bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personal Permanent Hair Dye Use Is Not Associated with Bladder Cancer Risk: Evidence from a Case-Control Study
Authors: Lin Jie , Dinney Colin P. , Grossman H. Barton , Wu Xifeng 
Published: September 2006

Abstract
Whether personal hair dye use is associated with an increased bladder cancer risk has been controversial and there are limited available data addressing this issue. We used a large case-control study of 712 incident bladder cancer cases and 712 age-, gender-, and ethnicity-matched controls to evaluate this association. After adjusting for confounding variables, the use of permanent hair dye was not associated with bladder cancer risk in all subjects [odds ratio (OR), 0.81; 95% confidence interval (95% CI), 0.50-1.30], in women (OR, 0.90; 95% CI, 0.41-1.96), or in men (OR, 0.68; 95% CI, 0.36-1.29). The lack of association was not modified by duration of use, frequency of use, lifetime use, age at first use, or color of use in subsequent stratified analyses. Our data do not support personal hair dye use as an important risk factor for bladder cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1746–9)
Proteomic Profiling Identifies Cyclooxygenase-2-Independent Global Proteomic Changes by Celecoxib in Colorectal Cancer Cells
Authors: Lou Jianrong , Fatima Naheed , Xiao Zhen , Stauffer Stacy , Smythers Gary , Greenwald Peter , Ali Iqbal Unnisa 
Published: September 2006

Abstract
Celecoxib, a selective inhibitor of the enzyme cyclooxygenase-2 (COX-2), has been shown to be a promising chemoprevention agent. The chemopreventive efficacy of celecoxib is believed to be a consequence of its COX-2-dependent and COX-2-independent effects on a variety of cellular processes including proliferation, apoptosis, angiogenesis, and immunosurveillance. In an attempt to identify proteomic markers modulated by celecoxib that are independent of its inhibitory effect on COX-2, the colorectal cancer cell line HCT-116, a nonexpresser of COX-2, was treated with celecoxib. We used the powerful, state-of-the-art two-dimensional difference gel electrophoresis technology coupled with mass spectrometric sequencing to compare global proteomic profiles of HCT-116 cells before and after treatment with celecoxib. Among the differentially expressed proteins identified following celecoxib treatment were proteins involved in diverse cellular functions including glycolysis, protein biosynthesis, DNA synthesis, mRNA processing, protein folding, phosphorylation, redox regulation, and molecular chaperon activities. Our study presents a comprehensive analysis of large-scale celecoxib-modulated proteomic alterations, at least some of which may be mechanistically related to the COX-2-independent chemopreventive effect of celecoxib. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1598–606)
Association of Polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 Genes with Levels of DNA Damage in Peripheral Blood Lymphocytes among Coke-Oven Workers
Authors: Chen Yongwen , Bai Yun , Yuan Jing , Chen Weihong , Sun Jianya , Wang Hong , Liang Huashan , Guo Liang , Yang Xiaobo , Tan Hao , Su Yougong , Wei Qingyi , Wu Tangchun 
Published: September 2006

Abstract
Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non–coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. We found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group (P &lt; 0.001). Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys554 variant genotype were higher than those with the AhR Arg554/Arg554 genotype (P = 0.021). Similarly, the Olive TM values in the non–coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype (P = 0.005). However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1703–7)
Approaches to DNA/RNA Extraction and Whole Genome Amplification
Authors: Santella Regina M. 
Published: September 2006

AbstractAnalysis of DNA and/or RNA is an important component of most epidemiologic studies. The methods used for their preparation vary depending on the number of samples in the study as well as the amount of tissue or cells available, the specific downstream assay, and the resources available. They range from classic phenol/chloroform extractions to robotic methods suitable for large-scale studies. Several methods are also available for the quantitation of DNA/RNA, including UV or fluorescence measurements and PCR. For DNA samples of limited quantity, it is also now possible to use whole genome amplification to increase the amount of DNA suitable for genotyping. Finally, a major issue in quality control is the careful labeling and handling of samples. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1585–7)
Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells
Authors: García-Morales Pilar , Hernando Eva , Carrasco-García Estefanía , Menéndez-Gutierrez María Piedad , Saceda Miguel , Martínez-Lacaci Isabel 
Published: September 2006

