bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor apoptosis in cervical cancer: Its role as a prognostic factor in 42 radiotherapy patients
Authors: Kim Joo‐Young , Cho Hyun‐Yee , Lee Kyu‐Chan , Hwang You‐Jin , Lee Myung‐Hak , Roberts Stephen A. , Kim Chul Hwan 
Published: August 2002

AbstractTo investigate tumor apoptosis as a prognostic factor for outcome following radiation therapy, comparisons were made of apoptotic index (AI) as a predictor of short‐ vs. long‐term response and pretreatment vs. radiation‐induced apoptosis. Forty‐two patients with proven squamous cell carcinoma of the uterine cervix were treated by radiation alone. Apoptosis was measured by light microscopic observation of hematoxylin and eosin‐stained sections from biopsies taken before treatment and 4 and 24 hr after 2 Gy. Patients were evaluated at the end of the external radiation for determination of short‐term response and for long‐term outcome as well (median follow‐up of 27 months). Patients with high spontaneous AI showed poor short‐term response, local control, and survival. The significance of AI as a predictor of short‐term response was lost after allowing for differences in tumor size. The positive predictive value of AI for local control and survival was independent of tumor size and stage. High AI was associated with poor local control and long‐term prognosis in advanced squamous cell carcinoma of the cervix. The in vivo radiation‐induced AI after 4 or 24 hr did not predict radiation therapy outcome. © 2001 Wiley‐Liss, Inc.
Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head‐and‐neck cancer xenografts
Authors: Verel Iris , Heider Karl‐Heinz , Siegmund Miranda , Ostermann Elínborg , Patzelt Erik , Sproll Marlies , Snow Gordon B. , Adolf Günther R. , van Dongen Guus A.M.S. 
Published: August 2002

AbstractThe CD44 protein family consists of isoforms with tissue‐specific expression, which are encoded by standard exons and up to 9 alternatively spliced variant exons (v2–v10) of the same gene. The murine MAbs U36 and BIWA‐1, directed against overlapping epitopes within the v6 region of CD44, have previously been shown to efficiently target HNSCC. We herein report on the construction of 1 chimeric (BIWA‐2) and 2 humanized (BIWA‐4 and BIWA‐8) derivatives of BIWA‐1. Together with U36 and BIWA‐1, these new antibodies were evaluated for affinity to the antigen in vitro as well as for biodistribution and efficacy in RIT using nude mice bearing the HNSCC xenograft line HNX‐OE. As determined by surface plasmon resonance, the MAbs bound to CD44v6 with an up to 46‐fold difference in affinity (Kd ranging from 1.1 × 10−8 to 2.4 × 10−10 M) with the following ranking: mMAb U36 < hMAb BIWA‐4 < hMAb BIWA‐8 < mMAb BIWA‐1 ∼ cMAb BIWA‐2. To evaluate their in vivo tumor‐targeting properties, 2 MAbs with identical murine or human isotype were labeled with either 131I or 125I and administered simultaneously (50 μg/10 μCi each) as pairs showing a stepwise decrease in the difference in affinity: U36 vs. BIWA‐1 (35.0‐fold difference), BIWA‐4 vs. BIWA‐2 (14.0‐fold) and BIWA‐4 vs. BIWA‐8 (4.0‐fold). Biodistribution was assessed at 1, 2, 3 or 4 and 7 days after injection. Remarkably, for all 3 MAb pairs tested, the lower‐affinity MAb showed a higher degree and specificity of tumor localization. The difference in tumor localization was more pronounced when the difference in affinity was larger. For example, 3 days after injection, the lower‐affinity mMAb U36 showed a 50% higher tumor uptake than the higher‐affinity mMAb BIWA‐1, while blood levels and uptake in organs were similar. After labeling with 186Re (300 or 400 μCi), the same MAb pairs showed RIT efficacy consistent with the biodistribution data: 186Re‐U36 was more effective than 186Re‐BIWA‐1, 186Re‐BIWA‐4 was slightly more effective than 186Re‐BIWA‐2 and 186Re‐BIWA‐4 and 186Re‐BIWA‐8 demonstrated similar efficacy. Based on these data, we conclude that antibodies with markedly lower affinity to a given target antigen (e.g., U36, BIWA‐4) may show superior tumor targeting in comparison with higher‐affinity versions of these antibodies. © 2002 Wiley‐Liss, Inc.
Body mass index in relation to ovarian cancer: A multi‐centre nested case‐control study
Authors: Lukanova Annekatrin , Toniolo Paolo , Lundin Eva , Micheli Andrea , Akhmedkhanov Arslan , Muti Paola , Zeleniuch‐Jacquotte Anne , Biessy Carine , Lenner Per , Krogh Vittorio , Berrino Franco , Hallmans Goran , Riboli Elio , Kaaks Rudolf 
Published: August 2002

