bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediagnostic levels of C‐peptide, IGF‐I, IGFBP ‐1, ‐2 and ‐3 and risk of endometrial cancer
Authors: Lukanova Annekatrin , Zeleniuch‐Jacquotte Anne , Lundin Eva , Micheli Andrea , Arslan Alan A. , Rinaldi Sabina , Muti Paola , Lenner Per , Koenig Karen L. , Biessy Carine , Krogh Vittorio , Riboli Elio , Shore Roy E. , Stattin Par , Berrino Franco , Hallmans Göran , Toniolo Paolo , Kaaks Rudolf 
Published: June 2004

AbstractConditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF‐I and decreased levels of IGF‐binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre‐diagnostic blood concentrations of C‐peptide (a marker of pancreatic insulin production), IGF‐I, IGFBP‐1, ‐2 and ‐3 with endometrial cancer risk. A case‐control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C‐peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91–11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65–11.7)]. IGFBP‐1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15–0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22–1.07)]. Risk was unrelated to levels of IGF‐I, IGFBP‐2 and IGFBP‐3. Chronic hyperinsulinemia, as reflected by increased circulating C‐peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer. © 2003 Wiley‐Liss, Inc.
p53 polymorphic variants at codon 72 exert different effects on cell cycle progression
Authors: Pim David , Banks Lawrence 
Published: June 2004

AbstractTwo common polymorphic forms of the p53 tumor suppressor protein are widely distributed throughout the human population. These encode either proline or arginine at position 72, and this difference results in a marked alteration in the primary structure of the protein. A number of previous studies have shown significant differences in the biochemical properties of the p53 protein, depending on the particular polymorphic form. There is little information, however, on their respective biologic activities. In this study, we have used an inducible switch system for expressing both polymorphic forms of p53 within Saos‐2 cells. Cell cycle analysis postinduction of p53 function reveals striking differences in how the 2 forms of p53 bring about a cessation of cell growth. Thus, the Arg72 form of p53 is significantly more efficient than the Pro72 form at inducing apoptosis. In contrast, the Pro72 form appears to induce a higher level of G1 arrest than the Arg72 form. These results demonstrate significant differences in how the codon 72 polymorphism affects the biological activity of p53. © 2003 Wiley‐Liss, Inc.
Short tandem repeat polymorphism in a novel esophageal cancer‐related gene (ECRG2) implicates susceptibility to esophageal cancer in Chinese population
Authors: Yue Chun‐mei , Bi Mei‐xia , Tan Wen , Deng Da‐jun , Zhang Xin‐yu , Guo Li‐ping , Lin Dong‐xin , Lu Shih‐Hsin 
Published: June 2004

AbstractWe have previously cloned and identified a novel esophageal cancer related gene 2 (ECRG2; GenBank Accession Number AF268198), which is down‐regulated in esophageal squamous cell carcinoma (ESCC) and involved in the induction of the apoptosis in esophageal cancer cell lines. In the present study, we have found a short tandem repeat (STR) polymorphism in the noncoding region of the exon 4 of the ECRG2 gene by using PCR‐denaturing high‐performance liquid chromatography (DHPLC). Three STR genotypes, TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 were revealed and confirmed by DNA sequencing analysis. A total of 661 objects including 228 patients with ESCC and 373 normal controls were analyzed to investigate the impact of this ECRG2 STR polymorphism on risk of ESCC in case‐control studies. Genotypes were determined in 231 controls and 162 cases from Beijing, which is a low risk area of ESCC, and in 142 controls and 126 cases from Linxian, a well‐known high‐risk area of ESCC. In both of the Beijing and Linxian population, subjects who carried the TCA3/TCA3 genotype were at an increased risk of ESCC compared to those carrying the TCA4/TCA4 genotype, with the adjusted odds ratios (ORs) being 2.05 [95% confidence interval (CI), 1.02–4.06] for the subjects from Beijing and 4.40 (95% CI, 1.93–10.01) for the subjects from Linxian. Furthermore, comparison of the genotype distributions among other cancer sites might suggest that risk of the ECRG2 STR polymorphism might be specific to the esophagus. These findings indicate for the first time that the ECRG2 STR is a genetic susceptibility factor for ESCC and the TCA3/TCA3 allele might play a role in the development of this cancer. © 2003 Wiley‐Liss, Inc.
Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index
Authors: Pruneri Giancarlo , Valentini Stefano , Fabris Sonia , Del Curto Barbara , Laszlo Daniele , Bertolini Francesco , Martinelli Giovanni , Leocata Pietro , Viale Giuseppe , Neri Antonino 
Published: June 2004

