bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target
Authors: Spanjaard Remco A. , Whren Kara M. , Graves Carole , Bhawan Jag 
Published: December 2006

AbstractIncidence of melanoma continues to rise, and a better understanding of its genetics will be critical to improve diagnosis and develop new treatments. Here, we search for novel melanoma‐specific genes that may serve as biomarkers and therapeutic targets by using an in vitro genetic screen. One identified cDNA encoded TROY, a member of the tumor necrosis factor receptor superfamily (TNFRSF). TROY is widely expressed during embryogenesis, but in adults expression is restricted to hair follicles and brain. However, TROY had never been associated with melanoma, and it was selected for further study. First we show that expression in melanoma is specific by semiquantitative RT‐PCR analysis of a large panel of established tumor cell lines. Next, specificity of expression was evaluated by immunohistochemistry analysis of primary cell cultures and patient tissues. TROY is expressed in 2/2 primary melanoma cells and 45/45 melanoma tissue samples (p < 0.0001). With the exception of sebaceous glands, TROY is not expressed in normal skin biopsies (p < 0.0001) or primary skin cell cultures that contain keratinocytes and epidermal melanocytes, nor is it expressed in other skin tumor cells (p < 0.0001). Finally, we show that TROY regulates melanoma growth, because replication of melanoma cells with reduced TROY levels through treatment with short‐interfering RNA was significantly decreased relative to control cells (p < 0.004). In summary, TROY is the first TNFRSF member that is a biomarker for melanoma. TROY also presents a potentially novel cell surface signaling target for inhibitors, cell and/or antibody‐based immunotherapies. © 2006 Wiley‐Liss, Inc.
Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population
Authors: Jin Guangfu , Wang Lina , Chen Wensen , Hu Zhibin , Zhou Yan , Tan Yongfei , Wang Jianming , Hua Zhaolai , Ding Weiliang , Shen Jing , Zhang Zuofeng , Wang Xinru , Xu Yaochu , Shen Hongbing 
Published: December 2006

AbstractGrowing evidence suggests that the transforming growth factor β (TGF‐β) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGF‐β1 and its receptor TGF‐βRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C‐509T and Leu10Pro polymorphisms in TGFB1 and G‐875A variant in TGFBR2, using the primer‐introduced restriction analysis (PIRA)‐PCR assay, in a case–control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C‐509T and TGFBR2 G‐875A, were associated with a significantly decreased risk of gastriccancer [adjusted odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52–0.82 for −509CT/TT and adjusted OR = 0.67, 95% CI = 0.53–0.85 for −875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C‐509T and TGFBR2 G‐875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR = 0.44, 95% CI = 0.32–0.62). These findings indicate, for the first‐time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. © 2006 Wiley‐Liss, Inc.
Fibrinolytic properties of lysine‐derivatized polyethylene in contact with flowing whole blood (Chandler loop model)
Authors: McClung W.G. , Babcock D.E. , Brash J.L. 
Published: December 2006

AbstractThis article reports on the concept of a fibrinolytic surface based on the preferential adsorption of endogenous plasminogen from blood. Data are presented indicating that such a surface, when pretreated with tissue‐type plasminogen activator (tPA), is able to dissolve nascent thrombus generated in contact with flowing whole blood. Polyethylene (PE) surfaces were modified by attaching a lysine‐containing polymer using photochemical methods as reported previously (McClung et al., J Biomed Mater Res 2000;49:409–414). The lysine residues were bound chemically to the polymer via the α‐amino groups leaving the ε‐amino groups free (ε‐Lys surface). Control surfaces were (a) unmodified PE, (b) PE modified with the coating polymer containing no lysine, and (c) PE modified with the polymer containing lysine bound via the ε‐amino group. The materials in tubing form were evaluated in contact with nonanticoagulated flowing human whole blood in a modified Chandler Loop experiment. They were first treated with tPA to allow activation of adsorbed plasminogen to plasmin. It was found that thrombus formation was initiated within 15–25 min (depending on donor blood) on all surfaces, as indicated by the formation of platelet aggregates. On the controls (including the lysine‐containing material in which the ε‐amino group was used in the binding reaction) thrombogenesis continued till the tubing was occluded and blood flow ceased. On the ε‐Lys surface, thrombogenesis was interrupted at various stages depending on the donor blood; in all cases any thrombus generated was dissolved within minutes. It was shown that thrombolysis was due to the fibrinolytic action of plasmin generated at the surface and not to plasmin formed by traces of tPA released into the blood. This work provides further evidence of the efficacy of this approach to the development of a fibrinolytic surface. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A:, 2007
Thermo‐responsive poly(NiPAAm‐co‐DEGMA) substrates for gentle harvest of human corneal endothelial cell sheets
Authors: Nitschke Mirko , Gramm Stefan , Götze Thomas , Valtink Monika , Drichel Juliane , Voit Brigitte , Engelmann Katrin , Werner Carsten 
Published: December 2006

