bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype‐associated gene expression signatures
Authors: Braconi Chiara , Meng Fanyin , Swenson Erica , Khrapenko Lyudmyla , Huang Nianyuan , Patel Tushar 
Published: June 2009

AbstractBACKGROUND:The presence of vascular invasion in hepatocellular cancer (HCC) correlates with prognosis, and is a critical determinant of both the therapeutic approach and the recurrence or intrahepatic metastases. The authors sought to identify candidate therapeutic agents capable of targeting the invasive phenotype in HCC.METHODS:A gene expression signature associated with vascular invasion derived from 81 human cases of HCC was used to screen a database of 453 genomic profiles associated with 164 bioactive molecules using the connectivity map. Candidate agents were identified by their inverse correlation to the query gene signature. The efficacy of the candidate agents to target invasion was experimentally verified in PLC/PRF‐5 and HepG2 HCC cells.RESULTS:The gene signature associated with vascular invasion in HCC comprised of 47 up‐regulated and 26 down‐regulated genes. Computational bioinformatics analysis revealed several putative candidates, including resveratrol and 17‐allylamino‐geldanamycin (17‐AAG). Both of these agents reduced HCC cell invasion at noncytotoxic concentrations. 17‐AAG, a heat shock protein 90 (HSP‐90) inhibitor, was shown to modulate the expression of several diverse cancer‐associated genes, including ADAMTS1, part of the query signature, and maspin, an HSP‐90–associated protein with a tumor suppressor role in HCC.CONCLUSIONS:Candidates for further evaluation as therapies to limit invasion in HCC have been identified using a computational bioinformatics analysis of phenotype‐associated gene expression. Phenotype targeting using genomic profiling is a rational approach for drug discovery. Therapeutic strategies targeting a defined cancer‐associated phenotype can be identified without a detailed knowledge of individual downstream targets. Cancer 2009. © 2009 American Cancer Society.
Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long‐term outcome of patients with early chronic myeloid leukemia in chronic phase
Authors: Alvarado Yesid , Kantarjian Hagop , O'Brien Susan , Faderl Stefan , Borthakur Gautam , Burger Jan , Wierda William , Garcia‐Manero Guillermo , Shan Jianqin , Cortes Jorge 
Published: June 2009

AbstractBACKGROUND:The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined.METHODS:The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard‐dose (n = 73) or high‐dose (n = 208) imatinib was investigated.RESULTS:Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event‐free survival (EFS) and transformation‐free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose.CONCLUSIONS:The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required. Cancer 2009. © 2009 American Cancer Society.
Dynamics and management of cytopenias associated with dasatinib therapy in patients with chronic myeloid leukemia in chronic phase after imatinib failure
Authors: Quintás‐Cardama Alfonso , De Souza Santos Fabio Pires , Kantarjian Hagop , O'Brien Susan , Faderl Stefan , Awais Ahmed , Borthakur Gautam , Cortes Jorge 
Published: June 2009

AbstractBACKGROUND:The incidence, dynamics, and management of cytopenias were investigated in patients with chronic myeloid leukemia in chronic phase (CP CML) who received dasatinib therapy after imatinib failure.METHODS:Data were analyzed from 130 patients with CP CML who were treated with dasatinib from November 2003 to March 2006 in phase 1 (n = 22) or phase 2 or 3 (n = 108) studies for the development of grade 2 to 4 cytopenia (according to the National Cancer Institute Common Terminology Criteria [version 3.0]).RESULTS:Grade 2 to 4 neutropenia and/or thrombocytopenia occurred in 94 (72%) patients during dasatinib therapy and grade 3 to 4 occurred in 67 (52%) patients. Of the 94 patients who developed grade 2 to 4 neutropenia and/or thrombocytopenia, 64 (68%) also developed at least grade 2 anemia, and 16 (17%) developed grade 3 to 4 anemia. Management of cytopenias included transient dasatinib interruption in 35 (37%) patients, filgrastim in 12 (14%) patients, recombinant erythropoietin in 29 (45%) patients, and interleukin‐11 in 3 (5%) patients. Factors associated with an increased risk for developing grade 2 to 4 cytopenias were longer time from diagnosis to treatment, prior interferon or imatinib therapy, and a lower white blood cell count at the initiation of dasatinib therapy.CONCLUSIONS:Hematologic toxicity was frequent during dasatinib therapy in patients with CP CML, particularly at doses >100 mg daily. Treatment interruption and/or dose reduction as well as growth factor support were found to be safe and efficacious strategies to facilitate the continuous administration of dasatinib. Cancer 2009. © 2009 American Cancer Society.
Pancreatic resection
Authors: Murphy Melissa M. , Simons Jessica P. , Hill Joshua S. , McDade Theodore P. , Chau Ng Sing , Whalen Giles F. , Shah Shimul A. , Harrison Lynn H. , Tseng Jennifer F. 
Published: June 2009

