many topical treatments for cutaneous warts exist and previous reviews of trials did not follow intention-to-treat (ITT) principles for analysis. We aimed to perform a meta-analysis and pooled analysis of randomized controlled trials (RCTs) of topical treatment for cutaneous warts using ITT principles. Systematic electronic searches (Cochrane library, Medline, Embase, Clinical trial registers) were conducted in May 2009. Included trials reported completed cure of warts and data were extracted from these trials. We performed random-effects meta-analysis and assessed heterogeneity using the I(2) statistic and conducted a pooled analysis of each treatment. We found 77 relevant studies of which the majority were of low methodological quality. Salicylic acid (SA) was superior to placebo with a risk ratio (RR) for cure of 1·60 [95% confidence interval (CI) 1·15-2·24]. Cryotherapy was not statistically better than placebo, RR 0·89 (95% CI 0·27-2·92), but aggressive cryotherapy was significantly better than gentle cryotherapy with a RR of 2·06 (95% 1·20-3·52). Combined therapy of SA and cryotherapy had a higher cure rate than either SA or cryotherapy alone. The results of the pooled analysis found a cure rate of 23% (5-73%) in placebo trials, 52% (0-87%) in SA trials, 49% (0-69%) in cryotherapy trials, 54% (45-75%) in aggressive cryotherapy trials and 58% (38-78%) in the combined cryotherapy and SA trials. Aside from the use of SA and aggressive cryotherapy there is insufficient evidence from RCTs to support the use of other therapies. Higher quality evidence is needed to evaluate other therapies. PMID:21219294

Kwok, C S; Holland, R; Gibbs, S

2011-08-01

94

Equilibrium analysis of carbon pools and fluxes of forest biomes in the former Soviet Union  

SciTech Connect

Forests are an important component of the biosphere and sequestration of carbon in boreal forests may represent one of the few realistic alternatives to ameliorate changes in atmospheric chemistry. The former Soviet Union has the greatest expanse of boreal forests in the world; however, the role of these forests in the terrestrial carbon cycle is not fully understood because the carbon budget of the Soviet forest sector has not been established. In recognition of the need to determine the role of these forests in the global carbon cycle, the carbon budget of forest biomes in the former Soviet Union was assessed based on an equilibrium analysis of carbon cycle pools and fluxes. Net primary productivity was used to identify the rate of carbon turnover in the forest biomes.

Kolchugina, T.P.; Vinson, T.S.

1993-01-01

95

Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis  

PubMed Central

Background Topical nonsteroidal anti-inflammatory drug (NSAID) formulations, which produce less systemic exposure compared with oral formulations, are an option for the management of osteoarthritis (OA). However, the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial. Methods Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo) with oral diclofenac (ODiclo). Each study independently showed that TDiclo had similar efficacy to ODiclo. To compare the safety profiles of TDiclo and ODiclo, a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee. This pooled analysis included patients treated with TDiclo, containing 45.5% dimethyl sulfoxide (DMSO), and those treated with ODiclo. Safety assessments included monitoring of adverse events (AEs), recording of vital signs, dermatologic evaluation of the study knee, and clinical laboratory evaluation. Results AEs occurred in 312 (67.1%) patients using TDiclo versus 298 (64.5%) of those taking ODiclo. The most common AE with TDiclo was dry skin at the application site (24.1% vs 1.9% with ODiclo; P < 0.0001). Fewer gastrointestinal (25.4% vs 39.0%; P < 0.0001) and cardiovascular (1.5% vs 3.5%; P = 0.055) AEs occurred with TDiclo compared with ODiclo. ODiclo was associated with significantly greater increases in liver enzymes and creatinine, and greater decreases in creatinine clearance and hemoglobin (P < 0.001 for all). Conclusions These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA, with a more favorable safety profile. PMID:21811391

Roth, Sanford H; Fuller, Philip

2011-01-01

96

Clone-array pooled shotgun mapping and sequencing: design and analysis of experiments  

Microsoft Academic Search

This paper studies sequencing and mapping methods that rely solely on pooling\\u000aand shotgun sequencing of clones. First, we scrutinize and improve the recently\\u000aproposed Clone-Array Pooled Shotgun Sequencing (CAPSS) method, which delivers a\\u000aBAC-linked assembly of a whole genome sequence. Secondly, we introduce a novel\\u000aphysical mapping method, called Clone-Array Pooled Shotgun Mapping (CAPS-MAP),\\u000awhich computes the physical ordering

Bingshan Li; Aleksandar Milosavljevic

2003-01-01

97

Predictors of Local Recurrence Following Accelerated Partial Breast Irradiation: A Pooled Analysis  

SciTech Connect

Purpose: To analyze a pooled set of nearly 2,000 patients treated on the American Society of Breast Surgeons (ASBS) Mammosite Registry Trial and at William Beaumont Hospital (WBH) to identify factors associated with local recurrence following accelerated partial breast irradiation (APBI). Methods and Materials: A total of 1,961 women underwent partial breast irradiation between April 1993 and November 2010 as part of the ASBS Registry Trial or at WBH. Rates of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed for each group and for the pooled cohort. Clinical, pathologic, and treatment-related variables were analyzed including age, tumor stage/size, estrogen receptor status, surgical margins, and lymph node status to determine their association with IBTR. Results: The two groups weres similar, but WBH patients were more frequently node positive, had positive margins, and were less likely to be within the American Society for Radiation Oncology-unsuitable group. At 5 years, the rates of IBTR, RR, DM, DFS, CSS, and OS for the pooled group of patients were 2.9%, 0.5%, 2.4%, 89.1%, 98.5%, and 91.8%, respectively. The 5-year rate of true recurrence/marginal miss was 0.8%. Univariate analysis of IBTR found that negative estrogen receptor status (odds ratio [OR], 2.83, 95% confidence interval 1.55-5.13, p = 0.0007) was the only factor significantly associated with IBTR, while a trend was seen for age less than 50 (OR 1.80, 95% confidence interval 0.90-3.58, p = 0.10). Conclusions: Excellent 5-year outcomes were seen following APBI in over 1,900 patients. Estrogen receptor negativity was the only factor associated with IBTR, while a trend for age less than 50 was noted. Significant differences in factors associated with IBTR were noted between cohorts, suggesting that factors driving IBTR may be predicated based on the risk stratification of the patients being treated.

Shah, Chirag; Wilkinson, John Ben [Department of Radiation Oncology, Beaumont Cancer Institute, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Lyden, Maureen [Biostat Inc., Tampa, Florida (United States); Beitsch, Peter [Dallas Breast Center, Dallas, Texas (United States); Vicini, Frank A., E-mail: fvicini@pol.net [Department of Radiation Oncology, Beaumont Cancer Institute, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States)

2012-04-01

98

Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis  

PubMed Central

Objective To compare the incidence of cardiovascular events and mortality in patients with type 2 diabetes mellitus treated with sitagliptin or non-sitagliptin comparators. Methods A post hoc assessment of cardiovascular safety in 14,611 patients was performed by pooling data from 25 double-blind studies, which randomised patients at baseline to sitagliptin 100 mg/day or a non-sitagliptin comparator (i.e., non-exposed). Included studies were limited to those at least 12 weeks in duration (range: 12 to 104 weeks). Patient-level data were used in this analysis of major adverse cardiovascular events (MACE) including ischaemic events and cardiovascular deaths. Analyses were performed in three cohorts: the entire 25-study cohort, the cohort from placebo-controlled portions of studies (n=19), and the cohort from studies comparing sitagliptin to a sulphonylurea (n=3). Results In the entire cohort analysis, 78 patients had at least 1 reported MACE-related event, with 40 in the sitagliptin group and 38 in the non-exposed group. The exposure-adjusted incidence rate was 0.65 per 100 patient-years in the sitagliptin group and 0.74 in the non-exposed group (incidence rate ratio = 0.83 [95% confidence interval (CI): 0.53, 1.30]). In the analysis comparing sitagliptin to placebo, the exposure-adjusted incidence rate was 0.80 per 100-patient-years with sitagliptin and 0.76 with placebo (incidence rate ratio = 1.01 [95% CI: 0.55, 1.86]). In the analysis comparing sitagliptin to sulphonylurea, the exposure-adjusted incidence rate was 0.00 per 100 patient-years with sitagliptin and 0.86 with sulphonylurea (incidence rate ratio = 0.00 [95% CI: 0.00, 0.31]). Conclusion A pooled analysis of 25 randomised clinical trials does not indicate that treatment with sitagliptin increases cardiovascular risk in patients with type 2 diabetes mellitus. In a subanalysis, a higher rate of cardiovascular-related events was associated with sulphonylurea relative to sitagliptin. PMID:23286208

2013-01-01

99

Exciting Pools  

ERIC Educational Resources Information Center

Advocates the creation of swimming pool oscillations as part of a general investigation of mechanical oscillations. Presents the equations, procedure for deriving the slosh modes, and methods of period estimation for exciting swimming pool oscillations. (GS)

Wright, Bradford L.

1975-01-01

100

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials  

Microsoft Academic Search

Objectives: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. Study design: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5

Z. A. Bhutta; R. E. Black; K. H. Brown; J. Meeks Gardner; S. Gore; A. Hidayat; F. Khatun; R. Martorell; N. X. Ninh; M. E. Penny; J. L. Rosado; S. K. Roy; M. Ruel; S. Sazawal; A. Shankar

1999-01-01

101

Weld pool development during GTA and laser beam welding of Type 304 stainless steel; Part I - theoretical analysis  

SciTech Connect

A computational and experimental study was carried out to quantitatively understand the influence of the heat flow and the fluid flow in the transient development of the weld pool during gas tungsten arc (GTA) and laser beam welding of Type 304 stainless steel. Stationary gas tungsten arc and laser beam welds were made on two heats of Type 304 austenitic stainless steels containing 90 ppm sulfur and 240 ppm sulfur. A transient heat transfer model was utilized to simulate the heat flow and fluid flow in the weld pool. In this paper, the results of the heat flow and fluid flow analysis are presented.

Zacharia, T.; David, S.A.; Vitek, J.M. (Metals and Ceramics Div., Oak Ridge National Lab., Oak Ridge, TN (USA)); Debroy, T. (Dept. of Materials Science and Engineering, Pennsylvania State Univ., University Park, PA (USA))

1989-12-01

102

BNCT for locally recurrent head and neck cancer: preliminary clinical experience from a phase I/II trial at Tsing Hua Open-Pool Reactor.  

PubMed

To introduce our preliminary experience of treating locally and regionally recurrent Head and Neck cancer patients at Tsing Hua Open-Pool Reactor in Taiwan, four patients (M/F=3/1, median age 68 Y/O) were enrolled. BNCT with BPA (400 mg/kg) injected in 2 phases and prescription dose of 12-35 Gy (Eq.)/fraction for 2 fractions at 30 day interval can be given with sustained blood boron concentration and tolerable early toxicities for recurrent H & N cancer. PMID:21478023

Wang, L W; Wang, S J; Chu, P Y; Ho, C Y; Jiang, S H; Liu, Y W H; Liu, Y H; Liu, H M; Peir, J J; Chou, F I; Yen, S H; Lee, Y L; Chang, C W; Liu, C S; Chen, Y W; Ono, K

2011-12-01

103

Fractionated BNCT for locally recurrent head and neck cancer: experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor.  

PubMed

To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial. PMID:24369888

Wang, Ling-Wei; Chen, Yi-Wei; Ho, Ching-Yin; Hsueh Liu, Yen-Wan; Chou, Fong-In; Liu, Yuan-Hao; Liu, Hong-Ming; Peir, Jinn-Jer; Jiang, Shiang-Huei; Chang, Chi-Wei; Liu, Ching-Sheng; Wang, Shyh-Jen; Chu, Pen-Yuan; Yen, Sang-Hue

2014-06-01

104

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.  

PubMed Central

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population. PMID:11729160

Heo, M; Leibel, R L; Boyer, B B; Chung, W K; Koulu, M; Karvonen, M K; Pesonen, U; Rissanen, A; Laakso, M; Uusitupa, M I; Chagnon, Y; Bouchard, C; Donohoue, P A; Burns, T L; Shuldiner, A R; Silver, K; Andersen, R E; Pedersen, O; Echwald, S; Sørensen, T I; Behn, P; Permutt, M A; Jacobs, K B; Elston, R C; Hoffman, D J; Allison, D B

2001-01-01

105

Power analysis of QTL detection in half-sib families using selective DNA pooling  

PubMed Central

Individual loci of economic importance (QTL) can be detected by comparing the inheritance of a trait and the inheritance of loci with alleles readily identifiable by laboratory methods (genetic markers). Data on allele segregation at the individual level are costly and alternatives have been proposed that make use of allele frequencies among progeny, rather than individual genotypes. Among the factors that may affect the power of the set up, the most important are those intrinsic to the QTL: the additive effect of the QTL, and its dominance, and distance between markers and QTL. Other factors are relative to the choice of animals and markers, such as the frequency of the QTL and marker alleles among dams and sires. Data collection may affect the detection power through the size of half-sib families, selection rate within families, and the technical error incurred when estimating genetic frequencies. We present results for a sensitivity analysis for QTL detection using pools of DNA from selected half-sibs. Simulations showed that conclusive detection may be achieved with families of at least 500 half-sibs if sires are chosen on the criteria that most of their marker alleles are either both missing, or one is fixed, among dams. PMID:11403746

Baro, Jesus A; Carleos, Carlos; Corral, Norberto; Lopez, Teresa; Canon, Javier

2001-01-01

106

Power analysis of QTL detection in half-sib families using selective DNA pooling.  

PubMed

Individual loci of economic importance (QTL) can be detected by comparing the inheritance of a trait and the inheritance of loci with alleles readily identifiable by laboratory methods (genetic markers). Data on allele segregation at the individual level are costly and alternatives have been proposed that make use of allele frequencies among progeny, rather than individual genotypes. Among the factors that may affect the power of the set up, the most important are those intrinsic to the QTL: the additive effect of the QTL, and its dominance, and distance between markers and QTL. Other factors are relative to the choice of animals and markers, such as the frequency of the QTL and marker alleles among dams and sires. Data collection may affect the detection power through the size of half-sib families, selection rate within families, and the technical error incurred when estimating genetic frequencies. We present results for a sensitivity analysis for QTL detection using pools of DNA from selected half-sibs. Simulations showed that conclusive detection may be achieved with families of at least 500 half-sibs if sires are chosen on the criteria that most of their marker alleles are either both missing, or one is fixed, among dams. PMID:11403746

Baro JA; Carleos, C; Corral, N; López, T; Cañón, J

2001-01-01

107

Analysis of the polarity influence on nucleate pool boiling under a DC electric field  

SciTech Connect

An experimental study of the action of an intense electric field on the pool boiling of n-pentane is presented. By the application of a 25 kV/cm electric field strength, a threefold heat transfer enhancement is obtained. The effect of the electric field polarity has been researched. In nucleate boiling, the negative polarity allows to obtain a heat transfer enhancement, which is better than the one obtained in positive polarity. However, in natural convection and near the critical heat flux, the polarity of the electric field has a low influence on the heat transfer. The interpretations of the observed results are based on the action of the electric field on the boiling phenomenon and more particularly on the analysis of the electric field distribution between the electrodes. The influence of the space charge injection and the effect of the temperature on the electric field distribution have been investigated. The results obtained in the two cases of polarity are discussed in terms of effects of electrical and thermal phenomena on the distribution of the electric field between the electrodes.

Zaghdoudi, M.C.; Lallemand, M.

1999-11-01

108

Bleeding Risk and Mortality of Edoxaban: A Pooled Meta-Analysis of Randomized Controlled Trials  

PubMed Central

Objective(s) Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored. Methods Medline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of edoxaban with warfarin. Safety outcomes examined included bleeding risk and mortality. Results Five trials including 31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban was associated with a significant decrease in major or clinically relevant nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause mortality [RR 0.92, 95% CI0.85 to0.99, p?=?0.02] and cardiovascular mortality [RR 0.87, 95% CI0.79 to 0.96, p?=?0.004]. Subgroup analyses indicated that RRs of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p?=?0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p?=?0.002) respectively in any bleeding; as well as 0.86 (p?=?0.01), 0.87 (p?=?0.01) and 0.28 (p?=?0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor bleeding event (p?=?0.02) and any bleeding (p?=?0.002), but neither in all-cause death (p?=?0.66) nor cardiovascular death (p?=?0.70). Conclusions Edoxaban, a novel orally available direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to bleeding risk and non-inferior in mortality when compared to warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis. PMID:24736694

Xu, Dachun; Xu, Yawei

2014-01-01

109

Estimation of the Relative Sensitivity of qPCR Analysis Using Pooled Samples  

PubMed Central

The high sensitivity of qPCR makes it a desirable diagnostic method in epidemiological surveillance programs. However, due to high costs, the use of pooling has been suggested. In this paper, an algorithm based on the Montecarlo method has been designed and implemented. The algorithm had been tested in many different situations, and finally it was validated with a real dataset. Moreover, based on the results obtained and depending on pooling conditions, a drastic decrease of sensitivity is observed. PMID:24722485

Muniesa, Ana; Ferreira, Chelo; Fuertes, Hector; Halaihel, Nabil; de Blas, Ignacio

2014-01-01

110

Pool Purification  

NASA Technical Reports Server (NTRS)

Caribbean Clear, Inc. used NASA's silver ion technology as a basis for its automatic pool purifier. System offers alternative approach to conventional purification chemicals. Caribbean Clear's principal markets are swimming pool owners who want to eliminate chlorine and bromine. Purifiers in Caribbean Clear System are same silver ions used in Apollo System to kill bacteria, plus copper ions to kill algae. They produce spa or pool water that exceeds EPA Standards for drinking water.

1988-01-01

111

Coffee consumption and risk of endometrial cancer: findings from a large up-to-date meta-analysis.  

PubMed

Several epidemiological studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta-analysis of observational studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. A total of 16 studies (10 case-control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62-0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control studies and 0.70 (95% CI: 0.61-0.80) for cohort studies. By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; 95% CI: 0.25-0.63) than five studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60-0.79) or eight studies from Europe (pooled RR = 0.79; 95% CI: 0.63-0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90-0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control studies. More large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk. PMID:22190017

Je, Youjin; Giovannucci, Edward

2012-10-01

112

Analgesic use and the risk of kidney cancer: a meta-analysis of epidemiologic studies  

PubMed Central

Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for 3 categories of analgesics: acetaminophen, aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin, and 5 with other NSAIDs) that were performed in 6 countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR, 1.28; 95% CI, 1.15 to 1.44 and 1.25; 95% CI, 1.06 to 1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR, 1.10; 95% CI, 0.95 to 1.28), except for non-US studies (5 studies, pooled RR=1.17, 95% CI, 1.04 to 1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings. PMID:23400756

Choueiri, Toni K.; Je, Youjin; Cho, Eunyoung

2013-01-01

113

Identification of Breast Cancer Prognosis Markers via Integrative Analysis  

PubMed Central

Summary In breast cancer research, it is of great interest to identify genomic markers associated with prognosis. Multiple gene profiling studies have been conducted for such a purpose. Genomic markers identified from the analysis of single datasets often do not have satisfactory reproducibility. Among the multiple possible reasons, the most important one is the small sample sizes of individual studies. A cost-effective solution is to pool data from multiple comparable studies and conduct integrative analysis. In this study, we collect four breast cancer prognosis studies with gene expression measurements. We describe the relationship between prognosis and gene expressions using the accelerated failure time (AFT) models. We adopt a 2-norm group bridge penalization approach for marker identification. This integrative analysis approach can effectively identify markers with consistent effects across multiple datasets and naturally accommodate the heterogeneity among studies. Statistical and simulation studies demonstrate satisfactory performance of this approach. Breast cancer prognosis markers identified using this approach have sound biological implications and satisfactory prediction performance. PMID:22773869

Ma, Shuangge; Dai, Ying; Huang, Jian; Xie, Yang

2012-01-01

114

Well-characterized open pool experiment data and analysis for model validation and development.  

SciTech Connect

Four Well-Characterized Open Pool fires were conducted by Fire Science and Technology Department. The focus of the Well-Characterized Open Pool fire series was to provide environmental information for open pool fires on a physics first principal basis. The experiments measured the burning rate of liquid fuel in an open pool and the resultant heat flux to a weapon-sized object and the surrounding environment with well-characterized boundary and initial conditions. Results presented in this report include a general description of test observation (pre- and post-test), wind measurements, fire plume topology, average fuel recession and heat release rates, and incident heat flux to the pool and to the calorimeters. As expected, results of the experiments show a strong correlation between wind conditions, fuel vaporization (mass loss) rate, and incident heat flux to the fuel and ground surface and calorimeters. Numerical fire simulations using both temporally- and spatially-dependant wind boundary conditions were performed using the Vulcan fire code. Comparisons of data to simulation predictions showed similar trends; however, simulation-predicted incident heat fluxes were lower than measured.

Sundberg, David W.; Brown, Alexander L.; Blanchat, Thomas K.

2006-12-01

115

COX-2-765G>C Polymorphism Increases the Risk of Cancer: A Meta-Analysis  

PubMed Central

Background Chronic inflammation has been regarded as an important mechanism in carcinogenesis. Inflammation-associated genetic variants have been highly associated with cancer risk. Polymorphisms in the gene cyclooxygenase-2 (COX-2), a pro-inflammation factor, have been suggested to alter the risk of multiple tumors, but the findings of various studies are not consistent. Methods A literature search through February 2013 was performed using PubMed, EMBASE, and CNKI databases. We used odds ratios (ORs) with confidence intervals (CIs) of 95% to assess the strength of the association between the COX-2-765G>C polymorphism and cancer risk in a random-effect model. We also assessed heterogeneity and publication bias. Results In total, 65 articles with 29,487 cancer cases and 39,212 non-cancer controls were included in this meta-analysis. The pooled OR (95% CIs) in the co-dominant model (GC vs. GG) was 1.11 (1.02–1.22), and in the dominant model ((CC+GC) vs. GG), the pooled OR was 1.12 (1.02–1.23). In the subgroup analysis, stratified by cancer type and race, significant associations were found between the-765 C allele and higher risk for gastric cancer, leukemia, pancreatic cancer, and cancer in the Asian population. Conclusion In summary, the COX-2-765 C allele was related to increased cancer susceptibility, especially gastric cancer and cancer in the Asian population. PMID:24023834

Zhang, Xiao-wei; Hua, Rui-xi; Guo, Wei-jian

2013-01-01

116

Examining the Efficacy of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Analysis of 2 Studies  

PubMed Central

Background: Patients with major depressive disorder (MDD) who fail to achieve complete remission with antidepressant therapy may benefit from augmentation therapy with an atypical antipsychotic. Method: A pooled analysis was performed on 2 identical 14-week studies (8-week prospective antidepressant therapy treatment phase followed by 6-week randomized double-blind phase) evaluating the efficacy of adjunctive aripiprazole (2–20 mg/day) in DSM-IV-TR–defined MDD patients with an inadequate response to antidepressant therapy. Primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from end of the prospective phase (week 8) to end of randomized phase (week 14, last observation carried forward). Subgroup analyses were performed. The key secondary endpoint was mean change in Sheehan Disability Scale (SDS) mean score. Results: At endpoint, mean change in MADRS total score was significantly greater with adjunctive aripiprazole (–8.7) than with adjunctive placebo (–5.7; p < .001). Except for a differential treatment-by-sex interaction, change in MADRS total scores were consistently greater with adjunctive aripiprazole than with adjunctive placebo, regardless of race, age, episode duration, prior antidepressant therapy response, number of historical treatment failures, severity of depressive symptoms, and antidepressant. At endpoint, MADRS remission rates were significantly greater with adjunctive aripiprazole than with placebo (25.7% vs. 15.4%; p < .001). Adjunctive aripiprazole also demonstrated significantly greater improvements in mean change from baseline in SDS total score than adjunctive placebo (–1.2 vs. –0.6; p = .001). Conclusion: Augmentation of antidepressant therapy with the atypical antipsychotic aripiprazole resulted in significant efficacy benefits across a range of subgroups of patients with MDD. Further study of a treatment-by-sex interaction is needed. Trial Registration: www.clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758 PMID:19287552

Thase, Michael E.; Trivedi, Madhukar H.; Nelson, J. Craig; Fava, Maurizio; Swanink, Rene; Tran, Quynh-Van; Pikalov, Andrei; Yang, Huyuan; Carlson, Berit X.; Marcus, Ronald N.; Berman, Robert M.

2008-01-01

117

Rivaroxaban for thromboprophylaxis after orthopaedic surgery: pooled analysis of two studies.  

PubMed

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N = 722), and one in patients undergoing total knee replacement (TKR; N = 621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5-9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1-24.4% of per-protocol patients receiving rivaroxaban 5-60 mg, and 27.8% receiving enoxaparin (n = 914). There was a flat dose response relationship between rivaroxaban and total VTE (p = 0.39). Major bleeding (safety population, n = 1,317) increased dose-dependently with rivaroxaban (p < 0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5-20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery. PMID:17549294

Fisher, William D; Eriksson, Bengt I; Bauer, Kenneth A; Borris, Lars; Dahl, Ola E; Gent, Michael; Haas, Sylvia; Homering, Martin; Huisman, Menno V; Kakkar, Ajay K; Kälebo, Peter; Kwong, Louis M; Misselwitz, Frank; Turpie, Alexander G G

2007-06-01

118

Friends and Symptom Dimensions in Patients with Psychosis: A Pooled Analysis  

PubMed Central

Background Having friends is associated with more favourable clinical outcomes and a higher quality of life in mental disorders. Patients with schizophrenia have fewer friends than other mentally ill patients. No large scale studies have evaluated so far what symptom dimensions of schizophrenia are associated with the lack of friendships. Methods Data from four multi-centre studies on outpatients with schizophrenia and related disorders (ICD F20-29) were included in a pooled analysis (N?=?1396). We established whether patients had close friends and contact with friends by using the equivalent items on friendships of the Manchester Short Assessment of Quality of Life or of the Lancashire Quality of Life Profile. Symptoms were measured by the Brief Psychiatric Rating Scale or by the identical items included in the Positive and Negative Syndrome Scale. Results Seven hundred and sixty-nine patients (55.1%) had seen a friend in the previous week and 917 (65.7%) had someone they regarded as a close friend. Low levels of negative symptoms and hostility were significantly associated with having a close friend and contact with a friend. Overall, almost twice as many patients with absent or mild negative symptoms had met a friend in the last week, compared with those with moderate negative symptoms. Conclusions Higher levels of negative symptoms and hostility are specifically associated with the lack of friendships in patients with psychotic disorders. These findings suggest the importance of developing effective treatments for negative symptoms and hostility in order to improve the probability of patients with schizophrenia to have friends. PMID:23185552

Giacco, Domenico; McCabe, Rose; Kallert, Thomas; Hansson, Lars; Fiorillo, Andrea; Priebe, Stefan

2012-01-01

119

Association between Alcohol Consumption and Cancers in the Chinese Population--A Systematic Review and Meta-Analysis  

PubMed Central

Background Alcohol consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population. Methods Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P<.01 was considered statistically significant. Results Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47–2.17) EC, 1.40 (99% CI, 1.19–1.64) gastric cancer, 1.56 (99% CI, 1.16–2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00–1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20–2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60–0.97) and 0.70 (99% CI, 0.49–1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma. Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not significantly associated with lung cancer. Conclusions Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the interaction between alcohol consumption and other risk factors for cancers in Chinese and other populations. PMID:21526212

Li, Ying; Yang, Huan; Cao, Jia

2011-01-01

120

Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy  

Microsoft Academic Search

BackgroundNephronophthisis associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive

Edgar A Otto; Gokul Ramaswami; Sabine Janssen; Moumita Chaki; Susan J Allen; Weibin Zhou; Rannar Airik; Toby W Hurd; Amiya K Ghosh; Matthias T Wolf; Bernd Hoppe; Thomas J Neuhaus; Detlef Bockenhauer; David V Milford; Neveen A Soliman; Corinne Antignac; Sophie Saunier; Colin A Johnson; Friedhelm Hildebrandt

2010-01-01

121

The Cancer Genome Atlas Pan-Cancer Analysis Project  

PubMed Central

Cancer can take hundreds of different forms depending on the location, cell of origin and spectrum of genomic alterations that promote oncogenesis and affect therapeutic response. Although many genomic events with direct phenotypic impact have been identified, much of the complex molecular landscape remains incompletely charted for most cancer lineages. For that reason, The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumours to discover molecular aberrations at the DNA, RNA, protein, and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences, and emergent themes across tumour lineages. The Pan-Cancer initiative compares the first twelve tumour types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumour types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

Weinstein, John N.; Collisson, Eric A.; Mills, Gordon B.; Shaw, Kenna M.; Ozenberger, Brad A.; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M.

2014-01-01

122

Integrative Microarray Analysis of Pathways Dysregulated in Metastatic Prostate Cancer  

E-print Network

Integrative Microarray Analysis of Pathways Dysregulated in Metastatic Prostate Cancer Sunita R array data from localized and metastatic prostate cancer. Comparison of metastatic cancer and localized pathways that were significantly dysregulated (P prostate cancer metastasis. The pathway

Gerstein, Mark

123

Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta-analysis  

PubMed Central

Background Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association. Methods All studies published up to January 2014 on the association between XPC polymorphisms and gastric cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between XPC polymorphisms and gastric cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results Six studies with 1,355 gastric cancer cases and 2,573 controls were finally included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not observe a significant association when all studies were pooled into the meta-analysis. When stratified by ethnicity, source of control, and study quality, statistical significant association was not detected in all subgroups. With respect to Ala499Val and PAT?/+polymorphisms, we also did not observe any significant association with gastric cancer risk in the pooled analysis. Conclusions This meta-analysis based on current evidences suggested that the XPC polymorphisms (Lys939Gln, Val499Arg, and PAT?/+) did not contribute to gastric cancer risk. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069 PMID:24886180

2014-01-01

124

Cruciferous vegetables intake and the risk of colorectal cancer: a meta-analysis of observational studies  

PubMed Central

Background Epidemiological studies have reported inconsistent associations between cruciferous vegetable (CV) intake and colorectal cancer (CRC) risk. To our knowledge, a comprehensive and quantitative assessment of the association between CV intake and CRC has not been reported. Methods Relevant articles were identified by searching MEDLINE. We pooled the relative risks (RR) from individual studies using a random-effect model and carried out heterogeneity and publication bias analyses. Results Twenty-four case–control and 11 prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (RR: 0.82; 95% confidence interval 0.75–0.90) intake and CRC risk. Specific analysis for cabbage and broccoli yielded similar result. When separately analyzed, case–control studies of CV intake yield similar results, and the results from the prospective studies showed borderline statistical significance. Moreover, significant inverse associations were also observed in colon cancer and its distal subsite both among prospective and case–control studies. Conclusions Findings from this meta-analysis provide evidence that high intake of CV was inversely associated with the risk of CRC and colon cancer in humans. Further analysis on other specific CV, food preparation methods, stratified results by anatomic cancer site, and subsite of colon cancer should be extended in future study. PMID:23211939

Wu, Q. J.; Yang, Y.; Vogtmann, E.; Wang, J.; Han, L. H.; Li, H. L.; Xiang, Y. B.

2013-01-01

125

Probabilistic risk analysis for Test Area North Hot Shop Storage Pool Facility  

Microsoft Academic Search

A storage pool facility used for storing spent fuel and radioactive debris from the Three Mile Island (TMI) accident was evaluated to determine the risk associated with its normal operations. Several hazards were identified and examined to determine if any any credible accident scenarios existed. Expected annual occurrence frequencies were calculated for hazards for which accident scenarios were identified through

B. M. Meale; D. G. Satterwhite

1990-01-01

126

An Analysis of Growth, Differentiation and Apoptosis Genes with Risk of Renal Cancer  

Microsoft Academic Search

We conducted a case-control study of renal cancer (987 cases and 1298 controls) in Central and Eastern Europe and analyzed genomic DNA for 319 tagging single-nucleotide polymorphisms (SNPs) in 21 genes involved in cellular growth, differentiation and apoptosis using an Illumina Oligo Pool All (OPA). A haplotype-based method (sliding window analysis of consecutive SNPs) was used to identify chromosome regions

Linda M. Dong; Paul Brennan; Sara Karami; Rayjean J. Hung; Idan Menashe; Sonja I. Berndt; Meredith Yeager; Stephen Chanock; David Zaridze; Vsevolod Matveev; Vladimir Janout; Hellena Kollarova; Vladimir Bencko; Kendra Schwartz; Faith Davis; Marie Navratilova; Neonila Szeszenia-Dabrowska; Dana Mates; Joanne S. Colt; Ivana Holcatova; Paolo Boffetta; Nathaniel Rothman; Wong-Ho Chow; Philip S. Rosenberg; Lee E. Moore; Amanda Ewart Toland

2009-01-01

127

Incorporating Network Structure in Integrative Analysis of Cancer Prognosis Data  

PubMed Central

In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly-connected nodes (genes) are more likely to have related biological functions and similar regression coefficients. The goal of this study is to develop an analysis approach that can incorporate the gene network structure in integrative analysis. To this end, we adopt an AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has low computational cost, is adopted for estimation. For marker selection, we propose a new penalization approach. The proposed penalty is composed of two parts. The first part is a group MCP penalty, and conducts gene selection. The second part is a Laplacian penalty, and smoothes the differences of coefficients for tightly-connected genes. A group coordinate descent approach is developed to compute the proposed estimate. Simulation study shows satisfactory performance of the proposed approach when there exist moderate to strong correlations among genes. We analyze three lung cancer prognosis datasets, and demonstrate that incorporating the network structure can lead to the identification of important genes and improved prediction performance. PMID:23161517

Liu, Jin; Huang, Jian; Ma, Shuangge

2014-01-01

128

Lung cancer and DNA repair genes: multilevel association analysis from the International Lung Cancer Consortium  

PubMed Central

Lung cancer (LC) is the leading cause of cancer-related death worldwide and tobacco smoking is the major associated risk factor. DNA repair is an important process, maintaining genome integrity and polymorphisms in DNA repair genes may contribute to susceptibility to LC. To explore the role of DNA repair genes in LC, we conducted a multilevel association study with 1655 single nucleotide polymorphisms (SNPs) in 211 DNA repair genes using 6911 individuals pooled from four genome-wide case–control studies. Single SNP association corroborates previous reports of association with rs3131379, located on the gene MSH5 (P = 3.57 × 10-5) and returns a similar risk estimate. The effect of this SNP is modulated by histological subtype. On the log-additive scale, the odds ratio per allele is 1.04 (0.84–1.30) for adenocarcinomas, 1.52 (1.28–1.80) for squamous cell carcinomas and 1.31 (1.09–1.57) for other histologies (heterogeneity test: P = 9.1 × 10?3). Gene-based association analysis identifies three repair genes associated with LC (P < 0.01): UBE2N, structural maintenance of chromosomes 1L2 and POLB. Two additional genes (RAD52 and POLN) are borderline significant. Pathway-based association analysis identifies five repair pathways associated with LC (P < 0.01): chromatin structure, DNA polymerases, homologous recombination, genes involved in human diseases with sensitivity to DNA-damaging agents and Rad6 pathway and ubiquitination. This first international pooled analysis of a large dataset unravels the role of specific DNA repair pathways in LC and highlights the importance of accounting for gene and pathway effects when studying LC. PMID:22382497

Kazma, Remi; Babron, Marie-Claude; Gaborieau, Valerie; Genin, Emmanuelle; Brennan, Paul; Hung, Rayjean J.; McLaughlin, John R.; Krokan, Hans E.; Elvestad, Maiken B.; Skorpen, Frank; Anderssen, Endre; Vooder, Tonu; Valk, Kristjan; Metspalu, Andres; Field, John K.; Lathrop, Mark; Sarasin, Alain; Benhamou, Simone

2012-01-01

129

Toward a Comprehensive Genomic Analysis of Cancer  

Cancer.gov

The National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) convened a "Toward a Comprehensive Genomic Analysis of Cancer" workshop in Washington, D.C. This workshop brought together physicians, basic scientists and other members of the U.S. and international cancer communities to assist in outlining the most effective strategies for the development of a successful project. Information about this workshop is reported in the Executive Summary.