Abstract
Rapamycin and its analogues are being tested as new antitumor agents. Rapamycin binds to FKBP-12 and this complex inhibits the activity of FRAP/mammalian target of rapamycin, which leads to dephosphorylation of 4EBP1 and p70 S6 kinase, resulting in blockade of translation initiation. We have found that RAP inhibits the growth of HER-2-overexpressing breast cancer cells. The phosphorylation of mammalian target of rapamycin, p70 S6 kinase, and 4EBP1 is inhibited by rapamycin and cells are arrested in the G1 phase, as determined by growth assays, fluorescence-activated cell sorting analysis, and bromodeoxyuridine incorporation studies. Rapamycin causes down-regulation of cyclin D3 protein, retinoblastoma hypophosphorylation, loss of cyclin-dependent kinase (cdk) 4, cdk6, and cdk2 activity. The half-life of cyclin D3 protein decreases after rapamycin treatment, but not its synthesis, whereas the synthesis or half-life of cyclin D1 protein is not affected by the drug. Additionally, rapamycin caused accumulation of ubiquitinated forms of cyclin D3 protein, proteasome inhibitors blocked the effect of rapamycin on cyclin D3, and rapamycin stimulated the activity of the proteasome, showing that the effect of rapamycin on cyclin D3 is proteasome proteolysis dependent. This effect depends on the activity of HER-2 because Herceptin, a neutralizing antibody against HER-2, is able to block both the induction of proteasome activity and the cyclin D3 down-regulation due to rapamycin. Furthermore, inhibition of HER-2 gene expression by using small interfering RNA blocked the rapamycin effects on cyclin D3. These data indicate that rapamycin causes a G1 arrest in HER-2-overexpressing breast cancer cells that is associated with a differential destabilization and subsequent down-regulation of cyclin D3 protein. [Mol Cancer Ther 2006;5(9):2172–81]
Genetic alterations associated with acquired temozolomide resistance in SNB-19, a human glioma cell line
Authors: Auger Nathalie , Thillet Joëlle , Wanherdrick Krystell , Idbaih Ahmed , Legrier Marie-Emmanuelle , Dutrillaux Bernard , Sanson Marc , Poupon Marie-France 
Published: September 2006

AbstractGliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss of mismatch repair capacity. However, very few gliomas overexpress O6-methylguanine-DNA methyltransferase or are mismatch repair–deficient, suggesting that other mechanisms may be involved in the resistance to temozolomide. The purpose of the present study was to generate temozolomide-resistant variants from a human glioma cell line (SNB-19) and to use large-scale genomic and transcriptional analyses to study the molecular basis of acquired temozolomide resistance. Two independently obtained temozolomide-resistant variants exhibited no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1-nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p region and loss of amplification of chromosome 4 and 16q regions. The karyotypic alterations were compatible with clonal selection of preexistent resistant cells in the parental SNB-19 cell line. Microarray analysis showed that 78 out of 17,000 genes were differentially expressed between parental cells and both temozolomide-resistant variants. None are implicated in known resistance mechanisms, such as DNA repair, whereas interestingly, several genes involved in differentiation were down-regulated. The data suggest that the acquisition of resistance to temozolomide in this model resulted from the selection of less differentiated preexistent resistant cells in the parental tumor. [Mol Cancer Ther 2006;5(9):2182–92]
Nuclear factor-κB maintains TRAIL resistance in human pancreatic cancer cells
Authors: Khanbolooki Sanaz , Nawrocki Steffan T. , Arumugam Thiruvengadam , Andtbacka Robert , Pino Maria S. , Kurzrock Razelle , Logsdon Craig D. , Abbruzzese James L. , McConkey David J. 
Published: September 2006