AbstractBACKGROUND:Blacks are affected disproportionately by pancreatic adenocarcinoma and have been linked with poor survival. Surgical resection remains the only potential curative option. If surgical disparities exist, then they may provide insight into outcome discrepancies.METHODS:Patients with pancreatic adenocarcinoma were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results data from 1992 to 2002. Univariate analyses were used to compare demographics, tumor characteristics, and surgical data; and logistic regression was used to determine independent predictors for recommendation/performance of surgery. Kaplan‐Meier survival was assessed, and a Cox proportional hazards model was used to examine adjusted predictors of survival.RESULTS:In total, 27,828 patients were identified; 81.4% were white, 11.5% were black, 7.2% were of other race. White patients and black patients presented with similar stage and had surgery recommended at similar rates (34.5% vs 34%, respectively; P = .57). Black patients underwent fewer resections (10.6% vs 12.7%; P < .001). Multivariate analysis confirmed that black patients were less likely to undergo resection (adjusted odds ratio, 0.69; 95% confidence interval [95% CI], 0.57‐0.84). Overall, black patients had worse univariate survival. The survival among black patients who underwent resection did not differ statistically from the survival of similar white patients, although the median survival trended lower (11 months vs 13 months; P = .13). In a multivariate Cox model, black race predicted worse survival (hazards ratio, 1.11; 95% CI, 1.07‐1.16), and pancreatic resection was protective (hazards ratio, 0.56; 95% CI, 0.53‐0.59).CONCLUSIONS:Black and white patients with pancreatic adenocarcinoma presented with similar stages and were recommended for pancreatectomy at similar rates, yet black patients underwent fewer resections. After resection, crude survival did not differ significantly between white and black patients, although multivariate analysis demonstrated a survival disadvantage for blacks despite adjusting for resection. The current results suggested that pancreatectomy may be underused for blacks. Maximizing resection rates for appropriate patients may be an important component in reducing outcome disparities for pancreatic adenocarcinoma. Cancer 2009. © 2009 American Cancer Society.
Correlative analysis of gene expression profile and prognosis in patients with gliomatosis cerebri
Authors: D'Urso Oscar Fernando , D'Urso Pietro Ivo , Marsigliante Santo , Storelli Carlo , Luzi Giuseppe , Gianfreda Cosimo Damiano , Montinaro Antonio , Distante Alessandro , Ciappetta Pasqualino 
Published: June 2009

AbstractBACKGROUND:In modern clinical neuro‐oncology, the pathologic diagnoses are very challenging, creating significant clinical confusion and affecting therapeutic decisions and prognosis.METHODS:TP53 and PTEN gene sequences were analyzed, and microarray expression profiling was also performed. The authors investigated whether gene expression profiling, coupled with class prediction methodology, could be used to determine the prognosis of gliomatosis cerebri in a more consistent manner than standard pathology.RESULTS:The authors reported the results of a molecular study in 59 cases of gliomatosis cerebri, correlating these results with prognosis. The well‐known prognostic factors of gliomas (ie, age, Karnofsky performance status, histology [grade 2 vs 3], and contrast enhancement) were found to be predictive of response or outcome in only a percentage of patients but not in all patients. The authors identified a 23‐gene signature that was able to predict patient prognosis with microarray gene expression profiling. With the aim of producing a prognosis tool that is useful in clinical investigation, the authors studied the expression of this 23‐gene signature by real‐time quantitative polymerase chain reaction. Real‐time expression values relative to these 23 gene features were used to build a prediction method able to distinguish patients with a good prognosis (those more likely to be responsive to therapy) from patients with a poor prognosis (those less likely to be responsive to therapy).CONCLUSIONS:The results of the current study demonstrated not only a strong association between gene expression patterns and patient survival, but also a robust replicability of these gene expression–based predictors. Cancer 2009. © 2009 American Cancer Society.
Developing quality indicators for cancer end‐of‐life care
Authors: Seow Hsien , Snyder Claire F. , Shugarman Lisa R. , Mularski Richard A. , Kutner Jean S. , Lorenz Karl A. , Wu Albert W. , Dy Sydney M. 
Published: June 2009