130

MGMT Leu84Phe gene polymorphism and lung cancer risk: a meta-analysis.  

PubMed

Many studies have examined the association between the MGMT Leu84Phe polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to Nov. 2013. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 7 studies, comprising 3,094 lung cancer cases and 4,216 controls, were included. Overall, for (Phe/Phe+Phe/Leu) versus Leu/Leu, the pooled OR for all studies was 1.08 (95% CI?=?0.97-1.21 P?=?0.518 for heterogeneity); for Phe/Phe versus Leu/Leu and Phe versus Leu, the pooled OR was 1.10 (95% CI?=?0.99-1.21 P?=?0.445 for heterogeneity) and 1.46 (95% CI?=?1.05-2.02 P?=?0.352 for heterogeneity), respectively. In the stratified analysis by ethnicity, significantly risks were found among Caucasians not in Asians. This meta-analysis suggests that the MGMT Leu84Phe polymorphisms are associated with lung cancer risk among Caucasians not in Asians. PMID:24390665

Qiu, Zhi-xiong; Xue, Fei; Shi, Xuan-feng; He, Xiao; Ma, Hui-ni; Chen, Lan; Chen, Pin-zhong

2014-05-01

131

Impact of community based, specialist palliative care teams on hospitalisations and emergency department visits late in life and hospital deaths: a pooled analysis  

PubMed Central

Objective To determine the pooled effect of exposure to one of 11 specialist palliative care teams providing services in patients’ homes. Design Pooled analysis of a retrospective cohort study. Setting Ontario, Canada. Participants 3109 patients who received care from specialist palliative care teams in 2009-11 (exposed) matched by propensity score to 3109 patients who received usual care (unexposed). Intervention The palliative care teams studied served different geographies and varied in team composition and size but had the same core team members and role: a core group of palliative care physicians, nurses, and family physicians who provide integrated palliative care to patients in their homes. The teams’ role was to manage symptoms, provide education and care, coordinate services, and be available without interruption regardless of time or day. Main outcome measures Patients (a) being in hospital in the last two weeks of life; (b) having an emergency department visit in the last two weeks of life; or (c) dying in hospital. Results In both exposed and unexposed groups, about 80% had cancer and 78% received end of life homecare services for the same average duration. Across all palliative care teams, 970 (31.2%) of the exposed group were in hospital and 896 (28.9%) had an emergency department visit in the last two weeks of life respectively, compared with 1219 (39.3%) and 1070 (34.5%) of the unexposed group (P<0.001). The pooled relative risks of being in hospital and having an emergency department visit in late life comparing exposed versus unexposed were 0.68 (95% confidence interval 0.61 to 0.76) and 0.77 (0.69 to 0.86) respectively. Fewer exposed than unexposed patients died in hospital (503 (16.2%) v 887 (28.6%), P<0.001), and the pooled relative risk of dying in hospital was 0.46 (0.40 to 0.52). Conclusions Community based specialist palliative care teams, despite variation in team composition and geographies, were effective at reducing acute care use and hospital deaths at the end of life. PMID:24906901

Brazil, Kevin; Sussman, Jonathan; Pereira, Jose; Marshall, Denise; Austin, Peter C; Husain, Amna; Rangrej, Jagadish; Barbera, Lisa

2014-01-01

132

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)  

PubMed Central

Background To evaluate the dose–response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. Methods We analyzed data from 12 case–control studies within the International Pancreatic Cancer Case–Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. Results Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0–1.3) for former smokers and 2.2 (95% CI 1.7–2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR = 3.4 for ?35 cigarettes per day, P for trend <0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR = 2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. Conclusions This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ?20 years after quitting. PMID:22104574

Bosetti, C.; Lucenteforte, E.; Silverman, D. T.; Petersen, G.; Bracci, P. M.; Ji, B. T.; Negri, E.; Li, D.; Risch, H. A.; Olson, S. H.; Gallinger, S.; Miller, A. B.; Bueno-de-Mesquita, H. B.; Talamini, R.; Polesel, J.; Ghadirian, P.; Baghurst, P. A.; Zatonski, W.; Fontham, E.; Bamlet, W. R.; Holly, E. A.; Bertuccio, P.; Gao, Y. T.; Hassan, M.; Yu, H.; Kurtz, R. C.; Cotterchio, M.; Su, J.; Maisonneuve, P.; Duell, E. J.; Boffetta, P.; La Vecchia, C.

2012-01-01

133

An Innovative Hybrid Loop-Pool SFR Design and Safety Analysis Methods: Today and Tomorrow  

SciTech Connect

Investment in commercial sodium cooled fast reactor (SFR) power plants will become possible only if SFRs achieve economic competitiveness as compared to light water reactors and other Generation IV reactors. Toward that end, we have launched efforts to improve the economics and safety of SFRs from the thermal design and safety analyses perspectives at Idaho National Laboratory. From the thermal design perspective, an innovative hybrid loop-pool SFR design has been proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to further improve economics and safety. From the safety analyses perspective, we have initiated an effort to develop a high fidelity reactor system safety code.

Hongbin Zhang; Haihua Zhao; Vincent Mousseau

2008-04-01

134

Single cell analysis of cancer genomes.  

PubMed

Genomic studies have provided key insights into how cancers develop, evolve, metastasize and respond to treatment. Cancers result from an interplay between mutation, selection and clonal expansions. In solid tumours, this Darwinian competition between subclones is also influenced by topological factors. Recent advances have made it possible to study cancers at the single cell level. These methods represent important tools to dissect cancer evolution and provide the potential to considerably change both cancer research and clinical practice. Here we discuss state-of-the-art methods for the isolation of a single cell, whole-genome and whole-transcriptome amplification of the cell's nucleic acids, as well as microarray and massively parallel sequencing analysis of such amplification products. We discuss the strengths and the limitations of the techniques, and explore single-cell methodologies for future cancer research, as well as diagnosis and treatment of the disease. PMID:24531336

Van Loo, Peter; Voet, Thierry

2014-02-01

135

Socioeconomic differences in lung cancer incidence: a systematic review and meta-analysis  

Microsoft Academic Search

Objective  To investigate the associations between various socioeconomic indicators and lung cancer incidence.\\u000a \\u000a \\u000a \\u000a Methods  We searched PubMed and EMBASE databases for studies on socioeconomic position (SEP) and lung cancer incidence published through\\u000a October 2007. Random-effect model was used to pool the risk estimates from the individual studies. We stratified the analysis\\u000a by adjustment strategy to investigate the influence of smoking on socioeconomic

Anna Sidorchuk; Emilie E. Agardh; Olatunde Aremu; Johan Hallqvist; Peter Allebeck; Tahereh Moradi

2009-01-01

136

New genetic risk variants identified in multiethnic analysis of prostate cancer  

Cancer.gov

Researchers have newly identified 23 common genetic variants—one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs—that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNPs in data pooled from studies that included over 43,000 men with prostate cancer and nearly 44,000 men without the disease. Study participants were from Australia, Ghana, Japan, the United Kingdom, and the United States and were of diverse ancestry.

137

New genetic risk variants identified in multiethnic analysis of prostate cancer  

Cancer.gov

Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNPs in data pooled from studies that included over 43,000 men with prostate cancer and nearly 44,000 men without the disease. Study participants were from Australia, Ghana, Japan, the United Kingdom, and the United States and were of diverse ancestry.

138

Analysis of participatory photojournalism in a widely disseminated skin cancer prevention program.  

PubMed

This article describes the content of pictures submitted to a photo contest as part of a nationally disseminated skin cancer prevention program called Pool Cool. The aims of this analysis are to describe sun-safety behaviors and environmental supports depicted in the photos and to gain insight into pool staff perceptions of the program. A directed approach was used to assess the content of 1,886 photos submitted in 2005 and 2006. Staying in the shade and applying sunscreen were the most common sun-safety behaviors shown among children. Among adults and lifeguards, wearing sunglasses and a shirt with sleeves were most common. Most photos contained at least one sun-safety support, and half showed use of Pool Cool program materials. Most photos promoted the use of Pool Cool materials, sun-safety behaviors, or sun-safe pool environments. Participatory photojournalism is a low-cost and effective way to generate widespread interest and support for community health promotion programs. PMID:20421408

Hall, Dawn; Kline, Melissa; Glanz, Karen

2011-09-01

139

Experimental analysis of bubble growth, departure and interactions during pool boiling on artificial nucleation sites  

SciTech Connect

The present work describes experimental results of pentane pool boiling, simplified to the cases of boiling on a single or on two adjacent nucleation sites. Bubbles growths have been recorded by a high speed camera under various wall superheat conditions. Bubble volume has been plotted as a function of time, and an experimental growth law has been proposed. Oscillations were observed during growth, showing the interaction of one bubble with the preceding bubble released from the same nucleation site. Lateral coalescence has been visualized and the images have brought to the fore the capillary effects on the distortion of the interface. (author)

Siedel, S.; Cioulachtjian, S.; Bonjour, J. [CETHIL - UMR5008 CNRS INSA-Lyon Univ. Lyon1, Bat. Sadi Carnot, 9 rue de la Physique, INSA-Lyon, F-69621 Villeurbanne Cedex (France)

2008-09-15

140

Association between DAPK1 Promoter Methylation and Cervical Cancer: A Meta-Analysis  

PubMed Central

Background Death-associated protein kinase1 (DAPK1) is an important tumor suppressor gene. DNA methylation can inactivate genes, which has often been observed in the carcinogenesis of cervical cancer. During the past several decades, many studies have explored the association between DAPK1 promoter methylation and cervical cancer. However, many studies were limited by the small samples size and the findings were inconsistent among them. Thus, we conducted a meta-analysis to assess the association between DAPK1 promoter methylation and cervical cancer. Methods We systematically searched eligible studies in the PubMed, Web of Science, EMBASE and CNKI databases. Using meta-regression, subgroup analysis and sensitivity analysis, we explored the potential sources of heterogeneity. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated by Meta-Analysis in R. Results A total of 15 studies from 2001 to 2012, comprising 818 tumor tissues samples and 671 normal tissues samples, were analyzed in this meta-analysis. The frequencies of DAPK1 promoter methylation ranged from 30.0% to 78.6% (median, 59.3%) in cervical cancer tissue and 0.0% to 46.7% (median, 7.8%) in normal cervical tissue. The pooled OR was 19.66 (95%CI?=?8.72–44.31) with the random effects model, and heterogeneity was found through the sensitivity analysis. The I2?=?60% (P?=?0.002) decreased to I2?=?29.2% (P?=?0.144) when one heterogeneous study was excluded, and the pooled OR increased to 21.80 (95%CI?=?13.44–35.36) with the fixed effects model. Conclusion The results suggested a strong association between DAPK1 promoter methylation and cervical cancer. This study also indicated that DAPK1 promoter methylation may be a biomarker during cervical carcinogenesis that might serve as an early indication of cervical cancer. PMID:25268905

Xiong, Jiaqiang; Li, Ya; Huang, Kecheng; Lu, Meixia; Shi, Hao; Ma, Lanfang; Luo, Aiyue; Yang, Shuhong; Lu, Zhiyong; Zhang, Jinjin; Yang, Lilan; Wang, Shixuan

2014-01-01

141

Lung cancer risk and solid fuel smoke exposure: a systematic review and meta-analysis.  

PubMed

The aim of this systematic review was to quantify the impact of biomass fuel and coal use on lung cancer and to explore reasons for heterogeneity in the reported effect sizes. A systematic review of primary studies reporting the relationship between solid fuel use and lung cancer was carried out, based on pre-defined criteria. Studies that dealt with confounding factors were used in the meta-analysis. Fuel types, smoking, country, cancer cell type and sex were considered in sub-group analyses. Publication bias and heterogeneity were estimated. The pooled effect estimate for coal smoke as a lung carcinogen (OR 1.82, 95% CI 1.60-2.06) was greater than that from biomass smoke (OR 1.50, 95% CI 1.17-1.94). The risk of lung cancer from solid fuel use was greater in females (OR 1.81, 95% CI 1.54-2.12) compared to males (OR 1.16, 95% CI 0.79-1.69). The pooled effect estimates were 2.33 (95% CI 1.72-3.17) for adenocarcinoma, 3.58 (1.58-8.12) for squamous cell carcinoma and 1.57 (1.38-1.80) for tumours of unspecified cell type. These findings suggest that in-home burning of both coal and biomass is consistently associated with an increased risk of lung cancer. PMID:22653775

Kurmi, Om Prakash; Arya, Pallavi Huma; Lam, Kin-Bong Hubert; Sorahan, Tom; Ayres, Jon G

2012-11-01

142

Genetic polymorphisms in Glutathione S-transferase Omega (GSTO) and cancer risk: a meta-analysis of 20 studies.  

PubMed

Glutathione S-transferase Omega (GSTO) plays an important role in the development of cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms on GSTO and susceptibility to cancer; however, the results remain inconclusive. We performed a meta-analysis of 20 studies, involving 4770 cases and 5701 controls to identify the strength of association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall, the pooled results revealed a significantly increased risk of susceptibility for GSTO2 polymorphism (GG vs. AA: OR = 1.20, 95%CI: 1.02-1.41, Pheterogeneity = 0.116), but no significant association was found for GSTO1 polymorphism. Subgroup analysis showed that GSTO2 polymorphism significantly increased cancer risk in Caucasian population (GG vs. AA: OR = 1.32, 95%CI 1.06-1.64, Pheterogeneity = 0.616) and GSTO2 polymorphism was significantly associated with elevated risk of breast cancer (GG vs. AA OR = 1.37, 95%CI: 1.06-1.77; Pheterogeneity = 0.281). This meta-analysis demonstrates that GSTO2 polymorphism may significantly increase cancer risk in Caucasian population and is associated with elevated risk of breast cancer; while GSTO1 polymorphism is not associated with cancer risk. PMID:25300926

Xu, You-Tao; Wang, Jun; Yin, Rong; Qiu, Man-Tang; Xu, Lei; Wang, Jie; Xu, Lin

2014-01-01

143

Genetic polymorphisms in Glutathione S-transferase Omega (GSTO) and cancer risk: a meta-analysis of 20 studies  

PubMed Central

Glutathione S-transferase Omega (GSTO) plays an important role in the development of cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms on GSTO and susceptibility to cancer; however, the results remain inconclusive. We performed a meta-analysis of 20 studies, involving 4770 cases and 5701 controls to identify the strength of association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall, the pooled results revealed a significantly increased risk of susceptibility for GSTO2 polymorphism (GG vs. AA: OR = 1.20, 95%CI: 1.02–1.41, Pheterogeneity = 0.116), but no significant association was found for GSTO1 polymorphism. Subgroup analysis showed that GSTO2 polymorphism significantly increased cancer risk in Caucasian population (GG vs. AA: OR = 1.32, 95%CI 1.06–1.64, Pheterogeneity = 0.616) and GSTO2 polymorphism was significantly associated with elevated risk of breast cancer (GG vs. AA OR = 1.37, 95%CI: 1.06–1.77; Pheterogeneity = 0.281). This meta-analysis demonstrates that GSTO2 polymorphism may significantly increase cancer risk in Caucasian population and is associated with elevated risk of breast cancer; while GSTO1 polymorphism is not associated with cancer risk. PMID:25300926

Xu, You-Tao; Wang, Jun; Yin, Rong; Qiu, Man-Tang; Xu, Lei; Wang, Jie; Xu, Lin

2014-01-01

144

Vitamin E Intake and Risk of Amyotrophic Lateral Sclerosis: A Pooled Analysis of Data From 5 Prospective Cohort Studies  

PubMed Central

The authors investigated whether vitamin E intake was associated with amyotrophic lateral sclerosis (ALS) in the Nurses’ Health Study (1976–2004), the Health Professionals Follow-up Study (1986–2004), the Cancer Prevention Study II Nutrition Cohort (1992–2004), the Multiethnic Cohort Study (1993–2005), and the National Institutes of Health-AARP Diet and Health Study (1995–2005). ALS deaths were identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal ALS cases were also included. Cohort-specific results were estimated using Cox proportional hazards models and pooled using random-effects models. Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend = 0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for ?1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2–4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for ?5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend = 0.002) but not in men (P-trend = 0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration. PMID:21335424

Wang, Hao; O'Reilly, Eilis J.; Weisskopf, Marc G.; Logroscino, Giancarlo; McCullough, Marjorie L.; Schatzkin, Arthur; Kolonel, Laurence N.; Ascherio, Alberto

2011-01-01

145

Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer.  

PubMed

Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitative RT-PCR on a cohort of colorectal cancer patients. From a pool of more than 6000 genes identified unambiguously in the analysis, we found 2124 genes that were selectively expressed in colon cancer tissue and 147 genes that were differentially expressed to a significant degree between normal and cancer cells. Differential expression of many genes was confirmed by RT-PCR on a cohort of patients. Despite the fact that deregulated genes were involved in many different cellular pathways, we found that genes expressed in the extracellular space were significantly over-represented in colorectal cancer. Strikingly, we identified a transcript from a chromosome X-linked member of the human endogenous retrovirus (HERV) H family that was frequently and selectively expressed in colon cancer but not in normal tissues. Our data suggest that this sequence should be considered as a target of immunological interventions against colorectal cancer. PMID:18581998

Alves, Pedro M S; Lévy, Nicole; Stevenson, Brian J; Bouzourene, Hanifa; Theiler, Grégory; Bricard, Gabriel; Viatte, Sebastien; Ayyoub, Maha; Vuilleumier, Henri; Givel, Jean-Claude R; Rimoldi, Donata; Speiser, Daniel E; Jongeneel, C Victor; Romero, Pedro J; Lévy, Frédéric

2008-01-01

146

BAC-Pool Sequencing and Analysis of Large Segments of A12 and D12 Homoeologous Chromosomes in Upland Cotton  

PubMed Central

Although new and emerging next-generation sequencing (NGS) technologies have reduced sequencing costs significantly, much work remains to implement them for de novo sequencing of complex and highly repetitive genomes such as the tetraploid genome of Upland cotton (Gossypium hirsutum L.). Herein we report the results from implementing a novel, hybrid Sanger/454-based BAC-pool sequencing strategy using minimum tiling path (MTP) BACs from Ctg-3301 and Ctg-465, two large genomic segments in A12 and D12 homoeologous chromosomes (Ctg). To enable generation of longer contig sequences in assembly, we implemented a hybrid assembly method to process ~35x data from 454 technology and 2.8-3x data from Sanger method. Hybrid assemblies offered higher sequence coverage and better sequence assemblies. Homology studies revealed the presence of retrotransposon regions like Copia and Gypsy elements in these contigs and also helped in identifying new genomic SSRs. Unigenes were anchored to the sequences in Ctg-3301 and Ctg-465 to support the physical map. Gene density, gene structure and protein sequence information derived from protein prediction programs were used to obtain the functional annotation of these genes. Comparative analysis of both contigs with Arabidopsis genome exhibited synteny and microcollinearity with a conserved gene order in both genomes. This study provides insight about use of MTP-based BAC-pool sequencing approach for sequencing complex polyploid genomes with limited constraints in generating better sequence assemblies to build reference scaffold sequences. Combining the utilities of MTP-based BAC-pool sequencing with current longer and short read NGS technologies in multiplexed format would provide a new direction to cost-effectively and precisely sequence complex plant genomes. PMID:24116150

Buyyarapu, Ramesh; Kantety, Ramesh V.; Yu, John Z.; Xu, Zhanyou; Kohel, Russell J.; Percy, Richard G.; Macmil, Simone; Wiley, Graham B.; Roe, Bruce A.; Sharma, Govind C.

2013-01-01

147

DNA pooling: a comprehensive, multi-stage association analysis of ACSL6 and SIRT5 polymorphisms in schizophrenia.  

PubMed

Many candidate gene association studies have evaluated incomplete, unrepresentative sets of single nucleotide polymorphisms (SNPs), producing non-significant results that are difficult to interpret. Using a rapid, efficient strategy designed to investigate all common SNPs, we tested associations between schizophrenia and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5). We initially evaluated the utility of DNA sequencing traces to estimate SNP allele frequencies in pooled DNA samples. The mean variances for the DNA sequencing estimates were acceptable and were comparable to other published methods (mean variance: 0.0008, range 0-0.0119). Using pooled DNA samples from cases with schizophrenia/schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders edition IV criteria) and controls (n=200, each group), we next sequenced all exons, introns and flanking upstream/downstream sequences for ACSL6 and SIRT5. Among 69 identified SNPs, case-control allele frequency comparisons revealed nine suggestive associations (P<0.2). Each of these SNPs was next genotyped in the individual samples composing the pools. A suggestive association with rs 11743803 at ACSL6 remained (allele-wise P=0.02), with diminished evidence in an extended sample (448 cases, 554 controls, P=0.062). In conclusion, we propose a multi-stage method for comprehensive, rapid, efficient and economical genetic association analysis that enables simultaneous SNP detection and allele frequency estimation in large samples. This strategy may be particularly useful for research groups lacking access to high throughput genotyping facilities. Our analyses did not yield convincing evidence for associations of schizophrenia with ACSL6 or SIRT5. PMID:16827919

Chowdari, K V; Northup, A; Pless, L; Wood, J; Joo, Y H; Mirnics, K; Lewis, D A; Levitt, P R; Bacanu, S-A; Nimgaonkar, V L

2007-04-01

148

Stability analysis of NbTi-Ta-based high field conductor cooled by pool boiling below 4 K  

SciTech Connect

Stability analysis has been performed for cabled NbTi-Ta-based superconductors intended for the high field (12 T) toroidal field coils for a large scale tokamak device such as ETF. Ternary NbTi-Ta was selected as the superconductor because of its superior critical current density at high field as compared to the binary alloy NbTi. The operating temperature was chosen to be 2.5 K or below to optimize the performance of the superconductor. A cabled conductor was selected to minimize the pulsed field losses. The conductor is cooled by pool boiling in a subcooled (approx. 2.5 K, 0.25 atm) bath, or in a superfluid helium (He-II) bath (approx. 1.8 K, 0.02 atm). The analysis was based on numerically simulating the evolution of a normal zone in the conductor. Appropriate superconductor properties and heat transfer characteristics were utilized in the simulation.

Chen, W.Y.; Alcorn, J.S.; Hsu, Y.H.; Purcell, J.R.

1980-09-01

149

Analysis of an open-air swimming pool solar heating system by using an experimentally validated TRNSYS model  

SciTech Connect

In the case of private outdoor swimming pools, seldom larger than 100 m{sup 2}, conventional auxiliary heating systems are being installed less and less. Solar heating is an option to extend the swimming season. The temperature evolution of an open-air swimming pool highly depends on the wind speed directly on the water surface, which at the same time is influenced by the surroundings of the pool. In this paper, the TRNSYS model of a private open-air pool with a 50-m{sup 2} surface was validated by registering the water temperature evolution and the meteorological data at the pool site. Evaporation is the main component of energy loss in swimming pools. Six different sets of constants found in literature were considered to evaluate the evaporative heat transfer coefficient with the purpose of finding the most suitable one for the TRNSYS pool model. In order to do that, the evolution of the pool water temperature predicted by the TRNSYS pool model was compared with the experimentally registered one. The simulation with TRNSYS of the total system, including the swimming pool and the absorber circuit integrated into the existing filter circuit, provided information regarding the increase of the pool temperature for different collector areas during the swimming season. This knowledge, together with the economic costs, support the decision about the absorber field size. (author)

Ruiz, Elisa; Martinez, Pedro J. [Universidad Miguel Hernandez - Edificio Torreblanca, Avda. de la Universidad s/n, 03202 Elche (Spain)

2010-01-15

150

Analysis of IL-1? Release from Cryopreserved Pooled Lymphocytes in Response to Lipopolysaccharide and Lipoteichoic Acid  

PubMed Central

Pyrogens are heterogeneous group of fever-inducing substances derived from Gram-positive and Gram-negative bacteria, fungi, and viruses. They incite immune response by producing endogenous pyrogens such as prostaglandins and other proinflammatory cytokines like IL-1?, IL-6, and TNF-?. The present study was to analyze the influence of cryopreservation in IL-1? release, a marker for inflammatory response from human lymphocytes, in response to exogenous pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and 60 days and were challenged with LPS and LTA in vitro. The inflammatory cytokine, IL-1? release, was measured by ELISA method. It was observed that the release of IL-1? increases instantaneously after the initiation of incubation and reaches a maximum at 3 to 5 hours and then gradually decreases and gets stabilized for both pyrogens. Moreover it was also observed that the effect of cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for short-term storage, but DMSO-preserved lymphocytes yielded a better viability for long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a promising approach for the total replacement/alteration to animal experimentation for pyrogenicity evaluation. PMID:24024208

Nair, Sreelekshmi R.; Geetha, C. S.; Mohanan, P. V.

2013-01-01

151

Pooled Analysis of Rofecoxib Placebo-Controlled Clinical Trial Data: Lessons for Post-Market Pharmaceutical Safety Surveillance  

PubMed Central

Background In September 2004, rofecoxib was voluntarily withdrawn from the worldwide market. Our objective was to determine whether and when analysis of published and unpublished placebo-controlled trials could have revealed cardiovascular risk associated with rofecoxib before its withdrawal as an example to inform future post-market pharmaceutical safety surveillance efforts. Methods We conducted a cumulative subject-level pooled analysis of data from all randomized, placebo-controlled trials of rofecoxib conducted by the manufacturer before September 2004. Our main outcome measurement was incidence of any investigator-reported death from any cause or cardiovascular thromboembolic (CVT) adverse event. Results We identified 30 randomized, placebo-controlled trials of rofecoxib that enrolled 20,152 subjects. Trial duration ranged from 4 weeks to 4 years, enrollment ranged from 17 to 2586 subjects prescribed either rofecoxib or placebo, and rofecoxib dosage ranged from 12.5 mg to 50 mg. As of December 2000, 21 (70%) of these trials had been completed and the risk of CVT adverse event or death was greater among subjects assigned to rofecoxib, with the difference being borderline statistically significant (Rate Ratio [RR]=2.18, 95% Confidence Interval [CI], 0.93–5.81; p=0.07). Subsequently collected data strengthened the statistical association (as of June 2001: RR=1.35, 95% CI, 1.00–1.96; p=0.05; as of April 2002: RR=1.39, 95% CI, 1.07–1.80; p=0.02). Conclusion Cumulative pooled analysis of all randomized, placebo-controlled trials demonstrates a progressing trend toward increased cardiovascular risk associated with rofecoxib compared with placebo as early as December 2000, reaching a P value of 0.05 by June 2001, nearly 3 and a half years before the manufacturer’s voluntary market withdrawal. PMID:19933959

Ross, Joseph S.; Madigan, David; Hill, Kevin P.; Egilman, David S.; Wang, Yongfei; Krumholz, Harlan M.

2010-01-01

152

Exhaled breath analysis for lung cancer  

PubMed Central

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

Sutedja, Tom G.; Zimmerman, Paul V.

2013-01-01

153

Confirmatory factor analysis of the M5-50: an implementation of the International Personality Item Pool item set.  

PubMed

Goldberg's International Personality Item Pool (IPIP; Goldberg, 1999) provides researchers with public-domain, free-access personality measurement scales that are proxies of well-established published scales. One of the more commonly used IPIP sets employs 50 items to measure the 5 broad domains of the 5-factor model, with 10 items per factor. The M5-50 (McCord, 2002) is a specific ordering and presentation of this 50-item set. Using data from a sample of 760 faculty, staff, and students at a midsized university, the authors assessed the reliability and construct validity of the M5-50. Cronbach's alphas on the 5 scales ranged from acceptable to excellent. Confirmatory factor analysis indicated reasonably good model fit. Researchers who wish to measure personality would be well advised to consider using the M5-50. PMID:20230150

Socha, Alan; Cooper, Christopher A; McCord, David M

2010-03-01

154

Coffee consumption and risk of prostate cancer: a meta-analysis of prospective cohort studies.  

PubMed

Observational studies and animal evidence suggest an association between coffee consumption and the risk of prostate cancer. However, the results are inconsistent. We evaluated the association by conducting a meta-analysis of prospective cohort studies. PubMed and Embase were searched through June 2013 to identify studies that met predetermined inclusion criterion. A random-effects model was used to calculate the pooled risk estimates. Ten prospective cohort studies involving 8973 patients with prostate cancer and 206 096 participants were included in this systematic review. Compared with individuals who seldom or never drink coffee, the pooled relative risk of prostate cancer was 0.88 (95% confidence interval: 0.82-0.95) for regular coffee drinkers. Exclusion of any single study did not materially alter the combined risk estimate. Visual inspection of a funnel plot and Begg's and Egger's tests did not indicate evidence of publication bias. In summary, integrated evidence from prospective cohort studies supports the hypothesis that coffee consumption may decrease the risk of prostate cancer. PMID:24343360

Cao, Shiyi; Liu, Ling; Yin, Xiaoxu; Wang, Yunxia; Liu, Junan; Lu, Zuxun

2014-02-01

155

A new method for Fourier analysis in ECG-gated cardiac blood pool emission computed tomography (ECT)  

SciTech Connect

An integrated technique for Fourier analysis in multigated blood pool ECT study has been developed. Following the administration of 15-20 mCi of Tc-99m RBC, ECG-gated cardiac blood pool data were acquired using an ECT system with dual opposed gamma cameras. Fundamental studies for data acquisition showed that acquisition time of 10 sec. for each projection, 14 divisions of one cardiac cycle and angular interval of 6/sup 0/ (60 projections over 360/sup 0/) were reasonable for clinical purpose. Total acquisition time was about 5 minutes under these conditions. Data were processed as follows: 1) Transaxial (TA) tomographic images in every phase of cardiac cycle were reconstructed by convolution algorithm; 2) TA images were rotated to construct sagittal (SAG) and short axial (S-A) oblique-angle tomography which are respectively parallel and perpendicular to the long axis of either of the ventricles; 3) Images covering the portion other than the purposed ventricle were eliminated from the series of SAG images in every phase of the cycle; 4) Images in the same phase were summed to construct a series of SAG and S-A planar images; and 5) Fourier analysis was made to construct phase and amplitude images. The advantages of this method are that the phase and amplitude images from arbitrary directions can be obtained, that the region of interest can be selected on a three dimensional basis, eliminating the overlapping activity of the other ventricle or neighbouring tissues, that the diseased areas can be easily and accurately localized even in small inferior wall myocardial infarction and that patient study can be finished within 5 minutes.

Ito, T.; Maeda, H.; Takeda, K.; Nakagawa, T.; Yamaguchi, N.; Konishi, T.; Ichikawa, T.

1984-01-01

156

Breast Cancer Risk in Rheumatoid Arthritis: An Update Meta-Analysis  

PubMed Central

Background. The incidence of breast cancer in RA patients remains controversial. Thus we performed a meta-analysis to investigate the impact of RA on breast cancer. Methods. Published literature was available from PubMed, Embase, and Cochrane Library. Pooled standardized incidence rate (SIR) was computed by random-effect model analysis. Results. We identified 16 separate studies in the present study, in which the number of patients ranged from 458 to 84,475. We did not find the increased cancer risk in RA patients (SIR = 0.86, 95% CI = 0.72–1.02). However, subgroup analysis showed that breast cancer risk in RA patients was positively different in Caucasians (SIR = 0.82, 95% CI = 0.73–0.93) and non-Caucasians (SIR = 1.21, 95% CI = 1.19–1.23), respectively. In subgroup analysis by style, a reduced incidence was found in hospital-based case subjects (SIR = 0.82, 95% CI = 0.69–0.97). Similarly, subgroup analysis for adjusted factors indicated that in A3 (age and sex) and A4 (age, sex, and race/ethnicity) the risk was decreased (SIR = 0.87, 95% CI = 0.76–0.99; SIR = 0.63, 95% CI = 0.59–0.67). Conclusions. The meta-analysis revealed no increased breast cancer risk in RA patients. However, in the subgroup analysis, the risk of breast cancer is increased in non-Caucasians patients with RA while it decreased in Caucasian population, hospital-based case subjects, and A3 group. Such relationship may provide preference for risk of breast cancer in different population.

Liang, Jia-Ning; Wang, Zhuo-Yun

2014-01-01

157

Independent review of design and analysis for Holtec spent fuel storage racks of CPP 666 Pool 1  

SciTech Connect

This document summarizes the analyses and review performed to develop and validate the design of the new fuel storage racks for the Idaho Chemical Processing Plant (ICPP) Fuel Storage Area (FSA). Holtec International is responsible for the design and fabrication of the storage racks. This report describes the issues raised in the review effort and the resolutions to these issues. The conclusion is reached that the review issues for the racks of Pool 1 have been satisfactorily resolved in the final design and analysis for these racks. Section 1 of this report gives a brief description of the project. Section 2 describes the approach that Holtec used in analyzing the racks and results from these analyses. Section 3 describes the independent review process. Section 4 discusses the identification of and resolution to comments on the design analysis. Section 5 describes additional analysis performed to address major concerns with the Holtec design analysis. Section 6 presents a summary of AEC`s independent review, which is based on AEC`s final review report. Finally, Section 7 gives the Lockheed Idaho Technologies Company (LITCO) position on the acceptability of Holtec`s design.

Miller, G.K.

1996-03-01

158

Alert but less alarmed: a pooled analysis of terrorism threat perception in Australia  

PubMed Central

Background Previous Australian research has highlighted disparities in community perceptions of the threat posed by terrorism. A study with a large sample size is needed to examine reported concerns and anticipated responses of community sub-groups and to determine their consistency with existing Australian and international findings. Methods Representative samples of New South Wales (NSW) adults completed terrorism perception questions as part of computer assisted telephone interviews (CATI) in 2007 (N = 2081) and 2010 (N = 2038). Responses were weighted against the NSW population. Data sets from the two surveys were pooled and multivariate multilevel analyses conducted to identify health and socio-demographic factors associated with higher perceived risk of terrorism and evacuation response intentions, and to examine changes over time. Results In comparison with 2007, Australians in 2010 were significantly more likely to believe that a terrorist attack would occur in Australia (Adjusted Odd Ratios (AOR) = 1.24, 95%CI:1.06-1.45) but felt less concerned that they would be directly affected by such an incident (AOR = 0.65, 95%CI:0.55-0.75). Higher perceived risk of terrorism and related changes in living were associated with middle age, female gender, lower education and higher reported psychological distress. Australians of migrant background reported significantly lower likelihood of terrorism (AOR = 0.52, 95%CI:0.39-0.70) but significantly higher concern that they would be personally affected by such an incident (AOR = 1.57, 95%CI:1.21-2.04) and having made changes in the way they live due to this threat (AOR = 2.47, 95%CI:1.88-3.25). Willingness to evacuate homes and public places in response to potential incidents increased significantly between 2007 and 2010 (AOR = 1.53, 95%CI:1.33-1.76). Conclusion While an increased proportion of Australians believe that the national threat of terrorism remains high, concern about being personally affected has moderated and may reflect habituation to this threat. Key sub-groups remain disproportionately concerned, notably those with lower education and migrant groups. The dissonance observed in findings relating to Australians of migrant background appears to reflect wider socio-cultural concerns associated with this issue. Disparities in community concerns regarding terrorism-related threat require active policy consideration and specific initiatives to reduce the vulnerabilities of known risk groups, particularly in the aftermath of future incidents. PMID:21992446

2011-01-01

159

Microarray analysis in gastric cancer: A review  

PubMed Central

Gastric cancer is one of the most common tumors worldwide. Although several treatment options have been developed, the mortality rate is increasing. Lymph node involvement is considered the most reliable prognostic indicator in gastric cancer. Early diagnosis improves the survival rate of patients and increases the likelihood of successful treatment. The most reliable diagnostic method is endoscopic examination, however, it is expensive and not feasible in poorer countries. Therefore, many innovative techniques have been studied to develop a new non-invasive screening test and to identify specific serum biomarkers. DNA microarray analysis is one of the new technologies able to measure the expression levels of a large number of genes simultaneously. It is possible to define the gene expression profile of the tumor and to correlate it with the prognosis and metastasis formation. Several studies in the literature have been published on the role of microarray analysis in gastric cancer and the mechanisms of proliferation and metastasis formation. The aim of this review is to analyze the importance of microarray analysis and its clinical applications to better define the genetic characteristics of gastric cancer and its possible implications in a more decisive treatment.

