bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin‐linked kinase expression increases with ovarian tumour grade and is sustained by peritoneal tumour fluid
Authors: Ahmed Nuzhat , Riley Clyde , Oliva Karen , Stutt Emma , E Rice Greg , A Quinn Michael 
Published: September 2003

AbstractIntegrin‐linked kinase (ILK) is a serine threonine kinase, overexpression of which promotes tumour growth and invasion through deregulation of the cell cycle. This study demonstrates the relative expression of ILK in normal, benign, low‐grade, and high‐grade (borderline, grade I/II, and grade III) ovarian tumours of serous, mucinous, endometrioid, and clear cell types in order to assess its potential as a marker for epithelial ovarian cancer progression. Seventy‐three specimens including ten normal, ten benign, 14 borderline, 17 grade I/II, and 22 grade III were evaluated by immunohistochemistry. Immunoreactive ILK was not detectable in normal ovarian surface epithelium. All 53 carcinomas studied were positive and the staining intensity correlated significantly with the grade of the tumour. Ovarian cancer cell lines had high expression of ILK, while immortalized normal ovarian surface epithelial cell lines (HOSE) showed low basal expression of ILK by western blotting. Peritoneal tumour fluid (PTF) upregulated ILK expression in ovarian cancer cell lines but had no effect on HOSE cells. PTF‐induced up‐regulation of ILK expression in ovarian cancer cell lines correlated with the activation of the downstream protein kinase B (PKB/Akt) pathway. Collectively, these data demonstrate that ILK expression increases with ovarian cancer progression and that soluble factors in PTF mediate sustained overexpression of ILK in ovarian cancer cells. Suppression of ILK expression may therefore represent a novel and an efficient mechanism for controlling ovarian tumour growth. Copyright © 2003 John Wiley & Sons, Ltd.
Epstein–Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas
Authors: Wong NACS , Herbst H , Herrmann K , Kirchner T , Krajewski AS , Moorghen M , Niedobitek F , Rooney N , Shepherd NA , Niedobitek G 
Published: September 2003

AbstractEpstein–Barr virus (EBV) is associated with several lymphoid and epithelial human malignancies. The latter include gastric adenocarcinomas, while sporadic colorectal adenocarcinomas (CRCs) have been reported to be EBV‐negative. Recently, increased numbers of EBV‐infected B lymphocytes have been detected in intestinal mucosal samples affected by ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD). Both CRC and colorectal non‐Hodgkin's lymphoma (NHL) are recognized complications of inflammatory bowel disease (IBD), but it is unclear to what extent EBV contributes to the development of these neoplasms. Seventeen cases of IBD‐associated CRC and nine cases of IBD‐associated colorectal NHL were therefore studied for the presence of EBV by in situ hybridization. EBV‐positive cases were further studied for the expression of the EBV‐encoded nuclear antigen (EBNA) 2 and the latent membrane protein (LMP) 1 of EBV by immunohistochemistry. Four out of seven cases of colorectal NHL associated with UC were shown to be EBV‐positive. In addition, two of two colorectal NHLs developing in patients with CD were EBV‐positive. Of the EBV‐positive lymphomas, three displayed a pattern of EBV latent gene expression consistent with type I latency (EBNA2−/LMP1−), two a type II pattern (EBNA2−/LMP1+), and one a type III pattern (EBNA2+/LMP1+). These findings suggest that EBV infection is involved in the pathogenesis of a proportion of colorectal NHLs developing in IBD. Iatrogenic immunosuppression may contribute to the development of these lymphomas. By contrast, all 17 IBD‐associated CRCs were EBV‐negative, including a case of CRC occurring synchronously with an EBV‐positive NHL. In conjunction with previous reports on sporadic CRCs, this suggests that EBV is not involved in the pathogenesis of CRC. Copyright © 2003 John Wiley & Sons, Ltd.
Differential expression of CD146 in tissues and endothelial cells derived from infantile haemangioma and normal human skin
Authors: Li Qing , Yu Ying , Bischoff Joyce , Mulliken John B , Olsen Bjorn R 
Published: September 2003