AbstractQuality indicators applicable to cancer end‐of‐life care exist, but have not been widely implemented. To advance this field, the authors worked with the Agency for Health Care Research and Quality and the National Cancer Institute to organize a national symposium to discuss key issues and future goals, based on a conceptual framework. Discussions focused on 8 key domains in end‐of‐life cancer care: pain; dyspnea; communication, care planning, and decision making; psychosocial care; communication about chemotherapy; depression; continuity, coordination, and care transitions; and spirituality and closure. Key themes included the need for clarity on definitions and key aspects of care within domains, the need to start implementing indicators in more developed domains, and the importance of high‐quality symptom assessment and documentation of key processes. Key areas for future work include development of more outcome indicators, methods to better incorporate indicators and patient‐reported outcomes into clinical processes of care, and coordination across domains and settings. Measuring the quality of end‐of‐life cancer care is essential to understanding how best to improve patient outcomes and care. Cancer 2009. © 2009 American Cancer Society.
Assessment of the performance of the Stanford Online Calculator for the prediction of nonsentinel lymph node metastasis in sentinel lymph node‐positive breast cancer patients
Authors: Scow Jeffrey S. , Degnim Amy C. , Hoskin Tanya L. , Reynolds Carol , Boughey Judy C. 
Published: June 2009

AbstractBACKGROUND:Several models for the prediction of nonsentinel lymph node (NSLN) metastasis in sentinel lymph node (SLN)‐positive breast cancer patients have been proposed. In this study, the authors evaluate the Stanford Online Calculator (SOC), which was designed to predict the likelihood of NSLN metastasis using only 3 variables: primary tumor size, SLN metastasis size, and angiolymphatic invasion status. They compared it with the Mayo and Memorial Sloan‐Kettering Cancer Center (MSKCC) nomograms.METHODS:The SOC was used to calculate the probability of NSLN metastasis in 464 breast cancer patients with SLN metastasis who underwent completion axillary lymph node dissection at the Mayo Clinic. The area under the receiver operating characteristic curve (AUC) was calculated for each model. Mean probabilities of patients with and without NSLN metastasis were compared. Patients with ≤5%, ≤10%, and 100% NSLN metastasis probabilities were examined.RESULTS:The AUCs of the Stanford, MSKCC, and Mayo models were 0.72, 0.74, and 0.77, respectively (P = .13). The mean Stanford probabilities for patients with and without NSLN metastasis were 0.75 (range, 0.06‐1.0) and 0.50 (range, 0.05‐1.0), respectively (P < .0001). The false‐negative rates for patients with a Stanford probability of ≤5% and ≤10% were 0% and 13%, respectively. Of the patients with a Stanford probability of 100%, 26% did not have NSLN metastasis.CONCLUSIONS:Despite using only 3 variables, the Stanford nomogram appears to perform on a par with, but not better than, the MSKCC and Mayo nomograms. Further validation in other patient populations is needed. Cancer 2009. © 2009 American Cancer Society.
Transgenesis in Xenopus using the Sleeping Beauty transposon system
Authors: Yergeau Donald A. , Johnson Hamlet Michelle R. , Kuliyev Emin , Zhu Haiqing , Doherty Joanne R. , Archer Taylor D. , Subhawong Andrea P. , Valentine Marc B. , Kelley Clair M. , Mead Paul E. 
Published: June 2009

