bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project
Authors: Grisoni Marie-Lise , Proust Carole , Alanne Mervi , DeSuremain Maylis , Salomaa Veikko , Kuulasmaa Kari , Cambien François , Nicaud Viviane , Wiklund Per-Gunnar , Virtamo Jarmo , Kee Frank , Tiret Laurence , Evans Alun , Tregouet David-Alexandre 
Published: May 2009

AbstractBackgroundInterleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of theIL18gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes,IL18R1andIL18RAP, with the risk of developing CVD.MethodsEleven tagging SNPs, 5 inIL18R1and 6 inIL18RAP, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD.ResultsWe did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5IL18SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful.ConclusionOur analysis suggests that the variability ofIL18R1andIL18RAPgenes are unlikely to contribute to modulate the risk of CVD.
Biochemical typing of pathological prion protein in aging cattle with BSE
Authors: Tester Seraina , Juillerat Valerie , Doherr Marcus G , Haase Bianca , Polak Miroslaw , Ehrensperger Felix , Leeb Tosso , Zurbriggen Andreas , Seuberlich Torsten 
Published: May 2009

AbstractBackgroundThe broad enforcement of active surveillance for bovine spongiform encephalopathy (BSE) in 2000 led to the discovery of previously unnoticed, atypical BSE phenotypes in aged cattle that differed from classical BSE (C-type) in biochemical properties of the pathological prion protein. Depending on the molecular mass and the degree of glycosylation of its proteinase K resistant core fragment (PrPres), mainly determined in samples derived from the medulla oblongata, these atypical cases are currently classified into low (L)-type or high (H)-type BSE. In the present study we address the question to what extent such atypical BSE cases are part of the BSE epidemic in Switzerland.ResultsTo this end we analyzed the biochemical PrPrestype by Western blot in a total of 33 BSE cases in cattle with a minimum age of eight years, targeting up to ten different brain regions. Our work confirmed H-type BSE in a zebu but classified all other cases as C-type BSE; indicating a very low incidence of H- and L-type BSE in Switzerland. It was documented for the first time that the biochemical PrPrestype was consistent across different brain regions of aging animals with C-type and H-type BSE, i.e. independent of the neuroanatomical structure investigated.ConclusionTaken together this study provides further characteristics of the BSE epidemic in Switzerland and generates new baseline data for the definition of C- and H-type BSE phenotypes, thereby underpinning the notion that they indeed represent distinct prion disease entities.
Biofilm forming abilities of Salmonellaare correlated with persistence in fish meal- and feed factories
Authors: Vestby Lene K , Møretrø Trond , Langsrud Solveig , Heir Even , Nesse Live L 
Published: May 2009

Abstract

Background
Feed contaminated with Salmonella spp. constitutes a risk of Salmonella infections in animals, and subsequently in the consumers of animal products. Salmonella are occasionally isolated from the feed factory environment and some clones of Salmonella persist in the factory environment for several years. One hypothesis is that biofilm formation facilitates persistence by protecting bacteria against environmental stress, e.g. disinfection. The aim of this study was to investigate the biofilm forming potential of Salmonella strains from feed- and fishmeal factories. The study included 111 Salmonella strains isolated from Norwegian feed and fish meal factories in the period 1991–2006 of serovar Agona, serovar Montevideo, serovar Senftenberg and serovar Typhimurium.

Results
Significant differences were found between serovars regarding the abilities to form biofilm on polystyrene (microtiter plate assay) and in the air-liquid interface of nutrient broth (pellicle assay). Strains of serovar Agona and serovar Montevideo were good biofilm producers. In Norwegian factories, clones of these serovars have been observed to persist for several years. Most serovar Senftenberg clones appear to persist for a shorter period, and strains of this serovar were medium biofilm producers in our test systems. Strains of the serovar Typhimurium were relatively poor biofilm producers. Salmonella ser. Typhimurium clones have not been observed to persist even though this serovar is resident in Norwegian wild life. When classifying strains according to persistence or presumed non-persistence, persistent strains produced more biofilm than presumed non-persisting strains.

Conclusion
The results indicate a correlation between persistence and biofilm formation which suggests that biofilm forming ability may be an important factor for persistence of Salmonella in the factory environment.
Unraveling the disease pathogenesis behind lethal hydrolethalus syndrome revealed multiple changes in molecular and cellular level
Authors: Honkala Heli , Lahtela Jenni , Fox Heli , Gentile Massimiliano , Pakkasjärvi Niklas , Salonen Riitta , Wartiovaara Kirmo , Jauhiainen Matti , Kestilä Marjo 
Published: May 2009

