bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody‐guided enzyme therapy of cancer producing cyanide results in necrosis of targeted cells
Authors: Kousparou Christina A. , Epenetos Agamemnon A. , Deonarain Mahendra P. 
Published: August 2002

AbstractA number of enzyme/prodrug activation approaches for the treatment of cancer have been reported to date with varying success. We describe progress in the development of a system based on a β‐glucosidase enzyme in combination with a naturally occurring “prodrug,” the sugar linamarin, which releases the cytotoxin cyanide. A recombinant fusion protein, composed of an scFv (MFE‐23) reactive against carcinoembryonic antigen (CEA) and a plant‐derived β‐glucosidase (linamarase), was produced and its cytotoxic potential was investigated. The fusion protein was expressed in a supersecretory mutant strain of Saccharomyces cerevisiae and purified by affinity chromatography. Extensive functional in vitro characterisation of the fusion protein showed that it retained antigen binding activity but that its catalytic activity was impaired, a problem not related to its fusion with the scFv. Nevertheless, we demonstrated complete tumour cell killing at doses of prodrug that are completely nontoxic to nontargeted cells. Preliminary in vivo characterisation showed that extensive glycosylation of the fusion protein caused its rapid clearance through the hepatic route. Aggregational properties also led to poor pharmacokinetics. Furthermore, we present some data analysing the mode of cell death resulting from exposure to this system. Enzymic catalysis of the substrate generates cyanide, a metabolic poison that asphyxiates cells and leads them to a necrotic‐like cell death. This system has been called antibody‐guided enzyme nitrile therapy (AGENT). © 2002 Wiley‐Liss, Inc.
Grand multiparity and incidence of endometrial cancer: A population‐based study in Finland
Authors: Hinkula Marianne , Pukkala Eero , Kyyrönen Pentti , Kauppila Antti 
Published: August 2002

AbstractThe hormonal background of endometrial cancer is insufficiently characterised. We investigated the significance of parity, age at first birth, intensity between births, length of time from the first to the last birth and length of delivery‐free premenopausal period in a cohort of grand multiparous (GM) women, i.e., women with at least 5 births. Data of the Population Register of Finland (86,978 GM‐women) and the population‐based Finnish Cancer Registry were combined. Standardised incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases by the expected number based on the national incidence rates. Multivariate relative risks (RRs) were estimated by Poisson regression analysis. The SIR for endometrial cancer among GM‐women was low [419 cases; SIR=0.57, 95% confidence interval (CI) 0.52–0.63]. The RR of endometrial cancer was 0.58 (95% CI 0.34–0.97) among women giving their first birth at an age of more than 30 years compared to women with first birth before the age of 20. In ages 50+ (94% of endometrial cancer cases), the RR for women with at least 8 births was 0.63 (95% CI 0.44–0.92) compared to those with 5 births, and those with a birth period of 20+ years had RR=0.57 (95% CI 0.34–0.96) compared to those with a period of <10 years, while prolonged average intensity between births showed only a small protective effect. The RR of endometrial cancer also correlated with the length of premenopausal delivery‐free period (RR = 0.61, 95% CI 0.44–0.86) for women with a short (<10 years) period compared to women with a long (>15 years) period. Our findings, that a large number of births, old age at first birth, a long birth period and a short premenopausal delivery‐free period reduced the risk of postmenopausal endometrial cancer of GM‐women, emphasise the protective role of progesterone and the stimulatory role of estradiol in the hormonal background of this disease. © 2002 Wiley‐Liss, Inc.
Kinetics of the early recruitment of leukocyte subsets at the sites of tumor cells in the lungs: Natural killer (NK) cells rapidly attract monocytes but not lymphocytes in the surveillance of micrometastasis
Authors: Shingu Kiyoshi , Helfritz Andreas , Kuhlmann Susanne , Zielinska‐Skowronek Margot , Jacobs Roland , Schmidt Reinhold E. , Pabst Reinhard , von Hörsten Stephan 
Published: August 2002

