bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity in Relation to Total, Advanced, and Fatal Prostate Cancer
Authors: Moore Steven C. , Peters Tricia M. , Ahn Jiyoung , Park Yikyung , Schatzkin Arthur , Albanes Demetrius , Ballard-Barbash Rachel , Hollenbeck Albert , Leitzmann Michael F. 
Published: September 2008

AbstractPhysical activity has been inconsistently related to total prostate cancer and few studies have examined whether this association varies by disease aggressiveness. We examined physical activity in relation to total, advanced, and fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995-1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about current frequency of vigorous exercise of at least 20 min of duration, as well as frequency of exercise during adolescence (ages 15-18). We used proportional hazards regression to calculate multivariate relative risks (RR) and 95% confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872 prostate cancer cases were identified, including 1,942 advanced and 513 fatal cases. Comparing frequent (5+ times per week) versus infrequent (less than once per week) vigorous exercise, exercise at baseline was not associated with risk of total prostate cancer (RR, 1.01; 95% CI, 0.96-1.07; Ptrend = 0.78), advanced prostate cancer (RR, 1.14; 95% CI, 0.97-1.33; Ptrend = 0.25), or fatal prostate cancer (RR, 0.90; 95% CI, 0.67-1.20; Ptrend = 0.12). Increasing level of vigorous exercise during adolescence was associated with a small 3% reduction in total prostate cancer risk (frequent versus infrequent exercise during adolescence: RR, 0.97; 95% CI, 0.91-1.03; Ptrend = 0.03) but was not associated with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78-1.14; Ptrend = 0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67-1.36; Ptrend = 0.99). Neither vigorous exercise at baseline nor exercise during adolescence was related to risk of total, advanced, or fatal prostate cancer in this large prospective cohort. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2458–66)
Tumor Necrosis Factor Alpha Extended Haplotypes and Risk of Gastric Carcinoma
Authors: Canedo Paulo , Durães Cecília , Pereira Fábio , Regalo Gonçalo , Lunet Nuno , Barros Henrique , Carneiro Fátima , Seruca Raquel , Rocha Jorge , Machado José C. 
Published: September 2008

AbstractThe tumor necrosis factor α (TNFA)-308*A allele has been found to confer an increased risk of gastric carcinoma. Inconsistency in risk estimates across populations lead us to hypothesize about the presence of an alternative causal locus in the same chromosomal region. A suitable approach is to determine the tumor necrosis factor haplotypic structure in order to clarify whether the association between the *A allele and the increased risk of gastric carcinoma is etiologic or secondary to linkage disequilibrium. Firstly, we assessed the association between the TNFA-308G&gt;A polymorphism and the risk of gastric carcinoma in a population from Northern Portugal (508 gastric carcinoma patients, 713 controls); secondly, we genotyped five microsatellite loci (TNFa, b, c, d, e) flanking the TNFA-308G&gt;A locus to establish the haplotypic structure associated with this single-nucleotide polymorphism in cases (122 patients) and controls (169 individuals). We found a significant association between the *A allele and increased risk of gastric carcinoma (odds ratio, 1.7; 95% confidence interval, 1.3-2.2) confirming previous results in our population. Regarding the *A allele–associated haplotypes, the most relevant difference was found for the H1A haplotype present in 33.1% of the cases and 12.5% of the controls. We also observed haplotypes associated with the *A allele that were found only in cases or controls. A population differentiation test showed that the gastric carcinoma and the control groups were significantly different for the *A allele haplotypic structure. This suggests that the association between the TNFA-308G&gt;A polymorphism and increased risk of gastric carcinoma is dependent on linkage disequilibrium with an as yet unidentified locus. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2416–20)
Mitochondrial Genetic Polymorphisms Do Not Predict Survival in Patients with Pancreatic Cancer
Authors: Halfdanarson Thorvardur R. , Wang Liang , Bamlet William R. , de Andrade Mariza , McWilliams Robert R. , Cunningham Julie M. , Petersen Gloria M. 
Published: September 2008

Abstract
Pancreatic cancer is a highly lethal malignancy, and the majority of patients succumb to the disease within 2 years. We evaluated the role of variants of mitochondrial DNA and mitochondrial haplogroups in predicting prognosis of patients with pancreatic cancer. A total of 24 mitochondrial single nucleotide polymorphisms were genotyped in 990 patients with pancreatic cancer. After adjusting for covariates and multiple comparisons, no association between any of the mitochondrial single nucleotide polymorphisms or haplogroups and survival was observed. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2512–3)
Age-Incidence Curves of Nasopharyngeal Carcinoma Worldwide: Bimodality in Low-Risk Populations and Aetiologic Implications
Authors: Bray Freddie , Haugen Marion , Moger Tron A. , Tretli Steinar , Aalen Odd O. , Grotmol Tom 
Published: September 2008