AbstractBackgroundHydrolethalus syndrome (HLS) is a severe fetal malformation syndrome characterized by multiple developmental anomalies, including central nervous system (CNS) malformation such as hydrocephaly and absent midline structures of the brain, micrognathia, defective lobation of the lungs and polydactyly. Microscopically, immature cerebral cortex, abnormalities in radial glial cells and hypothalamic hamartoma are among key findings in the CNS of HLS fetuses. HLS is caused by a substitution of aspartic acid by glycine in the HYLS1 protein, whose function was previously unknown.ResultsTo provide insight into the disease mechanism(s) of this lethal disorder we have studied different aspects of HLS and HYLS1. A genome-wide gene expression analysis indicated several upregulated genes in cell cycle regulatory cascades and in specific signal transduction pathways while many downregulated genes were associated with lipid metabolism. These changes were supported by findings in functional cell biology studies, which revealed an increased cell cycle rate and a decreased amount of apoptosis in HLS neuronal progenitor cells. Also, changes in lipid metabolism gene expression were reflected by a significant increase in the cholesterol levels of HLS liver tissues. In addition, based on our functional studies of HYLS1, we propose that HYLS1 is a transcriptional regulator that shuffles between the cytoplasm and the nucleus, and that when HYLS1 is mutated its function is significantly altered.ConclusionIn this study, we have shown that theHYLS1mutation has significant consequences in the cellular and tissue levels in HLS fetuses. Based on these results, it can be suggested that HYLS1 is part of the cellular transcriptional regulatory machinery and that the genetic defect has a widespread effect during embryonic and fetal development. These findings add a significant amount of new information to the pathogenesis of HLS and strongly suggest an essential role for HYLS1 in normal fetal development.
Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies
Authors: Miceli-Richard Corinne , Gestermann Nicolas , Amiel Corinne , Sellam Jérémie , Ittah Marc , Pavy Stephan , Urrutia Alejandra , Girauld Isabelle , Carcelain Guislaine , Venet Alain , Mariette Xavier 
Published: May 2009

Abstract
Introduction
There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy.

Methods
Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNγ-producing T cells in response to EBV latent-cycle and lytic-cycle peptides.

Results
The EBV load and the number of IFNγ-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution.

Conclusions
These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.
WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth
Authors: Matsuda Yutaka , Schlange Thomas , Oakeley Edward J , Boulay Anne , Hynes Nancy E 
Published: May 2009

Abstract
Introduction
In breast cancer, deregulation of the WNT signaling pathway occurs by autocrine mechanisms. WNT ligands and Frizzled receptors are coexpressed in primary breast tumors and cancer cell lines. Moreover, many breast tumors show hypermethylation of the secreted Frizzled-related protein 1 (sFRP1) promoter region, causing low expression of this WNT antagonist. We have previously shown that the WNT pathway influences proliferation of breast cancer cell lines via activation of canonical signaling and epidermal growth factor receptor transactivation, and that interference with WNT signaling reduces proliferation. Here we examine the role of WNT signaling in breast tumor cell migration and on xenograft outgrowth.

Methods
The breast cancer cell line MDA-MB-231 was used to study WNT signaling. We examined the effects of activating or blocking the WNT pathway on cell motility by treatment with WNT ligands or by ectopic sFPR1 expression, respectively. The ability of sFRP1-expressing MDA-MB-231 cells to grow as xenografts was also tested. Microarray analyses were carried out to identify targets with roles in MDA-MB-231/sFRP1 tumor growth inhibition.

Results
We show that WNT stimulates the migratory ability of MDA-MB-231 cells. Furthermore, ectopic expression of sFRP1 in MDA-MB-231 cells blocks canonical WNT signaling and decreases their migratory potential. Moreover, the ability of MDA-MB-231/sFRP1-expressing cells to grow as xenografts in mammary glands and to form lung metastases is dramatically impaired. Microarray analyses led to the identification of two genes, CCND1 and CDKN1A, whose expression level is selectively altered in vivo in sFRP1-expressing tumors. The encoded proteins cyclin D1 and p21Cip1 were downregulated and upregulated, respectively, in sFRP1-expressing tumors, suggesting that they are downstream mediators of WNT signaling.

Conclusions
Our results show that the WNT pathway influences multiple biological properties of MDA-MB-231 breast cancer cells. WNT stimulates tumor cell motility; conversely sFRP1-mediated WNT pathway blockade reduces motility. Moreover, ectopic sFRP1 expression in MDA-MB-231 cells has a strong negative impact on tumor outgrowth and blocked lung metastases. These results suggest that interference with WNT signaling using sFRP1 to block the ligand- receptor interaction may be a valid therapeutic approach in breast cancer.
Significantly Longer Progression-Free Survival With nab-Paclitaxel Compared With Docetaxel As First-Line Therapy for Metastatic Breast Cancer
Authors: Gradishar William J. , Krasnojon Dimitry , Cheporov Sergey , Makhson Anatoly N. , Manikhas Georgiy M. , Clawson Alicia , Bhar Paul 
Published: May 2009