AbstractEarly host defense mechanisms play a critical role for the outcome of metastatic disease but most of the initial steps of such responses against tumor cells are still unknown. Here, the specificity and kinetics of leukocyte subsets in response to intravenous inoculation of vital dye labeled Fischer 344 rat syngeneic MADB106 tumor cells were monitored in lungs in situ by immunohistochemistry and image analysis over a time‐period of 6 hr. In comparison with sham injections, tumor cell inoculation induces a dynamic sequence of rapidly increasing granulocyte (+40% at 5 min), NK and T cell (+60% at 15 min) as well as monocyte (+100% at 30 min) numbers in lung tissue. Already within the first minutes frequent colocalizations of granulocytes and NK cells with tumor targets were found in situ. Within the first hour NK cells selectively kill tumor targets, because depletion of NK cells in vivo drastically increases both the number of MADB106 cells retained in lungs and the emerging numbers of lung tumor colonies. In addition, the tumor‐cell‐induced increase of monocytes strictly depends on the presence of NK cells because NK‐depletion completely abrogates the time specific response of monocytes. Under NK depleted conditions the tumor‐induced recruitment of CD4+ T cells is more pronounced suggesting a compensatory mechanism. In contrast, B cell numbers progressively decrease within hours after cell inoculation. These findings demonstrate that NK and T cells mediate the initial steps in the surveillance of lung metastasis. NK cells rapidly kill tumor cells and subsequently recruit monocytes in vivo. © 2002 Wiley‐Liss, Inc.
Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas
Authors: Yan Pu , Benhattar Jean , Coindre Jean‐Michel , Guillou Louis 
Published: August 2002

AbstractIn a previous study, we showed that telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA expression were undetectable in benign mesenchymal lesions and low‐grade soft tissue sarcomas (STSs), but detectable in about 50% of intermediate‐/high‐grade STSs. We wondered if this lack of TA or hTERT mRNA expression could be related to the tumor sample examined and if there was a relationship between the former 2 parameters and telomere length. Two separate tumor samples from 37 STSs were examined for telomerase activity, using the telomerase repeat amplification protocol (TRAP) assay and for hTERT mRNA expression, using RT‐PCR. Telomere length was determined in each tumor sample, using the terminal restriction fragments (TRF) technique. Significant variations in telomere length, TA and hTERT mRNA expression between 2 samples of the same tumor were observed in 27%, 11% and 27% of STSs, respectively. Telomere length did not correlate with TA or hTERT mRNA expression. Despite great intratumoral heterogeneity in telomere length, short and long telomeres were more often seen in the low/intermediate‐grade and high‐grade STS categories, respectively. Few STSs that showed a TRF pattern suggestive of alternative lengthening of telomeres (ALT) may contain ALT subpopulations. © 2002 Wiley‐Liss, Inc.
Cheng W, Chan KH, Chen H, Luo R, Ng SP, Luk W, Zheng B, Ji M, Liang M, Sham JST, Wang DK, Y Zong Y, Ng MH. Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum. International Journal of Cancer 2002;97(4): 489–492.
Authors: Cheng W , Chan KH , Chen H , Luo R , Ng SP , Luk W , Zheng B , Ji M , Liang M , Sham JST , Wang DK , Zong Y , Ng MH 
Published: August 2002

AbstractThe original article to which this Erratum refers was published in International Journal of Cancer; 2002; 97(4) 489–492.
Cell type‐ and promoter‐dependent modulation of the Wnt signaling pathway by sodium butyrate
Authors: Bordonaro Michael , Lazarova Darina L. , Augenlicht Leonard H. , Sartorelli Alan C. 
Published: August 2002

