bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Ly‐6 antigen E48 (Ly‐6D) regulates important interaction parameters between endothelial cells and head‐and‐neck squamous carcinoma cells
Authors: Eshel Rinat , Zanin Alexandra , Kapon Dina , Sagi‐Assif Orit , Brakenhoff Ruud , van Dongen Guus , Witz Isaac P. 
Published: August 2002

AbstractSelectin ligands are crucial components in the interaction between endothelial cells and extravasating cancer cells and, thus, play an important role in metastasis formation. Head‐and‐neck squamous cell carcinoma (HNSCC) variants expressing high levels of E48, a human Ly‐6 protein (E48hi), expressed higher levels of the fucose‐generating FX enzyme and of the fucosylated E‐selectin ligand sLea than cells expressing low levels of E48 (E48lo). Signaling through E48 upregulated expression levels of these molecules in HNSCC. In this work, we provide further evidence supporting the E48–FX–sLea link by showing that FX antisense oligonucleotides reduced sLea expression levels in HNSCC. We also show that E48 may be causally involved in regulating expression levels in HNSCC of 2 additional enzymes involved in the biosynthesis of sLea, namely, ST‐30 and FucTIII. Also, selectin‐mediated adhesion of E48hi variants to activated HUVECs was significantly higher than that of E48lo variants. Transfection experiments utilizing sense or antisense E48 cDNA indicated that E48 may be causally involved in this adhesion. Chemokines are involved in the extravasation process of tumor cells. The release of chemoattractants from HNSCC variants differing in E48 expression was therefore analyzed. HNSCC did not release any chemoattractants but induced the release of such factors from HUVECs. Supernatants from E48hi variants were significantly more efficient than E48lo cells at inducing the release of chemoattractants from HUVECs. Transfection experiments indicated that E48 may be causally involved in the induction of chemoattractant release from HUVECs. Angiogenesis is an important manifestation of cancer–endothelium interactions. We therefore assayed for the presence of angiogenic factors in culture supernatants of HNSCC. Supernatants from E48lo variants contained significantly higher amounts of PDGF than E48hi cells. Transfection experiments indicated that E48 may be causally involved. Taken together, our results suggest that E48 controls important interaction parameters between HNSCC and endothelial cells. © 2002 Wiley‐Liss, Inc.
Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets
Authors: Vihinen Pia , Kähäri Veli‐Matti 
Published: August 2002

AbstractDegradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc‐dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer. © 2002 Wiley‐Liss, Inc.
Heparin‐derived disaccharides modulate proliferation and Erb‐B2–mediated signal transduction in colon cancer cell lines
Authors: Fishman Sigal , Brill Shlomo , Papa Moshe , Halpern Zamir , Zvibel Isabel 
Published: August 2002

AbstractOrgan‐specific extracellular matrix (ECM) determines metastasis formation by regulating tumor cell proliferation. Hepatocyte‐derived ECM enhances proliferation of colon cancer cell lines by increasing expression of tyrosine kinase receptors of the erb‐B family. The active components in the ECM are the heparan sulfates, which are highly heterogenous in their chemistry and size. We determined the effect of heparan sulfate disaccharides, of defined chemistry and present in high amounts in the liver heparan sulfate chains, on the proliferation of colon cancer cell lines and investigated the mechanism involved. The low‐metastatic cell line KM12 was stimulated to proliferate by a highly sulfated disaccharide, found in the highest amounts in hepatocyte‐derived heparan sulfate. Growth of the highly metastatic cell line KM12SM was inhibited by the second most common disaccharide in hepatocyte‐derived heparan sulfate. The effect of both disaccharides was not accompanied by changes in the expression of erb‐B1, erb‐B2, erb‐B3 or heregulin‐α. We determined whether the disaccharides modified the signal‐transduction pathways mediated by the erb‐B receptors. The erb‐B2‐specific tyrosine kinase inhibitor AG825 abolished the enhancement of KM12 cell proliferation by the stimulatory disaccharide. This disaccharide increased tyrosine phosphorylation of erb‐B1 and erb‐B2 receptors, effects that were abolished by AG825. Moreover, the disaccharide caused increased expression of cyclin D1 and of activated MAP kinase, again reduced in the presence of the inhibitor AG825. The growth‐inhibitory disaccharide reduced phosphorylation of erb‐B1, but not of erb‐B2, receptors in KM12SM cells. In conclusion, not only hepatocyte‐derived heparan sulfate but also disaccharide molecules derived from heparan sulfate can affect colon cancer cell proliferation. Their effect is mediated by modulation of the erb‐B signal transduction. © 2002 Wiley‐Liss, Inc.
Laminin‐γ2 overexpression in head‐and‐neck squamous cell carcinoma
Authors: Patel Vyomesh , Aldridge Kay , Ensley John F. , Odell Edward , Boyd Andrea , Jones Judith , Gutkind J. Silvio , Yeudall W. Andrew 
Published: August 2002