AbstractGentle harvesting of corneal endothelial cell sheets grown in culture is of interest for the development of cornea replacement strategies. Thin films of a fast responding copolymer of N‐isopropylacrylamide (NiPAAm) and diethyleneglycol methacrylate (DEGMA) with a phase transition temperature of 32°C were prepared and evaluated for that purpose. The polymer layers were immobilized onto fluorocarbon substrates using low pressure argon plasma treatment. Cell culture and detachment experiments were performed with L929 mouse fibroblasts and human corneal endothelial cells (HCEC) at standard conditions. The hydrogel‐coated supports were found to permit adhesion, spreading, and proliferation of both cell types. Harvesting of cell sheets was achieved upon lowering the temperature to about 30°C. The formation of a closed monolayer as a crucial prerequisite for maintaining ionic pump function in HCEC was proven by ZO‐1 immunostainung. Labeling of fibronectin indicated that the vast majority of the extracellular matrix is detached from the hydrogel coatings together with the cell layer. Inspired by this result, the reuse of the hydrogel‐coated culture carriers was investigated confirming the suitability of the substrates for repeated cell harvesting. Altogether, the introduced thermoresponsive coating was found advantageous for the efficient generation of HCEC sheets and will be further utilized in transplantation strategies. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A:, 2007
Continuous requirement for pp60‐Src and phospho‐paxillin during fibronectin matrix assembly by transformed cells
Authors: Wierzbicka‐Patynowski Iwona , Mao Yong , Schwarzbauer Jean E. 
Published: December 2006

AbstractFibronectin (FN) matrix assembly is an integrin‐mediated process that is regulated by both the extracellular environment and intracellular signaling pathways. The activity of Src‐family kinases is important for initiation of FN assembly by normal fibroblasts. Here we report that in HT1080 fibrosarcoma cells, Src kinase activity is required not only for the assembly of FN matrix but also for the maintenance of FN matrix fibrils at the cell surface. Dexamethasone‐induced FN fibril formation by these cells was completely blocked for at least 24 h when Src‐family kinase activity was inhibited by either PP1 or SU6656. Inhibition of Src after significant matrix had already been assembled, resulted in an increased rate of loss of detergent‐insoluble FN. Binding of activation‐dependent integrin antibodies reveals a role for Src in maintaining integrin activity. The requirement for Src kinase activity appears to depend, in part, on phosphorylation of paxillin at tyrosine 118 (Y118). Phospho‐paxillin co‐localized with FN fibrils, and overexpression of GFP‐paxillin but not of GFP‐paxillinY118F enhanced cell‐mediated assembly of FN. Our results indicate that Src maintains FN matrix at the cell surface through its effect on integrin activity and paxillin phosphorylation. J. Cell. Physiol. 210: 750–756, 2007. © 2006 Wiley‐Liss, Inc.
Pathwidth of outerplanar graphs
Authors: Coudert David , Huc Florian , Sereni Jean‐Sébastien 
Published: December 2006

