bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public wage differentials and the treatment of occupational differences
Authors: Belman Dale , Heywood John S. 
Published: December 2003

AbstractPast research demonstrates that the estimated size of the federal government earnings differential shrinks
substantially with the addition of detailed occupational controls. Possible explanations for this reduction are:
controlling for the differing sectoral distributions of common occupations, and controlling for detailed
occupations unique to each sector. While occupational detail does not eliminate the federal differential, more
than two‐thirds of the reduction in the federal differential comes from controlling for unique occupations
and, moreover, this is equivalent to excluding all observations in unique occupations. This finding is contrasted
with that for the local sector in which the differing distribution of common occupations largely explains the
pattern of the differential. © 2004 by the Association for Public Policy Analysis and Management.
Not just angiogenesis—wider roles for the angiopoietins
Authors: Jones Pamela F 
Published: December 2003

AbstractSince the discovery of the angiopoietins, much interest has been focused on their biological actions and their potential use as therapeutic targets. It is generally accepted that the angiopoietins play an important role in angiogenesis and hence are described as angiogenic factors. However, it is becoming increasingly clear that this is not their only role and it is likely that the angiopoietins have important roles in a wider range of biological and pathological functions. Copyright © 2003 John Wiley & Sons, Ltd.
NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia
Authors: Yu Chunying , Le Anh‐Thy , Yeger Herman , Perbal Bernard , Alman Benjamin A 
Published: December 2003

AbstractGrowth plate chondrocytes undergo a coordinated differentiation process resulting in terminal differentiation and new bone formation. Enchondromas are pre‐malignant, benign cartilaginous lesions that arise from growth plate chondrocytes that fail to undergo terminal differentiation. NOV (nephroblastoma overexpressed) is a member of the CCN family of proteins, which share a common multi‐modular organization. While the role of NOV in chondrocyte development and cartilage neoplasia is not known, other CCN family members play a role in chondrocyte differentiation, or are differentially regulated in cartilage neoplasia. In embryonic murine growth plates, NOV was expressed in pre‐hypertrophic and early hypertrophic chondrocytes. PTHrP treatment (which inhibits terminal differentiation) decreased NOV expression in murine femurs maintained in organ culture, and decreased the activity of a NOV reporter construct in vitro. Expression of the CCN family members NOV, CTGF, CYR61, and WISP‐1 was examined in 15 chondrosarcomas of various grades and in three enchondromas. Expression of all of the family members was lower in the higher‐grade tumours. As identification of the grade of cartilage neoplasia can sometimes be difficult using histology alone, the level of expression of CCN family members could be a useful adjunct in the determination of tumour grade. Copyright © 2003 John Wiley & Sons, Ltd.
Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma
Authors: Cassia Raúl , Moreno‐Bueno Gema , Rodríguez‐Perales Sandra , Hardisson David , Cigudosa Juan C , Palacios José 
Published: December 2003

AbstractCyclin E overexpression occurs in a subset of endometrial carcinomas (ECs), but the molecular mechanisms underlying this alteration remain to be established. The present study has analysed amplification of the cyclin E gene (CCNE) and mutation in hCDC4, the gene coding for the F‐box protein, which tags phosphorylated cyclin E for proteosomal degradation, to ascertain whether these alterations might be responsible for cyclin E overexpression in ECs. Cyclin E and p53 expression was studied by immunohistochemistry in eight atypical endometrial hyperplasias (AEHs), 51 endometrioid endometrial carcinomas (EECs), and 22 non‐endometrioid endometrial carcinomas (NEECs). CCNE amplification was analysed by fluorescence in situ hybridization (FISH). Mutations in exons 2–11 of the hCDC4 gene were screened by PCR–SSCP–sequencing. Finally, the polymorphic marker D4S1610 was used to assess loss of heterozygosity (LOH) in the hCDC4 gene. Cyclin E overexpression was found in 26/81 (32%) cases and was associated with the histological type of the lesion, since it was not found in any AEHs but was present in 27% of EECs and 54.5% of NEECs (p = 0.035). Cyclin E overexpression was associated with histological grade (p = 0.011) and p53 immunostaining in EECs (p = 0.033). CCNE amplification was found in 6 of 37 (16%) ECs examined. There was a significant association between CCNE amplification and the histological type of the lesion, since five (83%) of the six cases with amplification were NEECs (p = 0.008). One EEC harboured an hCDC4 mutation: a CGA to CAA (Arg/Gln) change at codon 479. In addition, D4S1610 LOH was found in 7 of 23 (30%) informative cases analysed, but no correlation with cyclin E overexpression was found. However, the tumour with hCDC4 mutation also showed LOH. This is the first study demonstrating that cyclin E overexpression is associated with gene amplification in ECs, these alterations being more frequent in NEECs. Although hCDC4 exhibits a low mutation frequency in ECs overexpressing cyclin E, it seems to function as a tumour suppressor gene that is involved in endometrial carcinogenesis. Copyright © 2003 John Wiley & Sons, Ltd.
The presence of high‐risk HPV combined with specific p53 and p16INK4a expression patterns points to high‐risk HPV as the main causative agent for adenocarcinoma in situ and adenocarcinoma of the cervix
Authors: Zielinski G Denise , Snijders Peter JF , Rozendaal Lawrence , Daalmeijer Nathalie Fransen , Risse Elle KJ , Voorhorst Feja J , Jiwa N Medi , van der Linden Hans C , de Schipper Frits A , Runsink Arnold P , Meijer Chris JLM 
Published: December 2003

