bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Growth Inhibition by 9-cis-Retinoic Acid Plus Trastuzumab in Human Hepatocellular Carcinoma Cells
Authors: Tatebe Hideharu , Shimizu Masahito , Shirakami Yohei , Tsurumi Hisashi , Moriwaki Hisataka 
Published: May 2008

Abstract
Purpose: A malfunction of retinoid X receptor-α (RXRα) due to phosphorylation by the Ras/mitogen-activated protein kinase signaling pathway is associated with the development of hepatocellular carcinoma (HCC). The humanized anti-HER2 monoclonal antibody trastuzumab inhibits the activation of HER2 and its multiple downstream signaling pathways, including the Ras/mitogen-activated protein kinase pathway. In this study, the effects of phosphorylation of RXRα on the ability of RXRα ligand 9-cis-retinoic acid (9cRA) and trastuzumab to inhibit growth of HCC cells was examined.
Experimental Design: The effects of a combination of 9cRA plus trastuzumab on the inhibition of cell growth in HLF human HCC cells which express constitutive activation of HER2 protein were examined.
Results: The combination of 9cRA plus trastuzumab synergistically inhibited the growth of HLF cells without affecting the growth of Hc normal human hepatocytes. Combined treatment with these agents acted synergistically to induce apoptosis in HLF cells. The treatment of HLF cells with trastuzumab alone inhibited the phosphorylation of HER2, RXRα, ERK, Akt, and Stat3 proteins and these effects were enhanced when the cells were cotreated with 9cRA. Reporter assays indicated that the combination of 9cRA plus trastuzumab markedly increased both the retinoic acid responsive element and retinoid X responsive element promoter activities in HLF cells.
Conclusion: 9cRA and trastuzumab cooperatively inhibit the activation of HER2 and its downstream signaling pathways, subsequently inhibiting the phosphorylation of RXRα and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.
Prognostic Value of the Molecular Detection of Circulating Tumor Cells Using a Multimarker Reverse Transcription-PCR Assay for Cytokeratin 19, Mammaglobin A, and HER2 in Early Breast Cancer
Authors: Ignatiadis Michail , Kallergi Galatea , Ntoulia Maria , Perraki Maria , Apostolaki Stella , Kafousi Maria , Chlouverakis Grigorios , Stathopoulos Efstathios , Lianidou Evi , Georgoulias Vassilis , Mavroudis Dimitris 
Published: May 2008

Abstract
Purpose: To investigate the prognostic value of the molecular detection of circulating tumor cells (CTCs) using three markers [cytokeratin 19 (CK19), mammaglobin A (MGB1), and HER2] in early breast cancer.
Experimental Design: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected using real-time (CK19) and nested (MGB1 and HER2) reverse transcription-PCR in the peripheral blood of 175 women with stage I to III breast cancer before the initiation of adjuvant chemotherapy. The detection of CTCs was correlated with clinical outcome. In 10 patients, immunofluorescence staining experiments were done to investigate the coexpression of cytokeratin, MGB1, and HER2 in CTCs.
Results: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected in 41.1%, 8%, and 28.6% of the 175 patients, respectively. Patients had one of the following molecular profiles: CK19mRNA+/MGB1mRNA+/HER2mRNA+ (n = 8), CK19mRNA+/MGB1mRNA+/HER2mRNA− (n = 1), CK19mRNA+/MGB1mRNA−/HER2mRNA+ (n = 42), CK19mRNA+/MGB1mRNA−/HER2mRNA− (n = 21), CK19mRNA−/MGB1mRNA+/HER2mRNA− (n = 5), and CK19mRNA−/MGB1mRNA−/HER2mRNA− (n = 98). Double-immunofluorescence experiments confirmed the following CTC phenotypes: CK+/MGB1+, CK+/MGB1−, CK−/MGB1+, CK+/HER2+, CK+/HER2−, MGB1+/HER2−, and MGB1+/HER2+. In univariate analysis, the detection of CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells was associated with shorter disease-free survival (DFS; P &lt; 0.001, P = 0.001, and P &lt; 0.001, respectively), whereas the detection of CK19mRNA+ and MGB1mRNA+ cells was associated with worse overall survival (P = 0.044 and 0.034, respectively). In multivariate analysis, estrogen receptor–negative tumors and the detection of CK19mRNA+ and MGB1mRNA+ cells were independently associated with worse DFS.
Conclusion: The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer.
PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy
Authors: Morote Juan , Fernández Sara , Alaña Lide , Iglesias Carmela , Planas Jacques , Reventós Jaume , Ramón y Cajal Santiago , Paciucci Rosanna , de Torres Inés M. 
Published: May 2008

