Sample records for cancer pooled analysis

  1. Fulvestrant and male breast cancer: a pooled analysis.

    PubMed

    Zagouri, Flora; Sergentanis, Theodoros N; Chrysikos, Dimosthenis; Dimopoulos, Meletios-Athanasios; Psaltopoulou, Theodora

    2015-01-01

    Male breast cancer is an uncommon malignancy; little is known regarding hormonal manipulations for tamoxifen-resistant male breast cancer patients. This is the first pooled analysis of the literature to synthesize all available data and to evaluate the efficacy and safety of fulvestrant in male breast cancer. This study was performed in accordance with the PRISMA guidelines. All studies that examined the efficacy of fulvestrant in male breast cancer, regardless of sample size, were considered eligible. The search strategy retrieved 31 articles; of these, five articles were eligible (23 patients) for this pooled analysis. The mean age of the study sample was 63.1 years. Adjuvant hormonal treatment was administered in 87.5 % of cases. Fulvestrant was given as first or second line in 40 % of patients, while as third line or beyond in 60 % of patients. 79.0 % of patients at fulvestrant administration had visceral metastases. Regarding best response, in 26.1 % PR was achieved, in 47.8 % of cases SD was recorded, whereas in 26.1 % of patients PD was noted. The median PFS was equal to 5 months. No grade 3 and 4 adverse events were recorded; of note, hot flashes were reported in 18.2 % of male breast cancer patients. Fulvestrant may potentially play a promising role in the optimal therapeutic strategy for male patients with breast cancer diagnosis. However, further clinical and pharmacokinetic investigations are more than warranted before fulvestrant use becomes a common practice in male breast cancer patients. PMID:25519043

  2. Aromatase inhibitors in male breast cancer: a pooled analysis.

    PubMed

    Zagouri, Flora; Sergentanis, Theodoros N; Azim, Hatem A; Chrysikos, Dimosthenis; Dimopoulos, Meletios-Athanassios; Psaltopoulou, Theodora

    2015-05-01

    Although several studies have shown the efficacy of third-generation aromatase inhibitors (AIs) in women with breast cancer, the role of such molecules remains elusive in male breast cancer patients. It is also unknown whether the addition of gonadotropin-releasing hormone (GnRH) analogues to AIs would be a superior strategy or not. This pooled analysis was conducted in accordance with the PRISMA guidelines. All studies that examined the efficacy of AIs in metastatic male breast cancer were considered eligible. Overall, 15 studies (105 cases) were eligible for this pooled analysis. The mean age of the study sample was 62.8 years. ER status was positive in all eligible cases. AI was given as first line in 61.5 % of cases. GnRH analogue was co-administered with AI in 37.1 % of cases (n = 39). CR, PR, SD and PD were achieved in 5.7, 23.8, 37.2 and 33.3 % of cases, respectively. The median PFS and OS were equal to 10.0 and 39.0 months, respectively. Co-administration of GnRH analogues was associated with more than threefold increase in rates of clinical benefit (OR = 3.37, 95 % CI 1.30-8.73) but did not seem to correlate with better PFS or OS. No statistically significant associations between the examined outcomes and the other parameters were noted. Available data suggest that AIs may potentially play a promising role in the optimal therapeutic strategy for metastatic male breast cancer patients. Especially, co-administration of AI with a GnRH analogue seems to increase the rate of clinical benefit and could be more effective, warranting further consideration. PMID:25850534

  3. Colorectal cancers soon after colonoscopy: a pooled multicohort analysis

    PubMed Central

    Robertson, Douglas J; Lieberman, David A; Winawer, Sidney J; Ahnen, Dennis J; Baron, John A; Schatzkin, Arthur; Cross, Amanda J; Zauber, Ann G; Church, Timothy R; Lance, Peter; Greenberg, E Robert; Martínez, María Elena

    2015-01-01

    Objective Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps. Design Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection. Results 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection. Conclusions Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy. PMID:23793224

  4. A POOLED ANALYSIS OF 14 COHORT STUDIES OF ANTHROPOMETRIC FACTORS AND PANCREATIC CANCER RISK

    PubMed Central

    Genkinger, Jeanine M.; Spiegelman, Donna; Anderson, Kristin E.; Bernstein, Leslie; van den Brandt, Piet A.; Calle, Eugenia E.; English, Dallas R.; Folsom, Aaron R.; Freudenheim, Jo L.; Fuchs, Charles S.; Giles, Graham G.; Giovannucci, Edward; Horn-Ross, Pamela L.; Larsson, Susanna C; Leitzmann, Michael; Männistö, Satu; Marshall, James R; Miller, Anthony B.; Patel, Alpa V.; Rohan, Thomas E.; Stolzenberg-Solomon, Rachael Z.; Verhage, Bas AJ; Virtamo, Jarmo; Willcox, Bradley J.; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

    2011-01-01

    Epidemiologic studies of pancreatic cancer risk have reported null or non-significant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21–22.9kg/m2, pancreatic cancer risk was 47% higher (95%CI:23–75%) among obese (BMI?30kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI=1.09–1.56 comparing BMI?25kg/m2 to a BMI between 21–22.9kg/m2). Compared to individuals who were not overweight in early adulthood (BMI<25kg/m2) and not obese at baseline (BMI<30kg/m2), pancreatic cancer risk was 54% higher (95%CI=24–93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ?10kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR=1.35 comparing the highest versus lowest quartile, 95%CI=1.03–1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer. PMID:21105029

  5. ALCOHOL INTAKE AND PANCREATIC CANCER RISK: A POOLED ANALYSIS OF FOURTEEN COHORT STUDIES

    PubMed Central

    Genkinger, Jeanine M.; Spiegelman, Donna; Anderson, Kristin E.; Bergkvist, Leif; Bernstein, Leslie; van den Brandt, Piet A.; English, Dallas R.; Freudenheim, Jo L.; Fuchs, Charles S.; Giles, Graham G.; Giovannucci, Edward; Hankinson, Susan E.; Horn-Ross, Pamela L.; Leitzmann, Michael; Männistö, Satu; Marshall, James R.; McCullough, Marjorie L.; Miller, Anthony B.; Reding, Douglas J.; Robien, Kim; Rohan, Thomas E.; Schatzkin, Arthur; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Verhage, Bas AJ; Wolk, Alicja; Ziegler, Regina; Smith-Warner, Stephanie A.

    2009-01-01

    BACKGROUND Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk. METHODS We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model. RESULTS A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate RR =1.22, 95% CI 1.03–1.45 comparing ? 30 to 0 grams/day of alcohol; p-value, test for between-studies heterogeneity= 0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (p-value, test for interaction = 0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of ? 5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared to overweight and obese individuals (p-value, test for interaction = 0.01). DISCUSSION Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day. PMID:19258474

  6. Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

    PubMed

    Genkinger, J M; Wang, M; Li, R; Albanes, D; Anderson, K E; Bernstein, L; van den Brandt, P A; English, D R; Freudenheim, J L; Fuchs, C S; Gapstur, S M; Giles, G G; Goldbohm, R A; Håkansson, N; Horn-Ross, P L; Koushik, A; Marshall, J R; McCullough, M L; Miller, A B; Robien, K; Rohan, T E; Schairer, C; Silverman, D T; Stolzenberg-Solomon, R Z; Virtamo, J; Willett, W C; Wolk, A; Ziegler, R G; Smith-Warner, S A

    2014-06-01

    Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ?500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ?1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk. PMID:24631943

  7. HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies

    PubMed Central

    2012-01-01

    Objective The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. Methods A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. Results Out of 574 cancers, 24 (4.2%) were HPV negative. HPV 16 and 18 were responsible for 74.4% (378/508) and 80.3% (49/61) of the squamous cancers and adenocarcinomas, respectively. Other frequent types were 31 (9.5%), 45 (6.4%), and 58 (3.3%) for squamous cancers and 45 (13.3%), 31, 35, and 58 (5.0%) for adenocarcinomas. The proportion of HPV 16 and/or 18 decreased with age (p-value for trend <0.03), while it increased in cancers diagnosed in more recent years (p-value for trend?cancer will be greater for early onset cancers. In vaccinated women, screening could be started at an older age without reducing protection. PMID:23110797

  8. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

    PubMed Central

    Faber, Mette T.; Kjær, Susanne K.; Dehlendorff, Christian; Chang-Claude, Jenny; Andersen, Klaus K.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Doherty, Jennifer A.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Ness, Roberta B.; Modugnos, Francesmary; Edwards, Robert P.; Bunker, Clareann H.; Goode, Ellen L.; Fridley, Brooke L.; Vierkant, Robert A.; Larson, Melissa C.; Schildkraut, Joellen; Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.; Bandera, Elisa V.; Olson, Sara H.; King, Melony; Chandran, Urmila; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H.; Brinton, Louise; Wentzensen, Nicolas; Lissowska, Jolanta; Yang, Hannah P.; Moysich, Kirsten B.; Odunsi, Kunle; Kasza, Karin; Odunsi-Akanji, Oluwatosin; Song, Honglin; Pharaoh, Paul; Shah, Mitul; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Sutphen, Rebecca; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H.; Pike, Malcolm C.; Risch, Harvey A.

    2013-01-01

    Purpose The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. Methods We used data from 21 case–control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Results Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03–1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39–2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12–1.50). For these histological types, consistent dose– response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Conclusions Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease. PMID:23456270

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

    PubMed

    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 Bas; Schüz, Joachim; Straif, Kurt

    2015-01-15

    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 < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung 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

  10. Circulating Carotenoids and Risk of Breast Cancer: Pooled Analysis of Eight Prospective Studies

    PubMed Central

    2012-01-01

    Background Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. Methods We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world’s published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Results Statistically significant inverse associations with breast cancer were observed for ?-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), ?-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). ?-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER?) than for ER+ tumors (eg, ?-carotene: ER?: top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER+: RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). Conclusions This comprehensive prospective analysis suggests women with higher circulating levels of ?-carotene, ?-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer. PMID:23221879

  11. Diet and thyroid cancer: a pooled analysis of four European case-control studies.

    PubMed

    Franceschi, S; Levi, F; Negri, E; Fassina, A; La Vecchia, C

    1991-05-30

    The relationship between frequencies of consumption of selected indicator foods and the risk of thyroid cancer was investigated in a pooled analysis of 4 case-control studies conducted in 3 areas of northern Italy and the Swiss Canton of Vaud, on a total of 385 histologically confirmed cases of thyroid cancer and 798 controls in hospital for acute, non-neoplastic, non-hormone-related diseases. Cases tended to consume significantly more frequently a number of starchy foods: the odds ratio (OR) for the highest vs. lowest tertile was 1.8 for pasta or rice, 2.1 for bread, 1.6 for pastry and 2.0 for potatoes. ORs also tended to be above unity for several types of meat and significantly so for chicken and poultry, cooked ham, salami and sausages. Raw ham and fish were significantly protective (OR = 0.7 in the highest tertile for both). Significant direct associations were observed with cheese (OR = 1.4 for the highest tertile), butter (OR = 2.1) and oils other than olive (OR = 1.6). The risk estimates were below unity for most types of vegetables and fruits, and the inverse trends were significantly for carrots (OR = 0.6 for the highest tertile), green salad (OR = 0.6) and citrus fruits (OR = 0.7). No association was observed with alcohol intake. These results were consistent and reproducible across various study centers. PMID:2040535

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

    PubMed Central

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

    2013-01-01

    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

  13. Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies

    PubMed Central

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie; Weber, Rachel Palmieri; Terry, Kathryn L; Rossing, Mary Anne; Risch, Harvey; Wu, Anna H; Webb, Penelope M; Moysich, Kirsten; Doherty, Jennifer A; Felberg, Anna; Miller, Dianne; Jordan, Susan J; Goodman, Marc T; Lurie, Galina; Chang-Claude, Jenny; Rudolph, Anja; Kjær, Susanne Krüger; Jensen, Allan; Høgdall, Estrid; Bandera, Elisa V; Olson, Sara H; King, Melony G; Rodriguez-Rodriguez, Lorna; Kiemeney, Lambertus A; Marees, Tamara; Massuger, Leon F; van Altena, Anne M; Ness, Roberta B; Cramer, Daniel W; Pike, Malcolm C; Pearce, Celeste Leigh; Berchuck, Andrew; Schildkraut, Joellen M; Whittemore, Alice S

    2013-01-01

    Background Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. Methods We pooled primary data from 13 population-based case-control studies, including 10 157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13 904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. Results Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P < 0.001), endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P < 0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P < 0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P = 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P < 0.0001) and clear cell (P = 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. Conclusions We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation. PMID:23569193

  14. Comparison of RECIST 1.0 and RECIST 1.1 in Patients with Metastatic Cancer: A Pooled Analysis

    PubMed Central

    Kim, Jung Han; Min, Seon Jeong; Jang, Hyun Joo; Cho, Ji Woong; Kim, Soo Ho; Kim, Hyeong Su

    2015-01-01

    Background:We conducted this pooled analysis to investigate the impact of RECIST 1.1 on the selection of target lesions and classification of tumor response, in comparison with RECIST 1.0. Methods: We searched MEDLINE and EMBASE for articles with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual meeting presentations from the conferences of ASCO and ESMO between 2009 and 2013. Results: There were six articles in the literature comparing the clinical impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total of 359 patients were recruited from the six trials; 217 with non-small cell lung cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid cancer. The number of target lesions by RECIST 1.1 was significantly lower than that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed high concordance with RECIST 1.0 in the assessment of tumor responses (k = 0.903). Sixteen patients (4.8%) showed disagreement between the two criteria. Conclusion: This pooled study demonstrated that RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in patients with metastatic cancer. PMID:25767610

  15. Risk of Colon Cancer and Coffee, Tea, and Sugar-Sweetened Soft Drink Intake: Pooled Analysis of Prospective Cohort Studies

    PubMed Central

    Zhang, Xuehong; Albanes, Demetrius; Beeson, W. Lawrence; van den Brandt, Piet A.; Buring, Julie E.; Flood, Andrew; Freudenheim, Jo L.; Giovannucci, Edward L.; Goldbohm, R. Alexandra; Jaceldo-Siegl, Karen; Jacobs, Eric J.; Krogh, Vittorio; Larsson, Susanna C.; Marshall, James R.; McCullough, Marjorie L.; Miller, Anthony B.; Robien, Kim; Rohan, Thomas E.; Schatzkin, Arthur; Sieri, Sabina; Spiegelman, Donna; Virtamo, Jarmo; Wolk, Alicja; Willett, Walter C.; Zhang, Shumin M.

    2010-01-01

    Background The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. Methods We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731?441 participants followed for up to 6–20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. Results Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, Ptrend = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, Ptrend = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, Ptrend = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05). Conclusions Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study. PMID:20453203

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

    PubMed Central

    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

    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

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

    PubMed

    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

    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

  18. Pooled Analysis of Phosphatidylinositol 3-kinase Pathway Variants and Risk of Prostate Cancer

    PubMed Central

    Koutros, Stella; Schumacher, Fredrick R.; Hayes, Richard B.; Ma, Jing; Huang, Wen-Yi; Albanes, Demetrius; Canzian, Federico; Chanock, Stephen J.; Crawford, E. David; Diver, W. Ryan; Feigelson, Heather Spencer; Giovanucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hunter, David J.; Kaaks, Rudolf; Kolonel, Laurence N.; Kraft, Peter; Le Marchand, Loïc; Riboli, Elio; Siddiq, Afshan; Stampfer, Mier J.; Stram, Daniel O.; Thomas, Gilles; Travis, Ruth C.; Thun, Michael J.; Yeager, Meredith; Berndt, Sonja I.

    2010-01-01

    The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking and may impact prostate carcinogenesis. Thus, we explored the association between single nucleotide polymorphisms (SNPs) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk (ORper allele=1.08 (95% CI: 1.03, 1.14), p-trend = 0.0017) after adjustment for multiple testing (Padj=0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association (ORper allele=1.21 (95% CI: 1.09, 1.34); p-trend =0.0003). The adjusted association was stronger for men who were diagnosed before 65 years (ORper allele= 1.47 (95% CI: 1.20, 1.79), p-trend = 0.0001) or had a family history (ORper allele= 1.57 (95% CI: 1.11, 2.23), p-trend = 0.0114), and was strongest in those with both characteristics (ORper allele= 2.31 (95% CI: 1.07, 5.07), p-interaction = 0.005). Increased risks were observed among men in the top tertile of circulating insulin like growth factor-1 (IGF-1) levels (ORper allele= 1.46 (95% CI: 1.04, 2.06), p-trend=0.075). No differences were observed with disease aggressiveness (?8/stage T3/T4/fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early onset disease, which may be attributable to IGF-dependent PI3K signaling. PMID:20197460

  19. Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer.

    PubMed

    Koutros, Stella; Schumacher, Fredrick R; Hayes, Richard B; Ma, Jing; Huang, Wen-Yi; Albanes, Demetrius; Canzian, Federico; Chanock, Stephen J; Crawford, E David; Diver, W Ryan; Feigelson, Heather Spencer; Giovanucci, Edward; Haiman, Christopher A; Henderson, Brian E; Hunter, David J; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Le Marchand, Loïc; Riboli, Elio; Siddiq, Afshan; Stampfer, Mier J; Stram, Daniel O; Thomas, Gilles; Travis, Ruth C; Thun, Michael J; Yeager, Meredith; Berndt, Sonja I

    2010-03-15

    The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [OR(per allele), 1.08 (95% CI, 1.03-1.14); P(trend) = 0.0017] after adjustment for multiple testing (P(adj) = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [OR(per allele), 1.21 (95% CI, 1.09-1.34); P(trend) = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR(per allele), 1.47 (95% CI, 1.20-1.79); P(trend) = 0.0001] or had a family history [OR(per allele) = 1.57 (95% CI, 1.11-2.23); P(trend) = 0.0114], and was strongest in those with both characteristics [OR(per allele) = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [OR(per allele) = 1.46 (95% CI, 1.04-2.06); P(trend) = 0.075]. No differences were observed with disease aggressiveness (Gleason grade >or=8 or stage T(3)/T(4) or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling. PMID:20197460

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

    SciTech Connect

    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

    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.

  1. Estrogen Receptor Beta rs1271572 Polymorphism and Invasive Ovarian Carcinoma Risk: Pooled Analysis within the Ovarian Cancer Association Consortium

    PubMed Central

    Lurie, Galina; Wilkens, Lynne R.; Thompson, Pamela J.; Shvetsov, Yurii B.; Matsuno, Rayna K.; Carney, Michael E.; Palmieri, Rachel T.; Wu, Anna H.; Pike, Malcolm C.; Pearce, Celeste L.; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Pharoah, Paul D. P.; Song, Honglin; Gronwald, Jacek; Jakubowska, Anna; Cybulski, Cezary; Lubinski, Jan; Schildkraut, Joellen M.; Berchuck, Andrew; Krüger Kjær, Susanne; Høgdall, Estrid; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Chenevix-Trench, Georgia; Webb, Penelope M.; Beesley, Jonathan; Goodman, Marc T.

    2011-01-01

    The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC). All participants were non-Hispanic white women. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR?=?1.10; 95%; CI: 1.01–1.21; p?=?0.04); the OR was 1.09 (CI: 0.99–1.20; p?=?0.07) after excluding data from the center (Hawaii) that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ?50 years versus older women (OR?=?1.35; CI: 1.12–1.62; p?=?0.002; p for interaction?=?0.02) that remained statistically significant after excluding Hawaii data (OR?=?1.34; CI: 1.11–1.61; p?=?0.009). No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women. PMID:21673961

  2. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies

    PubMed Central

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne; Lee, Alice; Near, Aimee M; Webb, Penelope M; Nagle, Christina M; Doherty, Jennifer A; Cushing-Haugen, Kara L; Wicklund, Kristine G; Chang-Claude, Jenny; Hein, Rebecca; Lurie, Galina; Wilkens, Lynne R; Carney, Michael E; Goodman, Marc T; Moysich, Kirsten; Kjaer, Susanne K; Hogdall, Estrid; Jensen, Allan; Goode, Ellen L; Fridley, Brooke L; Larson, Melissa C; Schildkraut, Joellen M; Palmieri, Rachel T; Cramer, Daniel W; Terry, Kathryn L; Vitonis, Allison F; Titus, Linda J; Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda; Gentry-Maharaj, Alexandra; Ramus, Susan J; Anderson, A Rebecca; Brueggmann, Doerthe; Fasching, Peter A; Gayther, Simon A; Huntsman, David G; Menon, Usha; Ness, Roberta B; Pike, Malcolm C; Risch, Harvey; Wu, Anna H; Berchuck, Andrew

    2012-01-01

    Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13?226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13?226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45). Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation. PMID:22361336

  3. Myeloperoxidase G-463A polymorphism and lung cancer: a HuGE genetic susceptibility to environmental carcinogens pooled analysis.

    PubMed

    Taioli, Emanuela; Benhamou, Simone; Bouchardy, Christine; Cascorbi, Ingolf; Cajas-Salazar, Nohelia; Dally, Heike; Fong, Kwun M; Larsen, Jill E; Le Marchand, Loic; London, Stephanie J; Risch, Angela; Spitz, Margaret R; Stucker, Isabelle; Weinshenker, Brian; Wu, Xifeng; Yang, Ping

    2007-02-01

    Myeloperoxidase is a phase I metabolic enzyme that converts the metabolites of benzo[a]pyrene from tobacco smoke into highly reactive epoxides. A polymorphism in the promoter region of myeloperoxidase (463G-->A) has been found to be inversely associated with lung cancer; differences in the association with age and gender have been suggested. We conducted a pooled analysis of individual data from 10 studies (3688 cases and 3874 controls) from the Genetic Susceptibility to Environmental Carcinogens database. The odds ratio for lung cancer was 0.88 (95% confidence interval: 0.80-0.97) for the AG variant of myeloperoxidase G-463A polymorphism, and 0.71 (95% confidence interval: 0.57-0.88) for the AA variant after adjusting for smoking, age, gender, and ethnicity. The inverse association between lung cancer and myeloperoxidase G-463A polymorphism was equally found in males and females (odds ratio for the AA genotype 0.73 [95% confidence interval: 0.56-0.96] and 0.67 [95% confidence interval: 0.46-0.98], respectively), without differences in the association according to age in the two genders. The myeloperoxidase G-463A polymorphism was significantly protective in "ever" smokers but not in "never" smokers. Myeloperoxidase is a key enzyme in tobacco-induced carcinogenesis. PMID:17304047

  4. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    PubMed Central

    Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubi?ski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35?568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (?12 years) was less frequent in case patients with PR? than PR+ tumors (P = .001). Nulliparity (P = 3 × 10?6) and increasing age at first birth (P = 2 × 10?9) were less frequent in ER? than in ER+ tumors. Obesity (body mass index [BMI] ? 30 kg/m2) in younger women (?50 years) was more frequent in ER?/PR? than in ER+/PR+ tumors (P = 1 × 10?7), whereas obesity in older women (>50 years) was less frequent in PR? than in PR+ tumors (P = 6 × 10?4). The triple-negative (ER?/PR?/HER2?) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. Conclusions This study shows that reproductive factors and BMI are most clearly associated with hormone receptor–positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology. PMID:21191117

  5. Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium

    PubMed Central

    2014-01-01

    Background Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. Methods We analyzed pooled data from 12 population-based case–control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. Results Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (?500mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). Conclusions Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use. PMID:24503200

  6. Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies

    Microsoft Academic Search

    Satu Mannisto; Shiaw-Shyuan Yaun; David J. Hunter; Donna Spiegelman; Hans-Olov Adami; Demetrius Albanes; Brandt van den Piet A; Julie E. Buring; James R. Cerhan; Graham A. Colditz; Jo L. Freudenheim; Charles S. Fuchs; Edward Giovannucci; R. Alexandra Goldbohm; Lisa Harnack; Michael Leitzmann; Marjorie L. McCullough; Anthony B. Miller; Thomas E. Rohan; Arthur Schatzkin; Jarmo Virtamo; Walter C. Willett; Alicja Wolk; Shumin M. Zhang; Stephanie A. Smith-Warner

    2007-01-01

    Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein þ zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in

  7. Complementary and Alternative Medicine Use and Breast Cancer Prognosis: A Pooled Analysis of Four Population-Based Studies of Breast Cancer Survivors

    PubMed Central

    Pagano, Ian S.; Maskarinec, Gertraud; Issell, Brian F.; Gotay, Carolyn C.

    2012-01-01

    Abstract Background Complementary and alternative medicine (CAM) use is common among breast cancer survivors, but little is known about its impact on survival. Methods We pooled data from four studies conducted in Hawaii in 1994–2003 and linked to the Hawaii Tumor Registry to obtain long-term follow-up information. The effect of CAM use on the risk of breast cancer-specific death was evaluated using Cox regression. Results The analysis included 1443 women with a median follow-up of 11.8 years who had a primary diagnosis of in situ and invasive breast cancer. The majority were Japanese American (36.4%), followed by white (26.9%), Native Hawaiian (15.9%), other (10.6%), and Filipino (10.3%). CAM use was highest in Native Hawaiians (60.7%) and lowest in Japanese American (47.8%) women. Overall, any use of CAM was not associated with the risk of breast cancer-specific death (hazard ratio [HR] 1.47, confidence interval [CI] 0.91-2.36) or all-cause death (HR 0.82, 95% CI 0.63-1.06). However, energy medicine was associated with an increased risk of breast cancer-specific death (HR 3.19, 95% CI 1.06-8.52). When evaluating CAM use within ethnic subgroups, Filipino women who used CAM were at increased risk of breast cancer death (HR 6.84, 95% CI 1.23-38.19). Conclusions Our findings suggest that, overall, CAM is not associated with breast cancer-specific death but that the effects of specific CAM modalities and possible differences by ethnicity should be considered in future studies. PMID:23075455

  8. 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

  9. Familial Aggregation of Glioma: A Pooled Analysis

    PubMed Central

    Scheurer, Michael E.; Etzel, Carol J.; Liu, Mei; Barnholtz-Sloan, Jill; Wiklund, Fredrik; Tavelin, Björn; Wrensch, Margaret R.; Melin, Beatrice S.; Bondy, Melissa L.

    2010-01-01

    In genome-wide association studies, inherited risk of glioma has been demonstrated for rare familial syndromes and with common variants from 3–5 chromosomal regions. To assess the degree of familial aggregation of glioma, the authors performed a pooled analysis of data from 2 large glioma case-control studies in the United States (MD Anderson Cancer Center, Houston, Texas (1994–2006) and University of California, San Francisco (1991–2004)) and from the Swedish Cancer Registry (1958–2006) to measure excess cases of cancer among first-degree relatives of glioma probands. This analysis included 20,377 probands with glioma and 52,714 first-degree relatives. No overall increase was found in the expected number of cancers among family members; however, there were 77% more gliomas than expected. There were also significantly more sarcoma and melanoma cases than expected, which is supported by evidence in the literature, whereas there were significantly fewer-than-expected cases of leukemia, non-Hodgkin lymphoma, and bladder, lung, pancreatic, prostate, and uterine cancers. This large pooled analysis provided sufficient numbers of related family members to examine the genetic mechanisms involved in the aggregation of glioma with other cancers in these families. However, misclassification due to unvalidated cancers among family members could account for the differences seen by study site. PMID:20858744

  10. Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies123

    PubMed Central

    Spiegelman, Donna; Baglietto, Laura; Bernstein, Leslie; Boggs, Deborah A; van den Brandt, Piet A; Buring, Julie E; Gapstur, Susan M; Giles, Graham G; Giovannucci, Edward; Goodman, Gary; Hankinson, Susan E; Helzlsouer, Kathy J; Horn-Ross, Pamela L; Inoue, Manami; Jung, Seungyoun; Khudyakov, Polyna; Larsson, Susanna C; Lof, Marie; McCullough, Marjorie L; Miller, Anthony B; Neuhouser, Marian L; Palmer, Julie R; Park, Yikyung; Robien, Kim; Rohan, Thomas E; Ross, Julie A; Schouten, Leo J; Shikany, James M; Tsugane, Shoichiro; Visvanathan, Kala; Weiderpass, Elisabete; Wolk, Alicja; Willett, Walter C; Zhang, Shumin M; Ziegler, Regina G; Smith-Warner, Stephanie A

    2012-01-01

    Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: ?-Carotene, ?-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER?) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): ?-carotene (0.87; 95% CI: 0.78, 0.97), ?-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): ?-carotene (1.04; 95% CI: 0.99, 1.09), ?-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for ?-cryptoxanthin were not significant, inverse trends were observed for ER? and ER+ breast cancer (P-trend ? 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of ?-carotene, ?-carotene, and lutein/zeaxanthin were inversely associated with risk of ER?, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources. PMID:22277553

  11. Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan)

    Microsoft Academic Search

    Dominique S. Michaud; Alina Vrieling; Li Jiao; Julie B. Mendelsohn; Emily Steplowski; Shannon M. Lynch; Jean Wactawski-Wende; Alan A. Arslan; H. Bas Bueno-de-Mesquita; Charles S. Fuchs; Myron Gross; Kathy Helzlsouer; Eric J. Jacobs; Andrea LaCroix; Gloria Petersen; Wei Zheng; Naomi Allen; Laufey Ammundadottir; Manuela M. Bergmann; Paolo Boffetta; Julie E. Buring; Federico Canzian; Stephen J. Chanock; Françoise Clavel-Chapelon; Sandra Clipp; Matthew S. Freiberg; J. Michael Gaziano; Edward L. Giovannucci; Susan Hankinson; Patricia Hartge; Robert N. Hoover; F. Allan Hubbell; David J. Hunter; Amy Hutchinson; Kevin Jacobs; Charles Kooperberg; Peter Kraft; Jonas Manjer; Carmen Navarro; Petra H. M. Peeters; Xiao-Ou Shu; Victoria Stevens; Gilles Thomas; Anne Tjønneland; Geoffrey S. Tobias; Dimitrios Trichopoulos; Rosario Tumino; Paolo Vineis; Jarmo Virtamo; Robert Wallace; Brian M. Wolpin; Kai Yu; Anne Zeleniuch-Jacquotte; Rachael Z. Stolzenberg-Solomon

    2010-01-01

    The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer;\\u000a however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to\\u000a detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed\\u000a these associations using 1,530 pancreatic

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

    PubMed Central

    Fan, Yun; Xu, Xiaoling; Xie, Conghua

    2014-01-01

    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. PMID:25419145

  13. Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

    PubMed

    Galeone, Carlotta; Edefonti, Valeria; Parpinel, Maria; Leoncini, Emanuele; Matsuo, Keitaro; Talamini, Renato; Olshan, Andrew F; Zevallos, Jose P; Winn, Deborah M; Jayaprakash, Vijayvel; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Bosetti, Cristina; Kelsey, Karl; McClean, Michael; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Lee, Yuan-Chin Amy; Hashibe, Mia; La Vecchia, Carlo; Boccia, Stefania

    2015-02-15

    There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR?=?0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR?=?0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR?=?4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk. PMID:24974959

  14. Cigarette smoking and lung cancer – relative risk estimates for the major histological types from a pooled analysis of case-control studies

    PubMed Central

    Pesch, Beate; Kendzia, Benjamin; Gustavsson, Per; Jöckel, Karl-Heinz; Johnen, Georg; Pohlabeln, Hermann; Olsson, Ann; Ahrens, Wolfgang; Gross, Isabelle Mercedes; Brüske, Irene; Wichmann, Heinz-Erich; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Fortes, Cristina; Siemiatycki, Jack; Parent, Marie-Elise; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Zaridze, David; Cassidy, Adrian; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Stücker, Isabelle; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudin, Charles M.; Brennan, Paul; Boffetta, Paolo; Straif, Kurt; Brüning, Thomas

    2011-01-01

    Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. Using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% CI 74.8-143.2) for SqCC, 111.3 (95% CI 69.8-177.5) for SCLC, and 21.9 (95% CI 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI 31.5-124.6), 108.6 (95% CI 50.7-232.8), and 16.8 (95% CI 9.2-30.6), respectively. Whereas ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development. PMID:22052329

  15. Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium

    PubMed Central

    Lurie, Galina; Wilkens, Lynne R.; Thompson, Pamela J.; Carney, Michael E.; Palmieri, Rachel T.; Pharoah, Paul D. P.; Song, Honglin; Hogdall, Estrid; Kjaer, Susanne Kruger; DiCioccio, Richard A.; McGuire, Valerie; Whittemore, Alice S.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J.; Goodman, Marc T.

    2010-01-01

    The association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non-Hispanic cases and 3479 controls in a pooled analysis of five population-based case-control studies within the Ovarian Cancer Association Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Carriers of the rare T allele were at increased risk of ovarian carcinoma compared to women with the CC genotype in all studies combined; each copy of the T allele was associated with a modest 9% increased risk (OR=1.09; 95% CI:1.01–1.19; p=0.04). No significant heterogeneity among studies was observed (p=0.37) and, after excluding the dataset from the Hawaii study, the risk association for rs2228570 among replication studies was unchanged (OR=1.09; 95% CI: 1.00–1.19; p=0.06). A stronger association of rs2228570 with risk was observed among younger women (aged < 50 years versus 50 years or older) (p=0.04). In all studies combined, the increased risk per copy of the T allele among younger women was 24% (OR=1.24; 95% CI: 1.04–1.47; p=0.02). This association remained statistically significant after excluding the Hawaii data (OR= 1.20; 95% CI: 1.01–1.43; p=0.04). No heterogeneity of the association was observed by stage (p= 0.46), tumor histology (p=0.98), or time between diagnosis and interview (p=0.94). This pooled analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility. PMID:20473893

  16. Analysis of deoxyribonucleotide pools in human cancer cell lines using a liquid chromatography coupled with tandem mass spectrometry technique

    PubMed Central

    Zhang, Wei; Tan, Shenglan; Paintsil, Elijah; Dutschman, Ginger E.; Gullen, Elizabeth A.; Chu, Edward; Cheng, Yung-Chi

    2011-01-01

    Endogenous ribonucleotides and deoxyribonucleotides play a critical role in cell function, and determination of their levels is of fundamental importance in understanding key cellular processes involved in energy metabolism and molecular and biochemical signaling pathways. In this study, we determined the respective ribonucleotide and deoxyribonucleotide pool sizes in different human cell lines using a simple sample preparation method and LC/MS/MS. This assay was used to determine alterations in deoxyribonucleotide pools in human pancreatic PANC-1 cells in response to hypoxia and to treatment with either hydroxyurea or aphidicolin. The levels of all deoxyribonucleotide metabolites decreased with hypoxia treatment, except for dUMP, which increased by two-fold. This LC/MS/MS assay is simple, fast, and sensitive, and it represents a significant advance over previously published methodologies. PMID:21620803

  17. 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

    2013-01-01

    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

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

    Microsoft Academic Search

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

    2009-01-01

    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

  19. Impact of body mass index on neoadjuvant treatment outcome: a pooled analysis of eight prospective neoadjuvant breast cancer trials.

    PubMed

    Fontanella, Caterina; Lederer, Bianca; Gade, Stephan; Vanoppen, Mieke; Blohmer, Jens Uwe; Costa, Serban Dan; Denkert, Carsten; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Hilfrich, Jörn; Huober, Jens; Schneeweiss, Andreas; Paepke, Stefan; Jackisch, Christian; Mehta, Keyur; Nekljudova, Valentina; Untch, Michael; Neven, Patrick; von Minckwitz, Gunter; Loibl, Sibylle

    2015-02-01

    Obesity is associated with an increased risk of breast cancer (BC) and poorer outcome. We assessed the impact of body mass index (BMI) on pathological complete response (pCR), disease-free (DFS), and overall survival (OS), according to BC subtypes in patients with primary BC treated with neoadjuvant chemotherapy. 8,872 patients with primary BC from eight neoadjuvant trials were categorized according to BMI: underweight (<18.5 kg/m(2)), normal weight (18.5 to <25 kg/m(2)), overweight (25 to <30 kg/m(2)), obese (30 to <40 kg/m(2)), and very obese (?40 kg/m(2)). BC subtypes were defined as luminal-like (ER/PgR-positive and HER2-negative), HER2/luminal (ER/PgR-positive and HER2-positive), HER2-like (ER/PgR-negative and HER2-positive), and triple-negative (TNBC; ER/PgR- and HER2-negative). pCR rate was higher in normal weight patients compared with all other BMI groups (P = 0.003). Mean DFS and OS were shorter in obese (87.3 months, P = 0.014 and 94.9 months, P = 0.001, respectively) and very obese (66.6 months, P < 0.001 and 75.3 months, P < 0.001, respectively) compared with normal weight patients (91.5 and 98.8 months, respectively) which was confirmed by subpopulation treatment effect pattern plot analyses and was consistent in luminal-like and TNBC. No interaction was observed between BMI and pCR. Normal weight patients experienced less non-hematological adverse events (P = 0.002) and were more likely to receive full taxane doses (P < 0.001) compared with all other BMI groups. In multivariable analysis, the dose of taxanes was predictive for pCR (P < 0.001). Higher BMI was associated with lower pCR and a detrimental impact on survival. Normal weight patients had the best compliance to chemotherapy and received the highest taxane doses, which seems to be related with treatment outcomes. PMID:25677740

  20. Adjuvant chemotherapy in rectal cancer: Defining subgroups who may benefit after neoadjuvant chemoradiation and resection: A pooled analysis of 3,313 patients.

    PubMed

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja M J; Beets-Tan, Regina G H; Beets, Geerard L

    2015-07-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. PMID:25418551

  1. Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.

    PubMed

    Conway, David I; Brenner, Darren R; McMahon, Alex D; Macpherson, Lorna M D; Agudo, Antonio; Ahrens, Wolfgang; Bosetti, Cristina; Brenner, Hermann; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Curioni, Otávio A; Dal Maso, Luigino; Daudt, Alexander W; de Gois Filho, José F; D'Souza, Gypsyamber; Edefonti, Valeria; Fabianova, Eleonora; Fernandez, Leticia; Franceschi, Silvia; Gillison, Maura; Hayes, Richard B; Healy, Claire M; Herrero, Rolando; Holcatova, Ivana; Jayaprakash, Vijayvel; Kelsey, Karl; Kjaerheim, Kristina; Koifman, Sergio; La Vecchia, Carlo; Lagiou, Pagona; Lazarus, Philip; Levi, Fabio; Lissowska, Jolanta; Luce, Daniele; Macfarlane, Tatiana V; Mates, Dana; Matos, Elena; McClean, Michael; Menezes, Ana M; Menvielle, Gwenn; Merletti, Franco; Morgenstern, Hal; Moysich, Kirsten; Müller, Heiko; Muscat, Joshua; Olshan, Andrew F; Purdue, Mark P; Ramroth, Heribert; Richiardi, Lorenzo; Rudnai, Peter; Schantz, Stimson; Schwartz, Stephen M; Shangina, Oxana; Simonato, Lorenzo; Smith, Elaine; Stucker, Isabelle; Sturgis, Erich M; Szeszenia-Dabrowska, Neonila; Talamini, Renato; Thomson, Peter; Vaughan, Thomas L; Wei, Qingyi; Winn, Deborah M; Wunsch-Filho, Victor; Yu, Guo-Pei; Zhang, Zuo-Feng; Zheng, Tongzhang; Znaor, Ariana; Boffetta, Paolo; Chuang, Shu-Chun; Ghodrat, Marianoosh; Amy Lee, Yuan-Chin; Hashibe, Mia; Brennan, Paul

    2015-03-01

    Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels. PMID:24996155

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

    PubMed

    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

    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

  3. 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

    2013-01-01

    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

  4. Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results

    PubMed Central

    Brinton, Louise A.

    2014-01-01

    Background The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. Methods In the Male Breast Cancer Pooling Project, a consortium of 11 case–control and 10 cohort investigations involving 2405 case patients (n = 1190 from case–control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design–specific (case–control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. Results Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86). Conclusions Consistent findings across case–control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones. PMID:24552677

  5. 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

    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

    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.

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

    E-print Network

    Csürös, Miklós

    College of Medicine, Houston, TX 77030, USA. Human Genome Sequencing Center, Department of MolecularPooled genomic indexing (PGI): analysis and design of experiments Mikl´os Csur¨os Aleksandar Milosavljevic July 29, 2004 Abstract Pooled Genomic Indexing (PGI) is a novel method for physical mapping

  7. Urban logistics pooling viabililty analysis via a multicriteria multiactor method

    E-print Network

    Paris-Sud XI, Université de

    Urban logistics pooling viabililty analysis via a multicriteria multiactor method Jesus Gonzalez transportation and logistics pooling are relatively new concepts in research, but are very popular in practice. In the last years, collaborative transportation seems a good city logistics alternative to classical urban

  8. Swimming Pools, Hot Rods, and Qualitative Analysis.

    ERIC Educational Resources Information Center

    Clyde, Dale D.

    1988-01-01

    Describes some reactions for the identification and application of cyanuric acid. Suggests students may find this applied chemistry interesting because of the use of cyanuric acid in swimming pools and diesel engines. Lists three tests for cyanate ion and two tests for cyanuric acid. (MVL)

  9. 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

    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

    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.