AbstractWe are interested in the relation between the pathwidth of a biconnected outerplanar graph and the pathwidth of its (geometric) dual. Bodlaender and Fomin [3], after having proved that the pathwidth of every biconnected outerplanar graph is always at most twice the pathwidth of its (geometric) dual plus two, conjectured that there exists a constant c such that the pathwidth of every biconnected outerplanar graph is at most c plus the pathwidth of its dual. They also conjectured that this was actually true with c being one for every biconnected planar graph. Fomin [10] proved that the second conjecture is true for all planar triangulations. First, we construct for each p ≥ 1, a biconnected outerplanar graph of pathwidth 2p + 1 whose (geometric) dual has pathwidth p + 1, thereby disproving both conjectures. Next, we also disprove two other conjectures (one of Bodlaender and Fomin [3], implied by one of Fomin [10]. Finally we prove, in an algorithmic way, that the pathwidth of every biconnected outerplanar graph is at most twice the pathwidth of its (geometric) dual minus one. A tight interval for the studied relation is therefore obtained, and we show that all cases in the interval happen. © 2006 Wiley Periodicals, Inc. J Graph Theory 55: 27–41, 2007
Progress toward remediation of the Sydney Tar Ponds: A major Canadian PCB/PAH “superfund” site
Authors: Lee G. Fred , Jones‐Lee Anne 
Published: December 2006

AbstractThe Muggah Creek estuary in Sydney, Nova Scotia, received liquid and solid wastes from a steel mill and its associated coke ovens for approximately 100 years. This resulted in pollution of soils and sediments with polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), heavy metals, and other pollutants, including those in untreated domestic wastewaters. The Canadian federal and Nova Scotia provincial governments organized the Sydney Tar Ponds Agency (STPA) to develop a remediation approach for the Coke Ovens site soils and Sydney Tar Ponds sediments. The STPA developed a remediation approach for the Sydney Tar Ponds sediments, involving solidification/stabilization (S/S) through mixing cement and other materials into the sediments, and then capping them as a waste pile. High‐density polyethylene (HDPE) plastic sheeting vertical barriers are proposed to be used to divert groundwater and surface water from entering into the S/S‐treated sediments and to collect any water and associated pollutants released from the S/S‐treated sediments. The Coke Ovens site soils are proposed to be landfarmed to reduce some of the PAHs and other pollutants and then capped with a layer of soil. This remediation program is estimated to cost on the order of $400 million (CAN). This article presents a review of the significant potential problems with the STPA proposed remediation strategy of the Sydney Tar Ponds sediments and Coke Ovens site soils. © 2006 Wiley Periodicals, Inc.
Comparing Data Collected by Computerized and Written Surveys for Adolescence Health Research
Authors: Wu Ying , Newfield Susan A. 
Published: December 2006

ABSTRACTBackground:  This study assessed whether data‐collection formats, computerized versus paper‐and‐pencil, affect response patterns and descriptive statistics for adolescent health assessment surveys. Youth were assessed as part of a health risk reduction program.Methods:  Baseline data from 1131 youth were analyzed. Participants completed the questionnaire either by computer (n = 390) or by paper‐and‐pencil (n = 741).Results:  The rate of returned surveys meeting inclusion requirements was 90.6% and did not differ by methods. However, the computerized method resulted in significantly less incompleteness but more identical responses. Multiple regression indicated that the survey methods did not contribute to problematic responses. The two survey methods yielded similar scale internal reliability and descriptive statistics for behavioral and psychological outcomes, although the computerized method elicited higher reports of some risk items such as carrying a knife, beating up a person, selling drugs, and delivering drugs.Conclusions:  Overall, the survey method did not produce a significant difference in outcomes. This provides support for program personnel selecting survey methods based on study goals with confidence that the method of administration will not have a significant impact on the outcome.
Mechanisms ofegfrGene Transcription Modulation: Relationship to Cancer Risk and Therapy Response
Authors: Brandt Burkhard , Meyer-Staeckling Sönke , Schmidt Hartmut , Agelopoulos Konstantin , Buerger Horst 
Published: December 2006