AbstractTo identify molecular markers for the progression of head‐and‐neck squamous cell carcinoma (HNSCC), we used RNA arbitrarily primed (RAP) PCR to determine the qualitative and quantitative differences in gene expression between normal epithelial cells, those derived from dysplastic oral mucosa and invasive and metastatic HNSCC. Three differentially expressed DNA fragments (RAP20, RAP21, RAP26) that were upregulated in a tumor cell line (T45) were identified as being regions of the γ2 subunit of human laminin‐5. Northern blot analysis of total cellular RNA revealed overexpression of these transcripts in 6 of 7 HNSCC cell lines compared with normal epidermal keratinocytes. In contrast, no differences were observed in HeLa (cervical carcinoma) or HCT116 (colon carcinoma) cells. Immunostaining of HNSCC cells derived from primary (HN4) and metastatic (HN12) tumors indicated elevated levels of endogenous laminin‐γ2 protein. Furthermore, HNSCC tissues demonstrated strong laminin‐γ2 staining, particularly in the peripheral basaloid cells of tumor islands at the invasion front. In contrast, only minimal staining of laminin‐γ2 was detected in basal cells of the normal epithelium. The data indicate that laminin‐γ2 is frequently overexpressed in HNSCCs and derivative cell lines and that its overexpression is likely to be useful as a marker of head‐and‐neck squamous malignancy. © 2002 Wiley‐Liss, Inc.
Expression of UPA and UPAR is associated with the clinical course of urinary bladder neoplasms
Authors: Seddighzadeh Maria , Steineck Gunnar , Larsson Per , Wijkström Hans , Norming Ulf , Onelöv Erik , Linder Stig 
Published: August 2002

AbstractThe expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNA was determined in 194 subjects with newly detected bladder neoplasms, selected from a larger population‐based series. An association was found between uPA and uPAR expression (n = 172; Spearman rs = 0.60, p < 0.001). Both uPA and uPAR mRNA levels were higher in muscle invasive (T2+) tumors than in noninvasive mucosal tumors (Ta) or those invading submucosa (T1). The relative hazard ratios (RHRs) for cancer‐specific death associated with elevated expression (95% CI), adjusted for age and gender in a Cox proportional hazard model, were 1.8 (1.0–3.3) for uPA (upper quartile cut‐line), 2.2 (1.3–4.0) for uPAR (median quartile cut‐line) and 2.5 (1.3–4.9) for uPA + uPAR. An RHR for metastatic disease of 4.0 (1.6–9.9) was observed for uPAR. Restricting the analyses to T2+ tumors, the corresponding figures were: 2.1 (1.1–3.9) for uPA, 1.6 (0.8–3.3) for uPAR and 2.5 (1.1–5.6) for both. We conclude that expression of uPA and uPAR is associated with the clinical behaviour of bladder neoplasms, possibly providing means for refined staging of muscle invasive tumors and target proteins for novel therapies. © 2002 Wiley‐Liss, Inc.
Cancer risk in persons receiving prescriptions for paracetamol: A Danish cohort study
Authors: Friis Søren , Nielsen Gunnar Lauge , Mellemkjær Lene , McLaughlin Joseph K. , Thulstrup Ane Marie , Blot William J. , Lipworth Loren , Vilstrup Hendrik , Olsen Jørgen H. 
Published: August 2002