AbstractThe Wnt signaling pathway modulates the transcription of genes linked to proliferation, differentiation and tumor progression. β‐Catenin‐Tcf (BCT)‐dependent Wnt signaling is influenced by the short‐chain fatty acid sodium butyrate, which induces growth arrest and/or maturation of colonic carcinoma cells. We have compared the effects of sodium butyrate on BCT‐dependent signaling in 2 colon carcinoma cell lines that differ in their physiologic response to butyrate, with SW620 cells responding to butyrate by undergoing terminal differentiation and apoptosis, and HCT‐116 cells undergoing reversible growth arrest, but no significant apoptotic cell death. Furthermore, these colon carcinoma cell lines differ in their mechanism of Wnt pathway activation, with adenomatous polyposis coli (APC) mutant SW620 cells having high levels of BCT complexes and APC wild‐type HCT‐116 cells having mutant β‐catenin, low levels of BCT complexes and correspondingly higher levels of free Tcf. We have demonstrated that in SW620 cells, butyrate downregulates BCT‐dependent expression of the Tcf‐TK, matrilysin and cyclin D1 promoters, whereas in HCT‐116 cells, butyrate upregulates expression of these promoters. Cotransfection with expression vectors that interfere with the Wnt pathway suggests that butyrate enhances BCT complex‐DNA binding. Butyrate reduces the expression of Tcf4 in HCT‐116 cells, consistent with the induction by butyrate of Tcf‐repressible promoters in these cells. These findings indicate that sodium butyrate modulates the Wnt pathway in SW620 and HCT‐116 cells in a different manner and that these differences have consequences for promoter activity that may influence the physiologic response to butyrate. © 2002 Wiley‐Liss, Inc.
Pegylated liposomal tumor necrosis factor‐α results in reduced toxicity and synergistic antitumor activity after systemic administration in combination with liposomal doxorubicin (Doxil®) in soft tissue sarcoma‐bearing rats
Authors: ten Hagen Timo L.M. , Seynhaeve Ann L.B. , van Tiel Sandra T. , Ruiter Dirk J. , Eggermont Alexander M.M. 
Published: August 2002

AbstractPreviously we reported that encapsulation of tumor necrosis factor‐α (TNF) in pegylated (STEALTH®) liposomes (TNF‐PEGL) dramatically improved circulation times of the protein and augmented accumulation in tumor tissue. We and others have demonstrated enhanced antitumor activity of doxorubicin or melphalan by free TNF when used in high doses in an isolated limb perfusion setting. In the present study the antitumor activity of TNF‐PEGL was studied in combination with liposomal chemotherapy. BN rats with subcutaneous BN175 sarcomas (8–12 mm diameter) received no treatment or pegylated liposomal doxorubicin (Doxil®) alone or in combination with various doses of TNF‐PEGL (15–200 μg/kg). The evaluated endpoints were tumor response and toxicity of the treatment regimens. Here we demonstrate that TNF‐PEGL at a dose of 15 μg/kg markedly augments the antitumor activity of liposomal doxorubicin, without resulting in the increased toxic side effects observed with free TNF at doses resulting in a similar enhancement of the antitumor effects. Even at a TNF dose of 200 μg/kg TNF, repeated administration of TNF‐PEGL did not result in severe weight loss or cause diarrhea. Repeated dosing of free TNF at this dose resulted in severe, life‐threatening weight loss and occurrence of diarrhea in all animals. These results indicate that pegylated liposomal encapsulation may be effective in systemic application of TNF for combined treatment with liposomal chemotherapy of advanced solid tumors. © 2002 Wiley‐Liss, Inc.
Event study concerning international bond price effects of credit rating actions
Authors: Steiner Manfred , Heinke Volker G. 
Published: August 2002

AbstractThe influence of credit ratings on eurobond prices has been neglected for a long time. It is questionable whether non‐US investors relate their investment decisions on US ratings and whether ratings from US agencies are relevant information sources for international capital markets. This paper examines daily excess eurobond returns associated with announcements of watchlistings and rating changes by Standard & Poor's and Moody's. Significant bond price reactions are observed for announcements of downgradings and negative watchlistings while upgradings and positive watchlistings do not cause announcement effects. Distinct from the results on national capital markets the international evidence shows that besides actual yield level and issuer type the issuer nationality is a key factor that determines the intensity of price reactions after downgrades. The price reaction is also significantly stronger for downgrades into speculative grade. This indicates, that the announcement effects can in part be explained by price pressure effects due to regulatory constraints rather than original information content of rating changes. Copyright © 2001 John Wiley & Sons, Ltd.
Developing countries' borrowing in the international financial market with an uncertain credit ceiling?
Authors: Isgut Alberto E. 
Published: August 2002