AbstractTransposon‐based integration systems have been widely used for genetic manipulation of invertebrate and plant model systems. In the past decade, these powerful tools have begun to be used in vertebrates for transgenesis, insertional mutagenesis, and gene therapy applications. Sleeping Beauty (SB) is a member of Tc1/mariner class of transposases and is derived from an inactive form of the gene isolated from Atlantic salmon. SB has been used extensively in human cell lines and in whole animal vertebrate model systems such as the mouse, rat, and zebrafish. In this study, we describe the use of SB in the diploid frog Xenopus tropicalis to generate stable transgenic lines. SB transposon transgenes integrate into the X. tropicalis genome by a noncanonical process and are passed through the germline. We compare the activity of SB in this model organism with that of Tol2, a hAT (hobo, Ac1, TAM)‐like transposon system. Developmental Dynamics 238:1727–1743, 2009. © 2009 Wiley‐Liss, Inc.
Rnf19a, a ubiquitin protein ligase, and Psmc3, a component of the 26S proteasome, Tether to the acrosome membranes and the head–tail coupling apparatus during rat spermatid development
Authors: Rivkin Eugene , Kierszenbaum Abraham L. , Gil Mara , Tres Laura L. 
Published: June 2009

AbstractWe report the cDNA cloning of rat testis Rnf19a, a ubiquitin protein ligase, and show 98% and 93% protein sequence identity of testicular mouse and human Rnf19a, respectively. Rnf19a interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome. During spermatid development, Rnf19a and Psmc3 are initially found in Golgi‐derived proacrosomal vesicles. Later on, Rnf19a, Psmc3, and ubiquitin are seen along the cytosolic side of the acrosomal membranes and the acroplaxome, a cytoskeletal plate linking the acrosome to the spermatid nuclear envelope. Rnf19a and Psmc3 accumulate at the acroplaxome marginal ring–manchette perinuclear ring region during spermatid head shaping and in the developing sperm head–tail coupling apparatus and tail. Rnf19a and Psmc3 may interact directly or indirectly with each other, presumably pointing to the participation of the ubiquitin–proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head‐tail coupling apparatus and tail. Developmental Dynamics 238:1851–1861, 2009. © 2009 Wiley‐Liss, Inc.
Microinjection of Cre recombinase protein into zygotes enables specific deletion of two eukaryotic selection cassettes and enhances the expression of a DsRed2 reporter gene in Ccr2/Ccr5 double‐deficient mice
Authors: Luckow Bruno , Hänggli Amy , Maier Holger , Chilla Silvia , Loewe Robert P. , Dehmel Stefan , Schlöndorff Detlef , Loetscher Pius , Zerwes Hans‐Günter , Müller Matthias 
Published: June 2009

AbstractThe chemokine receptors CCR2 and CCR5 represent potential novel therapeutic targets to treat important inflammatory and infectious diseases, including atherosclerosis and HIV infection. To study the functions of both receptors in vivo, we aimed to generate Ccr2/Ccr5 double‐deficient mice. As these genes are separated by <20 kb, they were inactivated consecutively by two rounds of gene targeting in embryonic stem (ES) cells. Thereby neomycin and hygromycin selection cassettes flanked by four identical loxP recognition sequences for Cre recombinase were integrated into the ES cell genome together with EGFP and DsRed2 reporter genes. Both selection cassettes could be deleted in vitro by transiently transfecting ES cells with Cre expression vectors. However, after blastocyst microinjection these cells yielded only weak chimeras, and germline transmission was not achieved. Therefore, Ccr2/Ccr5 double‐deficient mice were generated from ES cells still carrying both selection cassettes. Microinjection of zygotes with a recombinant fusion protein consisting of maltose‐binding protein and Cre (MBP‐Cre) allowed the selective deletion of both cassettes. All sequences in between and both reporter genes were left intact. Deletion of both selection cassettes resulted in enhanced DsRed2 reporter gene expression. Cre protein microinjection of zygotes represents a novel approach to perform complex recombination tasks. genesis 47:545–558, 2009. © 2009 Wiley‐Liss, Inc.
Commentaries on ‘Abstinence‐plus programs for HIV infection prevention in high‐income countries’
Authors: Flicker Sarah , Guilamo‐Ramos Vincent , Bouris Alida 
Published: June 2009