Abstract
The distinct geographic variation in the global incidence of nasopharyngeal carcinoma reflects a complex etiology involving viral, environmental, and genetic components. The high to intermediate rates observed in endemic areas contrast markedly with the uniformly low rates seen in much of the world. An interesting epidemiologic observation is the early peak in age-incidence curves observed in certain geographically disparate populations, suggestive of distinct causal entities and the possible exhaustion of susceptible individuals from the population at a certain age. The aim of this study was to systematically evaluate the age-incidence profiles of NPC worldwide on partitioning populations according to level of risk, in an effort to provide clues about the importance of early-in-life factors and genetic susceptibility. Using data from 23 high-quality population-based cancer registries for the period 1983-1997, a key finding was the consistent pattern of bimodality that emerged across low-risk populations, irrespective of geographic location. Continual increases in NPC risk by age up to a first peak in late adolescence/early adulthood (ages 15-24 years) were observed, followed by a second peak later in life (ages 65-79 years). No such early peak in NPC incidence by age group was evident among the high-risk populations studied. These findings are discussed according to existing lines of biological and epidemiologic evidence related to level of population risk, age at diagnosis, and histologic subtype. A modified model for NPC tumor development is proposed on the basis of these observations. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2356–65)
Tamoxifen Treatment in Danish Breast Cancer Patients and 5-Year Risk of Arterial Atherosclerotic Events: A Null Association
Authors: Hernandez Rohini K. , Sørensen Henrik Toft , Jacobsen Jacob , Pedersen Lars , Lash Timothy L. 
Published: September 2008

Abstract
Although the effectiveness of tamoxifen in preventing the recurrence of breast cancer is well established, associations between tamoxifen and the occurrence of atherosclerotic events are not as clear. Breast cancer patients taking tamoxifen have lower serum cholesterol and other lipid levels than those not taking tamoxifen, suggesting that tamoxifen might prevent atherosclerotic events, but the existing studies are conflicting. We examined the relation between tamoxifen and incident hospitalization of angina pectoris, acute myocardial infarction, heart failure, and stroke. The study population of 16,289 women was identified from the Danish Breast Cancer Cooperative Group nationwide clinical database and includes women diagnosed with stage I or II estrogen receptor–positive breast cancer between 1990 and 2004 at ages 45 to 69. Use of a large population-based sample with complete outcome ascertainment allowed us to calculate precise measures of risks, risk ratios, and adjusted hazard ratios comparing tamoxifen-treated patients with untreated patients. We found strong evidence for null associations for each of the four outcomes of interest during the first year and first 5 years after the start of therapy. These findings are important in risk/benefit analyses as tamoxifen therapy in postmenopausal women is being replaced with aromatase inhibitors. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2509–11)
Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans
Authors: Huang R. Stephanie , Duan Shiwei , Kistner Emily O. , Hartford Christine M. , Dolan M. Eileen 
Published: September 2008

Abstract
To gain a better understanding of the genetic variants associated with carboplatin-induced cytotoxicity in individuals of African descent, we present a step-wise approach integrating genotypes, gene expression, and sensitivity of HapMap cell lines to carboplatin. Cell lines derived from 30 trios of African descent (YRI) were used to develop a preclinical model to identify genetic variants and gene expression that contribute to carboplatin-induced cytotoxicity. Cytotoxicity was determined as cell growth inhibition at increasing concentrations of carboplatin for 72 h. Gene expression of 89 HapMap YRI cell lines was determined using the Affymetrix GeneChip Human Exon 1.0 ST Array. Single nucleotide polymorphism genotype and the percent survival at different treatment concentrations along with carboplatin IC50 were linked through whole genome association. A second association test was done between single nucleotide polymorphism genotype and gene expression, and linear regression was then used to capture those genes whose expression correlated to drug sensitivity phenotypes. This approach allows us to identify genetic variants that significantly associate with sensitivity to the cytotoxic effects of carboplatin through their effect on gene expression. We found a gene (GPC5) whose expression is important in all carboplatin treatment concentrations as well as many genes unique to either low (e.g., MAPK1) or high (e.g., BRAF, MYC, and BCL2L1) concentrations of drug. Our whole genome approach enables us to evaluate the contribution of genetic and gene expression variation to a wide range of cellular phenotypes. The identification of concentration specific genetic signatures allows for potential integration of pharmacokinetics, pharmacodynamics, and pharmacogenetics in tailoring chemotherapy. [Mol Cancer Ther 2008;7(9):3038–46]
Gene expression profiling-based identification of cell-surface targets for developing multimeric ligands in pancreatic cancer
Authors: Balagurunathan Yoganand , Morse David L. , Hostetter Galen , Shanmugam Vijayalakshmi , Stafford Phillip , Shack Sonsoles , Pearson John , Trissal Maria , Demeure Michael J. , Von Hoff Daniel D. , Hruby Victor J. , Gillies Robert J. , Han Haiyong 
Published: September 2008