AbstractAn abnormal expression of cyclin D3, a key regulator of the cell cycle, has been documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 6p21, may be deregulated in plasma cell myeloma and non‐Hodgkin's lymphoma as a result of the t(6;14)(p21.1;q32.3) translocation and/or gene amplification. In the current study, we for the first time investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) the prevalence of cyclin D3 abnormalities in follicular lymphomas (FLs), comparing the results with traditional clinicopathologic characteristics, p27 and skp2 immunoreactivity (IR) and Ki‐67 labeling index (LI). Cyclin D3, skp2 and Ki‐67 IR significantly increased from grade I to grade III FL (p = 0.0003, p = 0.0001 and p < 0.0001, respectively), while p27 IR was significantly (p < 0.0001) more prevalent in low‐grade tumors. Cyclin D3 IR was directly correlated with the Ki‐67 LI (p < 0.0001) and inversely correlated with p27 IR (p = 0.050). None of the 13 cases analyzed by FISH showed the t(6;14) translocation, but in 2 (15.3%) grade I FLs 3 cyclin D3 signals were detected. Cohybridization with probes specific for the centromeric region and the long arm of the chromosome 6 indicated trisomy in one case and a pattern highly suggestive for the presence of an isochromosome 6p in the other case. Our data suggest that the t(6;14) translocation may be extremely uncommon in FL and that a deregulated expression of cyclin D3, possibly due to epigenetic mechanisms, may be involved in the pathogenesis of high‐grade tumors. © 2004 Wiley‐Liss, Inc.
EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen‐sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR)
Authors: Bonaccorsi Lorella , Carloni Vinicio , Muratori Monica , Formigli Lucia , Zecchi Sandra , Forti Gianni , Baldi Elisabetta 
Published: June 2004

AbstractWe previously demonstrated that expression of androgen receptor (AR) by transfection of the androgen‐independent prostate cancer cell line PC3 decreases invasion and adhesion of these cells (PC3‐AR) through modulation of α6β4 integrin expression. The treatment with androgens further reduced invasion of the cells without modifying α6β4 expression, suggesting an interference with the invasion process by androgens. Here, we investigated EGF‐mediated signal transduction processes that lead to invasion in PC3‐AR cells. We show that EGF‐induced EGFR autotransphosphorylation is reduced in PC3‐AR cells compared to PC3 cells transfected only with the vector (PC3‐Neo). EGF‐stimulated PI3K activity, a key signaling pathway for invasion of these cells, and EGF‐PI3K interaction are also decreased in PC3‐AR cells and further reduced by treatment with androgen. Finally, we show that EGFR internalization process was reduced in PC3‐AR and LNCaP cells compared to PC3‐Neo. Investigations on the location of AR in PC3‐AR transfected cells were also conducted. Immunoconfocal microscopy and coimminoprecipitation studies demonstrated the presence of an interaction between EGFR and AR at membrane level in PC3‐AR and LNCaP cells. In conclusion, our results suggest that the expression of AR by transfection in PC3 cells confers a less‐malignant phenotype by interfering with EGFR signaling leading to invasion through a mechanism involving an interaction between AR and EGFR. © 2004 Wiley‐Liss, Inc.
Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer
Authors: Ekici Sinan , Cerwinka Wolfgang H. , Duncan Robert , Gomez Pablo , Civantos Francisco , Soloway Mark S. , Lokeshwar Vinata B. 
Published: June 2004

AbstractDespite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL‐1‐type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL‐1‐type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow‐up of 72 months (range 72–131 months, mean 103 months). For HA, HYAL‐1 and CD44v6 staining and MVD determination, a biotinylated HA‐binding protein, an anti‐HYAL‐1 IgG, an anti‐CD44v6 IgG and an anti‐CD34 IgG were used, respectively. HA and HYAL‐1 staining was classified as either low‐ or high‐grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low‐ or high‐grade. Using 72 months as the cut‐off limit for evaluating biochemical recurrence, HA, HYAL‐1, combined HA–HYAL‐1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL‐1), 87.8% (HA–HYAL‐1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow‐up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL‐1, HA–HYAL‐1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL‐1 (hazard ratio = 8.196, p = 0.0009)/HA–HYAL‐1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL‐1 staining inference was not included in the multivariate model. In our retrospective study with 72‐ to 131‐month follow‐up, EPE, preoperative PSA and HYAL‐1 either alone or together with HA (i.e., combined HA–HYAL‐1) were independent prognostic indicators for PCa. © 2004 Wiley‐Liss, Inc.
Polymorphisms and haplotype structures in genes for transforming growth factor β1 and its receptors in familial and unselected breast cancers
Authors: Jin Qianren , Hemminki Kari , Grzybowska Ewa , Klaes Rüdiger , Söderberg Magnus , Zientek Helena , Rogozinska‐Szczepka Jadwiga , Utracka‐Hutka. Beata , Pamula Jolanta , Pekala Wioletta , Försti Asta 
Published: June 2004