AbstractIn the sovereign debt literature of the 1980s, countries formulated optimal borrowing plans subject to a credit ceiling imposed by their lenders. This paper analyzes the case where the credit ceiling is not known with certainty. The baseline deterministic model shows that consumption, investment and the current account deficit depend positively on the credit ceiling, implying more optimistic expectations about the country's future access to external financing led to larger current account deficits today. An extension of the model shows that when the country recognizes the uncertainty about future access to borrowing, optimal current account deficits are more moderate. Copyright © 2001 John Wiley & Sons, Ltd.
Mobility as a driver of change in rural Britain: an analysis of the links between migration, commuting and travel to shop patterns
Authors: Findlay A. M. , Stockdale Aileen , Findlay Anne , Short David 
Published: August 2002

AbstractPolicy‐makers are concerned with issues relating commuting to service provision. To make informed judgements on such topics requires an understanding of the nature of mobility cultures. This article explores the mobility cultures of rural residents. In particular, it investigates the association between migration, travel to work and travel to shop. Log‐linear analysis is used to show that the journey to work is a defining variable in mobility cultures and that commuting to work is likely to be associated with commuting for other activities such as shopping in the areas most favoured by migrants. Copyright © 2001 John Wiley & Sons, Ltd.
Maternal sensitivity behavior and infant behavior in early interaction
Authors: Kivijärvi Marja , Voeten Marinus J.M. , Niemelä Pirkko , Räihä Hannele , Lertola Kalle , Piha Jorma 
Published: August 2002

AbstractMaternal sensitivity behavior and infant behavior in early interaction were investigated among 57 Finnish mother–child pairs. Their interaction was video‐recorded at home in free‐play situation when the infants were 3 months and 12 months of age, and evaluated using the Parent–Child Early Relational Assessment Scale (PCERA). Maternal sensitivity behavior was mainly related to infant's positive aspects of mood, social and play behavior, and visual contact, both at 3 months and 12 months of age. Even though maternal sensitivity behavior correlated to infant behavior at 3 months and 12 months, infant behavior at 3 months of age contributed to later maternal sensitivity behavior. ©2001 Michigan Association for Infant Mental Health.
MIOS: a decision tool for determination of optimal irrigated cropping pattern of a multicrop system under water scarcity constraints
Authors: Kipkorir E. C. , Sahli A. , Raes D. 
Published: August 2002

AbstractThis paper develops a dynamic programming optimisation model that considers the competition of crops in a season, both for irrigation water and cultivated area. Decision variables are the cultivated area and water allocated to each crop. The objective function of the model is based on crop‐water production functions, production costs and crop prices. The model is solved using the CSUDP generalised dynamic programming package for conditions existing in northern Tunisia where a large fraction of the irrigation water is stored in a reservoir mainly during the winter period. The model gives the optimal distribution of area and water to each crop and the profit. Sensitivity analysis of the optimal solution to costs, area and changes in crop prices is carried out. The analysis results show that changes in prices and costs have a large impact on profits. Results indicate that the model can be a valuable tool for regional agencies or irrigation authorities in determining seasonal cropping pattern for a region at the beginning of the season. Copyright © 2002 John Wiley & Sons, Ltd.
A longitudinal study of applicable decision aids for detailed tasks in a financial audit
Authors: Abdolmohammadi Mohammad , Usoff Catherine 
Published: August 2002