D'Angelo, Giovanna; Di Rienzo, Teresa; Ojetti, Veronica

2014-01-01

160

Prognostic Significance of Lymphovascular Invasion in Radical Cystectomy on Patients with Bladder Cancer: A Systematic Review and Meta-Analysis  

PubMed Central

Purpose The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI) in radical cystectomy specimens. Materials and Methods Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. Results A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26–2.06), cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38–2.01), and overall survival (pooled HR, 1.67; 95% CI, 1.38–2.01), despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. Conclusions This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer. PMID:24586637

Kim, Hwanik; Kim, Myong; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

2014-01-01

161

ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis  

PubMed Central

Background Many published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of this relationship. Methods A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. Results Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T) and XbaI (A>G) polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T) polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C), codon 325 (C>G), codon 594 (G>A) and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed. Conclusion Results from the current meta-analysis indicate that ESR1 PvuII (C>T) polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may increase the risk of prostate cancer among American population. PMID:23805288

Wang, Yu-Mei; Liu, Zu-Wang; Guo, Jing-Bo; Wang, Xiao-Fang; Zhao, Xin-Xin; Zheng, Xuan

2013-01-01

162

Proteomic Analysis in Cancer Patients  

Microsoft Academic Search

\\u000a The term proteome means the total protein complement of a genome, and proteomics means the analysis for proteome. The combination of two-dimensional\\u000a gel electrophoresis (2-DE) and mass spectrometry (MS) is a proteomic method of high-throughput analysis of protein expression.\\u000a By using this 2-DE and MS, proteomic studies have identified many proteins that may be involved in the pathogenic mechanism\\u000a of

Yasuhiro Kuramitsu; Kazuyuki Nakamura

163

The Prognostic Value of Global DNA Hypomethylation in Cancer: A Meta-Analysis  

PubMed Central

Background Aberrant methylation of the global genome has been investigated as a prognostic indicator in various cancers, but the results are controversial and ambiguous. Methods and Findings This meta-analysis presents pooled estimates of the evidence to elucidate this issue. We searched the electronic databases: PubMed, Embase, ISI Web of Science and the Cochrane library (up to August 2013) to identify all of the relevant studies. The association between the level of surrogates' indexes of genome-wide hypomethylation (LINE-1, Alu and Sat–?) and the overall survival (OS) of cancer patients was examined. In addition, the pooled hazard ratios (HRs) with their 95% confidence interval (95%CI) were calculated to estimate the influences through fixed-effects and random-effects model. Finally, twenty studies with total population of 5447 met the inclusion criteria. The results indicate that the summary HRs for the studies employing LINE-1, Alu, and Sat-? repetitive elements also show that the global DNA hypomethylation have significant desirable effects on the tumour prognostic value. The pooled HRs (and CIs) of LINE-1, Alu and Sat-? were 1.83 (1.38–2.44), 2.00 (1.16–3.45), and 2.92 (1.04–8.25), with a heterogeneity measure index of I2 (and p-value) shows of 66.6% (p?=?0.001), 57.1% (p?=?0.053) and 68.2% (p?=?0.076) respectively. The meta-regression and subgroup analysis indicated that the percentage of hypomethylated sample of cancer patients is one source of heterogeneity. Conclusion Our meta-analysis findings support the hypothesis that the global DNA hypomethylation is associated with a detrimental prognosis in tumour patients. PMID:25184628

Zeng, Fangfang; Li, Wenxue; He, Zhini; Chen, Wen; Zhu, Wei; Zhang, Bo

2014-01-01

164

A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer.  

PubMed

This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work. PMID:23975662

Wang, F; Yeung, K L; Chan, W C; Kwok, C C H; Leung, S L; Wu, C; Chan, E Y Y; Yu, I T S; Yang, X R; Tse, L A

2013-11-01

165

Analysis of Senate Bill 961: Cancer Treatment  

E-print Network

endometrial cancer, uterine sarcoma Treatment Role Preoperative and postoperative treatment of postmenopausal women with early stage or locally advanced estrogen-endometrial cancer, ovarian cancer, uterine sarcoma Treatment Role Preoperative and postoperative treatment of postmenopausal women with early stage or locally advanced estrogen-endometrial cancer, ovarian cancer, uterine cancer, and prostate cancer. Tamoxifen, a medication that prevents tumors from using estrogen,

California Health Benefits Review Program (CHBRP)

2010-01-01

166

Stakeholder Analysis and Social-Biophysical Interdependencies for Common Pool Resource Management: La Brava Wetland (Argentina) as a Case Study  

NASA Astrophysics Data System (ADS)

This article gives an account of the implementation of a stakeholder analysis framework at La Brava Wetland Basin, Argentina, in a common-pool resource (CPR) management context. Firstly, the context in which the stakeholder framework was implemented is described. Secondly, a four-step methodology is applied: (1) stakeholder identification, (2) stakeholder differentiation-categorization, (3) investigation of stakeholders' relationships, and (4) analysis of social-biophysical interdependencies. This methodology classifies stakeholders according to their level of influence on the system and their potential in the conservation of natural resources. The main influential stakeholders are La Brava Village residents and tourism-related entrepreneurs who are empowered to make the more important decisions within the planning process of the ecosystem. While these key players are seen as facilitators of change, there are other groups (residents of the inner basin and fishermen) which are seen mainly as key blockers. The applied methodology for the Stakeholder Analysis and the evaluation of social-biophysical interdependencies carried out in this article can be seen as an encouraging example for other experts in natural sciences to learn and use these methods developed in social sciences. Major difficulties and some recommendations of applying this method in the practice by non-experts are discussed.

Romanelli, Asunción; Massone, Héctor E.; Escalante, Alicia H.

2011-09-01

167

Stakeholder analysis and social-biophysical interdependencies for common pool resource management: La Brava Wetland (Argentina) as a case study.  

PubMed

This article gives an account of the implementation of a stakeholder analysis framework at La Brava Wetland Basin, Argentina, in a common-pool resource (CPR) management context. Firstly, the context in which the stakeholder framework was implemented is described. Secondly, a four-step methodology is applied: (1) stakeholder identification, (2) stakeholder differentiation-categorization, (3) investigation of stakeholders' relationships, and (4) analysis of social-biophysical interdependencies. This methodology classifies stakeholders according to their level of influence on the system and their potential in the conservation of natural resources. The main influential stakeholders are La Brava Village residents and tourism-related entrepreneurs who are empowered to make the more important decisions within the planning process of the ecosystem. While these key players are seen as facilitators of change, there are other groups (residents of the inner basin and fishermen) which are seen mainly as key blockers. The applied methodology for the Stakeholder Analysis and the evaluation of social-biophysical interdependencies carried out in this article can be seen as an encouraging example for other experts in natural sciences to learn and use these methods developed in social sciences. Major difficulties and some recommendations of applying this method in the practice by non-experts are discussed. PMID:21667179

Romanelli, Asunción; Massone, Héctor E; Escalante, Alicia H

2011-09-01

168

Statin use and risk of liver cancer: an update meta-analysis  

PubMed Central

Objective Statins are commonly prescribed cholesterol-lowering drugs. Preclinical studies suggest that statins may possess cancer preventive properties. The primary objective of this meta-analysis was to determine the association between statin use and risk of liver cancer. Design Meta-analysis. Setting International. Participants A comprehensive literature search of PubMed, BIOSIS Previews, Web of Science, EMBASE, EBSCO and Cochrane Library was conducted through March 2014. The effect estimate was reported as pooled relative risk (RR) with 95% CIs, using the random-effects model. Results A total of 12 studies (1 individual patient data analysis of 22 randomised controlled trials, 5 cohorts and 6 case–controls) were qualified for this meta-analysis, involving 5?640?313 participants including 35?756 liver cancer cases. Our results indicated a significant risk reduction of liver cancer among all statin users (RR=0.58, 95% CIs 0.51 to 0.67). The difference of the study designs can partly explain the significant heterogeneity found in the overall analysis (I2=65%, p=0.0006). No evidence of publication bias was observed in this meta-analysis. Similar risk reductions were found in the subgroups analysis of Western and Asian countries, lipophilic and hydrophilia statins. There was a trend towards more risk reductions in subgroups with higher baseline risk, inadequate adjustment and higher cumulative dosage of statin use. Conclusions This meta-analysis suggests that statin is associated with a significant risk reduction of liver cancer when taken daily for cardiovascular event prevention. However, this preventive effect might be overestimated due to the exposure period, the indication and contraindication of statins and other confounders. Statins might be considered as an adjuvant in the treatment of liver cancer. PMID:25227628

Shi, Meng; Zheng, Huiling; Nie, Biao; Gong, Wei; Cui, Xiaobing

2014-01-01

169

MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project.  

PubMed

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects. PMID:24917043

Pasquali, Elena; García-Borrón, José C; Fargnoli, Maria Concetta; Gandini, Sara; Maisonneuve, Patrick; Bagnardi, Vincenzo; Specchia, Claudia; Liu, Fan; Kayser, Manfred; Nijsten, Tamar; Nagore, Eduardo; Kumar, Rajiv; Hansson, Johan; Kanetsky, Peter A; Ghiorzo, Paola; Debniak, Tadeusz; Branicki, Wojciech; Gruis, Nelleke A; Han, Jiali; Dwyer, Terry; Blizzard, Leigh; Landi, Maria Teresa; Palmieri, Giuseppe; Ribas, Gloria; Stratigos, Alexander; Council, M Laurin; Autier, Philippe; Little, Julian; Newton-Bishop, Julia; Sera, Francesco; Raimondi, Sara

2015-02-15

170

RDA Analysis of Breast Cancer  

Cancer.gov

Dr. Michael Wigler, of Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, has been examining genetic changes in breast tumor tissue from patients on Long Island using a technique called representational difference analysis (RDA). In this pilot study, he demonstrated that the technique permits cloning of DNA probes that mark the presence of genetic lesions in tumors.

171

SNP genotyping on pooled DNAs: comparison of genotyping technologies and a semi automated method for data storage and analysis  

Microsoft Academic Search

We have compared the accuracy, efficiency and robustness of three methods of genotyping single nucleotide polymorphisms on pooled DNAs. We conclude that (i) the frequencies of the two alleles in pools should be corrected with a factor for unequal allelic amplification, which should be estimated from the mean ratio of a set of heterozygotes (k); (ii) the repeatability of an

Stephanie Le Hellard; Stephane J. Ballereau; Peter M. Visscher; Helen S. Torrance; Jeni Pinson; Stewart W. Morris; Marian L. Thomson; Colin A. M. Semple; Walter J. Muir; Douglas H. R. Blackwood; David J. Porteous; Kathryn L. Evans

2002-01-01

172

Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis  

PubMed Central

Background The morbidity and mortality of cancer increase remarkably every year. It's a heavy burden for family and society. The detection of prognostic biomarkers can help to improve the theraputic effect and prolong the lifetime of patients. microRNAs have an influential role in cancer prognosis. The results of articles discussing the relationship between microRNA polymorphisms and cancer prognosis are inconsistent. Methods We conduct a meta-analysis of 19 publications concerning the association of four common polymorphisms, mir-146a rs2910164, mir-149 rs2292832, mir-196a2 rs11614913 and mir-499 rs3746444, with cancer prognosis. Pooled Hazard Ratios with 95% Confidence Intervals for the relationship between four genetic polymorphisms and Overall Survival, Recurrence-free Survival, Disease-free survival, recurrence are calculated. Subgroup analysis by population and type of tumor are conducted. Results GG genotype of mir-146a may be the protective factor for overall survival, especially in Caucasian population. C-containing genotypes of mir-196a2 act as a risk role for overall survival. The same result exists in Asian population, in Non-Small Cell Lung Cancer and digestive cancer. The patients with C allele of mir-149 have a better overall survival, especially in Non-Small Cell Lung Cancer. No significant results are obtained for mir-499 polymorphisms. Conclusions Genetic polymorphisms in mir-146a, mir-196a2 and mir-149 may be associated with overall survival. This effect varies with different types of cancer. Genetic polymorphism in mir-499 may have nothing to do with cancer prognosis. PMID:25337946

Xia, Lingzi; Ren, Yangwu; Fang, Xue; Yin, Zhihua; Li, Xuelian; Wu, Wei; Guan, Peng; Zhou, Baosen

2014-01-01

173

E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma  

PubMed Central

Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which is rare in west countries but has high incidence in Southern Asia especially South China. Although NPC is relatively sensitive to radiotherapy, the prognosis of patients is poor due to the advanced stage at the time of diagnosis. Therefore, it is important to understand the mechanisms involved in tumorigenesis and develop early diagnostic techniques. S-phase kinase associated protein 2 (Skp2) is overexpressed in several human cancers and associates with poor prognosis. However, its function in NPC has not been fully addressed. In this study we found Skp2 was highly expressed in NPC specimen and correlated with poor prognosis. We generated Skp2 knockdown cells to further delineate its role in NPC development. Knockdown of Skp2 partially reduced cell proliferation, promoted cellular senescence, and decreased the population of stem cell like aldehyde dehydrogenase1 positive cells as well as their self-renewal ability. Our study not only interprets the predictive role of Skp2 in the poor prognosis of NPC patients, but also reveals that Skp2 regulates the NPC cancer stem cell maintenance, which shed lights on the target therapy and early diagnosis of NPC in clinical application. PMID:25015320

Su, Hong-kai; Zhang, Wei; Yue, Cai-feng; Yan, Min; Guan, Su; Qiang Liu, Quentin

2014-01-01

174

Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations  

SciTech Connect

Berylliosis or Chronic Beryllium Disease is a chronic granulomatous disorder primarily involving the lung associated with the exposition to low doses of Beryllium (Be) in the workplace. Berylliosis risk has been associated with the presence of a glutamate at position 69 of the HLA-DP beta chain (HLA-DPbetaGlu69) that is expressed in about 97% of disease cases and in 27% of the unaffected Be-exposed controls (p<0.0001) (Richeldi et al. Science 1993; 262: 242-244.12). Since this first observation of an immunogenetic association between berylliosis and HLA-DPbetaGlu69 a number of studies have confirmed the role of this marker as the primary gene of susceptibility of berylliosis (Richeldi et al Am J Ind Med. 1997; 32:337-40; Wang et al J. Immunol. 1999; 163: 1647-53; Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94). Moreover, a structure/function interaction between HLA-DP molecules carrying Glu69 and beryllium in driving and developing the immune response against beryllium itself has been observed as: (1) Be-specific T-cells clones obtained from berylliosis patients recognize beryllium as antigen only when presented in the context of the HLA-DP{beta}Glu69 molecules but not in the context of HLA-DP allelic variants carrying Lys69 (Lombardi G et al. J Immunol 2001; 166: 3549-3555), and (2) beryllium presents an affinity for the HLA-DP2, carrying the berylliosis marker of susceptibility HLA-DPGlu69, from 40 to 100 times higher that the HLA-DP molecule carrying Lys69 (Amicosante M. et al Hum. Immunol. 2001; 62: 686-93). However, although the immunogenetic studies performed have been addressed a number of different questions about the genetic association between berylliosis and/or beryllium sensitization, exposure levels to beryllium and HLA markers, a number of questions are still open in the field mainly due to the limitation imposed by the low number of subjects carrying berylliosis or beryllium sensitization enrolled in each immunogenetic study. In this context, the populations of the study already performed in this field by the University of Modena and Rome (by Prof. C. Saltini) and the University of Pennsylvania (by Prof. M. Rossman) have been evaluated by using similar HLA molecular typing methodologies and that both populations have now been followed up for a period of 4 to 7 years. The general objective of this study has to generate a larger data base comprising the two population with which analyze gene disease association with greater statistical power and ascertain the effect of lesser common gener variants which may be missed when analyzing associations on small populations. In particular addressing the role suggested in previous study such as: (1) the role of HLA-DP rare alleles and polymorphisms, and (2) the role of the HLA markers in disease progression from sensitization. The two populations from the already published studies (Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94) present similar aspects about: ethnicity, type and length of exposure to Be dust, a broadly similar association between beryllium related abnormalities and HLA. The two population have been pooled and evaluated using common criteria of diagnosis (Sensitized subject: at least 2 positive BeLPT tests each with 2 positive wells; CBD-affected subject: identification of well formed non-caseating granulomas on biopsy), follow up and HLA typing technique (complete HLA-DRB, DQB, DPB high resolution typing using amplification with sequence specific primers or sequence based typing). The two populations included 137 subjects with Beryllium hypersensitized (BH) and 155 Be-exposed controls. Inclusion criteria were met by one hundred and six subjects with Be-hypersensitivity of whom 55 were affected by CBD (age 52 {+-} 11 years; 50 caucasians, 2 African-Americans 2 Hispanics and 1 Asian; 46 males and 9 females; mean duration of Be-exposure 15 {+-} 9 years) and 51 showed Be-sensitization without lung granulomas detected by trans-bronchial biopsy (ag

Cesare Saltini, Massimo Amicosante

2009-12-19

175

Methylomics analysis identifies epigenetically silenced genes and implies an activation of ?-catenin signaling in cervical cancer.  

PubMed

Using DNA methylation biomarkers in cancer detection is a potential direction in clinical testing. Some methylated genes have been proposed for cervical cancer detection; however, more reliable methylation markers are needed. To identify new hypermethylated genes in the discovery phase, we compared the methylome between a pool of DNA from normal cervical epithelium (n?=?19) and a pool of DNA from cervical cancer tissues (n?=?38) using a methylation bead array. We integrated the differentially methylated genes with public gene expression databases, which resulted in 91 candidate genes. Based on gene expression after demethylation treatment in cell lines, we confirmed 61 genes for further validation. In the validation phase, quantitative MSP and bisulfite pyrosequencing were used to examine their methylation level in an independent set of clinical samples. Fourteen genes, including ADRA1D, AJAP1, COL6A2, EDN3, EPO, HS3ST2, MAGI2, POU4F3, PTGDR, SOX8, SOX17, ST6GAL2, SYT9, and ZNF614, were significantly hypermethylated in CIN3+ lesions. The sensitivity, specificity, and accuracy of POU4F3 for detecting CIN3+ lesions were 0.88, 0.82, and 0.85, respectively. A bioinformatics function analysis revealed that AJAP1, EDN3, EPO, MAGI2, and SOX17 were potentially implicated in ?-catenin signaling, suggesting the epigenetic dysregulation of this signaling pathway during cervical cancer development. The concurrent methylation of multiple genes in cancers and in subsets of precancerous lesions suggests the presence of a driver of methylation phenotype in cervical carcinogenesis. Further validation of these new genes as biomarkers for cervical cancer screening in a larger population-based study is warranted. PMID:24310984

Chen, Yu-Chih; Huang, Rui-Lan; Huang, Yung-Kai; Liao, Yu-Ping; Su, Po-Hsuan; Wang, Hui-Chen; Chang, Cheng-Chang; Lin, Ya-Wen; Yu, Mu-Hsien; Chu, Tang-Yuan; Lai, Hung-Cheng

2014-07-01

176

Risk of Primary Liver Cancer Associated with Gallstones and Cholecystectomy: A Meta-Analysis  

PubMed Central

Background Recent epidemiological evidence points to an association between gallstones or cholecystectomy and the incidence risk of liver cancer, but the results are inconsistent. We present a meta-analysis of observational studies to explore this association. Methods We identified studies by a literature search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant conference proceedings up to March 2014. A random-effects model was used to generate pooled multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran’s Q statistic and the I2. Results Fifteen studies (five case-control and 10 cohort studies) were included in this analysis. There were 4,487,662 subjects in total, 17,945 diagnoses of liver cancer, 328,420 exposed to gallstones, and 884,507 exposed to cholecystectomy. Pooled results indicated a significant increased risk of liver cancer in patients with a history of gallstones (OR?=?2.54; 95% CI, 1.71–3.79; n?=?11 studies), as well as cholecystectomy (OR?=?1.62; 95% CI, 1.29–2.02; n?=?12 studies), but there was considerable heterogeneity among these studies. The effects estimates did not vary markedly when stratified by gender, study design, study region, and study quality. The multivariate meta-regression analysis suggested that study region and study quality appeared to explain the heterogeneity observed in the cholecystectomy analysis. Conclusions Our results suggest that individuals with a history of gallstones and cholecystectomy may have an increased risk of liver cancer. PMID:25290940

Liu, Yanqiong; He, Yu; Li, Taijie; Xie, Li; Wang, Jian; Qin, Xue; Li, Shan

2014-01-01

177

Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies  

Microsoft Academic Search

Objective: To investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a meta-analysis using individual patient data to adjust for recognised confounders.\\u000aResearch design and methods: Relevant studies published before June 2009 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies were contacted and asked to provide individual patient

Chris R Cardwell; Lars C Stene; Geir Joner; Max K Bulsara; Ondrej Cinek; Joachim Rosenbauer; Johnny Ludvigsson; Mireia Jané; Jannet Svensson; Michael J Goldacre; Thomas Waldhoer; Przamyslawa Jarosz-Chobot; Suely GA Gimeno; Lee-Ming Chuang; Roger C Parslow; Emma JK Wadsworth; Amanda Chetwynd; Paolo Pozzilli; Girts Brigis; Brone Urbonait?; Sandra Sipetic; Edith Schober; Gabriele Devoti; Constantin Ionescu-Tirgoviste; Carine E de Beaufort; Denka Stoyanov; Karsten Buschard; Chris C Patterson

2010-01-01

178

BIOINFORMATICS ANALYSIS OF OMICS DATA TOWARDS CANCER DIAGNOSIS AND PROGNOSIS  

E-print Network

BIOINFORMATICS ANALYSIS OF OMICS DATA TOWARDS CANCER DIAGNOSIS AND PROGNOSIS by Jianjun Yu: AN INTEGRATIVE APPRAOCH TO MODEL PROSTATE CANCER PROGRESSION CHAPTER 7. Integrative Genomic and Proteomic Analysis Reveals Signatures of Prostate Cancer Progression 146 PART 5: CONCLUSION CHAPTER 8. Conclusion 181

Fernandez, Thomas

179

Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies  

Microsoft Academic Search

incident prostate cancer and 6438 control subjects were pooled by the Endogenous Hormones and Prostate Cancer Collaborative Group. Relative risks (RRs) of prostate cancer by fifths of serum hormone concentration were estimated by use of conditional logistic regression with stratification by study, age at recruitment, and year of recruitment. All statistical tests were two-sided. Results No associations were found between

Andrew W. Roddam; D. Phil

2008-01-01

180

SPECT gated blood pool phase analysis of lateral wall motion for prediction of CRT response.  

PubMed

Amplitude, defined as the magnitude of contraction of the myocardium, is obtained from phase analysis but has not been investigated to the same extent as phase-based parameters for predicting the outcome of cardiac resynchronization therapy (CRT). The size of scar present in the lateral wall of the left ventricle (LV) has been shown in some studies to predict response to CRT. Scar is associated with impaired regional LV wall motion and is expected to result in a reduction in the corresponding amplitude values derived from phase analysis. Our objective was to determine the correlation between amplitude and scar, and to evaluate amplitude parameters as surrogates for scar in predicting response to CRT. 49 patients underwent a single photon emission computed tomography (SPECT) radionuclide angiography (RNA) scan as well as FDG viability and Rubidium-82 perfusion PET scans prior to undergoing CRT. Phase analysis was performed on the SPECT RNA data to extract amplitude values used to define amplitude size (AmpSize) and amplitude score (AmpScore) parameters. Scar size and scar score were obtained from the PET scans based on a 5 segment model. Scar parameters were then compared to amplitude parameters in the lateral wall for the whole population as well as both ischemic (N = 27) and non-ischemic (N = 22) populations using Pearson correlation. The ability of amplitude parameters to predict response to CRT was also investigated and compared to scar parameters. The largest ROC AUC values were obtained in the ischemic population where values of 0.67 and 0.68 were observed for lateral wall AmpSize and AmpScore respectively. Both parameters produced the same sensitivity and specificity values of 83 and 67 %. Amplitude size in the lateral wall showed significant correlation with lateral wall scar size in all patients (r = 0.51), which was further strengthened in the ischemic patient sub-group (r = 0.64). Lateral wall amplitude-based parameters obtained from SPECT RNA phase analysis produced an overall accuracy in predicting CRT response in ischemic patients that was not significantly different to that of PET lateral wall scar parameters. A significant correlation existed between amplitude size and scar size in the lateral wall. PMID:24402886

Lalonde, Michel; Birnie, David; Ruddy, Terrence D; deKemp, Robert A; Beanlands, Rob S B; Wassenaar, Richard; Wells, R Glenn

2014-03-01

181

Alcohol drinking and the risk of colorectal cancer death: a meta-analysis.  

PubMed

A causal link between alcohol consumption and colorectal cancer (CRC) was established only recently by the International Agency for Research on Cancer. However, the quantitative association between alcohol drinking and CRC mortality is still an open question. We performed a systemic review and meta-analysis on epidemiological studies to quantify the risk for CRC mortality at different levels of alcohol consumption. A literature search was carried out in PubMed and Web of Science to identify all relevant studies published from January 1966 to June 2013. The pooled relative risk (RR) and the corresponding 95% confidence interval (CI) were estimated by categorical meta-analysis. A dose-risk relation was also analyzed. Nine cohort studies exploring the association between CRC mortality and alcohol drinking were identified. Compared with non/occasional drinkers, the pooled RR was 1.03 (95% CI, 0.93-1.15) for any, 0.97 (95% CI, 0.86-1.10) for light (?12.5?g/day of ethanol), 1.04 (95% CI, 0.94-1.16) for moderate (12.6-49.9?g/day of ethanol), and 1.21 (1.01-1.46) for heavy drinkers (?50?g/day of ethanol). For heavy drinkers, the pooled estimate was apparently higher for men (RR=1.28; 95% CI, 1.13-1.46) than for women (RR=0.79; 95% CI, 0.40-1.54; Pheterogeneity=0.007). The dose-response analysis showed a J-shaped relationship between alcohol consumption and CRC mortality. The present meta-analysis provides the evidence for an association between heavy alcohol drinking (?50?g/day of ethanol) and CRC mortality. PMID:25170915

Cai, Shaofang; Li, Yingjun; Ding, Ye; Chen, Kun; Jin, Mingjuan

2014-11-01

182

A Meta Analysis of Pancreatic Microarray Datasets Yields New Targets as Cancer Genes and Biomarkers  

PubMed Central

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a five year survival rate of less than 5%. Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. Though many serum markers have been reported to be elevated in patients with PC, so far, most of these markers have not been implemented into clinical routine due to low sensitivity or specificity. In this study, we have identified genes that are significantly upregulated in PC, through a meta-analysis of large number of microarray datasets. We demonstrate that the biological functions ascribed to these genes are clearly associated with PC and metastasis, and that that these genes exhibit a strong link to pathways involved with inflammation and the immune response. This investigation has yielded new targets for cancer genes, and potential biomarkers for pancreatic cancer. The candidate list of cancer genes includes protein kinase genes, new members of gene families currently associated with PC, as well as genes not previously linked to PC. In this study, we are also able to move towards developing a signature for hypomethylated genes, which could be useful for early detection of PC. We also show that the significantly upregulated 800+ genes in our analysis can serve as an enriched pool for tissue and serum protein biomarkers in pancreatic cancer. PMID:24740004

Goonesekere, Nalin C. W.; Wang, Xiaosheng; Ludwig, Lindsey; Guda, Chittibabu

2014-01-01

183

Impact of XRCC2 Arg188His Polymorphism on Cancer Susceptibility: A Meta-Analysis  

PubMed Central

Background Association between the single nucleotide polymorphism rs3218536 (known as Arg188His) located in the X-ray repair cross complementing group 2 (XRCC2) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. Methods PubMed and Embase databases were searched systematically until September 7, 2013 to obtain all the records evaluating the association between the XRCC2 Arg188His polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on breast cancer, ovarian cancer and other cancers. All the analyses were carried out in STATA 12.0. Results With 30868 cases and 38656 controls, a total of 45 case-control studies from 26 publications were eventually included in our meta-analysis. No significant association was observed between the XRCC2 Arg188His polymorphism and breast cancer susceptibility (dominant model: OR?=?0.94, 95%CI?=?0.86–1.04, P?=?0.232). However, a significant impact of this polymorphism was detected on decreased ovarian cancer risk (dominant model: OR?=?0.83, 95%CI?=?0.73–0.95, P?=?0.007). In addition, we found this polymorphism was associated with increased upper aerodigestive tract (UADT) cancer susceptibility (dominant model: OR?=?1.51, 95%CI?=?1.04–2.20, P?=?0.032). Conclusion The Arg188His polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with breast cancer susceptibility. However, this polymorphism might contribute to decreased gynecological cancer risk and increased UADT cancer risk. More preclinical and epidemiological studies were still imperative for further evaluation. PMID:24621646

Deng, Xiangbing; Wei, Mingtian; Wu, Qingbin; Yang, Tinghan; Zhou, Yanhong; Wang, Ziqiang

2014-01-01

184

P53 codon 72 Arg/Pro polymorphism and lung cancer risk in Asians: an updated meta-analysis.  

PubMed

The polymorphism of p53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Asians have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case-control studies to estimate the effect of p53 codon 72 Arg/Pro polymorphism on the development of lung cancer. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 %CIs) were calculated to assess this effect. A total of 14 individual studies involving 7,929 cases and 5,924 controls were included into this meta-analysis according to the inclusion criteria. The overall OR for the dominant genetic model indicated that the p53 codon 72 Arg/Pro variant was positively correlated with lung cancer risk (ORArg/Pro + Pro/Pro vs. Arg/Arg = 1.14, 95 %CI 1.07-1.23, P OR < 0.001). Similar results were found in the stratified analysis of population-based studies. The histological types of lung cancer and smoking status seemed to exert no effect on the lung cancer risk. Sensitivity analysis confirmed the stability of the above findings. The updated meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism is a risk factor for lung cancer in the Asian population. However, the potential role of gene-environment interaction in lung cancer susceptibility needs further investigation in future studies with high quality. PMID:23812725

Wang, Siyang; Lan, Xingang; Tan, Sheng; Wang, Siwen; Li, Yu

2013-10-01

185

Flux Imbalance Analysis and the Sensitivity of Cellular Growth to Changes in Metabolite Pools  

PubMed Central

Stoichiometric models of metabolism, such as flux balance analysis (FBA), are classically applied to predicting steady state rates - or fluxes - of metabolic reactions in genome-scale metabolic networks. Here we revisit the central assumption of FBA, i.e. that intracellular metabolites are at steady state, and show that deviations from flux balance (i.e. flux imbalances) are informative of some features of in vivo metabolite concentrations. Mathematically, the sensitivity of FBA to these flux imbalances is captured by a native feature of linear optimization, the dual problem, and its corresponding variables, known as shadow prices. First, using recently published data on chemostat growth of Saccharomyces cerevisae under different nutrient limitations, we show that shadow prices anticorrelate with experimentally measured degrees of growth limitation of intracellular metabolites. We next hypothesize that metabolites which are limiting for growth (and thus have very negative shadow price) cannot vary dramatically in an uncontrolled way, and must respond rapidly to perturbations. Using a collection of published datasets monitoring the time-dependent metabolomic response of Escherichia coli to carbon and nitrogen perturbations, we test this hypothesis and find that metabolites with negative shadow price indeed show lower temporal variation following a perturbation than metabolites with zero shadow price. Finally, we illustrate the broader applicability of flux imbalance analysis to other constraint-based methods. In particular, we explore the biological significance of shadow prices in a constraint-based method for integrating gene expression data with a stoichiometric model. In this case, shadow prices point to metabolites that should rise or drop in concentration in order to increase consistency between flux predictions and gene expression data. In general, these results suggest that the sensitivity of metabolic optima to violations of the steady state constraints carries biologically significant information on the processes that control intracellular metabolites in the cell. PMID:24009492

Reznik, Ed; Mehta, Pankaj; Segre, Daniel

2013-01-01

186

Flux imbalance analysis and the sensitivity of cellular growth to changes in metabolite pools.  

PubMed

Stoichiometric models of metabolism, such as flux balance analysis (FBA), are classically applied to predicting steady state rates - or fluxes - of metabolic reactions in genome-scale metabolic networks. Here we revisit the central assumption of FBA, i.e. that intracellular metabolites are at steady state, and show that deviations from flux balance (i.e. flux imbalances) are informative of some features of in vivo metabolite concentrations. Mathematically, the sensitivity of FBA to these flux imbalances is captured by a native feature of linear optimization, the dual problem, and its corresponding variables, known as shadow prices. First, using recently published data on chemostat growth of Saccharomyces cerevisae under different nutrient limitations, we show that shadow prices anticorrelate with experimentally measured degrees of growth limitation of intracellular metabolites. We next hypothesize that metabolites which are limiting for growth (and thus have very negative shadow price) cannot vary dramatically in an uncontrolled way, and must respond rapidly to perturbations. Using a collection of published datasets monitoring the time-dependent metabolomic response of Escherichia coli to carbon and nitrogen perturbations, we test this hypothesis and find that metabolites with negative shadow price indeed show lower temporal variation following a perturbation than metabolites with zero shadow price. Finally, we illustrate the broader applicability of flux imbalance analysis to other constraint-based methods. In particular, we explore the biological significance of shadow prices in a constraint-based method for integrating gene expression data with a stoichiometric model. In this case, shadow prices point to metabolites that should rise or drop in concentration in order to increase consistency between flux predictions and gene expression data. In general, these results suggest that the sensitivity of metabolic optima to violations of the steady state constraints carries biologically significant information on the processes that control intracellular metabolites in the cell. PMID:24009492

Reznik, Ed; Mehta, Pankaj; Segrè, Daniel

2013-01-01

187

Bayesian Pathway Analysis of Cancer Microarray Data  

PubMed Central

High Throughput Biological Data (HTBD) requires detailed analysis methods and from a life science perspective, these analysis results make most sense when interpreted within the context of biological pathways. Bayesian Networks (BNs) capture both linear and nonlinear interactions and handle stochastic events in a probabilistic framework accounting for noise making them viable candidates for HTBD analysis. We have recently proposed an approach, called Bayesian Pathway Analysis (BPA), for analyzing HTBD using BNs in which known biological pathways are modeled as BNs and pathways that best explain the given HTBD are found. BPA uses the fold change information to obtain an input matrix to score each pathway modeled as a BN. Scoring is achieved using the Bayesian-Dirichlet Equivalent method and significance is assessed by randomization via bootstrapping of the columns of the input matrix. In this study, we improve on the BPA system by optimizing the steps involved in “Data Preprocessing and Discretization”, “Scoring”, “Significance Assessment”, and “Software and Web Application”. We tested the improved system on synthetic data sets and achieved over 98% accuracy in identifying the active pathways. The overall approach was applied on real cancer microarray data sets in order to investigate the pathways that are commonly active in different cancer types. We compared our findings on the real data sets with a relevant approach called the Signaling Pathway Impact Analysis (SPIA). PMID:25036210

Korucuoglu, Melike; Isci, Senol; Ozgur, Arzucan; Otu, Hasan H.