  10. IS URBAN LOGISTICS POOLING VIABLE? A MULTISTAKEHOLDER MULTICRITERIA ANALYSIS

    E-print Network

    Boyer, Edmond

    -after" comparative analysis. In this framework, a demand generation model is combined with a route optimization system (TMS), a risk management module and a multi- criteria analysis method. In this paper we focusIS URBAN LOGISTICS POOLING VIABLE? A MULTISTAKEHOLDER MULTICRITERIA ANALYSIS Jesus Gonzalez

  11. ORIGINAL ARTICLE: RESEARCH Chemokine polymorphisms and lymphoma: a pooled analysis

    E-print Network

    California at Berkeley, University of

    (HIV)-related non-Hodgkin lymphoma (NHL) but are understudied in non-HIV-related NHL. Associations conservatively. Continued investigation is warranted to confirm these findings. Keywords: Lymphoma non-HodgkinORIGINAL ARTICLE: RESEARCH Chemokine polymorphisms and lymphoma: a pooled analysis PAIGE M. BRACCI1

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

    E-print Network

    Csürös, Miklós

    Human Genome Sequencing Center, Department of Molecular and Human Genetics Baylor College of Medicine 3Pooled genomic indexing (PGI): mathematical analysis and experiment design Miklâ??os Cs�urË?os 1 Bioinformatics Research Laboratory, Department of Molecular and Human Genetics, Baylor College of Medicine

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

    PubMed

    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

    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

  14. Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis

    PubMed Central

    2013-01-01

    Background The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. Methods A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. Results Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer’s disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer’s disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. Conclusions This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered. PMID:23679869

  15. MMAPPR: Mutation Mapping Analysis Pipeline for Pooled RNA-seq

    PubMed Central

    Hill, Jonathon T.; Demarest, Bradley L.; Bisgrove, Brent W.; Gorsi, Bushra; Su, Yi-Chu; Yost, H. Joseph

    2013-01-01

    Forward genetic screens in model organisms are vital for identifying novel genes essential for developmental or disease processes. One drawback of these screens is the labor-intensive and sometimes inconclusive process of mapping the causative mutation. To leverage high-throughput techniques to improve this mapping process, we have developed a Mutation Mapping Analysis Pipeline for Pooled RNA-seq (MMAPPR) that works without parental strain information or requiring a preexisting SNP map of the organism, and adapts to differential recombination frequencies across the genome. MMAPPR accommodates the considerable amount of noise in RNA-seq data sets, calculates allelic frequency by Euclidean distance followed by Loess regression analysis, identifies the region where the mutation lies, and generates a list of putative coding region mutations in the linked genomic segment. MMAPPR can exploit RNA-seq data sets from isolated tissues or whole organisms that are used for gene expression and transcriptome analysis in novel mutants. We tested MMAPPR on two known mutant lines in zebrafish, nkx2.5 and tbx1, and used it to map two novel ENU-induced cardiovascular mutants, with mutations found in the ctr9 and cds2 genes. MMAPPR can be directly applied to other model organisms, such as Drosophila and Caenorhabditis elegans, that are amenable to both forward genetic screens and pooled RNA-seq experiments. Thus, MMAPPR is a rapid, cost-efficient, and highly automated pipeline, available to perform mutant mapping in any organism with a well-assembled genome. PMID:23299975

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

    PubMed Central

    2013-01-01

    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

  17. Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC

    PubMed Central

    Paz-Ares, Luis; Soulières, Denis; Moecks, Joachim; Bara, Ilze; Mok, Tony; Klughammer, Barbara

    2014-01-01

    Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n = 731), 54 gefitinib studies (n = 1802) and 20 chemotherapy studies (n = 984) provided median PFS values for each treatment. The pooled median PFS was: 12.4 months (95% accuracy intervals [AI] 11.6–13.4) for erlotinib-treated patients; 9.4 months (95% AI 9.0–9.8) for gefitinib-treated patients; and 5.6 months (95% AI 5.3–6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P = 0.000 and P = 0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy. PMID:25100284

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

    Microsoft Academic Search

    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

    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

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

    PubMed Central

    2012-01-01

    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

  20. Identifying Sexual Orientation Health Disparities in Adolescents: Analysis of Pooled Data From the Youth Risk Behavior Survey, 2005 and 2007

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

    Hemminki, E.; McPherson, K.

    1997-01-01

    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

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

    E-print Network

    Stevenson, Paul

    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

  3. Admixture Aberration Analysis: Application to Mapping in Admixed Population Using Pooled DNA

    NASA Astrophysics Data System (ADS)

    Bercovici, Sivan; Geiger, Dan

    Admixture mapping is a gene mapping approach used for the identification of genomic regions harboring disease susceptibility genes in the case of recently admixed populations such as African Americans. We present a novel method for admixture mapping, called admixture aberration analysis (AAA), that uses a DNA pool of affected admixed individuals. We demonstrate through simulations that AAA is a powerful and economical mapping method under a range of scenarios, capturing complex human diseases such as hypertension and end stage kidney disease. The method has a low false-positive rate and is robust to deviation from model assumptions. Finally, we apply AAA on 600 prostate cancer-affected African Americans, replicating a known risk locus. Simulation results indicate that the method can yield over 96% reduction in genotyping. Our method is implemented as a Java program called AAAmap and is freely available.

  4. Pooled analysis of tiotropium Respimat(®) pharmacokinetics in cystic fibrosis.

    PubMed

    Sharma, Ashish; Geller, David E; Moroni-Zentgraf, Petra; Kattenbeck, Sabine; Schmid, Marion; Boland, Katja; Rapp, Barbara; Konstan, Michael W; Ratjen, Felix; Elborn, J Stuart; Koker, Paul

    2014-12-01

    Tiotropium is the first bronchodilator to be studied systematically in cystic fibrosis (CF). We investigated whether any intrinsic or extrinsic factors affected pharmacokinetic (PK) parameters of inhaled tiotropium delivered by Respimat(®) in adults and children with CF. Tiotropium PK in patients with CF was compared with that of healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). This pooled analysis summarizes the PK parameters of inhaled tiotropium Respimat(®) across 9 early- and late-phase trials involving 27 healthy volunteers (1 trial), 409 patients with CF (3 trials), and 281 patients with COPD (5 trials). Patients with CF aged 5 to 11, 12 to 17, and ? 18 years had similar tiotropium plasma concentrations (geometric mean C(0.083,ss,norm): 2.22 pg/mL/?g; not determined for patients aged <5 years). The fraction excreted unchanged in the urine was 3.4-fold lower for patients aged 0.4 to <5 years than for those aged 5 to 11 years (fe(0-4,ss): 1.19% vs 4.09%). Tiotropium PK parameters were similar between CF patients and COPD patients. PMID:25161072

  5. MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

    PubMed Central

    Sekhar, Deepa; Francis, Amirtharaj; Gupta, Nishi; Konwar, Rituraj; Kumar, Sandeep; Kumar, Surender; Thangaraj, Kumarasamy; Rajender, Singh

    2015-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent. Methods and Results We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067). Conclusion 677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer. PMID:25803740

  6. Operating Systems Review 34(2), 42-55, 2000 Analysis of Optimal Thread Pool Size

    E-print Network

    Mullen, Tracy

    Operating Systems Review 34(2), 42-55, 2000 Analysis of Optimal Thread Pool Size 1 Yibei Ling, 1. However, creating and destroying a thread is far from free, requiring run-time memory allocation behind system slowdowns. A thread-pool architecture addresses this problem by prespawning

  7. 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

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

    E-print Network

    McSharry, Patrick E.

    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

  9. Microbiological Analysis in Three Diverse Natural Geothermal Bathing Pools in Iceland

    PubMed Central

    Thorolfsdottir, Berglind Osk Th.; Marteinsson, Viggo Thor

    2013-01-01

    Natural thermal bathing pools contain geothermal water that is very popular to bathe in but the water is not sterilized, irradiated or treated in any way. Increasing tourism in Iceland will lead to increasing numbers of bath guests, which can in turn affect the microbial flora in the pools and therefore user safety. Today, there is no legislation that applies to natural geothermal pools in Iceland, as the water is not used for consumption and the pools are not defined as public swimming pools. In this study, we conducted a microbiological analysis on three popular but different natural pools in Iceland, located at Lýsuhóll, Hveravellir and Landmannalaugar. Total bacterial counts were performed by flow cytometry, and with plate count at 22 °C, 37 °C and 50 °C. The presence of viable coliforms, Enterococcus spp. and pseudomonads were investigated by growth experiments on selective media. All samples were screened for noroviruses by real time PCR. The results indicate higher fecal contamination in the geothermal pools where the geothermal water flow was low and bathing guest count was high during the day. The number of cultivated Pseudomonas spp. was high (13,000–40,000 cfu/100 mL) in the natural pools, and several strains were isolated and classified as opportunistic pathogens. Norovirus was not detected in the three pools. DNA was extracted from one-liter samples in each pool and analyzed by partial 16S rRNA gene sequencing. Microbial diversity analysis revealed different microbial communities between the pools and they were primarily composed of alpha-, beta- and gammaproteobacteria. PMID:23493033

  10. POOLED ANALYSIS OF STUDIES ON DNA ADDUCTS AND DIETARY VITAMINS

    PubMed Central

    Ragin, Camille; Minor, Aerie; Agudo, Antonio; Farmer, Peter; Garte, Seymour; Gonzales, Carlos; Kalina, Ivan; Matullo, Pino; Popov, Todor; Palli, Domenico; Peluso, Marco; Riccieri, Fulvio; Sram, Radim; Vineis, Paolo; Taioli, Emanuela

    2010-01-01

    Objectives There is some evidence that dietary components that are rich in antioxidant and vitamins are inversely associated with DNA adduct levels induced by environmental carcinogens such as polycyclic aromatic hydrocarbons, although the epidemiologic data are inconsistent. This study addresses the association between vitamins, DNA adducts and smoking. Methods A combined analysis of individual data on the association between bulky DNA adducts and dietary vitamins were conducted. A Medline search was performed to identify studies on healthy subjects in which smoking and vitamins intake information were available, and bulky DNA adducts were measured in peripheral blood with 32P post labeling. Eight published studies met the eligibility criteria, and individual data from 7 data sets including 2,758 subjects were obtained. GSTM1 and GSTT1 were also available on all the subjects. Results Vitamin E was inversely significantly associated with DNA adducts after adjustment for possible confounding factors. Vitamin A and C were not independent predictors of DNA adducts. A stratified analysis showed that vitamin A had a significant inverse association with DNA adducts in ever smokers only. Conclusions This result is relevant to planning any future chemo-preventive interventions directed to high risk subgroups of the population, for cancer prevention. PMID:20399891

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

    SciTech Connect

    Hall, B.W.

    1996-09-25

    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.

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

    SciTech Connect

    Hall, B.W.

    1996-09-25

    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.

  13. Analysis of the TRIGA reactor pool water. Technical report

    SciTech Connect

    Dickson, J.; George, R.; Moore, L.; Moore, M.

    1993-08-01

    The reactor at AFRRI is a Mark F, 1 megawatt TRIGA (training, research, isotope, General Atomic) reactor. The reactor hangs in a cloverleaf-shaped tank that contains 15,000 gallons of demineralized water. The aluminum tank varies in thickness from 1/4 inch for the exposure room projections to 1/2 inch for the tank bottom. Eighty percent of the reactor building and all of the reactor tank are below ground level. Algae growth in the reactor tank stimulated efforts to remove the algae from the pool. The source of nutrients for the algae had not been explored until recently. Reports that aluminum reactor tanks develop leaks prompted the reactor staff to begin a reactor pool water quality monitoring program to establish a baseline of measureable contaminants. Baseline data would be used to provide early detection of leaks because a change in baseline contaminants could indicate the start of a leak. This report summarizes the data collected, the steps taken to reduce the impurities, and the efforts to kill the algae and bacteria in the pool.

  14. Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies

    PubMed Central

    Nitti, V W; Khullar, V; Kerrebroeck, P; Herschorn, S; Cambronero, J; Angulo, J C; Blauwet, M B; Dorrepaal, C; Siddiqui, E; Martin, N E

    2013-01-01

    Introduction To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results. Methods This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ? 50% reduction in incontinence episodes/24 h, ? 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate). Results Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (? 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine. Conclusion The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB. PMID:23692526

  15. 76 FR 72923 - Pool Corporation; Analysis To Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ...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...

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

    PubMed Central

    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

    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

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

    SciTech Connect

    Hongbin Zhang; Haihua Zhao; Cliff Davis

    2008-06-01

    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.

  18. Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis

    PubMed Central

    2011-01-01

    Background Chemotherapy dose delay and/or reduction lower relative total dose intensity (RTDI) and may affect short- and long-term outcome of metastatic breast cancer (MBC) patients. Methods Based on 933 individual patients' data of from 3 randomized MBC trials using an anthracycline and taxane we examined the impact of RTDI on efficacy and determined the lowest optimal RTDI for MBC patients. Results Median time to disease progression (TTDP) and overall survival (OS) of all patients were 39 and 98 weeks. Overall higher RTDI was correlated with a shorter TTDP (log-rank p = 0.0525 for 85% RTDI cut-off). Proportional hazards assumption was violated, there was an early drop in the TTDP-curve for the high RTDI group. It was explained by the fact that patients with primary disease progression (PDP) do have a high RTDI per definition. Excluding those 114 patients with PDP the negative correlation between RTDI and TTDP vanished. However, non-PDP patients with RTDI-cut-off levels <85% showed a shorter OS than patients with higher RTDI levels (p = 0.0086). Conclusions Optimizing RTDI above 85% appears to improve long-term outcome of MBC patients receiving first-line chemotherapy. Lowering RTDI had no negative influence on short term outcome like OR and TTDP. PMID:21486442

  19. Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis

    SciTech Connect

    Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Eppinga, Wietse; Lagerwaard, Frank [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands)] [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands); Cloughesy, Timothy [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Slotman, Benjamin [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands)] [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands); Nghiemphu, Phioanh L. [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Neuro-Oncology Program, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)] [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Selch, Michael T.; Steinberg, Michael [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States) [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California (United States); Kang, Jung Julie [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)] [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-07-15

    Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

  20. Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

    PubMed Central

    Ricci, Giampaolo; Astolfi, Annalisa; Remondini, Daniel; Cipriani, Francesca; Formica, Serena; Dondi, Arianna; Pession, Andrea

    2011-01-01

    Background Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach. Methodology/Principal Findings We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. Conclusion/Significance Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population. PMID:21359210

  1. Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies

    PubMed Central

    2013-01-01

    Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials. Design Systematic review of observational studies. Data sources Medline, Embase, to December 2012. Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals. Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up). Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management. Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450. PMID:24191270

  2. Transcranial laser therapy for acute ischemic stroke: a pooled analysis of NEST-1 and NEST-2

    PubMed Central

    Huisa, Branko N; Stemer, Andrew B; Walker, Michael G; Rapp, Karen; Meyer, Brett C.; Zivin, Justin A

    2011-01-01

    Background NeuroThera Effectiveness and Safety Trials (NEST) 1 and 2 have demonstrated safety of transcranial laser therapy for human treatment in acute ischemic stroke. The NEST-1 study suggested efficacy of transcranial laser therapy but the following NEST-2, despite strong signals, missed reaching significance on its primary efficacy endpoint. In order to assess efficacy in a larger cohort, a pooled analysis was therefore performed. Methods The two studies were first compared for heterogeneity, and then a pooled analysis was performed to assess overall safety and efficacy, and examined particular subgroups. The primary endpoint for the pooled analysis was dichotomized modified Rankin scale (mRS 0–2) at 90 days. Results Efficacy analysis for the Intention-To-Treat population was based on a total of 778 patients. Baseline characteristics and prognostic factors were balanced between the two groups. The transcranial laser therapy group (n=410) success rate measured by the dichotomized 90 day mRS was significantly higher compared with the Sham group (n=368) (p=0.003, OR 1.67, 95% CI 1.19– 2.35). The distribution of scores on the 90-day mRS was significantly different in transcranial laser therapy compared with Sham (p=0.0005 Cochran-Mantel-Haenszel). Subgroup analysis identified moderate strokes as a predictor of better treatment response. Conclusions This pooled analysis support the likelihood that transcranial laser therapy is effective for the treatment of acute ischemic stroke when initiated within 24 h of stroke onset. If ultimately confirmed, transcranial laser therapy will change management for ischemic stroke and improve outcomes of far more patients with acute ischemic stroke. PMID:22299818

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

    PubMed Central

    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.

    2013-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

    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.

  5. Phase II trials in patients with carcinoma of unknown primary: a pooled data analysis

    Microsoft Academic Search

    Antoine Adenis; Charles Ferté; Nicolas Penel

    2010-01-01

    Summary  \\u000a Background The management of carcinoma of unknown primary site remains debatable. The literature data consists of about 29 phase-II\\u000a studies investigating 38 regimens, providing a broad range of response rates (RR). Methods We performed a pooled published data analysis to identify the factors influencing RR in these 29 studies. Results In front-line treatment, the overall RR was 31% (430\\/1,380).

  6. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents

    Microsoft Academic Search

    Christian Spaulding; Joost Daemen; H. Boersma; Donald E. Cutlip; Patrick W. Serruys

    2007-01-01

    BACKGROUND: Although randomized studies have shown a beneficial effect of drug-eluting stents in reducing the risk of repeated revascularization, these trials were underpowered to compare rates of death and myocardial infarction. The long-term safety of drug-eluting stents has been questioned recently. METHODS: We performed a pooled analysis of 1748 patients in four randomized trials evaluating the safety of sirolimus-eluting stents

  7. A Pooled Analysis of Data Comparing Sirolimus-Eluting Stents with Bare-Metal Stents

    Microsoft Academic Search

    Christian Spaulding; Joost Daemen; Eric Boersma; Donald E. Cutlip; Patrick W. Serruys

    2010-01-01

    Background Although randomized studies have shown a beneficial effect of drug-eluting stents in reducing the risk of repeated revascularization, these trials were underpowered to compare rates of death and myocardial infarction. The long-term safety of drug-elut- ing stents has been questioned recently. Methods We performed a pooled analysis of 1748 patients in four randomized trials evaluating the safety of sirolimus-eluting

  8. Systematic review and meta-analysis of cyclodiene insecticides and breast cancer.

    PubMed

    Khanjani, Narges; Hoving, Jan Lucas; Forbes, Andrew Benjamin; Sim, Malcolm Ross

    2007-01-01

    Cyclodienes are a group of organochlorine pesticides that have been the focus of increasing numbers of breast cancer etiology studies in recent years. The aim of this systematic review and meta-analysis was to summarize and pool the results of breast cancer and cyclodiene insecticide contamination studies. We used databases from 1966 to 7/2006 and included 21 case-control studies. Pooled odds ratios or differences in means as geometric means ratios were calculated. Meta-analysis of the chemicals did not reveal any statistically significant association except for heptachlor. The heterogeneity among the different studies and the methodology limitations are discussed. PMID:17365341

  9. STATISTICAL ANALYSIS OF CORTICAL MORPHOMETRICS USING POOLED DISTANCES BASED ON LABELED CORTICAL DISTANCE MAPS

    PubMed Central

    Ceyhan, E.; Hosakere, M.; Nishino, T.; Alexopoulos, J.; Todd, R.D.; Botteron, K.N.; Miller, M.I.; Ratnanather, J.T.

    2010-01-01

    Neuropsychiatric disorders have been demonstrated to manifest shape differences in cortical structures. Labeled Cortical Distance Mapping (LCDM) is a powerful tool in quantifying such morphometric differences and characterizes the morphometry of the laminar cortical mantle of cortical structures. Specifically, LCDM data are distances of labeled gray matter (GM) voxels with respect to the gray/white matter cortical surface. Volumes and descriptive measures (such as means and variances for each subject) based on LCDM distances provide descriptive summary information on some of the shape characteristics. However, additional morphometrics are contained in the data and their analysis may provide additional clues to underlying differences in cortical characteristics. To use more of this information, we pool (merge) LCDM distances from subjects in the same group. These pooled distances can help detect morphometric differences between groups, but do not provide information about the locations of such differences in the tissue in question. In this article, we check for the influence of the assumption violations on the analysis of pooled LCDM distances. We demonstrate that the classical parametric tests are robust to the non-normality and within sample dependence of LCDM distances and nonparametric tests are robust to within sample dependence of LCDM distances. We specify the types of alternatives for which the tests are more sensitive. We also show that the pooled LCDM distances provide powerful results for group differences in distribution of LCDM distances. As an illustrative example, we use GM in the ventral medial prefrontal cortex (VMPFC) in subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy subjects. Significant morphometric differences were found in VMPFC due to MDD or being at HR. In particular, the analysis indicated that distances in left and right VMPFCs tend to decrease due to MDD or being at HR, possibly as a result of thinning. The methodology can also be applied to other cortical structures. PMID:21765611

  10. Testing homeopathy in mouse emotional response models: pooled data analysis of two series of studies.

    PubMed

    Bellavite, Paolo; Conforti, Anita; Marzotto, Marta; Magnani, Paolo; Cristofoletti, Mirko; Olioso, Debora; Zanolin, Maria Elisabetta

    2012-01-01

    Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1?mg/kg body weight) or buspirone (5?mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD) choice test and the open-field (OF) exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter "time spent in central area" and of Gelsemium s. 5C, 9C, and 30C on the LD parameters "time spent in lit area" and "number of light-dark transitions," without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization. PMID:22548123

  11. Testing Homeopathy in Mouse Emotional Response Models: Pooled Data Analysis of Two Series of Studies

    PubMed Central

    Bellavite, Paolo; Conforti, Anita; Marzotto, Marta; Magnani, Paolo; Cristofoletti, Mirko; Olioso, Debora; Zanolin, Maria Elisabetta

    2012-01-01

    Two previous investigations were performed to assess the activity of Gelsemium sempervirens (Gelsemium s.) in mice, using emotional response models. These two series are pooled and analysed here. Gelsemium s. in various homeopathic centesimal dilutions/dynamizations (4C, 5C, 7C, 9C, and 30C), a placebo (solvent vehicle), and the reference drugs diazepam (1?mg/kg body weight) or buspirone (5?mg/kg body weight) were delivered intraperitoneally to groups of albino CD1 mice, and their effects on animal behaviour were assessed by the light-dark (LD) choice test and the open-field (OF) exploration test. Up to 14 separate replications were carried out in fully blind and randomised conditions. Pooled analysis demonstrated highly significant effects of Gelsemium s. 5C, 7C, and 30C on the OF parameter “time spent in central area” and of Gelsemium s. 5C, 9C, and 30C on the LD parameters “time spent in lit area” and “number of light-dark transitions,” without any sedative action or adverse effects on locomotion. This pooled data analysis confirms and reinforces the evidence that Gelsemium s. regulates emotional responses and behaviour of laboratory mice in a nonlinear fashion with dilution/dynamization. PMID:22548123

  12. 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.

  13. Swimming Pools.

    ERIC Educational Resources Information Center

    Ministry of Housing and Local Government, London (England).

    Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

  14. Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control.

    PubMed

    Legrand, G; Humez, S; Slomianny, C; Dewailly, E; Vanden Abeele, F; Mariot, P; Wuytack, F; Prevarskaya, N

    2001-12-14

    The present study demonstrates for the first time that intracellular calcium-ATPases and calcium pool content are closely associated with prostate cancer LNCaP cell growth. Cell growth was modulated by changing the amount of epidermal growth factor, serum, and androgene in culture media. Using the microspectrofluorimetric method with Fura-2 and Mag Fura-2 as probes, we show that in these cells, the growth rate is correlated with intracellular calcium pool content. Indeed, an increased growth rate is correlated with an increase in the calcium pool filling state, whereas growth-inhibited cells show a reduced calcium pool load. Using Western blotting and immunocytochemistry, we show that endoplasmic reticulum calcium pump expression is closely linked to LNCaP cell growth, and are a common target of physiological stimuli that control cell growth. Moreover, we clearly demonstrate that inhibition of these pumps, using thapsigargin, inhibits LNCaP cell growth and prevents growth factor from stimulating cell proliferation. Our results thus provide evidence for the essential role of functional endoplasmic reticulum calcium pumps and calcium pool in control of prostate cancer LNCaP cell growth, raising the prospect of new targets for the treatment of prostate cancer. PMID:11606580

  15. A Pooled Analysis of Melanocytic Naevus Phenotype and the Risk of Cutaneous Melanoma at Different Latitudes

    PubMed Central

    Chang, Yu-mei; Newton-Bishop, Julia A; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Green, Adèle C; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Reich, Kristian; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus-Ernstoff, Linda; Zens, Michael S; Ziegler, Andreas; Barrett, Jennifer H

    2008-01-01

    An abnormal naevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual naevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify better the risk, and to determine whether relative risk varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with naevus characteristics. Participants with whole body naevus counts in the highest of four population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged <50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged ?50). The pOR for presence compared with absence of any clinically atypical naevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1–2 and ?3 large naevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of naevus phenotype, except for the analysis of naevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal naevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of naevi, large naevi and clinically atypical naevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes. PMID:18792098

  16. Methods for cancer epigenome analysis.

    PubMed

    Nagarajan, Raman P; Fouse, Shaun D; Bell, Robert J A; Costello, Joseph F

    2013-01-01

    Accurate detection of epimutations in tumor cells is crucial for -understanding the molecular pathogenesis of cancer. Alterations in DNA methylation in cancer are functionally important and clinically relevant, but even this well-studied area is continually re-evaluated in light of unanticipated results, such as the strong association between aberrant DNA methylation in adult tumors and polycomb group profiles in embryonic stem cells, cancer-associated genetic mutations in epigenetic regulators such as DNMT3A and TET family genes, and the discovery of altered 5-hydroxymethylcytosine, a product of TET proteins acting on 5-methylcytosine, in human tumors with TET mutations. The abundance and distribution of covalent histone modifications in primary cancer tissues relative to normal cells is an important but largely uncharted area, although there is good evidence for a mechanistic role of cancer-specific alterations in histone modifications in tumor etiology, drug response, and tumor progression. Meanwhile, the discovery of new epigenetic marks continues, and there are many useful methods for epigenome analysis applicable to primary tumor samples, in addition to cancer cell lines. For DNA methylation and hydroxymethylation, next-generation sequencing allows increasingly inexpensive and quantitative whole-genome profiling. Similarly, the refinement and maturation of chromatin immunoprecipitation with next-generation sequencing (ChIP-seq) has made possible genome-wide mapping of histone modifications, open chromatin, and transcription factor binding sites. Computational tools have been developed apace with these epigenome methods to better enable accurate interpretation of the profiling data. PMID:22956508

  17. CPAP: Cancer Panel Analysis Pipeline.

    PubMed

    Huang, Po-Jung; Yeh, Yuan-Ming; Gan, Ruei-Chi; Lee, Chi-Ching; Chen, Ting-Wen; Lee, Cheng-Yang; Liu, Hsuan; Chen, Shu-Jen; Tang, Petrus

    2013-10-01

    Targeted sequencing using next-generation sequencing technologies is currently being rapidly adopted for clinical sequencing and cancer marker tests. However, no existing bioinformatics tool is available for the analysis and visualization of multiple targeted sequencing datasets. In the present study, we use cancer panel targeted sequencing datasets generated by the Life Technologies Ion Personal Genome Machine Sequencer as an example to illustrate how to develop an automated pipeline for the comparative analyses of multiple datasets. Cancer Panel Analysis Pipeline (CPAP) uses standard output files from variant calling software to generate a distribution map of SNPs among all of the samples in a circular diagram generated by Circos. The diagram is hyperlinked to a dynamic HTML table that allows the users to identify target SNPs by using different filters. CPAP also integrates additional information about the identified SNPs by linking to an integrated SQL database compiled from SNP-related databases, including dbSNP, 1000 Genomes Project, COSMIC, and dbNSFP. CPAP only takes 17 min to complete a comparative analysis of 500 datasets. CPAP not only provides an automated platform for the analysis of multiple cancer panel datasets but can also serve as a model for any customized targeted sequencing project. PMID:23893859

  18. Tea consumption and prostate cancer: an updated meta-analysis

    PubMed Central

    2014-01-01

    Objectives Tea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis. Methods A total of 21 published articles were retrieved via both computerized searches and review of references. Estimates of OR/RR for highest versus non/lowest tea consumption levels were pooled on the basis of random effect model or fixed effect model as appropriate. Stratified analyses on tea type, population and study design were also conducted. Results No statistical significance was detected between tea consumption and prostate cancer risk in meta-analysis of all included studies (odds ratio (OR)?=?0.86, 95% CI (0.69-1.04)). Furthermore, stratified analyses on population (Asian, OR?=?0.81, 95% CI (0.55-1.08); non-Asian, OR?=?0.89, 95% CI (0.72-1.07)) and tea type (green tea, OR?=?0.79, 95% CI (0.43-1.14); black tea, OR?=?0.88, 95% CI (0.73-1.02)) also yielded non-significant association. Only the case–control study subgroup demonstrated a borderline protective effect for tea consumption against prostate cancer (OR?=?0.77, 95% CI (0.55-0.98)). Conclusion Our analyses did not support the conclusion that tea consumption could reduce prostate cancer risk. Further epidemiology studies are needed. PMID:24528523

  19. An international pooled analysis for obtaining a benchmark dose for environmental lead exposure in children.

    PubMed

    Budtz-Jørgensen, Esben; Bellinger, David; Lanphear, Bruce; Grandjean, Philippe

    2013-03-01

    Lead is a recognized neurotoxicant, but estimating effects at the lowest measurable levels is difficult. An international pooled analysis of data from seven cohort studies reported an inverse and supra-linear relationship between blood lead concentrations and IQ scores in children. The lack of a clear threshold presents a challenge to the identification of an acceptable level of exposure. The benchmark dose (BMD) is defined as the dose that leads to a specific known loss. As an alternative to elusive thresholds, the BMD is being used increasingly by regulatory authorities. Using the pooled data, this article presents BMD results and applies different statistical techniques in the analysis of multistudy data. The calculations showed only a limited variation between studies in the steepness of the dose-response functions. BMD results were quite robust to modeling assumptions with the best fitting models yielding lower confidence limits (BMDLs) of about 0.1-1.0 ? g/dL for the dose leading to a loss of one IQ point. We conclude that current allowable blood lead concentrations need to be lowered and further prevention efforts are needed to protect children from lead toxicity. PMID:22924487

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

    E-print Network

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

    2006-01-01

    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...

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

    PubMed Central

    2013-01-01

    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

  2. PWR core and spent fuel pool analysis using scale and nestle

    SciTech Connect

    Murphy, J. E.; Maldonado, G. I. [Dept. of Nuclear Engineering, Univ. of Tennessee, Knoxville, TN 37996-2300 (United States); St Clair, R.; Orr, D. [Duke Energy, 526 S. Church St, Charlotte, NC 28202 (United States)

    2012-07-01

    The SCALE nuclear analysis code system [SCALE, 2011], developed and maintained at Oak Ridge National Laboratory (ORNL) is widely recognized as high quality software for analyzing nuclear systems. The SCALE code system is composed of several validated computer codes and methods with standard control sequences, such as the TRITON/NEWT lattice physics sequence, which supplies dependable and accurate analyses for industry, regulators, and academia. Although TRITON generates energy-collapsed and space-homogenized few group cross sections, SCALE does not include a full-core nodal neutron diffusion simulation module within. However, in the past few years, the open-source NESTLE core simulator [NESTLE, 2003], originally developed at North Carolina State Univ. (NCSU), has been updated and upgraded via collaboration between ORNL and the Univ. of Tennessee (UT), so it now has a growingly seamless coupling to the TRITON/NEWT lattice physics [Galloway, 2010]. This study presents the methodology used to couple lattice physics data between TRITON and NESTLE in order to perform a three-dimensional full-core analysis employing a 'real-life' Duke Energy PWR as the test bed. The focus for this step was to compare the key parameters of core reactivity and radial power distribution versus plant data. Following the core analysis, following a three cycle burn, a spent fuel pool analysis was done using information generated from NESTLE for the discharged bundles and was compared to Duke Energy spent fuel pool models. The KENO control module from SCALE was employed for this latter stage of the project. (authors)

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

    PubMed

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

    2011-08-01

    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

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

    SciTech Connect

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

    1993-01-01

    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.

  5. Chlorination, chlorination by-products, and cancer: a meta-analysis.

    PubMed Central

    Morris, R D; Audet, A M; Angelillo, I F; Chalmers, T C; Mosteller, F

    1992-01-01

    OBJECTIVES. Individual epidemiological investigations into the association between chlorination by-products in drinking water and cancer have been suggestive but inconclusive. Enough studies exist to provide the basis for a meaningful meta-analysis. METHODS. An extensive literature search was performed to identify pertinent case-control studies and cohort studies. Consumption of chlorinated water, surface water, or water with high levels of chloroform was used as a surrogate for exposure to chlorination by-products. Relative risk estimates were abstracted from the individual studies and pooled. RESULTS. A simple meta-analysis of all cancer sites yielded a relative risk estimate for exposure to chlorination by-products of 1.15 (95% CI: 1.09, 1.20). Pooled relative risk estimates for organ-specific neoplasms were 1.21 (95% CI: 1.09, 1.34) for bladder cancer and 1.38 (95% CI: 1.01, 1.87) for rectal cancer. When studies that adjusted for potential confounders were pooled separately, estimates of relative risks did not change substantially. CONCLUSIONS. The results of this meta-analysis suggest a positive association between consumption of chlorination by-products in drinking water and bladder and rectal cancer in humans. PMID:1535181

  6. Alcohol and Cancer Risk

    MedlinePLUS

    ... increased alcohol consumption is associated with a decreased risk of cancer ( 10 , 11 ). A meta-analysis of the NHL studies (which included 18,759 ... Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology ...

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

    SciTech Connect

    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

    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.

  8. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    NASA Astrophysics Data System (ADS)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an ?/? value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  9. Analysis and improvement of data-set level file distribution in Disk Pool Manager

    NASA Astrophysics Data System (ADS)

    Cadellin Skipsey, Samuel; Purdie, Stuart; Britton, David; Mitchell, Mark; Bhimji, Wahid; Smith, David

    2014-06-01

    Of the three most widely used implementations of the WLCG Storage Element specification, Disk Pool Manager[1, 2] (DPM) has the simplest implementation of file placement balancing (StoRM doesn't attempt this, leaving it up to the underlying filesystem, which can be very sophisticated in itself). DPM uses a round-robin algorithm (with optional filesystem weighting), for placing files across filesystems and servers. This does a reasonable job of evenly distributing files across the storage array provided to it. However, it does not offer any guarantees of the evenness of distribution of that subset of files associated with a given "dataset" (which often maps onto a "directory" in the DPM namespace (DPNS)). It is useful to consider a concept of "balance", where an optimally balanced set of files indicates that the files are distributed evenly across all of the pool nodes. The best case performance of the round robin algorithm is to maintain balance, it has no mechanism to improve balance. In the past year or more, larger DPM sites have noticed load spikes on individual disk servers, and suspected that these were exacerbated by excesses of files from popular datasets on those servers. We present here a software tool which analyses file distribution for all datasets in a DPM SE, providing a measure of the poorness of file location in this context. Further, the tool provides a list of file movement actions which will improve dataset-level file distribution, and can action those file movements itself. We present results of such an analysis on the UKI-SCOTGRID-GLASGOW Production DPM.

  10. Community analysis of plant biomass-degrading microorganisms from Obsidian Pool, Yellowstone National Park.

    PubMed

    Vishnivetskaya, Tatiana A; Hamilton-Brehm, Scott D; Podar, Mircea; Mosher, Jennifer J; Palumbo, Anthony V; Phelps, Tommy J; Keller, Martin; Elkins, James G

    2015-02-01

    The conversion of lignocellulosic biomass into biofuels can potentially be improved by employing robust microorganisms and enzymes that efficiently deconstruct plant polysaccharides at elevated temperatures. Many of the geothermal features of Yellowstone National Park (YNP) are surrounded by vegetation providing a source of allochthonic material to support heterotrophic microbial communities adapted to utilize plant biomass as a primary carbon and energy source. In this study, a well-known hot spring environment, Obsidian Pool (OBP), was examined for potential biomass-active microorganisms using cultivation-independent and enrichment techniques. Analysis of 33,684 archaeal and 43,784 bacterial quality-filtered 16S rRNA gene pyrosequences revealed that archaeal diversity in the main pool was higher than bacterial; however, in the vegetated area, overall bacterial diversity was significantly higher. Of notable interest was a flooded depression adjacent to OBP supporting a stand of Juncus tweedyi, a heat-tolerant rush commonly found growing near geothermal features in YNP. The microbial community from heated sediments surrounding the plants was enriched in members of the Firmicutes including potentially (hemi)cellulolytic bacteria from the genera Clostridium, Anaerobacter, Caloramator, Caldicellulosiruptor, and Thermoanaerobacter. Enrichment cultures containing model and real biomass substrates were established at a wide range of temperatures (55-85 °C). Microbial activity was observed up to 80 °C on all substrates including Avicel, xylan, switchgrass, and Populus sp. Independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures. PMID:25319238

  11. Pooled ANOVA

    Microsoft Academic Search

    Michael Last; Gheorghe Luta; Alexandro Orso; Adam A. Porter; Stan Young

    2008-01-01

    We introduce Pooled ANOVA, a greedy algorithm to sequentially select the rare important factors from a large set of factors. Problems such as computer simulations and software performance tuning involve a large number of factors, few of which have an important effect on the outcome or performance measure. We pool multiple factors together, and test the pool for significance. If

  12. Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis

    PubMed Central

    Halpin, David MG; Dahl, Ronald; Hallmann, Christoph; Mueller, Achim; Tashkin, Donald

    2015-01-01

    Introduction Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 ?g once daily) or Respimat® Soft Mist™ inhaler (5 ?g once daily). The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles. This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials. Methods Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 ?g and Respimat® 5 ?g randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ?4 weeks). Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately. Results In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure. Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted). The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]). The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group. Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium. Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs. Conclusion This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. PMID:25709423

  13. Clinicopathological and prognostic role of SIRT1 in breast cancer patients: a meta-analysis

    PubMed Central

    Cao, Yu-Wen; Li, Yu-Cong; Wan, Guo-Xing; Du, Xiao-Ming; Li, Feng

    2015-01-01

    Background: Silent mating type information regulation 2 homolog-1 (SIRT1) plays an important role in the progression and development of cancer, including breast cancer. However, the association between SIRT1 expression and clinicopathological parameters and prognosis in breast cancer remains inconclusive. To accurately evaluate the significance of SIRT1 expression in breast cancer, a meta-analysis based on published studies was performed. Methods: The PubMed, Embase, ISI Web of Science, Science Direct, and Chinese National Knowledge Infrastructure databases were screened to retrieve relevant literature. The reported odds ratios (ORs) and hazard ratios (HRs) and their 95% corresponding confidence intervals (CIs) were pooled to estimate the strength of specific associations. Results: Six studies involving 604 patients were included in the meta-analysis. The pooled analyses showed a significant correlation between SIRT1 expression and poor disease-free survival (DFS) (HR = 3.07, 95% CI: 1.92-4.91, Z = 4.69, P < 0.001) and overall survival (OS) (HR = 3.94, 95% CI: 2.19-7.10, Z = 4.57, P < 0.001). SIRT1 expression also significantly correlated with high TNM stage (pooled OR = 2.92, 95% CI: 1.84-4.63) and lymph node metastasis (pooled OR = 3.22, 95% CI: 0.98-10.57). Conclusions: Our meta-analysis shows that SIRT1 expression correlates with unfavorable clinical outcomes. We suggest that SIRT1 expression may have potential value in the pathological diagnosis and clinical treatment of patients with breast cancer. More studies are warranted to investigate the effect of SIRT1 on the survival of breast cancer patients. PMID:25785036

  14. Diagnosis and Management of Seminal Vesicle Cysts Associated with Ipsilateral Renal Agenesis: A Pooled Analysis of 52 Cases

    Microsoft Academic Search

    D. van den Ouden; J. H. M. Blom; C. Bangma; A. H. V. C. de Spiegeleer

    1998-01-01

    Objective: Seminal vesicle cysts combined with ipsilateral renal agenesis represent a rare urological anomaly. We searched the literature to review the clinical presentation, diagnosis and therapeutic treatment options of this anomaly. Methods: A pooled analysis was performed of 52 cases of seminal vesicle cysts combined with ipsilateral renal agenesis, including our own observation. The evaluation included: patient age at diagnosis,

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

    PubMed

    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

    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

  16. Gamma glutamyltransferase, alanine aminotransferase and risk of cancer: systematic review and meta-analysis.

    PubMed

    Kunutsor, Setor K; Apekey, Tanefa A; Van Hemelrijck, Mieke; Calori, Giliola; Perseghin, Gianluca

    2015-03-01

    The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is uncertain. We conducted a systematic review and meta-analysis of published prospective observational studies evaluating the associations of baseline levels of GGT and ALT with risk of overall (incidence and/or mortality) and site-specific cancers. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, reference lists of relevant studies to April 2014 and email contact with investigators. Study specific relative risks (RRs) were meta-analyzed using random effects models. Fourteen cohort studies with data on 1.79 million participants and 57,534 cancer outcomes were included. Comparing top versus bottom thirds of baseline circulating GGT levels, pooled RRs (95% confidence intervals) were 1.32 (1.15-1.52) for overall cancer, 1.09 (0.95-1.24) for cancers of the breast and female genital organs, 1.09 (1.02-1.16) for cancers of male genital organs, 1.94 (1.35-2.79) for cancers of digestive organs and 1.33 (0.94-1.89) for cancers of respiratory and intrathoracic organs. For ALT, corresponding RRs for overall cancer were 0.96 (0.94-0.99) and 1.65 (1.52-1.79) in European and Asian populations, respectively. There was an increased risk of cancers of the digestive organs 2.44 (1.23-4.84). The pooled RR for overall cancer per 5 U/L increment in GGT levels was 1.04 (1.03-1.05). Available observational data indicate a positive log-linear association of GGT levels with overall cancer risk. The positive association was generally evident for site-specific cancers. There are geographical variations in the association of ALT and overall cancer. PMID:25043373

  17. Clinical characteristics of incidental or unsuspected gallbladder cancers diagnosed during or after cholecystectomy: A systematic review and meta-analysis

    PubMed Central

    Choi, Kui Sun; Choi, Sae Byeol; Park, Pyoungjae; Kim, Wan Bae; Choi, Sang Yong

    2015-01-01

    AIM: To perform a systematic review of incidental or unsuspected gallbladder (GB) cancer diagnosed during or after cholecystectomy. METHODS: Data in PubMed, EMBASE, and Cochrane Library were reviewed and 26 publications were included in the meta-analysis. The inclusion criterion for incidental GB cancer was GB cancer diagnosed during or after cholecystectomy that was not suspected at a preoperative stage. Pooled proportions of the incidence, distribution of T stage, and revisional surgery of incidental GB cancer were analyzed. RESULTS: The final pooled population comprised 2145 patients with incidental GB cancers. Incidental GB cancers were found in 0.7% of cholecystectomies performed for benign gallbladder diseases on preoperative diagnosis (95%CI: 0.004-0.012). Nearly 50% of the incidental GB cancers were stage T2 with a pooled proportion of 47.0% (95%CI: 0.421-0.519). T1 and T3 GB cancers were found at a similar frequency, with pooled proportions of 23.0% (95%CI: 0.178-0.291) and 25.1% (95%CI: 0.195-0.317), respectively. The pooled proportion that completed revisional surgery for curative intent was 40.9% (95%CI: 0.329-0.494). The proportion of patients with unresectable disease upon revisional surgery was 23.0% (95%CI: 0.177-0.294). CONCLUSION: A large proportion of incidental GB cancers were T2 and T3 lesions. Revisional surgery for radical cholecystectomy is warranted in T2 and more advanced cancers. PMID:25632207

  18. Monitoring of high-power fiber laser welding based on principal component analysis of a molten pool configuration

    NASA Astrophysics Data System (ADS)

    Xiangdong, Gao; Qian, Wen

    2013-12-01

    There exists plenty of welding quality information on a molten pool during high-power fiber laser welding. An approach for monitoring the high-power fiber laser welding status based on the principal component analysis (PCA) of a molten pool configuration is investigated. An infrared-sensitive high-speed camera was used to capture the molten pool images during laser butt-joint welding of Type 304 austenitic stainless steel plates with a high-power (10 kW) continuous wave fiber laser. In order to study the relationship between the molten pool configuration and the welding status, a new method based on PCA is proposed to analyze the welding stability by comparing the situation when the laser beam spot moves along, and when it deviates from the weld seam. Image processing techniques were applied to process the molten pool images and extract five characteristic parameters. Moreover, the PCA method was used to extract a composite indicator which is the linear combination of the five original characteristics to analyze the different status during welding. Experimental results showed that the extracted composite indicator had a close relationship with the actual welding results and it could be used to evaluate the status of the high-power fiber laser welding, providing a theoretical basis for the monitoring of laser welding quality.