AbstractAdenocarcinoma in situ (ACIS) and adenocarcinoma (AdCA) of the cervix are frequently missed in population‐based screening programmes. Adding high‐risk HPV (hrHPV) testing to cervical cancer screening might improve the detection rate of ACIS and AdCA. Since the exact proportion of AdCAs of the cervix that can be attributed to hrHPV infection is still a matter of debate, a comprehensive study was performed of hrHPV presence in ACIS and AdCA of the cervix. Archival formalin‐fixed specimens of indisputable ACIS (n = 65) and AdCA (n = 77) of the cervix were tested for hrHPV DNA by GP5+/6+ PCR‐enzyme immunoassay (EIA) and type‐specific E7 PCR for 14 hrHPV types. Further immunostaining for p16INK4A and p53 was performed to assess alternative pathways of carcinogenesis potentially unrelated to HPV. hrHPV DNA was found in all (100%) ACISs and 72 (94%) cervical AdCAs, whereas none of 20 endometrial AdCAs scored hrHPV‐positive. HPV 18 was most prevalent and found as single or multiple infection in 68% of ACISs and 55% of cervical AdCAs. Diffuse immunostaining for p16INK4a, a potential marker of hrHPV E7 function, was significantly more frequent in hrHPV‐positive cervical AdCAs (19/20; 95%) than in those without hrHPV (1/5; 20%; p < 0.001). Immunostaining for p53, pointing to stabilized wild‐type or mutant p53 protein, was significantly more frequent in hrHPV cervical AdCAs negative for hrHPV (p = 0.01). No difference in p16INK4a and p53 immunostaining was found between hrHPV‐negative cervical AdCAs and endometrial AdCAs. Hence, only a minority of cervical AdCAs displayed absence of HPV DNA and immunostaining profiles suggestive of an aetiology independent of HPV. Since all ACISs and nearly all cervical AdCAs were hrHPV‐positive, the incorporation of hrHPV testing in cervical cancer screening programmes is likely to decrease markedly the incidence of cervical AdCA. Copyright © 2003 John Wiley & Sons, Ltd.
High‐throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer
Authors: Zaharieva Boriana M , Simon Ronald , Diener Pierre‐Andre , Ackermann Daniel , Maurer Robert , Alund Göran , Knönagel Hartmut , Rist Marcus , Wilber Kim , Hering Franz , Schönenberger Andreas , Flury Renata , Jäger Peter , Fehr Jean Luc , Mihatsch Michael J , Gasser Thomas , Sauter Guido , Toncheva Draga I 
Published: December 2003

AbstractGene amplification is a common mechanism for oncogene overexpression. High‐level amplifications at 11q13 have been repeatedly found in bladder cancer by comparative genomic hybridization (CGH) and other techniques. Putitative candidate oncogenes located in this region are CCND1 (PRAD1, bcl‐1), EMS1, FGF3 (Int‐2), and FGF4 (hst1, hstf1). To evaluate the involvement of these genes in bladder cancer, a tissue microarray (TMA) containing 2317 samples was screened by fluorescence in situ hybridization (FISH). The frequency of gains and amplifications of all genes increased significantly from stage pTa to pT1–4 and from low to high grade. In addition, amplification was associated with patient survival and progression of pT1 tumours. Among 123 tumours with amplifications, 68.3% showed amplification of all four genes; 19.5% amplification of CCND1, FGF4, and FGF3; and 0.8% co‐amplification of FGF4, FGF3, and EMS1. Amplification of CCND1 alone was found in 9% of the tumours, while EMS1 alone was amplified in 1.6% and FGF4 in 0.8%. Overall, the amplification frequency decreased with increasing genomic distance from CCND1, suggesting that, among the genes examined, CCND1 is the major target gene in the 11q13 amplicon in bladder cancer. Copyright © 2003 John Wiley & Sons, Ltd.
Productive infection of dendritic cells by simian immunodeficiency virus in macaque intestinal tissues
Authors: Choi Yang Kyu , Whelton Kelly M , Mlechick Brandy , Murphey‐Corb Michael A , Reinhart Todd A 
Published: December 2003