AbstractThe use of paracetamol has been associated with increased risks for urinary tract cancers and decreased risk for ovarian cancer, although results have been inconsistent. We conducted a population‐based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry. Cancer incidence among 39,946 individuals receiving prescriptions for paracetamol was compared with expected incidence based on the North Jutland population who did not receive paracetamol prescriptions, during a 9‐year follow‐up period. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. Overall, 2,173 cancers were observed with 1,973 expected, yielding a SIR of 1.10 (95% CI, 1.06–1.15). Significantly elevated SIRs were found for cancers of the esophagus (1.9; 95% CI, 1.3–2.8) and lung (1.6; 95% CI, 1.4–1.7). Nonsignificantly increased SIRs were observed for cancers of the liver (1.5; 95% CI, 0.96–2.2), renal parenchyma (1.3; 95% CI, 0.9–1.7) and renal pelvis/ureter (1.6; 95% CI, 0.96–2.6), whereas the SIR for cancer of the urinary bladder was close to unity (1.1; 95% CI, 0.9–1.4). For ovarian cancer, the SIR was close to expectation (0.9; 95% CI, 0.6–1.2) with no evidence of trends with duration of follow‐up or number of prescriptions. A similar risk pattern was observed after exclusion of person‐time experience following prescription for aspirin or other nonsteroidal antiinflammatory drugs in the study cohort and reference population. Our results do not support a major role for paracetamol in the development of cancers of the urinary tract, and we found little evidence of a protective effect of paracetamol against ovarian cancer. The elevated risks for cancers of the esophagus, lung and liver are most likely a result of confounding variables, but may warrant further investigation. © 2002 Wiley‐Liss, Inc.
Proficient mismatch repair protein expression in Hodgkin and Reed Sternberg cells
Authors: Re Daniel , Benenson Lena , Wickenhauser Claudia , Starostik Petr , Staratschek‐Jox Andrea , Müller‐Hermelink Hans Konrad , Diehl Volker , Wolf Jürgen 
Published: August 2002

AbstractHodgkin and Reed‐Sternberg (H/RS) cells are characterized by chromosomal instability. Nevertheless, neither specific nor consistent chromosomal alterations could be characterized in H/RS cells. Microsatellite instability (MSI) is another form of genomic instability but its role in the pathogenesis of classical Hodgkin's disease (cHD) has not been investigated so far. We analyzed MSI and mismatch repair (MMR) protein expression in H/RS cells of cHD in order to assess genomic instability in these cells. Using a sensitive single cell approach, MSI‐low was detected in a portion of single cells of the H/RS cell line L1236. Mutations of genes encoding for hMSH2 and hMLH1 were excluded by RT‐PCR in L1236 cells. An analysis of pooled single H/RS cells of seven primary cases of cHD showed loss of heterozygosity for some allelic markers but absence of MSI in all 7 cases. Owing to a tight correlation between MSI‐high, inactivating mutations of MMR genes and MMR protein expression in colon cancer, MMR protein expression commonly is used as a marker for MSI. In order to screen additional primary cases of cHD for MSI, we performed immunohistochemistry for hMSH2 and hMLH1 in 6 of the 7 cases analyzed by single cell PCR and 20 additional cases of cHD. H/RS cells from 25 out of 26 cases showed a nuclear staining pattern for hMSH2 and hMLH1 similar to germinal center B cells of non‐malignant lymph nodes. These results indicate a proficient MMR system in most H/RS cells. It is concluded that a defect MMR system is unlikely to contribute to the malignant phenotype and genomic instability of H/RS cells in cHD. © 2002 Wiley‐Liss, Inc.
Diet, reproductive factors and lung cancer risk among Chinese women in Singapore: Evidence for a protective effect of soy in nonsmokers
Authors: Seow Adeline , Poh Wee‐Teng , Teh Ming , Eng Philip , Wang Yee‐Tang , Tan Wan‐Cheng , Chia Kee‐Seng , Yu Mimi C. , Lee Hin‐Peng 
Published: August 2002