AbstractThese are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Underhill K, Montgomery P, Operario D. Abstinence‐plus programs for HIV infection prevention in high‐income countries. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD007006. DOI: 10.1002/14651858.CD007006.Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Two commentaries on ‘Family‐based programmes for preventing smoking by children and adolescents’
Authors: Priest Naomi , Waters Elizabeth , Norman Cameron D. , Best Allan 
Published: June 2009

AbstractThese are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Thomas RE, Baker PRA, Lorenzetti D. Family‐based programmes for preventing smoking by children and adolescents. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD004493. DOI: 10.1002/14 651 858.CD004493.pub2.Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Ilicic Acid as a Natural Quiron for the Efficient Preparation of Bioactive α‐ and β‐Eudesmol
Authors: Barrero Alejandro F. , Herrador M. Mar , Arteaga Pilar , Catalán Julieta V. 
Published: June 2009

AbstractAn efficient procedure for the isolation of the sesquiterpene ilicic acid (3) on a multigram scale of extracts obtained from aerial parts of Inula viscosa (Asteraceae) was developed. Acid 3 is an appropriate starting material for short, enantiospecific syntheses of β‐eudesmol (1) and α‐eudesmol (2), natural products featuring significant antiangiogenic and anti‐Alzheimer properties. Synthesis of 1 was achieved in six steps and the synthesis of 2 in seven, producing overall yields of 52 and 41 %, respectively.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Reagentless Biosensor for Hydrogen Peroxide Based on the Immobilization of Hemoglobin in Platinum Nanoparticles Enhanced Poly(chloromethyl thiirane) Cross‐linked Chitosan Hybrid Film
Authors: Jia Shanshan , Fei Junjie , Tian Tian , Zhou Fangqin 
Published: June 2009

AbstractAn unmediated hydrogen peroxide (H2O2) biosensor was prepared by co‐immobilizing hemoglobin (Hb) with platinum nanoparticles enhanced poly(chloromethyl thiirane) cross‐linked chitosan (CCCS‐PNs) hybrid film. CCCS could provide a biocompatible microenvironment for Hb and PNs could accelerate the electron transfer between Hb and the electrode. Spectroscopic analysis indicated that the immobilized Hb could maintain its native structure in the CCCS‐PNs hybrid film. Entrapped Hb exhibited direct electrochemistry for its heme Fe(III)/Fe(II) redox couples at −0.396 V in the CCCS‐PNs hybrid film, as well as peroxidase‐like activity to the reduction of hydrogen peroxide without the aid of an electron mediator.
Fabrication of Redox‐Mediator Supported Potentiometric Nitrate Biosensor with Nitrate Reductase
Authors: Sohail Manzar , Adeloju Samuel B. 
Published: June 2009

AbstractFabrication of a more superior nitrate potentiometric biosensor than previously achieved with NaR and NADH has been accomplished by co‐entrapment of redox mediators and NaR into polypyrrole (PPy) film during galvanostatic polymerization of pyrrole. The replacement of NADH with redox mediators such as thionin acetate (ThAc), safranin (Saf), and azure A (AzA) gave more sensitive potentiometric responses, better minimum detectable concentration, linear concentration range and response time for nitrate than possible with NADH. The co‐entrapment of ThAc, Saf, AzA and methyl viologen (MV) with NaR into PPy films also improved the Nernstian behavior of the electrode process beyond the capability of the PPy‐NaR‐NADH biosensor. Substantial reduction in volume and quantity of cofactor/mediator and, hence cost, was achieved by the replacement of NADH with a redox mediator. Only 50 μM of AzA was required to form a PPy‐NaR‐AzA biosensor which gave the most sensitive potentiometric response for nitrate, achieving a minimum detectable concentration of 10 μM, a linear concentration range of 50–5000 μM and a response time of 2–4 s.