bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimetastatic Activity of a Preventive Cancer Vaccine
Authors: Nanni Patrizia , Nicoletti Giordano , Palladini Arianna , Croci Stefania , Murgo Annalisa , Antognoli Agnese , Landuzzi Lorena , Fabbi Marina , Ferrini Silvano , Musiani Piero , Iezzi Manuela , De Giovanni Carla , Lollini Pier-Luigi 
Published: November 2007

Abstract
The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of mammary carcinoma progression in HER-2/neu transgenic mice. The vaccine consisted of transgenic mammary carcinoma cells expressing HER-2/neu and two adjuvants: allogeneic class I histocompatibility antigens and interleukin (IL)-12. Vaccination of mice bearing lung micrometastases resulted in a 90% inhibition of metastasis development, whereas vaccination of mice with incipient local tumors was ineffective. The antimetastatic response was hampered by immune tolerance, as the protection of transgenic mice was lower than that of wild-type congenics not tolerant to HER-2/neu. A significant gain in immunotherapeutic activity in transgenic mice was obtained through the coadministration of anti-CD25 monoclonal antibody targeting regulatory T cells, which resulted in a &gt;99% inhibition of metastasis. The immune responses elicited in transgenic mice comprised the activation of lung granulocytes and macrophages and of systemic adaptive responses based on helper T cells and their cytokines (IFN-γ and IL-4) and anti-HER-2/neu antibodies. Dissection of relevant antimetastatic mechanisms by means of knockout mice and of depleting antibodies revealed a major difference between tumor prevention, which was completely dependent on anti-HER-2/neu antibodies, and metastasis therapy, which was antibody independent. In conclusion, a vaccine successfully developed for cancer immunoprevention showed a strong therapeutic activity against lung metastases mediated by protective immune mechanisms distinct from those preventing the onset of primary mammary carcinoma. [Cancer Res 2007;67(22):11037–44]
Nitric Oxide–Donating Aspirin Derivatives Suppress Microsatellite Instability in Mismatch Repair–Deficient and Hereditary Nonpolyposis Colorectal Cancer Cells
Authors: McIlhatton Michael A. , Tyler Jessica , Burkholder Susan , Ruschoff Josef , Rigas Basil , Kopelovich Levy , Fishel Richard 
Published: November 2007

Abstract
Nitric oxide–donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as cancer chemopreventive agents. Aspirin and sulindac have been shown to be effective in selecting for cells with reduced microsatellite instability (MSI) that is inherent in mismatch repair (MMR)–deficient hereditary nonpolyposis colorectal cancer (HNPCC) cells. The effect of NO-NSAIDs on MSI in MMR-deficient HNPCC cells is unknown. Here, we have examined genetically defined MMR-deficient murine embryo fibroblasts, murine colonocytes, and isogenic human HNPCC tumor cell lines treated with acetylsalicylic acid (aspirin; ASA) and three isomeric derivatives of NO-aspirin (NO-ASA). The MSI profiles were determined and compared with the Bethesda Criteria. We found that the ASA- and NO-ASA–treated MMR-deficient cell lines displayed a dose-dependent suppression of MSI that appeared as early as 8 weeks and gradually increased to include up to 67% of the microsatellite sequences examined after 19 to 20 weeks of continuous treatment. Residual resistance to microsatellite stabilization was largely confined to mononucleotide repeat sequences. Control (MMR-proficient) cells showed no changes in microsatellite status with or without treatment. The relative dose-dependent stabilization selection was: ortho-NO-ASA ≈ para-NO-ASA &gt; meta-NO-ASA ≫ ASA. Moreover, the doses required for stabilization by the ortho- and para-NO-ASA were 300- to 3,000-fold lower than ASA. These results suggest that NO-ASA derivatives may be more effective at suppressing MSI in MMR-deficient cell lines than ASA and should be considered for chemopreventive trials with HNPCC carriers. [Cancer Res 2007;67(22):10966–75]
Haplotype ofN-Acetyltransferase 1 and 2 and Risk of Pancreatic Cancer
Authors: Jiao Li , Doll Mark A. , Hein David W. , Bondy Melissa L. , Hassan Manal M. , Hixson James E. , Abbruzzese James L. , Li Donghui 
Published: November 2007