  19. Striking life events associated with primary breast cancer susceptibility in women: a meta-analysis study

    PubMed Central

    2013-01-01

    Purpose The association between striking life events, an important stress and acute anxiety disorder, and the occurrence of primary breast cancer is unclear. The current meta-analysis was designed to assess the relationship between striking life events and primary breast cancer incidence in women. Methods Systematic computerized searching of the PubMed, ScienceDirect, Embase, and BMJ databases with the combinations of controlled descriptors from Mesh, including breast cancer, breast tumor, cancer of breast, mammary carcinoma, life events, life change events, case–control studies, case-base studies, cohort study, and cohort analysis and identified a total of 307 papers published from January 1995 to April 2012. Following evaluation of methodological quality with the Downs & Black criteria, seven case–control or cohort studies were selected and the association between striking life events and primary breast cancer incidence in women was measured using random effect or fixed-effect odds ratios combined with 95% confidence interval. Results The seven studies included in the final meta-analysis included 99,807 women. A meta-analysis showed that the pooled OR for striking life events and breast cancer was 1.51 (95% CI 1.15 - 1.97, P = 0.003), indicating that women with striking life events were at 1.5-fold greater risk of developing breast cancer. The pooled OR for severe striking life events and breast cancer was 2.07 (95% CI 1.06 - 4.03), indicating that women with severe striking life events were at 2-fold greater risk of developing breast cancer. Conclusions The current meta-analysis showed significant evidence for a positive association between striking life events and primary breast cancer incidence in women. PMID:23941600

  20. Analysis of urine from pooled urinals - a novel method for the detection of novel psychoactive substances.

    PubMed

    Archer, J R H; Hudson, S; Wood, D M; Dargan, P I

    2013-06-01

    Current data on the epidemiology of recreational drug use is largely based on population and self-population surveys of drug use. In addition, increasingly, particularly for novel psychoactive substances, data collected from web monitoring systems is used to collect information on early trends in the use of NPS and the drugs available to users. All of these indicators rely on users self-report of the drug(s) that they are using, or more accurately the drugs that they perceive they are using. Numerous recent studies have demonstrated significant variation in the content of both classical recreational drugs and novel psychoactive substances. The technique of waste-water analysis has allowed estimation of population level use of a number of established recreational drugs such as cocaine and MDMA. However this technique is limited for novel psychoactive substances because of limitations in the knowledge of the stability and metabolism of these compounds. Our group has developed a technique that involves the collection and analysis of pooled-urine from standalone portable urinals and demonstrated that this technique can be used to detect the use of both classical, established recreational drugs and novel psychoactive substances. We discuss this technique in this paper and the ways in which this can be further developed to allow detection of use of new NPS and trends in use of these substances over time and across geographical regions. PMID:24308525

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

    PubMed

    Je, Youjin; Giovannucci, Edward

    2012-10-01

    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

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

    PubMed Central

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

    2013-01-01

    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

  3. INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET EN AUTOMATIQUE Analysis of the Balancing Process in a Pool of Self-Service

    E-print Network

    Paris-Sud XI, Université de

    , is currently under development in some European cities. It consists of a pool of cars (some time electric cars Process in a Pool of Self-Service Cars Cyril Duron, Michel Parent et Jean-Marie Proth N°3949 Mai 2000. inria-00072700,version1-24May2006 #12;3 Analysis of the balancing process in a pool of self-service cars

  4. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis.

    PubMed

    Al-Adra, D P; Gill, R S; Axford, S J; Shi, X; Kneteman, N; Liau, S-S

    2015-01-01

    Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC. PMID:25449754

  5. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: A systematic review and pooled analysis

    PubMed Central

    Al-Adra, D.P.; Gill, R.S.; Axford, S.J.; Shi, X.; Kneteman, N.; Liau, S.-S.

    2015-01-01

    Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC. PMID:25449754

  6. Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies

    PubMed Central

    Kaasch, Achim J.; Barlow, Gavin; Edgeworth, Jonathan D.; Fowler, Vance G.; Hellmich, Martin; Hopkins, Susan; Kern, Winfried V.; Llewelyn, Martin J.; Rieg, Siegbert; Rodriguez-Baño, Jesús; Scarborough, Matthew; Seifert, Harald; Soriano, Alex; Tilley, Robert; T?r?k, M. Estée; Wei?, Verena; Wilson, A. Peter R.; Thwaites, Guy E.

    2014-01-01

    Summary Objectives Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. Methods We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. Results The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). Conclusion The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus. PMID:24247070

  7. Pool Purification

    NASA Technical Reports Server (NTRS)

    1988-01-01

    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.

  8. Selenium and Lung Cancer: A Systematic Review and Meta Analysis

    PubMed Central

    Fritz, Heidi; Kennedy, Deborah; Fergusson, Dean; Fernandes, Rochelle; Cooley, Kieran; Seely, Andrew; Sagar, Stephen; Wong, Raimond; Seely, Dugald

    2011-01-01

    Background Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. Methods and Findings Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (?121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61–1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70–3.24); and all-cause-death, OR 0.93 (95%CI 0.79–1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. Conclusions Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context. PMID:22073154

  9. Volatile disinfection by-product analysis from chlorinated indoor swimming pools.

    PubMed

    Weaver, William A; Li, Jing; Wen, Yuli; Johnston, Jessica; Blatchley, Michael R; Blatchley, Ernest R

    2009-07-01

    Chlorination of indoor swimming pools is practiced for disinfection and oxidation of reduced compounds that are introduced to water by swimmers. However, there is growing concern associated with formation for chlorinated disinfection by-products (DBPs) in these settings. Volatile DBPs are of particular concern because they may promote respiratory ailments and other adverse health effects among swimmers and patrons of indoor pool facilities. To examine the scope of this issue, water samples were collected from 11 pools over a 6month period and analyzed for free chlorine and their volatile DBP content. Eleven volatile DBPs were identified: monochloramine (NH(2)Cl), dichloramine (NHCl(2)), trichloramine (NCl(3)), chloroform (CHCl(3)), bromoform (CHBr(3)), dichlorobromomethane (CHBrCl(2)), dibromochloromethane (CHBr(2)Cl), cyanogen chloride (CNCl), cyanogen bromide (CNBr), dichloroacetonitrile (CNCHCl(2)), and dichloromethylamine (CH(3)NCl(2)). Of these 11 DBPs, 10 were identified as regularly occurring, with CHBrCl(2) only appearing sporadically. Pool water samples were analyzed for residual chlorine compounds using the DPD colorimetric method and by membrane introduction mass spectrometry (MIMS). These two methods were chosen as complementary measures of residual chlorine, and to allow for comparisons between the methods. The DPD method was demonstrated to consistently overestimate inorganic chloramine content in swimming pools. Pairwise correlations among the measured volatile DBPs allowed identification of dichloromethylamine and dichloroacetonitrile as potential swimming pool water quality indicator compounds. PMID:19501873

  10. Comparative efficacy of different modalities for treatment of right heart thrombi in transit: A pooled analysis.

    PubMed

    Athappan, Ganesh; Sengodan, Prasanna; Chacko, Paul; Gandhi, Sanjay

    2015-04-01

    The objective was to compare the efficacy of treatment options for right heart thrombi (RHT) in transit. All published reports between 1992 and 2013 were identified and pooled. We analyzed 328 patients with RHT and pulmonary embolism (PE). The treatments administered were none in 11 patients (3.4%), anticoagulation (AC) with heparin in 70 patients (21.3%), thrombolytics in 122 patients (37.2%), catheter-related treatments in five patients (1.5%) and surgical embolectomy in 120 patients (36.6%). The overall short-term mortality for the entire cohort was 23.2%. The mortality rate associated with no therapy was highest at 90.9%. The mortality associated with AC alone was significantly higher than surgical embolectomy or thrombolysis (37.1% vs 18.3% vs 13.7%, respectively). In univariate analysis, any therapy was better than no therapy with a favorable odds of 16.92 (95% CI 2.05-139.87) for AC, 61.76 (95% CI 7.42-513.81) for thrombolysis and 44.54 (95% CI 5.42-366.32) for surgical embolectomy. In multivariate analysis with age and hemodynamic status entered as covariates, thrombolytic therapy was better than AC with favorable odds of 4.83 (95% CI 1.52-15.36). Similarly, there was a trend in favor of surgical embolectomy with an odds of 2.61 (95% CI 0.90-7.58). The estimated probability of survival in hemodynamically unstable patients with AC, surgical embolectomy and thrombolysis was 47.7%, 70.45% and 81.5%, respectively. There was no significantly increased risk of complications with thrombolytic therapy. In conclusion, left untreated, patients with RHT and PE have very high mortality. Aggressive management with thrombolysis or surgical thrombectomy may be more effective than AC alone in the management of these patients. PMID:25832601

  11. Integrative Microarray Analysis of Pathways Dysregulated in Metastatic Prostate Cancer

    E-print Network

    Gerstein, Mark

    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

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

    PubMed Central

    2014-01-01

    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

  13. XPG Asp1104His polymorphism and gastrointestinal cancers risk: a meta-analysis

    PubMed Central

    Luo, Jian-Fei; Yan, Rui-Cheng; Zou, Li

    2014-01-01

    Several studies have reported the association between the Asp1104His polymorphism in xeroderma pigmentosum group G (XPG) gene and risk of gastrointestinal cancers. However, the results are inconsistent. This meta-analysis was performed to assess the association between XPG Asp1104His polymorphism and gastrointestinal cancers risk. Relevant studies were identified using PubMed, Web of Science, CNKI, WanFang and VIP databases up to July 22, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed- or random effects model. 13 case-control studies from twelve publications with 4275 patients and 5735 controls were included. Overall, a significant association was found between the XPG Asp1104His polymorphism and the risk of gastrointestinal cancers (dominant model: OR = 1.15, 95% CI: 1.05-1.26; His/His vs. Asp/Asp: OR = 1.15, 95% CI: 1.01-1.32). When the analysis was stratified by ethnicity, similar results were observed in Asians under homozygote model; in stratification analysis by cancer type, increased cancer risk was detected in colorectal and hepatocellular carcinoma, but not for other gastrointestinal cancers. Furthermore, in subgroup analysis by source of control, we failed to detect any association among population, hospital and family-based populations. This meta-analysis indicated that the XPG Asp1104His polymorphism may be a risk factor for gastrointestinal cancers, especially of colorectal cancer. PMID:25550928

  14. Prognostic Role of microRNA-21 in Colorectal Cancer: a Meta-Analysis

    PubMed Central

    Xia, Xiaochun; Yang, Baixia; Zhai, Xiaogang; Liu, Xiangyang; Shen, Kang; Wu, Zhijun; Cai, Jing

    2013-01-01

    Background To date, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. The present meta-analysis summarizes the recent advances in the use of microRNA-21 (miR-21) in the assessment of colorectal cancer and analyzes the prognostic role of miR-21 for survival outcome. Methodology/Principal Findings The present meta-analysis was performed by searching PubMed through multiple search strategies. Data were extracted from studies comparing overall survival (OS) in patients with colorectal cancer who showed higher expression of miR-21 than similar patients. Pooled hazard ratios (HRs) of miR-21 for survival and 95% confidence intervals (CI) were calculated. Seven studies with a total of 1174 patients were included this meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in colorectal cancer was 1.76 (95% CI: 1.34–2.32, P=0.000). After elimination of heterogeneity, the pooled HR was 2.32 (95% CI: 1.82–2.97, P=0.000), which was found to significantly predict poorer survival. The subgroup analysis suggested that elevated miR-21 level and patients’ survival correlated with III/IV stage (HR=5.35, 95% CI: 3.73–7.66). Conclusions/Significance The present findings suggest that high expression of miR-21 might predict poor prognosis in patients with colorectal cancer. PMID:24265822

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

    PubMed Central

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

    2012-01-01

    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

  16. Incorporating Network Structure in Integrative Analysis of Cancer Prognosis Data

    PubMed Central

    Liu, Jin; Huang, Jian; Ma, Shuangge

    2014-01-01

    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

  17. The Cancer Genome Atlas Pan-Cancer analysis project.

    PubMed

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

    2013-10-01

    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 major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

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

    SciTech Connect

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

    2006-12-01

    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.

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

    PubMed

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

    2014-05-01

    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

  20. 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.

  1. Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts

    PubMed Central

    2012-01-01

    Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (?50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates. PMID:22692650

  2. Association between tea and coffee consumption and risk of laryngeal cancer: a meta-analysis

    PubMed Central

    Ouyang, Zhiguo; Wang, Zhaoyan; Jin, Jian

    2014-01-01

    Objective: Epidemiological studies evaluating the association of tea and coffee consumption and the risk of laryngeal cancer have produced inconsistent results. Thus, we conducted a meta-analysis to assess the relationship between tea and coffee consumption and laryngeal cancer risk. Methods: Pertinent studies were identified by a search in PubMed, Web of Knowledge and Wan Fang Med Online. The random effect model was used based on heterogeneity test. Publication bias was estimated using Egger’s regression asymmetry test. As a result, 11 articles were included in this meta-analysis. Results: For tea consumption and laryngeal cancer, data from 8 studies including 2167 laryngeal cancer cases were used, and the pooled results suggested that highest tea consumption versus lowest level wasn’t associated with the risk of laryngeal cancer [summary RR = 0.909, 95% CI = 0.674-1.227]. Eight studies comprising 2596 laryngeal cancer cases for coffee consumption and laryngeal cancer risk were included, and no association was found (summary RR = 1.218, 95% CI = 0.915-1.622). Conclusions: Finding from this meta-analysis suggested that tea and coffee consumption weren’t associated with the risk of laryngeal cancer. Since the potential biases and confounders could not be ruled out completely in this meta-analysis, further studies are warranted to confirm this result. PMID:25664021

  3. Development of a Self-Report Physical Function Instrument for Disability Assessment: Item Pool Construction and Factor Analysis

    PubMed Central

    McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Marfeo, Elizabeth E; Brandt, Diane E; Chan, Leighton; Meterko, Mark; Haley, Stephen M.; Rasch, Elizabeth K.

    2014-01-01

    Objectives To build a comprehensive item pool representing work-relevant physical functioning and to test the factor structure of the item pool. These developmental steps represent initial outcomes of a broader project to develop instruments for the assessment of function within the context of Social Security Administration (SSA) disability programs. Design Comprehensive literature review; gap analysis; item generation with expert panel input; stakeholder interviews; cognitive interviews; cross-sectional survey administration; and exploratory and confirmatory factor analyses to assess item pool structure. Setting In-person and semi-structured interviews; internet and telephone surveys. Participants A sample of 1,017 SSA claimants, and a normative sample of 999 adults from the US general population. Interventions Not Applicable. Main Outcome Measure Model fit statistics Results The final item pool consisted of 139 items. Within the claimant sample 58.7% were white; 31.8% were black; 46.6% were female; and the mean age was 49.7 years. Initial factor analyses revealed a 4-factor solution which included more items and allowed separate characterization of: 1) Changing and Maintaining Body Position, 2) Whole Body Mobility, 3) Upper Body Function and 4) Upper Extremity Fine Motor. The final 4-factor model included 91 items. Confirmatory factor analyses for the 4-factor models for the claimant and the normative samples demonstrated very good fit. Fit statistics for claimant and normative samples respectively were: Comparative Fit Index = 0.93 and 0.98; Tucker-Lewis Index = 0.92 and 0.98; Root Mean Square Error Approximation = 0.05 and 0.04. Conclusions The factor structure of the Physical Function item pool closely resembled the hypothesized content model. The four scales relevant to work activities offer promise for providing reliable information about claimant physical functioning relevant to work disability. PMID:23542402

  4. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    SciTech Connect

    Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER?) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  5. 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.

  6. 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.

  7. Association of cholesterol with risk of pancreatic cancer: A meta-analysis

    PubMed Central

    Wang, Jia; Wang, Wei-Jing; Zhai, Long; Zhang, Dong-Feng

    2015-01-01

    AIM: To evaluate the effect of dietary cholesterol and serum total cholesterol (TC) on the risk of pancreatic cancer. METHODS: A literature search was performed up to June 2014 in PubMed, EMBASE, China National Knowledge Infrastructure and China Biology Medical literature database for relevant articles published in English or Chinese. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS: We included 14 published articles with 439355 participants for dietary cholesterol, and 6 published articles with 1805697 participants for serum TC. For the highest vs lowest category of dietary cholesterol, the pooled RR (95%CI) of pancreatic cancer was 1.308 (1.097-1.559). After excluding two studies (RR > 3.0), the pooled RR (95%CI) was 1.204 (1.050-1.380). In subgroup analysis stratified by study design, the pooled RRs (95%CIs) were 1.523 (1.226-1.893) for case-control studies and 1.023 (0.871-1.200) for cohort studies. The association of dietary cholesterol with the risk of pancreatic cancer was significant for studies conducted in North America [1.275 (1.058-1.537)] and others [2.495 (1.565-3.977)], but not in Europe [1.149 (0.863-1.531)]. No significant association [1.003 (0.859-1.171)] was found between the risk of pancreatic cancer and serum TC. CONCLUSION: Dietary cholesterol may be associated with an increased risk of pancreatic cancer in worldwide populations, except for Europeans. The results need to be confirmed further.

  8. A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Meta-analyses reached conflicting results regarding vitamin D and fracture reduction. We pooled individual participant-level data from 11 double-blind RCTs of oral vitamin D supplementation (daily, weekly, 4-monthly) with or without calcium compared with placebo or calcium in seniors age 65 and olde...

  9. Myeloperoxidase Polymorphism, Menopausal Status, and Breast Cancer Risk: An Update Meta-Analysis

    PubMed Central

    Peng, Qi-Liu; Huang, Xiu-Li; Mo, Cui-Ju; Li, Shan; Zhao, Jin-Min

    2013-01-01

    Myeloperoxidase (MPO) is a metabolic/oxidative lysosomal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during phagocytosis. MPO has been either directly or indirectly linked to neoplasia, which is a well-established risk factor for many types of cancer. A large number of studies have reported the role of MPO G-463A polymorphism regarding breast-cancer risk. However, the published findings are inconsistent. Therefore, we conducted a meta-analysis to determine more precise estimations for the relationship. Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. According to the inclusion criteria and exclusion criteria, a total of five eligible studies were included in the pooled analyses. When the five eligible studies concerning MPO G-463A polymorphism were pooled into this meta-analysis, there was no evidence found for a significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. We also categorized by ethnicity (Caucasian or Asian) for subgroup analysis; according to this subgroup analysis, we found no significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. However, in the stratified analysis for the premenopausal group, women carrying the AA genotype were found to have a significantly reduced risk (OR?=?0.56, 95% CI 0.34–0.94, p?=?0.027). Under the recessive model, there was a significant association between MPO G-463A polymorphism and breast-cancer risk (OR?=?0.57, 95% CI 0.34–0.93, p?=?0.025). We conclude that MPO-G463A polymorphism might not be a good predictor of breast-cancer risk, though menopausal status modified women’s risk of developing breast cancer. PMID:23991124

  10. Is ioflupane I123 injection diagnostically effective in patients with movement disorders and dementia? Pooled analysis of four clinical trials

    PubMed Central

    O'Brien, John T; Oertel, Wolfgang H; McKeith, Ian G; Grosset, Donald G; Walker, Zuzana; Tatsch, Klaus; Tolosa, Eduardo; Sherwin, Paul F; Grachev, Igor D

    2014-01-01

    Objectives To pool clinical trials of similar design to assess overall sensitivity and specificity of ioflupane I123 injection (DaTSCAN or ioflupane (123I)) to detect or exclude a striatal dopaminergic deficit disorder (SDDD), such as parkinsonian syndrome and dementia with Lewy bodies. Design Pooled analysis of three phase 3 and one phase 4 clinical trials. These four trials were selected because they were the four studies used for the US new drug application to the Food and Drug Administration (FDA). Setting Multicentre, open-label, non-randomised. Participants Patients with either a movement disorder or dementia, and healthy volunteers. Interventions Ioflupane (123I) was administered. Outcome measures Images were assessed by panels of 3–5 blinded experts and/or on-site nuclear medicine physicians, classified as normal or abnormal and compared with clinical diagnosis (reference standard) to determine sensitivity and specificity. Results Pooling the four studies, 928 participants were enrolled, 849 were dosed and 764 completed their study. Across all studies, when images were assessed by on-site readers, ioflupane (123I) diagnostic effectiveness had an overall (95% CI) sensitivity of 91.9% (88.7% to 94.5%) and specificity of 83.6% (78.7% to 87.9%). When reads were conducted blindly by a panel of independent experts, the overall sensitivity was 88.7% (86.8% to 90.4%) and specificity was 91.2% (89.0% to 93.0%). Conclusions In this pooled analysis, the visual assessment of ioflupane (123I) images provided high levels of sensitivity and specificity in detecting the presence/absence of an SDDD. Ioflupane (123I) imaging has the potential to improve diagnostic accuracy in patients with signs and symptoms of a movement disorder and/or dementia. Trial registration number NCT00209456. PMID:24993764

  11. Cellular Levels of 8-Oxoguanine in either DNA or the Nucleotide Pool Play Pivotal Roles in Carcinogenesis and Survival of Cancer Cells

    PubMed Central

    Nakabeppu, Yusaku

    2014-01-01

    8-Oxoguanine, a major oxidized base lesion formed by reactive oxygen species, causes G to T transversion mutations or leads to cell death in mammals if it accumulates in DNA. 8-Oxoguanine can originate as 8-oxo-dGTP, formed in the nucleotide pool, or by direct oxidation of the DNA guanine base. MTH1, also known as NUDT1, with 8-oxo-dGTP hydrolyzing activity, 8-oxoguanine DNA glycosylase (OGG1) an 8-oxoG DNA glycosylase, and MutY homolog (MUTYH) with adenine DNA glycosylase activity, minimize the accumulation of 8-oxoG in DNA; deficiencies in these enzymes increase spontaneous and induced tumorigenesis susceptibility. However, different tissue types have different tumorigenesis susceptibilities. These can be reversed by combined deficiencies in the defense systems, because cell death induced by accumulation of 8-oxoG in DNA is dependent on MUTYH, which can be suppressed by MTH1 and OGG1. In cancer cells encountering high oxidative stress levels, a high level of 8-oxo-dGTP accumulates in the nucleotide pool, and cells therefore express increased levels of MTH1 in order to eliminate 8-oxo-dGTP. Suppression of MTH1 may be an efficient strategy for killing cancer cells; however, because MTH1 and OGG1 protect normal tissues from oxidative-stress-induced cell death, it is important that MTH1 inhibition does not increase the risk of healthy tissue degeneration. PMID:25029543

  12. Aspirin for the primary prevention of skin cancer: A meta-analysis

    PubMed Central

    ZHU, YUN; CHENG, YANG; LUO, RONG-CHENG; LI, AI-MIN

    2015-01-01

    Skin cancer is one of the most common cancers worldwide. There are three major skin cancer types: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. General risk factors for skin cancer include fair skin, a history of tanning and sunburn, family history of skin cancer, exposure to ultraviolet rays and a large number of moles. The incidence of skin cancer has increased in the USA in recent years. Aspirin intake is associated with chemoprotection against the development of a number of types of cancer. However, whether aspirin intake can reduce the risk of development of skin cancer is unclear. The present meta-analysis of available human studies is aimed at evaluating the association between aspirin exposure and the risk of skin cancer. All available human observational studies on aspirin intake for the primary prevention of skin cancer were identified by searching MEDLINE (Pubmed), BIOSIS, EMBASE, Cochrane Library and China National Knowledge Infrastructure prior to March 2013. The heterogeneity and publication bias of all studies were evaluated using Cochran’s Q and I2 statistics, followed by a random-effect model where applicable. The pooled data were analyzed by odds ratios (ORs) and 95% confidence intervals (CIs). A total of eight case-control and five prospective cohort studies from 11 publications were selected for this analysis. There was no evidence of publication bias in these studies. Statistical analyses of the pooled data demonstrated that that a daily dose of 50–400 mg aspirin was significantly associated with a reduced risk of skin cancers (OR, 0.94; 95% CI, 0.90–0.99; P=0.02). Stratification analysis indicated that the continual intake of low dose aspirin (?150 mg) reduced the risk of developing skin cancer (OR, 0.95; CI, 0.90–0.99; P=0.15) and that aspirin intake was significantly associated with a reduced risk of non-melanoma skin cancers (OR, 0.97; CI, 0.95–0.99; P=0.22). Overall, these findings indicated that aspirin intake was associated with a reduced risk of developing skin cancer. However, more well-designed randomized controlled trials to measure the effects of aspirin intake are required to confirm this. PMID:25663859

  13. Three-Dimensional Ignition and Flame Propagation Above Liquid Fuel Pools: Computational Analysis

    NASA Technical Reports Server (NTRS)

    Cai, Jinsheng; Sirignano, William A.

    2001-01-01

    A three-dimensional unsteady reactive Navier-Stokes code is developed to study the ignition and flame spread above liquid fuels initially below the flashpoint temperature. Opposed air flow to the flame spread due to forced and/or natural convection is considered. Pools of finite width and length are studied in air channels of prescribed height and width. Three-dimensional effects of the flame front near the edge of the pool are captured in the computation. The formation of a recirculation zone in the gas phase similar to that found in two-dimensional calculations is also present in the three-dimensional calculations. Both uniform spread and pulsating spread modes are found in the calculated results.

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

    SciTech Connect

    Hongbin Zhang; Haihua Zhao; Vincent Mousseau

    2008-04-01

    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.

  15. The Diagnostic Accuracy of HE4 in Lung Cancer: A Meta-Analysis

    PubMed Central

    Cheng, Daye; Sun, Ying; He, Hu

    2015-01-01

    The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68–0.75), SPE 0.85 (95% CI: 0.81–0.88), PLR 4.68 (95% CI: 3.23–6.78), NLR 0.31 (95% CI: 0.24–0.39), and DOR 17.14 (95% CI: 9.72–30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.

  16. Morphometric analysis of pulmonary intracapillary leukocyte pools in ex vivo-perfused rabbit lungs.

    PubMed

    Ermert, L; Duncker, H R; Rosseau, S; Schütte, H; Seeger, W

    1994-07-01

    Characterization and quantification of lung intracapillary leukocytes is of interest for a better understanding of immunological and inflammatory features in this organ. We developed a technique of computer-assisted measurement of digitalized electron-microscopic images and electronic data processing for morphometry of intracapillary leukocyte pools in rabbit lungs (L. Ermert, W. Seeger, and H.-R. Duncker, Cell Tissue Res. 271: 469-476, 1993). Measurements were undertaken in buffer-perfused isolated lungs (avoiding any reentry of washed-out cells); perfusion fixation was performed 7.5, 35, and 185 min after onset of artificial circulation (n = 5 each). Data were compared with that of nonperfused lungs fixed by tracheal instillation (baseline). Total lung capillary neutrophil counts were 1.41 x 10(9), 1.35 x 10(9), 1.37 x 10(9), and 0.69 x 10(9) (baseline, 7.5, 35, and 185 min perfusion, respectively). Corresponding data for intracapillary lymphocytes were 1.07 x 10(9), 0.84 x 10(9), 0.81 x 10(9), and 0.57 x 10(9); and for microvascular monocytes, data were 0.21 x 10(9), 0.19 x 10(9), 0.18 x 10(9), and 0.08 x 10(9). Ratios of cell volume and surface variables of the different intracapillary leukocyte types did not change during ex vivo lung perfusion. We conclude that the rabbit pulmonary capillary bed harbors large pools of different leukocytes, which surpass pool sizes of corresponding circulating cells and display very slow washout kinetics under conditions of lung-buffer perfusion. A major impact of these intracapillary leukocyte pools on immunological and inflammatory events in isolated-perfused and transplanted lungs must be assumed. PMID:8048543

  17. NaK pool-boiler solar receiver durability bench test. Volume 2: Metallurgical analysis

    NASA Astrophysics Data System (ADS)

    Goods, S. H.; Bradshaw, R. W.

    1995-01-01

    The principal materials used in the construction of a NaK based pool-boiler were analyzed. The device, operated for 7500 hours, accumulated 1000 thermal cycles to a peak temperature of 750 C. Haynes 230, used to fabricate the pool-boiler vessel, was found to perform satisfactorily. Air-side corrosion of the pool-boiler vessel was insignificant. Internal surface of the alloy exhibited some NaK-induced elemental dissolution; this dissolution was somewhat more extensive where the alloy was exposed to the liquid metal compared to regions exposed only to NaK vapor; however, the corresponding metal loss in all regions was inconsequential, never exceeding more than a few microns. Autogenous seam welds of the alloy responded in a similar fashion, exhibiting only minimal metal loss over the course of the experiment. While there was 50% loss in ductility of the alloy there remained adequate ductility for the anticipated operating environment. An enhanced boiling nucleation surface comprised of stainless steel powder brazed to the vessel ID showed no change in its structure. It remained intact, showing no cracking after repeated thermal cycling. Other materials used in the experiment showed more extensive degradation after exposure to the NaK. IN 600, used to fabricate thermowells, exhibited extensive surface and intergranular dissolution. Grain boundary dissolution was sufficiently severe in one of the thermowells to cause an air leak, resulting in experiment termination. BNi-3, a brazing alloy used to join the pool-boiler vessel, endcaps and thermowells, showed some dissolution where it was exposed to the NaK as well as thermal aging effects. However, all brazes remained structurally sound. A nickel metal ribbon showed catastrophic dissolution, resulting in the formation of deep (greater than 30 (mu)m) pits and cavities. A zirconium metal foil used to getter oxygen from the NaK became extremely brittle.

  18. Fission matrix-based Monte Carlo criticality analysis of fuel storage pools

    SciTech Connect

    Farlotti, M. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States); Ecole Polytechnique, Palaiseau, F 91128 (France); Larsen, E. W. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-07-01

    Standard Monte Carlo transport procedures experience difficulties in solving criticality problems in fuel storage pools. Because of the strong neutron absorption between fuel assemblies, source convergence can be very slow, leading to incorrect estimates of the eigenvalue and the eigenfunction. This study examines an alternative fission matrix-based Monte Carlo transport method that takes advantage of the geometry of a storage pool to overcome this difficulty. The method uses Monte Carlo transport to build (essentially) a fission matrix, which is then used to calculate the criticality and the critical flux. This method was tested using a test code on a simple problem containing 8 assemblies in a square pool. The standard Monte Carlo method gave the expected eigenfunction in 5 cases out of 10, while the fission matrix method gave the expected eigenfunction in all 10 cases. In addition, the fission matrix method provides an estimate of the error in the eigenvalue and the eigenfunction, and it allows the user to control this error by running an adequate number of cycles. Because of these advantages, the fission matrix method yields a higher confidence in the results than standard Monte Carlo. We also discuss potential improvements of the method, including the potential for variance reduction techniques. (authors)

  19. The Assessment of Tumor Response by Measuring the Single Largest Lesion per Organ in Metastatic Tumors: A Pooled Analysis of Previously Reported Data

    PubMed Central

    Jang, Hyun Joo; Cho, Ji Woong; Park, Bumjung; Choi, Hyun Chang; Kim, Hyeong Su; Kim, Jung Han

    2015-01-01

    Background: The RECIST 1.1 adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. Recently, we reported that the modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a high level of concordance with the original RECIST 1.1 in patients with advanced or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and colorectal cancer (CRC). However, each study had a major limitation of a small number of patients. Methods: We conducted a pooled analysis using the data from the three individual studies to improve statistical power. Tumor responses were compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1). Results: A total of 153 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51 with GC, and 38 with CRC. Regardless of primary sites, the number of target lesions according to the mRECIST 1.1 was significantly lower than that according to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high concordance between the two criteria (k = 0.908). Only eight patients (5.2%) showed disagreement in the tumor response assessment between the two criteria. The overall response rates of chemotherapy were not significantly different between the two criteria (33.3% versus 33.3%, P=1.0). Conclusions: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response in clinical practice. PMID:25561982

  20. Performance Characteristics of Endoscopic Ultrasound in the Staging of Pancreatic Cancer: A Meta-Analysis

    PubMed Central

    Nawaz, Haq; Yi-Fan, Chen; Kloke, John; Khalid, Asif; McGrath, Kevin; Landsittel, Douglas; Papachristou, Georgios I

    2014-01-01

    Context The optimal approach to pre-operative imaging assessment of pancreatic cancer is unknown. Objective The aim of this meta-analysis was to assess accuracy and performance characteristics of EUS in determining nodal staging, vascular invasion, and prediction of resectability of pancreatic cancer. A secondary aim was to perform head to head comparison of performance characteristics between EUS and CT for nodal staging, vascular invasion and resectability. Design Data from EUS studies were pooled according to bivariate generalized random effects model. Pooled estimates for CT were obtained from studies which performed head to head comparison between EUS and CT. Patients Patients with pancreatic cancer undergoing pre-operative imaging assessment. Intervention EUS. Main outcome measure Pooled sensitivity, specificity, positive and negative predictive values of EUS for nodal staging, vascular invasion and resectability. Results Forty-nine studies were considered of which 29 met inclusion criteria with a total of 1,330 patients. Pooled summary estimates for EUS-nodal staging were 69% for sensitivity and 81% for specificity. For vascular invasion, sensitivity was 85% and specificity was 91%. The sensitivity and specificity for resectability was 90% and 86%, respectively. CT scan showed lower sensitivity than EUS for nodal staging (24% vs. 58%) and vascular invasion (58% vs. 86%); however, the specificities for nodal staging (88% vs. 85%) and vascular invasion (95% vs. 93%) were comparable in studies where both imaging techniques were performed. The sensitivity and specificity of CT in determining resectability (90% and 69%) was similar to that of EUS (87% and 89%). Conclusions EUS is an accurate pre-operative tool in the assessment of nodal staging, vascular invasion and resectability in patients with pancreatic cancer. PMID:24018593

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

    PubMed Central

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

    2014-01-01

    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

  2. Individual and setting level predictors of the implementation of a skin cancer prevention program: a multilevel analysis

    Microsoft Academic Search

    Borsika A Rabin; Eric Nehl; Tom Elliott; Anjali D Deshpande; Ross C Brownson; Karen Glanz

    2010-01-01

    Background  To achieve widespread cancer control, a better understanding is needed of the factors that contribute to successful implementation\\u000a of effective skin cancer prevention interventions. This study assessed the relative contributions of individual- and setting-level\\u000a characteristics to implementation of a widely disseminated skin cancer prevention program.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A multilevel analysis was conducted using data from the Pool Cool Diffusion Trial from 2004

  3. Reflux pool-boiler as a heat-transport device for Stirling engines - Postmortem analysis and next-generation design

    NASA Astrophysics Data System (ADS)

    Moreno, J. B.; Andraka, C. E.; Diver, R. B.; Moss, T. A.; Hoffman, E. L.; Stone, C. M.

    In a prior study, operation of a 75-kWt sodium reflux pool-boiler solar receiver was demonstrated and its performance characterized at Sandia National Laboratories. Subsequently, during the final testing phase, the receiver developed a leak, releasing part of the sodium inventory to the atmosphere. The possible causes of the leak are examined, including materials selection, thermal stresses, fatigue, high local solar flux, film boiling, and flooding limits. The results of the failure analysis are applied to the next-generation receiver design, which is presented. Plans for bench-scale testing of some design modifications are also presented.

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

    PubMed

    Liu, Huan; Hu, Guang-Hui; Wang, Xing-Chun; Huang, Tian-Bao; Xu, Liang; Lai, Peng; Guo, Zhui-Feng; Xu, Yun-Fei

    2015-04-01

    This meta-analysis was conducted to assess the association between coffee consumption and prostate cancer risk. Thirteen cohort studies with 34,105 cases and 539,577 participants were included in the meta-analysis. The summary relative risks (RRs) with 95% confidence intervals (CIs) for different coffee intake levels were calculated. Dose-response relationship was assessed using generalized least square trend estimation. The pooled RR for the highest vs. lowest coffee intake was 0.90 (95% CI: 0.85-0.95), with no significant heterogeneity across studies (P = 0.267; I(2)= 17.5%). The dose-response analysis showed a lower cancer risk decreased by 2.5% (RR = 0.975; 95% CI: 0.957-0.995) for every 2 cups/day increment in coffee consumption. Stratifying by geographic region, there was a statistically significant protective influence of coffee on prostate cancer risk among European populations. In subgroup analysis of prostate cancer grade, the summary RRs were 0.89 (95% CI: 0.83-0.96) for nonadvanced, 0.82 (95% CI: 0.61-1.10) for advanced and 0.76 (95% CI: 0.55-1.06) for fatal diseases. Our findings suggest that coffee consumption may be associated with a reduced risk of prostate cancer and it also has an inverse association with nonadvanced prostate cancer. Because of the limited number of studies, more prospective studies with large sample size are needed to confirm this association. PMID:25706900

  5. C-Reactive Protein and the Incidence of Macular Degeneration – Pooled Analysis of 5 Cohorts

    PubMed Central

    Mitta, Vinod P.; Christen, William G.; Glynn, Robert J.; Semba, Richard D.; Ridker, Paul M.; Rimm, Eric B.; Hankinson, Susan E.; Schaumberg, Debra A.

    2013-01-01

    Objectives To investigate the relationship between high-sensitivity C-reactive protein (hsCRP) and future risk of age-related macular degeneration (AMD) in US men and women. Methods We measured hsCRP in baseline blood samples from participants in five ongoing cohort studies. Patients were initially free of AMD. We prospectively identified 647 incident cases of AMD and selected age- and sex-matched controls for each AMD case (2 controls for each case with dry AMD, or 3 controls for each case of neovascular AMD). We used conditional logistic regression models to examine the relationship between hsCRP and AMD, and pooled findings using meta-analytic techniques. Results After adjusting for cigarette smoking status, participants with high (> 3 mg/L) compared with low (< 1 mg/L) hsCRP levels, had cohort-specific odds ratios (OR) for incident AMD ranging from 0.94 (95% CI 0.58-1.51) in the Physicians’ Health Study to 2.59 (95% CI 0.58-11.67) in the Women’s Antioxidant and Folic Acid Cardiovascular Study. After testing for heterogeneity between studies (Q=5.61, p=0.23), we pooled findings across cohorts, and observed a significantly increased risk of incident AMD for high versus low hsCRP levels (OR=1.49, 95% CI 1.06-2.08). Risk of neovascular AMD was also increased among those with high hsCRP levels (OR=1.84, 95% CI 1.14-2.98). Conclusion Overall these pooled findings from 5 prospective cohorts add further evidence that elevated levels of hsCRP predict greater future risk of AMD. This information might shed light on underlying mechanisms, and could be of clinical utility in the identification of persons at high risk of AMD who may benefit from increased adherence to lifestyle recommendations, eye examination schedules, and therapeutic protocols. PMID:23392454

  6. Long Noncoding RNA HOTAIR as an Independent Prognostic Marker in Cancer: A Meta-Analysis

    PubMed Central

    Yang, Guang; Gu, Fang; Li, Minrui; Zhong, Bihui; Hu, Jifan; Hoffman, Andrew; Chen, Minhu

    2014-01-01

    Background HOTAIR, a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in many types of cancers. This meta-analysis summarizes its potential role as a biomarker in malignancy. Methods A quantitative meta-analysis was performed through a systematic search in Pubmed, Medline and Web of Science for eligible papers on the prognostic impact of HOTAIR in cancer from inception to Feb. 28, 2014. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results Nineteen studies were included in the study, with a total of 2033 patients. A significant association was observed between high HOTAIR expression and poor overall survival (OS) in patients with cancer (pooled HR 2.22, 95% CI: 1.68–2.93). Place of residence (Asian or Western countries), type of cancer (digestive or non-digestive disease), sample size (more or less than 100), and paper quality (score more or less than 85%) did not alter the significant predictive value of HOTAIR in OS from various kinds of cancer but preoperative status did. By combining HRs from Cox multivariate analyses, we found that HOTAIR expression was an independent prognostic factor for cancer patients (pooled HR 2.26, 95% CI: 1.62–3.15). Subgroup analysis showed that HOTAIR abundance was an independent prognostic factor for cancer metastasis (HR 3.90, 95% CI: 2.25–6.74). For esophageal carcinoma, high HOTAIR expression was significantly associated with TNM stage (III/IV vs. I/II: OR 6.90, 95% CI: 2.81–16.9) without heterogeneity. In gastric cancer, HOTAIR expression was found to be significantly associated with lymph node metastases (present vs. absent: OR 4.47, 95% CI: 1.88–10.63) and vessel invasion (positive vs. negative: OR 2.88, 95% CI: 1.38–6.04) without obvious heterogeneity. Conclusions HOTAIR abundance may serve as a novel predictive factor for poor prognosis in different types of cancers in both Asian and Western countries. PMID:25157956

  7. Diagnostic performance of contrast-enhanced ultrasound for ovarian cancer: a meta-analysis.

    PubMed

    Wu, Ying; Peng, Hongling; Zhao, Xia

    2015-04-01

    This meta-analysis is the first study aimed at assessing the overall diagnostic performance of contrast-enhanced ultrasound for ovarian cancer. PubMed, Embase and Medline databases were systematically searched for relevant articles published up to June 2014. Data were pooled to yield summary sensitivity, specificity, diagnostic odds ratio and receiver operating characteristic curves using Meta-Disc Version 1.4 software. Ten independent studies with 579 ovarian tumors were enrolled in this meta-analysis. The pooled sensitivity, specificity and diagnostic odds ratio statistics were 0.89 (0.83-0.94), 0.91 (0.88-0.93) and 91.70 (41.41-203.05), respectively, and the area under the summary receiver operating characteristic curve was 0.9619 (standard error: 0.0125), all indicating that contrast-enhanced ultrasound has high diagnostic accuracy in differentiation of malignant from benign ovarian tumors. PMID:25701533

  8. CHRNA3 rs1051730 polymorphism and lung cancer susceptibility in Asian population: a meta-analysis

    PubMed Central

    Zhan, Ping

    2015-01-01

    Many studies have examined the association between the CHRNA3 rs1051730 polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. The PubMed was searched for case-control studies published up to Jan 01, 2015. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. In this meta-analysis, we assessed four published studies involving comprising 2,890 lung cancer cases and 2,521 controls of the association between CHRNA3 rs1051730 polymorphism and lung cancer risk. For the T allele carriers (C/T + T/T) and the homozygote T/T, the pooled ORs for all studies combined 2,890 cases and 2,521 controls were 1.93 (95% CI =1.48-2.53, P=0.34 for heterogeneity) and 1.63 (95% CI =1.27-1.99, P=0.46 for heterogeneity), when compared with the homozygous wild-type genotype (C/C). There was no observable publication bias for both polymorphisms. These results from the meta-analysis suggest that CHRNA3 rs1051730 polymorphism contributes to risk of lung cancer among Asian population.