AbstractThe factors associated with risk of lung cancer among nonsmokers have not been fully elucidated, but dietary factors have consistently been shown to play a role. Chinese women are unique in having a high incidence of lung cancer despite a low smoking prevalence. This population is also known to have a high intake of soy, a dietary source of phytoestrogens. We conducted a hospital‐based case‐control study among Singapore Chinese women, comprising 303 cases and 765 age‐matched controls, of whom 176 cases and 663 controls were lifetime nonsmokers. Data on demographic background, reproductive factors and dietary intake of fruit, vegetables and soy foods were obtained by in‐person interview. We observed an inverse association between intake of total, cruciferous and non‐cruciferous vegetables and risk of lung cancer among smokers. Although smokers in the highest tertile of fruit intake also had a lower risk, this was not statistically significant. Higher intake of soy foods significantly reduced risk of lung cancer among lifetime nonsmokers, but not among smokers. When soy isoflavonoid intake in mg/week was computed based on frequency and portion size of intake of eight common local soy foods, the adjusted OR among nonsmokers for the highest tertile compared to the lowest was 0.56, 95% CI 0.37–0.85 (p for trend <0.01). Fruit intake was also significantly associated with reduced lung cancer risk among nonsmokers, but the effect was not significant after adjustment for soy intake. On the other hand, soy intake remained an independent predictor of risk after controlling for fruit intake. Reproductive effects were also primarily confined to lifetime nonsmokers, among whom having 3 or more livebirths (adjusted OR 0.65, 0.44–0.96) and a menstrual cycle length of more than 30 days (OR 0.46, 0.25–0.84) accorded a significantly reduced risk of lung cancer. Place of birth was significantly associated with risk among nonsmokers (OR 2.6, 1.7–3.9 for China‐born vs. local born) but not among smokers. When analysis was restricted to nonsmokers with adenocarcinomas, the dietary effects were consistent or enhanced. On stepwise regression, soy intake and cycle length emerged as the independent dietary and reproductive predictors of lung cancer risk in nonsmokers. These findings are consistent with other evidence suggesting an involvement of estrogen‐related pathways in lung cancer among non‐smoking women. © 2001 Wiley‐Liss, Inc.
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population
Authors:   German Consortium for Hereditary Breast and Ovarian Cancer
Published: August 2002

AbstractThe main focus of this German‐wide multi‐center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than ⅓ of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure. © 2001 Wiley‐Liss, Inc.
The myxoid liposarcoma specific TLS‐CHOP fusion protein localizes to nuclear structures distinct from PML nuclear bodies
Authors: Thelin‐Järnum Sofia , Göransson Melker , Burguete Alondra Schweizer , Olofsson Anita , Åman Pierre 
Published: August 2002