AbstractWe examined the association between N-acetyltransferase 1 and 2 (NAT1 and NAT2) haplotype and risk of pancreatic cancer by genotyping eight NAT1 and seven NAT2 single nucleotide polymorphisms in 532 patients and in 581 healthy controls (all non-Hispanic white) who were recruited at M. D. Anderson Cancer Center from January 2000 to December 2006. Haplotypes were reconstructed by using an expectation-maximization algorithm. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression models. Covariates included age (continuous variable), sex, pack-year of smoking (categorical), and history of diabetes when appropriate. NAT1 and NAT2 genotype was mutually adjusted. The prevalence of haplotype NAT1*10-NAT2*6A was 4.3% versus 2.7% (P = 0.06) and NAT1*11-NAT2*6A was 1.2% versus 0.4% (P = 0.05) in patients and controls, respectively. The diplotype NAT1*10/*10 or NAT1*10/*11 and NAT2*6A/any slow allele was associated with a higher risk of pancreatic cancer compared with other diplotypes (multivariate odds ratio, 4.15; 95% confidence interval, 1.15-15.00; P = 0.03). NAT2 slow genotype were associated with increased risk of pancreatic cancer among heavy smokers and among individuals with a history of diabetes. We for the first time found that rare NAT1*10 or NAT1*11-NAT2*6A diplotype may be an “at-risk” genetic variant for pancreatic cancer. The NAT2*6A/any slow acetylation genotype may be a predisposing factor for pancreatic cancer among diabetics with smoking exposure. Our observations must be confirmed in larger independent studies. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2379–86)
Sex- and Kindred-Specific Familial Risk of Non–Hodgkin's Lymphoma
Authors: Czene Kamila , Adami Hans-Olov , Chang Ellen T. 
Published: November 2007

AbstractA family history of non–Hodgkin's lymphoma (NHL) confers increased risk of NHL, but it is unknown whether the excess risk in males and females varies by the sex or kinship of the affected relative. We linked nationwide Swedish registries to identify parents and siblings of NHL patients who developed NHL between January 1, 1961 and December 31, 2002. In males, parental risks were approximately the same from fathers and mothers, whereas sibling risks were higher from brothers [standardized incidence ratio (SIR), 1.8; 95% confidence interval (95% CI), 1.0-2.9] than sisters (SIR, 0.9; 95% CI, 0.2-1.9). In females, parental and sibling risks were higher from same-sex relatives (SIR from mothers, 1.9; 95% CI, 1.2-2.7; SIR from sisters, 6.3; 95% CI, 4.0-9.3) than from opposite-sex relatives (SIR from fathers, 1.2; 95% CI, 0.7-1.9; SIR from brothers, 0.7; 95% CI, 0.2-1.6). These findings did not vary substantially by the age of diagnosis of the offspring. Risk of NHL in offspring was also increased among those with a parent diagnosed with multiple myeloma or leukemia. The relative risk of NHL among those with a parent diagnosed with any hematopoietic cancer was 1.5 (95% CI, 1.4-1.7) and that for having a sibling with any hematopoietic cancer was also 1.5 (95% CI, 1.2-1.9). Our results suggest that part of the familial risk of NHL may be attributable to shared environmental exposures, particularly between same-sex siblings. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2496–9)
Autoantibody Approach for Serum-Based Detection of Head and Neck Cancer
Authors: Lin Ho-Sheng , Talwar Harvinder S. , Tarca Adi L. , Ionan Alexei , Chatterjee Madhumita , Ye Bin , Wojciechowski Jerzy , Mohapatra Saroj , Basson Marc D. , Yoo George H. , Peshek Brian , Lonardo Fulvio , Pan Chuan-Ju G. , Folbe Adam J. , Draghici Sorin , Abrams Judith , Tainsky Michael A. 
Published: November 2007