AbstractThe incidence of ovarian cancer is up to 10 times higher in Western countries than in rural Asia and Africa. One common consequence of a Western lifestyle is the development of excessive body weight and obesity. A multi‐centre prospective study was conducted to investigate the association between body mass index (BMI) and ovarian cancer risk. A case‐control study was nested within 3 prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Information on anthropometry, demographic characteristics, medical history and lifestyle was obtained at the time of subjects' recruitment in each cohort. Women diagnosed with primary, invasive epithelial ovarian cancer from the 3 cohorts (n = 122) diagnosed 12 months or later after recruitment into the respective cohort served as case subjects. For each case subject, 2 control subjects that matched the case subject on cohort, menopausal status, age and date of recruitment were randomly identified. Data were analyzed by conditional logistic regression. There was an inverse association between BMI and ovarian cancer risk. For increasing quartiles of BMI above the lowest, the ORs were 0.62 (0.32–1.21), 0.59 (0.30–1.17) and 0.46 (0.23–0.92), p = 0.03. Analyses limited to women diagnosed 3 or more years after recruitment into the cohorts did not alter these findings. When obese women (BMI > 30) were compared to lean women (BMI ≤ 23), the inverse association became stronger, with an OR of 0.38 (0.17–0.85), p < 0.02. There was some evidence of direct association of ovarian cancer with height, which was limited to cancers diagnosed before age 55. Our data suggest that increasing body weight may confer a protection against ovarian cancer. © 2002 Wiley‐Liss, Inc.
A HLA‐A2 restricted human CTL line recognizes a novel tumor cell expressed p53 epitope
Authors: Würtzen Peter A. , Claesson Mogens H. 
Published: August 2002

AbstractA p53 peptide‐specific CTL line was generated through stimulation with autologous monocyte‐derived dendritic cells (DC) pulsed with wild‐type HLA‐A2 binding p53 derived peptides. A p53 peptide‐specific CD8+ CTL line was established from a healthy HLA‐A2 positive donor. The CTL line was characterized with respect to specificity, affinity and killing of cell lines derived from p53 mutated spontaneous tumors. The CTL line demonstrated lysis of p53139–147 pulsed target cells and cold target inhibition experiments as well as antibody blocking confirmed that the killing was epitope‐specific, HLA‐A2 restricted and dependent on CD8‐binding. Interestingly, the affinity of the CTL line was only in the micromole per liter range and target cells pulsed with less than 0.01 μM peptide were not recognized. Furthermore, 3 HLA‐A2+ p53 mutated tumor cell lines were efficiently lysed by the CTL line, indicating that this novel p53 peptide epitope is endogenously processed and presented by the HLA‐A2 molecules of the tumor cells. In conclusion, CTL reactivity towards a wild‐type p53 peptide was revealed through induction with DC pulsed with a pool of HLA‐A2 binding p53 peptides. In addition, the CTL line, which expressed relatively low affinity for the HLA‐A2/peptide complex, was able to kill 3 different HLA‐A2+ p53 mutated tumor cell lines. The present and our previous observations expand the number of p53‐derived peptides suitable for vaccination protocols for cancer patients with p53 positive tumors. © 2002 Wiley‐Liss, Inc.
Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses
Authors: Panagopoulos Ioannis , Mertens Fredrik , Dêbiec‐Rychter Maria , Isaksson Margareth , Limon Janusz , Kardas Iwona , Domanski Henryk A. , Sciot Raf , Perek Danuta , Crnalic Sead , Larsson Olle , Mandahl Nils 
Published: August 2002