AbstractHaemangioma is the most common tumour of endothelial origin, occurring in 4–10% of Caucasian infants. It is characterized by rapid growth during the first year of postnatal life, followed by spontaneous regression from 1 to 7 years of age. The cell surface adhesion molecule CD146 has been identified as an endothelial cell marker. Despite advances in understanding the functional role of CD146 in normal endothelial cells and tumour progression, its expression and a possible role in an endothelial tumour have not been studied. As part of an investigation of endothelial cell alterations in infantile haemangioma, differential expression studies were performed with several known antigens and endothelial cell markers. Using immunohistochemical and flow cytometric analyses, cultured human dermal microvascular endothelial cells isolated from newborn foreskin (HDMEC) were compared with endothelial cells derived from haemangioma tissue (HemECs). In addition, immunohistochemistry was used to compare haemangioma tissues with normal human skin. Unexpectedly, cultured HemECs showed a significantly lower level of CD146 than HDMECs by both flow cytometric analysis and immunofluorescence staining. Using immunohistochemical studies, it was further demonstrated that endothelia in all haemangioma tissues, regardless of the tumour phase, showed negative immunoreactivity for CD146. In contrast, strong positive staining for CD146 was observed in the pericyte‐like cells that surround the endothelial layers. These findings are believed to be relevant to the molecular basis of haemangioma. Furthermore, it is possible that antibodies against CD146 may be useful for separating haemangioma‐derived endothelial cells from normal endothelial cells and pericytes. Copyright © 2003 John Wiley & Sons, Ltd.
A novel immunohistochemical method to estimate cell‐cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer
Authors: Scott Ian S , Morris Lesley S , Bird Kate , Davies R Justin , Vowler Sarah L , Rushbrook Simon M , Marshall Aileen E , Laskey Ronald A , Miller Richard , Arends Mark J , Coleman Nicholas 
Published: September 2003

AbstractAn immunohistochemical method for assessing cell‐cycle phase distribution in colorectal resection specimens would enable phase data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in colorectal cancer. In contrast to flow cytometry, an immunohistochemical method would also allow the phase distribution to be examined within morphologically heterogeneous regions of neoplasms. Paraffin sections of normal colon (n = 25), colonic adenoma (n = 15), and colonic adenocarcinoma (n = 30) were analysed by immunohistochemistry using antibodies against markers of cell‐cycle entry, Mcm‐2 and Ki67, and putative markers of the cell‐cycle phase, cyclins D1 and E (putative markers of G1 phase), cyclin A (S phase), cytoplasmic cyclin B1 (G2 phase), and phosphohistone H3 (M phase). The phase specificity of each marker was assessed by examining the degree of co‐expression of adjacent phase markers using double‐antibody fluorescence confocal microscopy and by comparison with flow cytometric analysis performed on adjacent tissue sections. The S‐phase specificity of detectable cyclin A was also assessed in combination with in situ DNA replication using fluorescence confocal microscopy. All cells expressing phase markers co‐expressed Mcm‐2. Adjacent phase markers were not significantly co‐expressed, confirming the relative specificity of these markers in tissue sections of colon. Cell‐cycle phase distribution, calculated by immunohistochemistry, compared well with phase analyses obtained by flow cytometry. No cells expressed cyclin A in the absence of active DNA replication. The S‐phase labelling index, as defined by detectable cyclin A expression, showed a positive correlation with the Mcm‐2 labelling index and increased in the progression from normal colon to adenocarcinoma. In conclusion, a combination of these cell‐cycle phase markers can be used to calculate the distribution of cells throughout each phase of the cell cycle in colorectal tissue sections. Detectable cyclin A can be used as a surrogate marker of S phase and may be of value in predicting prognosis and response to adjuvant therapy. Copyright © 2003 John Wiley & Sons, Ltd.
Detection of apoptosis using in situ markers for DNA strand breaks in the failing human heart. Fact or epiphenomenon?
Authors: Hughes Siân E 
Published: September 2003

AbstractThe role of apoptosis and the methods used for its detection in failing human hearts are controversial. Recent data have challenged the hypothesis that in situ markers for DNA strand breaks mirror apoptotic (TUNEL and Taq in situ ligation assay) and/or necrotic (Pfu in situ ligation assay) cell death, and thus provide evidence that apoptotic cell loss contributes to the progression of heart failure. Experimental data cast doubt not only upon the specificity of the TUNEL technique but also the Taq in situ ligation assay as a reliable method for the detection of apoptotic cell death and provide compelling new evidence that the occurrence of cardiomyocyte cell death as defined by the detection of DNA strand breaks using either TUNEL or Taq and Pfu in situ ligation assays is an epiphenomena that is not related to the evolution of heart failure. Cardiomyocyte positivity for in situ markers of DNA strand breaks is a feature of hypertrophic cardiomyopathic hearts, irrespective of the underlying pathology or the presence or absence of heart failure. These data raise concerns regarding the extent of apoptosis in cardiomyopathy and the contribution of this process to the progression of heart failure. Copyright © 2003 John Wiley & Sons, Ltd.
Beta‐catenin accumulation in the progression of human hepatocarcinogenesis correlates with loss of E‐cadherin and accumulation of p53, but not with expression of conventional WNT‐1 target genes
Authors: Prange Wilhelm , Breuhahn Kai , Fischer Frank , Zilkens Christoph , Pietsch Torsten , Petmecky Katharina , Eilers Renate , Dienes Hans‐Peter , Schirmacher Peter 
Published: September 2003