AbstractAlterations in TGF‐β signaling appear to be associated with an altered risk of developing cancer, including breast cancer. We carried out a case‐control study on 8 polymorphisms, including 5 in the TGF‐β1 gene (G‐800A, C‐509T, Leu10→Pro, Arg25→Pro and Thr263→Ile), a polyalanine polymorphism (9A→6A) in the TGF‐βRI gene and 2 (G‐875A and A‐364G) in the TGF‐βRII gene, using samples from 2 different populations, Polish familial and Finnish unselected breast cancer cases, together with ethnically and geographically matched controls. Additionally, familial breast cancer cases with respective controls from Sweden and Germany were studied in the Leu10→Pro polymorphism, making the total number of familial cases 659. Allele, genotype and haplotype analysis on the TGF‐β1 gene as well as an analysis of the combinations of genotypes of the TGF‐β1 and its receptor genes in each individual were performed. Population differences in the allele and genotype distributions were found from 5 of the polymorphisms and 3 common haplotypes from the TGF‐β1 gene between the Finnish and other populations. However, no statistically significant difference between the breast cancer and healthy control groups was found for any of the 8 polymorphisms nor did the haplotype or genotype combination analysis reach statistical significance. Thus, none of the studied polymorphisms from the TGF‐β1 and its receptor genes was found to influence significantly susceptibility to breast cancer. The possible contribution of 6A/6A homozygosity in the TGF‐βRI gene to breast cancer needs to be confirmed in an independent study. © 2004 Wiley‐Liss, Inc.
Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis
Authors: Missiaglia Edoardo , Blaveri Ekaterini , Terris Benoit , Wang Yao‐He , Costello Eithne , Neoptolemos John P. , Crnogorac‐Jurcevic Tatjana , Lemoine Nicholas R. 
Published: June 2004

AbstractPancreatic cancer is a highly aggressive type of malignancy and the prognosis for disease presenting typically at a late stage is extremely poor. A comprehensive understanding of its molecular genetics is required in order to develop new approaches to clinical management. To date, serial analysis of gene expression and more recently oligo/cDNA microarray technologies have been employed in order to identify genes involved in pancreatic neoplasia that can be developed as diagnostic markers and drug targets for this dismal disease. This study describes the expression profile obtained from 20 pancreatic cell lines using cDNA microarrays containing 9,932 human gene elements. Numerous genes were identified as being differentially expressed, some of which have been previously implicated in pancreatic adenocarcinoma (S100P, S100A4, prostate stem cell antigen, lipocalin 2, claudins 3 and 4, trefoil factors 1 and 2) as well as several novel genes. The differentially expressed genes identified are involved in a variety of cellular functions, including control of transcription, regulation of the cell cycle, proteolysis, cell adhesion and signaling. Validation of our array results was performed by exploring the SAGEmap database and by immunohistochemistry for a selection of 4 genes that have not previously been studied in pancreatic cancer: anterior gradient 2 homologue (Xenopus laevis), insulin‐like growth factor binding protein 3 and 4 and Forkhead box J1. Immunostaining was performed using pancreas‐specific tissue microarrays containing core biopsies from 305 clinical specimens. In addition, using statistical group comparison and hierarchical clustering, a selection of genes was identified that may be linked to the site of metastasis from which these cell lines were isolated. © 2004 Wiley‐Liss, Inc.
Tumor‐specific exon creation of the HELLS/SMARCA6 gene in non‐small cell lung cancer
Authors: Yano Masaaki , Ouchida Mamoru , Shigematsu Hisayuki , Tanaka Noriyoshi , Ichimura Koichi , Kobayashi Kazuyasu , Inaki Yasuhiko , Toyooka Shinichi , Tsukuda Kazunori , Shimizu Nobuyoshi , Shimizu Kenji 
Published: June 2004

AbstractTo identify tumor‐suppressor genes on chromosome 10 in non‐small cell lung cancers, we isolated 10 types of splicing variant of the HELLS/SMARCA6 gene transcripts. HELLS/SMARCA6 is a novel member of SNF2 family, which is implicated in cellular functions like chromatin remodeling. Variant 1 was an alternatively spliced isoform containing an insertion of a 44 ntd intronic sequence between exons 3 and 4, giving rise to a premature termination of translation. Expression of variant 1 was detected exclusively in lung cancer specimens (11 of 43 cases, 26%) but was not detected in corresponding normal tissues. The D10S520 marker in the proximity of the HELLS/SMARCA6 gene showed prevalent allelic loss (41%) compared to flanking markers (25–31%). These results suggest that loss of function of HELLS/SMARCA6 by allelic loss and aberrant proteins by tumor‐specific exon creation may result in epigenetic deregulation, leading lung cells to malignancy or its progression. © 2004 Wiley‐Liss, Inc.
Use of sol–gel‐derived titania coating for direct soft tissue attachment
Authors: Areva Sami , Paldan Hannu , Peltola Timo , Närhi Timo , Jokinen Mika , Lindén Mika 
Published: June 2004