Abstract
Multimeric ligands are ligands that contain multiple binding domains that simultaneously target multiple cell-surface proteins. Due to cooperative binding, multimeric ligands can have high avidity for cells (tumor) expressing all targeting proteins and only show minimal binding to cells (normal tissues) expressing none or only some of the targets. Identifying combinations of targets that concurrently express in tumor cells but not in normal cells is a challenging task. Here, we describe a novel approach for identifying such combinations using genome-wide gene expression profiling followed by immunohistochemistry. We first generated a database of mRNA gene expression profiles for 28 pancreatic cancer specimens and 103 normal tissue samples representing 28 unique tissue/cell types using DNA microarrays. The expression data for genes that encode proteins with cell-surface epitopes were then extracted from the database and analyzed using a novel multivariate rule-based computational approach to identify gene combinations that are expressed at an efficient binding level in tumors but not in normal tissues. These combinations were further ranked according to the proportion of tumor samples that expressed the sets at efficient levels. Protein expression of the genes contained in the top ranked combinations was confirmed using immunohistochemistry on a pancreatic tumor tissue and normal tissue microarrays. Coexpression of targets was further validated by their combined expression in pancreatic cancer cell lines using immunocytochemistry. These validated gene combinations thus encompass a list of cell-surface targets that can be used to develop multimeric ligands for the imaging and treatment of pancreatic cancer. [Mol Cancer Ther 2008;7(9):3071–80]
HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924
Authors: Haluska Paul , Carboni Joan M. , TenEyck Cynthia , Attar Ricardo M. , Hou Xiaonan , Yu Chunrong , Sagar Malvika , Wong Tai W. , Gottardis Marco M. , Erlichman Charles 
Published: September 2008

Abstract
We have reported previously the activity of the insulin-like growth factor-I (IGF-IR)/insulin receptor (InsR) inhibitor, BMS-554417, in breast and ovarian cancer cell lines. Further studies indicated treatment of OV202 ovarian cancer cells with BMS-554417 increased phosphorylation of HER-2. In addition, treatment with the pan-HER inhibitor, BMS-599626, resulted in increased phosphorylation of IGF-IR, suggesting a reciprocal cross-talk mechanism. In a panel of five ovarian cancer cell lines, simultaneous treatment with the IGF-IR/InsR inhibitor, BMS-536924 and BMS-599626, resulted in a synergistic antiproliferative effect. Furthermore, combination therapy decreased AKT and extracellular signal-regulated kinase activation and increased biochemical and nuclear morphologic changes consistent with apoptosis compared with either agent alone. In response to treatment with BMS-536924, increased expression and activation of various members of the HER family of receptors were seen in all five ovarian cancer cell lines, suggesting that inhibition of IGF-IR/InsR results in adaptive up-regulation of the HER pathway. Using MCF-7 breast cancer cell variants that overexpressed HER-1 or HER-2, we then tested the hypothesis that HER receptor expression is sufficient to confer resistance to IGF-IR-targeted therapy. In the presence of activating ligands epidermal growth factor or heregulin, respectively, MCF-7 cells expressing HER-1 or HER-2 were resistant to BMS-536924 as determined in a proliferation and clonogenic assay. These data suggested that simultaneous treatment with inhibitors of the IGF-I and HER family of receptors may be an effective strategy for clinical investigations of IGF-IR inhibitors in breast and ovarian cancer and that targeting HER-1 and HER-2 may overcome clinical resistance to IGF-IR inhibitors. [Mol Cancer Ther 2008;7(9):2589–98]
Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy
Authors: Tuunanen Helena , Engblom Erik , Naum Alexandru , Någren Kjell , Scheinin Mika , Hesse Birger , Juhani Airaksinen K.E. , Nuutila Pirjo , Iozzo Patricia , Ukkonen Heikki , Opie Lionel H. , Knuuti Juhani 
Published: September 2008