AbstractCurrently, no effective tool exists for screening or early diagnosis of head and neck squamous cell carcinoma (HNSCC). Here, we describe an approach for cancer detection based on analysis of patterns of serum immunoreactivity against a panel of biomarkers selected using microarray-based serologic profiling and specialized bioinformatics. We biopanned phage display libraries derived from three different HNSCC tissues to generate 5,133 selectively cloned tumor antigens. Based on their differential immunoreactivity on protein microarrays against serum immunoglobulins from 39 cancer and 41 control patients, we reduced the number of clones to 1,021. The performance of a neural network model (Multilayer Perceptron) for cancer classification on a data set of 80 HNSCC and 78 control samples was assessed using 10-fold cross-validation repeated 100 times. A panel of 130 clones was found to be adequate for building a classifier with sufficient sensitivity and specificity. Using these 130 markers on a completely new and independent set of 80 samples, an accuracy of 84.9% with sensitivity of 79.8% and specificity of 90.1% was achieved. Similar performance was achieved by reshuffling of the data set and by using other classification models. The performance of this classification approach represents a significant improvement over current diagnostic accuracy (sensitivity of 37% to 46% and specificity of 24%) in the primary care setting. The results shown here are promising and show the potential use of this approach toward eventual development of diagnostic assay with sufficient sensitivity and specificity suitable for detection of early-stage HNSCC in high-risk populations. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2396–405)
Intra-individual Variation of Plasma Adipokine Levels and Utility of Single Measurement of These Biomarkers in Population-Based Studies
Authors: Lee Sang-Ah , Kallianpur Asha , Xiang Yong-Bing , Wen Wanqing , Cai Qiuyin , Liu Dake , Fazio Sergio , Linton MacRae F. , Zheng Wei , Shu Xiao Ou 
Published: November 2007

Abstract
Adipokines, soluble mediators produced by adipocytes, may link adipose tissue to the inflammatory, metabolic, and immune dysregulation that characterize many obesity-related diseases. The stability of plasma adipokine levels within individuals, their seasonal variability, intercorrelations, and relationships to well-established measures of adiposity are incompletely defined. We measured levels of 12 adipokines [interleukin 1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), leptin, adiponectin, hepatocyte growth factor (HGF), and resistin] in four seasonal random plasma samples of 48 male participants of a population-based cohort study. The representativeness of single measurements was assessed by correlating the adipokine levels of a single, random sample with the mean levels from the remaining three samples using a bootstrap approach and using intra-class correlation coefficients (ICC). Spearman correlations between adipokine levels, age, body mass index (BMI), and waist-to-hip ratio (WHR) were estimated. Correlations between plasma adipokine levels from one random sample and the mean of the remaining three seasonal samples ranged from 0.57 to 0.89. Over the 1-year study period, the ICCs for adipokine levels ranged from 0.44 (PAI-1) to 0.83 (HGF). IL-8, MCP-1, and resistin levels were positively associated with age; HGF and PAI-1 levels were correlated with BMI and WHR. This study suggests that adipokine levels in a single blood sample may be useful biomarkers of inflammation in population-based studies of obesity-related disease. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2464–70)
Common Genetic Variation in GATA-Binding Protein 3 and Differential Susceptibility to Breast Cancer by Estrogen Receptor α Tumor Status
Authors: Garcia-Closas Montserrat , Troester Melissa A. , Qi Ying , Langerød Anita , Yeager Meredith , Lissowska Jolanta , Brinton Louise , Welch Robert , Peplonska Beata , Gerhard Daniela S. , Gram Inger Torhild , Kristensen Vessela , Børresen-Dale Anne-Lise , Chanock Stephen , Perou Charles M. 
Published: November 2007

Abstract
GATA-binding protein 3 (GATA3) is a transcription factor and a putative tumor suppressor that is highly expressed in normal breast luminal epithelium and estrogen receptor α (ER)–positive breast tumors. We hypothesized that common genetic variation in GATA3 could influence breast carcinogenesis. Four tag single-nucleotide polymorphisms (SNP) in GATA3 and its 3′ flanking gene FLJ4598 were genotyped in two case control studies in Norway and Poland (2,726 cases and 3,420 controls). Analyses of pooled data suggested a reduced risk of breast cancer associated with two intronic variants in GATA3 in linkage disequilibrium (rs3802604 in intron 3 and rs570613 in intron 4). Odds ratio (95% confidence interval) for rs570613 heterozygous and rare homozygous versus common homozygous were 0.85 (0.75-1.95) and 0.82 (0.62-0.96), respectively (Ptrend = 0.004). Stronger associations were observed for subjects with ER-negative, than ER-positive, tumors (Pheterogeneity = 0.01 for rs3802604; Pheterogeneity = 0.09 for rs570613). Although no individual SNPs were associated with ER-positive tumors, two haplotypes (GGTC in 2% of controls and AATT in 7% of controls) showed significant and consistent associations with increased risk for these tumors when compared with the common haplotype (GATT in 46% of controls): 1.71 (1.27-2.32) and 1.26 (1.03-1.54), respectively. In summary, data from two independent study populations showed two intronic variants in GATA3 associated with overall decreases in breast cancer risk and suggested heterogeneity of these associations by ER status. These differential associations are consistent with markedly different levels of GATA3 protein by ER status. Additional epidemiologic studies are needed to clarify these intriguing relationships. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2269–75)
Cholesterol-Lowering Drugs and Prostate Cancer Risk: A Population-based Case-Control Study
Authors: Murtola Teemu J. , Tammela Teuvo L.J. , Lahtela Jorma , Auvinen Anssi 
Published: November 2007