2014-01-01

188

Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies  

PubMed Central

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APO?4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10?11) and APO?2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10?15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10?5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond?2 and ?4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. PMID:21882290

McKay, Gareth J.; Patterson, Chris C.; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R.; Ho, Lintje; de Jong, Paulus T.V.M.; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D.; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M.; Peter, Inga; Webster, Andrew R.; Moore, Anthony T.; Yates, John R.W.; Cipriani, Valentina; Fritsche, Lars G.; Weber, Bernhard H.F.; Keilhauer, Claudia N.; Lotery, Andrew J.; Ennis, Sarah; Klein, Michael L.; Francis, Peter J.; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B.; Weeks, Daniel E.; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R.; Wright, Alan F.; Hayward, Caroline; Baird, Paul N.; Guymer, Robyn H.; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

2011-01-01

189

Integrated DNA Copy Number and Gene Expression Regulatory Network Analysis of Non-small Cell Lung Cancer Metastasis  

PubMed Central

Integrative analysis of multi-level molecular profiles can distinguish interactions that cannot be revealed based on one kind of data in the analysis of cancer susceptibility and metastasis. DNA copy number variations (CNVs) are common in cancer cells, and their role in cell behaviors and relationship to gene expression (GE) is poorly understood. An integrative analysis of CNV and genome-wide mRNA expression can discover copy number alterations and their possible regulatory effects on GE. This study presents a novel framework to identify important genes and construct potential regulatory networks based on these genes. Using this approach, DNA copy number aberrations and their effects on GE in lung cancer progression were revealed. Specifically, this approach contains the following steps: (1) select a pool of candidate driver genes, which have significant CNV in lung cancer patient tumors or have a significant association with the clinical outcome at the transcriptional level; (2) rank important driver genes in lung cancer patients with good prognosis and poor prognosis, respectively, and use top-ranked driver genes to construct regulatory networks with the COpy Number and EXpression In Cancer (CONEXIC) method; (3) identify experimentally confirmed molecular interactions in the constructed regulatory networks using Ingenuity Pathway Analysis (IPA); and (4) visualize the refined regulatory networks with the software package Genatomy. The constructed CNV/mRNA regulatory networks provide important insights into potential CNV-regulated transcriptional mechanisms in lung cancer metastasis. PMID:25392690

Iranmanesh, Seyed M; Guo, Nancy L

2014-01-01

190

Comparison of dust related respiratory effects in Dutch and Canadian grain handling industries: a pooled analysis.  

PubMed Central

OBJECTIVES: Four previously conducted epidemiological studies in more than 1200 grain workers were used to compare exposure-response relations between exposure to grain dust and respiratory health. METHODS: The studies included Dutch workers from an animal feed mill and a transfer grain elevator and Canadian workers from a terminal grain elevator and the docks. Relations between forced expiratory volume in one second (FEV1) and exposure were analysed with multiple regression analysis corrected for smoking, age, and height. Exposure variables examined included cumulative and current dust exposure and the numbers of years a subject was employed in the industry. Sampling efficiencies of the Dutch and Canadian measurement techniques were compared in a pilot study. Results of this study were used to correct slopes of exposure-response relations for differences in dust fractions sampled by Dutch and Canadian personal dust samplers. RESULTS: Negative exposure-response relations were shown for regressions of FEV1 on cumulative and current exposure and years employed. Slopes of the exposure-response relations differed by a factor of three to five between industries, apart from results for cumulative exposure. Here the variation in slopes differed by a factor of 100, from -1 to -0.009 ml/mg.y/m3. The variation in slopes between industries reduced to between twofold to fivefold when the Dutch transfer elevator workers were not considered. There was evidence that the small exposure-response slope found for this group is caused by misclassification of exposure and a strong healthy worker effect. Alternative, but less likely explanations for the variation in slopes were differences in exposure concentrations, composition of grain dust, exposure characteristics, and measurement techniques. CONCLUSION: In conclusion, this study showed moderately similar negative exposure-response relations for four different populations from different countries, despite differences in methods of exposure assessment and exposure estimation. PMID:8983468

Peelen, S J; Heederik, D; Dimich-Ward, H D; Chan-Yeung, M; Kennedy, S M

1996-01-01

191

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.  

PubMed

Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer. PMID:24832084

Setiawan, Veronica Wendy; Schumacher, Fredrick; Prescott, Jennifer; Haessler, Jeffrey; Malinowski, Jennifer; Wentzensen, Nicolas; Yang, Hannah; Chanock, Stephen; Brinton, Louise; Hartge, Patricia; Lissowska, Jolanta; Park, S Lani; Cheng, Iona; Bush, William S; Crawford, Dana C; Ursin, Giske; Horn-Ross, Pamela; Bernstein, Leslie; Lu, Lingeng; Risch, Harvey; Yu, Herbert; Sakoda, Lori C; Doherty, Jennifer; Chen, Chu; Jackson, Rebecca; Yasmeen, Shagufta; Cote, Michele; Kocarnik, Jonathan M; Peters, Ulrike; Kraft, Peter; De Vivo, Immaculata; Haiman, Christopher A; Kooperberg, Charles; Le Marchand, Loic

2014-09-01

192

Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies  

PubMed Central

Nyberg ST, Heikkilä K, Fransson EI, Alfredsson L, De Bacquer D, Bjorner JB, Bonenfant S, Borritz M, Burr H, Casini A, Clays E, Dragano N, Erbel R, Geuskens GA, Goldberg M, Hooftman WE, Houtman IL, Jöckel K-H, Kittel F, Knutsson A, Koskenvuo M, Leineweber C, Lunau T, Madsen IEH, Magnusson Hanson LL, Marmot MG, Nielsen ML, Nordin M, Oksanen T, Pentti J, Rugulies R, Siegrist J, Suominen S, Vahtera J, Virtanen M, Westerholm P, Westerlund H, Zins M, Ferrie JE, Theorell T, Steptoe A, Hamer M, Singh-Manoux A, Batty GD, Kivimäki M, for the IPD-Work Consortium (Finnish Institute of Occupational Health, Helsinki, Finland; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Jönköping University, Jönköping, Sweden; Ghent University, Ghent, Belgium; National Research Centre for the Working Environment, Copenhagen, Denmark; Versailles-Saint Quentin University, Versailles, France; Centre for Research in Epidemiology and Population Health, Villejuif, France; Bispebjerg University Hospital, Copenhagen, Denmark; Centre for Maritime Health and Safety, Esbjerg, Denmark; Université Libre de Bruxelles, Brussels, Belgium; University Duisburg-Essen, Essen, Germany; West-German Heart Center Essen, University Duisburg-Essen, Essen, Germany; TNO, Hoofddorp, the Netherlands; Mid Sweden University, Sundsvall, Sweden; University of Helsinki, Helsinki, Finland; Stockholm University, Stockholm, Sweden; University College London, London, UK; Bispebjerg University Hospital, Copenhagen, Denmark; Umeå University, Umeå, Sweden; Finnish Institute of Occupational Health, Turku, Finland; Harvard School of Public Health, Boston, MA, USA; University of Copenhagen, Copenhagen, Denmark; University of Düsseldorf, Düsseldorf, Germany; University of Turku, Turku; Folkhälsan Research Center, Helsinki; Turku University Hospital, Turku, Finland; Uppsala University, Uppsala; Karolinska Institutet, Stockholm, Sweden; University of Bristol, Bristol; University of Edinburgh, Edinburgh, UK; and University of Helsinki, Helsinki, Finland). Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies. J Intern Med 2012; 272: 65–73. Background Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. Objectives To examine the association between job strain and body mass index (BMI) in a large adult population. Methods We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). Results A total of 86 429 participants were of normal weight (BMI 18.5–24.9 kg m?2), 2149 were underweight (BMI < 18.5 kg m?2), 56 572 overweight (BMI 25.0–29.9 kg m?2) and 13 523 class I (BMI 30–34.9 kg m?2) and 3073 classes II/III (BMI ? 35 kg m?2) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.00–1.25], obese class I (odds ratio 1.07, 95% CI 1.02–1.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.01–1.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. Conclusions In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a ‘U’-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a popu

Nyberg, S T; Heikkila, K; Fransson, E I; Alfredsson, L; De Bacquer, D; Bjorner, J B; Bonenfant, S; Borritz, M; Burr, H; Casini, A; Clays, E; Dragano, N; Erbel, R; Geuskens, G A; Goldberg, M; Hooftman, W E; Houtman, I L; Jockel, K-H; Kittel, F; Knutsson, A; Koskenvuo, M; Leineweber, C; Lunau, T; Madsen, I E H; Hanson, L L Magnusson; Marmot, M G; Nielsen, M L; Nordin, M; Oksanen, T; Pentti, J; Rugulies, R; Siegrist, J; Suominen, S; Vahtera, J; Virtanen, M; Westerholm, P; Westerlund, H; Zins, M; Ferrie, J E; Theorell, T; Steptoe, A; Hamer, M; Singh-Manoux, A; Batty, G D; Kivimaki, M

2012-01-01

193

Thyroid cancer after exposure to external radiation: A pooled analysis of seven studies  

Microsoft Academic Search

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged

Elaine Ron; Jay H. Lubin; L. M. Pottern; M. A. Tucker; J. D. Jr. Boice; R. E. Shore; Kiyohiko Mabuchi; B. Modan; A. B. Schneider

1995-01-01

194

Association between CD14 Gene Polymorphisms and Cancer Risk: A Meta-Analysis  

PubMed Central

Background Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. Methods All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of this association in fixed- or random-effects model. Results 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls) for -260C/T polymorphism and three studies (832 cases and 1190 controls) for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori) infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. Conclusions This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings. PMID:24978812

Wang, Jun; Guo, Xufeng; Yu, Shijie; Song, Jia; Zhang, Jixiang; Cao, Zhuo; Wang, Jing; Liu, Min; Dong, Weiguo

2014-01-01

195

Coffee Consumption and Risk of Gastric Cancer: A Large Updated Meta-Analysis of Prospective Studies  

PubMed Central

The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93–1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06–1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00–1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13–1.93). There was some evidence of publication bias (P for Egger’s test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation. PMID:25237829

Xie, Feiyue; Wang, Dan; Huang, Zhifang; Guo, Yajun

2014-01-01

196

Statins and the Risk of Lung Cancer: A Meta-Analysis  

PubMed Central

Purpose Several epidemiologic studies have evaluated the association between statins and lung cancer risk, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. We conducted a meta-analysis of all relevant studies to examine this association. Methods A systematic literature search up to March 2012 was performed in PubMed database. Study-specific risk estimates were pooled using a random-effects model. Results Nineteen studies (5 RCTs and 14 observational studies) involving 38,013 lung cancer cases contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of lung cancer either among RCTs (relative risk [RR] 0.91, 95% confidence interval [CI] 0.76–1.09), among cohort studies (RR 0.94, 95% CI 0.82–1.07), or among case-control studies (RR 0.82, 95% CI 0.57–1.16). Low evidence of publication bias was found. However, statistically significant heterogeneity was found among cohort studies and among case-control studies. After excluding the studies contributing most to the heterogeneity, summary estimates were essentially unchanged. Conclusion The results of our meta-analysis suggest that there is no association between statin use and the risk of lung cancer. PMID:23468972

Tan, Min; Song, Xiaolian; Zhang, Guoliang; Peng, Aimei; Li, Xuan; Li, Ming; Liu, Yang; Wang, Changhui

2013-01-01

197

Coffee consumption and risk of gastric cancer: a large updated meta-analysis of prospective studies.  

PubMed

The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed and Embase databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93-1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06-1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00-1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13-1.93). There was some evidence of publication bias (P for Egger's test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation. PMID:25237829

Xie, Feiyue; Wang, Dan; Huang, Zhifang; Guo, Yajun

2014-09-01

198

Meta-Analysis of the Prognostic Value of Smad4 Immunohistochemistry in Various Cancers  

PubMed Central

Background Accumulating evidence indicates that Smad4 (DPC4) plays a fundamental role in the development and prognosis of several types of cancer. The objective of this study was to conduct a meta-analysis to evaluate whether the loss of Smad4 staining could serve as a prognostic marker. Methods A comprehensive meta-analysis was conducted using major useful databases to determine the relationship between the immunohistochemical detection of Smad4 and the survival of patients with various cancers. We used hazard ratios (HRs) with 95% confidence interval (CIs) as the effect estimation to evaluate the association of Smad4 with overall survival (OS), cancer-specific survival (CSS) or recurrence-free survival (RFS). The relationship between the clinical characteristics of patients and Smad4 was also evaluated using the odds ratio (OR). Results A total of 7570 patients from 26 studies were included in the analysis. The pooled results showed that loss of Smad4 staining was a negative predictor of OS with an HR of 1.97 (95% CI: 1.55–2.51; Pheterogeneity<0.001) and CSS/RFS (HR?=?1.81; 95% CI: 1.30–2.54; Pheterogeneity<0.001). In addition, loss of Smad4 staining was more likely to be found in older (OR?=?1.69, 95% CI: 1.09–2.61; Pheterogeneity?=?0.648) colorectal cancer patients with a late tumor stage (OR?=?2.31, 95% CI: 1.71–3.10; Pheterogeneity?=?0.218) and in gastric cancer patients with lymph node metastasis (OR?=?2.11, 95% CI: 1.03–4.34; Pheterogeneity?=?0.038). Conclusion Based on these results, our meta-analysis provided evidence that loss of Smad4 staining could act as an unfavorable biomarker in the prognosis of various cancers and should be used as a powerful tool in future clinical trials. PMID:25333693

Huang, Zebo; Qiu, Tianzhu; Wang, Jian; Zhu, Wei; Wang, Tongshan; Liu, Ping

2014-01-01

199

Polymorphisms in the vitamin D Receptor (VDR) and the risk of ovarian cancer: a meta-analysis.  

PubMed

The vitamin D receptor (VDR) principally mediates the anticancer activities of vitamin D. Various epidemiological studies have investigated the associations of VDR gene polymorphisms with ovarian cancer; however, the results have been inconclusive. In the current study, we evaluated, in a meta-analysis, the association of five common single nucleotide polymorphisms (SNPs) in the VDR gene (ApaI, BsmI, Cdx-2, FokI, and TaqI) with the risk of ovarian cancer. Six eligible studies, with a total of 4,107 cases and 6,661 controls, which evaluated the association of these variants and ovarian cancer risk, were identified from the MEDLINE and PubMed databases. The meta-analysis indicated that FokI was associated with an increased ovarian cancer risk, with a pooled odds ratio (OR) of 1.10 [95% confidence intervals (95% CI)?=?1.00-1.20] for CT heterozygotes and 1.16 (95% CI?=?1.02-1.30) for TT homozygotes relative to common CC carriers. Carriers of the T allele (also known as the f allele) showed an 11% (pooled OR?=?1.11, 95% CI?=?1.02-1.21; TT/CT vs. CC) increased risk of ovarian cancer relative to CC carriers. For FokI, no significant heterogeneity between the studies was found (I(2)?=?0%, P?=?0.62 for the Q test). There was no statistically significant association between the other four variants (ApaI, BsmI, Cdx-2 and TaqI) and risk of ovarian cancer. These data indicate that the polymorphism FokI on the VDR is a susceptibility factor for ovarian cancer. Nevertheless, more studies are warranted to elucidate the underlying mechanisms of the VDR in development of ovarian cancer. PMID:23826116

Liu, Yanling; Li, Chenglin; Chen, Peizhan; Li, Xiaoguang; Li, Mian; Guo, He; Li, Jingquan; Chu, Ruiai; Wang, Hui

2013-01-01

200

Smokeless Tobacco and Oral Cancer in South Asia: A Systematic Review with Meta-Analysis  

PubMed Central

Introduction. Smokeless tobacco is considered one of the major risk factors for oral cancer. It is estimated that over 90% of the global smokeless tobacco use burden is in South Asia. This paper aims to systematically review publications reporting epidemiological observational studies published in South Asia from 1984 till 2013. Methods. An electronic search in “Medline” and “ISI Web of Knowledge” yielded 734 publications out of which 21 were included in this review. All publications were assessed for quality using a standard quality assessment tool. Effect estimates (odds ratios (OR)) were abstracted or calculated from the given data. A random effects meta-analysis was performed to assess the risk of oral cancer with the use of different forms of smokeless tobacco. Results and Conclusion. The pooled OR for chewing tobacco and risk of oral cancer was 4.7 [3.1–7.1] and for paan with tobacco and risk of oral cancer was 7.1 [4.5–11.1]. The findings of this study suggest a strong causal link between oral cancer and various forms of smokeless tobacco. Public health policies in affected countries should consider SLT specific cessation programs in addition to campaigns and activities incorporated into smoking cessation programs. PMID:25097551

Khan, Zohaib; Tonnies, Justus; Muller, Steffen

2014-01-01

201

Occupational Exposure to Asbestos and Ovarian Cancer: A Meta-analysis  

PubMed Central

Objective: A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association. Data sources: Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos. Data extraction: Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. Data synthesis: All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37–2.28), with a moderate degree of heterogeneity among the studies (I2 = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger’s test p-value = 0.162). Conclusions: Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer. PMID:21642044

Camargo, M. Constanza; Straif, Kurt; Reina, Margarita; Al-Alem, Umaima; Demers, Paul A.; Landrigan, Philip J.

2011-01-01

202

Proteomics Analysis of Bladder Cancer Exosomes*  

PubMed Central

Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the exosome proteomics data set presented is of unrivaled quality. The data will aid in the development of urine exosome-based clinical tools for monitoring disease and will inform follow-up studies into varied aspects of exosome manufacture and function. PMID:20224111

Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

2010-01-01

203

Cancer Nursing Education: Literature Review and Documentary Analysis.  

ERIC Educational Resources Information Center

The knowledge and skills needed by cancer nurses and the content and strategies of England's existing cancer nursing education programs were examined. The study included a comprehensive literature review and an analysis of course documents from selected English National Board-approved post-qualifying cancer nursing and palliative care courses…

Langton, Helen; Blunden, Gillian; Hek, Gill

204

Machine Learning in DNA Microarray Analysis for Cancer Classification  

E-print Network

because understanding the functions of genome sequences is essential at that time. The development of DNAMachine Learning in DNA Microarray Analysis for Cancer Classification Sung-Bae Cho and Hong-Hee Won and diagnosis of cancer, so that it expectedly helps us to exactly predict and diagnose cancer. To precisely

Cho, Sung-Bae

205

An analysis and hypothesis generation platform for heterogeneous cancer  

E-print Network

An analysis and hypothesis generation platform for heterogeneous cancer databases. Philip Roy QUINLAN a,1, Alastair THOMPSON a and Chris REED b a Dundee Cancer Centre, University of Dundee, Ninewells Hospital, Dundee b School of Computing, University of Dundee, Dundee Abstract. The field of cancer research

Reed, Chris

206

Psychosocial Intervention for Adults With Cancer: A Meta-Analysis  

Microsoft Academic Search

Cancer affects a significant number of people and their families. In addition to physical symptoms, people with cancer experience considerable levels of psychosocial distress. Psychosocial oncology has been developed to address this distress. In this meta-analysis, psychosocial interventions for adults with cancer were systematically reviewed. A central finding was the dearth of clinical trials published by social work researchers and

Michèle Preyde; Emily Synnott

2009-01-01

207

Case-control and prospective studies of dietary ?-linolenic acid intake and prostate cancer risk: a meta-analysis  

PubMed Central

Objective ?-Linolenic acid (ALA) is considered to be a cardioprotective nutrient; however, some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer. The main objective was to conduct a systematic review and meta-analysis of case–control and prospective studies investigating the association between dietary ALA intake and prostate cancer risk. Design A systematic review and meta-analysis were conducted by searching MEDLINE and EMBASE for relevant prospective and case–control studies. Included studies We included all prospective cohort, case–control, nested case-cohort and nested case–control studies that investigated the effect of dietary ALA intake on the incidence (or diagnosis) of prostate cancer and provided relative risk (RR), HR or OR estimates. Primary outcome measure Data were pooled using the generic inverse variance method with a random effects model from studies that compared the highest ALA quantile with the lowest ALA quantile. Risk estimates were expressed as RR with 95% CIs. Heterogeneity was assessed by ?2 and quantified by I2. Results Data from five prospective and seven case–control studies were pooled. The overall RR estimate showed ALA intake to be positively but non-significantly associated with prostate cancer risk (1.08 (0.90 to 1.29), p=0.40; I2=85%), but the interpretation was complicated by evidence of heterogeneity not explained by study design. A weak, non-significant protective effect of ALA intake on prostate cancer risk in the prospective studies became significant (0.91 (0.83 to 0.99), p=0.02) without evidence of heterogeneity (I2=8%, p=0.35) on removal of one study during sensitivity analyses. Conclusions This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk. Larger and longer observational and interventional studies are needed to define the role of ALA and prostate cancer. PMID:23674441

Carleton, Amanda J; Sievenpiper, John L; de Souza, Russell; McKeown-Eyssen, Gail; Jenkins, David J A

2013-01-01

208

A Pooled Analysis of Alcohol Consumption and Risk of Multiple Myeloma in the International Multiple Myeloma Consortium  

PubMed Central

Background Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma (MM). Methods To better understand this relationship, we conducted an analysis of six case-control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary odds ratios (ORs) and 95% confidence intervals (CI) relating different measures of alcohol consumption and MM risk were computed by unconditional logistic regression with adjustment for age, race, and study center. Results Cases were significantly less likely than controls to report ever drinking alcohol (men: OR 0.72, 95% CI 0.59-0.89, women: OR 0.81, 0.68-0.95). The inverse association with MM was stronger when comparing current to never drinkers (men: OR=0.57, 95% CI 0.45-0.72, women: OR=0.55, 95% CI 0.45-0.68), but null among former drinkers. We did not observe an exposure-response relationship with increasing alcohol frequency, duration or cumulative lifetime consumption. Additional adjustment for body mass index, education, or smoking did not affect our results; and the patterns of association were similar for each type of alcohol beverage examined. Conclusions Our study is, to our knowledge, the largest of its kind to date, and our findings suggest that alcohol consumption may be associated with reduced risk of MM. Impact Prospective studies, especially those conducted as pooled analyses with large sample sizes, are needed to confirm our findings and further explore whether alcohol consumption provides true biologic protection against this rare, highly fatal malignancy. PMID:23964064

Andreotti, Gabriella; Birmann, Brenda; De Roos, Anneclaire J.; Spinelli, John; Cozen, Wendy; Camp, Nicola J.; Moysich, Kirsten; Chiu, Brian; Steplowski, Emily; Krzystan, Joseph; Boffetta, Paolo; Benhaim-Luzon, Veronique; Brennan, Paul; de Sanjose, Silvia; Costas, Laura; Seniori Costantini, Adele; Miligi, Lucia; Cocco, Pierluigi; Becker, Nikolaus; Foretova, Lenka; Maynadie, Marc; Nieters, Alexandra; Staines, Anthony; Tricot, Guido; Milliken, Kevin; Weisenburger, Dennis; Zheng, Tongzhang; Baris, Dalsu; Purdue, Mark P.

2013-01-01

209

Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials  

PubMed Central

Abstract Background: Secondary peritonitis is an advanced form of complicated intra-abdominal infection (cIAI) requiring hospitalization, surgical source control, and empiric antibiotic therapy against causative aerobic and anaerobic bacteria. Methods: This pooled analysis of four prospective, active-controlled randomized clinical trials compared the efficacy and safety of moxifloxacin with that of comparator antibiotics in patients with confirmed secondary peritonitis. The primary efficacy endpoint was clinical success rate at test-of-cure (TOC) between day 10 and 45 post-therapy in the per-protocol (PP) population. Safety and clinical efficacy were assessed also in the intent-to-treat population (ITT). Bacteriological success was assessed at TOC in the microbiologically-valid population as a secondary efficacy endpoint. Results: Overall clinical success rates at TOC were 85.3% (431 of 505 patients) in the moxifloxacin and 88.4% (459 of 519 patients) in the comparator treatment groups (PP population, point estimate for the difference in success rates: ?3.0%; 95% CI ?7.06%, 1.05%), respectively. Similar clinical success rates between moxifloxacin and comparators were observed by anatomical site of infection, and ranged from 80.6% to 100% for moxifloxacin and from 71.4% to 96.6% for comparators, respectively. Bacteriologic success rates were similar with moxifloxacin (82.4%) and comparators (86.8%), respectively. The proportion of patients experiencing any treatment-emergent adverse events was slightly higher with moxifloxacin (67.3%) versus comparators (59.8%). Rates of drug-related adverse events (20.9% versus 20.0%) and deaths (4.3% versus 3.4%) were similar in moxifloxacin and comparator groups; none of the deaths were drug-related. Conclusions: The data suggests that once-daily IV (or IV/PO) moxifloxacin has a comparable efficacy and safety profile to antibiotic regimens approved previously in the subgroup of patients with secondary peritonitis of mild-to-moderate severity. PMID:24833256

Tellado, Jose M.; Weiss, Gunter; Alder, Jeffrey; Kruesmann, Frank; Arvis, Pierre; Hussain, Tajamul; Solomkin, Joseph S.

2014-01-01

210

Geographic and Temporal Trends in the Management of Occult Primary Breast Cancer: A Systematic Review and Meta-Analysis  

PubMed Central

Background Management of occult primary breast cancer (OPBC), including the role of magnetic resonance imaging (MRI), is controversial. We conducted a pooled analysis of OPBC patients and a meta-analysis of MRI accuracy in OPBC in order to elucidate current practices. Methods A literature search yielded 201 studies. Patient-level data for clinically/mammographically OPBC from studies published after 1993 and from our institution were pooled; logistic regression examined associations between patient/study data and outcomes, including treatments and recurrence. We report adjusted odds ratios (OR) and 95 % confidence intervals (95 % CI) significant at 2-tailed p<0.05. Meta-analysis included data for patients who received MRIs for workup of clinically/mammographically OPBC. We report pooled sensitivity and specificity with 95 % CIs. Results The pooled analysis included 92 patients (15 studies [n = 85] plus our institution [n = 7]). Patients from Asia were more likely to receive breast surgery (OR = 5.98, 95 % CI = 2.02–17.65) but not chemotherapy (OR = 0.32, 95 % CI = 0.13–0.82); patients from the United States were more likely to receive chemotherapy (OR = 13.08, 95 % CI = 2.64–64.78). Patients from studies published after 2003 were more likely to receive radiotherapy (OR = 3.86, 95 % CI = 1.41–10.55). Chemotherapy recipients were more likely to have distant recurrence (OR = 9.77, 95 % CI = 1.10–87.21). More patients with positive MRIs received chemotherapy than patients with negative MRIs (10 of 12 [83.3 %] vs 5 of 13 [38.5 %]; p = 0.0414). In the MRI-accuracy meta-analysis (10 studies, n = 262), pooled sensitivity and specificity were 96 % (95 % CI = 91–98 %) and 63 % (95 % CI = 42–81 %), respectively. Conclusions OPBC management varied geographically and over time. We recommend establishing an international OPBC patient registry to facilitate longitudinal study and develop global treatment standards. PMID:23975301

Fayanju, Oluwadamilola M.; Stoll, Carolyn R. T.; Fowler, Susan; Colditz, Graham A.; Jeffe, Donna B.; Margenthaler, Julie A.

2013-01-01

211

Association between the ERCC5 Asp1104His Polymorphism and Cancer Risk: A Meta-Analysis  

PubMed Central

Background Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair, removal of bulky lesions caused by environmental chemicals or UV light. Mutations in this gene cause a rare autosomal recessive syndrome, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity phenotype and cancer risk. However, a series of epidemiological studies on the association between the ERCC5 Asp1104His polymorphism (rs17655, G>C) and cancer susceptibility generated conflicting results. Methodology/Principal Findings To derive a more precise estimation of the association between the ERCC5 Asp1104His polymorphism and overall cancer risk, we performed a meta-analysis of 44 published case-control studies, in which a total of 23,490 cases and 27,168 controls were included. To provide additional biological plausibility, we also assessed the genotype-gene expression correlation from the HapMap phase II release 23 data with 270 individuals from 4 ethnic populations. When all studies were pooled, we found no statistical evidence for a significantly increased cancer risk in the recessive genetic models (His/His vs. Asp/Asp: OR?=?0.99, 95% CI: 0.92–1.06, P?=?0.242 for heterogeneity or His/His vs. Asp/His + Asp/Asp: OR?=?0.98, 95% CI: 0.93–1.03, P?=?0.260 for heterogeneity), nor in further stratified analyses by cancer type, ethnicity, source of controls and sample size. In the genotype-phenotype correlation analysis from 270 individuals, we consistently found no significant correlation of the Asp1104His polymorphism with ERCC5 mRNA expression. Conclusions/Significance This meta-analysis suggests that it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk. PMID:22815677

He, Jing; Shi, Ting-Yan; Xia, Kai-Qin; Qiu, Li-Xin; Wei, Qing-Yi

2012-01-01

212

Depression and anxiety in prostate cancer: a systematic review and meta-analysis of prevalence rates  

PubMed Central

Objectives To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with prostate cancer as a function of treatment stage. Design Systematic review and meta-analysis. Participants 4494 patients with prostate cancer from primary research investigations. Primary outcome measure The prevalence of clinical depression and anxiety in patients with prostate cancer as a function of treatment stage. Results We identified 27 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 4494 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 17.27% (95% CI 15.06% to 19.72%), 14.70% (95% CI 11.92% to 17.99%) and 18.44% (95% CI 15.18% to 22.22%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 27.04% (95% CI 24.26% to 30.01%), 15.09% (95% CI 12.15% to 18.60%) and 18.49% (95% CI 13.81% to 24.31%), respectively. Conclusions Our findings suggest that the prevalence of depression and anxiety in men with prostate cancer, across the treatment spectrum, is relatively high. In light of the growing emphasis placed on cancer survivorship, we consider that further research within this area is warranted to ensure that psychological distress in patients with prostate cancer is not underdiagnosed and undertreated. PMID:24625637

Watts, Sam; Leydon, Geraldine; Birch, Brian; Prescott, Philip; Lai, Lily; Eardley, Susan; Lewith, George

2014-01-01

213

Analysis of esophageal cancer time trends in China, 1989- 2008.  

PubMed

National cancer incidence data were utilized to analyze trends in esophageal cancer incidence in China in order to provide basic information for making cancer control strategy. We retrieved and re-sorted valid esophageal cancer incidence data from National Central Cancer Registry Database over 20 years period from 1989 to 2008. Crude incidence and age-standardized incidence rates were calculated for analysis, with annual percent change estimated by Joinpoint software for long term trend analysis. The crude incidence rate of esophageal cancer was found to have remained relatively stable in both urban and rural areas over the 20 year period. Age standardized incidence rate (ASR) in cancer registration areas decreased from 39.5/100,000 in 1989 to 23.0/100,000 in 2008 in all areas (AAPC=-3.3%, 95% CI:-2.8~-3.7). The trend was no change in urban areas and 2.1% average annual decrease observed in rural aras. Before the year of 2000, esophageal cancer incidence rates significant decreased with 2.8% annually and then the rates kept stable. Over 20 years from 1989 to 2008, esophageal cancer age standardized incidence rate in cancer registration areas decreased with time. However, esophageal cancer is still a big issue and efforts for control should be continuously enhanced. Cancer registration is playing an important role in cancer control with the number of registries increasing and data quality improving in China. PMID:23167389

Zhao, Jun; He, Yu-Tong; Zheng, Rong-Shou; Zhang, Si-Wei; Chen, Wan-Qing

2012-01-01

214

Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes  

Microsoft Academic Search

BACKGROUND: In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to

Debora Williams-Herman; Samuel S Engel; Elizabeth Round; Jeremy Johnson; Gregory T Golm; Hua Guo; Bret J Musser; Michael J Davies; Keith D Kaufman; Barry J Goldstein

2010-01-01

215

Association between matrix metalloproteinase 1 -1607 1G>2G polymorphism and cancer risk: a meta-analysis including 19706 subjects  

PubMed Central

The association between MMP1 -1607 1G>2G polymorphism and cancer risk has been reported, but results remained controversial and ambiguous. To assess the association between MMP1 -1607 1G>2G polymorphism and cancer risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase), and Chinese Biomedical Literature Database (CBM), we identified outcome data from all articles estimating the association between MMP1 -1607 1G>2G polymorphism and cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Thirty-eight studies involving 10178 cases and 9528 controls were included. Overall, significant association between MMP1 -1607 1G>2G polymorphism and cancer susceptibility was observed for additive model (OR = 1.21, 95% CI 1.09-1.35), for codominant model (OR = 1.34, 95% CI 1.10-1.63), for dominant model (OR = 1.17, 95% CI 1.01-1.34), for recessive model (OR = 1.31, 95% CI 1.14-1.52). In the subgroup analysis by ethnicity, the significant association was found among Asians but not among Caucasians. In the subgroup analysis by site of cancer, significant associations were found among lung cancer, colorectal cancer, head and neck cancer and bladder cancer. This meta-analysis demonstrated that the MMP1 -1607 1G>2G polymorphism was significantly associated with cancer risk. PMID:25356173

Han, Guoda; Wei, Zhijiang; Lu, Zhiliang; Cui, Haibin; Bai, Xiyong; Ge, Huai'e; Zhang, Wei

2014-01-01

216

Pooled genetic analysis in ultrasound measured non-alcoholic fatty liver disease in Indian subjects: A pilot study  

PubMed Central

AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease (NAFLD) by performing a pooled genetic study. METHODS: Study subjects (n = 306) were recruited and categorized into NAFLD and control groups based on ultrasound findings of fatty infiltration. Of the 306 individuals, 156 individuals had fatty infiltration and thus comprised the NAFLD group. One hundred and fifty (n = 150) individuals were normal, without fatty infiltration of the liver, comprising the control group. Blood samples, demographic and anthropometric data from the individuals were collected after obtaining informed consent. Anthropometric data, blood glucose, lipids and liver function tests were estimated using standard methods. Genome wide association studies done to date on NAFLD were identified, 19 single nucleotide polymorphisms (SNPs) were selected from these studies that were reported to be significantly associated with NAFLD and genotyping was performed on the Sequenom platform. Student’s t test for continuous variables and ?2 test was applied to variant carriers from both groups. Required corrections were applied as multiple testing was done. RESULTS The mean age of the control group was 39.78 ± 10.83 and the NAFLD group was 36.63 ± 8.20 years. The waist circumference of males and females in the control and NAFLD groups were 80.13 ± 10.35; 81.77 ± 13.65 and 94.09 ± 10.53; 92.53 ± 8.27 cms respectively. The mean triglyceride and alanine transaminase (ALT) levels in the control and NAFLD groups were 135.18 ± 7.77 mg/dL; 25.39 ± 14.73 IU/L and 184.40 ± 84.31 mg/dL; 110.20 ± 67.05 IU/L respectively. When ?2 test was applied to the number of individuals carrying the variant risk alleles between the control and NAFLD group, a significant association was seen between rs738409 of the patatin-like phospholipase domain containing 3 (PNPLA3) gene (P = 0.001), rs2073080 of the PARVB gene (P = 0.02), rs2143571 of SAMM50 gene (P = 0.05) and rs6487679 of the pregnancy zone protein (PZP) gene (P = 0.01) with the disease. Variant single nucleotide polymorphisms (SNPs) in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4B and COL13A1 were associated with high triglyceride levels. Apart from the above associations, rs2073080, rs343062 and rs6591182 were significantly associated with high BMI; rs2854117 and rs738409 with high triglyceride levels; and rs2073080, rs2143571, rs2228603, rs6487679 and rs738409 with high ALT levels. CONCLUSION: Pooled genetic analysis revealed an association of SNPs in PNPLA3, PARVB, SAMM50 and PZP genes with NAFLD. SNPs in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4B and COL13A1 were associated with high triglyceride levels. PMID:25018854

Kanth, Vishnubhotla Venkata Ravi; Sasikala, Mitnala; Rao, Padaki Nagaraja; Steffie Avanthi, Urmila; Rao, Kalashikam Rajender; Nageshwar Reddy, Duvvuru

2014-01-01

217

MiR-146a rs2910164 polymorphism increases risk of gastric cancer: A meta-analysis  

PubMed Central

AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer. METHODS: A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer. RESULTS: The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons. CONCLUSION: The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations. PMID:25386093

Xie, Wen-Qun; Tan, Shi-Yun; Wang, Xiao-Fan

2014-01-01

218

Association of Mild to Moderate Chronic Kidney Disease with Venous Thromboembolism: Pooled Analysis of Five Prospective General Population Cohorts  

PubMed Central

Background Recent findings suggest that chronic kidney disease (CKD) may be associated with increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. Methods and Results We pooled individual participant data from five community-based cohorts from Europe (HUNT2, PREVEND and Tromsø study) and United States (ARIC and CHS study) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria and CKD with objectively verified VTE. To estimate adjusted hazard ratios (HRs) for VTE, categorical and continuous spline models were fit using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1,178 VTE events occurred over 599,453 person-years follow-up. Relative to eGFR 100 mL/min/1.73m2, HRs for VTE were 1.29 (95%CI, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for 60, 1.82 (1.27-2.60) for 45 and 1.95 (1.26-3.01) for 30 mL/min/1.73m2. Compared with albumin-creatinine ratio (ACR) of 5.0 mg/g, the HRs for VTE were 1.34 (1.04-1.72) for 30 mg/g, 1.60 (1.08-2.36) for 300 mg/g and 1.92 (1.19-3.09) for 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted HR for CKD defined as eGFR <60 mL/min/1.73m2 or albuminuria ?30 mg/g (vs. no CKD) was 1.54 (95%CI, 1.15-2.06). Associations were consistent in subgroups according to age, gender, and comorbidities as well as for unprovoked versus provoked VTE. Conclusions Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges. PMID:22977129

Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.; Næss, Inger Anne; Lutsey, Pamela L.; Brækkan, Sigrid K.; Veeger, Nic J. G. M.; Brodin, Ellen E.; Meijer, Karina; Sang, Yingying; Matsushita, Kunihiro; Hallan, Stein I.; Hammerstrøm, Jens; Cannegieter, Suzanne C.; Astor, Brad C.; Coresh, Josef; Folsom, Aaron R.; Hansen, John-Bjarne; Cushman, Mary

2012-01-01

219

Pooled safety analysis of calcipotriol plus betamethasone dipropionate gel for the treatment of psoriasis on the body and scalp.  