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

    SciTech Connect

    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

    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)

  10. Association between cholesterol intake and pancreatic cancer risk: Evidence from a meta-analysis.

    PubMed

    Chen, Hongqiang; Qin, Shiyong; Wang, Minghai; Zhang, Tao; Zhang, Shuguang

    2015-01-01

    Quantification of the association between the intake of cholesterol and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to summarize the evidence from epidemiological studies of cholesterol intake and the risk of pancreatic cancer. Pertinent studies were delivered by PubMed and Web of Knowledge issued through April of 2014. A random effects model was used to process the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. With 4513 pancreatic cases exemplified, 16 articles were applied in the meta-analysis. Pooled results suggest that cholesterol intake level was significantly associated with the risk of pancreatic cancer [summary relative risk (RR) = 1.371, 95%CI = 1.155-1.627, I(2) = 58.2%], especially in America [summary RR = 1.302, 95%CI = 1.090-1.556]. A linear dose-response relation was attested that the risk of pancreatic cancer rises by 8% with 100?mg/day of cholesterol intake. [summary RR = 1.08, 95% CI = 1.04-1.13]. In conclusion, our analysis suggests that a high intake of cholesterol might increase the risk of pancreatic cancer, especially in America. PMID:25649888

  11. Association between cholesterol intake and pancreatic cancer risk: Evidence from a meta-analysis

    PubMed Central

    Chen, Hongqiang; Qin, Shiyong; Wang, Minghai; Zhang, Tao; Zhang, Shuguang

    2015-01-01

    Quantification of the association between the intake of cholesterol and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to summarize the evidence from epidemiological studies of cholesterol intake and the risk of pancreatic cancer. Pertinent studies were delivered by PubMed and Web of Knowledge issued through April of 2014. A random effects model was used to process the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. With 4513 pancreatic cases exemplified, 16 articles were applied in the meta-analysis. Pooled results suggest that cholesterol intake level was significantly associated with the risk of pancreatic cancer [summary relative risk (RR) = 1.371, 95%CI = 1.155–1.627, I2 = 58.2%], especially in America [summary RR = 1.302, 95%CI = 1.090–1.556]. A linear dose-response relation was attested that the risk of pancreatic cancer rises by 8% with 100?mg/day of cholesterol intake. [summary RR = 1.08, 95% CI = 1.04–1.13]. In conclusion, our analysis suggests that a high intake of cholesterol might increase the risk of pancreatic cancer, especially in America. PMID:25649888

  12. Association between Dairy Intake and Gastric Cancer: A Meta-Analysis of Observational Studies

    PubMed Central

    Tian, Shu-bo; Yu, Jian-chun; Kang, Wei-ming; Ma, Zhi-qiang; Ye, Xin; Cao, Zhan-jiang

    2014-01-01

    Purpose Observational studies have given inconsistent findings on the relationship between intake of dairy products and gastric cancer. We therefore conducted a systematic review with a meta-analysis of observational studies to summarize available evidence on this point. Methods We searched the electronic literature databases of PubMed (Medline), EMBASE and the Chinese Biomedical Literature Database up until August 30, 2013. All studies were limited to the English language. Random-effects models were used to pool study results between dairy products consumption and the risk of gastric cancer. We also performed subgroup, publication bias and sensitivity analysis. Results Eight prospective studies and 18 case-control studies were included in our analysis, with a total number of 7272 gastric cancer cases and 223,355 controls. Pooled relative risks of all studies showed no significant association between dairy intake and gastric cancer (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.96–1.25). When study design was separately analyzed, population-based case-control studies showed a positive association between dairy intake and gastric cancer risk (OR: 1.36; 95% CI: 1.07–1.74), whereas no associations were shown by hospital-based case-control studies (OR: 0.86, 95% CI: 0.72–1.02) or cohort studies (OR?=?1.01, 95% CI?=?0.91–1.13). Conclusions The meta-analysis shows that no clear association apparently exists between consumption of dairy products and gastric cancer risk. Further well-designed cohort and intervention studies should be conducted to verify this lack of association. PMID:25006674

  13. Cave Pool

    USGS Multimedia Gallery

    A pool in the Caverns of Sonora. This cave, like many others, was formed by water combining with carbon dioxide to create a weak carbonic acid. This acid then dissolved the limestone to carve out chambers. The dissolved calcium from the limestone then combined with the carbon dioxide to create calci...

  14. Analysis of trematode parasite communities in fish eye lenses by pyrosequencing of naturally pooled DNA.

    PubMed

    Rellstab, Christian; Louhi, Katja-Riikka; Karvonen, Anssi; Jokela, Jukka

    2011-08-01

    Infections by multiple parasite species are common in nature and have important consequences for between-species interactions and coevolutionary dynamics with the host populations. For example, ecological and evolutionary factors underlying the structure of parasite communities determine the range of hosts a parasite can infect and set the basis for both evolution of host defences and parasite virulence, as well as management of diseases. Studies investigating these factors have been facilitated in the recent past by genetic methods, which surmount difficulties of traditional morphological taxonomy in identifying individual parasite species. Here we take a step further and present a novel methodological approach to analyze parasite communities as a whole. We determined the relative frequencies of interspecific SNP alleles by pyrosequencing naturally pooled samples of closely related Diplostomum spp. trematodes infecting eye lenses of freshwater fish. Pyrosequencing allowed us to use naturally pooled community samples (lenses) to increase the sample size and statistical power, without sequencing single parasite specimens. In a case study, we applied this method to analyze the community structure of the eye flukes across fish host species of a freshwater system in Finland. We found that the fish species harboured significantly different parasite communities and that multiple species infections were common. Our study provides an example of how quantitative pyrosequencing can be used to answer evolutionary and ecological questions in natural communities of parasites. PMID:21554995

  15. p53 codon 72 polymorphism and breast cancer risk: A meta-analysis

    PubMed Central

    HOU, JING; JIANG, YUAN; TANG, WENRU; JIA, SHUTING

    2013-01-01

    p53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR=1.016, 95% CI=0.931–1.11, P=0.722). The symmetric funnel plot, Egger’s test (P=0.506) and Begg’s test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required. PMID:23737888

  16. AACR 2015: Pan-Cancer Analysis of Whole Genomes

    Cancer.gov

    The Pan-Cancer analysis of Whole Genomes (PCAWG) project of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) is co-ordinating analysis of more than 2,000 whole cancer genomes. Each genome is characterized through a suite of centralized algorithms, including alignment to the reference genome, standardized quality assessment and calling of all classes of somatic mutation.

  17. Prognostic significance of osteopontin in patients with lung cancer: a meta-analysis

    PubMed Central

    Peng, Bin; Wang, Yi-Han; Huang, Zhuo; Feng, Shi-Jian; Wang, Yong-Sheng

    2014-01-01

    Both plasma/serum/pleural effusion osteopontin concentration (PSPO) and tumor tissue osteopontin expression (TTO) have recently been reported to be involved in the prognosis of lung cancer. In this study, we performed a meta-analysis to demonstrate the association between PSPO/TTO and survival in patients with lung cancer. We searched in PubMed, EMBASE, Cochrane library, Web of Science and Chinese Biomedical database (CBM) for relevant literatures. Stata 12.0 was applied to pool the eligible studies and synthesize hazard ratios (HRs) and its corresponding 95% confidence interval (CI). For PSPO, a total of 8 studies with 1000 patients were included in final analysis. Combined HR suggested high PSPO predicted an unfavorable overall survival (OS) (HR=1.52, 95% CI: 1.13-2.05) and progress-free survival (PFS) (HR=1.73, 95% CI: 1.35-2.21). For TTO, 5 studies with a total of 747 patients were employed in final analysis. Pooled HR indicated that elevated TTO was associated with poor OS (HR=2.16, 95% CI: 1.65-2.83) and disease/relapse-free survival (D/RFS) (HR=2.36, 95% CI: 1.79-3.12). Subgroup analysis was performed to explore the causes of heterogeneity. Publication bias by begg’s test was not statistically significant. Sensitivity analysis showed that the pooled results were robust. This study revealed that both high TTO and PSPO are associated with poor prognosis in patients with lung cancer. PMID:25663958

  18. Sexual Orientation Disparities in Cancer-Related Risk Behaviors of Tobacco, Alcohol, Sexual Behaviors, and Diet and Physical Activity: Pooled Youth Risk Behavior Surveys

    PubMed Central

    Corliss, Heather L.; Everett, Bethany G.; Reisner, Sari L.; Austin, S. Bryn; Buchting, Francisco O.; Birkett, Michelle

    2014-01-01

    Objectives. We examined sexual orientation disparities in cancer-related risk behaviors among adolescents. Methods. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex orientation as sexual minority and the remainder as heterosexual. We compared the groups on risk behaviors and stratified by gender, age (?14 years), and race/ethnicity. Results. Sexual minorities (7.6% of the sample) reported more risk behaviors than heterosexuals for all 12 behaviors (mean?=?5.3 vs 3.8; P?cancer risk, morbidity, and mortality by sexual orientation are needed to track the potential but unknown burden of cancer among sexual minorities. PMID:24328632

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

    PubMed Central

    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

    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

  20. Prognostic value of osteopontin expression in breast cancer: A meta-analysis

    PubMed Central

    XU, YING-YI; ZHANG, YA-YA; LU, WEI-FENG; MI, YAN-JUN; CHEN, YU-QIANG

    2015-01-01

    Osteopontin (OPN) has been implicated in tumor development and progression over the last few years. However, the prognostic value of OPN overexpression in patients with breast cancer remains controversial. We performed a meta-analysis to investigate the association of OPN expression in the tumor with the clinicopathological characteristics and survival of breast cancer patients. A total of 8 studies met the inclusion criteria and were entered in the meta-analysis. The data analysis demonstrated that OPN expression was positively associated with lymph node metastasis [pooled odds ratio = 2.026, 95% confidence interval (CI): 1.199-3.425, P=0.008, random-effects model]. We also found that OPN expression was positively associated with overall survival [hazard ratio (HR) = 3. 69, 95% CI: 1. 45-9.42, P=0.000, random-effects model) and disease -free survival (pooled HR=2.40, 95% CI: 1.27-4.55, P=0.007, fix ed -effects model). Based on the results of this study, we concluded that OPN overexpression in the tumor is a candidate positive prognostic biomarker for breast cancer patients. PMID:25798267

  1. Meta-analysis in cancer genetics.

    PubMed

    Pabalan, Noel A

    2010-01-01

    Genetic association studies report potentially conflicting findings which meta-analysis seeks to quantify and objectively summarize. Attributing cancer to a single gene variant requires large sample sizes, which may strain resources in a primary study. Properly used, meta-analysis is a powerful tool for resolving discrepancies in genetic association studies given the exponential increase in sample sizes when data are combined. The several steps involved in this methodology require careful attention to critical issues in meta-analysis, heterogeneity and publication bias, evaluation of which can be graphical or statistical. Overall summary effects of a meta-analysis may or may not reflect similar associations when the component studies are sub grouped. Overall associations and that of the subgroups are evaluated for tenability using sensitivity analysis. The low association between a polymorphism and cancer is offset by detectable changes in cancer incidence in the general population making them an important issue from a public health point of view. Asian meta-analytic publications in cancer genetics come from six countries with an output that number from one to two. The exception is China, whose publication output has increased exponentially since 2008. PMID:20593927

  2. 'Chain pooling' model selection as developed for the statistical analysis of a rotor burst protection experiment

    NASA Technical Reports Server (NTRS)

    Holms, A. G.

    1977-01-01

    A statistical decision procedure called chain pooling had been developed for model selection in fitting the results of a two-level fixed-effects full or fractional factorial experiment not having replication. The basic strategy included the use of one nominal level of significance for a preliminary test and a second nominal level of significance for the final test. The subject has been reexamined from the point of view of using as many as three successive statistical model deletion procedures in fitting the results of a single experiment. The investigation consisted of random number studies intended to simulate the results of a proposed aircraft turbine-engine rotor-burst-protection experiment. As a conservative approach, population model coefficients were chosen to represent a saturated 2 to the 4th power experiment with a distribution of parameter values unfavorable to the decision procedures. Three model selection strategies were developed.

  3. Analysis of gravity anomaly over coral-reef oil field: Wilfred Pool, Sullivan County, Indiana

    SciTech Connect

    Dana, S.W.

    1980-03-01

    To compare the measured and theoretical gravity anomaly of a typical coral-reef oil field, data were collected from the wilfred Pool, Sullivan County, Indiana. Densities of available core samples from the field were determined and the anomaly was calculated, taking into account the lateral and vertical variation of density and the geologic structure known from core studies and drilling-log records of lithologic types penetrated by the wells. Comparison of the theoretical and actual anomalies indicated a rough correspondence except for several sharp negative anomalies on the flanks of the measured gravity anomaly. Further studies indicated that the negative anomalies are possibly due to fluvial erosion that produced, on the surface of the youngest Pennsylvanian sediments, channels which were later filled with glacial till of lower density than the sediments. 13 figures.

  4. Plasma effect on weld pool surface reconstruction by shape-from-polarization analysis

    SciTech Connect

    Coniglio, N.; Mathieu, A., E-mail: alexandre.mathieu@u-bourgogne.fr [Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303 CNRS/Université de Bourgogne, 12 rue de la Fonderie, 71200 Le Creusot (France); Aubreton, O.; Stolz, C. [Université de Bourgogne Laboratoire Le2i UMR CNRS 6306, allée Alain Savary, 21000 Dijon (France)

    2014-03-31

    The polarimetric state of the thermal radiations emitted by the weld metal contains geometric information about the emitting surface. Even though the analysed thermal radiation has a wavelength corresponding to a blind spectral window of the arc plasma, the physical presence of the arc plasma itself interferes with the rays radiated by the weld pool surface before attaining the polarimeter, thus modifying the geometric information transported by the ray. In the present work, the effect of the arc plasma-surrounding zone on the polarimetric state and propagation direction of the radiated ray is analyzed. The interaction with the arc plasma zone induces a drop in ray intensity and a refraction of ray optical path.

  5. Greater weight loss among men participating in a commercial weight loss program: a pooled analysis of 2 randomized controlled trials.

    PubMed

    Barraj, Leila M; Murphy, Mary M; Heshka, Stanley; Katz, David L

    2014-02-01

    Being overweight and obese are significant health concerns for men and women, yet despite comparable needs for effective weight loss and maintenance strategies, little is known about the success of commercial weight loss programs in men. This study tests the hypothesis that men participating in a commercial weight loss program (Weight Watchers) had significantly greater weight loss than men receiving limited support from health professionals for weight loss (controls). A pooled analysis of weight loss and related physiologic parameter data from 2 randomized clinical trials was conducted. After 12 months, analysis of covariance tests showed that men in the commercial program group (n = 85) lost significantly more weight (P < .01) than men in the control group (n = 84); similar significant differences were observed for body mass index and waist circumference. These results suggest that participation in a commercial weight loss program may be a more effective means to lose weight and maintain weight loss. PMID:24461320

  6. Sphingosine Kinase 1 and Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Yun; Wang, Yan; Wan, Zhi; Liu, Shiping; Cao, Yu; Zeng, Zhi

    2014-01-01

    Background Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis, progression, and metastasis processes. Many studies have demonstrated SK1 overexpressed in various cancers, but no meta-analysis has evaluated the relationship between SK1 and various cancers. Methods We retrieved relevant articles from the PubMed, EBSCO, ISI, and OVID databases. A pooled odds ratio (OR) was used to assess the associations between SK1 expression and cancer; hazard ratios (HR) were used for 5-year and overall survival. Review Manager 5.0 was used for the meta-analysis, and publication bias was evaluated with STATA 12.0 (Egger’s test). Results Thirty-four eligible studies (n?=?4,673 patients) were identified. SK1 positivity and high expression were significantly different between cancer, non-cancer, and benign tissues. SK1 mRNA and protein expression levels were elevated in the cancer tissues, compared with the normal tissues. SK1 positivity rates differed between various cancer types (lowest [27.3%] in estrogen receptor-positive breast cancer and highest [82.2%] in tongue squamous cell carcinoma). SK1 positivity and high expression were associated with 5-year survival; the HR was 1.86 (95% confidence interval [CI], 1.18–2.94) for breast cancer, 1.58 (1.08–2.31) for gastric cancer, and 2.68 (2.10–3.44) for other cancers; the total cancer HR was 2.21 (95% CI, 1.83–2.67; P < 0.00001). The overall survival HRs were 2.09 (95% CI, 1.35–3.22), 1.56 (1.08–2.25), and 2.62 (2.05–3.35) in breast, gastric, and other cancers, respectively. The total effect HR was 2.21 (95% CI, 1.83–2.66; P < 0.00001). Conclusions SK1 positivity and high expression were significantly associated with cancer and a shorter 5-year and overall survival. SK1 positivity rates vary tremendously among the cancer types. It is necessary to further explore whether SK1 might be a predictive biomarker of outcomes in cancer patients. PMID:24587339

  7. The Role of Adiponectin in Breast Cancer: A Meta-Analysis

    PubMed Central

    Liu, Li-Yuan; Wang, Meng; Ma, Zhong-Bing; Yu, Li-Xiang; Zhang, Qiang; Gao, De-Zong; Wang, Fei; Yu, Zhi-Gang

    2013-01-01

    Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future. PMID:23991180

  8. Association between PTEN Gene IVS4 Polymorphism and Risk of Cancer: A Meta-Analysis

    PubMed Central

    Sun, Liping; Liu, Jingwei; Yuan, Quan; Xing, Chengzhong; Yuan, Yuan

    2014-01-01

    Background Phosphatase and tensin homolog (PTEN) is a well established tumor suppressor gene. Recently, increasing studies investigated the association between PTEN IVS4 polymorphism (rs3830675) and risk of various types of cancer. However, the results from the individual studies were controversial. The aim of this meta-analysis was to elucidate whether PTEN IVS4 polymorphism was associated with cancer risk. Methods Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched to identify potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to assess the strength of association between PTEN IVS4 polymorphism and cancer risk. Results A total of seven case-control studies were finally included in this meta-analysis. The pooled analysis suggested that individuals with PTEN IVS4 (?/?) genotype were significantly associated with increased risk of cancer (OR?=?1.45, 95% CI?=?1.19–1.76, P<0.001) and subgroup of digestive tract cancer (OR?=?1.67, 95% CI?=?1.28–2.18, P<0.001) compared with (+/+) genotype. The allele analysis revealed that (?) allele was significantly associated with increased risk of cancer (OR?=?1.30, 95% CI?=?1.12–1.50, P?=?0.001) and subgroup of digestive tract cancer (OR?=?1.42, 95% CI?=?1.16–1.74, P?=?0.001) compared with (+) allele. No significant association was observed between PTEN IVS4 (+/?) genotype and risk of cancer. Conclusion PTEN IVS4 (?/?) genotype was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+/+) genotype. The (?) allele of PTEN IVS4 (rs3830675) polymorphism was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+) allele. The recessive effect model and dominant effect model also demonstrated significant association between PTEN IVS4 (rs3830675) polymorphism and increased cancer risk especially for digestive tract cancer. Further large-scale and well-designed studies regarding different ethnicities are still required to confirm the results of our meta-analysis. PMID:24901890

  9. Exhaled breath analysis for lung cancer

    PubMed Central

    Sutedja, Tom G.; Zimmerman, Paul V.

    2013-01-01

    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

  10. Content analysis of cancer blog posts*

    PubMed Central

    Kim, Sujin

    2009-01-01

    Objectives: The efficacy of user-defined subject tagging and software-generated subject tagging for describing and organizing cancer blog contents was explored. Methods: The Technorati search engine was used to search the blogosphere for cancer blog postings generated during a two-month period. Postings were mined for relevant subject concepts, and blogger-defined tags and Text Analysis Portal for Research (TAPoR) software–defined tags were generated for each message. Descriptive data were collected, and the blogger-defined tags were compared with software-generated tags. Three standard vocabularies (Opinion Templates, Basic Resource, and Medical Subject Headings [MeSH] Resource) were used to assign subject terms to the blogs, with results compared for efficacy in information retrieval. Results: Descriptive data showed that most of the studied cancer blogs (80%) contained fewer than 500 words each. The numbers of blogger-defined tags per posting (M?=?4.49 per posting) were significantly smaller than the TAPoR keywords (M?=?23.55 per posting). Both blogger-defined subject tags and software-generated subject tags were often overly broad or overly narrow in focus, producing less than effective search results for those seeking to extract information from cancer blogs. Conclusions: Additional exploration into methods for systematically organizing cancer blog postings is necessary if blogs are to become stable and efficacious information resources for cancer patients, friends, families, or providers. PMID:19851489

  11. Quantitative analysis of the association between CRP rs2808630 and rs1417938 polymorphisms and cancer risk

    PubMed Central

    WANG, JIAN-GONG; ZHANG, YANG; XIAO, TIAN-LIN

    2015-01-01

    Accumulating evidence indicates that polymorphisms in the CRP gene are important in the development of cancer. The current meta-analysis was performed to investigate the association between CRP polymorphisms 3407 A>G (rs2808630) and 29 A>T (rs1417938), and the risk of developing cancer. A search of the relevant literature was conducted using the PubMed database to identify eligible studies published up until March 25, 2014. Five case-control studies involving 888 cases and 3,167 controls for the 3407 A>G polymorphism, and six case-control studies involving 3,110 cases and 5,951 controls for the 29 A>T polymorphism were included in the current meta-analysis. The pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random-effects model. Meta-analysis identified no association between the CRP 3407 A>G and 29 A>T polymorphisms, and overall cancer risk. Additional stratified analysis by cancer type did not reveal any significant associations in the genetic models investigated. The findings of the present study indicated that CRP 3407 A>G and 29 A>T polymorphisms are not associated with cancer risk. PMID:25624919

  12. Thermal analysis of cancerous breast model.

    PubMed

    Chanmugam, Arjun; Hatwar, Rajeev; Herman, Cila

    2012-01-01

    Breast cancer is one of the most common and dangerous cancers. Subsurface breast cancer lesions generate more heat and have increased blood supply when compared to healthy tissue, and this temperature rise is mirrored in the skin surface temperature. The rise in temperature on the skin surface, caused by the cancerous lesion, can be measured noninvasively using infrared thermography, which can be used as a diagnostic tool to detect the presence of a lesion. However, its diagnostic ability is limited when image interpretation relies on qualitative principles. In this study, we present a quantitative thermal analysis of breast cancer using a 3D computational model of the breast. The COMSOL FEM software was used to carry out the analysis. The effect of various parameters (tumor size, location, metabolic heat generation and blood perfusion rate) on the surface temperature distribution (which can be measured with infrared thermography) has been analyzed. Key defining features of the surface temperature profile have been identified, which can be used to estimate the size and location of the tumor based on (measured) surface temperature data. In addition, we employed a dynamic cooling process, to analyze surface temperature distributions during cooling and thermal recovery as a function of time. In this study, the effect of the cooling temperature on the enhancement of the temperature differences between normal tissue and cancerous lesions is evaluated. This study demonstrates that a quantification of temperature distributions by computational modeling, combined with thermographic imaging and dynamic cooling can be an important tool in the early detection of breast cancer. PMID:25328914

  13. Thermal analysis of cancerous breast model

    PubMed Central

    Chanmugam, Arjun; Hatwar, Rajeev; Herman, Cila

    2013-01-01

    Breast cancer is one of the most common and dangerous cancers. Subsurface breast cancer lesions generate more heat and have increased blood supply when compared to healthy tissue, and this temperature rise is mirrored in the skin surface temperature. The rise in temperature on the skin surface, caused by the cancerous lesion, can be measured noninvasively using infrared thermography, which can be used as a diagnostic tool to detect the presence of a lesion. However, its diagnostic ability is limited when image interpretation relies on qualitative principles. In this study, we present a quantitative thermal analysis of breast cancer using a 3D computational model of the breast. The COMSOL FEM software was used to carry out the analysis. The effect of various parameters (tumor size, location, metabolic heat generation and blood perfusion rate) on the surface temperature distribution (which can be measured with infrared thermography) has been analyzed. Key defining features of the surface temperature profile have been identified, which can be used to estimate the size and location of the tumor based on (measured) surface temperature data. In addition, we employed a dynamic cooling process, to analyze surface temperature distributions during cooling and thermal recovery as a function of time. In this study, the effect of the cooling temperature on the enhancement of the temperature differences between normal tissue and cancerous lesions is evaluated. This study demonstrates that a quantification of temperature distributions by computational modeling, combined with thermographic imaging and dynamic cooling can be an important tool in the early detection of breast cancer. PMID:25328914

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

    SciTech Connect

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

    2010-01-15

    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)

  15. Clinical significance of DAPK promoter hypermethylation in lung cancer: a meta-analysis

    PubMed Central

    Li, Ying; Zhu, Min; Zhang, Xiaoju; Cheng, Dongjun; Ma, Xitao

    2015-01-01

    Death-associated protein kinase 1 (DAPK) is an important serine/threonine kinase involved in various cellular processes, including apoptosis, autophagy, and inflammation. DAPK expression and activity are deregulated in a variety of diseases including cancer. Methylation of the DAPK gene is common in many types of cancer and can lead to loss of DAPK expression. However, the association between DAPK promoter hypermethylation and the clinicopathological significance of lung cancer remains unclear. In this study, we searched the MEDLINE, PubMed, Web of Science, and Scopus databases, systematically investigated the studies of DAPK promoter hypermethylation in lung cancer and quantified the association between DAPK promoter hypermethylation and its clinicopathological significance by meta-analysis. We observed that the frequency of DAPK methylation was significantly higher in lung cancer than in non-malignant lung tissues (odds ratio 6.02, 95% confidence interval 3.17–11.42, P<0.00001). The pooled results also showed the presence of a prognostic impact of DAPK gene methylation in lung cancer patients (odds ratio 3.63, 95% confidence interval 1.09–12.06, P=0.04). In addition, we summarized these findings and discuss tumor suppressor function, clinicopathological significance, and potential drug targeting of DAPK in lung cancer.

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

    PubMed Central

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

    2010-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

  18. The determinants of health expenditure in the OECD countries: a pooled data analysis.

    PubMed

    Gerdtham, U G; Jönsson, B; MacFarlan, M; Oxley, H

    1998-01-01

    This paper uses international health expenditure and the latest OECD data to investigate the determinants of aggregate health expenditure. The study differs from most previous studies in two principal ways. First, it uses a somewhat larger sample for estimation, with pooled time-series, cross-section data for 22 OECD countries for a 20-year period. Most previous work has used a purely cross-section approach: in this case, the small sample size reduced the statistical reliability of results and limited the number of hypotheses that can be tested simultaneously. Second, and following from this, a more extensive range of hypotheses is tested, with particular emphasis on those relating to the contractual relations between payers, providers and patients. The findings show, for example, that the use of primary care "gatekeepers" seems to result in lower health expenditure and also that the way of remunerating physicians in the ambulatory care sector appears to influence health expenditure; capitation systems tend to lead to lower expenditure than fee-for-service systems. PMID:10662400

  19. Microarray analysis in gastric cancer: A review

    PubMed Central

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

    2014-01-01

    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. PMID:25232233

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

    PubMed Central

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

    2014-01-01

    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

  1. Patient-level pooled analysis of adjudicated gastrointestinal outcomes in celecoxib clinical trials: meta-analysis of 51,000 patients enrolled in 52 randomized trials

    PubMed Central

    2013-01-01

    Introduction Although the safety of celecoxib has been investigated, limited data are available on complications affecting the entire (upper and lower) gastrointestinal (GI) tract, with no patient-level pooled analyses of upper and lower GI outcomes available. We therefore evaluated the upper and lower GI safety of celecoxib by using patient-level data from randomized controlled trials (RCTs). Methods This patient-level pooled analysis included 52 prospective, randomized, double-blind parallel-group studies from the Celecoxib Clinical Database. Each study had a planned duration of continuous treatment with celecoxib or a nonselective nonsteroidal antiinflammatory drug (nsNSAID), rofecoxib, or the placebo comparator arm for at least 4 weeks. All studies with final reports completed by 1 October 2007 were included. The primary end point was the combined incidence of clinically significant upper and lower GI events (CSULGIEs). An independent blinded committee reviewed and adjudicated all end points by using predefined criteria and all available reported adverse events, laboratory data, and case narratives. All doses of celecoxib and all doses of all nsNSAIDs were pooled for analysis. Results The pooled analysis involved 51,048 patients; 28,614 were randomized to celecoxib; 15,278 to nsNSAIDs (including 3,248 patients taking naproxen, 2,640 taking ibuprofen, 8,066 taking diclofenac, 1,234 taking loxoprofen, and 90 taking ketoprofen); 5,827 to placebo and 1,329 to rofecoxib. The mean age was 60 years, and 65% were women. Data on 1,042 patients with potential GI events were reviewed for end-points adjudication; the adjudication committee confirmed 89 patients with CSULGIEs. The majority were in the celecoxib and nsNSAID groups (with raw incidence proportions of 37 (0.1%) and 40 (0.3%), respectively). The incidence rates were 0.3, 0.9 and 0.3 per 100 patient-years in the celecoxib, nsNSAID, and placebo groups, respectively. The time to incidence of CSULGIEs was significantly longer with celecoxib than with nsNSAIDs (P = 0.0004). Conclusions When compared with nsNSAIDs, celecoxib is associated with a significantly lower risk of all clinically significant GI events throughout the entire GI tract. This pooled analysis of 52 RCTs significantly advances the understanding of the upper and lower GI safety profile of celecoxib and its potential benefits to patients. PMID:23298471

  2. Association between Class III Obesity (BMI of 40–59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies

    PubMed Central

    Kitahara, Cari M.; Flint, Alan J.; Berrington de Gonzalez, Amy; Bernstein, Leslie; Brotzman, Michelle; MacInnis, Robert J.; Moore, Steven C.; Robien, Kim; Rosenberg, Philip S.; Singh, Pramil N.; Weiderpass, Elisabete; Adami, Hans Olov; Anton-Culver, Hoda; Ballard-Barbash, Rachel; Buring, Julie E.; Freedman, D. Michal; Fraser, Gary E.; Beane Freeman, Laura E.; Gapstur, Susan M.; Gaziano, John Michael; Giles, Graham G.; Håkansson, Niclas; Hoppin, Jane A.; Hu, Frank B.; Koenig, Karen; Linet, Martha S.; Park, Yikyung; Patel, Alpa V.; Purdue, Mark P.; Schairer, Catherine; Sesso, Howard D.; Visvanathan, Kala; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Hartge, Patricia

    2014-01-01

    Background The prevalence of class III obesity (body mass index [BMI]?40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19–83 y at baseline, classified as obese class III (BMI 40.0–59.9 kg/m2) compared with those classified as normal weight (BMI 18.5–24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976–2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences?=?238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences?=?36.7 and 62.3 in men and women, respectively) and diabetes (rate differences?=?51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40–44.9, 45–49.9, 50–54.9, and 55–59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7–7.3), 8.9 (95% CI: 7.4–10.4), 9.8 (95% CI: 7.4–12.2), and 13.7 (95% CI: 10.5–16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary PMID:25003901

  3. Pooled analysis of safety data from pediatric Phase II RTS,S/AS malaria candidate vaccine trials.

    PubMed

    Vekemans, Johan; Guerra, Yolanda; Lievens, Marc; Benns, Sarah; Lapierre, Didier; Leach, Amanda; Verstraeten, Thomas

    2011-12-01

    Prior to progression to Clinical Development Phase III, GlaxoSmithKline Biologicals performed a pooled analysis of phase two safety data following administration of 8860 doses of RTS,S/AS to 2981 children under 5 years old. RTS,S/AS was associated with increased rates of non-serious URTI, rash and diaper dermatitis graded mild or moderate. There was no significant increased rate of overall or single SAEs. Two episodes of simple febrile seizure were estimated to be related to vaccination. Significant decreased relative risks of death, any SAE, any SAE excluding malaria and pneumonia were observed. The results suggest a favourable risk-benefit balance which is to be confirmed in the ongoing Phase III trials. PMID:22108035

  4. Prognostic significance of neutrophil-to- lymphocyte ratio in esophageal cancer: a meta-analysis

    PubMed Central

    Yang, Xun; Huang, Ying; Feng, Ji-Feng; Liu, Jin-Shi

    2015-01-01

    Background The neutrophil-to-lymphocyte ratio (NLR) is a useful predictive factor in several cancers. However, the prognostic value of NLR in patients with esophageal cancer (EC) is still controversial. Therefore, it was necessary for us to perform a meta-analysis to evaluate the prognostic value of NLR in patients with EC. Methods A systematic literature search was performed by using Web of Science, PubMed Central, and Medline to evaluate the prognostic value of NLR in patients with EC. The deadline of our primary search was July 10, 2014. This meta-analysis was conducted in accordance with PRISMA guidelines. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to assess the association of NLR and overall survival (OS) and disease-free survival (DFS). Results Six studies involving 1,633 patients were included in our meta-analysis. Our pooled results demonstrated that high NLR was associated with poor OS (HR: 1.54, 95% CI: 1.32–1.80, I 2=25.3%, P=0.254) and DFS (HR: 1.74, 95% CI: 1.25–2.43, I 2=63.9%, P=0.096). Subgroup analysis between NLR and OS was performed in a further investigation. When the patients were segregated according to country, sample size, and pathological type, high NLR was also significantly correlated with OS. Conclusion High NLR is associated with poor prognosis in patients with EC. NLR may be a significant predictive biomarker in patients with EC.

  5. A Pooled Multisite Analysis of the Effects of Female Reproductive Hormones on Glioma Risk

    PubMed Central

    Krishnamachari, Bhuma; Il’yasova, Dora; Scheurer, Michael E.; Bondy, Melissa; Wrensch, Margaret; Davis, Faith

    2014-01-01

    Purpose The association between female reproductive factors and glioma risk is unclear, but most published studies have been limited by small sample size. We conducted a pooled multisite study of pre- and post-menopausal women, investigating the effect of female reproductive factors, including hormonal medications. Methods Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals assessing the effects of female reproductive factors and female hormonal medications in glioma cases and unrelated controls. Results Menarche over the age of 15 as compared to under 12 was associated with a statistically significant risk for glioma (OR = 2.00, 95% CI, 1.47–2.71). Use of Oral Contraceptive Pills (OCP) was inversely associated with risk of glioma (OR= 0.61, 95% CI, 0.50–0.74) and there was an inverse trend with longer duration of OCP use (p for trend< 0.0001). Use of Hormone Replacement Therapy (HRT) was also inversely associated with risk of glioma (OR=0.55, 95% CI, 0.44–0.68) and there was an inverse trend with longer duration of use (p for trend< 0.0001). Compared to those reporting neither OCP use nor HRT use, those who reported using both were less likely to have a diagnosis of glioma (OR = 0.34, 95% CI, 0.24–0.48). Conclusions Female reproductive hormones may decrease the risk for glioma. The association appears to be strongest with greater length of use and use of both HRT and OCP. PMID:24890803

  6. Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies

    PubMed Central

    McCormack, Valerie

    2008-01-01

    Background Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association. Methods and Findings Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ? 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. Conclusions This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood. PMID:18828667

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

    SciTech Connect

    Miller, G.K.

    1996-03-01

    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.

  8. Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

    PubMed Central

    Xu, Lei; Yu, Jing; Wu, Yan; Geng, Jiang; Yao, Xu-dong

    2015-01-01

    Background and Purpose Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships. Methods We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohort studies, while odds ratio (OR) were employed for case-control studies. The random effects and fixed effects models were used for analyses. Results 18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 – 1.16; I2: 10.3%, p value: 0.351). In case-control studies, standard aspirin use (>325mg) was related to lower lung cancer incidence, compared with low-dose aspirin use (75–100mg). A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years), insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men. Conclusions Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations. PMID:25849465

  9. [18F]Fluorodeoxyglucose-positron emission tomography screening for lung cancer: a systematic review and meta-analysis

    PubMed Central

    Chien, Chun-Ru; Liang, Ji-An; Chen, Jin-Hua; Wang, Hsiao-Nin; Lin, Cheng-Chieh; Chen, Chih-Yi; Wang, Pin-Hui; Yeh, Jun-Jun

    2013-01-01

    Abstract Rationale and objectives: Although low-dose computed tomography (CT) is a recommended modality for lung cancer screening in high-risk populations, the role of other modalities, such as [18F]fluorodeoxyglucose-positron emission tomography (PET), is unclear. We conducted a systematic review to describe the role of PET in lung cancer screening. Materials and methods: A systematic review was conducted by reviewing primary studies focusing on PET screening for lung cancer until July 2012. Two independent reviewers identified studies that were compatible for inclusion/exclusion criteria. The analysis was restricted to English and included studies published since 2000. A descriptive analysis was used to summarize the results, and the pooled diagnostic performance of selective PET screening was calculated by weighted average using individual sample sizes. Results: Among the identified studies (n?=?3497), 12 studies were included for analysis. None of the studies evaluated the efficacy of primary PET screening specific to lung cancer. Eight studies focused on primary PET screening for all types of cancer; the detection rates of lung cancer were low. Four studies reported evidence of lung cancer screening programs with selective PET, in which the estimated pooled sensitivity and specificity was 83% and 91%, respectively. Conclusions: The role of primary PET screening for lung cancer remains unknown. However, PET has high sensitivity and specificity as a selective screening modality. Further studies must be conducted to evaluate the use of PET or PET/computed tomography screening for high-risk populations, preferably using randomized trials or prospective registration. Advances in knowledge: Our meta-analysis indicates that PET has high sensitivity and specificity as a selective screening modality. PMID:24334433

  10. Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis

    PubMed Central

    Liao, Wei-Chih; Wu, Ming-Shiang; Lin, Jaw-Town; Wang, Hsiu-Po

    2015-01-01

    Objective To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer. Design Systematic review and dose-response meta-analysis of prospective observational studies. Data sources Search of PubMed, Scopus, and related reviews before 30 November 2013 without language restriction. Eligibility criteria Prospective studies evaluating the association between blood glucose concentration and pancreatic cancer. Retrospective and cross sectional studies excluded to avoid reverse causality. Data extraction and synthesis Two reviewers independently extracted relevant information and assessed study quality with the Newcastle-Ottawa scale. Random effects dose-response meta-analysis was conducted to assess potential linear and non-linear dose-response relations. Results Nine studies were included for analysis, with a total of 2408 patients with pancreatic cancer. There was a strong linear dose-response association between fasting blood glucose concentration and the rate of pancreatic cancer across the range of prediabetes and diabetes. No non-linear association was detected. The pooled rate ratio of pancreatic cancer per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose was 1.14 (95% confidence interval 1.06 to 1.22; P<0.001) without significant heterogeneity. Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 0.56 mmol/L increase in fasting blood glucose was 1.15, 95% confidence interval 1.05 to 1.27; P=0.003), strengthening the association between prediabetes and pancreatic cancer. Conclusions Every 0.56 mmol/L increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. As prediabetes can be improved or even reversed through lifestyle changes, early detection of prediabetes coupled with lifestyle changes could represent a viable strategy to curb the increasing incidence of pancreatic cancer. PMID:25556126

  11. 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.

  12. Meta-analysis of residential exposure to radon gas and lung cancer.

    PubMed Central

    Pavia, Maria; Bianco, Aida; Pileggi, Claudia; Angelillo, Italo F.

    2003-01-01

    OBJECTIVES: To investigate the relation between residential exposure to radon and lung cancer. METHODS: A literature search was performed using Medline and other sources. The quality of studies was assessed. Adjusted odds ratios with 95% confidence intervals (CI) for the risk of lung cancer among categories of levels of exposure to radon were extracted. For each study, a weighted log-linear regression analysis of the adjusted odds ratios was performed according to radon concentration. The random effect model was used to combine values from single studies. Separate meta-analyses were performed on results from studies grouped with similar characteristics or with quality scores above or equal to the median. FINDINGS: Seventeen case-control studies were included in the meta-analysis. Quality scoring for individual studies ranged from 0.45 to 0.77 (median, 0.64). Meta-analysis based on exposure at 150 Bq/m3 gave a pooled odds ratio estimate of 1.24 (95% CI, 1.11-1.38), which indicated a potential effect of residential exposure to radon on the risk of lung cancer. Pooled estimates of fitted odds ratios at several levels of randon exposure were all significantly different from unity--ranging from 1.07 at 50 Bq/m3 to 1.43 at 250 Bq/m3. No remarkable differences from the baseline analysis were found for odds ratios from sensitivity analyses of studies in which > 75% of eligible cases were recruited (1.12, 1.00-1.25) and studies that included only women (1.29, 1.04-1.60). CONCLUSION: Although no definitive conclusions may be drawn, our results suggest a dose-response relation between residential exposure to radon and the risk of lung cancer. They support the need to develop strategies to reduce human exposure to radon. PMID:14758433

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

    2011-01-01

    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

  15. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis

    PubMed Central

    Bhandari, Ruchi; Kelley, George A.; Hartley, Tara A.; Rockett, Ian R. H.