Abstract
Purpose: To analyze the expression of PTOV1 in high-grade prostatic intraepithelial neoplasia (HG-PIN) and to explore its usefulness to predict prostate cancer in patients with isolated HG-PIN in needle biopsy (prostate needle biopsy).
Experimental Design: PTOV1 expression in HG-PIN lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (Histo-score). HG-PIN derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively. Fifty patients with HG-PIN without concomitant cancer at their first prostate needle biopsy were chosen as the study group. Patients were followed by a mean of 2.5 repeated prostate needle biopsies (1-5), during a mean period of 12.4 months (1-39).
Results: PTOV1 expression in HG-PIN from radical prostatectomies showed a significantly higher Histo-score (162.6) compared with specimens from cistoprostatectomies (67.0). In the study group, PTOV1 expression was significantly higher in samples with cancer in the follow-up (11 patients, 22%) compared with samples in which cancer was not detected (151.4 versus 94.6). PTOV1 expression was the only independent predictor of cancer in the multivariate analysis and the area under the curve was 0.803 (95% confidence interval, 0.728-0.878). A threshold of 100 for PTOV1 expression provided 90.9% sensitivity, 51.3% specificity, 34.5% positive predictive value, and 95.2% negative predictive value.
Conclusions: PTOV1 is overexpressed in HG-PIN associated with cancer and is a potential marker for studying the carcinogenesis and progression of prostate cancer. Prostate needle biopsy with PTOV1 expression in HG-PIN above a threshold of 100 should be repeated immediately for the likely presence of undiagnosed cancer.
Regional Hypoxia in Glioblastoma Multiforme Quantified with [18F]Fluoromisonidazole Positron Emission Tomography before Radiotherapy: Correlation with Time to Progression and Survival
Authors: Spence Alexander M. , Muzi Mark , Swanson Kristin R. , O'Sullivan Finbarr , Rockhill Jason K. , Rajendran Joseph G. , Adamsen Tom C.H. , Link Jeanne M. , Swanson Paul E. , Yagle Kevin J. , Rostomily Robert C. , Silbergeld Daniel L. , Krohn Kenneth A. 
Published: May 2008

Abstract
Purpose: Hypoxia is associated with resistance to radiotherapy and chemotherapy and activates transcription factors that support cell survival and migration. We measured the volume of hypoxic tumor and the maximum level of hypoxia in glioblastoma multiforme before radiotherapy with [18F]fluoromisonidazole positron emission tomography to assess their impact on time to progression (TTP) or survival.
Experimental Design: Twenty-two patients were studied before biopsy or between resection and starting radiotherapy. Each had a 20-minute emission scan 2 hours after i.v. injection of 7 mCi of [18F]fluoromisonidazole. Venous blood samples taken during imaging were used to create tissue to blood concentration (T/B) ratios. The volume of tumor with T/B values above 1.2 defined the hypoxic volume (HV). Maximum T/B values (T/Bmax) were determined from the pixel with the highest uptake.
Results: Kaplan-Meier plots showed shorter TTP and survival in patients whose tumors contained HVs or tumor T/Bmax ratios greater than the median (P ≤ 0.001). In univariate analyses, greater HV or tumor T/Bmax were associated with shorter TTP or survival (P &lt; 0.002). Multivariate analyses for survival and TTP against the covariates HV (or T/Bmax), magnetic resonance imaging (MRI) T1Gd volume, age, and Karnovsky performance score reached significance only for HV (or T/Bmax; P &lt; 0.03).
Conclusions: The volume and intensity of hypoxia in glioblastoma multiforme before radiotherapy are strongly associated with poorer TTP and survival. This type of imaging could be integrated into new treatment strategies to target hypoxia more aggressively in glioblastoma multiforme and could be applied to assess the treatment outcomes.
A Five-Gene Molecular Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early Stage Breast Cancer
Authors: Ma Xiao-Jun , Salunga Ranelle , Dahiya Sonika , Wang Wilson , Carney Erin , Durbecq Virginie , Harris Adrian , Goss Paul , Sotiriou Christos , Erlander Mark , Sgroi Dennis 
Published: May 2008