PubMed

The fixed combination calcipotriol plus betamethasone dipropionate gel is a first-line treatment for psoriasis vulgaris. The objective was to perform a large-scale assessment of tolerability of fixed combination gel (Cal/BD). Analysis was performed on pooled 8-week safety data from nine clinical trials evaluating once-daily Cal/BD treatment of scalp (n = 6) and body (n = 3) psoriasis. Pharmacovigilance data were also assessed. Patients were treated with Cal/BD [n = 1953 (scalp), n = 824 (body)], betamethasone dipropionate gel (BD; n = 1214, n = 562), calcipotriol gel (Cal; n = 979, n = 175), gel vehicle (VEH; n = 173, n = 226), calcipotriol scalp solution [n = 104 (scalp only)] and tacalcitol ointment [TAC; n = 184 (body only)]. Most adverse events (AEs) were mild-moderate severity. The proportion of scalp psoriasis patients with ?1 AE was lowest with Cal/BD (35% versus 38-57%). A similar proportion was found with Cal/BD for body psoriasis (32%), however, lower proportions were reported with BD (24%) and Cal (29%). The most common AEs with Cal/BD included nasopharyngitis, pruritus and upper respiratory tract infection (2-5% of patients). Overall, only 5% of patients treated with Cal/BD reported ?1 lesional/perilesional AEs: the lowest incidence versus scalp comparators (6-19%) and second lowest to BD (3%) for body psoriasis. Similarly, Cal/BD treatment resulted in the lowest incidence of ?1 adverse drug reactions (ADRs) in scalp psoriasis patients (8% versus 9-27%) and second lowest to BD (6% versus 4%) for body psoriasis. Overall, incidence of serious AEs (SAEs) was low (0-1%). Data received postmarketing through spontaneous reporting revealed that SAEs reported more than once with Cal/BD treatment were psoriasis (n = 5); and alopecia, erythrodermic psoriasis, pruritus, skin atrophy and urticaria (n = 2 each). In this large subset of patients treated with Cal/BD, incidence of AEs and ADRs is consistently low. This analysis provides further evidence of the good tolerability of the fixed combination gel as treatment for psoriasis vulgaris. PMID:24684739

Kragballe, K; van de Kerkhof, P

2014-05-01

220

Uncertainty analysis of suppression pool heating during an ATWS in a BWR-5 plant. An application of the CSAU methodology using the BNL engineering plant analyzer  

SciTech Connect

The uncertainty has been estimated of predicting the peak temperature in the suppression pool of a BWR power plant, which undergoes an NRC-postulated Anticipated Transient Without Scram (ATWS). The ATWS is initiated by recirculation-pump trips, and then leads to power and flow oscillations as they had occurred at the LaSalle-2 Power Station in March of 1988. After limit-cycle oscillations have been established, the turbines are tripped, but without MSIV closure, allowing steam discharge through the turbine bypass into the condenser. Postulated operator actions, namely to lower the reactor vessel pressure and the level elevation in the downcomer, are simulated by a robot model which accounts for operator uncertainty. All balance of plant and control systems modeling uncertainties were part of the statistical uncertainty analysis that was patterned after the Code Scaling, Applicability and Uncertainty (CSAU) evaluation methodology. The analysis showed that the predicted suppression-pool peak temperature of 329.3 K (133{degrees}F) has a 95-percentile uncertainty of 14.4 K (26{degrees}F), and that the size of this uncertainty bracket is dominated by the experimental uncertainty of measuring Safety and Relief Valve mass flow rates under critical-flow conditions. The analysis showed also that the probability of exceeding the suppression-pool temperature limit of 352.6 K (175{degrees}F) is most likely zero (it is estimated as < 5-104). The square root of the sum of the squares of all the computed peak pool temperatures is 350.7 K (171.6{degrees}F).

Wulff, W.; Cheng, H.S.; Mallen, A.N. [Brookhaven National Lab., Upton, NY (United States); Johnsen, G.W. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Lellouche, G.S. [Technical Data Services, Chicago, IL (United States)

1994-03-01

221

Confirmatory Factor Analysis of the M5-50: An Implementation of the International Personality Item Pool Item Set  

ERIC Educational Resources Information Center

Goldberg's International Personality Item Pool (IPIP; Goldberg, 1999) provides researchers with public-domain, free-access personality measurement scales that are proxies of well-established published scales. One of the more commonly used IPIP sets employs 50 items to measure the 5 broad domains of the 5-factor model, with 10 items per factor. The…

Socha, Alan; Cooper, Christopher A.; McCord, David M.

2010-01-01

222

Institutional Boundaries and Common-Pool Resource Management: A Comparative Analysis of Water Management Programs in California  

ERIC Educational Resources Information Center

Policymakers and academics often identify institutional boundaries as one of the factors that shape the capacity of jurisdictions to manage natural resources such as water, forests, and scenic lands. This article examines two key bodies of literature--common-pool resource management theory and local public economy theory--to explain how the…

Heikkila, Tanya

2004-01-01

223

Analysis of Pools of Targeted Salmonella Deletion Mutants Identifies Novel Genes Affecting Fitness during Competitive Infection in Mice  

Microsoft Academic Search

Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled

Carlos A. Santiviago; M. Megan Reynolds; Steffen Porwollik; Sang-Ho Choi; Fred Long; Helene L. Andrews-Polymenis; Michael McClelland

2009-01-01

224

A Simulation-Based Analysis of Motor Unit Number Index (MUNIX) Technique Using Motoneuron Pool and Surface Electromyogram Models  

Microsoft Academic Search

Motor unit number index (MUNIX) measurement has recently achieved increasing attention as a tool to evaluate the progression of motoneuron diseases. In our current study, the sensitivity of the MUNIX technique to changes in motoneuron and muscle properties was explored by a simulation approach utilizing variations on published motoneuron pool and surface electromyogram (EMG) models. Our simulation results indicate that,

Xiaoyan Li; William Zev Rymer; Ping Zhou

2012-01-01

225

The risk of colorectal cancer in ulcerative colitis: a meta-analysis  

Microsoft Academic Search

BACKGROUND AND AIMSControversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates.METHODSA literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with

J A Eaden; K R Abrams; J F Mayberry

2001-01-01

226

The Cancer Genome Atlas Pan-Cancer analysis project  

E-print Network

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a ...

Lander, Eric S.

227

Gastroesophageal Reflux in Relation to Adenocarcinomas of the Esophagus: A Pooled Analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON)  

PubMed Central

Background Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Methods Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Results Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ?20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. Conclusions This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients. PMID:25075959

Cook, Michael B.; Corley, Douglas A.; Murray, Liam J.; Liao, Linda M.; Kamangar, Farin; Ye, Weimin; Gammon, Marilie D.; Risch, Harvey A.; Casson, Alan G.; Freedman, Neal D.; Chow, Wong-Ho; Wu, Anna H.; Bernstein, Leslie; Nyren, Olof; Pandeya, Nirmala; Whiteman, David C.; Vaughan, Thomas L.

2014-01-01

228

Telomerase Reverse Transcriptase Locus Polymorphisms and Cancer Risk: A Field Synopsis and Meta-Analysis  

PubMed Central

Background Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer. Methods A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is in linkage disequilibrium with TERT, CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as “strong,” “moderate,” and “weak” according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association. Results Eighty-five studies enrolling 490?901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types. Conclusions To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans. PMID:22523397

Verdi, Daunia; Pooley, Karen A.; Landi, Maria T.; Egan, Kathleen M.; Baird, Duncan M.; Prescott, Jennifer; De Vivo, Immaculata; Nitti, Donato

2012-01-01

229

Mitochondrial Common Deletion, a Potential Biomarker for Cancer Occurrence, Is Selected against in Cancer Background: A Meta-Analysis of 38 Studies  

PubMed Central

Mitochondrial dysfunction has been long proposed to play a major role in tumorigenesis. Mitochondrial DNA (mtDNA) mutations, especially the mtDNA 4,977 bp deletion has been found in patients of various types of cancer. In order to comprehend the mtDNA 4,977 bp deletion status in various cancer types, we performed a meta-analysis composed of 33 publications, in which a total of 1613 cancer cases, 1516 adjacent normals and 638 healthy controls were included. When all studies were pooled, we found that cancerous tissue carried a lower mtDNA 4,977 bp deletion frequency than adjacent non-cancerous tissue (OR?=?0.43, 95% CI?=?0.20–0.92, P?=?0.03 for heterogeneity test, I2?=?91.5%) among various types of cancer. In the stratified analysis by cancer type the deletion frequency was even lower in tumor tissue than in adjacent normal tissue of breast cancer (OR?=?0.19, 95% CI?=?0.06–0.61, P?=?0.005 for heterogeneity test, I2?=?82.7%). Interestingly, this observation became more significant in the stratified studies with larger sample sizes (OR?=?0.70, 95% CI?=?0.58–0.86, P?=?0.0005 for heterogeneity test, I2?=?95.1%). Furthermore, when compared with the normal tissue from the matched healthy controls, increased deletion frequencies were observed in both adjacent non-cancerous tissue (OR?=?3.02, 95% CI?=?2.13–4.28, P<0.00001 for heterogeneity test, I2?=?53.7%), and cancerous tissue (OR?=?1.36, 95% CI?=?1.04–1.77, P?=?0.02 for heterogeneity test, I2?=?83.5%). This meta-analysis suggests that the mtDNA 4,977 bp deletion is often found in cancerous tissue and thus has the potential to be a biomarker for cancer occurrence in the tissue, but at the same time being selected against in various types of carcinoma tissues. Larger and better-designed studies are still warranted to confirm these findings. PMID:23861839

Vartak, Rasika; Milstein, Amanda Claire; Mo, Yalin; Hu, Xiaoqin; Fang, Hezhi; Shen, Lijun; Ding, Zhinan; Lu, Jianxin; Bai, Yidong

2013-01-01

230

Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies  

Microsoft Academic Search

Background: Ezetimibe (SCH 58235) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol.Objective: Data from 2 multicenter, placebo-controlled, double-blind, randomized, parallel-group, 12-week studies of ezetimibe were pooled to evaluate the drug's effect on lipid parameters in patients with primary hypercholesterolemia.Methods: After dietary stabilization (National Cholesterol Education Program Step I diet or

Harold E Bays; Paul B Moore; Margaret A Drehobl; Sidney Rosenblatt; Phillip D Toth; Carlos A Dujovne; Robert H Knopp; Leslie J Lipka; Alexandre P LeBeaut; Bo Yang; Lillian E Mellars; Cynthia Cuffie-Jackson; Enrico P Veltri

2001-01-01

231

Pooled Peer Ratings, Self-Ratings, and Estimated Ratings of Therapeutic Communication and Popularity: A Relational Analysis  

Microsoft Academic Search

Two studies of therapeutic communication and popularity were conducted in the framework of Dialogic Action Therapy (Ho & Wang, 2009) that accords centrality to the bidirectional nature of interpersonal perceptions. Pooled peer ratings, self-ratings, and estimates of peer ratings were collected from 88 Chinese students in psychology who knew one another well. Self-inflation was operationally defined as the self-rating minus

David Y. F. Ho

2010-01-01

232

Association of the vascular endothelial growth factor -2578C/A polymorphism with cancer risk: A meta-analysis update  

PubMed Central

The vascular endothelial growth factor (VEGF) -2578C/A polymorphism has been previously reported to be associated with cancer risk; however, the results have been controversial. Therefore, the aim of the present study was to explore the association between the VEGF -2578C/A polymorphism with the cancer risk. A total of 37 case-control studies were identified. The pooled analysis showed that there was no association between VEGF -2578C/A and the risk of cancer, and the odds ratios (ORs) [with the corresponding 95% confidence intervals (95% CIs)] were 0.97 (0.91–1.04) for C vs. A, 0.94 (0.86–1.02) for CC vs. AA, 0.92 (0.80–1.06) for CA vs. AA, 0.96 (0.89–1.03) for CC/CA vs. AA and 0.97 (0.88–1.08) for CC vs. CA/AA. Subgroup analyses according to ethnicity, source of control and type of cancer showed that the VEGF -2578C/A polymorphism is associated with colorectal and lung cancers. Additionally, the polymorphism may decrease the risk of cancer in the Asian population. This VEGF polymorphism was not associated with a risk of cancer for the Caucasian [0.92 (0.76–1.11) for CC vs. AA] and African populations [1.31 (0.67–2.58) for CC vs. AA], and it was not associated with bladder [1.06 (0.74–1.53) for CC/AA] and breast cancers [1.01 (0.90–1.15) for CC/AA]. Therefore, the present meta-analysis indicates that VEGF -2578C/A may only be associated with the risk of colorectal cancer, lung cancer and the Asian population. More studies with larger sample sizes are required to provide more conclusive evidence.

CHEN, QUANCHI; ZHOU, ZIFEI; SHAN, LIANGCHENG; HUA, YINGQI; ZENG, HUI; LIU, PENGCHENG; CAI, ZHENGDONG

2014-01-01

233

Association between NFKB1 -94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis  

PubMed Central

Nuclear factor-?B is associated with the pathogenesis of numerous malignancies, and the functional polymorphism ?94ins/del ATTG (rs28362491) in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the ?94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. We found that the NFKB1 promoter ?94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35). Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect. PMID:24895544

Tao, Jun; Cao, Qiang; Gu, Jinbao; Deng, Xiaheng; Wang, Jun; Liu, Xuzhong; Wang, Zijie; Wu, Bian; Lu, Qiang; Yin, Changjun

2014-01-01

234

DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis.  

PubMed

The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR). Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. Numerous epidemiological studies have been conducted to evaluate the association between XRCC3 polymorphisms and bladder cancer risk. However, the results of these previous studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis of all available studies relating XRCC3 polymorphisms and bladder cancer. All studies published up to April 2013 on the association between XRCC3 polymorphisms and bladder cancer risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature databases. The association between the XRCC3 polymorphisms and bladder cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 16 case-control studies met the inclusion criteria and were selected. With respect to C18067T polymorphism, significant increased bladder cancer risk was found when all eligible studies were pooled into the meta-analysis (TT vs. CC: OR?=?1.174, 95%CI?=?1.033-1.335, P?=?0.014 and recessive model TT vs. TC?+?CC: OR?=?1.147, 95%CI?=?1.020-1.290, P?=?0.022, respectively). The results were still significant after excluding the Hardy-Weinberg equilibrium violation studies (TT vs. CC: OR?=?1.178, 95%CI?=?1.036-1.339, P?=?0.013 and recessive model TT vs. TC?+?CC: OR?=?1.144, 95%CI?=?1.017-1.287, P?=?0.025, respectively). In subgroup analysis by ethnicity, significant elevated risk was found among Asians (dominant model TT?+?TC vs. CC: OR?=?1.285, 95%CI?=?1.012-1.631). In the subgroup analyses according to smoking status, no significant association was detected in all genetic comparison models. With respect to A17893G and A4541G polymorphisms, no significant association with bladder cancer risk was observed in the overall and subgroup analyses. This meta-analysis suggests that the XRCC3 C18067T polymorphism was associated with increased bladder cancer risk especially among Asians. However, the XRCC3 A17893G and A4541G polymorphisms may not play important roles in bladder carcinogenesis. Further studies with larger sample sizes are needed to validate our finds. PMID:24104500

Peng, Qiliu; Mo, Cuiju; Tang, Weizhong; Chen, Zhiping; Li, Ruolin; Zhai, Limin; Yang, Shi; Wu, Junrong; Sui, Jingzhe; Li, Shan; Qin, Xue

2014-03-01

235

Citrus fruit intake and bladder cancer risk: a meta-analysis of observational studies.  

PubMed

Abstract Epidemiological studies have investigated the association between citrus fruit and bladder cancer risk; however, the results are inconsistent. To assess these issues, we conducted a meta-analysis of currently available studies. We identified relevant articles by searching the MEDLINE and EMBASE databases. We calculated the summary relative risk (RR) with 95% confidence interval (95% CI) using a random effect model. We included eight case-control studies and six cohort studies in the meta-analysis. There was a significant inverse association between citrus fruit intake and bladder cancer risk in all pooled studies (RR: 0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92), but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest that citrus fruit intake is related to decreased bladder cancer risk. Subsequent well-designed, large prospective studies are needed to obtain better understanding of this relationship. PMID:24932663

Liang, Sudong; Lv, Gaofei; Chen, Weikai; Jiang, Jianxin; Wang, Jingqun

2014-11-01

236

Swimming pool granuloma  

MedlinePLUS

A swimming pool granuloma is a long-term (chronic) skin infection. It is caused by the bacteria Mycobacterium marinum . ... A swimming pool granuloma occurs when water containing Mycobacterium marinum bacteria enters a break in the skin. Signs of ...

237

Swimming pool cleaner poisoning  

MedlinePLUS

Swimming pool cleaner poisoning occurs when someone swallows these substances, touches the chemicals and acids in them, ... breathes in their fumes. Chlorine, a chemical in swimming pool cleaners, is more likely than the acids ...

238

Polymorphism of DNA methyltransferase 3B -149C/T and cancer risk: a meta-analysis.  

PubMed

Published data on the association between DNA methyltransferase (DNMT) 3B -149C/T polymorphism and cancer risk remain inconclusive. To derive a more precise estimation for this association, we performed a meta-analysis of 5,903 cancer cases and 8,132 controls from 22 published case-control studies. We used odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the strength of the association. Our meta-analysis suggested that DNMT3B -149C/T polymorphism was associated with the risk of head and neck cancer under heterozygote comparison (OR 0.73, 95 % CI 0.59-0.90) and dominant model (OR 1.75, 95 % CI 0.62-0.92), although no evidence of association between DNMT3B -149C/T polymorphism and cancer risk was observed as we compared in the pooled analyses (homozygote comparison: OR 0.96, 95 % CI 0.86-1.09; heterozygote comparison: OR 1.07, 95 % CI 0.86-0.32; dominant model: OR 1.03, 95 % CI 0.85-1.25; recessive model: OR 0.93, 95 % CI 0.8-1.08). More studies are needed to detect DNMT3B -149C/T polymorphism and its association with cancer in different ethnic populations incorporated with environment exposures in the susceptibility of different kinds of cancer. PMID:25433949

Zhu, Jing; Du, Songtao; Zhang, Jiaqi; Wang, Yingnan; Wu, Qiaoling; Ni, Jixiang

2015-01-01

239

Human Lung Cancer Risks from Radon - Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis.  

PubMed

Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m(-3) there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

Leonard, Bobby E; Thompson, Richard E; Beecher, Georgia C

2012-01-01

240

Human Lung Cancer Risks from Radon - Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis  

PubMed Central

Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m?3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2012-01-01

241

Systematic analysis of RNAi reports identifies dismal commonality at gene-level and reveals an unprecedented enrichment in pooled shRNA screens.  

PubMed

RNA interference (RNAi) has opened promising avenues to better understand gene function. Though many RNAi screens report on the identification of genes, very few, if any, have been further studied and validated. Data discrepancy is emerging as one of RNAi main pitfalls. We reasoned that a systematic analysis of lethality-based screens, since they score for cell death, would examine the extent of hit discordance at inter-screen level. To this end, we developed a methodology for literature mining and overlap analysis of several screens using both siRNA and shRNA flavors, and obtained 64 gene lists censoring an initial list of 7,430 nominated genes. We further performed a comparative analysis first at a global level followed by hit re-assessment under much more stringent conditions. To our surprise, none of the hits overlapped across the board even for PLK1, which emerged as a strong candidate in siRNA screens; but only marginally in the shRNA ones. Furthermore, EIF5B emerges as the most common hit only in the shRNA screens. A highly unusual and unprecedented result was the observation that 5,269 out of 6,664 nominated genes (~80%) in the shRNA screens were exclusive to the pooled format, raising concerns as to the merits of pooled screens which qualify hits based on relative depletions, possibly due to multiple integrations per cell, data deconvolution or inaccuracies in intracellular processing causing off-target effects. Without golden standards in place, we would encourage the community to pay more attention to RNAi screening data analysis practices, bearing in mind that it is combinatorial in nature and one active siRNA duplex or shRNA hairpin per gene does not suffice credible hit nomination. Finally, we also would like to caution interpretation of pooled shRNA screening outcomes. PMID:23848309

Bhinder, Bhavneet; Djaballah, Hakim

2013-11-01

242

Systematic analysis of RNAi reports identifies dismal commonality at gene-level & reveals an unprecedented enrichment in pooled shRNA screens  

PubMed Central

RNA interference (RNAi) has opened promising avenues to better understand gene function. Though many RNAi screens report on the identification of genes, very few, if any, have been further studied and validated. Data discrepancy is emerging as one of RNAi main pitfalls. We reasoned that a systematic analysis of lethality-based screens, since they score for cell death, would examine the extent of hit discordance at inter-screen level. To this end, we developed a methodology for literature mining and overlap analysis of several screens using both siRNA and shRNA flavors, and obtained 64 gene lists censoring an initial list of 7,430 nominated genes. We further performed a comparative analysis first at a global level followed by hit re-assessment under much more stringent conditions. To our surprise, none of the hits overlapped across the board even for PLK1, which emerged as a strong candidate in siRNA screens; but only marginally in the shRNA ones. Furthermore, EIF5B emerges as the most common hit only in the shRNA screens. A highly unusual and unprecedented result was the observation that 5,269 out of 6,664 nominated genes (~80%) in the shRNA screens were exclusive to the pooled format, raising concerns as to the merits of pooled screens which qualify hits based on relative depletions, possibly due to multiple integrations per cell, data deconvolution or inaccuracies in intracellular processing causing off-target effects. Without golden standards in place, we would encourage the community to pay more attention to RNAi screening data analysis practices, bearing in mind that it is combinatorial in nature and one active siRNA duplex or shRNA hairpin per gene does not suffice credible hit nomination. Finally, we also would like to caution interpretation of pooled shRNA screening outcomes. PMID:23848309

Bhinder, Bhavneet; Djaballah, Hakim

2013-01-01

243

Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: A meta-analysis  

Microsoft Academic Search

Purpose: To provide a comparison between radiotherapy with photons, protons and carbon-ions in the treatment of Non-Small-Cell Lung Cancer (NSCLC), performing a meta-analysis of observational studies. Methods: Eligible studies on conventional radiotherapy (CRT), stereotactic radiotherapy (SBRT), concurrent chemoradiation (CCR), proton therapy and carbon-ion therapy were searched through a systematic review. To obtain pooled estimates of 2- and 5-year disease-specific and

Janneke P. C. Grutters; Alfons G. H. Kessels; Madelon Pijls-Johannesma; Dirk De Ruysscher; Manuela A. Joore; Philippe Lambin

2010-01-01

244

The diagnostic value of monoclonal gastric cancer 7 antigen: a systematic review with meta-analysis.  

PubMed

The aim of this study is to explore the clinical characteristic and the diagnostic role of MG7-Ag in detecting gastric cancer (GC) through a systematic review and meta-analysis. Relevant manuscripts aiming at the application of serum MG7-Ag level in GC diagnosis were searched in PubMed, Embase, Chinese National Knowledge Infrastructure, VIP, and Wan Fang Data independently,which were published between January 1, 1980 and February 28, 2013. The pooled sensitivity, specificity,positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), diagnostic odds ratio,and the area under the summary receiver operating characteristic(AUC) were used to evaluate the value of serum MG7-Ag in diagnosis of GC by using the Meta-DiSc and STATA 11.0 statistical software. 410 manuscripts were retrieved, and 7 manuscripts of high quality including 652 patients were of high quality in this meta-analysis. Overall,the pooled sensitivity, specificity, DLR+, DLR-, and AUC were 0.73 (95 % CI 0.63-0.82), 0.91 (95 % CI 0.84-0.94), 8.59 (95 % CI 5.62-13.11), 0.29 (95 % CI 0.21-0.42), and 0.92 (95 % CI 0.89-0.94), respectively. MG7-Ag is a potential biomarker for the diagnosis of GC.However, more studies are needed to confirm the standard criteria. PMID:23797567

Zeng, Zongyue; Fu, Sheng; Hu, Ping; Zhao, Liuyang; Zhang, Hailong; Tang, Xi; Yang, Xiaorong; Zeng, Zhaofang

2014-08-01

245

Prognostic Significance of Neutrophil Lymphocyte Ratio in Patients with Gastric Cancer: A Meta-Analysis  

PubMed Central

Background Several studies have shown that neutrophil lymphocyte ratio (NLR) may be associated with the prognosis of gastric cancer (GC), but the results are controversial. Methods This study was performed to evaluate the prognostic implications of neutrophil lymphocyte ratio of GC in all available studies. We surveyed 2 medical databases, PubMed and EMBASE, to identifyall relevant studies. Data were collected from studies comparing overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) in patients with GC. Results Ten studies (n?=?2,952) evaluated the role of NLR as a predictor of outcome were involved for this meta-analysis (10 for OS, 3 for DFS, and 2 for PFS). Overall and disease-free survival were significantly better in patients with low NLR value and the pooled HRs was significant at 1.83 ([95% CI], 1.62–2.07) and 1.58 ([95% CI], 1.12–2.21), respectively. For progression-free survival, the pooled hazard ratio of NLR was significant at 1.54 ([95% CI], 1.22–1.95). No evidence of significant heterogeneity or publication bias for OS and DFS was seen in any of the included studies. Conclusion This meta-analysis indicated that elevated NLR may be associated with a worse prognosis for patients with GC. PMID:25401500

Feng, Li-jin

2014-01-01

246

Virtual Tide Pool  

NSDL National Science Digital Library

Virtual Tide Pool features a three dimensional view of a tide pool during both low and high tides. Students can see animals that live under, above, and at the waters surface. This site offers the ability to pan the tide pool for a 360 degree view, with zoom options, and gives descriptions of the animals found during both low and high tides.

Science NetLinks (PBS;)

2003-04-29

247

Fish consumption and risk of gastrointestinal cancers: A meta-analysis of cohort studies  

PubMed Central

AIM: To assess quantitatively the relationship between fish intake and the incidence of gastrointestinal cancers in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and the bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to fish intake. When RRs were not available in the published article, they were computed from the exposure distributions. Two investigators extracted the data independently and discrepancies were resolved by discussion with a third investigator. We performed random-effect meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 20-g/d increment of fish consumption. RESULTS: Forty-two studies, comprising 27 independent cohorts, met our inclusion criteria. The studies included 2325040 participants and 24115 incident cases of gastrointestinal cancer, with an average follow-up of 13.6 years. Compared with individuals who did not eat, or seldom ate, fish, the pooled RR of gastrointestinal cancers was 0.93 (95%CI: 0.88-0.98) for regular fish consumers, 0.94 (0.89-0.99) for low to moderate fish consumers, and 0.91 (0.84-0.97) for high fish consumers. Overall, a 20-g increase in fish consumption per day was associated with a 2% reduced risk of gastrointestinal cancers (RR = 0.98; 95%CI: 0.96-1.01). In subgroup analyses, we noted that fish consumption was associated with reduced risk of colorectal (RR = 0.93; 95%CI: 0.87-0.99; P < 0.01), esophageal (RR = 0.91; 95%CI: 0.83-0.99; P < 0.05) and hepatocellular cancers (RR = 0.71; 95%CI: 0.48-0.95; P < 0.01). CONCLUSION: This meta-analysis suggested that fish consumption may reduce total gastrointestinal cancer incidence. Inverse relationships were also detected between fish consumption and specific types of cancers. PMID:25386090

Yu, Xiao-Feng; Zou, Jian; Dong, Jie

2014-01-01

248

Vitamin D Supplementation and Breast Cancer Prevention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials  

PubMed Central

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L. PMID:23894438

Maugeri-Sacca, Marcello; Stranges, Saverio; Santesso, Nancy; Mariani, Luciano; Giordano, Antonio; Sergi, Domenico; Pizzuti, Laura; Di Lauro, Luigi; Montella, Maurizio; Crispo, Anna; Barba, Maddalena

2013-01-01

249

Vitamin D supplementation and breast cancer prevention: a systematic review and meta-analysis of randomized clinical trials.  

PubMed

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the "Related Article" feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I(2) test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74-1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23-1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54-1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L. PMID:23894438

Sperati, Francesca; Vici, Patrizia; Maugeri-Saccà, Marcello; Stranges, Saverio; Santesso, Nancy; Mariani, Luciano; Giordano, Antonio; Sergi, Domenico; Pizzuti, Laura; Di Lauro, Luigi; Montella, Maurizio; Crispo, Anna; Mottolese, Marcella; Barba, Maddalena

2013-01-01

250

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis  

SciTech Connect

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Garg, Madhur K. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Aparo, Santiago; Kaubisch, Andreas [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Tome, Wolfgang [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kennedy, Timothy J. [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2013-06-01

251

Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes  

PubMed Central

Background In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to sitagliptin. The purpose of the present analysis is to update the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies. Methods The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group) or a comparator agent (placebo or an active comparator) (N = 4,817; non-exposed group). The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin). Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events. Results Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were also generally similar between the two groups, except for increased incidence rates of hypoglycemia, related to the greater use of a sulfonylurea, and diarrhea, related to the greater use of metformin, in the non-exposed group and constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events. Conclusions In this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration. PMID:20412573

2010-01-01

252

Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials.  

PubMed

Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment success was significantly more likely for candidemia than invasive candidiasis. Both survival and treatment success were significantly less likely for the non-removal of catheter versus removal, Asian-Indians versus Caucasians, APACHE II score >20 to 30 versus or=70 years versus <50 years, baseline corticosteroids, and persistent neutropenia. Survival was also significantly less likely for treatment in other regions versus North America and for patients with renal failure at baseline. These findings help to define non-antifungal drug factors that may impact survival and treatment success in invasive candidiasis or candidemia. PMID:20013016

Horn, D L; Ostrosky-Zeichner, L; Morris, M I; Ullmann, A J; Wu, C; Buell, D N; Kovanda, L L; Cornely, O A

2010-02-01

253

Screening for cervical cancer: a systematic review and meta-analysis  

PubMed Central

Background The systematic review on which this paper is based provided evidence for the Canadian Task Force on Preventive Health Care to update their guideline regarding screening for cervical cancer. In this article we highlight three questions covered in the full review that pertain to the effectiveness of screening for reducing cervical cancer mortality and incidence as well as optimal timing and frequency of screening. Methods We searched MEDLINE, Embase and Cochrane Central from 1995 to 2012 for relevant randomized controlled trials and observational studies with comparison groups. Eligible studies included women aged 15 to 70 years who were screened using conventional cytology, liquid-based cytology or human papillomavirus DNA tests. Relevance screening, data extraction, risk of bias analyses and quality assessments were performed in duplicate. We conducted a meta-analysis using a random-effects model on the one body of evidence that could be pooled. Results From the 15,145 screened citations, 27 papers (24 studies) were included; five older studies located in a United States Preventive Services Task Force review were also included. A randomized controlled trial in India showed even a single lifetime screening test significantly decreased the risk of mortality from and incidence of advanced cervical cancer compared to no screening (mortality: risk ratio 0.65, 95% confidence interval 0.47, 0.90; incidence: relative risk 0.56, 95% confidence interval 0.42, 0.75). Cytology screening was shown to be beneficial in a cohort study that found testing significantly reduced the risk of being diagnosed with invasive cervical cancer compared to no screening (risk ratio 0.38; 95% confidence interval 0.23, 0.63). Pooled evidence from a dozen case–control studies also indicated a significant protective effect of cytology screening (odds ratio 0.35; 95% confidence interval 0.30, 0.41). This review found no conclusive evidence for establishing optimal ages to start and stop cervical screening, or to determine how often to screen; however the available data suggests substantial protective effects for screening women 30 years and older and for intervals of up to five years. Conclusions The available evidence supports the conclusion that cervical screening does offer protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality. PMID:23706117

2013-01-01

254

The Association between RAD23B Ala249Val Polymorphism and Cancer Susceptibility: Evidence from a Meta-Analysis  

PubMed Central

Background A number of studies have investigated associations of genetic variation in RAD23B Ala249Val (rs1805329 C>T) with cancer susceptibility; however, the findings are inconsistent. We performed a meta-analysis to acquire a more precise estimation of the relationship. Method We searched literatures from PubMed, Embase and Web of Science. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association between Ala249Val polymorphism and cancer risk. Results A total of 23 studies consisting of 10837 cases and 13971 controls were included in this meta-analysis. Overall, no significant associations were found between RAD23B Ala249Val polymorphism and cancer risk (Val/Val vs. Ala/Ala: OR?=?0.97, 95% CI?=?0.75–1.25; Ala/Val vs. Ala/Ala: OR?=?1.08, 95% CI?=?0.96–1.22; recessive model: OR?=?0.93, 95% CI?=?0.76–1.14 and dominant model: OR?=?1.07, 95% CI?=?0.94–1.20). We did not find any significant associations in the further stratification analyses by cancer type, ethnicity and source of control. Conclusions Despite some limitations, this meta-analysis indicates that it is unlikely that the RAD23B 249Val/Val polymorphism may contribute to the individual susceptibility to cancer risk. However, further advanced designed studies with larger sample size and different ethnicities should be conducted to confirm our results. PMID:24643114

Ying, Xiaojiang; Song, Junmin; Zhang, Ruoxin; Li, Zhen; Chen, Hongliang; Ye, Pingjiang; Shen, Yi; Pan, Weihuo; Chen, Zhiliang

2014-01-01

255

The -1082A>G polymorphism in promoter region of interleukin-10 and risk of digestive cancer: a meta-analysis.  