AbstractBeta‐catenin integrates intracellular WNT signalling and the intercellular E‐cadherin–catenin adhesion system. To date, little is known about the role of β‐catenin activation and nuclear accumulation in hepatocarcinogenesis. This study has analysed β‐catenin expression patterns in human dysplastic nodules (DNs), as well as in hepatocellular carcinomas (HCCs) in comparison with proliferation, expression of WNT‐1 target genes, E‐cadherin, and p53. One hundred and seventy HCCs and 25 DNs were categorized according to established criteria and analysed for the expression pattern of β‐catenin. Analysis of the proliferative activity and expression of E‐cadherin, cyclin D1, MMP‐7, c‐myc, and p53 was performed on a representative subgroup of cases. All DNs lacked nuclear β‐catenin, while 36% of all HCCs were positive, with the number of nuclear stained cells ranging from less than 1% to more than 90%. Increasing nuclear accumulation of β‐catenin correlated with reduced membranous E‐cadherin expression and nuclear p53 but not with proliferation. Cyclin D1, MMP‐7, and c‐myc expression was detected in 54%, 26%, and 65% of HCCs, respectively, but did not correlate with nuclear β‐catenin, proliferation, or grading. Sequence analysis of the β‐catenin gene revealed no detectable mutations in DNs, but mutations in the GSK‐3β binding site were present in 14.3% of the HCCs. In conclusion, this study has demonstrated that nuclear accumulation of β‐catenin is a frequent progression event in human hepatocarcinogenesis which correlates with nuclear p53 accumulation and loss of membranous E‐cadherin, but not with the expression pattern of established WNT‐1 target genes. It is hypothesized that the role of β‐catenin in human HCC differs significantly from its established function in colon carcinogenesis. Copyright © 2003 John Wiley & Sons, Ltd.
WIF1, a component of the Wnt pathway, is down‐regulated in prostate, breast, lung, and bladder cancer
Authors: Wissmann Christoph , Wild Peter Johannes , Kaiser Simone , Roepcke Stefan , Stoehr Robert , Woenckhaus Matthias , Kristiansen Glen , Hsieh Jen‐Chih , Hofstaedter Ferdinand , Hartmann Arndt , Knuechel Ruth , Rosenthal André , Pilarsky Christian 
Published: September 2003

AbstractTo detect novel Wnt‐pathway genes involved in tumourigenesis, this study analysed the RNA expression levels of 40 genes of the Wnt pathway by chip hybridization of microdissected matched pairs of 54 primary prostate carcinomas. Eleven genes showed greater than two‐fold differential expression in at least 10% of prostate cancers. Three of these genes encode extracellular components of the Wnt pathway (WNT2, WIF1, SFRP4); two are receptors (FZD4, FZD6); two belong to the intracellular signal cascade (DVL1, PPP2CB); one regulates transcription (TCF4); and three represent genes regulated by this pathway (CCND2, CD44, MYC). While SFRP4, FZD4, FZD6, DVL1, TCF4, and MYC are up‐regulated, WIF1, WNT2, PPP2CB, CCND2, and CD44 are down‐regulated in certain prostate cancer patients. Wnt inhibitory factor 1 (WIF1) and secreted frizzled related protein (SFRP4) showed the most significant aberrant expression at the RNA level. WIF1 was down‐regulated in 64% of primary prostate cancers, while SFRP4 was up‐regulated in 81% of the patients. Immunohistochemical analysis using a polyclonal antibody revealed strong cytoplasmic perinuclear WIF1 expression in normal epithelial cells of the prostate, breast, lung, and urinary bladder. Strong reduction of WIF1 protein expression was found in 23% of prostate carcinomas, but also in 60% of breast, 75% of non‐small cell lung (NSCLC), and 26% of bladder cancers analysed. No significant association between WIF1 down‐regulation and tumour stage or grade was observed for prostate, breast or non‐small cell lung carcinomas, indicating that loss of WIF1 expression may be an early event in tumourigenesis in these tissues. However, down‐regulation of WIF1 correlated with higher tumour stage in urinary bladder tumours (pTa versus pT1–pT4; p = 0.038). Copyright © 2003 John Wiley & Sons, Ltd.
FANCD2 protein is expressed in proliferating cells of human tissues that are cancer‐prone in Fanconi anaemia
Authors: Hölzel Michael , van Diest Paul J , Bier Patrick , Wallisch Michael , Hoatlin Maureen E , Joenje Hans , de Winter Johan P 
Published: September 2003