Abstract
Background: Previous studies have shown that statin use may reduce prostate cancer risk. In the current study, we evaluated the association between serum cholesterol–lowering medication use and prostate cancer risk at the population level.
Materials and Methods: All newly diagnosed prostate cancer cases in Finland during 1995 to 2002 and matched controls (24,723 case control pairs) were identified from the Finnish Cancer Registry and the Population Register Center, respectively. Detailed information on cholesterol-lowering drug purchases during the study period was obtained from the prescription database of the Social Insurance Institution of Finland.
Results: After adjustment for potential confounders, having ever-use of any statin was associated with marginally elevated overall prostate cancer risk [odds ratio (OR), 1.07; 95% confidence interval (95% CI), 1.00-1.16]. However, none of the statins was associated with the overall prostate cancer risk when analyzed separately. On the other hand, the risk of advanced prostate cancer was decreased among users of atorvastatin, lovastatin, and simvastatin (OR 0.61, 95% CI 0.37-0.98; OR 0.61, 95% CI 0.43-0.85; and OR 0.78, 95% CI 0.61-1.01, respectively). The risk was not affected among users of other cholesterol drug groups.
Conclusions: Our large population-based study showed no evidence for reduced overall prostate cancer risk among users of cholesterol-lowering drugs, whereas the risk of advanced cancer was decreased among statin users. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2226–32)
Quality of Care Issues in Colorectal Cancer
Authors: Leonardi Michael J. , McGory Marcia L. , Ko Clifford Y. 
Published: November 2007

AbstractColorectal cancer is a common, detectable, and treatable malignancy. Given the aging of the population, the number of patients diagnosed with colorectal cancer will likely increase; thus, efforts to improve the quality and delivery of appropriate care to patients with colorectal cancer are needed. The overarching goal of this article is to summarize recent efforts to evaluate and improve the quality of colorectal cancer care through the use of selective referral, quality performance measures, and assessment of outcomes. First, we provide a framework for quality of care assessment, including a discussion of the structural, process, and outcome components of care for colorectal cancer. Second, we discuss the current level of assessment of colorectal cancer care quality, highlighting four potential targets for quality improvement: increased provider volume for colorectal cancer resection, process-based quality measures for colorectal cancer care (including measures specific to colorectal cancer surgery), data collection and feedback programs for colorectal cancer care, and evaluation of health-related quality of life in patients with colorectal cancer. Further research is needed to evaluate both the implementation and effectiveness of these quality improvement strategies for improving outcome in patients with colorectal cancer.
A Mycoplasma Peptide Elicits Heteroclitic CD4+ T Cell Responses against Tumor Antigen MAGE-A6
Authors: Vujanovic Lazar , Mandic Maja , Olson Walter C. , Kirkwood John M. , Storkus Walter J. 
Published: November 2007

Abstract
Purpose: Although T-helper (Th) epitopes have been previously reported for many tumor antigens, including MAGE-A6, the relevant HLA-DR alleles that present these peptides are expressed by only a minority of patients. The identification of tumor antigenic epitopes presented promiscuously by many HLA-DR alleles would extend the clinical utility of these peptides in vaccines and for the immunomonitoring of cancer patients.
Experimental Design: A neural network algorithm and in vitro sensitization assays were employed to screen candidate peptides for their immunogenicity.
Results: The MAGE-A6140-170, MAGE-A6172-187, and MAGE-A6280-302 epitopes were recognized by CD4+ T cells isolated from the majority of normal donors and melanoma patients evaluated. Peptide-specific CD4+ T cells also recognized autologous antigen-presenting cell pulsed with recombinant MAGE-A6 (rMAGE) protein, supporting the natural processing and MHC presentation of these epitopes. Given the strong primary in vitro sensitization of normal donor CD4+ T cells by the MAGEA6172-187 epitope, suggestive of potential cross-reactivity against an environmental stimulus, we identified a highly homologous peptide within the Mycoplasma penetrans HF-2 permease (MPHF2) protein. MPHF2 peptide–primed CD4+ T cells cross-reacted against autologous APC pulsed with the MAGE-A6172-187 peptide or rMAGE protein and recognized HLA-matched MAGE-A6+ melanoma cell lines. These responses seemed heteroclitic in nature because the functional avidity of MPHF2 peptide-primed CD4+ T cells for the MAGE-A6172-187 peptide was ∼1,000 times greater than that of CD4+ T cells primed with the corresponding MAGE-A6 peptide.
Conclusions: We believe that these novel “promiscuous” MAGE-A6/MPHF2 Th epitopes may prove clinically useful in the treatment and/or monitoring of a high proportion of cancer patients.
The Neural Correlate of Speech Rhythm as Evidenced by Metrical Speech Processing
Authors: Geiser Eveline , Zaehle Tino , Jancke Lutz , Meyer Martin 
Published: November 2007