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I2 statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I2 = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women. PMID:25653879

  16. Patient Satisfaction with Intravenous Acetaminophen: A Pooled Analysis of Five Randomized, Placebo-Controlled Studies in the Acute Postoperative Setting.

    PubMed

    Apfel, Christian C; Souza, Kimberly; Portillo, Juan; Dalal, Poorvi; Bergese, Sergio D

    2014-01-16

    Intravenous (IV) acetaminophen has been shown to reduce postoperative pain and opioid consumption, which may lead to increased patient satisfaction. To determine the effect IV acetaminophen has on patient satisfaction, a pooled analysis from methodologically homogenous studies was conducted. We obtained patient-level data from five randomized, placebo-controlled studies in adults undergoing elective surgery in which patient satisfaction was measured using a 4-point categorical rating scale. The primary endpoint was "excellent" satisfaction and the secondary endpoint was "good" or "excellent" satisfaction at 24 hr after first study drug administration. Bivariate analyses were conducted using the chi-square test and Student's t-test and multivariable analyses were conducted using logistic regression analysis. Patients receiving IV acetaminophen were more than twice as likely as those who received placebo to report "excellent" patient satisfaction ratings (32.3% vs. 15.9%, respectively). Of all variables that remained statistically significant in the multivariable analysis (i.e., type of surgery, duration of anesthesia, last pain rating, and opioid consumption), IV acetaminophen had the strongest positive effect on "excellent" patient satisfaction with an odds ratio of 2.76 (95% CI 1.81-4.23). Results for "excellent" or "good" satisfaction were similar. When given as part of a perioperative analgesic regimen, IV acetaminophen was associated with significantly improved patient satisfaction. PMID:24433365

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  20. Does party fragmentation matter? The micro-foundation of the 'common pool' model in public spending analysis

    Microsoft Academic Search

    Rune J. Sørensen

    The common pool problem is a classical thesis in political economy: interest groups and their elected representatives seek to expand particular items on public budgets. A common pool of public revenue is used to finance the additional outlays, and this leads to overexpansion of public spending. If the elected assembly is comprised of broad and centralized political parties, the problem

  1. Age at Menarche and Risk of Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Li, Chun-Yan; Song, Bo; Wang, Ying-Yan; Meng, Hua; Guo, Shi-Bin; Liu, Li-Na; Lv, Hai-Chen; Wu, Qi-Jun

    2013-01-01

    Background Various observational studies have focused on the relationship between menarcheal age and the risk of colorectal cancer (CRC). However, the association is still controversial because of inconsistent results. Therefore, we performed a meta-analysis to assess this issue from epidemiological studies. Methods After a literature search in MEDLINE, EMBASE, and Web of Science for studies of menarcheal age and CRC risk published through the end of January 2013, we pooled the relative risks (RRs) from included studies using a fixed- or random-effects model and performed heterogeneity and publication bias analyses. All statistical tests were two-sided. Results Eleven case-control and 11 cohort studies were eligible for inclusion in our analysis. The random-effects pooled RR for oldest versus youngest menarcheal age was 0.95 [95% confidence intervals (CIs)?=?0.85–1.06], with significant heterogeneity (Q?=?61.03, P<0.001, I2?=?65.6%). When separately analyzed, case-control (RR?=?0.95, 95% CI?=?0.75–1.21) and cohort studies (RR?=?0.97, 95% CI?=?0.90–1.04) yielded similar results. Moreover, similar results were also observed among the subgroup analyses by study quality, population, exposure assessment, anatomic cancer site, subsite of colon cancer, and several potential important confounders and risk factors. There was no evidence of publication bias and significant heterogeneity between subgroups detected by meta-regression analyses. Conclusions Findings from this meta-analysis demonstrated that menarcheal age was not associated with the risk of CRC in humans. Further studies are warranted to stratify results by the subsite of colon cancer and menopause status in the future. PMID:23762403

  2. Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis

    PubMed Central

    Fritz, Heidi; Kennedy, Deborah; Fergusson, Dean; Fernandes, Rochelle; Doucette, Steve; Cooley, Kieran; Seely, Andrew; Sagar, Stephen; Wong, Raimond; Seely, Dugald

    2011-01-01

    Background Despite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers. Methods and Findings Two independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation- therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13–1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087). Conclusions There is a lack of evidence to support the use of naturally occuring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study. PMID:21738614

  3. Bayesian pathway analysis of cancer microarray data.

    PubMed

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

    2014-01-01

    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

  4. Bayesian Pathway Analysis of Cancer Microarray Data

    PubMed Central

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

    2014-01-01

    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

  5. Meta-analysis in cancer epidemiology.

    PubMed Central

    Morris, R D

    1994-01-01

    Meta-analysis has seen increasing use as a tool in epidemiology over the past five years. Although this method is relatively well accepted for use in clinical trials, its use has proved somewhat more controversial in epidemiology. If meta-analysis is viewed as an evolutionary improvement over the review article, it may become more widely acceptable. Meta-analysis should incorporate the concern for study quality and differences in study design seen in classic review articles with the concern for rigor, objectivity, and quantitative precision characteristic of meta-analysis. Available tools for consideration of differences among studies are described with several examples from the literature. The extent to which various methods are used in published meta-analyses is described. Methods for assessing publication bias, and tools for combining dose-response data, are discussed also. Evaluation of risk factors and protective factors for cancer must be based on the weight of the evidence. Tools such as meta-analysis are essential if we are to interpret the vast number of completed studies in cancer epidemiology. PMID:7851334

  6. Efficacy of gemcitabine plus platinum agents for biliary tract cancers: a meta-analysis.

    PubMed

    Yang, Rui; Wang, Bing; Chen, Yong-jun; Li, Hong-bo; Hu, Jun-bo; Zou, Sheng-quan

    2013-09-01

    The objective of this study was to carry out a meta-analysis of the efficacy of gemcitabine+platinum agent regimens in the treatment of advanced biliary tract cancer (BTC). PubMed and Google Scholar were searched using the following combination of search terms: gemcitabine, oxaliplatin, cholangiocarcinoma, biliary, gallbladder, bile duct. Studies were eligible for inclusion in the meta-analysis if they were randomized trials on the use of gemcitabine plus a platinum agent for the treatment of advanced (unresectable or metastatic cancer) BTC. Outcomes of interest were response rate, overall survival, and progression-free survival. Pooled odds ratios/differences in median survival and 95% confidence intervals (CIs) were determined for each outcome. A total of 47 records were identified in the initial search. Ultimately, three open-label randomized trials (two phase 2 and one phase 3) met the eligibility criteria and were included in the meta-analysis. Two studies compared gemcitabine plus cisplatin with gemcitabine alone, whereas the other study compared gemcitabine plus oxaliplatin with fluorouracil-folinic acid. The total number of patients in the studies ranged from 54 to 410. The overall analyses revealed that all survival outcomes assessed were significantly more favorable for patients treated with gemcitabine plus platinum agents than for patients not treated with this combination. Response rates: odds ratio=2.639, 95% CI=1.210-5.757, Z=2.439, P=0.015; pooled difference in median overall survival=3.822 months, 95% CI=1.798-5.845 months, Z=3.702, P<0.001; pooled difference in median progression-free survival=3.268 months, 95% CI=1.996-4.541 months, Z=5.035, P<0.001. Patients with advanced BTC who are treated with gemcitabine plus platinum agents may experience better survival outcomes compared with patients who are not treated with this combination of chemotherapy. PMID:23799294

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

    PubMed Central

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

    2014-01-01

    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

  8. Hematologic toxicity assessment in solid tumor patients treated with cetuximab: a pooled analysis of 18 randomized controlled trials.

    PubMed

    Cui, Ran; Chu, Li; Liu, Zhu-qing; Xiao, Yuan-yuan; Zhu, Xiao-li; Chen, Yi-jing; Xu, Qing

    2015-02-15

    The role of cetuximab in treatment-related hematologic toxicity is not clear. We performed a meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of ?grade 3 hematologic toxicity events (HTEs) associated with cetuximab. PubMed, EMBASE, and Web of Knowledge databases as well as abstracts presented at American Society of Clinical Oncology conferences and ClinicalTrials.gov were searched to identify relevant studies. Eligible studies included RCTs in which cetuximab in combination with chemotherapy or chemoradiotherapy was compared with chemotherapy or chemoradiotherapy alone. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. A total of 11,234 patients with a variety of advanced solid tumors from 18 RCTs were included in the meta-analysis. Compared with chemotherapy alone, the addition of cetuximab was associated with increased risks of ?grade 3 leucopenia/neutropenia and anemia events in colorectal cancer, with RRs of 1.16 (95% CI 1.05-1.27, p=0.002; incidence, 21.0 vs. 18.0%) and 2.67 (95% CI 1.53-4.65, p=0.01; incidence, 4.0 vs. 2.0%), respectively. Cetuximab was also associated with an increased risk of leucopenia/neutropenia in nonsmall cell lung cancer (NSCLC) (RR: 1.15; 95% CI 1.08-1.22, p<0.01). Additionally, K-ras wild type in the case of colorectal cancer patients was more vulnerable to ?grade 3 leucopenia or neutropenia events in cetuximab group (RR: 1.31; 95% CI 1.11-1.54, p=0.001). With present evidence, cetuximab in conjunction with chemotherapy or chemoradiotherapy, compared with chemotherapy or chemoradiotherapy alone, was associated with increased slight risk of ?grade 3 HTEs, especially in colorectal cancer and NSCLC. PMID:24975040

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

    PubMed Central

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

    2014-01-01

    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

  10. Optical spectra analysis for breast cancer diagnostics

    NASA Astrophysics Data System (ADS)

    Belkov, S. A.; Kochemasov, G. G.; Lyubynskaya, T. E.; Maslov, N. V.; Nuzhny, A. S.; da Silva, L. B.; Rubenchik, A.

    2011-11-01

    Minimally invasive probe and optical biopsy system based on optical spectra recording and analysis seem to be a promising tool for early diagnostics of breast cancer. Light scattering and absorption spectra are generated continuously as far as the needle-like probe with one emitting and several collecting optical fibers penetrates through the tissues toward to the suspicious area. That allows analyzing not only the state of local site, but also the structure of tissues along the needle trace. The suggested method has the advantages of automated on-line diagnosing and minimal tissue destruction and in parallel with the conventional diagnostic procedures provides the ground for decision-making. 165 medical trials were completed in Nizhny Novgorod Regional Oncology Centre, Russia. Independent diagnoses were the results of fine biopsy and histology. Application of wavelet expansion and clasterization techniques for spectra analysis revealed several main spectral types for malignant and benign tumors. Automatic classification algorithm demonstrated specificity ˜90% and sensitivity ˜91%. Large amount of information, fuzziness in criteria and data noisiness make neural networks to be an attractive analytic tool. The model based on three-layer perceptron was tested over the sample of 29 `cancer' and 29 `non-cancer' cases and demonstrated total separation.

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

    SciTech Connect

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    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

  12. Identification of genes associated with multiple cancers via integrative analysis

    PubMed Central

    2009-01-01

    Background Advancement in gene profiling techniques makes it possible to measure expressions of thousands of genes and identify genes associated with development and progression of cancer. The identified cancer-associated genes can be used for diagnosis, prognosis prediction, and treatment selection. Most existing cancer microarray studies have been focusing on the identification of genes associated with a specific type of cancer. Recent biomedical studies suggest that different cancers may share common susceptibility genes. A comprehensive description of the associations between genes and cancers requires identification of not only multiple genes associated with a specific type of cancer but also genes associated with multiple cancers. Results In this article, we propose the Mc.TGD (Multi-cancer Threshold Gradient Descent), an integrative analysis approach capable of analyzing multiple microarray studies on different cancers. The Mc.TGD is the first regularized approach to conduct "two-dimensional" selection of genes with joint effects on cancer development. Simulation studies show that the Mc.TGD can more accurately identify genes associated with multiple cancers than meta analysis based on "one-dimensional" methods. As a byproduct, identification accuracy of genes associated with only one type of cancer may also be improved. We use the Mc.TGD to analyze seven microarray studies investigating development of seven different types of cancers. We identify one gene associated with six types of cancers and four genes associated with five types of cancers. In addition, we also identify 11, 9, 18, and 17 genes associated with 4 to 1 types of cancers, respectively. We evaluate prediction performance using a Leave-One-Out cross validation approach and find that only 4 (out of 570) subjects cannot be properly predicted. Conclusion The Mc.TGD can identify a short list of genes associated with one or multiple types of cancers. The identified genes are considerably different from those identified using meta analysis or analysis of marginal effects. PMID:19919702

  13. Calcium Channel Blockers and Risk of Breast Cancer: A Meta-Analysis of 17 Observational Studies

    PubMed Central

    Li, Wen; Shi, Qi; Wang, Weibing; Liu, Jianrong; Li, Qi; Hou, Fenggang

    2014-01-01

    Purpose Studies on the association between the use of calcium channel blockers (CCBs) and breast cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on the evidence from observational studies. Methods We searched PubMed, MEDLINE, EMBASE and the Cochrane Library for relevant studies published up to and including December 31, 2013. We calculated pooled risk ratios (RRs) for cancer risk. Results A total of 17 studies (9 cohort studies, 8 case-control studies) were selected for further study. These studies included 149,607 female subjects, of which 53,812 were CCBs users, who were followed for 2–16 years. The risks of breast cancer among patients receiving CCBs were significantly different for the pooled RRs (95% confidence interval) of cohort studies 1.08 (0.95, 1.20) and case-control studies 0.98 (0.86, 1.09). Differences were also noted for cancer risk, for CCBs use of <5 years 0.96 (0.78, 1.15), and for >5 years 1.01 (0.74, 1.28), as well as for ever used 1.08 (0.95, 1.20), and for current use 1.13 (0.83, 1.42). The RR for studies longer than 10 years was 1.71 (1.01, 2.42), and for studies evaluating nifedipine was 1.10 (0.87, 1.33) and diltiazem was 0.75 (0.40, 1.10). Conclusions The long-term use of CCBs appears to have a significant relationship with breast cancer. Well-designed clinical trials are needed to optimize the doses and types of these drugs needed to minimize their carcinogenic potential. PMID:25184210

  14. Analysis of CD8 T cell reactivity to cytomegalovirus using protein-spanning pools of overlapping pentadecapeptides.

    PubMed

    Kern, F; Faulhaber, N; Frömmel, C; Khatamzas, E; Prösch, S; Schönemann, C; Kretzschmar, I; Volkmer-Engert, R; Volk, H D; Reinke, P

    2000-06-01

    The frequencies of human cytomegalovirus (HCMV) protein-specific CD8 T cells, identified by the presence of intracellular IFN-gamma, were measured by flow cytometry following stimulation of freshly isolated peripheral blood mononuclear cells (PBMC) with comprehensive peptide pools. These pools spanned the entire amino acid sequences of the HCMV pp65 and major immediate early (IE-1) proteins and consisted of 15-amino acid peptides with at least nine overlaps between neighboring peptides. As a result all potential CD8 T cell epitopes contained in these proteins were provided by the complete pools and, therefore, unlike with single epitopes, testing was independent of donor HLA type. Individual stimulating peptides from the same pools were identified in parallel experiments. Thus we found that our results with the complete pools using PBMC from 26 healthy HCMV-seropositive donors were 100% sensitive and specific with respect to predicting the presence of recognized epitopes in the respective proteins. In addition, cells from 15 renal transplant patients were tested with complete pools alone. While our results confirmed our previous contention that HCMV IE-1 is an important CD8 T cell target, the technical improvement we made in order to address this question has clearly wider implications. Similar pools may be applied to examine the role of proteins from other pathogens, in autoimmune disease or following vaccination. PMID:10898504

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

    PubMed Central

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

    2014-01-01

    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

  16. Occupation related pesticide exposure and cancer of the prostate: a meta-analysis

    PubMed Central

    Van Maele-Fabry, G; Willems, J

    2003-01-01

    Aims: To summarise recent literature on the risk of prostate cancer in pesticide related occupations, to calculate the meta-rate ratio, and to compare it to data from meta-analyses previously published. Methods: A meta-analysis of 22 epidemiological studies, published between 1995 and 2001, was conducted in order to pool their rate ratio estimates. Studies were summarised and evaluated for homogeneity and publication bias. Results: The meta-rate ratio estimate, based on 25 estimators of relative risk from 22 studies, was 1.13 (95% CI 1.04 to 1.22). Significant heterogeneity of rate ratios existed among the different studies. Therefore, a stratified analysis was carried out. Major sources of heterogeneity identified were geographic location, study design, and healthy worker effect. Overall, pooled risk estimates for studies derived from Europe were lower than those derived from the USA/Canada. A significant increase in rate ratio was observed for the occupation category of pesticide applicators, whereas no significant increase was observed for farmers. There was no evidence of publication bias. Conclusion: This increased meta-rate ratio for prostate cancer in different pesticide related occupations, including farmers, is very similar to three, previously published, meta-rate ratios for prostate cancer in farmers calculated from studies published before 1995. Although the underlying data do not identify pesticide exposure as an independent cause for prostate cancer, the fact that an increased meta-rate ratio is again obtained points to occupational exposure to pesticides as a possible factor. Future epidemiological studies should focus, as far as possible, on reliable methods to estimate actual exposure. PMID:12937183

  17. The association between the migration inhibitory factor ?173G/C polymorphism and cancer risk: a meta-analysis

    PubMed Central

    Zhang, Xiao; Weng, Wenhao; Xu, Wen; Wang, Yulan; Yu, Wenjun; Tang, Xun; Ma, Lifang; Pan, Qiuhui; Wang, Jiayi; Sun, Fenyong

    2015-01-01

    Previous studies have suggested that macrophage migration inhibitory factor (MIF) ?173G/C polymorphism may be associated with cancer risk. However, previous research has demonstrated conflicting results. Therefore, we followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and the meta-analysis on genetic association studies checklist, and performed a meta-analysis to investigate the association between MIF ?173G/C polymorphisms and the risk of cancer. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were combined to measure the association between MIF promoter polymorphisms and cancer risk. The pooled ORs were performed for the dominant model, recessive model, allelic model, homozygote comparison, and heterozygote comparison. The publication bias was examined by Begg’s funnel plots and Egger’s test. A total of ten studies enrolling 2,203 cases and 2,805 controls met the inclusion criteria. MIF (?173G/C) polymorphism was significantly associated with increased cancer risk under the dominant model (OR=1.32, 95%, CI=1.00–1.74, P=0.01) and the heterozygote comparison (OR=1.38, CI=1.01–1.87, P=0.04). In subgroup analysis, MIF polymorphism and prostate were related to increased risk of prostate and non-solid cancer. In conclusion, MIF polymorphism was significantly associated with cancer risk in heterozygote comparison. The MIF ?173G/C polymorphism may be associated with increased cancer risk.

  18. The association between the migration inhibitory factor -173G/C polymorphism and cancer risk: a meta-analysis.

    PubMed

    Zhang, Xiao; Weng, Wenhao; Xu, Wen; Wang, Yulan; Yu, Wenjun; Tang, Xun; Ma, Lifang; Pan, Qiuhui; Wang, Jiayi; Sun, Fenyong

    2015-01-01

    Previous studies have suggested that macrophage migration inhibitory factor (MIF) -173G/C polymorphism may be associated with cancer risk. However, previous research has demonstrated conflicting results. Therefore, we followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and the meta-analysis on genetic association studies checklist, and performed a meta-analysis to investigate the association between MIF -173G/C polymorphisms and the risk of cancer. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were combined to measure the association between MIF promoter polymorphisms and cancer risk. The pooled ORs were performed for the dominant model, recessive model, allelic model, homozygote comparison, and heterozygote comparison. The publication bias was examined by Begg's funnel plots and Egger's test. A total of ten studies enrolling 2,203 cases and 2,805 controls met the inclusion criteria. MIF (-173G/C) polymorphism was significantly associated with increased cancer risk under the dominant model (OR=1.32, 95%, CI=1.00-1.74, P=0.01) and the heterozygote comparison (OR=1.38, CI=1.01-1.87, P=0.04). In subgroup analysis, MIF polymorphism and prostate were related to increased risk of prostate and non-solid cancer. In conclusion, MIF polymorphism was significantly associated with cancer risk in heterozygote comparison. The MIF -173G/C polymorphism may be associated with increased cancer risk. PMID:25792844

  19. Meta-Analysis of the Relationship between CXCR4 Expression and Metastasis in Prostate Cancer

    PubMed Central

    Lee, Joo Yong; Kang, Dong Hyuk; Chung, Doo Yong; Kwon, Jong Kyou; Lee, Hyungmin; Cho, Nam Hoon; Choi, Young Deuk; Hong, Sung Joon

    2014-01-01

    Purpose Experimental studies have suggested that the stromal-derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in several malignancies. We performed a meta-analysis to elucidate the relationship between CXCR4 expression and the clinicopathological features of prostate cancer. Materials and Methods Data were collected from studies comparing Gleason score, T stage, and the presence of metastasis with CXCR4 levels in human prostate cancer samples. The studies were pooled, and the odds ratio (OR) of CXCR4 expression for clinical and pathological variables was calculated. Results Five articles were eligible for the current meta-analysis. We found no relationship between CXCR4 expression and Gleason score (<7 vs. ?7). The forest plot using the fixed-effects model indicated an OR of 1.585 (95% confidence interval [CI]: 0.793~3.171; p=0.193). Further, CXCR4 expression was not associated with the T stage (analysis showed OR=1.803 (95% CI: 0.756~4.297, p=0.183). However, increased CXCR4 expression was strongly associated with metastatic disease with a fixed-effects pooled OR of 7.459 (95% CI: 2.665~20.878, p<0.001). Conclusions Our meta-analysis showed that the higher CXCR4 protein expression in prostate cancer specimens is significantly associated with the presence of metastatic disease. This supports previous experimental data supporting the role played by the SDF-1/CXCR4 axis in metastasis. PMID:25606566

  20. Meta-analysis of the association between APC promoter methylation and colorectal cancer

    PubMed Central

    Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

    2015-01-01

    Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50–8.76; P<0.01). Eleven studies with a total of 1,219 patients evaluated the association between APC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44–1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67–5.10; P=0.23). No significant correlation between APC promoter methylation and patients’ Dukes’ stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC. PMID:25632237

  1. Pool & Spa Safety Act

    MedlinePLUS

    ... Stories Pool Safely Home Consumer Product Safety Commission, CPSC CPSC Home The Pool & Spa Safety Act Contact Information About PoolSafely.gov and CPSC The U.S. Consumer Product Safety Commission (CPSC) is ...

  2. Human Papillomavirus Infection and Bladder Cancer Risk: A Meta-analysis

    PubMed Central

    Li, Ni; Yang, Lin; Zhang, Yawei; Zhao, Ping; Zheng, Tongzhang

    2011-01-01

    Background.?Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) infection and risk of bladder cancer, the studies remain inconclusive. Methods.?The prevalence of HPV in bladder cancer was estimated by pooling data from 52 studies, taking into consideration the heterogeneity from major related parameters including study region, histological type, HPV DNA specimen, publication calendar period, and detection method. Moreover, the association of HPV infection with bladder cancer was tested by a meta-analysis with 19 case-control studies. Results.?An HPV prevalence of 16.88% (95% confidence interval [CI], 15.53%–18.31%) among the bladder cancer cases was revealed, most of whom were high-risk HPV types (15.82% [95% CI, 14.37%–17.36%]). The prevalence varied by region, types of HPV DNA specimen, and polymerase chain reaction primers used. A significantly increased risk of bladder cancer was shown for the positivity of overall HPV (odds ratio, 2.84 [95% CI, 1.39–5.80]), which was also infuenced by HPV type, study region, HPV DNA specimen, and detection method. Conclusions.?Infection of high-risk HPV types, especially HPV16, may play a role in bladder carcinogenesis. PMID:21673031

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

    PubMed Central

    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

    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

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

    PubMed Central

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

    2013-01-01

    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

  5. Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis

    PubMed Central

    An, Han-Xiang

    2014-01-01

    Objective The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer. Methods A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed. Results A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR?=?0.45, 95% confidence interval [CI] ?=?0.32–0.63; P<0.00001), status of lymph nodes (OR?=?0.40, 95% CI?=?0.25–0.64; P?=?0.0001) and tumor node metastasis (TNM) stage (OR?=?0.56, 95% CI?=?0.41–0.77; P?=?0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR?=?1.99, 95% CI?=?1.29–3.07, P?=?0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications. Conclusion CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors. PMID:25503963

  6. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    PubMed

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk. PMID:20855349

  7. Mutational Analysis of the Tyrosine Phosphatome in Colorectal Cancers

    Microsoft Academic Search

    Zhenghe Wang; Dong Shen; D. Williams Parsons; Alberto Bardelli; Jason Sager; Steve Szabo; Janine Ptak; Natalie Silliman; Brock A. Peters; Michiel S. van der Heijden; Giovanni Parmigiani; Hai Yan; Tian-Li Wang; Greg Riggins; Steven M. Powell; James K. V. Willson; Sanford Markowitz; Kenneth W. Kinzler; Bert Vogelstein; Victor E. Velculescu

    2004-01-01

    Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations

  8. Applications of Innovative Technologies for the Molecular Analysis of Cancer

    Cancer.gov

    This program announcement provides support for a first phase for technology evaluation and a second phase for pilot application of the technology in a study of biological interest to cancer research. Studies might appropriately target analysis of precancerous, cancerous, or metastatic cells, or host derived samples, from model cancer systems, preclinical or clinical research, or from population based research.

  9. An analysis and hypothesis generation platform for heterogeneous cancer

    E-print Network

    Reed, Chris

    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

  10. Baseline participant characteristics and risk for dropout from ten obesity randomized controlled trials: a pooled analysis of individual level data

    PubMed Central

    Kaiser, Kathryn A.; Affuso, Olivia; Desmond, Renee; Allison, David B.

    2014-01-01

    Introduction Understanding participant demographic characteristics that inform the optimal design of obesity RCTs have been examined in few studies. The objective of this study was to investigate the association of individual participant characteristics and dropout rates (DORs) in obesity randomized controlled trials (RCT) by pooling data from several publicly available datasets for analyses. We comprehensively characterize DORs and patterns in obesity RCTs at the individual study level, and describe how such rates and patterns vary as a function of individual-level characteristics. Methods We obtained and analyzed nine publicly-available, obesity RCT datasets that examined weight loss or weight gain prevention as a primary or secondary endpoint. Four risk factors for dropout were examined by Cox proportional hazards including sex, age, baseline BMI, and race/ethnicity. The individual study data were pooled in the final analyses with a random effect for study, and HR and 95% CIs were computed. Results Results of the multivariate analysis indicated that the risk of dropout was significantly higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46). Hispanics and Non-Hispanic blacks had a significantly higher dropout rate compared to non-Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35, respectively). There was a significantly increased risk of dropout associated with advancing age (HR= 1.02, 95% CI = 1.01, 1.02) and increasing BMI (HR= 1.03, 95% CI = 1.03, 1.04). Conclusion/Significance As more studies may focus on special populations, researchers designing obesity RCTs may wish to oversample in certain demographic groups if attempting to match comparison groups based on generalized estimates of expected dropout rates, or otherwise adjust a priori power estimates. Understanding true reasons for dropout may require additional methods of data gathering not generally employed in obesity RCTs, e.g. time on treatment. PMID:25599077

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

    Microsoft Academic Search

    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

    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

  12. Analysis of pooling, equity capital and current assets of large producer marketing cooperatives with implications for export marketing

    E-print Network

    Tough, Cynthia H

    1985-01-01

    (Table 4). Of the pooling cooperatives, only those with marketing as the major function deducted per-unit retains. Retains in 1981 were $1. 8 million Table 2. Mean Values of Selected Financial Variables by Pooling Operations, U. S. Non... than the pure marketing cooperatives. The farm supply cooperatives averaged $22. 2 million more equity capital than the mixed category and $93. 4 million more than the market- ing cooperatives. The farm supply group also had the largest average net...

  13. Meta-analysis of genetic polymorphisms and gastric cancer risk: variability in associations according to race.

    PubMed

    Loh, Marie; Koh, King Xin; Yeo, Boon Huat; Song, Chun Meng; Chia, Kee Seng; Zhu, Feng; Yeoh, Khay Guan; Hill, Jeffrey; Iacopetta, Barry; Soong, Richie

    2009-09-01

    The goal of this study was to consolidate information on genetic risk factors for gastric cancer. An additional aim was to investigate the influence of race on these genetic risk associations. Relevant studies were identified from PubMed and references of retrieved articles. Meta-analysis techniques were used to summarise associations between genetic polymorphisms and gastric cancer. A total of 203 relevant studies were identified, assessing 225 polymorphisms across 95 genes. Subgroup analysis indicated that Chinese, Japanese and Korean data were consistent and could be pooled. However, 6 of 13 polymorphisms (ACE I/D, CCND1 870G>A, CDH1 -160C>A, IL1B -511C>T, IL4 -590C>T, IL10 -592A>C) displayed conflicting effects between Asian and Caucasian populations, three of which (ACE I/D, CCND1 870G>A, IL1B -511C>T) had significantly different odds ratios between the two racial groups. In total, 37 polymorphisms across 27 genes were found to be significantly associated with gastric cancer in Asians, and 12 polymorphisms across 11 genes in Caucasians. Consolidated panels of polymorphisms associated with gastric cancer risk were identified in Asians and Caucasians. The results caution against the assumption that genetic risk factors are consistent between races. PMID:19375306

  14. HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis.

    PubMed

    Diaz, Aaron A; Qin, Han; Ramalho-Santos, Miguel; Song, Jun S

    2015-02-18

    Genetic screens of an unprecedented scale have recently been made possible by the availability of high-complexity libraries of synthetic oligonucleotides designed to mediate either gene knockdown or gene knockout, coupled with next-generation sequencing. However, several sources of random noise and statistical biases complicate the interpretation of the resulting high-throughput data. We developed HiTSelect, a comprehensive analysis pipeline for rigorously selecting screen hits and identifying functionally relevant genes and pathways by addressing off-target effects, controlling for variance in both gene silencing efficiency and sequencing depth of coverage and integrating relevant metadata. We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens. HiTSelect is implemented as an open-source package, with a user-friendly interface for data visualization and pathway exploration. Binary executables are available at http://sourceforge.net/projects/hitselect/, and the source code is available at https://github.com/diazlab/HiTSelect. PMID:25428347

  15. HiTSelect: a comprehensive tool for high-complexity-pooled screen analysis

    PubMed Central

    Diaz, Aaron A.; Qin, Han; Ramalho-Santos, Miguel; Song, Jun S.

    2015-01-01

    Genetic screens of an unprecedented scale have recently been made possible by the availability of high-complexity libraries of synthetic oligonucleotides designed to mediate either gene knockdown or gene knockout, coupled with next-generation sequencing. However, several sources of random noise and statistical biases complicate the interpretation of the resulting high-throughput data. We developed HiTSelect, a comprehensive analysis pipeline for rigorously selecting screen hits and identifying functionally relevant genes and pathways by addressing off-target effects, controlling for variance in both gene silencing efficiency and sequencing depth of coverage and integrating relevant metadata. We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens. HiTSelect is implemented as an open-source package, with a user-friendly interface for data visualization and pathway exploration. Binary executables are available at http://sourceforge.net/projects/hitselect/, and the source code is available at https://github.com/diazlab/HiTSelect. PMID:25428347

  16. Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis[S

    PubMed Central

    Minicocci, Ilenia; Santini, Sara; Cantisani, Vito; Stitziel, Nathan; Kathiresan, Sekar; Arroyo, Juan Antonio; Martí, Gertrudis; Pisciotta, Livia; Noto, Davide; Cefalù, Angelo B.; Maranghi, Marianna; Labbadia, Giancarlo; Pigna, Giovanni; Pannozzo, Fabio; Ceci, Fabrizio; Ciociola, Ester; Bertolini, Stefano; Calandra, Sebastiano; Tarugi, Patrizia; Averna, Maurizio; Arca, Marcello

    2013-01-01

    Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation. PMID:24058201

  17. Integrative Analysis of High-throughput Cancer Studies with Contrasted Penalization

    PubMed Central

    Shi, Xingjie; Liu, Jin; Huang, Jian; Zhou, Yong; Shia, BenChang; Ma, Shuangge

    2015-01-01

    In cancer studies with high-throughput genetic and genomic measurements, integrative analysis provides a way to effectively pool and analyze heterogeneous raw data from multiple independent studies and outperforms “classic” meta-analysis and single-dataset analysis. When marker selection is of interest, the genetic basis of multiple datasets can be described using the homogeneity model or the heterogeneity model. In this study, we consider marker selection under the heterogeneity model, which includes the homogeneity model as a special case and can be more flexible. Penalization methods have been developed in the literature for marker selection. This study advances from the published ones by introducing the contrast penalties, which can accommodate the within- and across-dataset structures of covariates/regression coefficients and, by doing so, further improve marker selection performance. Specifically, we develop a penalization method that accommodates the across-dataset structures by smoothing over regression coefficients. An effective iterative algorithm, which calls an inner coordinate descent iteration, is developed. Simulation shows that the proposed method outperforms the benchmark with more accurate marker identification. The analysis of breast cancer and lung cancer prognosis studies with gene expression measurements shows that the proposed method identifies genes different from those using the benchmark and has better prediction performance. PMID:24395534

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

    PubMed Central

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

    2014-01-01

    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

  19. Analysis of Assembly Bill 1000: Cancer Treatment

    E-print Network

    California Health Benefits Review Program (CHBRP)

    2011-01-01

    kidney cancer, Waldenström's macroglobulinemia/ lymphoplasmacytic lymphoma Treatmenttreatment for advanced, metastatic, inoperable, progressive, and recurrent kidney andrecurrent kidney cancer who have not responded to treatment

  20. Perioperative blood transfusion adversely affects prognosis after resection of lung cancer: a systematic review and a meta-analysis

    PubMed Central

    2014-01-01

    Background It is speculated that blood transfusion may induce adverse consequences after cancer surgery due to immunosuppression. This study was intended to assess the impact of perioperative blood transfusion on the prognosis of patients who underwent lung cancer resection. Methods Eligible studies were identified through a computerized literature search. The pooled relative risk ratio (RR) with 95% confidence interval (CI) was calculated using Review Manager 5.1 Software. Results Eighteen studies with a total of 5915 participants were included for this meta-analysis. Pooled analysis showed that perioperative blood transfusion was associated with worse overall survival (RR: 1.25, 95% CI: 1.13-1.38; P <0.001) and recurrence-free survival (RR: 1.42, 95% CI: 1.20-1.67; P <0.001) in patients with resected lung cancer. Conclusions Perioperative blood transfusion appears be associated with a worse prognosis in patients undergoing lung cancer resection. These data highlight the importance of minimizing blood transfusion during surgery. PMID:24884867

  1. Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis

    PubMed Central

    Shah, Nirav R.; Borenstein, Jeff; Dubois, Robert W.

    2006-01-01

    Objective There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to examine the specific relationships of postmenopausal estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone therapy (CHT), and the incidence of breast cancer. Design We performed computerized searches of MEDLINE and CancerLit through September 2003 and reviewed reference lists of retrieved studies and meta-analyses. We included English-language studies that identified noncontraceptive postmenopausal hormone use; reported on the risks of “current use” of ET and/or CHT and breast cancer incidence; were case-control, cohort, or experimental; and reported either an odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were involved during all stages of study selection and independently extracted all data selected for inclusion in meta-analyses. Results Meta-analysis of 13 studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95% confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16 (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95% CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and more than 5 years use 1.63 (1.22, 2.18). Conclusions Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT. These represent the first pooled estimates for ET. CHT estimates correspond to those from randomized trials. PMID:16278609

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

    PubMed Central

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

    2014-01-01

    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

  3. Effect of Metformin on Cancer Risk and Treatment Outcome of Prostate Cancer: A Meta-Analysis of Epidemiological Observational Studies

    PubMed Central

    Yu, Hongliang; Yin, Li; Jiang, Xuesong; Sun, Xiujin; Wu, Jing; Tian, Hao; Gao, Xianshu; He, Xia

    2014-01-01

    Background Laboratory studies have shown the anti-tumor effect of metformin on prostate cancer. However, recent epidemiological studies have yielded inconclusive results. Methods We searched PubMed database from the inception to May 30 2014 for studies which assessed the effect of metformin use on cancer risk of prostate cancer, biochemical recurrence (BCR) and all-cause mortality of patients with prostate cancer. The pooled results and 95% confidence intervals (CIs) were estimated by random-effect model. Results Twenty-one studies were eligible according to the inclusion criteria. Based on the pooled results of available observational studies, metformin use was significantly associated with a decreased cancer risk (14 datasets, 963991 male subjects, odds ratio: 0.91, 95% CI: 0.85–0.97) and BCR (6 datasets, 2953 patients, hazard ratio: 0.81, 95% CI: 0.68–0.98) of prostate cancer. However, the association of metformin use with all-cause mortality of patients with prostate cancer was not significant (5 datasets, 9241 patients, hazard ratio: 0.86, 95% CI: 0.64–1.14). Conclusion Results suggest that metformin use appears to be associated with a significant reduction in the cancer risk and BCR of prostate cancer, but not in all-cause mortality of patients with prostate cancer. PMID:25545701

  4. Tea consumption and the risk of five major cancers: a dose–response meta-analysis of prospective studies

    PubMed Central

    2014-01-01

    Background We conducted a dose–response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer. Methods We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ?3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk. Results Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer (RR, 1.18; 95% CI, 1.05-1.32). Conclusion Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations. PMID:24636229

  5. A Systematic Review and Meta-Analysis of Diagnostic and Prognostic Serum Biomarkers of Colorectal Cancer

    PubMed Central

    Liu, Zhongyu; Zhang, Yingchong; Niu, Yulong; Li, Ke; Liu, Xin; Chen, Huijuan; Gao, Chunfang

    2014-01-01

    Background Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with >?=?3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347–3.744) and MMP-7 with lowest (1.099, CI: 1.018–1.187)) pooled HRs are presented. Conclusions The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. PMID:25105762

  6. XPA A23G polymorphism and risk of digestive system cancers: a meta-analysis

    PubMed Central

    He, Lei; Deng, Tao; Luo, Hesheng

    2015-01-01

    Background Several studies have reported an association between the A23G polymorphism (rs 1800975) in the xeroderma pigmentosum group A (XPA) gene and risk of digestive system cancers. However, the results are inconsistent. In this study, we performed a meta-analysis to assess the association between XPA A23G polymorphism and the risk of digestive system cancers. Methods Relevant studies were identified using the PubMed, Web of Science, China National Knowledge Infrastructure, WanFang, and VIP databases up to August 30, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed or random effects model. Results A total of 18 case-control studies from 16 publications with 4,170 patients and 6,929 controls were included. Overall, no significant association was found between XPA A23G polymorphism and the risk of digestive system cancers (dominant model: GA + AA versus GG, OR 0.89, 95% CI 0.74–1.08; recessive model: AA versus GA + GG, OR 0.94, 95% CI 0.74–1.20; GA versus GG, OR 0.89, 95% CI 0.77–1.03; and AA versus GG, OR 0.87, 95% CI 0.64–1.19). When the analysis was stratified by ethnicity, similar results were observed among Asians and Caucasians in all genetic models. In stratified analysis based on tumor type, we also failed to detect any association between XPA A23G polymorphism and the risk of esophageal, gastric, or colorectal cancers. Conclusion This meta-analysis indicates that the XPA A23G polymorphism is not associated with a risk of digestive system cancers. PMID:25709470

  7. PoolHap: Inferring Haplotype Frequencies from Pooled Samples by Next Generation Sequencing

    Microsoft Academic Search

    Quan Long; Daniel C. Jeffares; Qingrun Zhang; Kai Ye; Viktoria Nizhynska; Zemin Ning; Chris Tyler-Smith; Magnus Nordborg; Thomas Mailund

    2011-01-01

    With the advance of next-generation sequencing (NGS) technologies, increasingly ambitious applications are becoming feasible. A particularly powerful one is the sequencing of polymorphic, pooled samples. The pool can be naturally occurring, as in the case of multiple pathogen strains in a blood sample, multiple types of cells in a cancerous tissue sample, or multiple isoforms of mRNA in a cell.

  8. Analysis and simulation of a cold-air pool and high wintertime ozone episode in Utah's Uintah Basin

    NASA Astrophysics Data System (ADS)

    Neemann, Erik M.

    High ozone concentrations associated with a winter cold-air pool during the Uintah Basin Winter Ozone Study are investigated. Field campaign observations combined with numerical simulations are analyzed in Utah's Uintah Basin from 1-6 February 2013 when ozone concentrations exceeded 150 ppb. Cold-air pool sensitivity to cloud microphysics and snow cover variations within the Weather Research and Forecasting model simulations are examined, along with their impact on air quality in Community Multiscale Air Quality model simulations. Ice-dominant clouds are found to enhance cold-air pool strength compared to liquid-dominant clouds through increased nocturnal cooling and decreased longwave cloud forcing. The presence of snow cover also strengthens cold-air pool structure by lowering near-surface air temperatures and increasing boundary layer stability due to reduced absorbed solar insolation by the high-albedo snow surface. Snow cover also increases ozone levels by enhancing solar radiation available for photochemical reactions. Flow features affecting Uintah Basin cold-air pools that affect pollutant mixing and air quality within the basin are studied, including: penetration of clean air into the basin from across the surrounding mountains, elevated easterlies within the inversion layer, and diurnal upslope and drainage flows.

  9. Pooling techniques for bioassay screening

    SciTech Connect

    Sun, L.C.; Baum, J.W.; Kaplan, E; Moorthy, A.R.

    1996-03-01

    Pooling techniques commonly are used to increase the throughput of samples used for screening purposes. While the advantages of such techniques are increased analytical efficiency and cost savings, the sensitivity of measurements decreases because it is inversely proportional to the number of samples in the pools. Consequently, uncertainties in estimates of dose and risk which are based on the results of pooled samples increase as the number of samples in the pools increases in all applications. However, sensitivities may not be seriously degraded, for example, in urinalysis, if the samples in the pools are of known time duration, or if the fraction of some attribute of the grab urine samples to that in a 24-hour composite is known (e.g., mass, specific gravity, creatinine, or volume, per 24-h interval). This paper presents square and cube pooling schemes that greatly increase throughput and can considerably reduce analytical costs (on a sample basis). The benefit-cost ratios for 5{times}5 square and 5{times}5{times}5 cube pooling schemes are 2.5 and 8.3, respectively. Three-dimensional and higher arrayed pooling schemes would result in even greater economies; however, significant improvements in analytical sensitivity are required to achieve these advantages. These are various other considerations for designing a pooling scheme, where the number of dimensions and of samples in the optimum array are influenced by: (1) the minimal detectable amount (MDA) of the analytical processes, (2) the screening dose-rate requirements, (3) the maximum masses or volumes of the composite samples that can be analyzed, (4) the information already available from results of composite analysis, and (5) the ability of an analytical system to guard against both false negative and false positive results. Many of these are beyond the scope of this paper but are being evaluated.