AbstractFanconi anaemia (FA) is an inherited form of progressive pancytopenia associated with developmental defects, chromosomal instability, and cancer predisposition. At least seven distinct FA proteins function in concert to protect the genome, a key step being the activation of FANCD2 by mono‐ubiquitination. This paper reports an immunohistochemical analysis of FANCD2 expression in normal human tissue. The highest expression was observed in maturing spermatocytes and fetal oocytes (consistent with a role for FANCD2 in meiosis) and in germinal centre cells of the spleen, tonsil, and lymph nodes (consistent with a role in proliferation). FANCD2 expression was also seen in tissues predisposed to cancer development in FA patients: haematopoietic cells, especially in the fetus, and squamous cell epithelia, particularly in the head and neck region and uterine cervix. FANCD2 expression was also occasionally seen in the breast and Fallopian tube epithelium, the respiratory epithelium of the trachea, and the exocrine cells of the pancreas, indicating that these tissues may also be cancer‐prone in FA. FANCD2 expression is frequently expressed in proliferating cells as demonstrated by Ki‐67 immunofluorescence double staining, consistent with a function of FANCD2 in DNA replication. Copyright © 2003 John Wiley & Sons, Ltd.
Quantitative RT‐PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesis
Authors: Colombat Magali , Paradis Valérie , Bièche Ivan , Dargère Delphine , Laurendeau Ingrid , Belghiti Jacques , Vidaud Michel , Degott Claude , Bedossa Pierre 
Published: September 2003

AbstractCirrhosis is considered to be the precursor of most hepatocellular carcinomas. To gain insight into the early molecular mechanisms of liver carcinogenesis, this study compared, using real‐time quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR), the expression levels of 31 selected genes in normal livers, cirrhotic nodules, and hepatocellular carcinomas. Since cirrhosis is composed of a mixture of polyclonal and monoclonal nodules, gene expression levels were also compared according to the clonal status of the cirrhotic nodules. The expression of eight of the 31 genes studied was significantly increased (NEGF2, ANGPT1, ARF, KRT19, SFN, CLDN4, MMP7, and ETV4) in cirrhotic nodules compared with normal liver, while only one was decreased (LYVE1). The same trend of variation was observed in cirrhosis and hepatocellular carcinomas for all of these genes except KRT19. When gene expression variation was compared according to the clonal status of cirrhotic nodules, only the LYVE1 expression level was significantly different. The LYVE1 gene expression level decreased progressively from polyclonal cirrhotic nodules to monoclonal cirrhotic nodules (polyclonal nodules 0.39 ± 0.25; monoclonal nodules 0.20 ± 0.14; p < 0.05) and to hepatocellular carcinoma (0.07 ± 0.1). In conclusion, this study highlights the fact that among genes strongly dysregulated in hepatocellular carcinoma, some are already abnormally expressed in cirrhosis. The decrease in the expression level of one of these genes, LYVE1, was associated with monoclonality in cirrhotic nodules. Copyright © 2003 John Wiley & Sons, Ltd.
Compositional heterogeneity effects in multisticker associative polyelectrolytes prepared by micellar polymerization
Authors: Kujawa Piotr , Audibert‐Hayet Annie , Selb Joseph , Candau Françoise 
Published: September 2003

AbstractAn aqueous micellar radical polymerization technique has been used to prepare water‐soluble polyelectrolytes of acrylamide (AM) and sodium 2‐acrylamido‐2‐methylpropanesulfonate (NaAMPS) hydrophobically modified with low amounts (2–4 mol %) of N,N‐dihexylacrylamide (DiHexAM). This synthesis method leads to multisticker polymers, in which the number and length of the hydrophobic blocks vary with the degree of conversion. Kinetic studies show an appreciable compositional heterogeneity for these polymers, in contrast to their neutral analogues (i.e., AM/DiHexAM copolymers). The drift in composition observed for the AM/NaAMPS/DiHexAM terpolymers is attributed to the electrostatic repulsion between the negatively charged growing polymeric chains, located in the aqueous continuous medium, and the anionic sodium dodecyl sulfate micelles, inside of which the hydrophobic monomer is entrapped. It is shown that an optimization of the polymerization process can be achieved, which gives terpolymers of homogeneous and well‐defined compositions. The thickening ability of the hydrophobically modified polyelectrolytes is directly affected by the extent of their compositional heterogeneity: an increase in the sample homogeneity leads to a significant viscosity enhancement and marked elastic properties of the polymer solutions. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3261–3274, 2003
Complex polymer architectures through dimethoxymethyl 1,1‐diphenylethylene derivatives
Authors: Meyer Nicolas , Eddine Mohamad Nasser , Delaite Christelle , Hurtrez Guy , Dumas Philippe 
Published: September 2003