AbstractDendritic cells (DCs) are potent antigen‐presenting cells that likely play multiple roles in human immunodeficiency virus‐1 (HIV‐1) and simian immunodeficiency virus (SIV) pathogenesis. This paper describes the effects of pathogenic SIV infection on the networks of DCs in rhesus macaque (Macaca mulatta) intestinal tissues. Intestinal tissues were obtained from macaques at different stages of disease following infection with the pathogenic SIV/DeltaB670 isolate. The patterns and levels of expression of SIV and DC‐associated mRNAs were examined and quantitated directly in intestinal tissue sections. In situ hybridization was performed for SIV, DC‐specific ICAM3‐grabbing non‐integrin (DC‐SIGN), DC‐specific lysosome‐associated membrane glycoprotein (DC‐LAMP), DC‐specific C‐type lectin 1 (DECTIN‐1), CC chemokine receptor 6 (CCR6), CCR7, and macrophage inflammatory protein 3α (MIP‐3α/CCL20) mRNAs and quantitative image analysis was performed to measure mRNA expression levels. To identify the cell types productively infected by SIV, simultaneous in situ hybridization and immunohistochemical staining were performed. The DC networks in macaque intestinal tissues were found to be extensive and although they generally remained intact during the course of SIV infection, there were alterations in the expression of markers for immature DCs. One alteration was an increase in the expression in intestinal submucosa of DC‐SIGN, a molecule that binds to HIV‐1/SIV and increases its infectivity. Concomitant with this increase, it was found that during AIDS, the population of productively infected cells included DCs, based on co‐expression of DC‐SIGN and DECTIN‐1 mRNAs. These data indicate that SIV infection affects subpopulations of macaque intestinal DCs, including productive infection of DC‐SIGN+ DCs, the consequences of which are likely to be ongoing viral propagation and decreased immunostimulatory function. Copyright © 2003 John Wiley & Sons, Ltd.
Primary breast myoepithelial cells exert an invasion‐suppressor effect on breast cancer cells via paracrine down‐regulation of MMP expression in fibroblasts and tumour cells
Authors: Jones JL , Shaw JA , Pringle JH , Walker RA 
Published: December 2003

AbstractIn normal breast and ductal carcinoma in situ, myoepithelial cells form an incomplete layer separating the epithelial compartment from the stromal environment. Transition to invasive disease is marked by penetration of the myoepithelial–basement membrane (BM) interface. One mechanism involved in tumour invasion is breakdown of extracellular matrices by matrix metalloproteinases (MMPs). It was hypothesized that myoepithelial cells may modulate tumour invasion by controlling MMP gene expression, both in tumour cells and in peri‐ductal fibroblasts. To investigate this, myoepithelial cells from normal breast were purified and characterized and their effect on tumour cell invasive potential was assessed. The effect on MMP gene expression of breast cancer cells cultured alone or in combination with primary normal breast fibroblasts was also analysed using RT‐PCR with ELISA quantitation, with zymographic analysis to measure enzyme activity. Normal breast myoepithelial cells significantly reduced invasion by the breast cancer cell lines MCF‐7, T47D, MDA‐MB 231, and MDA‐MB 468 when they were cultured alone or in the presence of a fibroblast population. Reduced invasion was associated with changes in MMP gene expression. In those tumour cells expressing MMP, there was a significant down‐regulation of MMP‐2 (MDA‐MB 468, p < 0.001), MMP‐9 (MDA‐MB 231, p = 0.05; MDA‐MB 468, p < 0.001), and MT1‐MMP (p < 0.001 for both MDA‐MB 231 and MDA‐MB 468). Myoepithelial cells also caused a significant decrease in MMP gene expression in co‐cultured fibroblasts. Furthermore, this was associated with reduced gelatinolytic activity as identified by zymography. This study demonstrates for the first time that primary myoepithelial cells from normal breast reduce breast cancer cell invasion and that this is mediated via modulation of both tumour cell and fibroblast function. This emphasizes the importance of the myoepithelial cell in controlling the breast microenvironment and focuses on the potential significance of the loss of this population with disease progression. Copyright © 2003 John Wiley & Sons, Ltd.
Altered expression of the septin gene, SEPT9, in ovarian neoplasia
Authors: Burrows James F , Chanduloy Severine , McIlhatton Michael A , Nagar Hans , Yeates Karen , Donaghy Paul , Price John , Godwin Andrew K , Johnston Patrick G , Russell SE Hilary 
Published: December 2003