  10. Meta-Analysis of Efficacy of Interventions for Elevated Depressive Symptoms in Adults Diagnosed With Cancer

    PubMed Central

    2012-01-01

    Background Cancer patients are at increased risk for depression compared with individuals with no cancer diagnosis, yet few interventions target depressed cancer patients. Methods Efficacy of psychotherapeutic and pharmacologic interventions for depression in cancer patients who met an entry threshold for depressive symptoms was examined by meta-analysis. Five electronic databases were systematically reviewed to identify randomized controlled trials meeting the selection criteria. Effect sizes were calculated using Hedges’ g and were pooled to compare pre- and postrandomization depressive symptoms with a random effects model. Subgroup analyses tested moderators of effect sizes, such as comparison of different intervention modalities, with a mixed effects model. All statistical tests were two-sided. Results Ten randomized controlled trials (six psychotherapeutic and four pharmacologic studies) met the selection criteria; 1362 participants with mixed cancer types and stages had been randomly assigned to treatment groups. One outlier trial was removed from analyses. The random effects model showed interventions to be superior to control conditions on reducing depressive symptoms postintervention (Hedges’ g = 0.43, 95% confidence interval = 0.30 to 0.56, P < .001). In the four psychotherapeutic trials with follow-up assessment, interventions were more effective than control conditions up to 12–18 months after patients were randomly assigned to treatment groups (P < .001). Although each approach was more effective than the control conditions in improving depressive symptoms (P < .001), subgroup analyses showed that cognitive behavioral therapy appeared more effective than problem-solving therapy (P = .01), but not more effective than pharmacologic intervention (P = .07). Conclusions Our findings suggest that psychological and pharmacologic approaches can be targeted productively toward cancer patients with elevated depressive symptoms. Research is needed to maximize effectiveness, accessibility, and integration into clinical care of interventions for depressed cancer patients. PMID:22767203

  11. Personal history of diabetes, genetic susceptibility to diabetes, and risk of brain glioma: a pooled analysis of observational studies

    PubMed Central

    Kitahara, Cari M.; Linet, Martha S.; Brenner, Alina V.; Wang, Sophia S.; Melin, Beatrice S.; Wang, Zhaoming; Inskip, Peter D.; Beane Freeman, Laura E.; Braganza, Melissa Z.; Carreón, Tania; Feychting, Maria; Gaziano, J. Michael; Peters, Ulrike; Purdue, Mark P.; Ruder, Avima M.; Sesso, Howard D.; Shu, Xiao-Ou; Waters, Martha A.; White, Emily; Zheng, Wei; Hoover, Robert N.; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Hartge, Patricia; Rajaraman, Preetha

    2013-01-01

    Background Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the U.S. and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNPs). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression models. Results We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR=0.58, 95% CI: 0.40–0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological sub-type. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk. Conclusion These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. Impact These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma. PMID:24220915

  12. Development of an Instrument to Measure Behavioral Health Function for Work Disability: Item Pool Construction and Factor Analysis

    PubMed Central

    Marfeo, Elizabeth E.; Ni, Pengsheng; Haley, Stephen M.; Jette, Alan M.; Bogusz, Kara; Meterko, Mark; McDonough, Christine M.; Chan, Leighton; Brandt, Diane E.; Rasch, Elizabeth K.

    2014-01-01

    Objectives To develop a broad set of claimant-reported items to assess behavioral health functioning relevant to the Social Security disability determination processes, and to evaluate the underlying structure of behavioral health functioning for use in development of a new functional assessment instrument. Design Cross-sectional. Setting Community. Participants Item pools of behavioral health functioning were developed, refined, and field-tested in a sample of persons applying for Social Security disability benefits (N=1015) who reported difficulties working due to mental or both mental and physical conditions. Interventions None. Main Outcome Measure Social Security Administration Behavioral Health (SSA-BH) measurement instrument Results Confirmatory factor analysis (CFA) specified that a 4-factor model (self-efficacy, mood and emotions, behavioral control, and social interactions) had the optimal fit with the data and was also consistent with our hypothesized conceptual framework for characterizing behavioral health functioning. When the items within each of the four scales were tested in CFA, the fit statistics indicated adequate support for characterizing behavioral health as a unidimensional construct along these four distinct scales of function. Conclusion This work represents a significant advance both conceptually and psychometrically in assessment methodologies for work related behavioral health. The measurement of behavioral health functioning relevant to the context of work requires the assessment of multiple dimensions of behavioral health functioning. Specifically, we identified a 4-factor model solution that represented key domains of work related behavioral health functioning. These results guided the development and scale formation of a new SSA-BH instrument. PMID:23548542

  13. Adverse Events in Patients with Blood Loss: A Pooled Analysis of 51 Clinical Studies from the Celecoxib Clinical Trial Database

    PubMed Central

    Sands, GH; Shell, B; Zhang, R

    2012-01-01

    Background: Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of gastrointestinal (GI) toxicity, including occult blood loss and the development of clinically significant anemia. The aim of this study was to investigate the clinical importance of clinically significant anemia/blood loss. Methods: Pooled analysis of 51 blinded, controlled clinical studies ?4 weeks duration from the celecoxib clinical trial database, comparing celecoxib with NSAIDs or placebo. The adverse event (AE) profile in patients with clinically significant anemia/blood loss (defined as decreases in hemoglobin ?2 g/dL and/or hematocrit by ?10% from baseline) was compared with the AE profile in patients without blood loss. Events that occurred in <0.5% of patients were excluded from any comparisons. A threefold difference between groups was defined arbitrarily as being markedly higher. Results: Overall 932/51,048 patients experienced clinically significant anemia/blood loss. Baseline demographics were similar in both groups. The incidence of AEs was markedly higher in patients who experienced clinically significant anemia/blood loss than those who did not; the majority of these differences were for GI AEs or their likely sequelae. The incidence of the following non-GI related AEs was also markedly higher in patients with blood loss: coronary artery disease (1.2% vs 0.3%), myocardial infarction (0.6% vs 0.2%), and pneumonia (1.7% vs 0.4%). Withdrawals due to AEs were more common among patients who experienced blood loss (16.7% vs 10.4%). Conclusions: Clinically significant anemia/blood loss may have clinically important adverse consequences beyond the sequelae previously known to be associated with NSAID-related GI effects. PMID:22629288

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

    PubMed Central

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

    2014-01-01

    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

  15. Meta-analysis of methylenetetrahydrofolate reductase polymorphism and lung cancer risk in Chinese

    PubMed Central

    Wang, Xin; Yue, Kai; Hao, Liran

    2015-01-01

    Numerous studies have investigated association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with lung cancer (LC) susceptibility in Chinese; however, the findings are inconsistent. Therefore, we performed a meta-analysis. PubMed, ISI Web of Knowledge, Chinese National Knowledge Infrastructure, and Wanfang were searched. Pooled ORs and 95% CIs were used to assess the strength of the associations. Overall, 10 studies with 2487 cases and 3228 controls investigating the MTHFR C677T polymorphism and LC risk were included. We did not find a significant association between MTHFR C677T polymorphism and LC risk. However, significantly increased LC risk was found in the population from North China, which was not found in the population from South China. In conclusion, our meta-analysis suggested that MTHFR C677T polymorphism might influence the risk of LC.

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

    Microsoft Academic Search

    J A Eaden; K R Abrams; J F Mayberry

    2001-01-01

    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

  17. Tai Chi Chuan Exercise for Patients with Breast Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Pan, Yuanqing; Yang, Kehu; Shi, Xiue; Liang, Haiqian; Zhang, Fengwa; Lv, Qingfang

    2015-01-01

    Objective. Tai Chi Chuan (TCC) is a form of aerobic exercise that may be an effective therapy for improving psychosomatic capacity among breast cancer survivors. This meta-analysis analyzed the available randomized controlled trials (RCTs) on the effects of TCC in relieving treatment-related side effects and quality of life in women with breast cancer. Methods. RCTs were searched in PubMed, Embase, Web of Science, and Cochrane Library through April 2014. Data were analyzed on pathology (pain, interleukin-6, and insulin-like growth factor 1), physical capacity (handgrip, limb physical fitness, and BMI), and well-being (physical, social, emotional, and general quality of life). Results. Nine RCTs, including a total of 322 breast cancer patients, were examined. Compared with control therapies, the pooled results suggested that TCC showed significant effects in improving handgrip dynamometer strength, limb elbow flexion (elbow extension, abduction, and horizontal adduction). No significant differences were observed in pain, interleukin-6, insulin-like growth factor, BMI, physical well-being, social or emotional well-being, or general health-related quality of life. Conclusion. The short-term effects of TCC may have potential benefits in upper limb functional mobility in patients with breast cancer. Additional randomized controlled trials with longer follow-up are needed to provide more reliable evidence. PMID:25793000

  18. Tai chi chuan exercise for patients with breast cancer: a systematic review and meta-analysis.

    PubMed

    Pan, Yuanqing; Yang, Kehu; Shi, Xiue; Liang, Haiqian; Zhang, Fengwa; Lv, Qingfang

    2015-01-01

    Objective. Tai Chi Chuan (TCC) is a form of aerobic exercise that may be an effective therapy for improving psychosomatic capacity among breast cancer survivors. This meta-analysis analyzed the available randomized controlled trials (RCTs) on the effects of TCC in relieving treatment-related side effects and quality of life in women with breast cancer. Methods. RCTs were searched in PubMed, Embase, Web of Science, and Cochrane Library through April 2014. Data were analyzed on pathology (pain, interleukin-6, and insulin-like growth factor 1), physical capacity (handgrip, limb physical fitness, and BMI), and well-being (physical, social, emotional, and general quality of life). Results. Nine RCTs, including a total of 322 breast cancer patients, were examined. Compared with control therapies, the pooled results suggested that TCC showed significant effects in improving handgrip dynamometer strength, limb elbow flexion (elbow extension, abduction, and horizontal adduction). No significant differences were observed in pain, interleukin-6, insulin-like growth factor, BMI, physical well-being, social or emotional well-being, or general health-related quality of life. Conclusion. The short-term effects of TCC may have potential benefits in upper limb functional mobility in patients with breast cancer. Additional randomized controlled trials with longer follow-up are needed to provide more reliable evidence. PMID:25793000

  19. A meta-analysis of alcohol consumption in relation to risk of breast cancer.

    PubMed

    Longnecker, M P; Berlin, J A; Orza, M J; Chalmers, T C

    1988-08-01

    Epidemiologic findings regarding the relation between alcohol consumption and risk of breast cancer have been inconsistent. We performed a meta-analysis (a quantitative review) of the available data. To evaluate whether there was a dose-response relation between alcohol consumption and risk of breast cancer, we fitted mathematical models to the pooled data. There was strong evidence to support a dose-response relation in both the case-control and follow-up epidemiologic data. Using the dose-response curves that we calculated, the risk of breast cancer at an alcohol intake of 24 g (1 oz) of absolute alcohol daily (about two drinks daily) relative to nondrinkers was 1.4 (95% confidence interval, 1.0 to 1.8) in the case-control data and was 1.7 (95% confidence interval, 1.4 to 2.2) in the follow-up data. We interpret these findings not as proof of causality, but as strongly supportive of an association between alcohol consumption and risk of breast cancer. PMID:3392790

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

    PubMed Central

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

    2014-01-01

    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

  1. The Cancer Genome Atlas Pan-Cancer analysis project

    E-print Network

    Lander, Eric S.

    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 ...

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

    PubMed Central

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

    2013-01-01

    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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

  4. Analysis of signaling pathways in recurrent breast cancer.

    PubMed

    Wu, J Z; Yang, T J; Lu, P; Ma, W

    2014-01-01

    Breast cancer remains the second largest cause of death in women from cancer. By analyzing gene expression profiles in samples from breast cancer patients, 844 differentially expressed genes (DEGs) were identified in breast cancer metastasis. The 10 most significant signaling pathways identified through enrichment analysis contained DEGs were involved in oxidative phosphorylation, DNA replication, extracellular matrix-receptor interactions and others. Furthermore, survival analysis demonstrated that 5 of these signaling pathways were closely related to the survival time of breast cancer patients including basal transcription factors, cell cycle, ECM-receptor interaction, spliceosome, and DNA replication. Our findings increase the understanding of the network of signaling pathways involved in breast cancer metastasis and may provide theoretical support for further therapeutic study. PMID:25501221

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

    PubMed Central

    Maugeri-Saccà, 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

    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

  6. Obesity and Risk of Bladder Cancer: A Dose-Response Meta-Analysis of 15 Cohort Studies

    PubMed Central

    Sun, Jiang-Wei; Zhao, Long-Gang; Yang, Yang; Ma, Xiao; Wang, Ying-Ying; Xiang, Yong-Bing

    2015-01-01

    Background Epidemiological studies have reported inconsistent association between obesity and risk of bladder cancer, and the dose-response relationship between them has not been clearly defined. Methods We carried out a meta-analysis to summarize available evidence from epidemiological studies on this point. Relevant articles were identified by searching the PubMed and Web of Science databases through September 30, 2014. We pooled the relative risks from individual studies using random-effect model, and the dose—response relationship was estimated by using restricted cubic spline model. Results Fifteen cohort studies with 38,072 bladder cancer cases among 14,201,500 participants were included. Compared to normal weight, the pooled relative risks and corresponding 95% confidence intervals of bladder cancer were 1.07(1.01-1.14) and 1.10(1.06-1.14) for preobese and obesity, with moderate (I2 = 37.6%, P = 0.029) and low (I2 = 15.5%, P = 0.241) heterogeneities between studies, respectively. In a dose-response meta-analysis, body mass index (BMI) was associated with bladder cancer risk in a linear fashion (Pnon-linearity = 0.467) and the risk increased by 4.2% for each 5 kg/m2 increase. No significant publication bias was found (P = 0.912 for Begg’s test, P = 0.712 for Egger’s test). Conclusions Findings from this dose-response meta-analysis suggest obesity is associated with linear-increased risk of bladder cancer. PMID:25803438

  7. The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data

    PubMed Central

    2013-01-01

    Background Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. Methods and Findings A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n?=?7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan–Meier survival estimates were 97.7% (95% CI 97.3%–98.1%) at day 42 and 97.2% (95% CI 96.7%–97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3–2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%–96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%–21%) for every 5 mg/kg decrease in dose; p?=?0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed. Conclusions DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation. Please see later in the article for the Editors' Summary PMID:24311989

  8. The therapy of amblyopia: an analysis of the results of amblyopia therapy utilizing the pooled data of published studies.

    PubMed Central

    Flynn, J T; Schiffman, J; Feuer, W; Corona, A

    1998-01-01

    CONTEXT: Although the treatment of amblyopia with occlusion has changed little over the past 3 centuries, there is little agreement about which regimes are most effective and for what reasons. OBJECTIVE: To determine the outcome of occlusion therapy in patients with anisometropic, strabismic, and strabismic-anisometropic amblyopia employing the raw data from 961 patients reported in 23 studies published between 1965 and 1994. DESIGN: Analysis of the published literature on amblyopia therapy results during the above interval, utilizing primary data obtained from the authors of these articles or tables published in the articles detailing individual patient outcomes. PARTICIPANTS: 961 amblyopic patients, participants in 23 studies, undergoing patching therapy for amblyopia from 1965 to 1994 with anisometropia, strabismus, or anisometropia-strabismus. MAIN OUTCOMES: In the pooled data set, success of occlusion therapy was defined as visual acuity of 20/40 at the end of treatment. RESULTS: Success by the 20/40 criteria was achieved in 512 of 689 (74.3%) patients. By category, 312 of 402 (77.6%) were successful in strabismic amblyopia, 44 of 75 (58.7%) in strabismic-anisometropic amblyopia, and 72 of 108 (66.7%) in anisometropic amblyopia. Success was not related to the duration of occlusion therapy, type of occlusion used, accompanying refractive error, patient's sex, or eye. Univariate analyses showed that success was related to the age at which therapy was initiated; the type of amblyopia; the depth of visual loss before treatment for the anisometropic patients and the strabismic patients, but not for the anisometropic-strabismic patients; and the difference in spherical equivalents between eyes, for the anisometropic patients. Logistic/linear regression revealed that 3 were independent predictors of a successful outcome of amblyopia therapy. CONCLUSIONS: Factors that appear most closely related to a successful outcome are age, type of amblyopia, and depth of visual loss before treatment. These may be related to factors, as yet undetermined in the pathogenesis of amblyopia. With present emphasis on the value of screening and prevention and the development of new screening tools, such a look at the results of amblyopia therapy in a large population seems indicated. Images FIGURE 4 PMID:10360300

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

    PubMed Central

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

    2014-01-01

    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

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

    SciTech Connect

    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

    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.

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

    2013-01-01

    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

  13. Estrogen receptor alpha gene polymorphisms and risk of prostate cancer: a meta-analysis involving 18 studies.

    PubMed

    Gu, Zhenwei; Wang, Gang; Chen, Weiguo

    2014-06-01

    Genetic and epigenetic changes in the estrogen receptor alpha (ER-?) gene, according to multiple lines of evidence, might alter its expression and its downstream signaling thereby increasing the risk of developing prostate cancer. The purpose of this meta-analysis was to determine whether polymorphisms in two intronic restriction sites in the ER-? (PvuII and XbaI) gene contribute to prostate cancer. A literature search for eligible studies published before November 5, 2013 was conducted in the PubMed, Embase, China Biology Medicine (CBM), and CNKI databases. Pooled crude odds ratios (ORs) and their corresponding 95 % confidence intervals (CIs) were calculated. Eighteen case-control and cohort studies were included in this meta-analysis with a total 4,884 prostate cancer cases and 10,134 healthy controls. Two common ER-? polymorphisms were examined: IVS1-397 C>T (a.k.a. the PvuII restriction site, rs2234693) and IVS1-351 A>G (a.k.a. the XbaI restriction site, rs9340799). Results from this meta-analysis showed that the PvuII polymorphism was not significantly associated with prostate cancer risk in any of the racial subgroups, either by allelic or genotypic frequencies. However, this meta-analysis revealed that the G allele in the XbaI polymorphism was associated with a statistically significant increase in the risk of prostate cancer. In a stratified analysis based on ethnicity, the XbaI G allele remained significantly correlated with an increased risk of prostate cancer in Africans; this correlation, however, was not found in Caucasians or Asians. In summary, a positive association correlation was observed between frequencies of the XbaI (A>G) polymorphism and prostate cancer, especially in Africans, but not such correlation was found with regard to the frequency of the PvuII (C>T) polymorphism. PMID:24584714

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

    PubMed Central

    2013-01-01

    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

  15. Recent cancer survival in Germany: An analysis of common and less common cancers.

    PubMed

    Jansen, Lina; Castro, Felipe A; Gondos, Adam; Krilaviciute, Agne; Barnes, Benjamin; Eberle, Andrea; Emrich, Katharina; Hentschel, Stefan; Holleczek, Bernd; Katalinic, Alexander; Brenner, Hermann

    2015-06-01

    The monitoring of cancer survival by population-based cancer registries is a prerequisite to evaluate the current quality of cancer care. Our study provides 1-, 5- and 10-year relative survival as well as 5-year relative survival conditional on 1-year survival estimates and recent survival trends for Germany using data from 11 population-based cancer registries, covering around one-third of the German population. Period analysis was used to estimate relative survival for 24 common and 11 less common cancer sites for the period 2007-2010. The German and the United States survival estimates were compared using the Surveillance, Epidemiology and End Results 13 database. Trends in cancer survival in Germany between 2002-2004 and 2008-2010 were described. Five-year relative survival increased in Germany from 2002-2004 to 2008-2010 for most cancer sites. Among the 24 most common cancers, largest improvements were seen for multiple myeloma (8.0% units), non-Hodgkin lymphoma (6.2% units), prostate cancer (5.2% units) and colorectal cancer (4.6% units). In 2007-2010, the survival disadvantage in Germany compared to the United States was largest for cancers of the mouth/pharynx (-11.0% units), thyroid (-6.8% units) and prostate (-7.5% units). Although survival estimates were much lower for elderly patients in both countries, differences in age patterns were observed for some cancer sites. The reported improvements in cancer survival might reflect advances in the quality of cancer care on the population level as well as increased use of screening in Germany. The survival differences across countries and the survival disadvantage in the elderly require further investigation. PMID:25380088

  16. Cost Trend Analysis of Initial Cancer Treatment in Taiwan

    PubMed Central

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

    2014-01-01

    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

  17. Virtual Tide Pool

    NSDL National Science Digital Library

    Science NetLinks (PBS; )

    2003-04-29

    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.

  18. Evaluation of the p53 Arg72Pro polymorphism and its association with cancer risk: a HuGE review and meta-analysis.

    PubMed

    Khan, Mohammad Haroon; Khalil, Aftab; Rashid, Hamid

    2015-01-01

    Codon 72 is a hotspot of polymorphisms in the TP53 gene, which encodes a hub protein in the protein-protein interaction network of p53. It is thus a central player in the apoptotic pathway, preventing cancer. A large number of articles have been published exploring its association with an increased susceptibility to most common cancers. However, these studies have produced inconclusive results, which may be due to their small sample sizes or study designs. To comprehensively evaluate the potential correlation between the TP53 Pro72Arg polymorphism and cancer risk and to better characterize the Pro72Arg polymorphism, we performed a systematic HuGE review and meta-analysis of candidate studies through online resources, according to the proposal of MOOSE and the PRISMA statement. The identified articles were carefully examined according to the inclusion criteria. Pooled odds ratios were calculated on the basis of different genetic models, while heterogeneity was assessed through a chi-based Q-test and I2. After applying the inclusion filters, we obtained a pool of 54 eligible studies, representing 18 718 cases and 21 261 controls. Overall, non-significant cancer risk was observed in all the genetic models but their observed heterogeneity was extremely significant. In subgroup analysis, an increased susceptibility was observed in the case of colorectal cancer, while in cancers of the female reproductive system, significantly increased risk was detected in all the genetic models except the dominant model. In another subgroup analysis, significantly increased cancer risk was observed among Asians in homozygous and recessive models, while in Americans increased cancer risk was observed only in dominant and recessive models. No association was observed in the rest of the populations. In conclusion, pooled subgroup analysis on the basis of ethnicity proved that the TP53 Arg72Pro polymorphism is associated with an increased risk of cancer in Asians and Americans only and is not associated in other populations. It can therefore be concluded that this meta-analysis of available data suggests partial confirmation of the association between the TP53 Arg72Pro polymorphism and cancer risk susceptibility. PMID:25882871

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

    PubMed Central

    2010-01-01

    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

  20. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    PubMed Central

    Pharoah, Paul D. P.; Tsai, Ya-Yu; Ramus, Susan J.; Phelan, Catherine M.; Goode, Ellen L.; Lawrenson, Kate; Price, Melissa; Fridley, Brooke L.; Tyrer, Jonathan P.; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C.; Song, Honglin; Tessier, Daniel C.; Bacot, François; Vincent, Daniel; Cunningham, Julie M.; Dennis, Joe; Dicks, Ed; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M.; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brenton, James D.; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S.; Chang-Claude, Jenny; Chen, Y. Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S.; Coetzee, Gerhard; Cook, Linda S.; Cramer, Daniel W.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K.; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Konecny, Gottfried E.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubi?ski, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C.; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S.; van Altena, Anne M.; Berg, David Van Den; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T.; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N.A.; Gayther, Simon A.; Schildkraut, Joellen M.; Sellers, Thomas A.

    2013-01-01

    Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer. PMID:23535730

  1. Green tea consumption and risk of esophageal cancer: a meta-analysis of epidemiologic studies

    PubMed Central

    2012-01-01

    Background Green tea has shown the role of chemoprevention for cancer. Recently, several studies suggested that green tea intake may have effect on esophageal cancer risk, whereas the results were inconsistent. Methods We performed a meta-analysis of all English and Chinese language studies of green tea consumption and esophageal cancer risk indexed in Medline, Embase, the Science Citation Index, the Chinese Biomedical Database and Wanfang Data from 1980 to June 2012. After reviewing each study, extracting data, and evaluating heterogeneity (Chi-square-based Q test and ?2) and publication bias (Begg and Egger test), a meta-analysis was performed to evaluate the association between high/medium/low green tea consumption and non-drinking esophageal cancer risk. Pooled relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effect models. Results Ten eligible epidemiologic studies including 33731 participants and 3557 cases for esophageal cancer were included. Eight of which were case–control studies, and two were cohort studies. Overall, there were no association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer (High: highest vs non-drinker: RR/OR = 0.76, 95% CI: 0.49 to 1.02. Medium: drinker vs non-drinker: RR/OR = 0.86, 95% CI: 0.70 to 1.03. Low: lowest vs non-drinker: RR/OR = 0.83, 95% CI: 0.58 to 1.08). When stratified analyses according to study design (case–control and cohort studies), country (China and Japan), participates source (population-based and hospital-based case–control), and gender (female and male), there were significant association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer among female (High: RR/OR = 0.32, 95% CI: 0.10 to 0.54. Medium: RR/OR = 0.43, 95% CI: 0.21 to 0.66. Low: RR/OR = 0.45, 95% CI: 0.10 to 0.79), but not the others. Conclusions We did not found significant association between green tea consumption and non-drinking esophageal cancer risk, but an evidence of protective effect was observed among female. PMID:23170950

  2. Statistical analysis of end-points in cancer clinical trials

    E-print Network

    Campbell, Ian

    STATISTICAL ANALYSIS OF END-POINTS IN CANCER CLINICAL TRIALS IAN RONALD CAMPBELL MA, MB, B.Chir, FRCS, FRCR. CLATTERBRIDGE CENTRE FOR ONCOLOGY, MERSEYSIDE AND ST JOHN'S COLLEGE, CAMBRIDGE DISSERTATION SUBMITTED FOR THE DEGREE OF DOCTOR OF MEDICINE...

  3. Red and processed meat consumption and the risk of lung cancer: a dose-response meta-analysis of 33 published studies

    PubMed Central

    Xue, Xiu-Juan; Gao, Qing; Qiao, Jian-Hong; Zhang, Jie; Xu, Cui-Ping; Liu, Ju

    2014-01-01

    This meta-analysis was to summarize the published studies about the association between red/processed meat consumption and the risk of lung cancer. 5 databases were systematically reviewed, and random-effect model was used to pool the study results and to assess dose-response relationships. Results shown that six cohort studies and twenty eight case-control studies were included in this meat-analysis. The pooled Risk Radios (RR) for total red meat and processed meat were 1.44 (95% CI, 1.29-1.61) and 1.23 (95% CI, 1.10-1.37), respectively. Dose-response analysis revealed that for every increment of 120 grams red meat per day the risk of lung cancer increases 35% and for every increment of 50 grams red meat per day the risk of lung cancer increases 20%. The present dose-response meta-analysis suggested that both red and processed meat consumption showed a positive effect on lung cancer risk. PMID:25035778

  4. Association between Vitamin D Receptor Gene Polymorphisms and Breast Cancer Risk: A Meta-Analysis of 39 Studies

    PubMed Central

    Zhang, Kai; Song, Lihua

    2014-01-01

    Background The associations between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial. Methodology/Principal Findings An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between Fok1, poly-A repeat, Bsm1, Taq1 or Apa1 polymorphisms of the VDR gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI) were estimated based on a fixed-effect model (FEM) or random-effect model (REM), depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the Fok1 polymorphism of the VDR gene was associated with an increased risk of breast cancer (ff vs. Ff+FF, OR: 1.09, 95%CI: 1.02 to 1.16, p?=?0.007). No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies. Conclusion A meta-analysis of high-quality studies demonstrated that the Fok1 polymorphism of the VDR gene was closely associated with breast cancer risk. PMID:24769568

  5. Integrated quantitative fractal polarimetric analysis of monolayer lung cancer cells

    NASA Astrophysics Data System (ADS)

    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

    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.

  6. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis

    PubMed Central

    Yang, Jian-Jun; Hu, Zhi-Gao; Shi, Wu-Xiang; Deng, Te; He, Song-Qing; Yuan, Sheng-Guang

    2015-01-01

    AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer. METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters. RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009). CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients.

  7. Association between CTLA-4 60G/A and -1661A/G Polymorphisms and the Risk of Cancers: A Meta-Analysis

    PubMed Central

    Lu, Ailin; Zhao, Peng; Gu, Aihua

    2013-01-01

    Purpose CTLA-4 is one of the most fundamental immunosuppressive cotykines which belongs to the immunoglobulin super-family, and is expressed mainly on activated T cells. Previous studies have reported the existence of CTLA4 60G/A and CTLA4 -1661A/G polymorphism in cancers. However, the effects remain conflicting. Hence, we performed a meta-analysis to investigate the association between these polymorphisms and cancer risk. Methods We searched the Pubmed and Web of Science databases until October 24, 2013 to obtain relevant published studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between CTLA4 gene polymorphisms and cancer susceptibility were calculated by stata 11 software. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in our meta-analysis. Results A total of 22 articles comprising 31 case-control studies concerning the CTLA-4 60G/A and CTLA-4 -1661A/G polymorphisms were included in the meta-analysis. The pooled results suggested the CTLA-4 60G/A polymorphism was significantly associated with an increased skin cancer risk (AA vs. GG: OR?=?1.32, 95%CI?=?1.09-1.59; AA vs. GA+GG: OR?=?1.26, 95%CI?=?1.07-1.48). For CTLA-4 -1661 A/G polymorphism, the results showed that the CTLA-4 -1661A/G polymorphism was significantly associated with an increased cancer risk (GA vs. AA: OR?=?1.44, 95%CI?=?1.13–1.82; GA+GG vs. AA: OR?=?1.35, 95%CI?=?1.07–1.69; G vs. A: OR?=?1.21, 95%CI?=?1.01–1.47), especially in gastric cancer, breast cancer, other cancers and in Asians population subgroups. Conclusion Our meta-analysis suggests that the CTLA-4 -1661A/G polymorphism is a potential factor for the susceptibility of cancer, especially in gastric cancer, breast cancer and other cancers, and the CTLA-4 60G/A polymorphism is significantly associated with increased skin cancer risk. The effect of the CTLA-4 -1661A/G polymorphism on cancer susceptibility especially exists in Asians and population based subjects. PMID:24376736

  8. Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: pooled analysis of extension phases of two Phase III trials

    PubMed Central

    Blagden, M; Hafer, J; Duerr, H; Hopp, M; Bosse, B

    2014-01-01

    Background While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. Methods Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using ‘Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. Key Results Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (?12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. Conclusions & Inferences Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR. PMID:25346155

  9. Associations between TLR9 polymorphisms and cancer risk: evidence from an updated meta-analysis of 25,685 subjects.

    PubMed

    Wan, Guo-Xing; Cao, Yu-Wen; Li, Wen-Qin; Li, Yu-Cong; Zhang, Wen-Jie; Li, Feng

    2014-01-01

    A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488 controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084, rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk were systematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals (CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphism was significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28), specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CC vs TT: OR=1.31, 95% CI= 1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association was significantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphism had a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836 polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98). In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancer risk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breast and digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-control studies are warranted to verify associations between TLR9 polymorphisms and cancer. PMID:25339018

  10. Effect of Exercise Training on Peak Oxygen Consumption in Patients with Cancer: A Meta-Analysis

    PubMed Central

    Liang, Yuanyuan; Pituskin, Edith N.; Battaglini, Claudio L.; Scott, Jessica M.; Hornsby, Whitney E.; Haykowsky, Mark

    2011-01-01

    Background. We conducted a meta-analysis to determine the effects of supervised exercise training on peak oxygen consumption (VO2peak) in adults with cancer. Methods. A literature review using Ovid MEDLINE (1950–2010), the Cochrane Central Register of Controlled Trials (1991–2010), AMED (1985–2010), Embase (1988–2010), PubMed (1966–2010), Scopus (1950–2010), and Web of Science (1950–2010) was performed to identify randomized controlled trials examining the effects of supervised exercise training on measurement of VO2peak (via gas exchange analysis) in adults with cancer. Studies were selected using predetermined criteria, and two independent reviewers extracted data. Weighted mean differences (WMDs) were calculated using random effect models. Results. Six studies evaluated VO2peak involving a total of 571 adult cancer patients (exercise, n = 344; usual care control, n = 227). Pooled data indicated that exercise training was associated with a statistically significant increase in VO2peak (WMD, 2.90 ml·kg?1·min?1; 95% confidence interval [CI], 1.16–4.64); however, significant heterogeneity was evident in this estimate (I2, 87%). Usual care (control) was associated with a significant decline in VO2peak from baseline to postintervention (WMD, ?1.02 ml·kg?1·min?1; 95% CI, ?1.46 to ?0.58; I2, 22%). Sensitivity analyses indicated superior improvements in VO2peak for studies conducted for a shorter duration (<4 months) and following the completion of adjuvant therapy (p-values < .001). Exercise training was not associated with a higher incidence of adverse events, although safety was not rigorously monitored or reported. Conclusions. Supervised exercise training is associated with significant improvements in VO2peak following a diagnosis of early-stage cancer, with minimal adverse events. PMID:21212429

  11. Two-pool model analysis of data in hemodialysis by means of programmable pocket calculator TI 59.

    PubMed

    Guthke, R; Günther, K; Stein, G; Knorre, W A

    1985-01-01

    Four parameters of a two-pool model are evaluated by an iterative method using the explicit solutions of the linear differential equations. For this it was presumed that the residual renal clearance is sufficiently small. Five data pairs of measured plasma concentrations ci for the time points ti (i = 0 to 4), as well as the dialyzer and residual renal clearances (KD and KR), must be given and put in the calculator. A sample run is shown for urea kinetics. The parameter estimation takes about 10 min. The program is suitable to assist in the individualization of dialysis therapy. PMID:3839735

  12. 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

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

    2013-01-01

    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

  13. Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients

    Microsoft Academic Search

    Stefan L. S. Kwa; Joos V. Lebesque; Jacqueline C. M. Theuws; Lawrence B. Marks; Mike T. Munley; Gunilla Bentel; Dieter Oetzel; Uwe Spahn; Mary V. Graham; Robert E. Drzymala; James A. Purdy; Allen S. Lichter; Mary K. Martel; Randall K. Ten Haken

    1998-01-01

    Purpose: To determine the relation between the incidence of radiation pneumonitis and the three-dimensional dose distribution in the lung.Methods and Materials: In five institutions, the incidence of radiation pneumonitis was evaluated in 540 patients. The patients were divided into two groups: a Lung group, consisting of 399 patients with lung cancer and 1 esophagus cancer patient and a Lymph.\\/Breast group

  14. Sample Type Bias in the Analysis of Cancer Genomes

    PubMed Central

    Solomon, David A.; Kim, Jung-Sik; Ressom, Habtom W.; Sibenaller, Zita; Ryken, Timothy; Jean, Walter; Bigner, Darell; Yan, Hai; Waldman, Todd

    2013-01-01

    There is widespread agreement that cancer gene discovery requires high-quality tumor samples. However, whether primary tumors or cultured samples are superior for cancer genomics has been a longstanding subject of debate. This debate has recently become more important because federally funded cancer genomics has been centralized under The Cancer Genome Atlas, which has chosen to focus exclusively on primary tumors. Here, we provide a data-driven “perspective” on the effect of sample type selection on cancer genomics research. We show that, in the case of glioblastoma multiforme, primary tumors and xenografts are best for the identification of amplifications, whereas xenografts and cell lines are superior for the identification of homozygous deletions. We also note that many of the most important oncogenes and tumor suppressor genes have been discovered through the use of cell lines and xenografts, and highlight the lack of published evidence supporting the dogma that ex vivo culture generates artifactual genetic lesions. Based on this analysis, we suggest that cancer genomics projects such as The Cancer Genome Atlas should include a variety of sample types such as xenografts and cell lines in their integrated genomic analysis of cancer. PMID:19567670

  15. Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Donskov, Frede; Wang, Guanghui; Liu, Qi; Du, Jiajun

    2014-01-01

    Purpose Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer. Method Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed. Results A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I2?=?55.8%, p<0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I2?=?0%, p<0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I2?=?70.5%, p<0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I2?=?67.7%, p<0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I2?=?45.9%, p?=?0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15. Conclusion High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival. PMID:24906014

  16. Abnormal MGMT promoter methylation may contribute to the risk of esophageal cancer: a meta-analysis of cohort studies.

    PubMed

    Zhao, Jia-Jun; Li, Hong-Yu; Wang, Di; Yao, Hui; Sun, Da-Wei

    2014-10-01

    This meta-analysis was conducted aiming to evaluate the relationship between abnormal O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and the risk of esophageal cancer (EC). A range of electronic databases was searched: Web of Science (1945?~?2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966?~?2013), EMBASE (1980?~?2013), CINAHL (1982?~?2013), and the Chinese Biomedical Database (CBM) (1982?~?2013) without language restrictions. Meta-analysis was performed with the use of the STATA 12.0 software. In the present meta-analysis, 9 clinical cohort studies with a total of 861 EC patients were included. The pooled results revealed that the frequency of MGMT promoter methylation in cancer tissues was significantly higher than in adjacent and normal tissues (cancer tissues vs adjacent tissues, odds ratio (OR)?=?6.73, 95 % confidence intervals (95 % CI) 4.75?~?9.55, P?cancer tissues vs normal tissues, OR?=?13.68, 95 % CI 9.47?~?19.75, P?

  17. Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof from a meta-analysis

    PubMed Central

    Xue, Wenji; Zhu, Meiling; Wang, Yiwei; He, Jing; Zheng, Leizhen

    2015-01-01

    Phospholipase C epsilon 1 (PLCE1) plays an important role in cell growth, differentiation and oncogenesis. An increasing number of individual studies have investigated the association between PLCE1 rs2274223 polymorphism and cancer risk, but the conclusions are inconclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 22 studies with 13188 cases and 14666 controls. The pooled results indicated that PLCE1 rs2274223 A > G polymorphism was associated with an increased risk of overall cancer (G vs. A: OR = 1.15, 95% CI = 1.06–1.25; GG vs. AA: OR = 1.30, 95% CI = 1.10–1.55; GA vs. AA: OR = 1.18, 95% CI = 1.08–1.30; GG/GA vs. AA: OR = 1.20, 95% CI = 1.08–1.32; GG vs. GA/AA: OR = 1.22, 95% CI = 1.04–1.42). The stratification analysis showed the polymorphism was significantly associated with an increased risk of esophageal squamous cell carcinoma (ESCC) other than gastric cancer (GC), especially among the subgroups of Asian, high quality score, sample size > 1000 and the studies consistent with Hardy-Weinberg equilibrium (HWE). This meta-analysis demonstrated that PLCE1 rs2274223 A > G polymorphism may be associated with increased susceptibility to cancer, especially for ESCC. However, due to the substantial heterogeneities across the studies, the conclusion might be not conclusive that need more studies to confirm. PMID:25614244

  18. Prognostic significance of SOX2 in head and neck cancer: a meta-analysis

    PubMed Central

    Dong, Zhongyi; Liu, Gengchun; Huang, Baqun; Sun, Jingyuan; Wu, Dehua

    2014-01-01

    Sex determining region Y-box 2 (SOX2) has been identified as a putative cancer stem cells (CSCs) marker in Head and Neck Cancers (HNC). However, the clinicopathological and prognostic significance of SOX2 in HNC patients remains controversial. We reviewed the literature by performing a meta-analysis based on the data from 7 studies (9 cohorts) to evaluate the association between SOX2 and clinicopathological/prognostic parameters in patients with HNC. Pooled hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results suggested that high SOX2 expression predicted unfavorable OS (HR: 1.54, 95% CI: 1.09-2.18) and DFS (HR: 1.54, 95% CI: 1.13-2.10) of patients with HNC. In addition, increased SOX2 was also significantly associated with high tumor grade (OR: 1.86, 95% CI: 1.06-3.28), advanced TNM stage (OR: 4.22, 95% CI: 2.62-6.80), lymph node metastasis (OR: 2.25, 95% CI: 1.50-3.35) and distant metastasis (OR: 1.99, 95% CI: 1.26-3.15). Our study suggested that SOX2 expression can be served as a candidate unfavorable prognostic biomarker for HNC patients, indicating that it might be a potential therapeutic target. PMID:25664000

  19. What does cancer treatment look like in consumer cancer magazines? An exploratory analysis of photographic content in consumer cancer magazines.