AbstractThis paper reports on changes in the extent to which decision aids are perceived to be useful for performing detailed financial audit tasks. The decision aids investigated were automation (AU), decision support systems (DSS), and knowledge‐based expert systems (KES). Data were collected from highly experienced mangers and partners from various international accounting firms in 1988 and 1996. The participants were asked to select the decision aid they viewed as applicable for each task in a comprehensive inventory of audit tasks. While the data indicate an increase in the choice of tasks for decision aids use between the two years, the fact remains that a majority of the responses (79% in 1988 and 69% in 1996) indicated human processing (HP) only. We present a list of detailed tasks for which at least 50% of the responses indicated some form of an applicable decision aid in 1996. We also discuss implications for practice and research. Copyright © 2001 John Wiley & Sons, Ltd.
A score test for non‐nested hypotheses with applications to discrete data models
Authors: Santos Silva J. M. C. 
Published: August 2002

AbstractIn this paper it is shown that a convenient score test against non‐nested alternatives can be constructed from the linear combination of the likelihood functions of the competing models. This is essentially a test for the correct specification of the conditional distribution of the variable of interest. Given its characteristics, the proposed test is particularly attractive to check the distributional assumptions in models for discrete data. The usefulness of the test is illustrated with an application to models for recreational boating trips. Copyright © 2001 John Wiley & Sons, Ltd.
Comparative in vitro toxicity of cadmium and lead on redox cycling in type II pneumocytes
Authors: Tátrai Erzsébet , Kováciková Zuzana , Hudák Aranka , Adamis Zoltán , Ungváry György 
Published: August 2002

AbstractBoth cadmium and lead have pulmonary toxicity: cadmium can cause lung cancer, fibrosis and emphysema; lead can induce a moderate interstitial pulmonary fibrosis. Both metals give rise to depletion of glutathione and depletion of the protein‐bound sulfhydryl groups, and lead to the production of reactive oxygen species. In the primary culture of type II pneumocytes, which is one of the most important cell groups from the aspect of glutathione metabolism and thus redox balance, the effect of cadmium chloride and lead nitrate upon the enzymes of the glutathione cycle, upon superoxide dismutase and upon the structure of type II pneumocytes was examined. Depending on the concentration, cadmium inhibited each of these parameters, whereas lead nitrate significantly increased the activity of glutathione reductase while inhibiting other parameters. Both metals induced damage of the membranes of type II cells, depending on the concentration, although cadmium caused significantly more damage than lead. The data obtained suggest that both substances cause an imbalance in the redox cycle and diversely affect the function and membrane structure of type II pneumocytes. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of mitomycin‐C on the bioavailability of the radiopharmaceutical 99mtechnetium–phytic acid in mice: a model to evaluate the toxicological effect of a chemical drug
Authors: Gomes Maria Luisa , Braga Ana Cristina de Souza , Mattos Deise Mara Machado de , Freitas Rosimeire de Souza , Paula Emílio Faustino de , Bezerra Roberto José A.C. , Bernardo‐Filho Mario 
Published: August 2002

AbstractThe many desirable characteristics of technetium‐99m (99mTc) have stimulated the development of labelling techniques for different molecular and cellular structures. It is generally accepted that a variety of factors can alter the biodistribution of radiopharmaceuticals and one such factor is drug therapy. Because patients on chemotherapeutic treatment receive a radiopharmaceutical in a nuclear medicine procedure, we have studied in Balb/c mice the effect of mitomycin‐C on the biodistribution of the radiopharmaceutical 99mTc‐phytic acid (99mTc‐PHY) used in hepatic scintigraphy. Mitomycin‐C is an antineoplastic agent obtained from Streptomyces caesptosus and is used on the treatment of disseminated adenocarcinoma of the stomach or pancreas. Three doses of mitomycin‐C were administered via the ocular plexus into Balb/c mice. One hour after the last dose, 99mTc‐PHY was administered and the animals were sacrificed. The organs were isolated, the radioactivity was determined in a well counter and the percentages of radioactivity in the organs were calculated. The results have shown that the percentage radioactivity has been increased in stomach, spleen, lung, thyroid and bone, decreased in pancreas and thymus and not altered in ovary, uterus, kidney, heart, liver and brain. The changes in the distribution of 99mTc‐PHY may be the result of metabolic processes and/or therapeutic actions produced by the administration of mitomycin‐C. Copyright © 2002 John Wiley & Sons, Ltd.