AbstractAlthough it displays promising activity in other tumor models, the effects of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) on human pancreatic cancer cells have not been comprehensively explored. We report that a majority of human pancreatic cancer cell lines (seven of nine) underwent apoptosis when they were exposed to recombinant human TRAIL in vitro. Characterization of surface TRAIL receptors by fluorescence-activated cell sorting showed that TRAIL-resistant cells (Panc-1 and HS766T) expressed lower levels of DR4 and DR5 than did TRAIL-sensitive cells. The proteasome inhibitor bortezomib (PS-341, Velcade) further increased TRAIL responsiveness in the TRAIL-sensitive cells and synergized with TRAIL to reverse resistance in Panc-1 and HS776T cells. The effects of bortezomib were mimicked by transfection with a small interfering RNA construct specific for the p65 subunit of nuclear factor-κB (NF-κB) or exposure to a selective chemical inhibitor of IKK (PS-1145). Silencing IκBα prevented TRAIL sensitization by PS-1145, confirming that IκBα mediated the effects of PS-1145. NF-κB inhibition resulted in down-regulation of BCL-XL and XIAP, and silencing either restored TRAIL sensitivity in TRAIL-resistant cells. Finally, therapy with TRAIL plus PS-1145 reversed TRAIL resistance in vivo to produce synergistic growth inhibition in orthotopic Panc-1 tumors. Together, our results show that NF-κB inhibits TRAIL-induced apoptosis in human pancreatic cancer cells and suggest that combination therapy with TRAIL and NF-κB inhibitors, such as bortezomib, PS-1145, or curcumin, should be considered as a possible treatment strategy in patients with pancreatic cancer. [Mol Cancer Ther 2006;5(9):2251–60]
Role of Store-Operated Calcium Channels and Calcium Sensitization in Normoxic Contraction of the Ductus Arteriosus
Authors: Hong Zhigang , Hong Fangxiao , Olschewski Andrea , Cabrera Jesus A. , Varghese Anthony , Nelson Daniel P. , Weir E. Kenneth 
Published: September 2006

Background—At birth, the increase in oxygen causes contraction of the ductus arteriosus, thus diverting blood flow to the lungs. Although this contraction is modulated by substances such as endothelin and dilator prostaglandins, normoxic contraction is an intrinsic property of ductus smooth muscle. Normoxic inhibition of potassium channels causes membrane depolarization and calcium entry through L-type calcium channels. However, the studies reported here show that after inhibition of this pathway there is still substantial normoxic contraction, indicating the involvement of additional mechanisms.Methods and Results—Using ductus ring experiments, calcium imaging, reverse-transcription polymerase chain reaction, Western blot, and cellular electrophysiology, we find that this depolarization-independent contraction is caused by release of calcium from the IP3-sensitive store in the sarcoplasmic reticulum, by subsequent calcium entry through store-operated channels, and by increased calcium sensitization of actin-myosin filaments, involving Rho-kinase.Conclusions—Much of the normoxic contraction of the ductus arteriosus at birth is related to calcium entry through store-operated channels, encoded by the transient receptor potential superfamily of genes, and to increased calcium sensitization. A clearer understanding of the mechanisms involved in normoxic contraction of the ductus will permit the development of better therapy to close the patent ductus arteriosus, which constitutes ≈10% of all congenital heart disease and is especially common in premature infants.
VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors
Authors: Dasgupta Suryasarathi , Repessé Yohann , Bayry Jagadeesh , Navarrete Ana-Maria , Wootla Bharath , Delignat Sandrine , Irinopoulou Theano , Kamaté Caroline , Saint-Remy Jean-Marie , Jacquemin Marc , Lenting Peter J. , Borel-Derlon Annie , Kaveri Srinivas V. , Lacroix-Desmazes Sébastien 
Published: September 2006

Abstract
Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in patients with hemophilia A has been evoked but lacks clear cellular and molecular rationale. Here, we demonstrate that VWF protects FVIII from being endocytosed by human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells. The immunoprotective effect of VWF requires a physical interaction with FVIII because the endocytosis of FVIII was significantly restored on hindering the formation of the VWF-FVIII complex. Interestingly, VWF had no direct inhibitory effect either on the ability of DCs to present antigenic peptides or on the activation potency of CD4+ T cells. We thus propose that VWF may reduce the immunogenicity of FVIII by preventing, upstream from the activation of immune effectors, the entry of FVIII in professional antigen-presenting cells.
Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline
Authors: Lee Dong-Won , Shirley Shawna A , Lockey Richard F , Mohapatra Shyam S 
Published: September 2006

Abstract

Background
Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects.