    PubMed

    Phillips, Selene G; Della, Lindsay J; Sohn, Steve H

    2011-04-01

    In an exploratory analysis of several highly circulated consumer cancer magazines, the authors evaluated congruency between visual images of cancer patients and target audience risk profile. The authors assessed 413 images of cancer patients/potential patients for demographic variables such as age, gender, and ethnicity/race. They compared this profile with actual risk statistics. The images in the magazines are considerably younger, more female, and more White than what is indicated by U.S. cancer risk statistics. The authors also assessed images for visual signs of cancer testing/diagnosis and treatment. Few individuals show obvious signs of cancer treatment (e.g., head scarves, skin/nail abnormalities, thin body types). Most images feature healthier looking people, some actively engaged in construction work, bicycling, and yoga. In contrast, a scan of the editorial content showed that nearly two thirds of the articles focus on treatment issues. To explicate the implications of this imagery-text discontinuity on readers' attention and cognitive processing, the authors used constructs from information processing and social identity theories. On the basis of these models/theories, the authors provide recommendations for consumer cancer magazines, suggesting that the imagery be adjusted to reflect cancer diagnosis realities for enhanced message attention and comprehension. PMID:21294022

  20. Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies

    PubMed Central

    Dale, Ann Marie; Harris-Adamson, Carisa; Rempel, David; Gerr, Fred; Hegmann, Kurt; Silverstein, Barbara; Burt, Susan; Garg, Arun; Kapellusch, Jay; Merlino, Linda; Thiese, Matthew S; Eisen, Ellen A; Evanoff, Bradley

    2014-01-01

    Objectives Most studies of carpal tunnel syndrome (CTS) incidence and prevalence among workers have been limited by small sample sizes or restricted to a small subset of jobs. We established a common CTS case definition and then pooled CTS prevalence and incidence data across six prospective studies of musculoskeletal outcomes to measure CTS frequency and allow better studies of etiology. Methods Six research groups collected prospective data at >50 workplaces including symptoms characteristic of CTS and electrodiagnostic studies (EDS) of the median and ulnar nerves across the dominant wrist. While study designs and the timing of data collection varied across groups, we were able to create a common CTS case definition incorporating both symptoms and EDS results from data that were collected in all studies. Results At the time of enrollment, 7.8% of 4321 subjects met our case definition and were considered prevalent cases of CTS. During 8833 person-years of follow-up, an additional 204 subjects met the CTS case definition for an overall incidence rate of 2.3 CTS cases per 100 person-years. Conclusions Both prevalent and incident CTS were common in data pooled across multiple studies and sites. The large number of incident cases in this prospective study provides adequate power for future exposure– response analyses to identify work- and non-work-related risk factors for CTS. The prospective nature allows determination of the temporal relations necessary for causal inference. PMID:23423472

  1. Multiplex sequencing of pooled mitochondrial genomes—a crucial step toward biodiversity analysis using mito-metagenomics

    PubMed Central

    Tang, Min; Tan, Meihua; Meng, Guanliang; Yang, Shenzhou; Su, Xu; Liu, Shanlin; Song, Wenhui; Li, Yiyuan; Wu, Qiong; Zhang, Aibing; Zhou, Xin

    2014-01-01

    The advent in high-throughput-sequencing (HTS) technologies has revolutionized conventional biodiversity research by enabling parallel capture of DNA sequences possessing species-level diagnosis. However, polymerase chain reaction (PCR)-based implementation is biased by the efficiency of primer binding across lineages of organisms. A PCR-free HTS approach will alleviate this artefact and significantly improve upon the multi-locus method utilizing full mitogenomes. Here we developed a novel multiplex sequencing and assembly pipeline allowing for simultaneous acquisition of full mitogenomes from pooled animals without DNA enrichment or amplification. By concatenating assemblies from three de novo assemblers, we obtained high-quality mitogenomes for all 49 pooled taxa, with 36 species >15 kb and the remaining >10 kb, including 20 complete mitogenomes and nearly all protein coding genes (99.6%). The assembly quality was carefully validated with Sanger sequences, reference genomes and conservativeness of protein coding genes across taxa. The new method was effective even for closely related taxa, e.g. three Drosophila spp., demonstrating its broad utility for biodiversity research and mito-phylogenomics. Finally, the in silico simulation showed that by recruiting multiple mito-loci, taxon detection was improved at a fixed sequencing depth. Combined, these results demonstrate the plausibility of a multi-locus mito-metagenomics approach as the next phase of the current single-locus metabarcoding method. PMID:25294837

  2. Genetic 135G/C polymorphism of RAD51 gene and risk of cancer: a meta-analysis of 28,956 cases and 28,372 controls.

    PubMed

    Zhang, Bei-Bei; Wang, Dao-Gang; Xuan, Chao; Sun, Gui-Li; Deng, Kai-Feng

    2014-12-01

    The RAD51 gene is essential for the repair of damaged DNA related to tumor development. Although a number of genetic studies have attempted to link the 135G/C polymorphism of RAD51 gene to the risk of cancer, the results were inconclusive. The present study aimed at investigating the pooled association using the more comprehensive meta-analysis. The PubMed, EBSCO, and BIOSIS databases were searched to identify eligible studies which were published in English before March 2014. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95 % confidence interval (CI). Begg's test was used to measure publication bias. Sensitivity analyses were also performed to assess the stability of the results. A total of 45 eligible studies with 28,956 patients and 28,372 controls were included in this meta-analysis. Overall, significant association was detected between 135G/C polymorphism and increased cancer risk (C allele vs. G allele: OR 1.23, 95 % CI 1.18-1.28; CC vs. GG: OR 2.41, 95 % CI 2.12-2.74; CC vs. CG: OR 3.86, 95 % CI 3.41-4.37; recessive model: OR 3.57, 95 % CI 3.19-4.00). In further stratified analysis, significantly elevated cancer risk was observed among Caucasians but not Asians. Subgroup analysis by different cancers also showed their significant associations in breast cancer, hematologic malignances, ovarian cancer, colorectal cancer and endometrial cancer, but not in head and neck cancer. Our results indicated that the RAD51 135G/C polymorphism was a candidate for susceptibility of cancer. The effect of the variants on the expression levels and the possible functional role of the variants in different cancers should be addressed in further studies. PMID:24859942

  3. Dose-specific Meta-Analysis and Sensitivity Analysis of the Relation between Alcohol Consumption and Lung Cancer Risk

    Microsoft Academic Search

    Jeffrey E. Korte; Paul Brennan; S. Jane Henley; Paolo Boffetta

    Alcohol drinking increases the risk of several types of cancer, but studies of the relation between alcohol and lung cancer risk are complicated by smoking. The authors carried out meta-analyses for four study designs and conducted sensitivity analyses to assess the results. Pooled smoking-unadjusted relative risks (RRs) for brewery workers and alcoholics were 1.17 (95% confidence interval (CI): 0.99, 1.39)

  4. Association between Soy Isoflavone Intake and Breast Cancer Risk for Pre- and Post-Menopausal Women: A Meta-Analysis of Epidemiological Studies

    PubMed Central

    Zheng, Yi; Wei, Shiqing; Li, Ye; Guo, Tong; Yin, Ping

    2014-01-01

    Background Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women. Methodology and Principal Findings We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intake and breast cancer risk for pre- and/or post-menopausal women, calculated pooled odds ratios and their 95% confidence intervals of pre- and post-menopausal women respectively, and further explored soy isoflavone-breast cancer association on the basis of considering different study regions and designs. Summary results suggested that soy isoflavone intake has a protective effect against breast cancer for both pre- and post-menopausal women. However, they are influenced by study design and region. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavone’s protective effect exist in both pre- and post-menopausal women (OR?=?0.59, 95%CI: 0.48–0.69 for premenopausal women; OR?=?0.59, 95%CI: 0.44–0.74 for postmenopausal women). However, there are some differences between the results pooled from different study designs for women in Asian countries (test for consistency, P?=?0.04). Pooled OR of studies on postmenopausal women in Western countries suggested that soy isoflavone intake has a marginally significant protective effect (OR?=?0.92; 95%CI: 0.83?1.00), but further analyses stratifying by study design found no statistically significant association. Conclusions We meta-analyzed more and newer research results, and separated women according to menopausal status to explore soy isoflavone-breast cancer association. We founded that soy isoflavone intake could lower the risk of breast cancer for both pre- and post-menopausal women in Asian countries. However, for women in Western countries, pre- or post-menopausal, there is no evidence to suggest an association between intake of soy isoflavone and breast cancer. PMID:24586662

  5. Glutathione S-transferase P1 Ile105Val Polymorphism and Oral Cancer Risk: A Meta-Analysis

    PubMed Central

    Li, Weixing; Chen, Jiayu; Liu, Chibo

    2013-01-01

    Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk. Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I2=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I2=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I2=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I2=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I2=39.7%, p for heterogeneity=0.174). Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians. PMID:23471163

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

    PubMed Central

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

    2014-01-01

    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

  7. Lack of Association between Hsa-miR-149 rs2292832 Polymorphism and Cancer Risk: A Meta-Analysis of 12 Studies

    PubMed Central

    Qiu, Man-Tang; Yin, Rong; Wu, Ya-Qin; Xu, Lin

    2013-01-01

    Background MicroRNAs (miRNAs) participate in various cellular processes such as cell growth, differentiation, cell death and play an important role in a variety of diseases, especially in cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms (SNPs) on the hsa-miR-149 rs2292832 and susceptibility to cancer; however, the results remain inconclusive. Methodology/Principal Findings We carried out a meta-analysis of 12 studies including 5937 cases and 6081 controls from PubMed to assess the association between the hsa-miR-149 rs2292832 and cancer risk by pooled odds ratios (ORs) and 95% confidence intervals (CIs). However, our results showed that genotype distribution of the hsa-miR-149 rs2292832 was not associated with cancer risk in all genetic models. Subgroup analysis by cancer type, ethnicity or study design showed no significant association either. Conclusion Results of this meta-analysis suggest that the hsa-miR-149 rs2292832 polymorphism is not associated with cancer risk in spite of the potentially protective role of C allele in hepatocellular carcinoma and male gastric cancer. PMID:24040059

  8. A mitochondrial DNA variant 10398G>A in breast cancer among South Indians: an original study with meta-analysis.

    PubMed

    Francis, Amirtharaj; Pooja, Singh; Rajender, Singh; Govindaraj, Periyasamy; Tipirisetti, Nageswara Rao; Surekha, Daminani; Rao, Digumarthi Raghunatha; Rao, Lakshmi; Ramachandra, Lingadakai; Vishnupriya, Satti; Ramalingam, K; Satyamoorthy, Kapaettu; Thangaraj, Kumarasamy

    2013-11-01

    The m.10398G>A polymorphism in the MT-ND3 gene has been linked to the manifestation of several neurodegenerative disorders and cancers. Several research groups have analyzed the association between m.10398G>A polymorphism and breast cancer; however, the results do not follow a consensus. We have studied this polymorphism in three Dravidian populations from South India. Analysis on 716 cases and 724 controls found no association between m.10398G>A polymorphism and breast cancer [OR = 0.916 (0.743-1.128); P = 0.409]. Menopausal stratification also revealed no significant association in either pre-menopausal or post-menopausal breast cancer groups. In addition, we undertook a meta-analysis on 16 study groups, comprising a total of 7202 cases and 7490 controls. The pooled odds ratio suggested no significant association of m.10398G>A substitution with breast cancer [OR = 1.016 (0.85-1.22); P = 0.86]. In conclusion, there is no evidence of association between m.10398G>A polymorphism and breast cancer risk among South Indian women. Meta-analysis suggested no overall correlation between this polymorphism and breast cancer risk. PMID:23993954

  9. Role of cancer stem cell marker CD44 in gastric cancer: a meta-analysis

    PubMed Central

    Wang, Wei; Dong, Li-Ping; Zhang, Ning; Zhao, Cheng-Hai

    2014-01-01

    Cluster of differentiation 44 (CD44), a principal cell surface receptor for hyaluronic acid, has been implicated in tumorigenesis and metastasis. However, the relationship between CD44 expression and the patients with gastric cancer remains controversial. A meta-analysis was performed to quantitatively review the correlation of CD44 expression with the clinicopathological data of the patients with gastric cancer. We conducted a final analysis of the patients from 18 studies. Combined odds ratios (OR) suggested that CD44 expression was related with stage, tumor size, and LN metastasis of gastric cancer, and CD44v6 was related with LN metastasis, lymphatic invasion, and venous invasion. Our results suggested that CD44 and CD44v6 expression could be used to predict the metastasis of gastric cancer. PMID:25664005

  10. An HLA-DR-Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2Specific Immunity in Patients with Cancer

    Microsoft Academic Search

    Kimberly R. Kalli; Christopher J. Krco; Lynn C. Hartmann; Matthew J. Maurer; Elliot M. Johnson; Courtney L. Erskine; Mary L. Disis; Peter J. Wettstein; John D. Fikes; Melanie Beebe; Glenn Ishioka

    2008-01-01

    Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I-based vaccines. In this study, the goal was to identify an HLA-DR- degenerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2).

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

    E-print Network

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

    2003-01-01

    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.

  12. 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

  13. SILAC-based quantitative proteomic analysis of gastric cancer secretome

    PubMed Central

    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

    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

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

    PubMed Central

    2013-01-01

    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

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

    PubMed Central

    Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

    2013-01-01

    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, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size. PMID:22514208

  16. A simulation-based analysis of motor unit number index (MUNIX) technique using motoneuron pool and surface electromyogram models.

    PubMed

    Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

    2012-05-01

    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, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M-wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M-wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size. PMID:22514208

  17. Sentinel lymph node in oesophageal cancer—a systematic review and meta-analysis

    PubMed Central

    Nagaraja, Vinayak; Cox, Michael R.

    2014-01-01

    Background Sentinel lymph nodes (SLNs) have been used to predict regional lymph node metastasis in patients with melanoma and breast cancer. However, the validity of the SLN hypothesis is still controversial for oesophageal cancer. We performed this meta-analysis to evaluate the feasibility and accuracy of radio-guided SLN mapping for oesophageal cancer. Methods A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate a pooled event rates and 95% confidence interval (95% CI). Results The search identified 23 relevant articles. The overall detection rate was 0.93 (95% CI: 0.894-0.950), sensitivity 0.87 (95% CI: 0.811-0.908), negative predictive value 0.77 (95% CI: 0.568-0.890) and the accuracy was 0.88 (95% CI: 0.817-0.921). In the adenocarcinoma cohort, detection rate was 0.98 (95% CI: 0.923-0.992), sensitivity 0.84 (95% CI: 0.743-0.911) and the accuracy was 0.87(95% CI: 0.796-0.913). In the squamous cell carcinoma group, detection rate was 0.89 (95% CI: 00.792-0.943), sensitivity 0.91 (95% CI: 0.754-0.972) and the accuracy was 0.84 (95% CI: 0.732-0.914). Conclusions It is possible to identify and obtain a SLN before neoadjuvant therapy in oesophageal cancer. However, further work is needed to optimize radiocolloid type, refine the technique and develop a quick and accurate way to determine SLN status intraoperatively. This technique has to be further evaluated before it can be applied widely. PMID:24772341

  18. HUMAN VIRAL ONCOGENESIS: A CANCER HALLMARKS ANALYSIS

    PubMed Central

    Mesri, Enrique A.; Feitelson, Mark; Munger, Karl

    2014-01-01

    Approximately twelve percent of all human cancers are caused by oncoviruses. Human viral oncogenesis is complex and only a small percentage of the infected individuals develop cancer and often many years to decades after initial infection. This reflects the multistep nature of viral oncogenesis, host genetic variability and the fact that viruses contribute to only a portion of the oncogenic events. In this review, the Hallmarks of Cancer framework of Hanahan & Weinberg (2000 and 2011) is used to dissect the viral, host and environmental co-factors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. The viruses discussed include Epstein Barr Virus (EBV), high-risk Human Papillomaviruses (HPV16/18), Hepatitis B and C viruses (HBV, HCV respectively), Human T-cell lymphotropic virus-1 (HTLV-1) and Kaposi’s sarcoma herpesvirus (KSHV). PMID:24629334

  19. Red and processed meat intake and risk of breast cancer: a meta-analysis of prospective studies.

    PubMed

    Guo, Jingyu; Wei, Wei; Zhan, Lixing

    2015-05-01

    Epidemiological studies regarding the association between red and processed meat intake and the risk of breast cancer have yielded inconsistent results. Therefore, we conducted an updated and comprehensive meta-analysis which included 14 prospective studies to evaluate the association of red and processed meat intake with breast cancer risk. Relevant prospective cohort studies were identified by searching PubMed through October 31, 2014, and by reviewing the reference lists of retrieved articles. Study-specific relative risk (RR) estimates were pooled using a random-effects model. Fourteen prospective studies on red meat (involving 31,552 cases) and 12 prospective studies on processed meat were included in the meta-analysis. The summary RRs (95 % CI) of breast cancer for the highest versus the lowest categories were 1.10 (1.02, 1.19) for red meat, and 1.08 (1.01, 1.15) for processed meat. The estimated summary RRs (95 % CI) were 1.11 (1.05, 1.16) for an increase of 120 g/day of red meat, and 1.09 (1.03, 1.16) for an increase of 50 g/day of processed meat. Our findings indicate that increased intake of red and processed meat is associated with an increased risk of breast cancer. Further research with well-designed cohort or interventional studies is needed to confirm the association. PMID:25893586

  20. 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

  1. iTRAQ-based quantitative proteomic analysis of cervical cancer.

    PubMed

    Ding, Yibing; Yang, Min; She, Sha; Min, Haiyan; Xv, Xiaoming; Ran, Xiaoping; Wu, Yongzheng; Wang, Wei; Wang, Lei; Yi, Long; Yang, Yixuan; Gao, Qian

    2015-04-01

    Cervical cancer is the seventh most common cancer overall and the third among females. To obtain systematic insight into the protein profile that participates in cervical tumor oncogenesis and improve the current target therapies, iTRAQ labeling and NanoLC-MS/MS analysis were utilized to detect differentially expressed proteins in cervical cancer. As a result, 3,647 proteins were identified, among which the expression levels of 294 proteins in cervical cancer samples were distinct from the paired non-tumor samples. Further validation of the differentially expressed proteins, including G6PD, ALDH3A1, STAT1 and HSPB1, was carried out via qRT-PCR, western blot analysis and tissue microarray. Functional analysis of one of the highly expressed proteins, G6PD, was performed using RNA interference. Attenuated G6PD expression reduced the capacity of HeLa cells to migrate and invade in vitro. Our investigation complemented the understanding of cervical cancer progression. Furthermore, the present study supports the notion that suppressing the expression of G6PD may be a promising strategy in developing novel cancer therapeutic drugs. PMID:25633909

  2. Gene network-based cancer prognosis analysis with sparse boosting

    PubMed Central

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

    2013-01-01

    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

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

    SciTech Connect

    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

    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.

  4. Relationship between tea consumption and pancreatic cancer risk: a meta-analysis based on prospective cohort studies and case-control studies.

    PubMed

    Chen, Ke; Zhang, Qi; Peng, Min; Shen, Yanping; Wan, Peng; Xie, Guoming

    2014-09-01

    The aim of this study was to evaluate the relationship between regular tea consumption and the risk of pancreatic cancer by a meta-analysis. Two investigators independently performed a computer retrieve on the electronic databases of Embase, PubMed, and Ovidsp for prospective cohort studies and case-control studies on regular tea consumption and the risk of pancreatic cancer incidence. The keywords using for search were ('Pancreas' OR 'pancreatic') AND ('neoplasms' OR 'carcinoma' OR 'cancer') AND 'tea'. Risk ratios (RRs) and 95% confidence interval (CI) were used to determine the effect of tea consumption on pancreatic cancer. A total of 14 studies were included (8078 pancreatic cancer patients, with a total of 859 783 patients) in the present meta-analysis. The pooled results of effect size indicated that tea consumption has no significant relationship with risk of pancreatic cancer (RR=0.99, 95% CI: 0.89-1.11, P=0.922). However, the subgroup analysis of different countries showed a statistical decrease in pancreatic cancer risk by high consumption of tea in a Chinese population (RR=0.76, 95% CI: 0.59-0.98, P=0.036). Similar results were found in the elderly (>60 years old) (RR=0.76, 95% CI: 0.60-0.96, P=0.023). In conclusion, the present meta-analysis of 14 studies suggests that the correlation between tea consumption and the risk of pancreatic cancer in the general population is not significant, but an increase in tea consumption can reduce the risk of pancreatic cancer disease in Chinese populations and in individuals older than 60 years of age. It is necessary to formulate more rigorous designs of regional studies to further confirm the relationship between tea consumption and pancreatic cancer. PMID:24858717

  5. A Comparative Analysis of Gene-Expression Data of Multiple Cancer Types

    Microsoft Academic Search

    Kun Xu; Juan Cui; Victor Olman; Qing Yang; David Puett; Ying Xu; Vladimir Brusic

    2010-01-01

    A comparative study of public gene-expression data of seven types of cancers (breast, colon, kidney, lung, pancreatic, prostate and stomach cancers) was conducted with the aim of deriving marker genes, along with associated pathways, that are either common to multiple types of cancers or specific to individual cancers. The analysis results indicate that (a) each of the seven cancer types

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

    PubMed Central

    Eaden, J; Abrams, K; Mayberry, J

    2001-01-01

    BACKGROUND AND AIMS—Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates.?METHODS—A 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 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate.?RESULTS—The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8).?CONCLUSIONS—Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.???Keywords: ulcerative colitis; colorectal cancer; risk; meta-analysis PMID:11247898

  7. Pooled analysis of clinical trial data evaluating the safety and effectiveness of diclofenac epolamine topical patch 1.3% for the treatment of acute ankle sprain.

    PubMed

    Lionberger, David R; Joussellin, Eric; Yanchick, Jillmarie; Magelli, Merrell; Lanzarotti, Arturo

    2011-01-01

    This pooled analysis assessed the efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) for the treatment of acute mild-to-moderate ankle sprain. Data from 2 randomized, double-blind, placebo-controlled studies enrolling 274 male and female patients aged 18 to 65 years with acute ankle sprain were pooled and evaluated. The primary end point was pain reduction on movement assessed using a 100 mm visual analog scale (VAS). Safety and tolerability were also assessed. Beginning approximately 3 hours after initial treatment, DETP-treated patients experienced statistically significant and sustained lower mean VAS scores in pain intensity on movement (mean ± SD, 54.1 ± 20.0 mm versus 60.3 ± 16.8 mm) compared with placebo-treated patients, representing a 20% versus 13% reduction in VA S pain scores from baseline (P = 0.012). This statistically significant difference in mean VAS score was maintained through day 7 (9.4 ± 14.4 mm versus 18.4 ± 18.2 mm, P < 0.0001). The DETP and placebo patches were well tolerated. These results further confirm the efficacy and safety of DETP for the treatment of acute pain from ankle sprains. PMID:24198574

  8. Pooled analysis of clinical trial data evaluating the safety and effectiveness of diclofenac epolamine topical patch 1.3% for the treatment of acute ankle sprain

    PubMed Central

    Lionberger, David R; Joussellin, Eric; Yanchick, Jillmarie; Magelli, Merrell; Lanzarotti, Arturo

    2011-01-01

    This pooled analysis assessed the efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) for the treatment of acute mild-to-moderate ankle sprain. Data from 2 randomized, double-blind, placebo-controlled studies enrolling 274 male and female patients aged 18 to 65 years with acute ankle sprain were pooled and evaluated. The primary end point was pain reduction on movement assessed using a 100 mm visual analog scale (VAS). Safety and tolerability were also assessed. Beginning approximately 3 hours after initial treatment, DETP-treated patients experienced statistically significant and sustained lower mean VAS scores in pain intensity on movement (mean ± SD, 54.1 ± 20.0 mm versus 60.3 ± 16.8 mm) compared with placebo-treated patients, representing a 20% versus 13% reduction in VA S pain scores from baseline (P = 0.012). This statistically significant difference in mean VAS score was maintained through day 7 (9.4 ± 14.4 mm versus 18.4 ± 18.2 mm, P < 0.0001). The DETP and placebo patches were well tolerated. These results further confirm the efficacy and safety of DETP for the treatment of acute pain from ankle sprains. PMID:24198574

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

    NASA Astrophysics Data System (ADS)

    Rao, Peta Koteswara; Park, Byungguon; Lee, Sang-Tae; Noh, Young-Kyun; Kim, Moon-Deock; Oh, Jae-Eung

    2011-07-01

    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 (?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 × 10-14 cm2, 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.

  10. Semantic Science and Machine-Accessible Scientific Theories David Poole

    E-print Network

    Poole, David

    Semantic Science and Machine-Accessible Scientific Theories David Poole Department of Computer Science, University of British Columbia, http://www.cs.ubc.ca/spider/poole/ Clinton Smyth Georeference theories: e.g., one to predict whether the patient has cancer and another to predict the

  11. Modeling of LNG Pool Spreading and Vaporization

    E-print Network

    Basha, Omar 1988-

    2012-11-20

    sensitivity analysis was conducted to determine the effect of boiling heat transfer regimes, friction, thermal contact/roughness correction parameter and VLE/mixture thermodynamics on the pool spreading behavior. The aim was to provide a better understanding...

  12. Dietary acrylamide and cancer risk: An updated meta-analysis.

    PubMed

    Pelucchi, Claudio; Bosetti, Cristina; Galeone, Carlotta; La Vecchia, Carlo

    2015-06-15

    The debate on the potential carcinogenic effect of dietary acrylamide is open. In consideration of the recent findings from large prospective investigations, we conducted an updated meta-analysis on acrylamide intake and the risk of cancer at several sites. Up to July 2014, we identified 32 publications. We performed meta-analyses to calculate the summary relative risk (RR) of each cancer site for the highest versus lowest level of intake and for an increment of 10 µg/day of dietary acrylamide, through fixed-effects or random-effects models, depending on the heterogeneity test. Fourteen cancer sites could be examined. No meaningful associations were found for most cancers considered. The summary RRs for high versus low acrylamide intake were 0.87 for oral and pharyngeal, 1.14 for esophageal, 1.03 for stomach, 0.94 for colorectal, 0.93 for pancreatic, 1.10 for laryngeal, 0.88 for lung, 0.96 for breast, 1.06 for endometrial, 1.12 for ovarian, 1.00 for prostate, 0.93 for bladder and 1.13 for lymphoid malignancies. The RR was of borderline significance only for kidney cancer (RR?=?1.20; 95% confidence interval, CI, 1.00-1.45). All the corresponding continuous estimates ranged between 0.95 and 1.03, and none of them was significant. Among never-smokers, borderline associations with dietary acrylamide emerged for endometrial (RR?=?1.23; 95% CI, 1.00-1.51) and ovarian (RR?=?1.39; 95% CI, 0.97-2.00) cancers. This systematic review and meta-analysis of epidemiological studies indicates that dietary acrylamide is not related to the risk of most common cancers. A modest association for kidney cancer, and for endometrial and ovarian cancers in never smokers only, cannot be excluded. PMID:25403648

  13. 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...

  14. CERNA WORKING PAPER SERIES Strategic inputs into patent pools

    E-print Network

    Paris-Sud XI, Université de

    1 CERNA WORKING PAPER SERIES Strategic inputs into patent pools Justus Baron Henry Delcamp Working;2 Strategic inputs into patent pools1 Justus BARON2 Henry DELCAMP3 Abstract: This article explores what factors determine the decision of a patent pool to accept new inputs. We propose a dynamic analysis

  15. “Diabetes and colorectal cancer prognosis: a meta-analysis

    PubMed Central

    Mills, Katherine T; Bellows, Charles F; Hoffman, Aaron E; Kelly, Tanika N; Gagliardi, Giuseppe

    2013-01-01

    Background Diabetes mellitus is associated with an increased incidence of colorectal cancer, but the impact of diabetes on colorectal cancer prognosis is not clear. Objective We conducted a meta-analysis of observational studies to examine the association between pre-existing diabetes and colorectal cancer all-cause mortality, cancer-specific mortality and recurrence. Data Sources Medline and Embase were searched through August 22, 2012. Study Selection We included studies reporting all-cause mortality, cancer-specific mortality, disease-free survival, or recurrence in colorectal cancer patients according to diabetic status. Intervention Meta-analyses performed using random effects models. Main Outcome Measures All-cause mortality, cancer-specific mortality, diseases free survival. Results Twenty-six articles met our inclusion criteria. Colorectal cancer patients with diabetes had a 17% increased risk of all-cause mortality (RR = 1.17; 95% CI: 1.09-1.25) and a 12% increased risk of cancer-specific mortality (RR = 1.12; 95% CI: 1.01-1.24) compared to those without diabetes. Those with diabetes also had poorer disease-free survival (RR = 1.54; 95% CI: 1.08-2.18) compared to their non-diabetic counterparts. In subgroup analyses, diabetes was associated with all-cause mortality in both rectal (RR = 1.24; 95% CI: 1.07-1.29) and colon cancer patients (RR = 1.17; 95% CI: 1.07-1.29). Sensitivity analyses including only patients with non-metastatic disease identified stronger associations between diabetes and both all-cause (RR = 1.32; 95% CI: 1.21-1.44) and cancer-specific (RR = 1.27; 95% CI: 1.06-1.52) mortality. Limitations Some studies had short follow-up or did not report mean or median follow-up. The included studies were heterogeneous in study population, diabetes diagnostic criteria and outcome ascertainment. Conclusion Colorectal cancer patients with diabetes are at greater risk for all-cause and cancer-specific mortality and have worse disease-free survival compared to those without diabetes. Studies are warranted to determine if proper treatment could attenuate the excess mortality among diabetic colorectal cancer patients. PMID:24105007

  16. 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

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

    2013-01-01

    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

  17. 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

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

    2014-01-01

    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

  18. Fanfares & Fireworks Pool Party

    E-print Network

    Pilyugin, Sergei S.

    Highlights Fanfares & Fireworks Pool Party Notes from the Office Class Photo TheELIWeekly Fireworks & Pool Party This is a very exciting week! We have two activities for you to participate in. As always, feel free to bring your family and conversation partners. Fanfares & Fireworks On Tuesday, we

  19. Fanfares & Fireworks Pool Party

    E-print Network

    Pilyugin, Sergei S.

    Highlights Fanfares & Fireworks Pool Party Ramadan Reminder ELI Places of Origin Notes from the Office Birthdays TheELIWeekly Fireworks & Pool Party This is a very exciting week! We have two. Fanfares & Fireworks On Wednesday, we will be going to Fanfares and Fireworks. Come listen

  20. DDT/DDE and breast cancer: a meta-analysis.

    PubMed

    Ingber, Susan Z; Buser, Melanie C; Pohl, Hana R; Abadin, Henry G; Murray, H Edward; Scinicariello, Franco

    2013-12-01

    The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The objective of this study was to update a meta-analysis from 2004 which found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer. We searched PubMed and Web of Science for studies published through June 2012 assessing DDT/DDE exposure and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated for the prevalence of breast cancer in the highest versus the lowest exposed groups for DDT and DDE. Difference of means of exposure for cases versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46 were included in the meta-analysis. Slightly elevated, but not statistically significant summary ORs were found for DDE (1.05; 95% CI: 0.93-1.18) and DDT (1.02; 95% CI: 0.92-1.13). Lipid adjusted difference of means analysis found a significantly higher DDE concentration in cases versus controls (11.30 ng/g lipid; p=0.01). No other difference of means analysis found significant relationships. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans. PMID:24021539

  1. Clinical outcomes of self-expandable stent placement for benign esophageal diseases: A pooled analysis of the literature

    PubMed Central

    van Halsema, Emo E; van Hooft, Jeanin E

    2015-01-01

    AIM: To analyze the outcomes of self-expandable stent placement for benign esophageal strictures and benign esophageal leaks in the literature. METHODS: The PubMed, Embase and Cochrane databases were searched for relevant articles published between January 2000 and July 2014. Eight prospective studies were identified that analyzed the outcomes of stent placement for refractory benign esophageal strictures. The outcomes of stent placement for benign esophageal leaks, perforations and fistulae were extracted from 20 retrospective studies that were published after the inclusion period of a recent systematic review. Data were pooled and analyzed using descriptive statistics. RESULTS: Fully covered self-expandable metal stents (FC SEMS) (n = 85), biodegradable (BD) stents (n = 77) and self-expandable plastic stents (SEPS) (n = 70) were inserted in 232 patients with refractory benign esophageal strictures. The overall clinical success rate was 24.2% and according to stent type 14.1% for FC SEMS, 32.9% for BD stents and 27.1% for SEPS. Stent migration occurred in 24.6% of cases. The overall complication rate was 31.0%, including major (17.7%) and minor (13.4%) complications. A total of 643 patients were treated with self-expandable stents mainly for postsurgical leaks (64.5%), iatrogenic perforations (19.6%), Boerhaave’s syndrome (7.8%) and fistulae (3.7%). FC SEMS and partially covered SEMS were used in the majority of patients. Successful closure of the defect was achieved in 76.8% of patients and according to etiology in 81.4% for postsurgical leaks, 86.0% for perforations and 64.7% for fistulae. The pooled stent migration rate was 16.5%. Stent-related complications occurred in 13.4% of patients, including major (7.8%) and minor (5.5%) complications. CONCLUSION: The outcomes of stent placement for refractory benign esophageal strictures were poor. However, randomized trials are needed to put this into perspective. The evidence on successful stent placement for benign esophageal leaks, perforations and fistulae is promising. PMID:25685270

  2. Social stratification and science education: A longitudinal analysis, 1981-1986, of minorities' integration into the scientific talent pool

    NASA Astrophysics Data System (ADS)

    Mulkey, Lynn M.; Ellis, Ronald S.

    It is common knowledge that scientists are those persons who have the unique attributes required to perform in the role, but contrary to what is widely believed, scientists might also be those who have had access to resources of which other members of the population have been deprived. This study investigates the effectiveness of interventions designed to mediate the negative influence of ascription (race and ethnicity) on the scientific talent pool (students having interest and ability in science). Minorities refers to participants representing the major ethnic and racial groups in the New York City school system: Blacks and Hispanics. Cross-tabulations showed that urban underachieving public high school students take significantly more mathematics and science classes, more frequently graduate from high school and more often enroll in college as compared with students of the same population, who were not exposed to the program. These findings on the effectiveness of tutoring, career counseling, exposure to industrial and academic research sites and to scientist role models, and after-school and weekend classes in mathematics and science, reinforce the observations of Thomas (1986) of the importance of prerequisites for increasing participation of minorities in the natural and technical sciences and mathematics. They extend knowledge of factors which lessen the effects of ascription on educational attainment, and which promote meritocratic conditions for achieving a scientific occupation.

  3. Genome-wide analysis of oral cancer--early results from the Cancer Genome Anatomy Project.

    PubMed

    Shillitoe, E J; May, M; Patel, V; Lethanakul, C; Ensley, J F; Strausberg, R L; Gutkind, J S

    2000-01-01

    The Cancer Genome Anatomy Project (CGAP) is a large cooperative effort sponsored by the US National Institutes of Health designed to find, catalog and annotate genes that are expressed during cancer development. In the past 2 years, the CGAP has sequenced over 700,000 clones from approximately 140 cDNA libraries, resulting in the identification of over 30,000 new human genes. As a first step in applying this project to oral cancer we entered four cell lines--two from oral cancer, one from primary oral keratinocytes, and one from oral keratinocytes which had been immortalized by human papillomavirus. Libraries of cDNA were made and sequenced and the data were deposited in GenBank. The expressed genes were then identified where possible. The cell lines, and the total number of expressed genes that were cloned from each were: HN3 (oral cancer), 263 genes; HN4 (oral cancer), 550 genes; HN5 (primary keratinocytes), 237 genes; HN6 (immortalized keratinocytes), 408 genes. The total number of different genes that were found was 1160. A total of 38 new genes, of unknown function, were discovered. The data presented here represent a beginning of the application of the CGAP technology to oral cancer. Even though the data are still quite incomplete, they already represent a large quantity of new information and clones of potential utility to the oral cancer community, and provide a glimpse of the data sets to be forthcoming from the Project. It must therefore be expected that there will soon be a large expansion in the volume of data regarding the genetics of oral cancer. Those who study this disease must be prepared to develop new methods of analysis and storage for handling the oncoming volumes of information. PMID:10889913

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

    PubMed Central

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

    2014-01-01

    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

  5. Complex-based analysis of dysregulated cellular processes in cancer

    PubMed Central

    2014-01-01

    Background Differential expression analysis of (individual) genes is often used to study their roles in diseases. However, diseases such as cancer are a result of the combined effect of multiple genes. Gene products such as proteins seldom act in isolation, but instead constitute stable multi-protein complexes performing dedicated functions. Therefore, complexes aggregate the effect of individual genes (proteins) and can be used to gain a better understanding of cancer mechanisms. Here, we observe that complexes show considerable changes in their expression, in turn directed by the concerted action of transcription factors (TFs), across cancer conditions. We seek to gain novel insights into cancer mechanisms through a systematic analysis of complexes and their transcriptional regulation. Results We integrated large-scale protein-interaction (PPI) and gene-expression datasets to identify complexes that exhibit significant changes in their expression across different conditions in cancer. We devised a log-linear model to relate these changes to the differential regulation of complexes by TFs. The application of our model on two case studies involving pancreatic and familial breast tumour conditions revealed: (i) complexes in core cellular processes, especially those responsible for maintaining genome stability and cell proliferation (e.g. DNA damage repair and cell cycle) show considerable changes in expression; (ii) these changes include decrease and countering increase for different sets of complexes indicative of compensatory mechanisms coming into play in tumours; and (iii) TFs work in cooperative and counteractive ways to regulate these mechanisms. Such aberrant complexes and their regulating TFs play vital roles in the initiation and progression of cancer. Conclusions Complexes in core cellular processes display considerable decreases and countering increases in expression, strongly reflective of compensatory mechanisms in cancer. These changes are directed by the concerted action of cooperative and counteractive TFs. Our study highlights the roles of these complexes and TFs and presents several case studies of compensatory processes, thus providing novel insights into cancer mechanisms. PMID:25521701

  6. 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

    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

    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.

  7. Representation of Cancer in the Medical Literature - A Bibliometric Analysis

    PubMed Central

    Glynn, Ronan W.; Chin, Ji Z.; Kerin, Michael J.; Sweeney, Karl J.

    2010-01-01

    Background There exists a lack of knowledge regarding the quantity and quality of scientific yield in relation to individual cancer types. We aimed to measure the proportion, quality and relevance of oncology-related articles, and to relate this output to their associated disease burden. By incorporating the impact factor(IF) and Eigenfactor™(EF) into our analysis we also assessed the relationship between these indices and the output under study. Methods All publications in 2007 were retrieved for the 26 most common cancers. The top 20 journals ranked by IF and EF in general medicine and oncology, and the presence of each malignancy within these titles was analysed. Journals publishing most prolifically on each cancer were identified and their impact assessed. Principal Findings 63260 (PubMed) and 126845 (WoS) entries were generated, respectively. 26 neoplasms accounted for 25% of total output from the top medical publications. 5 cancers dominated the first quartile of output in the top oncology journals; breast, prostate, lung, and intestinal cancer, and leukaemia. Journals associated with these cancers were associated with much higher IFs and EFs than those journals associated with the other cancer types under study, although these measures were not equivalent across all sub-specialties. In addition, yield on each cancer was related to its disease burden as measured by its incidence and prevalence. Conclusions Oncology enjoys disproportionate representation in the more prestigious medical journals. 5 cancers dominate yield, although this attention is justified given their associated disease burden. The commonly used IF and the recently introduced EF do not correlate in the assessment of the preeminent oncology journals, nor at the level of individual malignancies; there is a need to delineate between proxy measures of quality and the relevance of output when assessing its merit. These results raise significant questions regarding the best method of assessment of research and scientific output in the field of oncology. PMID:21085482

  8. Analysis of PALB2/FANCN-associated breast cancer families.

    PubMed

    Tischkowitz, Marc; Xia, Bing; Sabbaghian, Nelly; Reis-Filho, Jorge S; Hamel, Nancy; Li, Guilan; van Beers, Erik H; Li, Lili; Khalil, Tayma; Quenneville, Louise A; Omeroglu, Atilla; Poll, Aletta; Lepage, Pierre; Wong, Nora; Nederlof, Petra M; Ashworth, Alan; Tonin, Patricia N; Narod, Steven A; Livingston, David M; Foulkes, William D

    2007-04-17

    No more than approximately 30% of hereditary breast cancer has been accounted for by mutations in known genes. Most of these genes, such as BRCA1, BRCA2, TP53, CHEK2, ATM, and FANCJ/BRIP1, function in DNA repair, raising the possibility that germ line mutations in other genes that contribute to this process also predispose to breast cancer. Given its close relationship with BRCA2, PALB2 was sequenced in affected probands from 68 BRCA1/BRCA2-negative breast cancer families of Ashkenazi Jewish, French Canadian, or mixed ethnic descent. The average BRCAPRO score was 0.58. A truncating mutation (229delT) was identified in one family with a strong history of breast cancer (seven breast cancers in three female mutation carriers). This mutation and its associated breast cancers were characterized with another recently reported but unstudied mutation (2521delA) that is also associated with a strong family history of breast cancer. There was no loss of heterozygosity in tumors with either mutation. Moreover, comparative genomic hybridization analysis showed major similarities to that of BRCA2 tumors but with some notable differences, especially loss of 18q, a change that was previously unknown in BRCA2 tumors and less common in sporadic breast cancer. This study supports recent observations that PALB2 mutations are present, albeit not frequently, in breast cancer families. The apparently high penetrance noted in this study suggests that at least some PALB2 mutations are associated with a substantially increased risk for the disease. PMID:17420451

  9. The Prognostic Role of Ki-67/MIB-1 in Cervical Cancer: A Systematic Review with Meta-Analysis

    PubMed Central

    Pan, Denghua; Wei, Kanglai; Ling, Yanxin; Su, Shitao; Zhu, Meilin; Chen, Gang

    2015-01-01

    Background A significant relationship has been reported in which Ki-67/MIB-1 expression is correlated with survival in cervical cancer patients. However, the prognostic value of Ki-67/MIB-1 in cervical cancer is still not well understood. Material/Method A meta-analysis was carried out to explore the prognostic value of Ki-67/MIB-1 on overall survival (OS) and/or disease-free survival (DFS) in cervical cancer. The databases of PubMed, ISI Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, and Wiley Online Library were used to identify relevant literature. Results We included 18 studies covering 1344 patients in the meta-analysis. The effect of Ki-67/MIB-1 on OS for pooled random effects HR estimate was 1.63 (95% confidence intervals (CI) 1.09–2.45; P<0.05). Subgroup analysis by ethnicity suggested that high expression of Ki-67/MIB-1 had association with Asians (1.84, 95% CI 1.04–3.23), but not with Africans (HR=1.53, 95% CI 0.34–6.86) or Europeans (HR=1.29, 95% CI 0.74–2.23). Furthermore, subgroup analysis of diverse treatments revealed no difference in surgery (HR=1.97, 95% CI 0.78–4.99) and radiation therapy (RT) (HR=1.56, 95% CI 0.93–2.63). The pooled HR for DFS was 1.26 (95% CI 0.58–2.73; P>0.05) and the subgroup analysis indicated Ki-67/MIB1 was associated with DFS (HR=3.67, 95% CI 2.65–5.09) in Asians. In the treatment subgroup analysis, no direct value was found among surgery (HR=1.13, 95% CI 0.10–13.53) and RT (HR=1.26, 95% CI 0.71–2.24). Conclusions Our meta-analysis concludes that Ki-67/MIB-1 had a prognostic value for OS in cervical cancer patients. To further evaluate the prognostic role of Ki-67/MIB-1 on DFS, studies with larger numbers of patients are needed to validate our findings. PMID:25807305

  10. 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

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

    2011-01-01

    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

  11. Integrative analysis of prognosis data on multiple cancer subtypes.

    PubMed

    Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

    2014-04-25

    In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

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

    PubMed Central

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

    2009-01-01

    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 of interest that remained significant at a false discovery rate of 10%. Subsequently, risk estimates were generated for regions with a high level of signal and individual SNPs by unconditional logistic regression adjusting for age, gender and study center. Three regions containing genes associated with renal cancer were identified: caspase 1/5/4/12(CASP 1/5/4/12), epidermal growth factor receptor (EGFR), and insulin-like growth factor binding protein-3 (IGFBP3). We observed that individuals with CASP1/5/4/12 haplotype (spanning area upstream of CASP1 through exon 2 of CASP5) GGGCTCAGT were at higher risk of renal cancer compared to individuals with the most common haplotype (OR:1.40, 95% CI:1.10–1.78, p-value?=?0.007). Analysis of EGFR revealed three strong signals within intron 1, particularly a region centered around rs759158 with a global p?=?0.006 (GGG: OR:1.26, 95% CI:1.04–1.53 and ATG: OR:1.55, 95% CI:1.14–2.11). A region in IGFBP3 was also associated with increased risk (global p?=?0.04). In addition, the number of statistically significant (p-value<0.05) SNP associations observed within these three genes was higher than would be expected by chance on a gene level. To our knowledge, this is the first study to evaluate these genes in relation to renal cancer and there is need to replicate and extend our findings. The specific regions associated with risk may have particular relevance for gene function and/or carcinogenesis. In conclusion, our evaluation has identified common genetic variants in CASP1, CASP5, EGFR, and IGFBP3 that could be associated with renal cancer risk. PMID:19603096

  13. Swimming Pools and Molluscum Contagiosum

    MedlinePLUS

    Molluscum Home > Swimming Pools > Swimming Pools and Molluscum Contagiosum Parents and others often ask if molluscum virus can be spread in swimming pools. There is also concern that it can be spread ...