AbstractThe epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation, and motility of normal as well as cancer cells. For predictive cancer diagnostics and therapeutic targeting of EGFR, it is important to know how the expression level of EGFR is controlled and related to receptor signaling. A novel transcriptional regulation mechanism has been described that depends on the length of a CA repeat in intron 1 [CA simple sequence repeat 1 (CA SSR I)] of the EGFR gene. Thereby, the number of CA repeats is inversely correlated to pre-mRNA synthesis. Indirect evidence for the importance of this mechanism includes the preferential occurrence of amplifications in cancer tissue harboring short CA repeats in this sequence and the discovery of distinct alleles in young breast cancer patients with a family history of the disease and in Japanese breast cancer patients. It can be postulated that the length of the CA repeat influences DNA bendability and, in consequence, the binding of repressor proteins. In summary, it seems that the CA SSR I represents an inherited variable for response to anti-EGFR therapies that could be determined before therapy. Moreover, the potential for synergistic effects with other polymorphism [e.g., EGFR R497K (HER-1 497K) and CCND1 A870G] leading to a simultaneous increase of EGFR signaling activity and expression should be investigated. From a practical perspective, assessment of the CA SSR I number of CA dinucleotide repeats as a predictor for clinical outcome is very attractive because it is a constant feature that does not change over time and can be easily measured in normal and cancer tissues (blood cells, skin, and tumor biopsies) in an assay that is technically simple, objective, and even quantitative.
Systemic Anthrax Lethal Toxin Therapy Produces Regressions of Subcutaneous Human Melanoma Tumors in Athymic Nude Mice
Authors: Abi-Habib Ralph J. , Singh Ravibhushan , Leppla Stephen H. , Greene John J. , Ding Yan , Berghuis Bree , Duesbery Nicholas S. , Frankel Arthur E. 
Published: December 2006

Abstract
Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic to BRAF mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. In this study, we determine the in vivo potency and safety of systemically administered LeTx.
Experimental Design: A s.c. xenograft melanoma model in athymic nude mice was treated with different i.p. doses of LeTx.
Results: In this study, we show that in vivo systemic LeTx treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial and complete tumor regressions with minor toxicity to mice. When animal toxicity was observed, we did not find any histologic evidence of tissue damage.
Conclusions: LeTx is one of the rare targeted agents to produce complete remissions of human melanomas in an animal model and thus warrants further preclinical development.
NF-κB–independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs
Authors: Kashkar Hamid , Deggerich Anke , Seeger Jens-Michael , Yazdanpanah Benjamin , Wiegmann Katja , Haubert Dirk , Pongratz Carola , Krönke Martin 
Published: December 2006

AbstractThe proteasome inhibitor bortezomib has been shown to possess promising antitumor activity and significant efficacy against a variety of malignancies. Different studies demonstrated that bortezomib breaks the chemoresistance in different tumor cells basically by altering nuclear factor–κB (NF-κB) activity. NF-κB has been shown to be constitutively active in most primary Hodgkin-Reed-Sternberg (H-RS) cells in lymph node sections and in Hodgkin lymphoma (HL) cell lines and was suggested to be a central molecular switch in apoptosis resistance in HL. Here we report a bimodal effect of bortezomib in HL cells. Whereas high-dose bortezomib induced direct cytotoxicity that correlated with decreased NF-κB activity, low-dose bortezomib sensitized HL cells against a variety of cytotoxic drugs without altering NF-κB action. Strikingly, bortezomib induced marked XIAP down-regulation at the posttranslational level that was independent of the NF-κB status. Similarly, RNA interference (RNAi)–mediated XIAP down-regulation generated susceptibility to cytostatic agents. The results identify XIAP as an NF-κB–independent target of bortezomib action that controls the chemoresistant phenotype of HL cells.
High magnetic field induced changes of gene expression in arabidopsis
Authors: Paul Anna-Lisa , Ferl Robert J , Meisel Mark W 
Published: December 2006

Abstract

Background
High magnetic fields are becoming increasingly prevalent components of non-invasive, biomedical imaging tools (such as MRI), thus, an understanding of the molecular impacts associated with these field strengths in biological systems is of central importance. The biological impact of magnetic field strengths up to 30 Tesla were investigated in this study through the use of transgenic Arabidopsis plants engineered with a stress response gene consisting of the alcohol dehydrogenase (Adh) gene promoter driving the β-glucuronidase (GUS) gene reporter.