Abstract
The present study investigates the neural correlates of rhythm processing in speech perception. German pseudosentences spoken with an exaggerated (isochronous) or a conversational (nonisochronous) rhythm were compared in an auditory functional magnetic resonance imaging experiment. The subjects had to perform either a rhythm task (explicit rhythm processing) or a prosody task (implicit rhythm processing). The study revealed bilateral activation in the supplementary motor area (SMA), extending into the cingulate gyrus, and in the insulae, extending into the right basal ganglia (neostriatum), as well as activity in the right inferior frontal gyrus (IFG) related to the performance of the rhythm task. A direct contrast between isochronous and nonisochronous sentences revealed differences in lateralization of activation for isochronous processing as a function of the explicit and implicit tasks. Explicit processing revealed activation in the right posterior superior temporal gyrus (pSTG), the right supramarginal gyrus, and the right parietal operculum. Implicit processing showed activation in the left supramarginal gyrus, the left pSTG, and the left parietal operculum. The present results indicate a function of the SMA and the insula beyond motor timing and speak for a role of these brain areas in the perception of acoustically temporal intervals. Secondly, the data speak for a specific task-related function of the right IFG in the processing of accent patterns. Finally, the data sustain the assumption that the right secondary auditory cortex is involved in the explicit perception of auditory suprasegmental cues and, moreover, that activity in the right secondary auditory cortex can be modulated by top-down processing mechanisms.
Radar and Lightning Observations of the 3 June 2000 Electrically Inverted Storm from STEPS
Authors: Tessendorf Sarah A. , Wiens Kyle C. , Rutledge Steven A. 
Published: November 2007

AbstractThis study addresses the kinematic, microphysical, and electrical evolution of an isolated convective storm observed on 3 June 2000 during the Severe Thunderstorm Electrification and Precipitation Study field campaign. Doppler-derived vertical velocities, radar reflectivity, hydrometeor classifications from polarimetric radar, and Lightning Mapping Array (LMA) charge structures are examined over a nearly 3-h period. This storm, characterized as a low-precipitation supercell, produced modest amounts of hail, determined by fuzzy-logic hydrometeor classification as mostly small (&lt;2 cm) hail, with one surface report of large (≥2 cm) hail. Doppler-derived updraft speeds peaked between 20 and 25 m s−1, and reflectivity was never greater than 60 dBZ. The most striking feature of this storm was its total lack of cloud-to-ground (CG) lightning. Though this storm was electrically active, with maximum flash rates near 30 per minute, no CG flashes of either polarity were detected. The charge structure inferred from the LMA observations was consistent with an inverted dipole, defined as having a midlevel positive charge region below upper-level negative charge. Inverted charge structures have typically been considered conducive to producing positive CG lightning; however, the 3 June storm appeared to lack the lower negative charge layer below the inverted dipole that is thought to provide the downward electrical bias necessary for positive CG lightning.
William Paley's Natural Theology: An Anglican Classic?
Authors: Cole Graham 
Published: November 2007

ABSTRACTThis article pursues the question of whether William Paley's Natural Theology is an Anglican classic. I place Paley's natural theology project in its historical context of skepticism about Christianity's truth claims and in the context of Paley's ‘system’. His teleological argument is briefly explained and four challenges, past and present, to its thesis are considered. The question of what makes a work a classic is explored in terms of its enduring interest, especially in the light of the controversy concerning Intelligent Design Theory, and its enduring value. It is argued that because of its enduring interest and value Paley's Natural Theology may be judged a classic but not of a peculiarly Anglican kind.