Purpose In patients with metastatic breast cancer (MBC), nab-paclitaxel produced significantly higher antitumor activity compared with patients who received solvent-based paclitaxel. This phase II study examined the antitumor activity and safety of weekly and every 3 week (q3w) nab-paclitaxel compared with docetaxel as first-line treatment in patients with MBC. Patients and Methods In this randomized, multicenter study, patients (N = 302) with previously untreated MBC received nab-paclitaxel 300 mg/m2 q3w, 100 mg/m2 weekly, or 150 mg/m2 weekly or docetaxel 100 mg/m2 q3w. Results nab-Paclitaxel 150 mg/m2 weekly demonstrated significantly longer progression-free survival (PFS) than docetaxel by both independent radiologist assessment (12.9 v 7.5 months, respectively; P = .0065) and investigator assessment (14.6 v 7.8 months, respectively; P = .012). On the basis of independent radiologist review, both 150 mg/m2 (49%) and 100 mg/m2 (45%) weekly of nab-paclitaxel demonstrated a higher overall response rate (ORR) than docetaxel (35%), but this did not reach statistical significance. This trend was supported by statistically significant investigator ORR for both weekly nab-paclitaxel doses versus docetaxel. nab-Paclitaxel q3w versus docetaxel was not different for PFS or ORR. On the basis of both the independent radiologist and investigator review, disease control rate was significantly higher for patients receiving either dose of weekly nab-paclitaxel compared with docetaxel. Grade 3 or 4 fatigue, neutropenia, and febrile neutropenia were less frequent in all nab-paclitaxel arms. The frequency and grade of peripheral neuropathy were similar in all arms. Conclusion This randomized study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel, with a statistically and clinically significant prolongation of PFS (> 5 months) in patients receiving nab-paclitaxel 150 mg/m2 weekly compared with docetaxel 100 mg/m2 q3w.
Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients
Authors: Pierce Brandon L. , Ballard-Barbash Rachel , Bernstein Leslie , Baumgartner Richard N. , Neuhouser Marian L. , Wener Mark H. , Baumgartner Kathy B. , Gilliland Frank D. , Sorensen Bess E. , McTiernan Anne , Ulrich Cornelia M. 
Published: May 2009

Purpose Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival. Patients and Methods We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs. Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07). Conclusion Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.
Duration of Chemotherapy for Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Soon Yu Yang , Stockler Martin R. , Askie Lisa M. , Boyer Michael J. 
Published: May 2009

Purpose To determine if it is preferable to extend chemotherapy beyond a standard number of cycles in patients receiving first-line chemotherapy for advanced non–small-cell lung cancer. Methods We searched biomedical literature databases and conference proceedings for randomized controlled trials (RCTs) comparing a defined number of cycles with continuation of the same chemotherapy until disease progression, a larger defined number of cycles of identical chemotherapy, and a defined number of cycles of identical initial chemotherapy followed by additional cycles of an alternative chemotherapy. Meta-analysis was performed using the fixed effect model. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), adverse events (AE), and health-related quality of life (HRQL). Results We found 13 RCTs including 3,027 patients. Extending chemotherapy improved PFS substantially (hazard ratio [HR], 0.75; 95% CI, 0.69 to 0.81; P < .00001) and OS modestly (HR, 0.92; 95% CI, 0.86 to 0.99; P = .03). Subgroup analysis revealed that effects on PFS were greater for trials extending chemotherapy with third-generation regimens rather than older regimens (HR, 0.70 interaction v 0.92 interaction; P = .003). Extending chemotherapy was associated with more frequent AE in all trials where it was reported and impaired HRQL in two of seven trials. Conclusion Extending chemotherapy, particularly with a third-generation regimen, improved PFS substantially, but OS less so. Future trials should test extending treatment with more effective and/or better-tolerated agents.
Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy
Authors: Kopetz Scott , Chang George J. , Overman Michael J. , Eng Cathy , Sargent Daniel J. , Larson David W. , Grothey Axel , Vauthey Jean-Nicolas , Nagorney David M. , McWilliams Robert R. 
Published: May 2009

Purpose Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified. Methods We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005. Results Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period. Conclusion Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006).
Insurance Status, Comorbidity Level, and Survival Among Colorectal Cancer Patients Age 18 to 64 Years in the National Cancer Data Base From 2003 to 2005
Authors: Robbins Anthony S. , Pavluck Alexandre L. , Fedewa Stacey A. , Chen Amy Y. , Ward Elizabeth M. 
Published: May 2009

Purpose Previous analyses have found that insurance status is a strong predictor of survival among patients with colorectal cancer aged 18 to 64 years. We investigated whether differences in comorbidity level may account in part for the association between insurance status and survival. Methods We used 2003 to 2005 data from the National Cancer Data Base, a national hospital-based cancer registry, to examine the relationship between baseline characteristics and overall survival at 1 year among 64,304 white and black patients with colorectal cancer. In race-specific analyses, we used Cox proportional hazards models to assess 1-year survival by insurance status, controlling first for age, stage, facility type, and neighborhood education level and income, and then further controlling for comorbidity level. Results Comorbidity level was lowest among those with private insurance, higher for those who were uninsured or insured by Medicaid, and highest for those insured by Medicare. Survival at 1 year was significantly poorer for patients without private insurance, even after adjusting for important covariates. In these multivariate models, risk of death at 1 year was approximately 50% to 90% higher for white and black patients without private insurance. Further adjustment for number of comorbidities had only a modest impact on the association between insurance status and survival. In multivariate analyses, patients with ≥ three comorbid conditions had approximately 40% to 50% higher risk of death at 1 year. Conclusion Among white and black patients aged 18 to 64 years, differences in comorbidity level do not account for the association between insurance status and survival in patients with colorectal cancer.