PubMed

The -1082A>G polymorphism is located in promoter region of interleukin-10 (IL-10) and it could affect the production of IL-10. Numerous studies have investigated the association between IL-10 -1082A>G and risk of digestive cancer. However, the conclusion is still inconsistent. Here, we have performed a meta-analysis and systematic review to determine the association between the IL-10 -1082A>G and susceptibility to digestive cancer. In this meta-analysis, we identified 40 eligible studies, involving 7195 patients of digestive cancer and 11755 controls. By pooling all eligible studies, we found the variant -1082G allele significantly increased risk of digestive cancer (G vs. A: OR = 1.181, 95% CI: 1.057-1.319). Further stratified analysis was performed to evaluate the influence of cancer types, ethnicities, study design, sample size and Hardy-Weinberg equilibrium. Stratified analysis suggested that, the -1082A>G polymorphism was only associated with increased risk for gastric cancer (G vs. A: OR = 1.281, 95% CI: 1.102-1.488) and in Asian population (G vs. A: OR = 1.399, 95% CI: 1.188-1.646). No significant publication bias was detected. Based on 40 studies and 18950 participants, we found the variant IL-10 -1082G allele significantly increased susceptibility to digestive cancer, especially for gastric cancer and in Asian population. PMID:25091209

Li, Chunxue; Tong, Weidong; Liu, Baohua; Zhang, Anping; Li, Fan

2014-01-01

256

The -1082A>G polymorphism in promoter region of interleukin-10 and risk of digestive cancer: a meta-analysis  

PubMed Central

The -1082A>G polymorphism is located in promoter region of interleukin-10 (IL-10) and it could affect the production of IL-10. Numerous studies have investigated the association between IL-10 -1082A>G and risk of digestive cancer. However, the conclusion is still inconsistent. Here, we have performed a meta-analysis and systematic review to determine the association between the IL-10 -1082A>G and susceptibility to digestive cancer. In this meta-analysis, we identified 40 eligible studies, involving 7195 patients of digestive cancer and 11755 controls. By pooling all eligible studies, we found the variant -1082G allele significantly increased risk of digestive cancer (G vs. A: OR = 1.181, 95% CI: 1.057–1.319). Further stratified analysis was performed to evaluate the influence of cancer types, ethnicities, study design, sample size and Hardy–Weinberg equilibrium. Stratified analysis suggested that, the -1082A>G polymorphism was only associated with increased risk for gastric cancer (G vs. A: OR = 1.281, 95% CI: 1.102–1.488) and in Asian population (G vs. A: OR = 1.399, 95% CI: 1.188–1.646). No significant publication bias was detected. Based on 40 studies and 18950 participants, we found the variant IL-10 -1082G allele significantly increased susceptibility to digestive cancer, especially for gastric cancer and in Asian population. PMID:25091209

Li, Chunxue; Tong, Weidong; Liu, Baohua; Zhang, Anping; Li, Fan

2014-01-01

257

Quantitative gated blood pool SPECT: Analysis of 3-dimensional models for the assessment of regional myocardial wall motion  

Microsoft Academic Search

Background  Gated blood pool single photon emission computed tomography (SPECT) (GBPS) uses truly 3-dimensional (3D) data, requiring attention\\u000a to appropriate reference systems and segmentation models for proper quantification. To date, optimal 3D reference models have\\u000a not been evaluated. In this study several techniques for 3D GBPS were evaluated.\\u000a \\u000a \\u000a \\u000a Methods and Results  Static and dynamic cardiac phantom evaluations were performed, and GBPS studies

Mark W. Groch; Dale J. Schippers; Robert C. Marshall; Paul J. Groch; William D. Erwin

2002-01-01

258

The role of acupoint stimulation as an adjunct therapy for lung cancer: a systematic review and meta-analysis  

PubMed Central

Background Lung cancer is the leading cause of death in cancer patients. Clinical studies showed that a variety of acupoint stimulations have been extensively used for lung cancer patients, including needle insertion, injection with herbal extraction, plaster application, and moxibustion. However, the role of acupoint stimulation in lung cancer treatment was not fully reviewed. Methods In the present study, we conducted a systematic review and meta-analysis on the role of acupoint stimulation in lung cancer treatment by electronic and manual searching in seven databases, including Ovid (Ovid MEDLINE, AMED, CAB Abstracts, EMBASE), EBSCOhost research databases (Academic Search premier, MEDLINE, CIHAHL Plus), PreQuest (British Nursing Index, ProQuest Medical Library, ProQuest Dissertations & Theses A&I, PsycINFO), and ISI web of knowledge (Web of Science, BIOSIS Citation Index, Biological Abstracts, Chinese Science Citation Database), CNKI, Wanfang Data, and CQVIP. Results Our study showed that acupoint stimulation has strong immunomodulatory effect for lung cancer patients as demonstrated by the significant increase of IL-2, T cell subtypes (CD3+ and CD4+, but not CD8+ cells), and natural killer cells. Further analysis revealed that acupoint stimulation remarkably alleviates the conventional therapy-induced bone marrow suppression (hemoglobin, platelet, and WBC reduction) in lung cancer patients, as well as decreases nausea and vomiting. The pooled studies also showed that acupoint stimulation can improve Karnofsky performance status, immediate tumor response, quality of life (EORCT-QLQ-C30), and pain control of cancer patients. Conclusions Acupoint stimulation is found to be effective in lung cancer treatment, further confirmatory evaluation via large scale randomized trials is warranted. PMID:24344728

2013-01-01

259

Cost Trend Analysis of Initial Cancer Treatment in Taiwan  

PubMed Central

Background Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment. Methodology/Principal Findings The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI) system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05). Hospitalization costs comprised the largest portion of payments for all cancers. During 1996–2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05). In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share. Conclusions/Significance In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit from these expensive treatments. PMID:25279947

Li, Tsai-Yun; Hsieh, Jan-Sing; Lee, King-Teh; Hou, Ming-Feng; Wu, Chia-Ling

2014-01-01

260

Associations of Suboptimal Growth with All-Cause and Cause-Specific Mortality in Children under Five Years: A Pooled Analysis of Ten Prospective Studies  

PubMed Central

Background Child undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies. Methods Pooled analysis involving children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (?2?Zanalysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality. Conclusions All degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases. PMID:23734210

Olofin, Ibironke; McDonald, Christine M.; Ezzati, Majid; Flaxman, Seth; Black, Robert E.; Fawzi, Wafaie W.; Caulfield, Laura E.; Danaei, Goodarz

2013-01-01

261

Integrative analysis of multiple cancer genomic datasets under the heterogeneity model.  

PubMed

In the analysis of cancer studies with high-dimensional genomic measurements, integrative analysis provides an effective way of pooling information across multiple heterogeneous datasets. The genomic basis of multiple independent datasets, which can be characterized by the sets of genomic markers, can be described using the homogeneity model or heterogeneity model. Under the homogeneity model, all datasets share the same set of markers associated with responses. In contrast, under the heterogeneity model, different studies have overlapping but possibly different sets of markers. The heterogeneity model contains the homogeneity model as a special case and can be much more flexible. Marker selection under the heterogeneity model calls for bi-level selection to determine whether a covariate is associated with response in any study at all as well as in which studies it is associated with responses. In this study, we consider two minimax concave penalty-based penalization approaches for marker selection under the heterogeneity model. For each approach, we describe its rationale and an effective computational algorithm. We conduct simulations to investigate their performance and compare with the existing alternatives. We also apply the proposed approaches to the analysis of gene expression data on multiple cancers. PMID:23519988

Liu, Jin; Huang, Jian; Ma, Shuangge

2013-09-10

262

Integrative analysis of multiple cancer genomic datasets under the heterogeneity model  

PubMed Central

In the analysis of cancer studies with high-dimensional genomic measurements, integrative analysis provides an effective way of pooling information across multiple heterogeneous datasets. The genomic basis of multiple independent datasets, which can be characterized by the sets of genomic markers, can be described using the homogeneity model or heterogeneity model. Under the homogeneity model, all datasets share the same set of markers associated with responses. In contrast, under the heterogeneity model, different studies have overlapping but possibly different sets of markers. The heterogeneity model contains the homogeneity model as a special case and can be much more flexible. Marker selection under the heterogeneity model calls for bi-level selection to determine whether a covariate is associated with response in any study at all as well as in which studies it is associated with responses. In this study, we consider two minimax concave penalty (MCP) based penalization approaches for marker selection under the heterogeneity model. For each approach, we describe its rationale and an effective computational algorithm. We conduct simulation to investigate their performance and compare with the existing alternatives. We also apply the proposed approaches to the analysis of gene expression data on multiple cancers. PMID:23519988

Liu, Jin; Huang, Jian; Ma, Shuangge

2013-01-01

263

Integrated quantitative fractal polarimetric analysis of monolayer lung cancer cells  

NASA Astrophysics Data System (ADS)

Digital diagnostic pathology has become one of the most valuable and convenient advancements in technology over the past years. It allows us to acquire, store and analyze pathological information from the images of histological and immunohistochemical glass slides which are scanned to create digital slides. In this study, efficient fractal, wavelet-based polarimetric techniques for histological analysis of monolayer lung cancer cells will be introduced and different monolayer cancer lines will be studied. The outcome of this study indicates that application of fractal, wavelet polarimetric principles towards the analysis of squamous carcinoma and adenocarcinoma cancer cell lines may be proved extremely useful in discriminating among healthy and lung cancer cells as well as differentiating among different lung cancer cells.

Shrestha, Suman; Zhang, Lin; Quang, Tri; Farrahi, Tannaz; Narayan, Chaya; Deshpande, Aditi; Na, Ying; Blinzler, Adam; Ma, Junyu; Liu, Bo; Giakos, George C.

2014-05-01

264

Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis comprising 9,911 cases and 11,171 controls.  

PubMed

Cyclin D1 represents a key molecule in the regulation of cell cycle. CCND1 G870A (rs603965) polymorphism has drawn considerable attention as the A allele may generate a variant splice product with possible oncogenic actions. A meta-analysis examining the association between CCND1 G870A polymorphism and breast cancer risk was performed. Separate analyses on Caucasian and Chinese populations were also implemented. Eligible articles were identified for the period up to July 2010. Pooled odds ratios (OR) were appropriately derived from fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg Equilibrium (HWE) was performed. Nine case-control studies on Caucasians (7,304 cases and 8,149 controls) and four case-control studies on Chinese (2,607 cases and 3,022 controls) were eligible. At the overall analysis the A allele seemed to be associated with elevated breast cancer risk; the effect seemed to be confined to homozygous carriers (pooled OR = 1.091, 95% CI: 1.008-1.179, P = 0.030, fixed effects) as heterozygous carriers did not exhibit significantly elevated breast cancer risk. No statistically significant associations were demonstrated in Caucasians. On the other hand, Chinese AA carriers exhibited marginally elevated breast cancer risk (pooled OR = 1.144, 95% CI: 0.984-1.329, P = 0.080, fixed effects). Nevertheless, the controls in two out of the four Chinese studies deviated from HWE. In conclusion, this meta-analysis suggests that the A allele of the CCND1 G870A polymorphism may confer additional breast cancer risk when it comes to homozygosity and Chinese populations. The need for additional, methodologically sound studies on Chinese populations seems warranted. PMID:21161398

Sergentanis, Theodoros N; Economopoulos, Konstantinos P

2011-11-01

265

Association of the Polymorphisms in the Fas/FasL Promoter Regions with Cancer Susceptibility: A Systematic Review and Meta-Analysis of 52 Studies  

PubMed Central

Fas and its ligand (FasL) play an important role in apoptosis and carcinogenesis. Therefore, the potential association of polymorphisms in the Fas (-670A>G, rs1800682; -1377G>A, rs2234767) and FasL (-844C>T, rs763110) with cancer risk has been widely investigated. However, all the currently available results are not always consistent. In this work, we performed a meta-analysis to further determine whether carriers of the polymorphisms in Fas and FasL of interest could confer an altered susceptibility to cancer. All relevant data were retrieved by PubMed and Web of Science, and 52 eligible studies were chosen for this meta-analysis. There was no association of the Fas -670A>G polymorphism with cancer risk in the pooled data. For the Fas -1377G>A and FasL -844C>T polymorphisms, results revealed that the homozygotes of -1377A and -844C were associated with elevated risk of cancer as a whole. Further stratified analysis indicated markedly increased risk for developing breast cancer, gastric cancer, and esophageal cancer, in particular in Asian population. We conclude that carriers of the Fas-1377A and the FasL -844C are more susceptible to the majority of cancers than non-carriers. PMID:24598538

Pan, Yuqin; Gao, Tianyi; Deng, Qiwen; Sun, Huiling; Song, Guoqi; Wang, Shukui

2014-01-01

266

Shotgun metagenomic analysis of metabolic diversity and microbial community structure in experimental vernal pools subjected to nitrate pulse  

PubMed Central

Background Human activities have greatly increased nitrogen (N) levels in natural habitats through atmospheric N deposition and nutrient leaching, which can have large effects on N cycling and other ecosystem processes. Because of the significant role microorganisms play in N cycling, high inputs of nitrogenous compounds, such as nitrate (NO3-), into natural ecosystems could have cascading effects on microbial community structure and the metabolic processes that microbes perform. To investigate the multiple effects of NO3- pollution on microbial communities, we created two shotgun metagenomes from vernal pool microcosms that were either enriched with a solution of 10 mg NO3--N (+NO3-) or received distilled water as a control (?N). Results After only 20 hours of exposure to NO3-, the initial microbial community had shifted toward one containing a higher proportional abundance of stress tolerance and fermentation environmental gene tags (EGTs). Surprisingly, we found no changes to N metabolism EGTs, even though large shifts in denitrification rates were seen between the?+NO3- and –N microcosms. Thus, in the absence of NO3- addition, it is plausible that the microbes used other respiratory pathways for energy. Respiratory pathways involving iron may have been particularly important in our –N microcosms, since iron acquisition EGTs were proportionally higher in the –N metagenome. Additionally, we noted a proportional increase in Acidobacteria and Alphaproteobacteria EGTs in response to NO3- addition. These community shifts in were not evident with TRFLP, suggesting that metagenomic analyses may detect fine-scale changes not possible with community profiling techniques. Conclusions Our results suggest that the vernal pool microbial communities profiled here may rely on their metabolic plasticity for growth and survival when certain resources are limiting. The creation of these metagenomes also highlights how little is known about the effects of NO3- pollution on microbial communities, and the relationship between community stability and function in response to disturbance. PMID:23574744

2013-01-01

267

Cancer epidemiology: study designs and data analysis  

Microsoft Academic Search

Among the scientific interests of cancer epidemiology is the identification of both environmental and genetic factors associated\\u000a with cancer development. Observational designs requiring sophisticated methodology are applied to control for potential confounding\\u000a factors. The enormous biotechnological potential developed in the last two decades has allowed the integration of a plethora\\u000a of new biomarkers in epidemiological studies to better define the

N. Malats; G. Castaño-Vinyals

2007-01-01

268

Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins  

PubMed Central

Background A limiting factor in performing proteomics analysis on cancerous cells is the difficulty in obtaining sufficient amounts of starting material. Cell lines can be used as a simplified model system for studying changes that accompany tumorigenesis. This study used two-dimensional gel electrophoresis (2DE) to compare the whole cell proteome of oral cancer cell lines vs normal cells in an attempt to identify cancer associated proteins. Results Three primary cell cultures of normal cells with a limited lifespan without hTERT immortalization have been successfully established. 2DE was used to compare the whole cell proteome of these cells with that of three oral cancer cell lines. Twenty four protein spots were found to have changed in abundance. MALDI TOF/TOF was then used to determine the identity of these proteins. Identified proteins were classified into seven functional categories – structural proteins, enzymes, regulatory proteins, chaperones and others. IPA core analysis predicted that 18 proteins were related to cancer with involvements in hyperplasia, metastasis, invasion, growth and tumorigenesis. The mRNA expressions of two proteins – 14-3-3 protein sigma and Stress-induced-phosphoprotein 1 – were found to correlate with the corresponding proteins’ abundance. Conclusions The outcome of this analysis demonstrated that a comparative study of whole cell proteome of cancer versus normal cell lines can be used to identify cancer associated proteins. PMID:24422745

2014-01-01

269

Diagnostic value of S100P for pancreatic cancer: a meta-analysis.  

PubMed

Pancreatic cancer (PC) is a fatal disease with a high mortality and poor prognosis. PC is the fourth leading cause of cancer death in America, and 80 % of PCs are diagnosed at an unresectable stage. Effective early detection assays are crucial since a successful operation at early stage is the best strategy for this disease. S100 calcium-binding protein P (S100P) has been reported as a predictive diagnostic index for PC and involves in the development of PC. However, the diagnostic accuracy of S100P in detecting PC has never been systematically assessed. The aim of the present study was to evaluate the diagnostic performance of S100P for PC. All relevant original articles about S100P in the diagnosis of PC published up to December 2013 were retrieved. The methodological quality of each study was assessed by QUADAS. The overall diagnostic sensitivity, specificity, diagnostic odds ratio (DOR), with 95 % confidence interval (CI), and area under the receiver operating characteristic curve (AUC) were pooled to evaluate the diagnostic value of S100P for PC using the Meta-DiSc1.4 statistical software. Eight studies met our criteria in the present meta-analysis. The pooled sensitivity, specificity, and DOR calculated by the bivariate random effects model were 0.87 (95 % CI 0.83-0.90), 0.88 (95 % CI 0.82-0.93), and 38.32 (95 % CI 11.22-130.87), respectively. The summary receiver operating characteristic (SROC) curve was located near the desirable left corner and the AUC was 0.9272. The current evidence suggests that S100P plays an important role in the diagnosis of PC with a high sensitivity and specificity. S100P may be regarded as a promising diagnostic marker to PC screening. PMID:25123266

Hu, Haolin; Zhang, Qi; Huang, Chenfei; Shen, Yi; Chen, Xundi; Shi, Xin; Tang, Wenhao

2014-10-01

270

Clinical significance of fibroblast growth factor receptor-3 mutations in bladder cancer: a systematic review and meta-analysis.  

PubMed

Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene are frequently found in bladder cancer, but their prognostic value remains controversial. To globally summarize the association between FGFR3 mutations and the grade and stage of bladder cancer, and to analyze the predictive role of FGFR3 mutations with respect to survival, eligible studies were identified and assessed for quality through multiple search strategies. Risk ratio (RR) data were collected from studies comparing the number of FGFR3 mutants among low-grade and early-stage bladder cancer patients to the number among high-grade and late-stage patients. Hazard ratio (HR) data were collected from studies comparing survival in patients with mutant FGFR3 genes to those with wild-type genes. Studies were pooled, and the RRs of grade and stage and the HRs of survival were calculated. Thirty studies were included in the present meta-analysis. FGFR3 mutations were found to be closely associated with low-grade and early-stage bladder cancer, showing pooled RRs = 2.948 [95% confidence interval (CI) = 2.357-3.688] and 2.845 (95%CI = 2.145- 3.773), respectively. Notably, patients with FGFR3 mutations tended to show better disease-, progress-, and recurrence-free survival (HR = 0.561, 95%CI = 0.405-0.779), and better disease-specific survival (HR = 0.363, 95%CI = 0.266-0.496). This study demonstrated that FGFR3 mutations are closely related to low grade, early stage, and better survival among bladder cancer patients. PMID:24634132

Liu, X; Zhang, W; Geng, D; He, J; Zhao, Y; Yu, L

2014-01-01

271

Analysis of leakage current mechanisms in Pt/Au Schottky contact on Ga-polarity GaN by Frenkel-Poole emission and deep level studies  

SciTech Connect

We report the Frenkel-Poole emission in Pt/Au Schottky contact on Ga-polarity GaN grown by molecular beam epitaxy using current-voltage-temperature (I-V-T) characteristics in the temperature ranging from 200 K to 375 K. Using thermionic emission model, the estimated Schottky barrier height is 0.49 eV at 200 K and 0.83 eV at 375 K, respectively, and it is observed that the barrier height increases with increase in temperature. The extracted emission barrier height ({phi}{sub t}) for Ga-polarity GaN Schottky diode by Frenkel-Poole theory is about 0.15 eV. Deep level transient spectroscopy study shows a deep level with activation energy of 0.44 eV, having capture cross-section 6.09 x 10{sup -14} cm{sup 2}, which is located between the metal and semiconductor interface, and trap nature is most probably associated with dislocations in Ga-polarity GaN. The analysis of I-V-T characteristics represents that the leakage current is due to effects of electrical field and temperature on the emission of electron from a trap state near the metal-semiconductor interface into continuum states associated with conductive dislocations in Ga-polarity GaN Schottky diode.

Rao, Peta Koteswara; Park, Byungguon; Lee, Sang-Tae; Noh, Young-Kyun; Kim, Moon-Deock [Department of Physics, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Oh, Jae-Eung [School of Electrical and Computer Engineering, Hanyang University, Ansan 425-791 (Korea, Republic of)

2011-07-01

272

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis.  

PubMed

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations. PMID:25339013

Fang, Xin-Yu; Xu, Wang-Dong; Huang, Qian; Yang, Xiao-Ke; Liu, Yan-Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2014-01-01

273

Genomic profile analysis of diffuse-type gastric cancers  

PubMed Central

Background Stomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome. Results We analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis. Conclusions We report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors. PMID:24690483

2014-01-01

274

Identification of circulating microRNAs as biomarkers in diagnosis of hematologic cancers: a meta-analysis.  

PubMed

Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for hematologic cancers. However, inconsistent results have been reported on the diagnostic performance of various kinds of miRNAs. To systematically assess the potential diagnostic value of miRNAs in hematologic cancers, we conducted the present meta-analysis. Multiple databases (PubMed, Cochrane Library, EMBASE, CNKI, and Wan Fang) were carefully searched for available studies up to April 4, 2014. Sensitivity and specificity were pooled using a random-effects model. Likelihood ratio (LR), diagnostic odds ratio (DOR), and the area under the curve (AUC) were used to measure the diagnostic values. Subgroup and meta-regression analyses were used to find potential sources of heterogeneity. Thirty-four studies from 14 publications, which involved 1,159 hematologic cancer patients and 826 healthy controls, were included in this meta-analysis. The pooled estimates indicated a moderately high diagnostic accuracy for circulating miRNAs, with a sensitivity of 0.83, a specificity of 0.85, a PLR of 5.7, a NLR of 0.20, a DOR of 29, and an AUC of 0.91. The subgroup analyses showed that diagnostic accuracy was better for acute myeloid leukemia (AML) patients and Asians compared with other subgroups. In addition, multiple miRNA assays displayed a better performance than single ones. Furthermore, we found that plasma might be a more promising matrix for detecting the expression of miRNAs than serum. Our results identified the potential use of circulating miRNAs in second-line diagnosis for hematologic cancers, especially the value of miRNA panels. However, further large cohort studies are still required to confirm our findings. PMID:25053601

Li, Quan; Liu, Long; Li, Weiming

2014-10-01

275

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer  

PubMed Central

Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. Results ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. Conclusions The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women. PMID:24758163

2014-01-01

276

SILAC-based quantitative proteomic analysis of gastric cancer secretome  

PubMed Central

Purpose Gastric cancer is a commonly occurring cancer in Asia and one of the leading causes of cancer deaths. However, there is no reliable blood-based screening test for this cancer. Identifying proteins secreted from tumor cells could lead to the discovery of clinically useful biomarkers for early detection of gastric cancer. Experimental design A SILAC-based quantitative proteomic approach was employed to identify secreted proteins that were differentially expressed between neoplastic and non-neoplastic gastric epithelial cells. Proteins from the secretome were subjected to SDS-PAGE and SCX-based fractionation, followed by mass spectrometric analysis on an LTQ-Orbitrap Velos mass spectrometer. Immunohistochemical labeling was employed to validate a subset of candidates using tissue microarrays. Results We identified 2,205 proteins in the gastric cancer secretome of which 263 proteins were overexpressed >4-fold in gastric cancer-derived cell lines as compared to non-neoplastic gastric epithelial cells. Three candidate proteins, proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin mannose binding 2 (LMAN2) and PDGFA associated protein 1 (PDAP1), were validated by immunohistochemical labeling. Conclusions and clinical relevance We report here the largest cancer secretome described to date. The novel biomarkers identified in the current study are excellent candidates for further testing as early detection biomarkers for gastric adenocarcinoma. PMID:23161554

Marimuthu, Arivusudar; Subbannayya, Yashwanth; Sahasrabuddhe, Nandini A.; Balakrishnan, Lavanya; Syed, Nazia; Sekhar, Nirujogi Raja; Katte, Teesta V.; Pinto, Sneha M.; Srikanth, Srinivas M.; Kumar, Praveen; Pawar, Harsh; Kashyap, Manoj K.; Maharudraiah, Jagadeesha; Ashktorab, Hassan; Smoot, Duane T; Ramaswamy, Girija; Kumar, Rekha V.; Cheng, Yulan; Meltzer, Stephen J; Roa, Juan Carlos; Chaerkady, Raghothama; Prasad, T.S. Keshava; Harsha, H. C.; Chatterjee, Aditi; Pandey, Akhilesh

2013-01-01

277

Plunge pools and paleoprecipitation  

Microsoft Academic Search

Sedimentary sequences in the form of ridges or terraces surrounding plunge pools at the base of waterfalls can provide records of past discharge and as a consequence an indirect measure of rainfall variations over many thousands of years. Waves generated by the waterfall deposit sands and pebbles as a beach at the perimeter of the plunge pool. As climatic conditions

Jonathan Nott; David Price

1994-01-01

278

Personality traits as risk factors for stroke and coronary heart disease mortality: pooled analysis of three cohort studies.  

PubMed

We examined whether personality traits are differently associated with coronary heart disease and stroke mortality. Participants were pooled from three prospective cohort studies (Health and Retirement Study, Wisconsin Longitudinal Study graduate and sibling samples; n = 24,543 men and women, mean age 61.4 years, mortality follow-up between 3 and 15 years). There were 423 coronary heart disease deaths and 88 stroke deaths during 212,542 person-years at risk. Higher extraversion was associated with an increased risk of stroke (hazard ratio per each standard deviation increase in personality trait HR = 1.41, 95 % CI 1.10-1.80) but not with coronary heart disease mortality (HR = 0.93, 0.83-1.05). High neuroticism, in turn, was more strongly related to the risk of coronary heart disease (HR = 1.16, 1.04-1.29) than stroke deaths (HR = 0.95, 0.78-1.17). High conscientiousness was associated with lower mortality risk from both coronary heart disease (HR = 0.74, 0.67-0.81) and stroke (HR = 0.78, 0.63-0.97). Cardiovascular risk associated with personality traits appears to vary between main cardiac and cerebral disease endpoints. PMID:24203126

Jokela, Markus; Pulkki-Råback, Laura; Elovainio, Marko; Kivimäki, Mika

2014-10-01

279

Insulin therapy contributes to the increased risk of colorectal cancer in diabetes patients: a meta-analysis  

PubMed Central

Background Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. Materials and methods A compressive search was conducted through MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature databases (CBM). Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Results A total of four studies with one case-controls study and three cohort studies comparing the insulin therapy and colorectal cancer susceptibility were identified. When all four studies were analyzed, the summary RRs were 1.61 (95% CI?=?1.18–1.35) in a random-effects model for individuals with insulin therapy, compared with individuals without insulin therapy, which suggests a statistically significant association between insulin use and colorectal cancer. Conclusions Our findings provides the evidence that insulin therapy may contribute to the risk of colorectal cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9339731010859509 PMID:24175949

2013-01-01

280

Reference Values and Age and Sex Differences in Physical Performance Measures for Community-Dwelling Older Japanese: A Pooled Analysis of Six Cohort Studies  

PubMed Central

Objectives To determine age- and sex-specific reference values for six physical performance measures, i.e. hand-grip strength, one-legged stance, and gait speed and step length at both usual and maximum paces, and to investigate age and sex differences in these measures among community-dwelling older Japanese adults. Methods We conducted a pooled analysis of data from six cohort studies collected between 2002 and 2011 as part of the Tokyo Metropolitan Institute of Gerontology-Longitudinal Interdisciplinary Study on Aging. The pooled analysis included cross-sectional data from 4683 nondisabled, community-dwelling adults aged 65 years or older (2168 men, 2515 women; mean age: 74.0 years in men and 73.9 years in women). Results Unweighted simple mean (standard deviation) hand-grip strength, one-legged stance, usual gait speed, usual gait step length, maximum gait speed, and maximum gait step length were 31.7 (6.7) kg, 39.3 (23.0) s, 1.29 (0.25) m/s, 67.7 (10.0) cm, 1.94 (0.38) m/s, and 82.3 (11.6) cm, respectively, in men and 20.4 (5.0) kg, 36.8 (23.4) s, 1.25 (0.27) m/s, 60.8 (10.0) cm, 1.73 (0.36) m/s, and 69.7 (10.8) cm, respectively, in women. All physical performance measures showed significant decreasing trends with advancing age in both sexes (all P<0.001 for trend). We also constructed age- and sex-specific appraisal standards according to quintiles. With increasing age, the sex difference in hand-grip strength decreased significantly (P<0.001 for age and sex interaction). In contrast, sex differences significantly increased in all other measures (all P<0.05 for interactions) except step length at maximum pace. Conclusion Our pooled analysis yielded inclusive age- and sex-specific reference values and appraisal standards for major physical performance measures in nondisabled, community-dwelling, older Japanese adults. The characteristics of age-related decline in physical performance measures differed between sexes. PMID:24923425

Seino, Satoshi; Shinkai, Shoji; Fujiwara, Yoshinori; Obuchi, Shuichi; Yoshida, Hideyo; Hirano, Hirohiko; Kim, Hun Kyung; Ishizaki, Tatsuro; Takahashi, Ryutaro

2014-01-01

281

Incidence and time course of extrapyramidal symptoms with oral and long-acting injectable paliperidone: a posthoc pooled analysis of seven randomized controlled studies  

PubMed Central

Background The purpose of this study was to compare incidence rates and time course of extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) between oral and long-acting injectable (LAI) paliperidone. Methods The analysis included pooled data (safety analysis set, 2,256 antipsychotic-treated and 865 placebo-treated patients with schizophrenia) from seven randomized, double-blind, placebo-controlled paliperidone studies (three oral [6 weeks each] and four LAI [9–13 weeks]) and assessed comparable doses (oral, 3–15 mg; LAI, 25–150 mg eq. [US doses 39–234 mg]). We summarized incidence rates and time of onset for EPS-related TEAE, categorized by EPS group terms, ie, tremor, dystonia, hyperkinesia, parkinsonism, and dyskinesia, and use of anti-EPS medication. Mean scores over time for the Abnormal Involuntary Movement Scale (AIMS, for dyskinesia), Barnes Akathisia Rating Scale (BARS, for akathisia), and Simpson Angus Rating Scale (SAS, for parkinsonism) were graphed. Results Incidence rates for all categories of spontaneously reported EPS-related TEAEs except for hyperkinesia, were numerically lower in pooled LAI studies than in pooled oral studies. Highest rates were observed in the first week of paliperidone-LAI (for all EPS symptoms except dyskinesia) and oral paliperidone treatment (except parkinsonism and tremor). Anti-EPS medication use was significantly lower in LAI (12%) versus oral studies (17%, P = 0.0035). Mean values for EPS scale scores were similar between LAI and oral treatment at endpoint, and no dose response was evident. Mean reductions (standard deviation) from baseline to endpoint in EPS scale scores were larger for LAI (AIMS, ?0.10 [1.27]; BARS, ?0.09 [1.06]; SAS, ?0.04 [0.20]) versus oral studies (AIMS, ?0.08 [1.32]; BARS, ?0.03 [1.24]; SAS, 0.0 [0.23]). These changes favored LAI for BARS (P = 0.023) and SAS (P < 0.0001), but not for AIMS (P = 0.49), at endpoint for the studies. Conclusion In this posthoc descriptive analysis, incidence rates of spontaneously reported EPS-related TEAEs were numerically lower following approximately 90 days of exposure with LAI and approximately 40 days with oral paliperidone at comparable doses. PMID:24092977

Gopal, Srihari; Liu, Yanning; Alphs, Larry; Savitz, Adam; Nuamah, Isaac; Hough, David

2013-01-01

282

Prognostic and clinicopathological significance of microRNA-21 overexpression in breast cancer: a meta-analysis  

PubMed Central

Recent studies have highlighted the role of microRNA-21 (miR-21) as a prognostic biomarker of breast cancer. However, controversy still remains. The present study aimed to summarize available evidences and obtain a more precise estimation of a prognostic role of miR-21 in breast cancer patients. All eligible studies were searched from PubMed and EMBASE through multiple search strategies. Data were extracted from studies comparing survival in breast cancer patients having higher miR-21 expression with those having lower expression. A meta-analysis was performed to clarify prognostic role of miR-21 in patients with breast cancer. Subgroup analysis was also performed according to patients’ ethnicity. A total of 6 eligible articles comprising 951 cases were selected for this meta-analysis. The combined hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall survival (OS) were 2.11 (1.09-4.08) and for disease free survival (DFS) was 1.6 (1.30-1.96). Subgroup analysis indicated high miR-21 expression was significantly associated with worse OS in Asian patients (HR = 4.39, 95% CI: 2.47-7.80) but not in non-Asian patients (HR = 1.18, 95% CI: 0.81-1.70). Sensitivity analysis revealed results of this meta-analysis were robust. Odds ratios (ORs) showed that miR-21 expression was closely associated with estrogen receptor (ER), progesterone receptor (PR), lymph node metastasis, histological grade, Her2/neu. The pooled ORs and 95% CIs were 0.53 (0.35-0.80), 0.49 (0.32-0.74), 2.32 (1.54-3.50), 2.44 (1.58-3.75), 4.29 (2.34-7.85), respectively. Our results indicated that elevated miR-21 expression could potentially predict poor survival in patients with breast cancer. PMID:25337203

Pan, Fei; Mao, Hui; Deng, Ling; Li, Guangchao; Geng, Peiliang

2014-01-01

283

Supplement To: Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer  

E-print Network

-Breast Cancer, PC-Prostate Cancer, CRC-Colorectal Cancer, RCC-Renal Cell Carcinoma, OC-Ovarian Cancer, GC(A-C), CS-Clinical Stage, rem.-Remission, GIC- Gastrointestinal Cancer, OC-Ovarian Cancer, LC ­ Lung Cancer1 Supplement To: Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer Carmen

Popel, Aleksander S.

284

Coupled Two-Way Clustering Analysis of Breast Cancer and Colon Cancer Gene Expression Data  

E-print Network

We present and review Coupled Two Way Clustering, a method designed to mine gene expression data. The method identifies submatrices of the total expression matrix, whose clustering analysis reveals partitions of samples (and genes) into biologically relevant classes. We demonstrate, on data from colon and breast cancer, that we are able to identify partitions that elude standard clustering analysis.

Getz, G; Kela, I; Domany, E; Notterman, D A; Getz, Gad; Gal, Hilah; Kela, Itai; Domany, Eytan; Notterman, Dan A.

2003-01-01

285

Improving Breast Cancer Survival Analysis through Competition-Based Multidimensional Modeling  

E-print Network

Improving Breast Cancer Survival Analysis through Competition-Based Multidimensional Modeling Erhan. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine Cancer Medicine Centre, Cambridge, United Kingdom, 20 Cambridge Breast Unit, Cambridge University

286

Gene network-based cancer prognosis analysis with sparse boosting.  

PubMed

High-throughput gene profiling studies have been extensively conducted, searching for markers associated with cancer development and progression. In this study, we analyse cancer prognosis studies with right censored survival responses. With gene expression data, we adopt the weighted gene co-expression network analysis (WGCNA) to describe the interplay among genes. In network analysis, nodes represent genes. There are subsets of nodes, called modules, which are tightly connected to each other. Genes within the same modules tend to have co-regulated biological functions. For cancer prognosis data with gene expression measurements, our goal is to identify cancer markers, while properly accounting for the network module structure. A two-step sparse boosting approach, called Network Sparse Boosting (NSBoost), is proposed for marker selection. In the first step, for each module separately, we use a sparse boosting approach for within-module marker selection and construct module-level 'super markers'. In the second step, we use the super markers to represent the effects of all genes within the same modules and conduct module-level selection using a sparse boosting approach. Simulation study shows that NSBoost can more accurately identify cancer-associated genes and modules than alternatives. In the analysis of breast cancer and lymphoma prognosis studies, NSBoost identifies genes with important biological implications. It outperforms alternatives including the boosting and penalization approaches by identifying a smaller number of genes/modules and/or having better prediction performance. PMID:22950901

Ma, Shuangge; Huang, Yuan; Huang, Jian; Fang, Kuangnan

2012-08-01

287

Gene network-based cancer prognosis analysis with sparse boosting  

PubMed Central

Summary High-throughput gene profiling studies have been extensively conducted, searching for markers associated with cancer development and progression. In this study, we analyse cancer prognosis studies with right censored survival responses. With gene expression data, we adopt the weighted gene co-expression network analysis (WGCNA) to describe the interplay among genes. In network analysis, nodes represent genes. There are subsets of nodes, called modules, which are tightly connected to each other. Genes within the same modules tend to have co-regulated biological functions. For cancer prognosis data with gene expression measurements, our goal is to identify cancer markers, while properly accounting for the network module structure. A two-step sparse boosting approach, called Network Sparse Boosting (NSBoost), is proposed for marker selection. In the first step, for each module separately, we use a sparse boosting approach for within-module marker selection and construct module-level ‘super markers ’. In the second step, we use the super markers to represent the effects of all genes within the same modules and conduct module-level selection using a sparse boosting approach. Simulation study shows that NSBoost can more accurately identify cancer-associated genes and modules than alternatives. In the analysis of breast cancer and lymphoma prognosis studies, NSBoost identifies genes with important biological implications. It outperforms alternatives including the boosting and penalization approaches by identifying a smaller number of genes/modules and/or having better prediction performance. PMID:22950901

Ma, Shuangge; Huang, Yuan; Huang, Jian; Fang, Kuangnan

2013-01-01

288

Cancerous tissues in forensic genetic analysis.  