AbstractA firm bond between an implant and the surrounding soft tissue is important for the performance of many medical devices (e.g., stents, canyls, and dental implants). In this study, the performance of nonresorbable and reactive sol–gel‐derived nano‐porous titania (TiO2) coatings in a soft tissue environment was investigated. A direct attachment between the soft tissue and the sol–gel‐derived titania coatings was found in vivo after 2 days of implantation, whereas the titanium control implants showed no evidence of soft tissue attachment. The coated implants were in immediate contact with the connective tissue, whereas the titanium controls formed a gap and a fibrous capsule on the implant‐tissue interface. The good soft tissue attachment of titania coatings may result from their ability to initiate calcium phosphate nucleation and growth on their surfaces (although the formation of poorly crystalline bonelike apatite does not occur). Thus, the formation of a bonelike CaP layer is not crucial for their integration in soft tissue. The formation of bonelike apatite was hindered by the adsorption of proteins onto the initially formed amorphous calcium phosphate growth centers, thus preventing the dissolution/reprecipitation processes required for the formation of poorly crystalline bonelike apatite. These findings might open novel application areas for sol–gel‐derived titania‐based coatings. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 169–178, 2004
Endothelial cell adhesion on RGD‐containing methacrylate terpolymers
Authors: Fussell Garland W. , Cooper Stuart L. 
Published: June 2004

AbstractHexyl methacrylate (HMA), methyl methacrylate (MMA), and methacrylic acid (MAA) were used as comonomers to produce a low glass transition temperature material, potentially useful in fabricating a small diameter vascular graft. Because it has been shown that grafts seeded with endothelial cells have better resistance to thrombosis, RGD‐based peptide sequences were incorporated into the terpolymer. The two methods used for incorporating peptide sequences were a chain transfer reaction during polymerization, and a coupling reaction between the amine terminus of the peptide and the carboxyl groups of the MAA. Polymers were synthesized using the chain transfer reaction with peptide concentrations ranging from 1.7 to 7.0 μmol/g. Weight‐average molecular weights decreased with increasing peptide concentration from 310,000 g/mol for the terpolymer without peptide, to 110,000 g/mol for a peptide concentration of 7.0 μmol/g. As a result, Young's modulus decreased with increasing peptide concentration. Terpolymers with peptides attached through a coupling reaction showed no decrease in molecular weight or mechanical properties. Confocal microscopy showed cells seeded on the RGD surfaces adhered and spread, while terpolymers with RGE sequences showed cells that were rounded and not spreading. Cell density on RGD surfaces increased with increasing peptide concentration up to a bulk peptide concentration of approximately 5 μmol/g and reached a plateau, which indicated the minimum peptide concentration necessary for maximum cell adhesion. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 265–273, 2004
The in vitro elution of gentamicin sulfate from a commercially available gentamicin‐loaded acrylic bone cement, VersaBond™ AB
Authors: Lewis Gladius , Janna Si 
Published: May 2004

AbstractThe present study was designed to yield results that would be used to contribute to the ongoing debate about the mechanism of the in vitro elution of an antibiotic from an antibiotic‐loaded acrylic bone cement. To this end, the elution rates (R) of gentamicin sulfate (expressed as a weight percentage of the initial mass of the antibiotic in the specimen, normalized with respect to the duration of the test) from statically loaded (STATIC) and dynamically loaded (±10 MPa; 2 Hz; until fracture; DYNAMIC) specimens fabricated from a commercially available acrylic bone cement (VersaBond™ AB), in phosphate‐buffered saline solution at 37°C, were obtained with the use of a spectrophotometric method. There was evidence of microcracking in the fracture surfaces of DYNAMIC specimens, but no such evidence in the case of STATIC specimens. The surface area of the DYNAMIC specimens, during the tensile phase of the cyclical loading, was estimated to be about 3% larger than for the STATIC specimens (1742 mm2 versus 1696 mm2). The bulk porosities P of the specimens in both sets were also determined and found to not be statistically different, with P for the STATIC and DYNAMIC specimens being 8.55 ± 0.10 and 8.88 ± 0.18%, respectively. At the end of the test period, R was found to be 0.36 ± 0.20 and 1.28 ± 0.14 wt %/day for the STATIC and DYNAMIC specimens, respectively. It is suggested that the present results provide support for the postulate that the elution mechanism of gentamicin in this cement is a surface phenomenon. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 71B: 77–83, 2004