Objectives
We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma.

Methods
A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline.

Results
Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs.

Conclusion
Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system.
Tuberculosis chemotherapy: current drug delivery approaches
Authors: du Toit Lisa Claire , Pillay Viness , Danckwerts Michael Paul 
Published: September 2006

Abstract
Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance.
Searching for interpretable rules for disease mutations: a simulated annealing bump hunting strategy
Authors: Jiang Rui , Yang Hua , Sun Fengzhu , Chen Ting 
Published: September 2006

AbstractBackgroundUnderstanding how amino acid substitutions affect protein functions is critical for the study of proteins and their implications in diseases. Although methods have been developed for predicting potential effects of amino acid substitutions using sequence, three-dimensional structural, and evolutionary properties of proteins, the applications are limited by the complication of the features and the availability of protein structural information. Another limitation is that the prediction results are hard to be interpreted with physicochemical principles and biological knowledge.ResultsTo overcome these limitations, we proposed a novel feature set using physicochemical properties of amino acids, evolutionary profiles of proteins, and protein sequence information. We applied the support vector machine and the random forest with the feature set to experimental amino acid substitutions occurring in theE. colilac repressor and the bacteriophage T4 lysozyme, as well as to annotated amino acid substitutions occurring in a wide range of human proteins. The results showed that the proposed feature set was superior to the existing ones. To explore physicochemical principles behind amino acid substitutions, we designed a simulated annealing bump hunting strategy to automatically extract interpretable rules for amino acid substitutions. We applied the strategy to annotated human amino acid substitutions and successfully extracted several rules which were either consistent with current biological knowledge or providing new insights for the understanding of amino acid substitutions. When applied to unclassified data, these rules could cover a large portion of samples, and most of the covered samples showed good agreement with predictions made by either the support vector machine or the random forest.ConclusionThe prediction methods using the proposed feature set can achieve larger AUC (the area under the ROC curve), smaller BER (the balanced error rate), and larger MCC (the Matthews' correlation coefficient) than those using the published feature sets, suggesting that our feature set is superior to the existing ones. The rules extracted by the simulated annealing bump hunting strategy have comparable coverage and accuracy but much better interpretability as those extracted by the patient rule induction method (PRIM), revealing that the strategy is more effective in inducing interpretable rules.
Sex-specific expression of alternative transcripts in Drosophila
Authors: McIntyre Lauren M , Bono Lisa M , Genissel Anne , Westerman Rick , Junk Damion , Telonis-Scott Marina , Harshman Larry , Wayne Marta L , Kopp Artyom , Nuzhdin Sergey V 
Published: September 2006

Abstract
Background
Many genes produce multiple transcripts due to alternative splicing or utilization of alternative transcription initiation/termination sites. This 'transcriptome expansion' is thought to increase phenotypic complexity by allowing a single locus to produce several functionally distinct proteins. However, sex, genetic and developmental variation in the representation of alternative transcripts has never been examined systematically. Here, we describe a genome-wide analysis of sex-specific expression of alternative transcripts in Drosophila melanogaster.

Results
We compared transcript profiles in males and females from eight Drosophila lines (OregonR and 2b, and 6 RIL) using a newly designed 60-mer oligonucleotide microarray that allows us to distinguish a large proportion of alternative transcripts. The new microarray incorporates 7,207 oligonucleotides, satisfying stringent binding and specificity criteria that target both the common and the unique regions of 2,768 multi-transcript genes, as well as 12,912 oligonucleotides that target genes with a single known transcript. We estimate that up to 22% of genes that produce multiple transcripts show a sex-specific bias in the representation of alternative transcripts. Sexual dimorphism in overall transcript abundance was evident for 53% of genes. The X chromosome contains a significantly higher proportion of genes with female-biased transcription than the autosomes. However, genes on the X chromosome are no more likely to have a sexual bias in alternative transcript representation than autosomal genes.

Conclusion
Widespread sex-specific expression of alternative transcripts in Drosophila suggests that a new level of sexual dimorphism at the molecular level exists.