PubMed

Microsatellites or short tandem repeats (STRs) markers are important tools for mapping disease-causing genes by linkage, for performing investigations in forensic medicine, for population genetic studies and for studying genetic modifications in tumors. In forensic applications neoplastic tissues can be used as a source of genetic information for personal identification or paternity testing when no other specimen is available. Cancer tissues can show microsatellite instability (MSI) and loss of heterozygosity (LOH) also for the STRs used in the forensic field. In this study, we screened 56 sporadic gastrointestinal carcinomas in order to provide further data for the evaluation of the incidence of allelic alterations for 15 STR loci and the suitability of using cancerous tissues in forensic applications. Sixty-six percent of the cancerous tissues were found to possess allelic alterations of the microsatellites analyzed with a high incidence of MSI-L (microsatellite instability low) when compared to the corresponding normal tissue. The most frequently altered loci were D18S51, VWA, and FGA. From a forensic perspective, great care must be taken in evaluating the DNA typing results obtained from cancerous tissue samples. PMID:18294056

Pelotti, Susi; Ceccardi, Stefania; Alù, Milena; Lugaresi, Federica; Trane, Rachele; Falconi, Mirella; Bini, Carla; Cicognani, Alberto

2007-01-01

289

Cancer detection by spectral analysis Samy Tindel  

E-print Network

) Specificity , i.e. P( Negative test | Healthy ) often not satisfying Samy T. (Nancy) Spectral classification treatment 2: Efficient, non-invasive and cheap diagnosis tests Possibility (experimental level): For certain study: Bladder cancer, animal experiment (rat) Samy T. (Nancy) Spectral classification Purdue - 2009 4

Tindel, Samy - Institut de Mathématiques �lie Cartan, Université Henri Poincaré

290

Integrative analysis of a cancer somatic mutome  

Microsoft Academic Search

BACKGROUND: The consecutive acquisition of genetic alterations characterizes neoplastic processes. As a consequence of these alterations, molecular interactions are reprogrammed in the context of highly connected and regulated cellular networks. The recent identification of the collection of somatically mutated genes in breast tumors (breast cancer somatic \\

Pilar Hernández; Xavier Solé; Joan Valls; Víctor Moreno; Gabriel Capellá; Ander Urruticoechea; Miguel Angel Pujana

2007-01-01

291

What?s in the Pool? A Comprehensive Identification of Disinfection By-Products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water  

EPA Science Inventory

Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in pool water and related those DBPs to the mutagenicity of pool wate...

292

Low Rates of Treatment Failure in Children Aged 2-59 Months Treated for Severe Pneumonia: A Multisite Pooled Analysis  

PubMed Central

Background.?Despite advances in childhood pneumonia management, it remains a major killer of children worldwide. We sought to estimate global treatment failure rates in children aged 2–59 months with World Health Organization–defined severe pneumonia. Methods.?We pooled data from 4 severe pneumonia studies conducted during 1999–2009 using similar methodologies. We defined treatment failure by day 6 as death, danger signs (inability to drink, convulsions, abnormally sleepy), fever (?38°C) and lower chest indrawing (LCI; days 2–3), LCI (day 6), or antibiotic change. Results.?Among 6398 cases of severe pneumonia from 10 countries, 564 (cluster adjusted: 8.5%; 95% confidence interval [CI], 5.9%–11.5%) failed treatment by day 6. The most common reasons for clinical failure were persistence of fever and LCI or LCI or fever alone (75% of failures). Seventeen (0.3%) children died. Danger signs were uncommon (<1%). Infants 6–11 months and 2–5 months were 2- and 3.5-fold more likely, respectively, to fail treatment (adjusted OR [AOR], 1.8 [95% CI, 1.4–2.3] and AOR, 3.5 [95% CI, 2.8–4.3]) as children aged 12–59 months. Failure was increased 7-fold (AOR, 7.2 [95% CI, 5.0–10.5]) when comparing infants 2–5 months with very fast breathing to children 12–59 months with normal breathing. Conclusions.?Our findings demonstrate that severe pneumonia case management with antibiotics at health facilities or in the community is associated with few serious morbidities or deaths across diverse geographic settings and support moves to shift management of severe pneumonia with oral antibiotics to outpatients in the community. PMID:23264361

Fox, Matthew P.; Thea, Donald M.; Sadruddin, Salim; Bari, Abdul; Bonawitz, Rachael; Hazir, Tabish; Bin Nisar, Yasir; Qazi, Shamim A.

2013-01-01

293

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies123  

PubMed Central

Background: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. Objective: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. Design: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. Results: During 4–10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. Conclusion: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes. PMID:19211817

Jakobsen, Marianne U; O'Reilly, Eilis J; Heitmann, Berit L; Pereira, Mark A; Balter, Katarina; Fraser, Gary E; Goldbourt, Uri; Hallmans, Goran; Knekt, Paul; Liu, Simin; Pietinen, Pirjo; Spiegelman, Donna; Stevens, June; Virtamo, Jarmo; Willett, Walter C; Ascherio, Alberto

2009-01-01

294

A GEOGRAPHIC ANALYSIS OF PROSTATE CANCER MORTALITY IN THE UNITED STATES, 197089  

E-print Network

of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA 2 DivisionA GEOGRAPHIC ANALYSIS OF PROSTATE CANCER MORTALITY IN THE UNITED STATES, 1970­89 Ahmedin JEMAL 1 of cancer mortality in the United States revealed that prostate cancer mortality rates were elevated among

Wright, Dawn Jeannine

295

Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials  

SciTech Connect

Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results: Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p < 0.0001). However, there was no difference in the mortality rate (p = 0.38) and specific prostate cancer mortality rates (p = 0.45) between the groups receiving HDRT and CDRT. However, there were more cases of late Grade >2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.

Viani, Gustavo Arruda [Department of Radiation Oncology, Marilia School of Medicine, Sao Paulo (Brazil)], E-mail: gusviani@gmail.com; Stefano, Eduardo Jose; Afonso, Sergio Luis [Department of Radiation Oncology, Marilia School of Medicine, Sao Paulo (Brazil)

2009-08-01

296

Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer  

PubMed Central

Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case–control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10?6, 1.6 × 10?5, 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10?5), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H. pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. PMID:22523087

Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gallinger, Steven; Gross, Myron; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Mandelson, Margaret T.; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J.Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Goran; Hankinson, Susan E.; Hoffman Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay-Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Shu, Xiao-Ou; Tj?nneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Watters, Joanne; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.

2012-01-01

297

Analysis of 3,000 Cancer Exomes to Identify Novel Cancer Drivers and Therapeutic Opportunities - Nickolay Khazanov, TCGA Scientific Symposium 2012  

Cancer.gov

Home News and Events Multimedia Library Videos Analysis of 3,000 Cancer Exomes - Nickolay Khazanov Analysis of 3,000 Cancer Exomes to Identify Novel Cancer Drivers and Therapeutic Opportunities - Nickolay Khazanov, TCGA Scientific Symposium 2012 You

298

Saturation of an Intra-Gene Pool Linkage Map: Towards a Unified Consensus Linkage Map for Fine Mapping and Synteny Analysis in Common Bean  

PubMed Central

Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364×G19833 (DG) and BAT93×JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning. PMID:22174773

Galeano, Carlos H.; Fernandez, Andrea C.; Franco-Herrera, Natalia; Cichy, Karen A.; McClean, Phillip E.; Vanderleyden, Jos; Blair, Matthew W.

2011-01-01

299

Evaluation of Current Consensus Statement Recommendations for Accelerated Partial Breast Irradiation: A Pooled Analysis of William Beaumont Hospital and American Society of Breast Surgeon MammoSite Registry Trial Data  

SciTech Connect

Purpose: To determine whether the American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) recommendations for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial. Methods and Materials: APBI was used to treat 2127 cases of early-stage breast cancer (WBH, n=678; ASBrS, n=1449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3-dimensional conformal radiation therapy, n=206), whereas all Registry Trial patients received balloon-based brachytherapy. Patients were divided according to the ASTRO CS into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CS group. Results: The median age was 65 years (range, 32-94 years), and the median tumor size was 10.0 mm (range, 0-45 mm). The median follow-up time was 60.6 months. The WBH cohort had more node-positive disease (6.9% vs 2.6%, P<.01) and cautionary patients (49.5% vs 41.8%, P=.06). The 5-year actuarial ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%. The rate of IBTR was not statistically higher between suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (P=.20). The nonsignificant increase in IBTR for the cautionary and unsuitable categories was due to increased elsewhere failures and new primaries (P=.04), not tumor bed recurrence (P=.93). Conclusions: Excellent outcomes after breast-conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CS guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure in this large patient cohort.

Wilkinson, J. Ben [Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States)] [Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Beitsch, Peter D. [Dallas Surgical Group, Dallas, Texas (United States)] [Dallas Surgical Group, Dallas, Texas (United States); Shah, Chirag [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States)] [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Arthur, Doug [Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia (United States)] [Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia (United States); Haffty, Bruce G. [Department of Radiation Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Camden, New Jersey (United States)] [Department of Radiation Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Camden, New Jersey (United States); Wazer, David E. [Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts and Rhode Island Hospital/Brown University, Providence, Rhode Island (United States)] [Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts and Rhode Island Hospital/Brown University, Providence, Rhode Island (United States); Keisch, Martin [Department of Radiation Oncology, Cancer Healthcare Associates, Miami, Florida (United States)] [Department of Radiation Oncology, Cancer Healthcare Associates, Miami, Florida (United States); Shaitelman, Simona F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lyden, Maureen [Biostat International, Inc, Tampa, Florida (United States)] [Biostat International, Inc, Tampa, Florida (United States); Chen, Peter Y. [Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States)] [Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Vicini, Frank A., E-mail: fvicini@pol.net [Department of Radiation Oncology, Michigan Healthcare Professionals/21st Century Oncology, Farmington Hills, Michigan (United States)

2013-04-01

300

Proteomics Analysis for Finding Serum Markers of Ovarian Cancer  

PubMed Central

A combination of peptide ligand library beads (PLLB) and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS) was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4) is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08?ng/mL with the mean value 89.13 ± 1.67?ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85 ± 2.38?ng/mL). Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.

Cheng, Yushan; Liu, Chongdong; Zhang, Nawei; Wang, Shengdian; Zhang, Zhenyu

2014-01-01

301

No Chemopreventive Effect of Nonsteroidal Anti-Inflammatory Drugs on Nonmelanoma Skin Cancer: Evidence from Meta-Analysis  

PubMed Central

Background Nonmelanoma skin cancer (NMSC),which includes squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is the most common form of cancer, and its incidence is increasing. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to be chemopreventive for NMSC. However, the results from published studies were controversial. Methods We searched the PubMed and Embase databases for relevant studies. Moreover, relevant reviews regarding the use of NSAIDs for NMSC patients were examined for potential inclusive studies. To measure the effects of NSAIDs, the relative risk (RR) was analyzed. Results A Total of 8 studies were included in our meta-analysis. We found that NSAIDs use was not associated with a reduced risk of SCC or BCC under the random effects model (pooled RR ?=? 0.86, 95% CI, 0.73–1.02, P ?=? 0.085; pooled RR ?=? 0.94, 95% CI 0.85–1.04, P ?=? 0.266; respectively). Conclusion From the included studies, we found no statistically significant chemopreventive effect on NMSC of NSAIDs. This finding warrants more prospective studies evaluating the relationship between NSAIDs and NMSC. PMID:24828489

Wang, Yungui

2014-01-01

302

Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression  

PubMed Central

One of the most persistent hallmarks of cancer biology is the preference of tumor cells to derive energy through glycolysis as opposed to the more efficient process of oxidative phosphorylation (OXPHOS). However, little is known about the molecular cascades by which oncogenic pathways bring about this metabolic switch. We carried out a quantitative proteomic and metabolic analysis of the MCF10A derived cell line model of breast cancer progression that includes parental cells and derivatives representing three different tumor grades of Ras-driven cancer with a common genetic background. A SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in conjunction with subcellular fractionation to measure dynamic subcellular localization in the nucleus, cytosol and mitochondria. Protein expression and localization across cell lines were compared to cellular metabolic rates as a measure of oxidative phosphorylation (OXPHOS), glycolysis and cellular ATP. Investigation of the metabolic capacity of the four cell lines revealed that cellular OXPHOS decreased with breast cancer progression independently of mitochondrial copy number or electron transport chain protein expression. Furthermore, glycolytic lactate secretion did not increase in accordance with cancer progression and decreasing OXPHOS capacity. However, the relative expression and subcellular enrichment of enzymes critical to lactate and pyruvate metabolism supported the observed extracellular acidification profiles. This analysis of metabolic dysfunction in cancer progression integrated with global protein expression and subcellular localization is a novel and useful technique for determining organelle-specific roles of proteins in disease. PMID:24086712

Shaw, Patrick G.; Chaerkady, Raghothama; Wang, Tao; Vasilatos, Shauna; Huang, Yi; Van Houten, Bennett; Pandey, Akhilesh; Davidson, Nancy E.

2013-01-01

303

Analysis of HOX gene expression patterns in human breast cancer.  

PubMed

HOX genes are highly conserved transcription factors that determine the identity of cells and tissues along the anterior-posterior body axis in developing embryos. Aberrations in HOX gene expression have been shown in various tumors. However, the correlation of HOX gene expression patterns with tumorigenesis and cancer progression has not been fully characterized. Here, to analyze putative candidate HOX genes involved in breast cancer tumorigenesis and progression, the expression patterns of 39 HOX genes were analyzed using breast cancer cell lines and patient-derived breast tissues. In vitro analysis revealed that HOXA and HOXB gene expression occurred in a subtype-specific manner in breast cancer cell lines, whereas most HOXC genes were strongly expressed in most cell lines. Among the 39 HOX genes analyzed, 25 were chosen for further analysis in malignant and non-malignant tissues. Fourteen genes, encoding HOXA6, A13, B2, B4, B5, B6, B7, B8, B9, C5, C9, C13, D1, and D8, out of 25 showed statistically significant differential expression patterns between non-malignant and malignant breast tissues and are putative candidates associated with the development and malignant progression of breast cancer. Our data provide a valuable resource for furthering our understanding of HOX gene expression in breast cancer and the possible involvement of HOX genes in tumor progression. PMID:23820980

Hur, Ho; Lee, Ji-Yeon; Yun, Hyo Jung; Park, Byeong Woo; Kim, Myoung Hee

2014-01-01

304

Prevalence of Human Papillomavirus and Cervical Intraepithelial Neoplasia in China: A pooled analysis of 17 Population-based Studies  

PubMed Central

High-risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR-HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly inform on the cervical cancer burden in the country. 30,207 women from 17 population-based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen), visual inspection with acetic acid, and liquid-based cytology. Women positive for any test received colposcopy-directed or 4-quadrant biopsies. 29,579 women had HR-HPV testing results, of whom 28,761 had biopsy-confirmed (9019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR-HPV prevalence was 17.7%. HR-HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25–29 years (11.3%) in rural and at age 35–39 (11.3%) in urban women. In rural and urban women, age-standardized CIN2 prevalence was 1.5% (95%CI: 1.4%–1.6%) and 0.7% (95%CI: 0.7%–0.8%), and CIN3+ prevalence was 1.2% (95%CI: 1.2%–1.3%) and 0.6% (95%CI: 0.5%–0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR-HPV positive women steadily increased with age, peaking in 45–49 year-old women. High prevalence of HR-HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group 45–49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is under-reported. PMID:22488743

Zhao, Fang-Hui; Lewkowitz, Adam K.; Hu, Shang-Ying; Chen, Feng; Li, Long-Yu; Zhang, Qing-Ming; Wu, Rui-Fang; Li, Chang-Qing; Wei, Li-Hui; Xu, Ai-Di; Zhang, Wen-Hua; Pan, Qin-Jing; Zhang, Xun; Belinson, Jerome L.; Sellors, John W.; Smith, Jennifer S.; Qiao, You-Lin; Franceschi, Silvia

2012-01-01

305

A model simulation analysis of soil nitrate concentrations—Does soil organic matter pool structure or catch crop growth parameters matter most?  

Microsoft Academic Search

Three different soil organic matter (SOM) submodels were tested within the framework of the soil–plant–atmosphere model Daisy. The three submodels were: the original Daisy SOM module (OLD) with relatively non-dynamic humus pools, a recalibrated Daisy SOM module (STD) with the same pool structure as the original, but with a more rapid turnover of the active humus pool, and a newly

Anders Pedersen; Bjørn M. Petersen; Jørgen Eriksen; Søren Hansen; Lars S. Jensen

2007-01-01

306

Nanobiodevice-based single biomolecule analysis, single-cell analysis, and in vivo imaging for cancer diagnosis, cancer theranostics, and iPS cell-based regenerative medicine.  

PubMed

Numerous nanobiodevices have been developed for cancer diagnosis through the analysis of cancer cells and cancer-related biomolecules, cancer gene therapy, and iPS cell-based regenerative medicine. A microchamber array, which is fabricated on a plastic chip, enables to develop a reliable circulating tumor cell (CTC) detection technique for cancer metastasis diagnosis. A nanopillar-array or a nanowire-array on a quartz chip allows ultrafast analysis of DNA and microRNA within 1 s for the molecular diagnosis of cancer. Immunopillar devices, which contain a tremendous amount of antibody-immobilized microparticles inside an immunopillar structure, have realized fast and low invasive "from blood to analysis" type biomarker detection of cancer with a pM detection sensitivity within 5 min. Quantum dots and gene delivery nanodevices are applied to single cancer cell diagnosis, in vivo imaging for iPS cell based regenerative medicine, and theranostic devices for cancer diagnosis and therapy. PMID:25213813

Kaji, Noritada; Baba, Yoshinobu

2014-01-01

307

Safety and tolerability of canakinumab, an IL-1? inhibitor, in type 2 diabetes mellitus patients: a pooled analysis of three randomised double-blind studies  

PubMed Central

Background We aimed to assess the safety and tolerability of different doses of canakinumab versus placebo in patients with type 2 diabetes mellitus (T2DM). Methods Data were pooled from three studies in 1026 T2DM patients with different routes of administration, treatment regimens and follow-up duration. Canakinumab groups were categorised as low (0.03 mg/kg i.v. once; N = 20), intermediate (0.1 and 0.3 mg/kg i.v. once, 5 and 15 mg s.c. monthly; N = 247), medium (1.5 mg/kg i.v. once, 50 mg s.c. monthly and 150 mg s.c. once; N = 268), and high doses (10 mg/kg i.v. once and 150 mg s.c. monthly; N = 137) and compared with placebo (N = 354). Incidences of adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs, deaths, AEs of special interest related to interleukin-1? inhibition and T2DM disease, and laboratory abnormalities related to haematology and biochemistry parameters were reported. Safety was also analysed by age (<65, ?65) and gender. Results Average exposure across all groups was???6 months (maximum ~17 months). No dose response in AEs was observed but a trend towards more patients having at least one AE across canakinumab groups relative to placebo (P?=?0.0152) was observed. SAEs were few and the incidence rate for most canakinumab groups was lower than that of placebo group except for the high-dose group (0.94% versus 0.58% per month in placebo). A total of five patients discontinued treatment due to AEs across treatment groups. No death was reported in any of the three studies. A small, non-significant increase in the incidence rate of infection AEs was observed on canakinumab groups relative to placebo. Canakinumab was associated with mostly mild decreases in WBC, neutrophils and platelet counts. Additionally, mild increases in SGPT, SGOT and bilirubin were reported. Overall, despite small differences, no clinically relevant findings were observed with respect to laboratory values and vital signs. Conclusions This pooled analysis demonstrated that canakinumab was safe and well tolerated over a treatment period up to 1.4 years at the four pooled doses evaluated, in agreement with safety findings reported in the individual studies. PMID:24884602

2014-01-01

308

Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis  

PubMed Central

Summary Background Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. Methods For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. Findings Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11–26·12). Interpretation Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4—the reduction of child mortality. Funding Bill & Melinda Gates Foundation. PMID:23746775

Katz, Joanne; Lee, Anne CC; Kozuki, Naoko; Lawn, Joy E; Cousens, Simon; Blencowe, Hannah; Ezzati, Majid; Bhutta, Zulfiqar A; Marchant, Tanya; Willey, Barbara A; Adair, Linda; Barros, Fernando; Baqui, Abdullah H; Christian, Parul; Fawzi, Wafaie; Gonzalez, Rogelio; Humphrey, Jean; Huybregts, Lieven; Kolsteren, Patrick; Mongkolchati, Aroonsri; Mullany, Luke C; Ndyomugyenyi, Richard; Nien, Jyh Kae; Osrin, David; Roberfroid, Dominique; Sania, Ayesha; Schmiegelow, Christentze; Silveira, Mariangela F; Tielsch, James; Vaidya, Anjana; Velaphi, Sithembiso C; Victora, Cesar G; Watson-Jones, Deborah; Black, Robert E

2013-01-01

309

A Descriptive Analysis of Lung Cancer in Montgomery County, Ohio  

Microsoft Academic Search

Background: Lung cancer statistics are alarming, especially when it is considered by many to largely be a preventable disease. Lung cancers are the leading cause of all cancer deaths, more than breast cancer, prostate cancer, and colon cancer combined. Cancers of the bronchus and lung make up the greatest percentage of the newly diagnosed cancers reported to the Ohio Cancer

Catherine Klose

2012-01-01

310

Association between cytochrome P450 1A1 MspI polymorphism and endometrial cancer risk: a meta-analysis.  

PubMed

Many studies proposed that cytochrome P450 1A1 (CYP1A1) MspI polymorphism may be associated with endometrial cancer risk, but the findings from previous studies reported conflicting results. A meta-analysis of all relevant studies was performed to get a comprehensive assessment of the association between CYP1A1 MspI polymorphism and endometrial cancer risk. Eligible studies were searched in PubMed and China National Knowledge Infrastructure databases. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association. Twelve studies with a total of 2,111 cases and 2,894 controls were finally included into the meta-analysis. Overall, meta-analysis of a total of 12 studies showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk (ORC vs. T = 0.97, 95 % CI 0.77-1.22, P OR = 0.808; ORCC vs. TT = 1.00, 95 % CI 0.57-1.76, P OR = 0.994; ORCC vs. TT/TC = 0.88, 95 % CI 0.65-1.20, P OR = 0.425; ORCC/TC vs. TT = 0.98, 95 % CI 0.74-1.29, P OR = 0.861). Subgroup analyses by ethnicity further showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk in both Caucasians and Asians. There was no obvious risk of publication bias. Therefore, the meta-analysis suggests that CYP1A1 MspI polymorphism is not associated with endometrial cancer risk. PMID:23918309

Han, Linxiao; Liu, Yanyan; Cao, Weiwei; Yuan, Xiuying; Li, Cuifeng

2013-10-01

311

Pools for the Handicapped.  

ERIC Educational Resources Information Center

Three institutions in Ohio now stress hydrotherapy and water recreation as important parts of individual educational programs for the handicapped. Specially designed and adapted pools provide freedom of movement and ego building as well as physical education and recreation. (Author)

American School and University, 1979

1979-01-01

312

The Vernal Pool Association  

NSDL National Science Digital Library

This site is based at Reading Memorial High School in Reading, MA. It features general information defining and describing vernal pools as a habitat type, including an illustrated cartoon series. Resources for educators and students include suggestions for classroom and field trip activities, examples of school projects, field guides, and teacher resources such as workshops. While this site contains several references to state-specific resources and regulations, it is relevant and useful outside of Massachusetts wherever vernal pools are found. The teacher responsible for the text on this site spent a sabbatical developing a resource kit for educators, which is available for purchase. Links are provided to scientific researchers conducting vernal pool studies, including their methods and results. There is an extensive page of resources, both digital in print. Educators and students are encouraged to download and use the collection of 78 slides of vernal pools and associated species on this site.

Kenney, Leo

313

Weld pool phenomena  

SciTech Connect

During welding, the composition, structure and properties of the welded structure are affected by the interaction of the heat source with the metal. The interaction affects the fluid flow, heat transfer and mass transfer in the weld pool, and the solidification behavior of the weld metal. In recent years, there has been a growing recognition of the importance of the weld pool transport processes and the solid state transformation reactions in determining the composition, structure and properties of the welded structure. The relation between the weld pool transport processes and the composition and structure is reviewed. Recent applications of various solidification theories to welding are examined to understand the special problems of weld metal solidification. The discussion is focussed on the important problems and issues related to weld pool transport phenomena and solidification. Resolution of these problems would be an important step towards a science based control of composition, structure and properties of the weld metal.

David, S.A.; Vitek, J.M.; Zacharia, T. [Oak Ridge National Lab., TN (United States); DebRoy, T. [Pennsylvania State Univ., University Park, PA (United States)

1994-09-01

314

Swimming Pool Accessibility.  

National Technical Information Service (NTIS)

This project was conducted for the U.S. Architecture and Transportation Barriers Compliance Board to identify and evaluate methods and standards related to enabling access to swimming pools by peolple with disabilities, It focuses on the appropriateness, ...

E. J. Hamilton, K. Mispagel, R. Bloomer

1996-01-01

315

Comprehensive analysis of microRNAs in breast cancer  

PubMed Central

Background MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22 nucleotides in length) that play important roles in breast cancer progression by downregulating gene expression. The detailed mechanisms and biological functions of miRNA molecules in breast carcinogenesis have yet to be fully elucidated. This study used bioinformatics and experimental approaches to conduct detailed analysis of the dysregulated miRNAs, arm selection preferences, 3' end modifications, and position shifts in isoforms of miRNAs (isomiRs) in breast cancer. Methods Next-generation sequencing (NGS) data on breast cancer was obtained from the NCBI Sequence Read Archive (SRA). The miRNA expression profiles and isomiRs in normal breast and breast tumor tissues were determined by mapping the clean reads back to human miRNAs. Differences in miRNA expression and pre-miRNA 5p/3p arm usage between normal and breast tumor tissues were further investigated using stem-loop reverse transcription and real-time polymerase chain reaction. Results The analysis identified and confirmed the aberrant expression of 22 miRNAs in breast cancer. Results from pathway enrichment analysis further indicated that the aberrantly expressed miRNAs play important roles in breast carcinogenesis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Data also indicated that the position shifts in isomiRs and 3' end modifications were consistent in breast tumor and adjacent normal tissues, and that 5p/3p arm usage of some miRNAs displayed significant preferences in breast cancer. Conclusions Expression pattern and arm selection of miRNAs are significantly varied in breast cancers through analyzing NGS data and experimental approach. These miRNA candidates have high potential to play critical roles in the progression of breast cancer and could potentially provide as targets for future therapy. PMID:23281739

2012-01-01

316

Assessment of the Potential Diagnostic Value of Serum p53 Antibody for Cancer: A Meta-Analysis  

PubMed Central

Background Mutant p53 protein over-expression has been reported to induce serum antibodies against p53. We assessed the diagnostic precision of serum p53 (s-p53) antibodies for diagnosis of cancer patients and compared the positive rates of the s-p53 antibody in different types of cancers. Methods We systematically searched PubMed and Embase, through May 31, 2012. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and Area under the curve(AUC). Meta regression and subgroup analyses were done, and heterogeneity and publication bias were assessed. Results Of 1089 studies initially identified, 100 eligible studies with 23 different types of tumor met the inclusion criteria for the meta-analysis (cases?=?15953, controls?=?8694). However, we could conduct independent meta analysis on only 13 of 36 types of tumors. Approximately 56% (56/100) of the included studies were of high quality (QUADAS score?8). The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of cancers were: PLR 5.75 (95% CI: 4.60–7.19), NLR 0.81 (95%CI: 0.79–0.83) and DOR 7.56 (95% CI: 6.02–9.50). However, for the 13 types of cancers on which meta-analysis was conducted, the ranges for PLR (2.33–11.05), NLR (0.74–0.97), DOR (2.86–13.80), AUC(0.29–0.81), and positive rate (4.47%–28.36%) indicated significant heterogeneity. We found that breast, colorectal, esophageal, gastric, hepatic, lymphoma, lung and ovarian cancer had relatively reasonable diagnostic accuracy. The remaining results of the five types of cancers suggested that s-p53 antibody had limited value. Conclusions The current evidence suggests that s-p53 antibody has potential diagnostic value for cancer, especially for breast, colorectal, esophageal, gastric, hepatic, lymphoma, lung and ovarian cancer. The results showed that s-p53 antibody had high correlation with cancers. PMID:24911057

Zhang, Jun; Xu, Zhiwei; Yu, Lingxiang; Chen, Meilan; Li, Ke

2014-01-01

317

Dose response of umeclidinium administered once or twice daily in patients with COPD: A pooled analysis of two randomized, double-blind, placebo-controlled studies.  

PubMed

Umeclidinium (UMEC) is an inhaled long-acting muscarinic antagonist approved in the US and EU for the once-daily (QD) treatment of chronic obstructive pulmonary disease (COPD); it is not indicated for the treatment of asthma. To fully characterize the dose-response relationship of UMEC in patients with COPD, a pooled analysis of data from two randomized, placebo-controlled, cross-over, dose-ranging studies was performed, evaluating UMEC at doses of 15.6-1000 mcg QD and 15.6-250 mcg twice daily (BID). The primary endpoint was trough forced expiratory volume in one second (FEV1 ) at the end of each study's treatment period (Day 8/Day 15). A population model-based analysis using total daily UMEC dose was used for the primary analysis comparing QD and BID dosing. A physiological effect (Emax ) model was optimal in defining the relationship between UMEC dose and the primary endpoint, demonstrating a clear monotonic dose response over QD and BID dosing regimens. UMEC doses ?62.5 mcg QD were differentiated from lower doses and BID dosing did not provide benefit over QD dosing. The potency (ED50 ) estimate was 33 mcg with QD dosing. These data indicate that UMEC 62.5 mcg and 125 mcg QD provide lung function benefits that warrant further investigation for the treatment of COPD. PMID:24895108

Donohue, James F; Kalberg, Christopher; Shah, Palvi; Beerahee, Misba; Mehta, Rashmi; Gunawan, Rudy; Church, Alison

2014-11-01

318

Postoperative bladder and sexual function in patients undergoing surgery for rectal cancer: a systematic review and meta-analysis of laparoscopic versus open resection of rectal cancer.  

PubMed

There have been conflicting opinions regarding the superiority of open and laparoscopic surgery in preserving bladder and sexual function after rectal cancer surgery. This systematic review and meta-analysis aims to pool the available data comparing the impact of surgical approaches on postoperative sexual and urinary function. A search of Pubmed, Medline, Cochrane and Embase was undertaken and studies from January 2000 to February 2013 were identified. We included, in our meta-analysis, both prospective and retrospective studies that compared laparoscopic surgery and open surgery for rectal cancer. A total of 876 patients undergoing rectal cancer surgery (lap n = 468, open n = 408) were examined. In men, postoperative ejaculatory function and erectile dysfunction evaluated from two studies comprising of 74 patients showed no difference between groups. The rate of overall sexual dysfunction evaluated from five studies comprising of 289 patients revealed a rate of 34 % in both the open and lap groups. Postoperative urinary function evaluated from five studies comprising of 312 patients showed no difference between groups. In women, postoperative sexual and urinary function were evaluated from five studies comprising of 321 patients. Three studies (n = 219) reported no difference in sexual function between groups. Postoperative urinary function evaluated from four studies comprising of 212 patients was found to be comparable. The available data are limited, but suggest that neither form of surgical approach be it laparoscopy or open surgery demonstrate superiority in preservation of sexual and bladder function. Further research into the technical aspects of surgery and evaluating newer minimally invasive technologies such as the robot may prove to be useful in improving functional outcomes of rectal cancer patients. PMID:25056719

Lim, R S; Yang, T X; Chua, T C

2014-11-01

319

Membrane proteomic analysis of pancreatic cancer cells  

PubMed Central

Background Pancreatic cancer is one of the most aggressive human tumors due to its high potential of local invasion and metastasis. The aim of this study was to characterize the membrane proteomes of pancreatic ductal adenocarcinoma (PDAC) cells of primary and metastatic origins, and to identify potential target proteins related to metastasis of pancreatic cancer. Methods Membrane/membrane-associated proteins were isolated from AsPC-1 and BxPC-3 cells and identified with a proteomic approach based on SDS-PAGE, in-gel tryptic digestion and liquid chromatography with tandem mass spectrometry (LC-MS/MS). X! Tandem was used for database searching against the SwissProt human protein database. Results We identified 221 & 208 proteins from AsPC-1 and BxPC-3 cells, respectively, most of which are membrane or membrane-associated proteins. A hundred and nine proteins were found in both cell lines while the others were present in either AsPC-1 or BxPC-3 cells. Differentially expressed proteins between two cell lines include modulators of cell adhesion, cell motility or tumor invasion as well as metabolic enzymes involved in glycolysis, tricarboxylic acid cycle, or nucleotide/lipid metabolism. Conclusion Membrane proteomes of AsPC-1 (metastatic) and BxPC-3 (primary) cells are remarkably different. The differentially expressed membrane proteins may serve as potential targets for diagnostic and therapeutic interventions. PMID:20831833

2010-01-01

320

The Detergent-Soluble Cytoplasmic Pool of Survivin Suppresses Anoikis and Its Expression Is Associated with Metastatic Disease of Human Colon Cancer  

PubMed Central

Survivin is a component of the chromosomal passenger complex (CPC) that is essential for accurate chromosome segregation. Interfering with the function of Survivin in mitosis leads to chromosome segregation errors and defective cytokinesis. Survivin contains a Baculovirus IAP Repeat (BIR) and therefore was originally classified as inhibitor of apopotosis protein (IAP), yet its role in apoptosis after cellular stress remains largely unknown. We demonstrate here, that Survivin predominantly suppresses anoikis, a form of programmed cell death induced by loss of cellular adhesion to extracellular matrix. Interestingly, cells ectopically overexpressing EGFP-Survivin showed after loss of cell-matrix-interaction a decreased expression of I?B-?. Subsequent subcellular protein fractionation and immunoprecipitation experiments revealed that XIAP interacts with detergent-soluble Survivin which is known to cooperatively activate NF-?B signaling. Examination of the expression levels of detergent soluble Survivin in colorectal cancer cell lines and in colorectal cancerous tissues revealed that detergent soluble cytoplasmic Survivin levels correlated inversely with anoikis susceptibility in colorectal cancer. Therefore, the detergent soluble cytoplasmic Survivin might be a promising predictive biomarker for lymph node and distant metastases of colorectal cancer. We conclude that an anti-apoptotic function of detergent-soluble Survivin in interphase cells experiencing anoikis is mediated at least via XIAP/I?B-?/NF-?B signaling. PMID:23405201

Hori, Masato; Miki, Tomoharu; Okamoto, Mayumi; Yazama, Futoshi; Konishi, Hiroaki; Kaneko, Hiroshi; Shimamoto, Fumio; Ota, Takahide; Temme, Achim; Tatsuka, Masaaki

2013-01-01

321

The detergent-soluble cytoplasmic pool of survivin suppresses anoikis and its expression is associated with metastatic disease of human colon cancer.  