AbstractClear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark is the translocation t(12;22)(q13;q12) resulting in a chimeric EWS/ATF1 gene in which the 3′‐terminal part of EWS at 22q is replaced by the 3′‐terminal part of ATF1 at 12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the transcription level, and there is no information about the breakpoints at the genomic level. In the present study, we describe the molecular genetic characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases, 7 of which showed the characteristic t(12;22). As an initial step in the characterization of the EWS/ATF1 and ATF1/EWS chimeras, we constructed an exon/intron map of the ATF1 gene. The entire ATF1 gene spanned >40 kb and was composed of 7 exons. Intron 3, in which most of the genomic breakpoints occurred, was to a large extent (83%) composed of repetitive elements. RT‐PCR amplified EWS/ATF1 cDNA fragments in all patients and ATF1/EWS cDNA fragments in 6 of 10 patients. Four types of EWS/ATF1 chimeric transcript, designated types 1–4, were identified. The most frequent chimeric transcript (type 1) was an in‐frame fusion of exon 8 of EWS with exon 4 of ATF1. This was the only chimeric transcript in 5 patients but found together with other variants in 3 tumors. The type 2 transcript of EWS/ATF1, an in‐frame fusion of exon 7 of EWS with exon 5 of ATF1, was detected in 4 patients, as the only transcript in 1 case and together with other variants in 3 cases. An in‐frame fusion of exon 10 of EWS with exon 5 of ATF1 (type 3) was found in 1 patient as the only transcript, and an out‐of‐frame fusion of EWS exon 7 with ATF1 exon 7 (type 4) was detected in 1 patient together with type 1 and type 2 transcripts. Sequencing of the amplified ATF1/EWS cDNA fragments showed in 5 patients that ATF1 exon 3 was fused with EWS exon 10, resulting in an out‐of‐frame chimeric transcript. In 1 case, nt 428 of ATF1 (exon 4) was fused with EWS exon 8; at the junction, there was an insertion of 4 nucleotides, also resulting in an out‐of‐frame transcript. Genomic extra long PCR and sequence analysis mapped the genomic breakpoints to introns 7, 8 and 9 of EWS and intron 3 and exon 4 of ATF1. While a simple end‐to‐end fusion was observed in 2 cases, additional nucleotides were found at the junctions in 2 other cases. In addition, topoisomerase I consensus sequences were found close to the junctions, suggesting that this enzyme may participate in the genesis of the EWS/ATF1 fusion. © 2002 Wiley‐Liss, Inc.
Large‐scale randomized prostate cancer screening trials: Program performances in the European randomized screening for prostate cancer trial and the prostate, lung, colorectal and ovary cancer trial
Authors: de Koning Harry J. , Auvinen Anssi , Berenguer Sanchez Antonio , Calais da Silva Fernando , Ciatto Stefano , Denis Louis , Gohagan John K. , Hakama Matti , Hugosson Jonas , Kranse Ries , Nelen Vera , Prorok Philip C. , Schröder Fritz H. ,   ERSPC and the PLCO Trials (the International Prostate Cancer Screening Trials Evaluation Group)
Published: August 2002

AbstractTwo large‐scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate‐specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55–69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut‐off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age‐specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55–59 years], 1.80 [60–64 years] and 2.18 [65–69 years) than in the ERSPC trial (1.28–1.71 [55–59], 1.75–2.87 [60–64] and 2.48–3.06 [65–69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population‐based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two‐thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005–2008. © 2002 Wiley‐Liss, Inc.
Lack of ifn‐γ‐mediated induction of the class II transactivator (CIITA) through promoter methylation is predominantly found in developmental tumor cell lines
Authors: van der Stoep Nienke , Biesta Paula , Quinten Edwin , van den Elsen Peter J. 
Published: August 2002