Abstract
Purpose: Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade–associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information.
Experimental Design: From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle–related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR.
Results: MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI.
Conclusions: We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin-embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup (∼30%) of early stage estrogen receptor–positive breast cancer patients with very poor outcome despite endocrine therapy.
MBL2and Hepatitis C Virus Infection among Injection Drug Users
Authors: Brown Elizabeth E , Zhang Mingdong , Zarin-Pass Rebecca , Bernig Toralf , Tseng Fan-Chen , Xiao Nianqing , Yeager Meredith , Edlin Brian R , Chanock Stephen J , O'Brien Thomas R 
Published: May 2008

AbstractBackgroundGenetic variations inMBL2that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whetherMBL2variants influence the outcome of hepatitis C virus (HCV) infection.MethodsParticipants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms inMBL2. Statistical analyses of European American and African American participants were conducted separately.ResultsThe analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, theMBL2-289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans.ConclusionThis study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation thatMBL2-289X was associated with the absence of HCV RNA in European Americans requires validation.
Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family
Authors: Patocs Attila , Gergics Peter , Balogh Katalin , Toth Miklos , Fazakas Ferenc , Liko Istvan , Racz Karoly 
Published: May 2008

Abstract
Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.
Implications of cellobiohydrolase glycosylation for use in biomass conversion
Authors: Jeoh Tina , Michener William , Himmel Michael E , Decker Stephen R , Adney William S 
Published: May 2008

Abstract
The cellulase producing ascomycete, Trichoderma reesei (Hypocrea jecorina), is known to secrete a range of enzymes important for ethanol production from lignocellulosic biomass. It is also widely used for the commercial scale production of industrial enzymes because of its ability to produce high titers of heterologous proteins. During the secretion process, a number of post-translational events can occur, however, that impact protein function and stability. Another ascomycete, Aspergillus niger var. awamori, is also known to produce large quantities of heterologous proteins for industry. In this study, T. reesei Cel7A, a cellobiohydrolase, was expressed in A. niger var. awamori and subjected to detailed biophysical characterization. The purified recombinant enzyme contains six times the amount of N-linked glycan than the enzyme purified from a commercial T. reesei enzyme preparation. The activities of the two enzyme forms were compared using bacterial (microcrystalline) and phosphoric acid swollen (amorphous) cellulose as substrates. This comparison suggested that the increased level of N-glycosylation of the recombinant Cel7A (rCel7A) resulted in reduced activity and increased non-productive binding on cellulose. When treated with the N-glycosidase PNGaseF, the molecular weight of the recombinant enzyme approached that of the commercial enzyme and the activity on cellulose was improved.
Audit Documentation Methods: A Path Model of Cognitive Processing, Memory, and Performance
Authors: Payne Elizabeth A. , Ramsay Robert J. 
Published: May 2008

One result of Public Company Accounting Oversight Board Auditing Standard No. 3 Audit Documentation (AS No. 3) (PCAOB 2004) is that audit firms are using more detailed audit workpapers and fewer summary memos to document their procedures. We explore implications of the choice of these two documentation methods. Specifically, we develop and test a model showing how different forms of documentation affect the cognitive processes auditors use during audit testing, and how differences in cognitive processing affect auditors' memory and two performance measures (error detection and recognition of a potentially fraudulent pattern in the evidence).
The results of path analysis show auditors who prepare detailed workpapers spend more total time on the task, and total time is associated with identifying more errors and better pattern recognition. Auditors who prepare summary memos examine the evidence items a greater number of times, which is associated with better pattern recognition and increased memory. The overall result is that each method enhances cognitive processing differently and the manner of cognitive processing affects performance measures differently. Documentation by summary memos is more efficient and results in better memory of the evidence. Documentation by detailed workpapers results in better error detection for one type of error and permits a self-review of documented evidence by the preparer, which enhances pattern recognition. Finally, documentation by detailed workpapers provides evidence that may potentially enhance pattern recognition at the reviewer level.
One‐Step Ionic‐Liquid‐Assisted Electrochemical Synthesis of Ionic‐Liquid‐Functionalized Graphene Sheets Directly from Graphite
Authors: Liu Na , Luo Fang , Wu Haoxi , Liu Yinghui , Zhang Chao , Chen Ji 
Published: May 2008