AbstractThe reactions of polystyryllithium and potassium on dimethoxymethyl 1,1‐diphenylethylene derivatives were studied in different solvents. In a polar medium, A3 and A6 star types were formed according to the stoichiometry, whereas in a nonpolar medium, hyperbranched structures were synthesized. Extensions of an already proposed mechanism in polar and nonpolar media were examined. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3329–3335, 2003
Synthesis and characterization of poly(methyl methacrylate)/casein nanoparticles with a well‐defined core‐shell structure
Authors: Zhu Junmin , Li Pei 
Published: September 2003

AbstractWell‐defined, core‐shell poly(methyl methacrylate) (PMMA)/casein nanoparticles, ranging from 80 to 130 nm in diameter, were prepared via a direct graft copolymerization of methyl methacrylate (MMA) from casein. The polymerization was induced by a small amount of alkyl hydroperoxide (ROOH) in water at 80 °C. Free radicals on the amino groups of casein and alkoxy radicals were generated concurrently, which initiated the graft copolymerization and homopolymerization of MMA, respectively. The presence of casein micelles promoted the emulsion polymerization of the monomer and provided particle stability. The conversion and grafting efficiency of the monomer strongly depended on the type of radical initiator, ROOH concentration, casein to MMA ratio, and reaction temperature. The graft copolymers and homopolymer of PMMA were isolated and characterized with Fourier transform infrared spectroscopy and differential scanning calorimetry. The molecular weight determination of both the grafted and homopolymer of PMMA suggested that the graft copolymerization and homopolymerization of MMA proceeded at a similar rate. The transmission electron microscopic image of the nanoparticles clearly showed a well‐defined core‐shell morphology, where PMMA cores were coated with casein shells. The casein shells were further confirmed with a zeta‐potential measurement. Finally, this synthetic method allowed us to prepare PMMA/casein nanoparticles with a solid content of up to 31%. Thus, our new process is commercially viable. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3346–3353, 2003
Synthesis and characterization of novel polyimides with 2,2‐bis[4(4‐aminophenoxy)phenyl]phthalein‐3′,5′‐bis(trifluoromethyl)anilide
Authors: Myung B. Y. , Kim J. S. , Kim J. J. , Yoon T. H. 
Published: September 2003

Abstract2,2‐Bis[4(4‐aminophenoxy)phenyl]phthalein‐3′,5′‐bis(trifluoromethyl)anilide (6FADAP), containing fluorine and phthalimide moieties, was synthesized via the Williamson ether condensation reaction from 1‐chloro‐4‐nitrobenzene and phenolphthalein‐3′,5′‐bis(trifluoromethyl)anilide, which was followed by hydrogenation. Monomers such as 2,2‐bis[4(4‐aminophenoxy)phenyl]phthalein‐anilide containing phthalimide groups and 2,2‐bis[4(4‐aminophenoxy)phenyl]phthalein containing only phthalein moieties were also synthesized for comparison. The monomers were first characterized by Fourier transform infrared (FTIR), 1H NMR, 19F NMR, elemental analysis, and titration and were then used to prepare polyimides with 2,2‐bis(3,4‐dicarboxyphenyl)hexafluoropropane dianhydride. The polyimides were designed to have molecular weights of 20,000 g/mol via off‐stoichiometry and were characterized by FTIR, NMR, gel permeation chromatography (GPC), differential scanning calorimetry, and thermogravimetric analysis. Their solubility, water absorption, dielectric constant, and refractive index were also evaluated. The polyimides prepared with 6FADAP, containing fluorine and phthalimide moieties, had excellent solubility in N‐methylpyrrolidinone, N,N‐dimethylacetamide, tetrahydrofuran, CHCl3, tetrachloroethane, and acetone, and GPC analysis showed a molecular weight of 18,700 g/mol. The polyimides also exhibited a high glass‐transition temperature (290 °C), good thermal stability (∼500 °C in air), low water absorption (1.9 wt %), a low dielectric constant (2.81), a low refractive index, and low birefringence (0.0041). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3361–3374, 2003