bluuebunny/crossref_metadata_2025_split huggingface dataset:
High speed sliding of axonemal microtubules produced by outer arm dynein
Authors: Seetharam Raviraja N. , Satir Peter 
Published: December 2004

AbstractTo study dynein arm activity at high temporal resolution, axonemal sliding was measured field by field for wild type and dynein arm mutants of Tetrahymena thermophila. For wt SB255 cells, when the rate of data acquisition was 60 fps, about 5× greater than previously published observations, sliding was observed to be discontinuous with very high velocity sliding (average 196 μm/sec) for a few msec (1 or 2 fields) followed by a pause of several fields. The sliding velocities measured were an order of magnitude greater than rates previously measured by video analysis. However, when the data were analyzed at 12 fps for the same axonemes, consistent with previous observations, sliding was linear as the axonemes extended several times their original length with an average velocity of ≈10 μm/sec. The pauses or stops occurred at approximately 200 and 300% of the initial length, suggesting that dynein arms on one axonemal doublet were initially active to the limit of extension, and then the arms on the next doublet became activated. In contrast, in a mutant where OADs are missing, sliding observed at 60 fps was continuous and slow (5 μm/sec), as opposed to the discontinuous high‐velocity sliding of SB255 and of the mutant at the permissive temperature where OADs are present. High‐velocity step‐wise sliding was also present in axonemes from an inner arm dynein mutant (KO6). These results indicate that the high‐speed discontinuous pattern of sliding is produced by the mechanochemical activity of outer arm dynein. The rate of sliding is consistent with a low duty ratio of the outer arm dynein and with the operation of each arm along a doublet once per beat. Cell Motil. Cytoskeleton 60:96–103, 2005. © 2004 Wiley‐Liss, Inc.
Leading the way? The European Union at the WSSD
Authors: Burchell Jon , Lightfoot Simon 
Published: December 2004

AbstractThe 2002 World Summit on Sustainable Development (WSSD) presented an important test of how far the European Union's (EU's) commitment to sustainable development had evolved. This article applies the conception of the EU as a normative power to the EU's role at Johannesburg. It examines how the EU operationalized the concept of sustainable development before analysing the role the EU played in the outcomes of the WSSD and the factors that facilitated or constrained the potential extension of an EU norm in this field. In doing so, the article questions the depth of the EU's current commitment to sustainable development, suggesting that while it may represent a leader in some fields of environmental policy it remains some way short of a coherent adoption of sustainable development as an EU norm. As a result, the factors constraining the development of a norm prevented the EU offering strong leadership at the WSSD. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment.
Numerical realization for analysis of real flows by integrating computation and measurement
Authors: Hayase Toshiyuki , Nisugi Keisuke , Shirai Atsushi 
Published: December 2004

AbstractIn this paper, we deal with a numerical realization, which is a numerical analysis methodology to reproduce real flows by integrating numerical simulation and measurement. It is difficult to measure or calculate field information of real three‐dimensional unsteady flows due to the lack of an experimental field measurement method, as well as of a way to specify the exact boundary or initial conditions in computation. Based on the observer theory, numerical realization is achieved by a combination of numerical simulation, experimental measurement, and a feedback loop to the simulation from the output signals of both methods. The present paper focuses on the problem of how an inappropriate model or insufficient grid resolution influences the performance of the numerical realization in comparison with ordinary simulation. For a fundamental flow with the Karman vortex street behind a square cylinder, two‐dimensional analysis is performed by means of numerical realization and ordinary simulation with three grid resolutions. Comparison of the results with those of the experiment proved that the feedback of the experimental measurement significantly reduces the error due to insufficient grid resolution and effectively reduces the error due to inappropriate model assuming two‐dimensionality. Copyright © 2004 John Wiley & Sons, Ltd.
Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas
Authors: Lomas Jesus , Bello M. Josefa , Arjona Dolores , Alonso M. Eva , Martinez‐Glez Victor , Lopez‐Marin Isabel , Amiñoso Cinthia , de Campos Jose M. , Isla Alberto , Vaquero Jesus , Rey Juan A. 
Published: December 2004