AbstractThe septin family of genes has been implicated in a variety of cellular processes including cytokinesis, membrane transport and fusion, exocytosis, and apoptosis. One member of the septin family maps to chromosome 17q25.3, a region commonly deleted in sporadic ovarian and breast tumours, and has also been identified as a fusion partner of MLL in acute myeloid leukaemias. The present study demonstrates that the pattern of expression of multiple splice variants of this septin gene is altered in ovarian tumours and cell lines. In particular, expression of the zeta transcript is detectable in the majority of tumours and cell lines, but not in a range of non‐malignant adult and fetal tissues. Zeta expression is accompanied by loss of the ubiquitous beta transcript. Somatic mutations of the gene were not detected in ovarian tumours, but it was demonstrated that beta expression in tumour cell lines can be reactivated by 5‐azacytidine treatment, suggesting a role for methylation in the control of expression of this gene. Copyright © 2003 John Wiley & Sons, Ltd.
Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade
Authors: Sowter Heidi Michelle , Ferguson Mary , Pym Caroline , Watson Peter , Fox Stephen B , Han Cheng , Harris Adrian L 
Published: December 2003

AbstractDuctal carcinoma in situ (DCIS) of the breast is an early, non‐invasive lesion and the prognosis is associated with the extent of necrosis and cell death within the tumour. Two cell death genes, BNip3 and NIX, are up‐regulated in response to hypoxia in breast carcinoma cells, although any involvement of either gene in disease progression is currently unknown. This study has analysed the expression of BNip3 and NIX in 56 samples of breast DCIS, as well as in adjacent benign and invasive breast tissue. Both genes are strongly expressed in the epithelial component of a subset of DCIS and invasive disease. The data show a correlation between high expression of BNip3 in the DCIS cells and a high‐grade, necrotic lesion that is likely to be associated with invasive tumour. BNip3 was present in tumour‐associated macrophages and in apocrine metaplastic lesions. Expression of NIX did not correlate with any of the parameters investigated Copyright © 2003 John Wiley & Sons, Ltd.
Long‐term infection with Helicobacter felis and inactivation of the tumour suppressor gene p53 cumulatively enhance the gastric mutation frequency in Big Blue® transgenic mice
Authors: Jenks Peter J , Jeremy Anthony HT , Robinson Philip A , Walker Marjorie M , Crabtree Jean E 
Published: December 2003

AbstractThe aims of this study were to determine whether colonization with Helicobacter felis resulted in the accumulation of mutations within murine gastric tissue and whether the degree of genetic damage was increased by p53 deficiency. Female C57BL/6 mice carrying either the lambda/lacI transgene (Big Blue® transgenic mice) or the lambda/lacI transgene and deficient in one allele of the p53 tumour suppressor gene (TSG‐p53®/Big Blue®) were inoculated with H felis. Seven months after inoculation, mutations in the target lacI gene were assessed using the Big Blue® transgenic mutagenesis assay system in these animals and in controls. There was an approximately two‐fold increase in lacI mutations in gastric mucosa harvested from mice infected with H felis and also from non‐infected mice heterozygous for the p53 allele relative to wild‐type mice. The mutation frequency in mice infected with H felis and deficient in one allele of p53 was increased approximately three‐fold. Active gastric inflammation was significantly greater in H felis‐infected p53 hemizygous mice compared with H felis p53 wild‐type mice. Gastric epithelial proliferation was similarly increased with infection in both of these latter groups of mice. In infected mice, there was a significant correlation between the mutation frequency and the degree of active gastric inflammation. These data suggest a synergistic action between infection with H felis and p53 deficiency in the accumulation of mutations within gastric tissue. Active neutrophil infiltration in gastric Helicobacter infection may contribute to the increased levels of mutation observed. Copyright © 2003 John Wiley & Sons, Ltd.
The patterns of relapse in osteosarcoma: The memorial Sloan‐Kettering experience
Authors: Chi Susan N. , Conklin Laurie S. , Qin Jing , Meyers Paul A. , Huvos Andrew G. , Healey John H. , Gorlick Richard 
Published: December 2003