AbstractDownregulation of major histocompatibility complex (MHC) molecules by tumor cells impairs cellular immune recognition and contributes to inefficient cell‐mediated tumor eradication. Low or lack of expression of MHC molecules is frequently observed in early developmental or embryonically derived tumor cells. Considering the central role of the class II transactivator (CIITA) in MHC class II‐ and class I‐mediated antigen presentation, we compared the induction of CIITA by interferon‐γ (IFN‐γ) in a diverse panel of developmental and more differentiated tumor cell lines. In contrast to the more differentiated tumor cell lines, none of the developmental tumor cell lines were capable of expressing CIITA after treatment with IFN‐γ. Remarkably, in transient transfection assays, CIITA promoter IV (CIITA‐PIV) was found to be induced by IFN‐γ. Southern blot analysis of genomic DNA obtained from the developmental tumor cell lines indicated that the absence of endogenous CIITA induction was due to methylation of the CIITA‐PIV region. Exposure to 5‐azacytidine restored induction of CIITA and congruent HLA‐DRA expression in these cells. The observation that only developmental tumor cell lines, originating from various tissues, employ methylation to silence CIITA expression may reflect the natural status of CIITA expression during early development rather than oncogenic transformation. © 2001 Wiley‐Liss, Inc.
Demographic responses to environmental stress in the drought‐ and famine‐prone areas of northern Ethiopia
Authors: Ezra Markos 
Published: August 2002

AbstractResearch on the demographic consequences of environmental stress (drought and famine, in particular) has not been conclusive. Using primary survey data on the demographic consequences of drought and famine in the drought‐prone areas of northern Ethiopia, this study argues that growing environmental stress and persisting food insecurity have stimulated changes in the demographic behaviours and attitudes of farming communities, including: an increase in acceptance rates of family planning services; changing attitudes towards early marriage and having a large number of children; actual reduction in fertility; migration (particularly of the youth) out of the communities; and the tendency by many farmers to be involved in non‐farm income‐generating activities and employment sectors. Copyright © 2001 John Wiley & Sons, Ltd.
Regional fertility differences in western Germany: an overview of the literature and recent descriptive findings
Authors: Hank Karsten 
Published: August 2002

AbstractIn the years following German unification, researchers' attention has been attracted mainly by the rapid fertility decline in eastern Germany. This has often resulted in neglect of regional fertility differentials within Germany, which reach much further back in time than those currently observed between the ‘old’ and the ‘new’ Länder of the Federal Republic. This paper provides an overview of studies investigating regional fertility differences in post‐war western Germany. Additionally, results of an analysis of official statistics for western German Kreise (districts) in the period 1995–97 are presented. Geographical patterns of high‐ and low‐fertility areas are detected, which have remained basically unchanged by the general fertility decline of the late 1960s and early 1970s. Consistent with findings from earlier studies, population density, family migration and the local occupational structure are still found to be closely associated with regional total fertility rates in the 1990s. The paper concludes with a call for more multilevel studies that –theoretically as well as empirically –link regional social contexts with individual (reproductive) behaviour. Copyright © 2001 John Wiley & Sons, Ltd.
Alcohol and drug‐related effects on development: A new emphasis on contextual factors
Authors: Jacobson Sandra W. , Jacobson Joseph L. 
Published: August 2002

AbstractThe articles in this special issue bring together two lines of research that reflect different perspectives on the effects of parental alcohol and drug abuse—the long‐term impact of teratogenic insult due to prenatal exposure and the developmental risks associated with being reared by a substance‐abusing parent. These articles reflect major methodological advances, including the use of moderator variables—particularly, parental psychopathology and child temperament—for detecting the adverse impact of parental substance abuse on child outcome. In several articles, more comprehensive sets of control variables are considered than in prior studies, and investigators examine the use of aggregate and cumulative risk factors in an attempt to better model underlying conditions of risk. Another advance is that most of these studies recognize the importance of quantifying levels of prenatal alcohol and drug exposure. In focusing our attention simultaneously on prenatal exposure, parental substance abuse and comorbid psychopathology, child temperament, and contextual factors, these studies offer a better understanding of the complex interrelated influences of risk factors on the child's cognitive and socio‐emotional development. © 2001 Michigan Association for Infant Mental Health.
Serially correlated variables in dynamic, discrete choice models
Authors: Stinebrickner Todd R. 
Published: August 2002