AbstractThe role of the NF2 gene in the development of meningiomas has recently been documented; inactivating mutations plus allelic loss at 22q, the site of this gene (at 22q12), have been identified in both sporadic and neurofibromatosis type 2–associated tumors. Although epigenetic inactivation through aberrant CpG island methylation of the NF2 5′ flanking region has been documented in schwannoma (another NF2‐associated neoplasm), data on participation of this epigenetic modification in meningiomas are not yet widely available. Using methylation‐specific PCR (MSP) plus sequencing, we assessed the presence of aberrant promoter NF2 methylation in a series of 88 meningiomas (61 grade I, 24 grade II, and 3 grade III), in which the allelic constitution at 22q and the NF2 mutational status also were determined by RFLP/microsatellite and PCR‐SSCP analyses. Chromosome 22 allelic loss, NF2 gene mutation, and aberrant NF2 promoter methylation were detected in 49%, 24%, and 26% of cases, respectively. Aberrant NF2 methylation with loss of heterozygosity (LOH) at 22q was found in five cases, and aberrant methylation with NF2 mutation in another; LOH 22q and the mutation were found in 16 samples. The aberrant methylation of the NF2 gene also was the sole alteration in 15 samples, most of which were from grade I tumors. These results indicate that aberrant NF2 hypermethylation may participate in the development of a significant proportion of sporadic meningiomas, primarily those of grade I. ©2005 Wiley‐Liss, Inc.
8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes
Authors: Belloni Elena , Trubia Maurizio , Gasparini Patrizia , Micucci Carla , Tapinassi Cinzia , Confalonieri Stefano , Nuciforo Paolo , Martino Bruno , Lo‐Coco Francesco , Pelicci Pier Giuseppe , Di Fiore Pier Paolo 
Published: December 2004

Abstract8p11 myeloproliferative syndrome (EMS) is a clinical‐pathologic entity characterized by rearrangements involving the FGFR1 gene, which encodes a receptor tyrosine kinase. These rearrangements invariably lead to aberrant fusion proteins in which the kinase activity is constitutively turned on, with resulting oncogenic properties. In this article, we describe a new translocation in EMS, t(7;8)(q34;p11), in which the FGFR1 gene is fused to a previously unidentified partner, the TIF1 gene. We show that both the TIF1–FGFR1 and FGFR1–TIF1 fusion proteins have the potential to be translated as a result of the translocation. Thus, our data extend the involvement of FGFR1 in EMS and lend support to the concept that there is a precise correlation between genotype and phenotype in this disease. © 2004 Wiley‐Liss, Inc.
ATP‐binding cassette superfamily transporter gene expression in human soft tissue sarcomas
Authors: Oda Yoshinao , Saito Tsuyoshi , Tateishi Naomi , Ohishi Yoshihiro , Tamiya Sadafumi , Yamamoto Hidetaka , Yokoyama Ryohei , Uchiumi Takeshi , Iwamoto Yukihide , Kuwano Michihiko , Tsuneyoshi Masazumi 
Published: December 2004

AbstractThe phenomenon of multidrug resistance (MDR) in various malignant neoplasms has been reported as being caused by one or multiple expressions of ATP‐binding cassette (ABC) superfamily protein, including P‐glycoprotein/multidrug resistance (MDR) 1 and the MDR protein (MRP) family. However, their expression levels and distribution within soft tissue sarcomas remain controversial. In 86 cases of surgically resected soft tissue sarcoma, intrinsic mRNA levels of MDR1, MRP1, MRP2 and MRP3 were assessed using a quantitative reverse transcriptase‐PCR (RT‐PCR) method. Moreover, immunohistochemical protein expressions of P‐glycoprotein (P‐gp), MRP1, MRP2, MRP3 and p53 protein were evaluated in concordant paraffin‐embedded material. The mRNA expression and immunohistochemical expression of ABC superfamily transporters were compared to clinicopathologic parameters and proliferative activities as evaluated by the MIB‐1‐labeling index (LI). Among the various histologic types, malignant peripheral nerve sheath tumor (MPNST) showed significantly high levels of MDR1 (p=0.017) and MRP3 (p=0.0384) mRNA expression, compared to the other tumor types. When the immunohistochemical method was compared to the RT‐PCR technique to assess ABC transported expression at the protein and mRNA levels, a significantly close relationship was found between the 2 methods (p<0.05). P‐gp expression was significantly correlated with large tumor size (≥5 cm, p=0.041) and high AJCC stage (stages III and IV) (p=0.0365). Furthermore, cases with nuclear expression of p53 revealed significantly higher levels of MDR1 mRNA expression, compared to those with negative immunoreaction for p53 (p=0.0328). Our results suggest that MDR1/P‐gp expression may have an important role to play in tumor progression in the cases of soft tissue sarcoma, and p53 may be one of the active regulators of the MDR1 transcript. In addition, the high levels of both MDR1 and MRP3 mRNA expression in MPNST may help to explain the poor response of this tumor to anticancer‐drugs.
High‐resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry
Authors: Rakha Emad A. , Armour John A.L. , Pinder Sarah E. , Paish Claire E. , Ellis Ian O. 
Published: December 2004