AbstractCHOP in 12q13, also called GADD153 or DDIT3, encodes a transcription factor of the C/EBP type. As a result of t(12;16) translocations, CHOP is rearranged and fused to TLS in 16p11 in about 90% of myxoid liposarcomas/round cell liposarcomas (MLS/RCLS). The TLS‐CHOP protein consists of the N‐terminal half of TLS juxtaposed to the N‐terminal of the entire CHOP. It is capable of forming dimers with the natural dimer partners of CHOP. Here we report that recombinant TLS‐CHOP‐green fluorescence protein localizes to nuclear structures, similar to, but distinct from, PML nuclear bodies. The TLS‐CHOP‐green fluorescent protein nuclear structures are resistant to high salt concentration and nuclease treatment. Transfection of TLS‐CHOP to normal fibroblasts causes a rapid down regulation and relocation of PML nuclear bodies. An abnormal extra nuclear localization of PML bodies was also found in TLS‐CHOP carrying cell lines established from myxoid liposarcomas. Transfection of TLS‐CHOP induced a rapid disappearance of PCNA. TLS‐CHOP may disturb the nuclear machinery by binding and sequestering important factors from their natural sites. © 2001 Wiley‐Liss, Inc.
Leaving Home in Europe: The Experience of Cohorts Born Around 1960
Authors: Billari Francesco C. , Philipov Dimiter , Baizán Pau 
Published: August 2002

AbstractIn the paper we analyse the leaving‐home experience of men and women born around 1960 in 16 European countries. We use extensive empirical evidence from Fertility and Family Survey data, providing a large‐scale comparison. We focus on some key indicators of the process of leaving home: the timing, sequencing and synchronisation of leaving home with the end of education and the formation of a first union. As far as these dimensions of leaving home are concerned, Europe appears to be extremely heterogeneous, and explaining this will undoubtedly be a challenge. The complex interplay between the present economic situation of young people and long‐term institutional and cultural factors is thought to be the main driving factor. Our findings constitute a benchmark against which subsequent behaviour, such as that of cohorts coming of age after the fall of the Iron Curtain, could be compared. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling the trend and seasonals within an AIDS model of the demand for alcoholic beverages in the United Kingdom
Authors: Moosa I. A. , Baxter J. L. 
Published: August 2002

AbstractThe argument that is put forward in this paper is that failure to represent stochastic trend and stochastic seasonality in an AIDS model leads to a misspecified and possibly structurally unstable model. This proposition is verified by estimating an AIDS model of the demand for alcoholic beverages in the United Kingdom. Three versions of the model are estimated, and it is demonstrated that the version allowing for stochastic trend and stochastic seasonality performs better than the other two versions of the model in terms of the diagnostics tests and goodness of fit measures. The best estimated model turns out to possess the properties of having common components and being homogenous. Further empirical testing reveals the presence of stochastic trends and cointegration between the budget shares of beer and wine. The results clearly indicate that there has been a shift away from the consumption of beer towards wine. Copyright © 2002 John Wiley & Sons, Ltd.
Cytokine fingerprinting and hazard assessment of chemical respiratory allergy
Authors: Dearman R. J. , Kimber I. 
Published: August 2002

AbstractAllergic sensitization of the respiratory tract resulting in occupational asthma and other symptoms can be caused by a variety of chemicals and represents an important occupational health problem. Although there is a need to identify and characterize those chemicals that are able to cause respiratory allergy, there are currently no well validated or widely accepted predictive test methods. Some progress has been made with guinea pig assays, but our attention in this laboratory has focused instead on the development of novel approaches based on an understanding of the nature of immune responses induced in mice by chemical allergens. We have shown that whereas contact allergens provoke in mice selective type 1 immune responses, characterized by the secretion by draining lymph node cells (LNC) of high levels of the cytokine interferon γ (IFN‐γ), chemical respiratory allergens stimulate instead preferential type 2 responses associated with comparatively high levels of interleukins 4 and 10 (IL‐4 and IL‐10). The divergent immune responses provoked by different classes of chemical allergens, and the phenotypes of selective cytokine secretion that characterize such responses, form the basis of a novel method—cytokine fingerprinting—that permits chemicals that have the potential to cause respiratory allergy to be identified and distinguished from those that are associated primarily with contact sensitization. In this article the immunobiological basis for cytokine fingerprinting is considered and the development, evaluation and practical application of the assay are reviewed. Copyright © 2001 John Wiley & Sons, Ltd.