Background—The anti-ischemic agent trimetazidine improves ejection fraction in heart failure that is hypothetically linked to inhibitory effects on cardiac free fatty acid (FFA) oxidation. However, FFA oxidation remains unmeasured in humans. We investigated the effects of trimetazidine on cardiac perfusion, efficiency of work, and FFA oxidation in idiopathic dilated cardiomyopathy.Methods and Results—Nineteen nondiabetic patients with idiopathic dilated cardiomyopathy on standard medication were randomized to single-blind trimetazidine (n=12) or placebo (n=7) for 3 months. Myocardial perfusion, FFA, and total oxidative metabolism were measured using positron emission tomography with [15O]H2O, [11C]acetate, and [11C]palmitate. Cardiac function was assessed echocardiographically; insulin sensitivity was assessed by the homeostasis model assessment index. Trimetazidine increased ejection fraction from 30.9±8.5% to 34.8±12% (P=0.027 versus placebo). Myocardial FFA uptake was unchanged, and β-oxidation rate constant decreased only 10%. Myocardial perfusion, oxidative metabolism, and work efficiency remained unchanged. Trimetazidine decreased insulin resistance (glucose: 5.9±0.7 versus 5.5±0.6 mmol/L,P=0.047; insulin: 10±6.9 versus 7.6±3.6 mU/L,P=0.031; homeostasis model assessment index: 2.75±2.28 versus 1.89±1.06,P=0.027). The degree of β-blockade and trimetazidine interacted positively on ejection fraction. Plasma high-density lipoprotein concentrations increased 11% (P<0.001).Conclusions—In idiopathic dilated cardiomyopathy with heart failure, trimetazidine increased cardiac function and had both cardiac and extracardiac metabolic effects. Cardiac FFA oxidation modestly decreased and myocardial oxidative rate was unchanged, implying increased oxidation of glucose. Trimetazidine improved whole-body insulin sensitivity and glucose control in these insulin-resistant idiopathic dilated cardiomyopathy patients, thus hypothetically countering the myocardial damage of insulin resistance. Additionally, the trimetazidine-induced increase in ejection fraction was associated with greater β1-adrenoceptor occupancy, suggesting a synergistic mechanism.
White Matter Integrity Predicts Delay Discounting Behavior in 9- to 23-Year-Olds: A Diffusion Tensor Imaging Study
Authors: Olson Elizabeth A. , Collins Paul F. , Hooper Catalina J. , Muetzel Ryan , Lim Kelvin O. , Luciana Monica 
Published: September 2008

AbstractHealthy participants (n = 79), ages 9–23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.
An ERP Investigation on Visuotactile Interactions in Peripersonal and Extrapersonal Space: Evidence for the Spatial Rule
Authors: Sambo Chiara F. , Forster Bettina 
Published: September 2008

AbstractThe spatial rule of multisensory integration holds that cross-modal stimuli presented from the same spatial location result in enhanced multisensory integration. The present study investigated whether processing within the somatosensory cortex reflects the strength of cross-modal visuotactile interactions depending on the spatial relationship between visual and tactile stimuli. Visual stimuli were task-irrelevant and were presented simultaneously with touch in peripersonal and extrapersonal space, in the same or opposite hemispace with respect to the tactile stimuli. Participants directed their attention to one of their hands to detect infrequent tactile target stimuli at that hand while ignoring tactile targets at the unattended hand, all tactile nontarget stimuli, and any visual stimuli. Enhancement of ERPs recorded over and close to the somatosensory cortex was present as early as 100 msec after onset of stimuli (i.e., overlapping with the P100 component) when visual stimuli were presented next to the site of tactile stimulation (i.e., perihand space) compared to when these were presented at different locations in peripersonal or extrapersonal space. Therefore, this study provides electrophysiological support for the spatial rule of visual–tactile interaction in human participants. Importantly, these early cross-modal spatial effects occurred regardless of the locus of attention. In addition, and in line with previous research, we found attentional modulations of somatosensory processing only to be present in the time range of the N140 component and for longer latencies with an enhanced negativity for tactile stimuli at attended compared to unattended locations. Taken together, the pattern of the results from this study suggests that visuotactile spatial effects on somatosensory processing occur prior and independent of tactile–spatial attention.
Cross-modal Emotional Attention: Emotional Voices Modulate Early Stages of Visual Processing
Authors: Brosch Tobias , Grandjean Didier , Sander David , Scherer Klaus R. 
Published: September 2008

Abstract
Emotional attention, the boosting of the processing of emotionally relevant stimuli, has, up to now, mainly been investigated within a sensory modality, for instance, by using emotional pictures to modulate visual attention. In real-life environments, however, humans typically encounter simultaneous input to several different senses, such as vision and audition. As multiple signals entering different channels might originate from a common, emotionally relevant source, the prioritization of emotional stimuli should be able to operate across modalities. In this study, we explored cross-modal emotional attention. Spatially localized utterances with emotional and neutral prosody served as cues for a visually presented target in a cross-modal dot-probe task. Participants were faster to respond to targets that appeared at the spatial location of emotional compared to neutral prosody. Event-related brain potentials revealed emotional modulation of early visual target processing at the level of the P1 component, with neural sources in the striate visual cortex being more active for targets that appeared at the spatial location of emotional compared to neutral prosody. These effects were not found using synthesized control sounds matched for mean fundamental frequency and amplitude envelope. These results show that emotional attention can operate across sensory modalities by boosting early sensory stages of processing, thus facilitating the multimodal assessment of emotionally relevant stimuli in the environment.