AbstractThis paper discusses the problems that are encountered when dynamic, discrete choice models are specified with continuous, serially correlated state variables. A variety of approximation methods that can deal with these problems is examined, and an empirical example that allows continuous variables to be serially correlated is presented. Copyright © 2000 John Wiley & Sons, Ltd.
A multivariate latent factor decomposition of international bond yield spreads
Authors: Dungey Mardi , Martin Vance L , Pagan Adrian R 
Published: August 2002

AbstractA factor analysis of long‐term bond spreads is performed by decomposing international interest rate spreads into national and global factors. The factors are latent, and are assumed to have GARCH‐type specifications as well as exhibiting serial dependence. An indirect estimator is used to compute estimates of the unknown parameters. The sampling performance of this estimator is investigated and compared with an alternative direct estimator based on the Kalman predictor. The factor model is applied to weekly data on long‐bond spreads between five countries ‐ Australia, Japan, Germany, Canada and the UK ‐ and the USA over the period 1991 to 1999. The resulting factor decomposition is used to examine the international investor's optimal portfolio decision in a mean‐variance framework. Copyright © 2000 John Wiley & Sons, Ltd.
Bayesian semiparametric estimation of discrete duration models: an application of the dirichlet process prior
Authors: Campolieti Michele 
Published: August 2002

AbstractThis paper proposes a Bayesian estimator for a discrete time duration model which incorporates a non‐parametric specification of the unobserved heterogeneity distribution, through the use of a Dirichlet process prior. This estimator offers distinct advantages over the Nonparametric Maximum Likelihood estimator of this model. First, it allows for exact finite sample inference. Second, it is easily estimated and mixed with flexible specifications of the baseline hazard. An application of the model to employment duration data from the Canadian province of New Brunswick is provided. Copyright © 2001 John Wiley & Sons, Ltd.
Trend‐stationary GNP: evidence from a new exact pointwise most powerful invariant unit root test
Authors: Shively Philip A. 
Published: August 2002

AbstractThere has been a substantial debate whether GNP has a unit root. However, statistical tests have had little success in distinguishing between unit‐root and trend‐reverting specifications because of poor statistical properties. This paper develops a new exact small‐sample, pointwise most powerful unit root test that is invariant to the unknown mean and scale of the time series tested, that generates exact small‐sample critical values, powers and p‐values, that has power which approximates the maximum possible power, and that is highly robust to conditional heteroscedasticity. This test decisively rejects the unit root null hypothesis when applied to annual US real GNP and US real per capita GNP series. This paper also develops a modified version of the test to address whether a time series contains a permanent, unit root process in addition to a temporary, stationary process. It shows that if these GNP series contain a unit root process in addition to the stationary process, then it is most likely very small. Copyright © 2001 John Wiley & Sons, Ltd.
Combined pulmonary toxicity of cadmium chloride and sodium diethyldithiocarbamate
Authors: Tátrai Erzsébet , Brózik Márta , Náray Miklós , Adamis Zoltán , Ungváry György 
Published: August 2002

AbstractThe pulmonary toxicity of sodium diethyldithiocarbamate and cadmium chloride, each separately and in combination, was compared in Sprague‐Dawley rats after single intratracheal instillation in sequential experiments by chemical, immunological and morphological methods. With combined exposure, the cadmium content of the lungs increased permanently relative to that of the lungs of just cadmium‐treated animals. Immunoglobulin levels of the whole blood did not change, whereas in bronchoalveolar lavage the IgA and IgG levels increased significantly. Morphological changes were characteristic of the effects of cadmium but were more extensive and more serious than in the case of cadmium administration alone: by the end of the first month, interstitial fibrosis, emphysema and injury of membranes of type I pneumocytes developed and hypertrophy and loss of microvilli in type II pneumocytes were detectable. These results showed that although dithiocarbamates as chelating agents are suitable for the removal of cadmium from organisms, they alter the redistribution of cadmium within the organism, thereby increasing the cadmium content in the lungs, and structural changes are more serious than observed upon cadmium exposure alone. Copyright © 2001 John Wiley & Sons, Ltd.