AbstractGraphite, inexpensive and available in large quantities, unfortunately does not readily exfoliate to yield individual graphene sheets. Here a mild, one‐step electrochemical approach for the preparation of ionic‐liquid‐functionalized graphite sheets with the assistance of an ionic liquid and water is presented. These ionic‐liquid‐treated graphite sheets can be exfoliated into functionalized graphene nanosheets that can not only be individuated and homogeneously distributed into polar aprotic solvents, but also need not be further deoxidized. Different types of ionic liquids and different ratios of the ionic liquid to water can influence the properties of the graphene nanosheets. Graphene nanosheet/polystyrene composites synthesized by a liquid‐phase blend route exhibit a percolation threshold of 0.1 vol % for room temperature electrical conductivity, and, at only 4.19 vol %, this composite has a conductivity of 13.84 S m−1, which is 3–15 times that of polystyrene composites filled with single‐walled carbon nanotubes.
Invention and modification of a new tool use behavior: ant‐fishing in trees by a wild chimpanzee (Pan troglodytes verus) at Bossou, Guinea
Authors: Yamamoto Shinya , Yamakoshi Gen , Humle Tatyana , Matsuzawa Tetsuro 
Published: May 2008

AbstractWild chimpanzees are known to have a different repertoire of tool use unique to each community. For example, “ant‐dipping” is a tool use behavior known in several chimpanzee communities across Africa targeted at driver ants (Dorylus spp.) on the ground, whereas “ant‐fishing,” which is aimed at carpenter ants (Camponotus spp.) in trees, has primarily been observed among the chimpanzees of Mahale in Tanzania. Although the evidence for differences between field sites is accumulating, we have little knowledge on how these tool use behaviors appear at each site and on how these are modified over time. This study reports two“ant‐fishing” sessions which occurred 2 years apart by a young male chimpanzee at Bossou, Guinea. Ant‐fishing had never been observed before in this community over the past 27 years. During the first session, at the age of 5, he employed wands of similar length when ant‐fishing in trees to those used for ant‐dipping on the ground, which is a customary tool use behavior of this community. Two years later, at the age of 7, his tools for ant‐fishing were shorter and more suitable for capturing carpenter ants. This observation is a rare example of innovation in the wild and does provide insights into problem‐solving and learning processes in chimpanzees. Am. J. Primatol. 70:699–702, 2008. © 2008 Wiley‐Liss, Inc.
Chirale Olefine als Steuerungsliganden in der asymmetrischen Katalyse
Authors: Defieber Christian , Grützmacher Hansjörg , Carreira Erick M. 
Published: May 2008

AbstractEinen direkten Weg zur Einführung stereogener Zentren bieten metallkatalysierte asymmetrische Prozesse. Aus diesem Grund ist die Entwicklung neuartiger chiraler Liganden, die effizient einen asymmetrischen Verlauf von Reaktionen bewirken können, essenziell in der modernen organischen Synthese. Während eine Vielzahl an chiralen Liganden bekannt ist, die über ein Heteroatom an das Metallzentrum binden, fanden Verbindungen, die über Kohlenstoffatome koordinieren, bisher wenig Beachtung. In dieser Übersicht stellen wir die zunehmende Zahl solcher chiraler, chelatisierender Olefinliganden und ihre Anwendung in metallkatalysierten Umsetzungen vor.
Gasspeicherung in nanoporösen Materialien
Authors: Morris Russell E. , Wheatley Paul S. 
Published: May 2008

AbstractDie Speicherung von Gasen in Festkörpern gewinnt zunehmend an Bedeutung. Anwendungen und Perspektiven dieser Technologie reichen von der Energiewirtschaft und dem Umweltschutz bis hin zur Biologie und Medizin. Hoch poröse Festkörper wie Zeolithe, Kohlenstoffmaterialien, Polymere und metall‐organische Netzwerke sind mit breit variierbaren chemischen Zusammensetzungen und Strukturen zugänglich. In diesen Architekturen können zahlreiche Gase adsorbiert und gespeichert werden – allen voran Wasserstoff, aber auch Methan, Stickstoffmonoxid und Kohlendioxid. Allerdings ist die Entwicklung von Materialien mit hinreichender Adsorptionskapazität und Lebensdauer, kontrollierbarem Gasfluss und effizienter Wiederbeladung nicht trivial. Das unterschiedliche chemische Verhalten der einzelnen Gase macht es erforderlich, die Eigenschaften des porösen Materials sorgfältig auf die gewünschte Anwendung abzustimmen.