AbstractLoss of the chromosomal material at 16q22.1 is one of the most frequent genetic aberrations found in both lobular and low‐grade nonlobular invasive carcinoma of the breast, indicating the presence of a tumour suppressor gene (TSG) at this region in these tumours. However, the TSG (s) at the 16q22.1 in the more frequent nonlobular carcinomas is still unknown. Multiplex Amplifiable Probe Hybridisation (MAPH) is a simple, accurate and a high‐resolution technique that provides an alternative approach to DNA copy‐number measurement. The aim of our study was to examine the most likely candidate genes at 16q22.1 using MAPH assay combined with protein expression analysis by immunohistochemistry. We identified deletion at 16q22.1 that involves some or all of these genes. We also noticed that the smallest region of deletion at 16q22.1 could be delineated to a 3 Mb region centromeric to the P‐cadherin gene. Apart from the correlation between E‐cadherin protein expression and its gene copy number, no correlation was detected between the expression of E2F‐4, CTCF, TRF2 or P‐cadherin with their gene's copy number. In the malignant tissues, no significant loss or decrease of protein expression of any gene other than E‐cadherin was seen in association with any specific tumour type. No expression of VE‐cadherin or Ksp‐cadherin was detected in the normal and/or malignant tissues of the breast in these cases. However, there was a correlation between increased nuclear expression of E2F‐4 and tumours with higher histological grade (p = 0.04) and positive lymph node disease (p = 0.02), suggesting that it may have an oncogenic rather than a tumour suppressor role. The malignant breast tissues also showed abnormal cytoplasmic cellular localisation of CTCF, compared to its expression in the normal parenchymal cells. In conclusion, we have demonstrated that MAPH is a potential technique for assessment of genomic imbalances in malignant tissues. Although our results support E‐cadherin as the TSG in invasive lobular carcinoma, they argue against the candidacy of E2F‐4, CTCF, TRF2, P‐cadherin, Ksp‐cadherin and VE‐cadherin as TSGs in breast cancer. © 2004 Wiley‐Liss, Inc.
GSK3 and PKB/Akt are associated with integrin‐mediated regulation of PTHrP, IL‐6 and IL‐8 expression in FG pancreatic cancer cells
Authors: Grzesiak John J. , Smith Kathy C. , Burton Douglas W. , Deftos Leonard J. , Bouvet Michael 
Published: December 2004

AbstractWe have demonstrated recently that PTHrP is upregulated in pancreatic adenocarcinoma and that the ECM exerts regulatory control, at least in part, over PTHrP expression. In our present study, we examined the potential signaling interactions between these 2 pathways. Our results demonstrate that, under serum‐free conditions, adhesion of FG pancreatic adenocarcinoma cells on Fn is mediated by the α5β1 integrin, whereas adhesion to Type I collagen is mediated by the α2β1 integrin. α5β1 integrin‐mediated adhesion to Fn results in a phenotype that includes a reduction in cell proliferation, increased E‐cadherin localization in cell–cell contacts, increased β‐catenin localization throughout the cell, inhibition of haptokinetic cell migration, and increased expression of PTHrP, IL‐6 and IL‐8 relative to α2β1 integrin‐mediated adhesion on Type I collagen. A phosphoprotein immunoblotting screen of FG pancreatic cancer cells grown on either Fn or Type I collagen indicates that GSK3 and PKB/Akt are differentially phosphorylated on these 2 substrates. These results implicate GSK3 and PKB/Akt in the integrin‐mediated regulation of PTHrP, IL‐6 and IL‐8 in pancreatic cancer. © 2004 Wiley‐Liss, Inc.
Estimating dose‐response relationship between ethanol and risk of cancer using regression spline models
Authors: Polesel Jerry , Dal Maso Luigino , Bagnardi Vincenzo , Zucchetto Antonella , Zambon Antonella , Levi Fabio , La Vecchia Carlo , Franceschi Silvia 
Published: December 2004