PubMed

Survivin is a component of the chromosomal passenger complex (CPC) that is essential for accurate chromosome segregation. Interfering with the function of Survivin in mitosis leads to chromosome segregation errors and defective cytokinesis. Survivin contains a Baculovirus IAP Repeat (BIR) and therefore was originally classified as inhibitor of apopotosis protein (IAP), yet its role in apoptosis after cellular stress remains largely unknown. We demonstrate here, that Survivin predominantly suppresses anoikis, a form of programmed cell death induced by loss of cellular adhesion to extracellular matrix. Interestingly, cells ectopically overexpressing EGFP-Survivin showed after loss of cell-matrix-interaction a decreased expression of I?B-?. Subsequent subcellular protein fractionation and immunoprecipitation experiments revealed that XIAP interacts with detergent-soluble Survivin which is known to cooperatively activate NF-?B signaling. Examination of the expression levels of detergent soluble Survivin in colorectal cancer cell lines and in colorectal cancerous tissues revealed that detergent soluble cytoplasmic Survivin levels correlated inversely with anoikis susceptibility in colorectal cancer. Therefore, the detergent soluble cytoplasmic Survivin might be a promising predictive biomarker for lymph node and distant metastases of colorectal cancer. We conclude that an anti-apoptotic function of detergent-soluble Survivin in interphase cells experiencing anoikis is mediated at least via XIAP/I?B-?/NF-?B signaling. PMID:23405201

Hori, Masato; Miki, Tomoharu; Okamoto, Mayumi; Yazama, Futoshi; Konishi, Hiroaki; Kaneko, Hiroshi; Shimamoto, Fumio; Ota, Takahide; Temme, Achim; Tatsuka, Masaaki

2013-01-01

322

Bcl-2 expression and patient survival in gastric cancer: a systematic review of the literature with meta-analysis.  

PubMed

The prognostic role of Bcl-2 in gastric cancer remains controversial. We systematically reviewed the evidence for the effect of Bcl-2 expression in gastric cancer to elucidate this issue. PubMed, EMBASE, and Web of Science were searched to identify eligible studies to evaluate the association between Bcl-2 expression and overall survival (OS) and clinicopathological features of gastric cancer. Hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence interval (95 % CI) were pooled to estimate the effect. Bcl-2 expression was not significantly correlated with OS of gastric cancer patients (combined HR 0.88, 95 % CI 0.62-1.25). Subgroup analysis indicated that Bcl-2 expression had a favorable impact on OS in Asian countries (HR 0.60, 95 % CI 0.47-0.77) and cutoff value <15 % (HR 0.69, 95 % CI 0.48-0.97). Furthermore, Bcl-2 expression was significantly associated with TNM stage (OR 0.58, 95 % CI 0.41-0.80), the depth of invasion (OR 0.53, 95 % CI 0.37-0.76), and lymph node metastasis (OR 0.55, 95 % CI 0.42-0.71). Bcl-2 expression predicts less invasion and malignancy in clinicopathological features. Moreover, Bcl-2 could be a favorable prognostic marker for patients of Asian countries. PMID:25428392

Cheng, Haidong; Wang, Xiumei; Li, Tao; Chen, Lin

2015-01-01

323

Metabolic control analysis of respiration in human cancer tissue  

PubMed Central

Bioenergetic profiling of cancer cells is of great potential because it can bring forward new and effective therapeutic strategies along with early diagnosis. Metabolic Control Analysis (MCA) is a methodology that enables quantification of the flux control exerted by different enzymatic steps in a metabolic network thus assessing their contribution to the system‘s function. Our main goal is to demonstrate the applicability of MCA for in situ studies of energy metabolism in human breast and colorectal cancer cells as well as in normal tissues. We seek to determine the metabolic conditions leading to energy flux redirection in cancer cells. A main result obtained is that the adenine nucleotide translocator exhibits the highest control of respiration in human breast cancer thus becoming a prospective therapeutic target. Additionally, we present evidence suggesting the existence of mitochondrial respiratory supercomplexes that may represent a way by which cancer cells avoid apoptosis. The data obtained show that MCA applied in situ can be insightful in cancer cell energetic research. PMID:23825460

Kaambre, Tuuli; Chekulayev, Vladimir; Shevchuk, Igor; Tepp, Kersti; Timohhina, Natalja; Varikmaa, Minna; Bagur, Rafaela; Klepinin, Aleksandr; Anmann, Tiia; Koit, Andre; Kaldma, Andrus; Guzun, Rita; Valvere, Vahur; Saks, Valdur

2013-01-01

324

The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis  

PubMed Central

Background NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association. Methods All studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results Ten studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR?=?1.145, 95% CI?=?1.008–1.301, P?=?0.038; Ser/Ser?+?Ser/Pro vs. Pro/Pro: OR?=?1.177, 95% CI?=?1.041–1.331, P?=?0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR?=?1.180, 95% CI?=?1.035–1.344, P?=?0.013; Ser/Ser?+?Ser/Pro vs. Pro/Pro: OR?=?1.191, 95% CI?=?1.050–1.350, P?=?0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected. Conclusions Our meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. Further large and well-designed studies are needed to confirm this association. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504 PMID:24884893

2014-01-01

325

Parametric and Nonparametric Analysis of Breast Cancer Treatments  

Microsoft Academic Search

The objective of the present research manuscript is to perform parametric, nonparametric, and decision tree analysis to evaluate two treatments that are being used for breast cancer patients. Our study is based on utilizing real data which was initially used in \\

Chunling Cong; P. Tsokos

2010-01-01

326

Genomic analysis and selected molecular pathways in rare cancers  

NASA Astrophysics Data System (ADS)

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

2012-12-01

327

Computer-based interaction analysis of the cancer consultation.  

PubMed Central

There are few data available on which to base recommendations for effective communication in the cancer consultation. This paper describes a computerised interaction analysis system designed specifically for the cancer consultation and its application in a study investigating the relationship between doctor-patient behaviour and patient outcomes. One hundred and forty-two cancer patients attending their first consultation with a cancer specialist were audio taped and a copy of the tape was retained for interaction analysis. Before the consultation patient anxiety and information and involvement preferences were measured. Outcomes included recall of information, patient satisfaction with the consultation and psychological adjustment to cancer. Doctor behaviour was shown to vary significantly according to the age, sex, involvement preferences and in/out-patient status of the patient. The ratio of doctor to patient talk was related to satisfaction with communication, while patients whose questions were answered showed better psychological adjustment at follow-up. The results suggest that patient-centred consultations lead to improved satisfaction and psychological adjustment. These data provide precise information about consultation behaviour which can be used in the documentation of current practice and the evaluation of new interventions to improve communication. PMID:7734311

Butow, P. N.; Dunn, S. M.; Tattersall, M. H.; Jones, Q. J.

1995-01-01

328

Systematic analysis of genotype-specific drug responses in cancer.  

PubMed

A systematic understanding of genotype-specific sensitivity or resistance to anticancer agents is required to provide improved patient therapy. The availability of an expansive panel of annotated cancer cell lines enables comparative surveys of associations between genotypes and compounds of various target classes. Thus, one can better predict the optimal treatment for a specific tumor. Here, we present a statistical framework, cell line enrichment analysis (CLEA), to associate the response of anticancer agents with major cancer genotypes. Multilevel omics data, including transcriptome, proteome and phosphatome data, were integrated with drug data based on the genotypic classification of cancer cell lines. The results reproduced known patterns of compound sensitivity associated with particular genotypes. In addition, this approach reveals multiple unexpected associations between compounds and mutational genotypes. The mutational genotypes led to unique protein activation and gene expression signatures, which provided a mechanistic understanding of their functional effects. Furthermore, CLEA maps revealed interconnections between TP53 mutations and other mutations in the context of drug responses. The TP53 mutational status appears to play a dominant role in determining clustering patterns of gene and protein expression profiles for major cancer genotypes. This study provides a framework for the integrative analysis of mutations, drug responses and omics data in cancers. PMID:22422301

Kim, Nayoung; He, Ningning; Kim, Changsik; Zhang, Fan; Lu, Yiling; Yu, Qinghua; Stemke-Hale, Katherine; Greshock, Joel; Wooster, Richard; Yoon, Sukjoon; Mills, Gordon B

2012-11-15

329

A Genome-Wide Systematic Analysis Reveals Different and Predictive Proliferation Expression Signatures of Cancerous vs. Non-Cancerous Cells  

PubMed Central

Understanding cell proliferation mechanisms has been a long-lasting goal of the scientific community and specifically of cancer researchers. Previous genome-scale studies of cancer proliferation determinants have mainly relied on knockdown screens aimed to gauge their effects on cancer growth. This powerful approach has several limitations such as off-target effects, partial knockdown, and masking effects due to functional backups. Here we employ a complementary approach and assign each gene a cancer Proliferation Index (cPI) that quantifies the association between its expression levels and growth rate measurements across 60 cancer cell lines. Reassuringly, genes found essential in cancer gene knockdown screens exhibit significant positive cPI values, while tumor suppressors exhibit significant negative cPI values. Cell cycle, DNA replication, splicing and protein production related processes are positively associated with cancer proliferation, while cellular migration is negatively associated with it – in accordance with the well known “go or grow” dichotomy. A parallel analysis of genes' non-cancerous proliferation indices (nPI) across 224 lymphoblastoid cell lines reveals surprisingly marked differences between cancerous and non-cancerous proliferation. These differences highlight genes in the translation and spliceosome machineries as selective cancer proliferation-associated proteins. A cross species comparison reveals that cancer proliferation resembles that of microorganisms while non-cancerous proliferation does not. Furthermore, combining cancerous and non-cancerous proliferation signatures leads to enhanced prediction of patient outcome and gene essentiality in cancer. Overall, these results point to an inherent difference between cancerous and non-cancerous proliferation determinants, whose understanding may contribute to the future development of novel cancer-specific anti-proliferative drugs. PMID:24068970

Waldman, Yedael Y.; Geiger, Tamar; Ruppin, Eytan

2013-01-01

330

An Empirical Test of Crisis, Social Selection, and Role Explanations of the Relationship between Marital Disruption and Psychological Distress: A Pooled Time-Series Analysis of Four-Wave Panel Data.  

ERIC Educational Resources Information Center

Reviews three theoretical explanations (social role theory, crisis theory, social selection theory) for the reasons for psychological distress of divorced individuals. Evaluates the efficacy of these theories in a pooled analysis of married persons followed over 12 years. Results provide evidence that higher stress levels of the divorced primarily…

Johnson, David R.; Wu, Jian

2002-01-01

331

Noninvasive detection of lung cancer by analysis of exhaled breath  

PubMed Central

Background Lung cancer is one of the leading causes of death in Europe and the western world. At present, diagnosis of lung cancer very often happens late in the course of the disease since inexpensive, non-invasive and sufficiently sensitive and specific screening methods are not available. Even though the CT diagnostic methods are good, it must be assured that "screening benefit outweighs risk, across all individuals screened, not only those with lung cancer". An early non-invasive diagnosis of lung cancer would improve prognosis and enlarge treatment options. Analysis of exhaled breath would be an ideal diagnostic method, since it is non-invasive and totally painless. Methods Exhaled breath and inhaled room air samples were analyzed using proton transfer reaction mass spectrometry (PTR-MS) and solid phase microextraction with subsequent gas chromatography mass spectrometry (SPME-GCMS). For the PTR-MS measurements, 220 lung cancer patients and 441 healthy volunteers were recruited. For the GCMS measurements, we collected samples from 65 lung cancer patients and 31 healthy volunteers. Lung cancer patients were in different disease stages and under treatment with different regimes. Mixed expiratory and indoor air samples were collected in Tedlar bags, and either analyzed directly by PTR-MS or transferred to glass vials and analyzed by gas chromatography mass spectrometry (GCMS). Only those measurements of compounds were considered, which showed at least a 15% higher concentration in exhaled breath than in indoor air. Compounds related to smoking behavior such as acetonitrile and benzene were not used to differentiate between lung cancer patients and healthy volunteers. Results Isoprene, acetone and methanol are compounds appearing in everybody's exhaled breath. These three main compounds of exhaled breath show slightly lower concentrations in lung cancer patients as compared to healthy volunteers (p < 0.01 for isoprene and acetone, p = 0.011 for methanol; PTR-MS measurements). A comparison of the GCMS-results of 65 lung cancer patients with those of 31 healthy volunteers revealed differences in concentration for more than 50 compounds. Sensitivity for detection of lung cancer patients based on presence of (one of) 4 different compounds not arising in exhaled breath of healthy volunteers was 52% with a specificity of 100%. Using 15 (or 21) different compounds for distinction, sensitivity was 71% (80%) with a specificity of 100%. Potential marker compounds are alcohols, aldehydes, ketones and hydrocarbons. Conclusion GCMS-SPME is a relatively insensitive method. Hence compounds not appearing in exhaled breath of healthy volunteers may be below the limit of detection (LOD). PTR-MS, on the other hand, does not need preconcentration and gives much more reliable quantitative results then GCMS-SPME. The shortcoming of PTR-MS is that it cannot identify compounds with certainty. Hence SPME-GCMS and PTR-MS complement each other, each method having its particular advantages and disadvantages. Exhaled breath analysis is promising to become a future non-invasive lung cancer screening method. In order to proceed towards this goal, precise identification of compounds observed in exhaled breath of lung cancer patients is necessary. Comparison with compounds released from lung cancer cell cultures, and additional information on exhaled breath composition in other cancer forms will be important. PMID:19788722

2009-01-01

332

Prognostic and clinicopathological significance of survivin expression in bladder cancer patients: a meta-analysis.  

PubMed

Survivin has been widely reported to play a role in diagnosis and prognosis of bladder cancer patients. However, published data on this subject are heterogeneous. Here, we conducted a meta-analysis to obtain a complete evaluation of the association between survivin and recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), and odds ratio (OR) in bladder cancer patients. Published studies on this subject were selected for further assessment by online articles in PubMed, MEDLINE, EMBASE, and OVID databases. Pooled hazard ratios (HR) with 95 % confidence interval (95 % CI) were estimated. Funnel plots were used to evaluate the publication bias. As well, heterogeneity and sensitivity were analyzed. In this meta-analysis, we included 13 studies with the total number of 1,963 patients. Positive survivin expression in bladder cancer was associated with a poor RFS (HR, 1.831; 95 % CI, 1.344-2.49), DSS (HR, 1.721; 95 % CI, 1.477-2.004), or OS (HR, 1.753; 95 % CI, 1.092-2.816) in patients. In addition, a significant association between expression of survivin and age (OR, 0.641; 95 % CI, 0.416-0.987) as well as stage (OR, 0.37; 95 % CI, 0.190-0.750) was revealed. Heterogeneity was observed among the included studies with RFS (x (2)?=29.58, p = 0.009, I (2)?= 52.7 %), OS (x (2)?= 15.67, p = 0.008, I (2)?= 68.1 %), and stage (x (2)?= 11.97, p = 0.035, I (2)?= 58.2 %). There was no publication bias according to Begg's and Egger's tests except for studies with gender. Furthermore, sensitivity analysis obtained the source of heterogeneity and confirmed opposite results of some studies. This study suggests that expression of survivin indicates poor prognosis in older patients and muscle invasive or advanced stage in bladder cancer. Survivin expression could be used in identifying a subgroup of patients with potential to benefit from a targeted therapy against survivin. PMID:24101190

Lv, Shunzeng; Turlova, Ekaterina; Zhao, Shigang; Kang, Huihui; Han, Mingzhi; Sun, Hong-Shuo

2014-02-01

333

Self-Advocacy and Cancer: A Concept Analysis  

PubMed Central

Aim This paper is a report of an analysis of the concept of self-advocacy among individuals with cancer to clarify its meaning, to differentiate this meaning with related concepts and to unify understanding of the concept in cancer research and practice. Background Cancer survivors are increasingly required to assume an active role in their healthcare. A thorough analysis of how survivors advocate for themselves is a crucial aspect in supporting survivors’ ability to engage and manage their care throughout all stages of cancer survivorship. Design Walker and Avant’s eight-step process of conducting a concept analysis was used. Data Sources PubMed, PsycINFO and CINAHL databases were searched for articles, reviews, editorials and gray literature directly addressing self-advocacy. Review Methods A broad inquiry into the literature from 1960 – 2012 that produces a definition of self-advocacy. Model and contrary cases of self-advocacy demonstrate the concept’s application and intricacies. Results Antecedents to self-advocacy include particular personal characteristics, learned skills and attainable support. The essential element of self-advocacy and what differentiates it from related concepts, is the internalization of these antecedent resources into self-advocacy thoughts and actions while incorporating personal values and priorities in a way that upholds the survivors’ goals and beliefs. A full realization of self-advocacy facilitates a cancer survivor attaining a strong self-concept, sense of control and adaptation to a life with cancer. Conclusions Self-advocacy is a process of internalizing skills and resources to act in a way that supports survivors’ needs and goals. PMID:23347224

Hagan, Teresa L.; Donovan, Heidi S.

2013-01-01

334

Trabectedin is a feasible treatment for soft tissue sarcoma patients regardless of patient age: a retrospective pooled analysis of five phase II trials  

PubMed Central

Background: This retrospective pooled analysis assessed the effect of age on the efficacy and safety of trabectedin in young and elderly patients with recurrent advanced soft tissue sarcoma (STS). Methods: Data from 350 adults with STS treated in five phase II trials with trabectedin were divided in the younger (<60 years; n=267) and the older cohort (?60 years; n=83). Results: The response rate did not differ with age (younger: 10.1% vs elderly 9.6%). No significant differences were found in median progression-free survival (PFS) in younger (2.5 months) and older (3.7 months) cohort with a comparable PFS rates at 3 (45.1% vs 55.1%) and 6 months (29.5% vs 36.4%). Similar median overall survival was observed in both cohorts (13.0 vs 14.0 months). Reversible neutropenia and aspartate aminotransferase/alanine aminotransferase elevation were the most common abnormalities. A higher incidence of grade 3/4 neutropenia (43.6% vs 60.2%) and fatigue (6.3% vs 14.4%) was observed in older patients. In 24 patients aged ?70 years, no significant differences in efficacy or safety outcomes were found. Conclusion: This analysis demonstrated that trabectedin is a feasible treatment in young and elderly patients with STS, with meaningful clinical benefits and an acceptable safety profile, essential in palliative treatment of elderly patients. PMID:24022187

Cesne, A L; Judson, I; Maki, R; Grosso, F; Schuetze, S; Mehren, M V; Chawla, S P; Demetri, G D; Nieto, A; Tanovic, A; Blay, J-Y

2013-01-01

335

Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: Insights from a patient-level pooled analysis of six randomized clinical trials?  

PubMed Central

Aims To quantify the effect of liraglutide on systolic blood pressure (SBP) and pulse in patients with type 2 diabetes (T2D), and assess the influence of covariates on observed SBP reductions. Methods A patient-level pooled analysis of six phase 3, randomized trials was conducted. Results The analysis included 2792 randomized patients. In the intention-to-treat population (n = 2783), mean [±SE] SBP reductions from baseline with liraglutide 1.2 mg (2.7 [0.8] mmHg) and 1.8 mg (2.9 [0.7] mmHg) once daily were significantly greater than with placebo (0.5 [0.9] mmHg; P = 0.0029 and P = 0.0004, respectively) after 26 weeks, and were evident after 2 weeks. Liraglutide was also associated with significantly greater SBP reductions than glimepiride and, at a dose of 1.8 mg, insulin glargine and rosiglitazone. SBP reductions with liraglutide weakly correlated with weight loss (Pearson’s correlation coefficient: 0.08–0.12; P ? 0.0148). No dependence of these reductions on concomitant antihypertensive medications was detected (P = 0.1304). Liraglutide 1.2 and 1.8 mg were associated with mean increases in pulse of 3 beats per minute (bpm), versus a 1 bpm increase with placebo (P < 0.0001 for each dose versus placebo). Conclusions Liraglutide reduces SBP in patients with T2D, including those receiving concomitant antihypertensive medication. PMID:24561125

Fonseca, Vivian A.; DeVries, J. Hans; Henry, Robert R.; Donsmark, Morten; Thomsen, Henrik F.; Plutzky, Jorge

2014-01-01

336

Risk factors associated with complications in lower-extremity reconstruction with the distally based sural flap: a systematic review and pooled analysis.  

PubMed

The distally based sural fasciocutaneous flap is one of the few options available for local flap reconstruction of soft-tissue defects in the lower one-third of the leg. Few studies have assessed risk factors associated with poor outcomes in this flap. A literature search was performed of MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles evaluating the use of sural artery fasciocutaneous flaps for soft-tissue reconstruction of the leg. Data were pooled and a univariate analysis was performed to identify characteristics associated with increased morbidity. A logistic regression model was created, and odds ratios and p values associated with the development of complications were calculated. Sixty-one papers were identified which included data on 907 patients. The majority of sural flaps were used to cover defects of the heel (28.2%), foot (14.4%) or ankle (25.8%). Trauma was the most common indication, followed by ulcers and open fractures. Flap complications were recorded in 26.4% of cases with a flap loss rate of 3.2%. With multivariate analysis, venous insufficiency and increasing age were independent risk factors for complications. Patients with venous insufficiency had nine times the risk of developing a complication compared to patients without venous insufficiency. PMID:24662152

de Blacam, Catherine; Colakoglu, Salih; Ogunleye, Adeyemi A; Nguyen, John T; Ibrahim, Ahmed M S; Lin, Samuel J; Kim, Peter S; Lee, Bernard T

2014-05-01

337

Comparison of serum human epididymis protein 4 and carbohydrate antigen 125 as markers in ovarian cancer: A meta-analysis  

PubMed Central

Ovarian cancer (OC) is the third most common type of gynecological cancer. Measurements of human epididymis protein 4 (HE4) levels have been suggested for improving the specificity of the laboratory identification of OC. For this meta-analysis, the Medline, Embase and Cochrane databases were searched to identify relevant studies. All the included studies for diagnostic performance were combined with sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), summary receiver operating characteristic (SROC) curves and areas under the SROC curves (AUC). A total of 25 studies including 4,729 patients were identified as eligible for inclusion in the final analysis. The pooled sensitivities and respective 95% CIs for HE4 and carbohydrate antigen 125 (CA125) were 0.74 (0.72–0.76) and 0.74 (0.72–0.76), respectively. The pooled specificities and respective 95% CIs for HE4 and CA125 were 0.90 (0.89–0.91) and 0.83 (0.81–0.84), respectively. The summary DORs and 95% CIs for HE4 and CA125 were 43.35 (29.13–64.51) and 17.06 (10.97–26.51), respectively and the AUCs for HE4 and CA125 were 0.8915 and 0.8538, respectively. In total, 9 studies investigated the diagnostic accuracy of HE4 combined with CA125 for the diagnosis of OC. The pooled sensitivity and 95% CIs of HE4, CA125 and HE4+CA125 in this subgroup were 0.71 (0.67–0.75), 0.74 (0.69–0.78) and 0.90 (0.87–0.92), respectively; the pooled specificity and 95% CIs of HE4, CA125 and HE4+CA125 were 0.92 (0.90–0.94), 0.73 (0.69–0.76) and 0.85 (0.82–0.87), respectively. The diagnostic accuracy of HE4 in distinguishing OC from other benign gynecological diseases was found to be to be superior to that of CA125 and the combination of HE4 and CA125 may enhance the diagnostic sensitivity. PMID:24940495

ZHEN, SHUAI; BIAN, LI-HONG; CHANG, LI-LI; GAO, XIN

2014-01-01

338

Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis  

NASA Astrophysics Data System (ADS)

Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

2011-07-01

339

Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.  

PubMed

Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity < 0.001). The largest risk reductions were observed for 4 cups/day for all-cause mortality (16%, 95% confidence interval: 13, 18) and 3 cups/day for CVD mortality (21%, 95% confidence interval: 16, 26). Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality. PMID:25156996

Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

2014-10-15

340

Methylenetetrahydrofolate Reductase C677T Polymorphism and Susceptibility to Cervical Cancer and Cervical Intraepithelial Neoplasia: A Meta-Analysis  

PubMed Central

Background A number of studies have explored the association between methyl enetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to cervical cancer and cervical intraepithelial neoplasia (CIN). However, results remained controversial. To address this gap, we decided to conduct a meta-analysis of all available published studies. Methods Electronic literature searches of the PubMed, EmBase and Medline databases were performed up to April 30, 2012. Fixed-effects or random-effects model was used to calculate the pooled ORs for different genetic models. Results A total of 12 case-control studies were ultimately identified. No statistical correlation was found between C677T variants and cervical cancer for the overall population. However, subgroup analyses on the White women pointed to a significant protective effect for individuals heterozygous or homozygous for the T-allele (for CT vs. CC: OR?=?0.72, 95% CI 0.59–0.88; for TT vs. CC: OR?=?0.69, 95% CI?=?0.49–0.97; for CT+TT vs. CC: OR?=?0.71, 95% CI 0.59–0.86). C677T variants were associated with neither combined nor stratified CIN among the overall population. Conclusions This meta-analysis suggests that White women with mutant C677T genotypes might have a lower risk of cervical cancer, yet lacking enough statistical robustness. Further investigations are needed to get more insight into the role of this polymorphism in cervical carcinogenesis. PMID:23029458

Zhang, Qiong Hua; Hu, Ting Ting; Luo, Min Hong; Li, Mei Qing; Chen, Qing

2012-01-01

341

Structural and Reliability Analysis of a Patient Satisfaction with Cancer-Related Care Measure: A Multi-Site Patient Navigation Research Program Study  

PubMed Central

Background Patient satisfaction (PS) is an important outcome measure of quality of cancer care and one of the four core study outcomes of the National Cancer Institute (NCI) sponsored Patient Navigation Research Program (PNRP) to reduce race/ethnicity-based disparities in cancer care. There is no existing PS measure that spans the spectrum of cancer-related care. Objective Develop a Patient Satisfaction with Cancer Care (PSCC) measure that is relevant to patients receiving diagnostic/therapeutic cancer-related care. Methods We developed a conceptual framework, an operational definition of PSCC, and an item pool based on literature review, expert feedback, group discussion and consensus. The 35-item PSCC measure was administered to 891 participants from the multi-site NCI-sponsored PNRP. Principal components analysis (PCA) was conducted for latent structure analysis. Internal consistency was assessed using Cronbach coefficient alpha (?). Divergent analysis was performed using correlation analyses between the PSCC, the Communication and Attitudinal Self-Efficacy (CASE-Cancer), and demographic variables. Results The PCA revealed a one-dimensional measure with items forming a coherent set explaining 62% of the variance in PS. Reliability assessment revealed high internal consistency (? ranging from 0.95 to 0.96). The PSCC demonstrated good face validity, convergent validity and divergent validity as indicated by moderate correlations with subscales of the CASE-Cancer (all ps < 0.01) and non-significant correlations with age, primary language, marital status, and scores on the Rapid Estimate of Adult Literacy in Medicine (REALM) Long Form (all ps > 0.05). Conclusion The PSCC is a valid tool for assessing satisfaction for cancer-related care for this sample. PMID:20922802

Jean-Pierre, Pascal; Fiscella, Kevin; Freund, Karen M; Clark, Jack; Darnell, Julie; Holden, Alan; Post, Doug; Patierno, Steven R; Winters, Paul C.

2010-01-01

342

Statin Therapy Improves Long-term Survival in Non-ischaemic Cardiomyopathy: A Pooled Analysis of 4500 Patients.  

PubMed

Statin therapy has demonstrated a beneficial effect in patients with chronic heart failure. While the majority of patients with ischaemic cardiomyopathy are prescribed these drugs, studies have demonstrated that less than one fifth of patients with dilated cardiomyopathy are on regular statin therapy. We have performed a meta-analysis of 4500 patients from six studies (four randomised controlled trials). Our results demonstrate that statin therapy significantly improves long-term survival in patients with non-ischaemic heart failure {Hazard ratio for mortality 0.45 (0.33-0.62); p<0.0001; I(2)=41%; p-value for heterogeneity=0.13}. PMID:24851827

Deo, Salil V; Rababa'h, Abeer; Altarabsheh, Salah E; Lim, Ju Yong; Cho, Yang Hyun; Park, Soon J

2014-10-01

343

Functional and genetic analysis of the colon cancer network  

PubMed Central

Cancer is a complex disease that has proven to be difficult to understand on the single-gene level. For this reason a functional elucidation needs to take interactions among genes on a systems-level into account. In this study, we infer a colon cancer network from a large-scale gene expression data set by using the method BC3Net. We provide a structural and a functional analysis of this network and also connect its molecular interaction structure with the chromosomal locations of the genes enabling the definition of cis- and trans-interactions. Furthermore, we investigate the interaction of genes that can be found in close neighborhoods on the chromosomes to gain insight into regulatory mechanisms. To our knowledge this is the first study analyzing the genome-scale colon cancer network. PMID:25079297

2014-01-01

344

Immunohistochemical analysis of FKBP51 in human cancers.  

PubMed

FKBP51 is a FK506-binding immunophilin involved in the regulation of several fundamental biological processes. A growing body of data indicates that this protein has also a role in the abnormal cell growth of cancers, and could be considered as a promising new marker of tumor progression and response to radio/chemotherapy. However, the data concerning the expression of FKBP51 in cancer are not conclusive, and partially contradictory. They delineate a very complex scenario, in which many molecular FKBP51-related pathways are variously intersected among different tumors. This review reports the available data concerning FKBP51 expression in normal tissues and human malignancies, outlining the role of the immunohistochemical analysis as a fundamental tool for better understanding the role of this immunophilin in cancer biology. PMID:21530399

Staibano, Stefania; Mascolo, Massimo; Ilardi, Gennaro; Siano, Maria; De Rosa, Gaetano

2011-08-01

345

Risk for lung cancer in workers exposed to benzidine and/or beta-naphthylamine: a protocol for systematic review and meta-analysis  

PubMed Central

Background Risk for lung cancer in workers exposed to benzidine (BZ) and/or beta-naphthylamine (BNA), which are well-known bladder carcinogens, has been examined in many epidemiological studies, but individual epidemiological studies generally lack the power to examine the association between BZ/BNA exposure and lung cancer. We conduct a systematic review and meta-analysis to determine the risk for lung cancer among workers exposed to BZ/BNA occupationally. Methods/design Studies will be identified by a MEDLINE, EMBASE, CDSR, and CINAHL search and by the reference lists of articles/relevant reviews. Eligible studies will be cohort and case-control studies that report occupational BZ/BNA exposure and the outcome of interest (lung cancer death/incidence). The method of meta-analysis will be used to combine standardized mortality ratios (SMRs) and/or standardized incidence ratios (SIRs) from retrospective and prospective cohort studies and odds ratios (ORs) from case-control studies. Two reviewers will independently screen articles, extract data, and assess scientific quality using standardized forms and published quality assessment tools tailored for each study design. Overall pooled risk estimates and their corresponding 95% confidence intervals (CIs) will be obtained using random effects model. This systematic review and meta-analysis will be conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, and results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Discussion This review will identify and synthesize studies of the association between occupational BZ/BNA exposure and lung cancer. The findings will help to identify whether BZ/BNA could cause lung cancer and might indicate whether workers with exposure to BZ/BNA have a need for preventive measures against non-urological cancer besides bladder cancer. Systematic review registration PROSPERO CRD42014010250 PMID:25281283

2014-01-01

346

Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis  

PubMed Central

Purpose The purpose of this meta-analysis was to determine the strength of the association between gynecologic surgeries, tubal ligation and hysterectomy, and ovarian cancer. Methods We searched the PubMed, Web of Science, and Embase databases for all English-language articles dated between 1969 through March 2011 using the keywords “ovarian cancer” and “tubal ligation” or “tubal sterilization” or “hysterectomy.” We identified 30 studies on tubal ligation and 24 studies on hysterectomy that provided relative risks for ovarian cancer and a p-value or 95% confidence interval (CI) to include in the meta-analysis. Summary RRs and 95% CIs were calculated using a random-effects model. Results The summary RR for women with vs. without tubal ligation was 0.70 (95%CI: 0.64, 0.75). Similarly, the summary RR for women with vs. without hysterectomy was 0.74 (95%CI: 0.65, 0.84). Simple hysterectomy and hysterectomy with unilateral oophorectomy were associated with a similar decrease in risk (summery RR?=?0.62, 95%CI: 0.49-0.79 and 0.60, 95%CI: 0.47-0.78, respectively). In secondary analyses, the association between tubal ligation and ovarian cancer risk was stronger for endometrioid tumors (summary RR?=?0.45, 95%CI: 0.33, 0.61) compared to serous tumors. Conclusion Observational epidemiologic evidence strongly supports that tubal ligation and hysterectomy are associated with a decrease in the risk of ovarian cancer, by approximately 26-30%. Additional research is needed to determine whether the association between tubal ligation and hysterectomy on ovarian cancer risk differs by individual, surgical, and tumor characteristics. PMID:22587442

2012-01-01

347

RESEARCH Open Access Analysis of primary risk factors for oral cancer  

E-print Network

RESEARCH Open Access Analysis of primary risk factors for oral cancer from select US states , Michelle Chino3 , Karl Kingsley1* Abstract Objectives: To examine the primary risk factor for oral cancer in oral cancer incidence and mortality. Methods: Population-based data on oral cancer morbidity

Ahmad, Sajjad

348

Coffee and pancreatic cancer: an analysis of international mortality data.  

PubMed

This study assessed the relationship of per capita coffee imports and consumption, total dietary fat, saturated fat, cholesterol, tobacco, cigarettes, and national income for 1957-1965 to age-adjusted pancreatic cancer death rates of men and women from 22 countries in 1971-1974. With simple correlation analysis, coffee, total dietary fat, saturated fat, and national income were each significantly correlated with both male and female pancreatic cancer mortality. Bivariate partial correlation coefficients of coffee with pancreatic cancer mortality were significant (one-tailed) in 11 of 12 analyses and borderline significant in two-way analyses of variance (ANOVA) (two-tailed) controlling for each of the other variables. Saturated fat and pancreatic cancer were also significantly related in univariate analyses, and in 11 of 12 bivariate partial correlation analyses; in ANOVA, significance was borderline in 10 of 12 analyses. Total fat and pancreatic mortality were also significantly associated in most of the univariate and bivariate correlation analyses, but not in the two-way analyses of variance. The findings of this study are consistent with the hypothesis that coffee and dietary lipid are involved in the etiology of pancreatic cancer. PMID:6637990

Binstock, M; Krakow, D; Stamler, J; Reiff, J; Persky, V; Liu, K; Moss, D

1983-11-01

349

Pancreatic cancer risk and prevention: association with PPARG gene and policy analysis of tabacco-related pancreatic cancer.  

E-print Network

??This study involved a genetic association analysis of variants in the peroxisome proliferator-activated receptor-gamma gene and pancreatic cancer risk, and a policy analysis of tobacco-related… (more)

Fesinmeyer, Megan Dann

2007-01-01

350

In-depth Proteomic Analysis of Nonsmall Cell Lung Cancer to Discover Molecular Targets and Candidate Biomarkers*  

PubMed Central

Advances in proteomic analysis of human samples are driving critical aspects of biomarker discovery and the identification of molecular pathways involved in disease etiology. Toward that end, in this report we are the first to use a standardized shotgun proteomic analysis method for in-depth tissue protein profiling of the two major subtypes of nonsmall cell lung cancer and normal lung tissues. We identified 3621 proteins from the analysis of pooled human samples of squamous cell carcinoma, adenocarcinoma, and control specimens. In addition to proteins previously shown to be implicated in lung cancer, we have identified new pathways and multiple new differentially expressed proteins of potential interest as therapeutic targets or diagnostic biomarkers, including some that were not identified by transcriptome profiling. Up-regulation of these proteins was confirmed by multiple reaction monitoring mass spectrometry. A subset of these proteins was found to be detectable and differentially present in the peripheral blood of cases and matched controls. Label-free shotgun proteomic analysis allows definition of lung tumor proteomes, identification of biomarker candidates, and potential targets for therapy. PMID:22761400

Kikuchi, Takefumi; Hassanein, Mohamed; Amann, Joseph M.; Liu, Qinfeng; Slebos, Robbert J. C.; Rahman, S. M. Jamshedur; Kaufman, Jacob M.; Zhang, Xueqiong; Hoeksema, Megan D.; Harris, Bradford K.; Li, Ming; Shyr, Yu; Gonzalez, Adriana L.; Zimmerman, Lisa J.; Liebler, Daniel C.; Massion, Pierre P.; Carbone, David P.

2012-01-01

351

Association Studies of ERCC1 Polymorphisms with Lung Cancer Susceptibility: A Systematic Review and Meta-Analysis  

PubMed Central

Background Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate