bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta‐iodobenzylguanidine induces growth inhibition and apoptosis of neuroendocrine gastrointestinal tumor cells
Authors: Höpfner Michael , Sutter Andreas P. , Beck Nikolai I. , Barthel Bettina , Maaser Kerstin , Jockers‐Scherübl Maria C. , Zeitz Martin , Scherübl Hans 
Published: August 2002

AbstractNeuroendocrine gastrointestinal tumors take up, decarboxylate and store large amounts of monoamines. Radioactive‐labeled monoamines like the norepinephrine analogue meta‐iodobenzylguanidine (MIBG) have been used for the imaging of neuroendocrine tumors for many years. MIBG is selectively taken up via norepinephrine transporters (NETs) localized in the plasma membrane of neuroendocrine gastrointestinal tumor cells and thereby offers the possibility for specific and innovative therapeutic approaches. We investigated the antiproliferative, cytotoxic, cell cycle‐arresting and apoptosis‐inducing effects of MIBG in the neuroendocrine gastrointestinal tumor cell line STC‐1 and for control in the nonneuroendocrine colorectal cancer cell line HT‐29. RT‐PCR revealed the expression of NET in STC‐1 but not in HT‐29 cells. MIBG dose‐dependently induced cytotoxicity and growth inhibition of STC‐1 cells. It potently induced apoptosis in STC‐1 cells as assessed by changes in the mitochondrial membrane potential, activation of caspase‐3 and DNA fragmentation. Moreover, MIBG altered the expression of several genes involved in proliferation, apoptosis and stress responses as shown by cDNA arrays. In contrast, neither cytotoxicity, nor growth inhibition nor induction of apoptosis were detected in response to MIBG in the NET‐deficient colorectal cancer cell line HT‐29. Our data show that MIBG induces growth inhibition and apoptosis in neuroendocrine gastrointestinal tumor cells. MIBG did not arrest the cell cycle in either cell line. Thus, monoamine transporters in the plasma membrane of neuroendocrine gastrointestinal tumor cells are promising targets for innovative and specific treatment strategies of these tumors. © 2002 Wiley‐Liss, Inc.
Inhibition of the mammary carcinoma angiogenic switch in C3(1)/SV40 transgenic mice by a mutated form of human endostatin
Authors: Calvo Alfonso , Yokoyama Yumi , Smith Lois E. , Ali Iqbal , Shih Shu‐Ching , Feldman Andrew L. , Libutti Steven K. , Sundaram Ramakrishnan , Green Jeffrey E. 
Published: August 2002

AbstractCancer therapies based on the inhibition of angiogenesis by endostatin have recently been developed. We demonstrate that a mutated form of human endostatin (P125A) can inhibit the angiogenic switch in the C3(1)/Tag mammary cancer model. P125A has a stronger growth‐inhibitory effect on endothelial cell proliferation than wild‐type endostatin. We characterize the angiogenic switch, which occurs during the transition from preinvasive lesions to invasive carcinoma in this model, and which is accompanied by a significant increase in total protein levels of vascular endothelial growth factor (VEGF) and an invasion of blood vessels. Expression of the VEGF188 mRNA isoform, however, is suppressed in invasive carcinomas. The VEGF receptors fetal liver kinase‐1 (Flk‐1) and Fms‐like tyrosine kinase‐1 (Flt‐1) become highly expressed in epithelial tumor and endothelial cells in the mammary carcinomas, suggesting a potential autocrine effect for VEGF on tumor cell growth. Angiopoietin‐2 mRNA levels are also increased during tumor progression. CD‐31 (platelet‐endothelial cell adhesion molecule [PECAM]) staining revealed that blood vessels developed in tumors larger than 1 mm The administration of P125A human endostatin in C3(1)/Tag females resulted in a significant delay in tumor onset, decreased tumor multiplicity and tumor burden and prolonged survival of the animals. Endostatin treatment did not reduce the number of preinvasive lesions, proliferation rates or apoptotic index, compared with controls. However, mRNA levels of a variety of proangiogenic factors (VEGF, VEGF receptors Flk‐1 and Flt‐1, angiopoietin‐2, Tie‐1, cadherin‐5 and PECAM) were significantly decreased in the endostatin‐treated group compared with controls. These results demonstrate that P125A endostatin inhibits the angiogenic switch during mammary gland adenocarcinoma tumor progression in the C3(1)/Tag transgenic model. © 2002 Wiley‐Liss, Inc.
Cyclosporin A enhances the apoptotic effects of N‐(4‐hydroxyphenyl)retinamide in breast cancer cells
Authors: Lim Soo‐Jeong , Simeone Ann‐Marie , Kim Chong‐Kook , Tari Ana M. 
Published: August 2002

Abstract4HPR, an analogue of ATRA, effectively induces growth inhibition and apoptosis in breast cancer cell lines and animal models but is ineffective against advanced human breast tumors. Different compounds, including tamoxifen, are currently being tested to increase 4HPR efficacy in the clinic. Here, we report that cyclosporin A selectively increases the ability of 4HPR, but not ATRA, to induce growth inhibition and apoptosis in ER+ and ER− breast cancer cell lines. Increased apoptosis by the 4HPR and cyclosporin A combination was correlated with increased production of the free radical nitric oxide. Thus, the 4HPR and cyclosporin A combination may potentially be a novel therapeutic modality against breast tumors. © 2002 Wiley‐Liss, Inc.
Increased risk of grade IV neutropenia after administration of 5‐fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: High prevalence of the IVS14+1g>a mutation
Authors: Van Kuilenburg André B.P. , Meinsma Rutger , Zoetekouw Lida , Van Gennip Albert H. 
Published: August 2002