AbstractCancers of the upper aero‐digestive tract (i.e., oral cavity, pharynx, larynx and oesophagus) are largely attributable to smoking and drinking habits, but the correct estimation of the dose‐response relationship between alcohol and cancer risk is challenging. Step functions are widely used to estimate risks and to evaluate trends of continuous exposure. However, results are influenced by the selection of the reference category and cutpoints. More flexible models, like spline regression and fractional polynomial models, may be an attractive alternative for avoiding strict assumptions about the dose‐response relationship. Data from a large series of hospital‐based case‐control studies conducted in Italy and the Swiss Canton of Vaud in the last 2 decades were reassessed to compare findings from logistic regression spline models and standard step function analysis. For all examined cancers, the risk increased to the consumption of 150 grams of ethanol per day (1.5 litre/day of wine), with a possible threshold effect emerging for cancer of the pharynx and larynx (<50 grams of ethanol per day) only. For higher consumptions, the risks flattened. Our study suggests that regression spline models can be useful to estimate the pattern of risk of a continuous exposure variable, such as alcohol consumption, and provide more accurate estimates than categorical analysis when ORs within each interval, especially in the reference category, are not homogeneous. © 2004 Wiley‐Liss, Inc.
Treatment of multi‐focal colorectal carcinoma metastatic to the liver of immune‐competent and syngeneic rats by hepatic artery infusion of oncolytic vesicular stomatitis virus
Authors: Shinozaki Katsunori , Ebert Oliver , Woo Savio L.C. 
Published: December 2004

AbstractViruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. We report an orthotopic model of multi‐focal colorectal cancer (CRC) metastases in the livers of syngeneic and immune‐competent rats, which permitted rigorous testing of oncolytic virus vectors as novel therapeutic agents through hepatic arterial infusion for efficacy and safety. Vesicular stomatitis virus (VSV) is a negative‐strand RNA virus with intrinsic oncolytic specificity due to attenuated anti‐viral responses in many tumors. After administration at the maximum tolerated dose, the recombinant VSV vector gained access to multi‐focal hepatic CRC lesions that led to tumor‐selective viral replication and oncolysis. No relevant vector‐associated toxicities were noted and in particular, no damage to the hepatic parenchyma was seen. Moreover, the survival rate of vector‐treated rats was significantly improved over that of animals in the control treatment group (p = 0.015). Our results demonstrate that hepatic arterial administration of oncolytic VSV is both effective and safe in an immune‐competent and syngeneic rat model of multi‐focal CRC liver metastasis, suggesting that it can be developed into an effective therapeutic modality in patients in the future. © 2004 Wiley‐Liss, Inc.
Loss of stearoyl‐CoA desaturase expression is a frequent event in prostate carcinoma
Authors: Moore Stacy , Knudsen Beatrice , True Lawrence D. , Hawley Sarah , Etzioni Ruth , Wade Christian , Gifford David , Coleman Ilsa , Nelson Peter S. 
Published: December 2004