AbstractBackgroundWith the introduction of intensive high‐dose chemotherapy for the treatment of osteosarcoma, changes in the pattern of metastases observed at relapse have been reported. To further investigate this hypothesis, the relapse patterns among groups receiving chemotherapy regimens of variable intensity at Memorial Sloan‐Kettering Cancer Center were analyzed.ProcedureAll patients treated with the protocols T4, T5, T7, T10, and T12 were included. Patients were divided into two groups, one including those patients treated with less intense therapy (T4, T5, and T7) and the other, those treated with current regimens (T10 and T12).ResultsOf the 25 patients who relapsed on the earlier protocols, 76% relapsed to the lungs, 8% had local recurrences, and 16% distant metastases to the bone. The median time to first relapse was 12 months. Of the 69 patients who relapsed on the T10 and T12 protocols, 75% relapsed in the lungs, 9% had local recurrences, and 16% distant bone metastases. The median time to first relapse was 17 months. There was no statistically significant difference in the timing of relapse between the two groups studied, although a longer median time to relapse was observed for patients treated on the later protocols. The range of time to relapse was also wider in the later protocols.ConclusionsThese data do not support the hypothesis that patterns of relapse are changing with alterations in osteosarcoma treatment. This limited single institutional experience can be explored further in the context of a multi‐institutional effort. © 2003 Wiley‐Liss, Inc.
Stature of young people with malignant bone tumors
Authors: Cotterill Simon J. , Wright Charlotte M. , Pearce Mark S. , Craft Alan W. 
Published: December 2003

AbstractBackgroundLittle is known about the aetiology of primary bone tumours. There have been conflicting reports relating to stature in young people with bone cancer.PatientsWe analysed height data at diagnosis for 364 patients with osteosarcoma and 356 patients with Ewing sarcoma registered on clinical trials run by the Medical Research Council (MRC) and the United Kingdom Children's Cancer Study Group (UKCCSG).Main Outcome MeasuresHeight at diagnosis for each patient was standardised for age and sex compared to national reference data with a standard deviation score (SDS) calculated for each subject.ResultsThose with osteosarcoma were significantly taller than the general population (mean height SDS 0.2, P = 0.001). Patients with osteosarcoma of the femur were significantly taller than patients with other primary sites (mean height SDS 0.45 vs. −0.06, P = 0.0001). Overall those with Ewing sarcoma were not significantly taller than the general population (mean height SDS 0.09, P = 0.1), but children presenting under 15 years were taller (SDS 0.2, P = 0.004) whilst older patients were not (SDS −0.07, P = 0.4). In both osteosarcoma and Ewing sarcoma the mean age at diagnosis for females was significantly younger than for males.ConclusionsThis study suggests that tall stature and an earlier pubertal growth spurt may be important factors in the aetiology of both osteosarcoma and Ewing sarcoma. © 2003 Wiley‐Liss, Inc.
Phase I study of oral cyclophosphamide and oral topotecan for children with recurrent or refractory solid tumors
Authors: Bowers Daniel C. , Aquino Victor M. , Leavey Patrick J. , Bash Robert O. , Journeycake Janna M. , Tomlinson Gail , Mulne Arlynn F. , Haynes Heidi J. , Winick Naomi J. 
Published: December 2003

AbstractBackgroundTo determine the maximum‐tolerated duration and dose‐limiting toxicity of a daily schedule of orally administered cyclophosphamide and topotecan in pediatric patients with recurrent or refractory malignant solid tumors.MethodsPatients received oral cyclophosphamide (50 mg/m2/dose) in the morning followed by topotecan (0.8 mg/m2/dose) 8–12 hr later for an escalating number of consecutive days (10, 14, and 17 days).ResultsSeventeen pediatric patients were treated with oral cyclophosphamide and topotecan for durations of 10–17 days for a total of 58 treatment courses. Reversible hematologic toxicity (neutropenia and thrombocytopenia) was the dose‐limiting toxicity. Nonhematologic toxicities of greater than grade 3 were not observed. A partial response (neuroblastoma following myeloablative chemotherapy and stem cell rescue) and prolonged stable disease (medulloblastoma) were each observed in one patient.ConclusionsThe recommended duration of therapy with a daily schedule of both oral cyclophosphamide (50 mg/m2/day) and topotecan (0.8 mg/m2/day) for previously treated pediatric patients with recurrent or refractory solid tumors is 14 consecutive days. The observed dose limiting toxicity (DLT) was reversible neutropenia. This regimen was well tolerated in heavily pretreated patients and demonstrated activity against recurrent pediatric solid tumors. © 2003 Wiley‐Liss, Inc.