  14. Genomic analysis: toward a new approach in breast cancer management.

    PubMed

    Cavallaro, Sebastiano; Paratore, Sabrina; de Snoo, Femke; Salomone, Edvige; Villari, Loredana; Buscarino, Calogero; Ferraù, Francesco; Banna, Giuseppe; Furci, Marco; Strazzanti, Angela; Cunsolo, Rosario; Pezzino, Salvatore; Gangi, Santi; Basile, Francesco

    2012-03-01

    Breast cancer is a clinically heterogeneous and complex disease that can affect differently individuals with seemingly identical clinicopathologic parameters. This heterogeneity is strictly linked to individuals and tumors genetic variability. Currently, the development of high-throughput technologies are proving novel tools to tackle this complexity. By DNA microarray technology, genomic analysis has been used successfully for breast carcinomas stratification into molecular subgroups with relevant implications for clinical outcomes, and detection of prognostic/treatment predictive signatures. Indeed, DNA microarray has rapidly improved becoming a powerful diagnostic tool. Information derived from these assays allows clinicians to estimate the risk for distant recurrence, and predict accurately which patients are likely to benefit from adjuvant therapy. This review will describe the state-of-the-art of genomic analysis in breast cancer and introduce the clinicians to a genomic approach to cancer management, illustrating how it can help in defying a better diagnosis, prognosis and therapeutic treatment. PMID:21511492

  15. Multi-Cancer Mutual Exclusivity Analysis of Genomic Alterations - Giovanni Ciriello, TCGA Scientific Symposium 2011

    Cancer.gov

    Home News and Events Multimedia Library Videos Multi-Cancer Mutual Exclusivity Analysis of Genomic Alterations - Giovanni Ciriello Multi-Cancer Mutual Exclusivity Analysis of Genomic Alterations - Giovanni Ciriello, TCGA Scientific Symposium 2011 You

  16. Virus Analysis in Head and Neck and Bladder Cancers - Michael Parfenov, TCGA Scientific Symposium 2012

    Cancer.gov

    Home News and Events Multimedia Library Videos Virus Analysis in Head and Neck and Bladder Cancers - Michael Parfenov Virus Analysis in Head and Neck and Bladder Cancers - Michael Parfenov, TCGA Scientific Symposium 2012 You will need Adobe Flash

  17. Pan-Cancer Analysis of APOBEC Mutagenesis - Dmitry A. Gordenin, TCGA Scientific Symposium 2014

    Cancer.gov

    Home News and Events Multimedia Library Videos Pan-Cancer Analysis of APOBEC Mutagenesis - Dmitry A. Gordenin Pan-Cancer Analysis of APOBEC Mutagenesis - Dmitry A. Gordenin, TCGA Scientific Symposium 2014 You will need Adobe Flash Player 8 or later

  18. Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ?45 Years in Asia: A Pooled Analysis of 21 Cohorts

    PubMed Central

    Zheng, Wei; McLerran, Dale F.; Rolland, Betsy A.; Fu, Zhenming; Boffetta, Paolo; He, Jiang; Gupta, Prakash Chandra; Ramadas, Kunnambath; Tsugane, Shoichiro; Irie, Fujiko; Tamakoshi, Akiko; Gao, Yu-Tang; Koh, Woon-Puay; Shu, Xiao-Ou; Ozasa, Kotaro; Nishino, Yoshikazu; Tsuji, Ichiro; Tanaka, Hideo; Chen, Chien-Jen; Yuan, Jian-Min; Ahn, Yoon-Ok; Yoo, Keun-Young; Ahsan, Habibul; Pan, Wen-Harn; Qiao, You-Lin; Gu, Dongfeng; Pednekar, Mangesh Suryakant; Sauvaget, Catherine; Sawada, Norie; Sairenchi, Toshimi; Yang, Gong; Wang, Renwei; Xiang, Yong-Bing; Ohishi, Waka; Kakizaki, Masako; Watanabe, Takashi; Oze, Isao; You, San-Lin; Sugawara, Yumi; Butler, Lesley M.; Kim, Dong-Hyun; Park, Sue K.; Parvez, Faruque; Chuang, Shao-Yuan; Fan, Jin-Hu; Shen, Chen-Yang; Chen, Yu; Grant, Eric J.; Lee, Jung Eun; Sinha, Rashmi; Matsuo, Keitaro; Thornquist, Mark; Inoue, Manami; Feng, Ziding; Kang, Daehee; Potter, John D.

    2014-01-01

    Background Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. Methods and Findings We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ?45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ?71% of Asia's total population. An approximately 1.44-fold (95% CI?=?1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI?=?14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ?45 y in the seven countries/regions combined, with a total number of estimated deaths of ?1,575,500 (95% CI?=?1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ?45 y. Conclusions Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ?45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary PMID:24756146

  19. p27Kip1 as a prognostic factor in breast cancer: a systematic review and meta-analysis

    PubMed Central

    Guan, Xiaoxiang; Wang, Yucai; Xie, Ruilian; Chen, Longbang; Bai, Jianling; Lu, Jia; Kuo, Macus Tien

    2010-01-01

    Abstract The aim of this study was to comprehensively evaluate via a meta-analysis the association between p27 expression and clinical outcome in breast cancer patients. We conducted a meta-analysis of 20 studies (n= 6463 patients) that evaluated the correlation between p27 expression and indicators of breast cancer clinical outcome, including overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS). Data pooling was performed by RevMan 4.2. A total of 60% (9 of 15) of the studies showed a significant association between p27 high expression and OS, whereas 25% (2 of 8) and 60% (3 of 5) studies demonstrated a correlation between p27 high expression and DFS and RFS, respectively. The relative risks (RRs) were 1.34 (1.26–1.42) for OS (P < 0.00001), 1.27 (1.10–1.47) for DFS (P= 0.001) and 1.49 (0.92–2.42) for RFS (P= 0.10). In lymph node-negative breast cancer patients, the RRs for OS and RFS were 1.84 (1.30–2.59; P= 0.0005) and 1.30 (0.20–8.50; P= 0.78), respectively. In lymph node-positive breast cancer patients, the RRs for OS and RFS were 2.99 (1.77–5.07; P < 0.0001) and 1.49 (0.80–2.77; P= 0.21), respectively. This meta-analysis indicates that reduced p27 is an independent prognostic factor for poor overall and disease-free cancer survival. PMID:19298520

  20. Prediction of Poor Prognosis in Breast Cancer Patients Based on MicroRNA-21 Expression: A Meta-Analysis

    PubMed Central

    Wang, Yanyan; Zhang, Yujie; Pan, Chi; Ma, Feixia; Zhang, Suzhan

    2015-01-01

    Background MicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer. Methods The meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI). Results Our meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics. Conclusion Our results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians. PMID:25706383

  1. Molecular sputum analysis for the diagnosis of lung cancer

    PubMed Central

    Hubers, A J; Prinsen, C F M; Sozzi, G; Witte, B I; Thunnissen, E

    2013-01-01

    Lung cancer is the leading cause of cancer mortality rate worldwide, mainly because of the presence of metastatic disease at the time of diagnosis. Early detection of lung cancer improves prognosis, and towards this end, large screening trials in high-risk individuals have been conducted since the past century. Despite all efforts, the need for novel (complementary) lung cancer diagnostic and screening methods still exists. In this review, we focus on the assessment of lung cancer-related biomarkers in sputum in the past decennium. Besides cytology, mutation and microRNA analysis, special attention has been paid to DNA promoter hypermethylation, of which all available literature is summarised without time restriction. A model is proposed to aid in the distinction between diagnostic and risk markers. Research on the use of sputum for non-invasive detection of early-stage lung cancer has brought new insights and advanced molecular techniques. The sputum shows a promising potential for routine diagnostic and possibly screening purposes. PMID:23868001

  2. Metabolic control analysis of respiration in human cancer tissue

    PubMed Central

    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

    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

  3. A meta-analysis of alcohol drinking and cancer risk

    PubMed Central

    Bagnardi, V; Blangiardo, M; Vecchia, C La; Corrao, G

    2001-01-01

    To evaluate the strength of the evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 18 neoplasms, we performed a search of the epidemiological literature from 1966 to 2000 using several bibliographic databases. Meta-regression models were fitted considering linear and non-linear effects of alcohol intake. The effects of characteristics of the studies, of selected covariates (tobacco) and of the gender of individuals included in the studies, were also investigated as putative sources of heterogeneity of the estimates. A total of 235 studies including over 117?000 cases were considered. Strong trends in risk were observed for cancers of the oral cavity and pharynx, oesophagus and larynx. Less strong direct relations were observed for cancers of the stomach, colon and rectum, liver, breast and ovary. For all these diseases, significant increased risks were found also for ethanol intake of 25?g per day. No significant nor consistent relation was observed for cancers of the pancreas, lung, prostate or bladder. Allowance for tobacco appreciably modified the relations with laryngeal, lung and bladder cancers, but not those with oral, oesophageal or colorectal cancers. This meta-analysis showed no evidence of a threshold effect for most alcohol-related neoplasms. The inference is limited by absence of distinction between lifelong abstainers and former drinkers in several studies, and the possible selective inclusion of relevant sites only in cohort studies. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11742491

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

    PubMed Central

    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

    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

  5. Genome Analysis Insights into the connection between cancer and

    E-print Network

    Ast, Gil

    Genome Analysis Insights into the connection between cancer and alternative splicing Eddo Kim* , Amir Goren* and Gil Ast Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel Computational and experimental evidence has

  6. A genome-wide systematic analysis reveals different and predictive proliferation expression signatures of cancerous vs. non-cancerous cells.

    PubMed

    Waldman, Yedael Y; Geiger, Tamar; Ruppin, Eytan

    2013-01-01

    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

  7. Membrane proteomic analysis of pancreatic cancer cells

    PubMed Central

    2010-01-01

    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

  8. Genomic analysis and selected molecular pathways in rare cancers

    NASA Astrophysics Data System (ADS)

    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

    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.

  9. Metabolic and transcriptional analysis of acid stress in Lactococcus lactis, with a focus on the kinetics of lactic acid pools.

    PubMed

    Carvalho, Ana Lúcia; Turner, David L; Fonseca, Luís L; Solopova, Ana; Catarino, Teresa; Kuipers, Oscar P; Voit, Eberhard O; Neves, Ana Rute; Santos, Helena

    2013-01-01

    The effect of pH on the glucose metabolism of non-growing cells of L. lactis MG1363 was studied by in vivo NMR in the range 4.8 to 6.5. Immediate pH effects on glucose transporters and/or enzyme activities were distinguished from transcriptional/translational effects by using cells grown at the optimal pH of 6.5 or pre-adjusted to low pH by growth at 5.1. In cells grown at pH 5.1, glucose metabolism proceeds at a rate 35% higher than in non-adjusted cells at the same pH. Besides the upregulation of stress-related genes (such as dnaK and groEL), cells adjusted to low pH overexpressed H(+)-ATPase subunits as well as glycolytic genes. At sub-optimal pHs, the total intracellular pool of lactic acid reached approximately 500 mM in cells grown at optimal pH and about 700 mM in cells grown at pH 5.1. These high levels, together with good pH homeostasis (internal pH always above 6), imply intracellular accumulation of the ionized form of lactic acid (lactate anion), and the concomitant export of the equivalent protons. The average number, n, of protons exported with each lactate anion was determined directly from the kinetics of accumulation of intra- and extracellular lactic acid as monitored online by (13)C-NMR. In cells non-adjusted to low pH, n varies between 2 and 1 during glucose consumption, suggesting an inhibitory effect of intracellular lactate on proton export. We confirmed that extracellular lactate did not affect the lactate: proton stoichiometry. In adjusted cells, n was lower and varied less, indicating a different mix of lactic acid exporters less affected by the high level of intracellular lactate. A qualitative model for pH effects and acid stress adaptation is proposed on the basis of these results. PMID:23844205

  10. The Vernal Pool Association

    NSDL National Science Digital Library

    Leo Kenney

    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.

  11. Weld pool phenomena

    SciTech Connect

    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

    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.

  12. Swimming Pool Safety

    MedlinePLUS

    ... ladders to prevent access by children. Other protection products, when used with an “isolation” fence, may be ... Never dive through inner tubes or other pool toys. Learn how to dive properly by taking classes. ...

  13. The E-cadherin gene polymorphism 160C->A and cancer risk: A HuGE review and meta-analysis of 26 case-control studies.

    PubMed

    Wang, Gui-Ying; Lu, Chen-Qi; Zhang, Rong-Mei; Hu, Xiao-Hua; Luo, Z W

    2008-01-01

    A single nucleotide polymorphism, - 160C-->A, has been identified in the promoter region of the E-cadherin gene and has been shown to alter its transcriptional activity. To assess susceptibility of -160A allele carriers to seven types of cancers, the authors conducted a comprehensive meta-analysis, up to November 2006, of 26 case-control studies comprising 7,042 cases and 7,011 controls. Pooled odds ratios and 95% confidence intervals were calculated by using the random-effects model. Publication bias, subgroup, and sensitivity analyses were also performed, which showed that -160A allele carriers, compared with noncarriers, had about a 17-19% increased risk of several invasive/metastatic tumors. Analyses of various types of cancers revealed that, in Europeans, the -160AA homozygote was associated with an increased risk of urothelial cancer, carriers of -160A were at increased risk of lung and prostate cancers, and carriers of -160A with gastric cancer were found to suffer a significantly increased risk, whereas their Asian counterparts seemed to be tolerant. No evidence was found that the -160A allele predisposed its carriers to breast, colorectal, or esophageal cancers. These findings indicate that -160A of the E-cadherin gene is emerging as a low-penetrance tumor susceptibility allele for the development of gastric, lung, prostate, and urothelial cancers. PMID:17971340

  14. Z-Spectrum Analysis Provides Proton Environment Data (ZAPPED): A New Two-Pool Technique for Human Gray and White Matter

    PubMed Central

    Miyazaki, Mitsue; Ouyang, Cheng; Zhou, Xiangzhi; Murdoch, James B.; Fushimi, Yasutaka; Okada, Tomohisa; Fujimoto, Koji; Kido, Aki; Arakawa, Yoshiki; Miyamoto, Susumu; Togashi, Kaori

    2015-01-01

    A new technique – Z-spectrum Analysis Provides Proton Environment Data (ZAPPED) – was used to map cross-relaxing free and restricted protons in nine healthy subjects plus two brain tumor patients at 3T. First, MT data were acquired over a wide symmetric range of frequency offsets, and then a trio of quantitative biomarkers, i.e., the apparent spin-spin relaxation times (T2,f, T2,r) in both free and restricted proton pools as well as the restricted pool fraction Fr, were mapped by fitting the measured Z-spectra to a simple two-Lorentzian compartment model on a voxel-by-voxel basis. The mean restricted exchangeable proton fraction, Fr, was found to be 0.17 in gray matter (GM) and 0.28 in white matter (WM) in healthy subjects. Corresponding mean values for apparent spin-spin relaxation times were 785 µs (T2,f) and 17.7 µs (T2,r) in GM, 672 µs (T2,f) and 23.4 µs (T2,r) in WM. The percentages of Ff and Fr in GM are similar for all ages, whereas Fr shows a tendency to decrease with age in WM among healthy subjects. The patient ZAPPED images show higher contrast between tumor and normal tissues than traditional T2-weighted and T1-weighted images. The ZAPPED method provides a simple phenomenological approach to estimating fractions and apparent T2 values of free and restricted MT-active protons, and it may offer clinical useful information. PMID:25768108

  15. 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

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

    2014-11-01

    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 (FEV(1)) 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 (E(max)) 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 (ED(50)) 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

  16. Self-Advocacy and Cancer: A Concept Analysis

    PubMed Central

    Hagan, Teresa L.; Donovan, Heidi S.

    2013-01-01

    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

  17. Noninvasive detection of lung cancer by analysis of exhaled breath

    PubMed Central

    2009-01-01

    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

  18. Molecular analysis of mutations in the hprt gene of V79 hamster fibroblasts: effects of imbalances in the dCTP, dGTP and dTTP pools.

    PubMed

    Darè, E; Zhang, L H; Jenssen, D; Bianchi, V

    1995-10-01

    dCMP-deaminase-deficient V79/dC hamster cells have highly imbalanced deoxyribonucleoside triphosphate (dNTP) pools, i.e. a 17-fold larger dCTP pool, a slightly reduced dTTP and a very low dGTP pool, compared to dCMP-deaminase-proficient V79/p cells. Nevertheless, the two lines showed the same rates of spontaneous mutation at the hprt and ouabain-resistance loci. Analysis of spontaneous hprt mutations indicated an increase in misincorporation of C in V79/dC cells, although it was not statistically significant. When the dCTP pool was further increased fivefold by incubating V79/dC cells with cytidine, C misincorporation increased to 88%, but the mutation frequency remained unchanged. The dNTP pools of V79/dC cells were also altered by treatment with thymidine, or with thymidine plus deoxycytidine. After incubation with thymidine alone, the dCTP pool all but disappeared, whereas it maintained a normal level in the presence of deoxycytidine. In both cases dTTP rose to nmol amounts, and dGTP accumulated. Incubation with 10 mM thymidine was the only treatment that increased the mutation frequency; T misincorporation then accounted for 94% of the base substitutions. In the presence of deoxycytidine the cells had a dTTP/dCTP ratio of 0.04, but 86% of the base substitutions involved C misincorporation and most probably originated from G mis-incorporation caused by excess dGTP. Alterations of RNA splicing and hot spots for base substitutions varied with the imbalance, the latter showed "next-nucleotide effects". Our results suggest that the fidelity of DNA replication in V79 cells is only affected by large changes in the pool and is more sensitive to changes in dGTP than in dCTP or dTTP. PMID:7563070

  19. The Impact of Matrix Metalloproteinase 2 on Prognosis and Clinicopathology of Breast Cancer Patients: A Systematic Meta-Analysis

    PubMed Central

    Chen, Yiping; Wang, Xiaochen; Chen, Guodi; Dong, Caixia; Zhang, Depu

    2015-01-01

    Backgrounds Matrix metalloproteinase 2 (MMP-2) plays a crucial role in the progression of breast cancer (BC). The prognostic role of MMP-2 expression in BC patients has been widely reported, but the results were inconsistent. Thus, a meta-analysis was conducted to gain a better insight into the impact of MMP-2 expression on survival and clinicopathological features of BC patients. Methods Identical search strategies were used to search relevant literatures in electronic databases update to August 1, 2014. Individual hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were extracted and pooled to evaluate the strength of the association between positive MMP-2 expression and survival results and clinicopathological features of BC patients. Begg’s tests, Egger’s tests and funnel plots were used to evaluate publication bias. Heterogeneity and sensitivity analysis were also assessed. All the work was completed using STATA. Results Pooled HRs and 95% CIs suggested that MMP-2 expression had an unfavorable impact on both OS (HR: 1.53, 95% CI: 1.29–1.82) and DFS/RFS/DDFS (HR: 1.41, 95% CI: 1.07–1.86) in BC patients. Furthermore, MMP-2 expression was significantly associated with lymph node metastasis (positive vs negative: OR 1.91, 95% CI 1.17–3.12). Conclusion In conclusion, positive MMP-2 expression might be a significant predictive factor for poor prognosis in patients with BC. PMID:25816052

  20. The Safety and Efficacy of Fentanyl Iontophoretic Transdermal System Compared with Morphine Intravenous Patient-Controlled Analgesia for Postoperative Pain Management: An Analysis of Pooled Data from Three Randomized, Active-Controlled Clinical Studies

    Microsoft Academic Search

    Eugene R. Viscusi; Matthew Siccardi; C. V. Damaraju; David J. Hewitt; Paul Kershaw

    2007-01-01

    BACKGROUND: Postoperative pain is often managed using IV patient-controlled anal- gesia (PCA). In this analysis of pooled data, we compared the safety and efficacy of the fentanyl iontophoretic transdermal system (ITS) with morphine IV PCA. METHODS: Data were obtained from three multicenter, randomized, active- controlled trials (N 1941). The primary efficacy measure was success (\\

  1. 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

    Johnson, David R.; Wu, Jian

    2002-01-01

    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…

  2. In-depth Proteomic Analysis of Nonsmall Cell Lung Cancer to Discover Molecular Targets and Candidate Biomarkers*

    PubMed Central

    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

    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

  3. A historical discourse analysis of the cancerous and non-cancerous body in secondary biology textbooks

    NASA Astrophysics Data System (ADS)

    Bowers, Neil Thomas

    This dissertation applies the archeological concepts developed by Michel Foucault to a study of thirteen biology textbooks (1993-2004) in order to develop an understanding of 'purchased truths' concerning cancer. This study focuses on the construction of the health/illness dialogue concerning cancer within the textbooks and not the meaning that the individual makes from reading the text; as such this study concerns itself with social truths rather than the search for an individual awareness of names, dates, or places. This study investigates the practices that allow the creation of dialogues that are inserted into a biology textbook and looks at how discursive formations create the 'truth regime' from which the biology textbook is said to speak. Using the Foucaultian themes of 'event', 'emergence', 'enunciation', and 'exteriority' a new reading of topics concerning cancer emerge from biology textbooks. Cancer is a disease that will impact the lives of countless individuals but coverage devoted to the pathology of cancer in secondary biology textbooks is very limited and no study textbook devoted a whole chapter to the discussion of cancer. There is an identified reduction in the number of pages and depth of coverage devoted to cancer in the newer biology texts compared to the older texts. Humans are pictured more than plants or animals in presentations concerning cancer with emphasis being placed on the digitalization of human cells via the scanning electron microscope. When the whole body is presented it is seldom located within the technology of disease diagnosis and treatment but rather is posed for specific social control. Just as each digitized picture of the cancerous cell in the texts is used to create a story so too are the pictures of the whole body in action. Possible story lines offered by the publishing houses concerning the reaction of the body to cancer are shown to intermingle with risk factor analysis to project a sense of Foucaultian 'governmentality' based on assumed control and self regulation by the informed reader. In conclusion a procedure is suggested to further analyze additional textbooks concerning biological/educational issues that have been recast as social problems.

  4. A Meta-Analysis of SMAD4 Immunohistochemistry as a Prognostic Marker in Colorectal Cancer12

    PubMed Central

    Voorneveld, Philip W.; Jacobs, Rutger J.; Kodach, Liudmila L.; Hardwick, James C.H.

    2015-01-01

    AIM: SMAD4 immunohistochemistry is considered a valuable prognostic marker in colorectal cancer, but individual studies have often been small and the results variable. A meta-analysis could potentially clarify these findings. METHODS: In September 2014, a Pubmed and Google Scholar search was conducted to find publications that reported the prognostic value of SMAD4 expression. A meta-analysis was performed to clarify the association between SMAD4 expression and survival outcomes. RESULTS: 137 studies were found, of which 13 were considered eligible. The studies consisted of a total of 3800 patients. Three different endpoints were taken into account, namely, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In addition, the studies were divided into univariate and multivariate analyses. The pooled hazard ratios were given as follows: univariate CSS = 1.75 [95% confidence interval (CI): 0.93-3.32; z= 1.69; P= .09]; multivariate CSS = 2.17 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate DFS = 2.11 (95% CI: 1.36-3.28; z= 3.32; P= .001); multivariate DFS = 2.15 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate OS and DFS = 2.30 (95% CI: 1.41-3.73; z= 3.36; P= .001); univariate OS = 2.28 (95% CI: 1.30-4.00; z= 2.89; P= .004). CONCLUSION: The results of the presented meta-analyses indicate that SMAD4 expression status using immunohistochemistry is a prognostic marker for patient survival. PMID:25749173

  5. Fish consumption and the risk of gastric cancer: systematic review and meta-analysis

    Microsoft Academic Search

    Shengjun Wu; Jie Liang; Lei Zhang; Xia Zhu; Xufeng Liu; Danmin Miao

    2011-01-01

    BACKGROUND: Gastric cancer is the fourth most frequently occurring malignancy after lung, breast, and colorectal cancer, and the second most common cause of death from cancer worldwide. Epidemiologic studies have examined the possible association between fish consumption and gastric cancer, but the results were inconclusive. We conducted a systematic review and meta-analysis to examine the association between fish intake and

  6. RESEARCH Open Access Analysis of primary risk factors for oral cancer

    E-print Network

    Ahmad, Sajjad

    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

  7. Dietary factors and risk of chronic lymphocytic leukemia and small lymphocytic lymphoma: a pooled analysis of two prospective studies

    PubMed Central

    Tsai, Huei-Ting; Cross, Amanda J.; Graubard, Barry I.; Oken, Martin; Schatzkin, Arthur; Caporaso, Neil E.

    2010-01-01

    Background Other than male sex, family history, advanced age, and race, risk factors for chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are unknown. Very few studies have investigated diet in relation to these leukemias, and no consistent associations are known. Methods Using two large prospective population-based studies, we evaluated the relationship between diet and CLL/SLL risk. Among 525,982 men and women free of cancer at enrollment, we identified 1,129 incident CLL/SLL cases during 11.2 years of follow-up. Results We found no associations between total fat, saturated fat, fiber, red meat, processed meat, fruit or vegetable intake and risk of CLL/SLL. We noted a suggestive positive association between body mass index (BMI) and CLL/SLL (hazard ratio =1.30; 95% confidence interval= 0.99-1.36). Conclusion We did not find any associations between foods or nutrients and CLL/SLL. Impact Our large prospective study indicates that diet may not play a role in CLL/SLL development. PMID:20929883

  8. Functional and genetic analysis of the colon cancer network

    PubMed Central

    2014-01-01

    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

  9. Association of GSTP1 Ile105Val polymorphism with risk of esophageal cancer: a meta-analysis of 21 case-control studies

    PubMed Central

    Song, Yipeng; Du, Yuanna; Zhou, Qi; Ma, Jinbo; Yu, Jinming; Tao, Xiaofeng; Zhang, Fenghua

    2014-01-01

    Background: The association of glutathione s-transferase P1 (GSTP1) Ile105Val polymorphism with risk of esophageal cancer (EC) has been evaluated in many studies; however, the results from these studies are controversial. Thus, further analysis on association between GSTP1 Ile105Val polymorphism and risk of EC is needed among a larger study population. Method: We searched the relevant electronic databases and performed a meta-analysis based on 21 published case-control studies. The Chi-square based I2-statistic test was performed to evaluate possible heterogeneity across the studies. Additionally, random-effects models were used to calculate crude pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Overall, this meta-analysis did support a significant association between GSTP1 Ile105Val polymorphism and risk of EC (pooled OR 1.25, 95% CI, 1.05-1.49). Furthermore, the stratified analysis showed that, in comparison to GSTP1 Ile105Val Ile/Ile genotype, the Val/Val genotype was significantly associated with risk of esophageal squamous cell carcinoma (ESCC) (pooled OR 1.45, 95% CI, 1.07-1.96), particularly in the Caucasian population (pooled OR 1.41, 95% CI, 1.01-1.95). Such a significant association was not observed for esophageal adenocarcinoma (EAC) patients or subjects of an Asian ethnicity. Moreover, substantial evidence of heterogeneity among the studies was not observed. Conclusion: The results from this meta-analysis support a significant association between the GSTP1 Ile105Val polymorphism and risk of EC, particularly in a subgroup with ESCC and in the Caucasian population. Further studies with larger sample sizes are needed to validate our findings. PMID:25419352

  10. Analysis of Assembly Bill 1000: Cancer Treatment

    E-print Network

    California Health Benefits Review Program (CHBRP)

    2011-01-01

    Oral Chemotherapy Drug Coverage Mandated Benefit Review.chemotherapy protocols Benzenesulfonates Deoxycytidine Drug costs Fluorouracil Health benefitBenefits Review Program (CHBRP). Analysis of Senate Bill 161: Health Care Coverage: Chemotherapy

  11. Vitamin D with Calcium Reduces Mortality: Patient Level Pooled Analysis of 70,528 Patients from Eight Major Vitamin D Trials

    PubMed Central

    Avenell, Alison; Masud, Tahir; Anderson, Frazer; Meyer, Haakon E.; Sanders, Kerrie M.; Salovaara, Kari; Cooper, Cyrus; Smith, Helen E.; Jacobs, Elizabeth T.; Torgerson, David; Jackson, Rebecca D.; Manson, JoAnn E.; Brixen, Kim; Mosekilde, Leif; Robbins, John A.; Francis, Roger M.; Abrahamsen, Bo

    2012-01-01

    Introduction: Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium. Subjects and Methods: Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies. Results: The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62–77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88–0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84–0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88–0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91–1.06). Conclusion: Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone. PMID:22605432

  12. Quantitative DNA Methylation Analysis of Candidate Genes in Cervical Cancer

    PubMed Central

    Siegel, Erin M.; Riggs, Bridget M.; Delmas, Amber L.; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D.

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97–1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated. PMID:25826459

  13. Diabetes and breast cancer risk: a meta-analysis

    PubMed Central

    Boyle, P; Boniol, M; Koechlin, A; Robertson, C; Valentini, F; Coppens, K; Fairley, L-L; Boniol, M; Zheng, T; Zhang, Y; Pasterk, M; Smans, M; Curado, M P; Mullie, P; Gandini, S; Bota, M; Bolli, G B; Rosenstock, J; Autier, P

    2012-01-01

    Background: The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research. Methods: A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk. Results: Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)). Conclusion: The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes. PMID:22996614

  14. Risk factors associated with complications in lower-extremity reconstruction with the distally based sural flap: a systematic review and pooled analysis.

    PubMed

    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

    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

  15. Tidal Pool on Folly Island

    USGS Multimedia Gallery

    A tidal pool on Folly Island. Tidal pools are small pools of water that are left when the tide recedes. Because these pools have water more or less permanently, distinct ecosystems can develop separate from the surrounding beach. Folly Island, a preserve owned by the Maine Coast Heritage Trust, is a...

  16. Diabetes mellitus carries a risk of gastric cancer: A meta-analysis

    PubMed Central

    Shimoyama, Shouji

    2013-01-01

    AIM: To investigate the association and quantify the relationship between diabetes mellitus (DM) and gastric cancer (GC) by an updated meta-analysis. METHODS: The initial PubMed search identified 1233 publications. Studies not reporting GC or those not reporting actual number of GC were excluded. Twelve pertinent studies were retrieved from the PubMed database or from a manual search and considered for the meta-analysis. Pooled risk ratios and 95%CI were estimated by a random-effects model. Subgroup analysis was performed according to gender or geographical regions. Heterogeneity and publication bias were evaluated by I2 and funnel plot analysis, respectively. RESULTS: DM was significantly associated with GC with a RR of 1.41 (P = 0.006) (95%CI: 1.10-1.81). Subgroup analyses revealed that both sexes showed a significant association with GC, with a greater magnitude of risk in females (RR = 1.90; 95%CI: 1.27-2.85; P = 0.002) than in males (RR = 1.24; 95%CI: 1.08-1.43; P = 0.002). In addition, the link between DM and GC was significant in East Asian DM patients (RR = 1.77; 95%CI: 1.38-2.26; P < 0.00001) but not in Western DM patients (RR = 1.23; 95%CI: 0.90-1.68; P = 0.2). There was no evidence of publication bias, but the results indicated significant heterogeneity. CONCLUSION: This updated meta-analysis has provided evidence of positive DM-GC associations. The limited information on potentially important clinical confounding factors in each study deserves further investigation. PMID:24187468

  17. Risk factors for developing a second upper aerodigestive cancer after radiotherapy with or without chemotherapy in patients with head-and-neck cancers: An exploratory outcomes analysis

    SciTech Connect

    Taussky, Daniel [Division of Radiation Oncology, University Hospital Geneva, Geneva (Switzerland)]. E-mail: daniel.taussky.chum@ssss.gouv.qc.ca; Rufibach, Kaspar M.Sc. [Swiss Group for Clinical Cancer Research (SAAK), Berne (Switzerland); Huguenin, Pia [Division of Radiation Oncology, University Hospital Zuerich, Zurich (Switzerland); Allal, Abdelkarim S. [Division of Radiation Oncology, University Hospital Geneva, Geneva (Switzerland)

    2005-07-01

    Purpose: The objective was to assess the influence of treatment-related and patient-related factors on the risk of developing a second primary tumor (SPT) of the upper aerodigestive tract (UADT) in patients with locoregionally advanced nonmetastatic carcinomas of the head-and-neck region. Methods and Materials: The data of 521 patients with a minimum follow-up of 1 year were pooled: 224 patients from the Swiss Group for Clinical Cancer Research (SAKK) 10/94 trial, treated with 1.2 Gy b.i.d. to 74.4 Gy, and randomized to receive or not to receive simultaneous chemotherapy with cisplatin (excluding nasopharyngeal and maxillary sinus carcinomas); and 297 patients from Geneva, all treated with accelerated radiotherapy with concomitant boost to 69.9 Gy and predominantly cisplatin-based concomitant chemotherapy in 33% of patients (including 21 patients with nasopharyngeal carcinomas). An exploratory analysis using competing risk methodology was performed. Results: A total of 65 SPT of the UADT were observed after a median observation time of 4.7 years. The overall risk of experiencing an SPT of the UADT at 10 years in the presence of all other possible events was estimated to be 33%. There were no SPTs after treatment for nasopharyngeal carcinoma. In a multivariate logistic regression analysis, there was no difference in occurrence of SPT at 3 years with respect to the administration of chemotherapy (p = 0.31), age (p 0.62), performance status (p = 0.61), gender (p = 0.27), presence of nodal disease (p = 0.51), or T stage (p = 0.72). However, patients treated with concomitant boost had fewer SPTs (p = 0.0093). Conclusions: Our data do not suggest that addition of chemotherapy to radiotherapy influences the incidence of second cancers in patients with head-and-neck cancer. The difference in the incidence of SPT between the two radiotherapy schedule groups merits further exploration.

  18. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    SciTech Connect

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-01

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  19. Fire safety distances for open pool fires

    NASA Astrophysics Data System (ADS)

    Sudheer, S.; Kumar, Lokendra; Manjunath, B. S.; Pasi, Amit; Meenakshi, G.; Prabhu, S. V.

    2013-11-01

    Fire accidents that carry huge loss with them have increased in the previous two decades than at any time in the history. Hence, there is a need for understanding the safety distances from different fires with different fuels. Fire safety distances are computed for different open pool fires. Diesel, gasoline and hexane are used as fuels for circular pool diameters of 0.5 m, 0.7 m and 1.0 m. A large square pool fire of 4 m × 4 m is also conducted with diesel as a fuel. All the prescribed distances in this study are purely based on the thermal analysis. IR camera is used to get the thermal images of pool fires and there by the irradiance at different locations is computed. The computed irradiance is presented with the threshold heat flux limits for human beings.

  20. Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

    PubMed Central

    Carlsen, Kai-Håkon; Mowinckel, Petter; Wijga, Alet H.; Brunekreef, Bert; Torrent, Maties; Roberts, Graham; Arshad, S. Hasan; Kull, Inger; Krämer, Ursula; von Berg, Andrea; Eller, Esben; Høst, Arne; Kuehni, Claudia; Spycher, Ben; Sunyer, Jordi; Chen, Chih-Mei; Reich, Andreas; Asarnoj, Anna; Puig, Carmen; Herbarth, Olf; Mahachie John, Jestinah M.; Van Steen, Kristel; Willich, Stefan N.; Wahn, Ulrich; Lau, Susanne; Keil, Thomas; Wickman, Magnus; Hallner, Eva; Alm, Johan; Almqvist, Catarina; Wennergren, Göran; Alm, Bernt; Heinrich, Joachim; Smit, Henriette A.; Thijs, Carel; Mommers, Monique; Bindslev-Jensen, Carsten; Halken, Susanne; Fantini, Maria Pia; Bravi, Francesca; Porta, Daniela; Forastiere, Francesco; Custovic, Adnan; Dubakiene, Ruta; Mahachie, Jestinah

    2012-01-01

    Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2?=?9%; p?=?0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2?=?0%, p?=?0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2?=?33%, p?=?0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given. PMID:22952649

  1. Meta-analysis of Hsa-mir-499 polymorphism (rs3746444) for cancer risk: evidence from 31 case-control studies.

    PubMed

    Chen, Chen; Yang, Shenglan; Chaugai, Sandip; Wang, Yan; Wang, Dao

    2014-11-30

    BackgroundMicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. Recent studies investigating the association between hsa-mir-499 polymorphism (rs3746444) and cancer risk have yielded conflicting results.MethodsIn this meta-analysis, we conducted a search of case¿control studies on the associations of SNP rs3746444 with susceptibility to cancer in electronic databases. A total of 31 studies involving 12799 cases and 14507 controls were retrieved and the strength of the association was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in controls. Subgroup analyses were done by racial descent and cancer type. Publication bias of literatures was evaluated by visual inspection of funnel plots and the linear regression asymmetry test by Egger et al. Sensitivity analysis was conducted by excluding one study at a time to examine the influence of individual data set on the pooled ORs.ResultsOverall, significant association between rs3746444 polymorphism and susceptibility to cancer was identified in TC versus TT and TC/CC versus TT (dominant) models. In the stratified analyses, increased risks were found in Asians, but not in Caucasians in all comparison models tested. Moreover, significant association with an increased risk was found in Chinese population. Also, much higher significant association with increased cancer risks were found in Iranian population. In different cancer types, a decreased risk was found in esophageal cancer.ConclusionOur meta-analysis suggested that hsa-mir-499 rs3746444 T¿>¿C polymorphism is associated with the risk of cancer in Asians, mainly in Iranian and Chinese population. However, rs3746444 T¿>¿C polymorphism is negatively associated with the risk of esophageal cancer. PMID:25433484

  2. Rice consumption and risk of cardiovascular disease: results from a pooled analysis of 3 U.S. cohorts1234

    PubMed Central

    Muraki, Isao; Wu, Hongyu; Imamura, Fumiaki; Laden, Francine; Rimm, Eric B; Hu, Frank B; Willett, Walter C; Sun, Qi

    2015-01-01

    Background: Health concerns have been raised about rice consumption, which may significantly contribute to arsenic exposure. However, little is known regarding whether habitual rice consumption is associated with cardiovascular disease (CVD) risk. Objective: We examined prospectively the association of white rice and brown rice consumption with CVD risk. Design: We followed a total of 207,556 women and men [73,228 women from the Nurses’ Health Study (1984–2010), 92,158 women from the Nurses’ Health Study II (1991–2011), and 42,170 men from the Health Professionals Follow-Up Study (1986–2010)] who were free of CVD and cancer at baseline. Validated semiquantitative food-frequency questionnaires were used to assess consumption of white rice, brown rice, and other food items. Fatal and nonfatal CVD (coronary artery disease and stroke) was confirmed by medical records or self-reports. Results: During 4,393,130 person-years of follow-up, 12,391 cases of CVD were identified. After adjustment for major CVD risk factors, including demographics, lifestyle, and other dietary intakes, rice consumption was not associated with CVD risk. The multivariable-adjuted HR of developing CVD comparing ?5 servings/wk with <1 serving/wk was 0.98 (95% CI: 0.84, 1.14) for white rice, 1.01 (0.79, 1.28) for brown rice, and 0.99 (0.90, 1.08) for total rice. To minimize the potential impact of racial difference in rice consumption, we restricted the analyses to whites only and obtained similar results: the HRs of CVD for ?5 servings/wk compared with <1 serving/wk were 1.04 (95% CI: 0.88, 1.22) for white rice and 1.01 (0.78, 1.31) for brown rice. Conclusions: Greater habitual consumption of white rice or brown rice is not associated with CVD risk. These findings suggest that rice consumption may not pose a significant CVD risk among the U.S. population when consumed at current amounts. More prospective studies are needed to explore these associations in other populations. PMID:25527760

  3. Genotoxic Effects in Swimmers Exposed to Disinfection By-products in Indoor Swimming Pool

    EPA Science Inventory

    BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk, and a recent study found an increased bladder cancer risk among subjects attending swimming pools. OBJECTIVES: To evaluate whether swimming in pools is associated with ...

  4. Statin therapy improves long-term survival in non-ischaemic cardiomyopathy: a pooled analysis of 4500 patients.

    PubMed

    Deo, Salil V; Rababa'h, Abeer; Altarabsheh, Salah E; Lim, Ju Yong; Cho, Yang Hyun; Park, Soon J

    2014-10-01

    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

  5. Trans-Study Projection of Genomic Biomarkers in Analysis of Oncogene Deregulation and Breast Cancer

    E-print Network

    West, Mike

    Trans-Study Projection of Genomic Biomarkers in Analysis of Oncogene Deregulation and Breast Cancer to the interventions into the in vivo data from breast cancers. Bayesian latent factor analysis of gene expression linked to these signatures in the breast cancer data then reveals the greater complexity of patterns

  6. High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

    SciTech Connect

    Viani, Gustavo Arruda, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil)] [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil)

    2012-08-01

    Purpose: To determine in a meta-