AbstractProstate carcinogenesis is influenced by genetic alterations resulting in a biochemical condition that favors cell proliferation and survival. Studies of prostate carcinoma using comparative genomic hybridization and cDNA microarray analysis indicate that numerous biochemical processes may be affected during cellular transformation and progression to an invasive phenotype. Among the consistently observed tumor‐associated changes are alterations in fatty acid metabolism that influence diverse cellular activities such as signaling, energy utilization, and membrane fluidity. Increases in fatty acid synthase (FAS) levels have been shown to be one of the earliest and most frequent molecular alterations in prostate carcinogenesis. We sought to identify tumor‐associated changes in the expression of genes with functional roles associated with lipid metabolism. Defined populations of normal and neoplastic prostate epithelium were acquired by laser capture microdissection and transcript levels were measured by cDNA microarray hybridization. We determined that stearoyl‐CoA desaturase (SCD) transcripts were downregulated in cancer relative to normal epithelium. These results were confirmed by quantitative PCR. Further analysis by immunohistochemical evaluation of radical prostatectomy samples employed a quantitative scoring system with a range of 0–300. The median SCD expression levels were 150, 45 and 10 for normal, PIN and carcinoma samples, respectively. Statistically significant differential SCD expression between normal and cancerous epithelium was determined at the p = 0.001 level, and between PIN and prostate carcinoma at the p = 0.03 level. Of these cases, 92% overexpressed fatty acid synthase (FAS) in cancerous cells and 84.7% exhibited the signature of FAS overexpression and SCD loss in prostate carcinoma as compared to normal prostate epithelium. These results indicate that loss of SCD expression is a frequent event in prostate adenocarcinoma, and further supports a role for altered lipid metabolism as a factor in the process of carcinogenesis. © 2004 Wiley‐Liss, Inc.
Dietary folate intake and k‐ras mutations in sporadic colon and rectal cancer in the Netherlands Cohort Study
Authors: Brink Mirian , Weijenberg Matty P. , de Goeij Anton F.P.M. , Roemen Guido M.J.M. , Lentjes Marjolein H.F.M. , de Bruïne Adriaan P. , van Engeland Manon , Goldbohm R. Alexandra , van den Brandt Piet A. 
Published: December 2004

AbstractWe studied the association between dietary folate and specific K‐ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow‐up, 448 colon and 160 rectal cancer patients and 3,048 sub‐cohort members (55–69 years at baseline) were available for data analyses. Mutation analysis of the K‐ras gene was carried out on all archival adenocarcinoma specimens. Case–cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K‐ras mutation status subgroups according to 100 μg/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K‐ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K‐ras mutated tumors, whereas an increased association was observed for women. Regarding the K‐ras mutation status in women, an increased association was observed for both wild‐type and mutated K‐ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43–5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01–0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K‐ras mutation status of the tumor. © 2004 Wiley‐Liss, Inc.
Role of cyclooxygenase‐2 in immunomodulation and prognosis of endometrial carcinoma
Authors: Ohno Yumiko , Ohno Satoshi , Suzuki Nobutaka , Kamei Tsutomu , Inagawa Hiroyuki , Soma Gen‐Ichiro , Inoue Masaki 
Published: December 2004

AbstractAlthough there are several hypotheses explaining the mechanisms of immune‐privileged status of malignant tumor, the exact pathway has yet to be explored. Cyclooxygenase (COX)‐2 plays a vital role in prognosis of cancer patients in terms of contribution to neoangiogenesis and apoptosis inhibition; however, the impact of COX‐2 in immunomodulation has not been reported. We have evaluated the expression of COX‐2 and its impact on infiltration of immune‐competent cells into the tumor cell nest in endometrial carcinoma. Tissue specimens from 70 endometrial carcinoma patients who had undergone a curative resection were evaluated for COX‐2 expression and host immune status (CD8+ T cells). COX‐2 expression was associated with FIGO stage and myometrial invasion, but there was no statistically significant impact. CD8+ T cells within cancer cell nest (Nest CD8) were inversely correlated with the expression level of COX‐2 (p = 0.0006). Nest CD8 became an independent predictor of patient survival (Hazard ratio = 10.300, p = 0.0304) in Cox's multivariate analysis. The expression level of COX‐2 was found to be a significant predictor of disease relapse in univariate analysis (p = 0.0294) but not in multivariate analysis (p = 0.5949). In conclusion, increased nest CD8 produced a survival advantage in endometrial carcinoma patients. Moreover, tumor‐produced COX‐2, which reduces the infiltration of CD8+ T cells into cancer cell nests, may allow tumors to avoid immune surveillance. © 2004 Wiley‐Liss, Inc.