Methods
Magnetic field induced Adh/GUS activity was evaluated with histochemical staining to assess tissue specific expression and distribution, and with quantitative, spectrofluometric assays to measure degree of activation. The evaluation of global changes in the Arabidopsis genome in response to exposure to high magnetic fields was facilitated with Affymetrix Gene Chip microarrays. Quantitative analyses of gene expression were performed with quantitative real-time polymerase-chain-reaction (qRT-PCR).

Results
Field strengths in excess of about 15 Tesla induce expression of the Adh/GUS transgene in the roots and leaves. From the microarray analyses that surveyed 8000 genes, 114 genes were differentially expressed to a degree greater than 2.5 fold over the control. These results were quantitatively corroborated by qRT-PCR examination of 4 of the 114 genes.

Conclusion
The data suggest that magnetic fields in excess of 15 Tesla have far-reaching effect on the genome. The wide-spread induction of stress-related genes and transcription factors, and a depression of genes associated with cell wall metabolism, are prominent examples. The roles of magnetic field orientation of macromolecules and magnetophoretic effects are discussed as possible factors that contribute to the mounting of this response.
Distinctive cell‐free DNA methylation characterizes presymptomatic genetic frontotemporal dementia
Authors: Giannini Lucia A. A. , Boers Ruben G. , van der Ende Emma L. , Poos Jackie M. , Jiskoot Lize C. , Boers Joachim B. , van IJcken Wilfred F. J. , Dopper Elise G. , Pijnenburg Yolande A. L. , Seelaar Harro , Meeter Lieke H. , van Rooij Jeroen G. J. , Scheper Wiep , Gribnau Joost , van Swieten John C. 
Published: March 2024

AbstractObjectiveMethylation of plasma cell‐free DNA (cfDNA) has potential as a marker of brain damage in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, we study methylation of cfDNA in presymptomatic and symptomatic carriers of genetic FTD pathogenic variants, next to healthy controls.MethodscfDNA was isolated from cross‐sectional plasma of 10 presymptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), 10 symptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), and 9 healthy controls. Genome‐wide methylation of cfDNA was determined using a high‐resolution sequencing technique (MeD‐seq). Cumulative scores based on the identified differentially methylated regions (DMRs) were estimated for presymptomatic carriers (vs. controls and symptomatic carriers), and reevaluated in a validation cohort (8 presymptomatic: 3 C9orf72, 3 GRN, and 2 MAPT; 26 symptomatic: 7 C9orf72, 6 GRN, 12 MAPT, and 1 TARDBP; 13 noncarriers from genetic FTD families).ResultsPresymptomatic carriers showed a distinctive methylation profile compared to healthy controls and symptomatic carriers. Cumulative DMR scores in presymptomatic carriers enabled to significantly differentiate presymptomatic carriers from healthy controls (p < 0.001) and symptomatic carriers (p < 0.001). In the validation cohort, these scores differentiated presymptomatic carriers from symptomatic carriers (p ≤ 0.007) only. Transcription‐start‐site methylation in presymptomatic carriers, generally associated with gene downregulation, was enriched for genes involved in ubiquitin‐dependent processes, while gene body methylation, generally associated with gene upregulation, was enriched for genes involved in neuronal cell processes.InterpretationA distinctive methylation profile of cfDNA characterizes the presymptomatic stage of genetic FTD, and could reflect neuronal death in this stage.
Nicolau syndrome following glatiramer acetate for multiple sclerosis: Case and review of reports
Authors: Udawatta Methma , Mateen Farrah J. 
Published: March 2024

AbstractNicolau syndrome is a rare, iatrogenic skin reaction after parental drug administration, characterized by severe pain at an injection site, followed by hemorrhage, ulceration, and often necrosis. We present a case of a patient on glatiramer acetate for many years (initially Copaxone then Glatopa) who developed Nicolau syndrome, the second reported case after generic glatiramer acetate. All reported cases of Nicolau syndrome after glatiramer acetate are reviewed. The case highlights the importance of prompt recognition of this skin reaction by neurologists and raises awareness of the risks of skin reactions even in low‐risk injectable DMTs.