AbstractDihydropyrimidine dehydrogenase (DPD) is the initial and rate‐limiting enzyme in the catabolism of 5‐fluorouracil (5‐FU), and it is suggested that patients with a partial deficiency of this enzyme are at risk of developing severe 5‐FU‐associated toxicity. We evaluated the importance of DPD deficiency, gender and the presence of the IVS14+1G>A mutation in the etiology of 5‐FU toxicity. In 61% of cases, decreased DPD activity could be detected in peripheral blood mononuclear cells. Furthermore, the number of females (65%) in the total group of patients appeared to be higher than the number of males (35%) (p = 0.03). Patients with partial DPD deficiency appeared to have a 3.4‐fold higher risk of developing grade IV neutropenia than patients with normal DPD activity. Analysis of the DPYD gene of patients suffering from grade IV neutropenia for the presence of the IVS14+1G>A mutation showed that 50% of the patients investigated were heterozygous or homozygous for the IVS14+1G>A mutation. Adopting a threshold level for DPD activity of 70% of that observed in the normal population, 14% of the population is prone to the development of severe 5‐FU‐associated toxicity. Below this threshold level, 90% of individuals heterozygous for a mutation in the DPYD gene can be identified. Considering the common use of 5‐FU in the treatment of cancer, the severe 5‐FU‐related toxicities in patients with low DPD activity and the apparently high prevalence of the IVS14+1G>A mutation, screening of patients at risk before administration of 5‐FU is warranted. © 2002 Wiley‐Liss, Inc.
Prognostic significance of cytokine modulation in non‐small cell lung cancer
Authors: Neuner A. , Schindel M. , Wildenberg U. , Muley T. , Lahm H. , Fischer J.R. 
Published: August 2002

AbstractIncreased production of immunosuppressive interleukin‐10 (IL‐10) by non‐small cell lung cancer (NSCLC) and increased serum IL‐10 concentrations in NSCLC‐patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL‐2 secretion in whole blood cell cultures of NSCLC‐patients. We now analyzed the influence of IL‐2 secretion on survival in NSCLC‐patients and the influence of IL‐10 on IL‐2 secretion. The correlation of the IL‐2 producing ability of whole blood cells in response to PHA in 90 NSCLC‐patients at the time of diagnosis to survival was calculated by Crit‐level, the Kaplan‐Meier method and the log‐rank test. With a cut‐off value of IL‐2 production of 1,100 pg/ml by whole blood cells the difference in survival was significant with ap‐value of 0.014. In the group with high and low IL‐2, median survival was 14.1 and 9.7 months, respectively. In the subgroup of 33 surgically‐treated patients the difference in survival was significant with ap‐value of 0.011. In 14 patients with surgical resection of the tumor and high IL‐2 at diagnosis and 19 patients with surgical resection, but low IL‐2 at diagnosis, median survival was 86.2 and 11.3 months, respectively. Secretion of IL‐2 in whole blood cell cultures from healthy individuals was inhibited in a dose‐dependent manner upon addition of IL‐10. Taken together, suppression of IL‐2 secretion has prognostic significance for survival of NSCLC‐patients and may be mediated by tumor‐derived IL‐10. © 2002 Wiley‐Liss, Inc.
BXD recombinant inbred mice represent a novel T cell–mediated immune response tumor model
Authors: Grizzle William E. , Mountz John D. , Yang Ping‐Ar , Xu Xin , Sun Sheher , Van Zant Gary E. , Williams Robert W. , Hsu Hui‐Chen , Zhang Huang‐Ge 
Published: August 2002

AbstractTo develop a better animal model for studying the effects of the host environment in neoplasia, we injected various genetically well‐characterized H‐2d RI strains of BXD mice with syngeneic breast cancer cells (TS/A) and monitored the growth of tumors over time. There was a marked difference in the growth of the implanted breast cancer cells among the 14 BXD RI strains, with 4 patterns of tumor development being observed: in type I, the implanted tumor cells grew rapidly in the first 2 weeks, necrosis of the tumors was observed and metastases to the intestinal lymph nodes and pancreas was observed, causing death; in type II, the implanted tumor cells grew slowly and attained a size after day 50 that required killing the animal, with tumor necrosis being rare and metastases absent; in type III, the implanted tumor cells grew initially but underwent a slow decline after 4 weeks; and in type IV, the implanted tumor cells failed to develop. Apoptosis of the implanted tumor cells was responsible for the regression of tumor nodules. The T‐cell immune response minimized tumor development in types III and IV since T‐cell depletion of the BXD RI mice resulted in aggressively growing tumors in these strains. © 2002 Wiley‐Liss, Inc.
Devaluation Expectations and the Stock Market: a new measure and an application to Mexico 1994/95
Authors: Becker Torbjörn , Gelos R. Gaston , Richards Anthony J. 
Published: August 2002

AbstractThis paper develops a market‐based measure of devaluation expectations derived from the relative stock market performance of companies with different exposures of current and future profits to exchange‐rate changes. The measure can be viewed as a complement to measures of devaluation expectations based on interest‐rate‐parity conditions, survey data or macroeconomic models. Some of the benefits of the measure are that data are available on a timely basis and that the stock market has traditionally been free of central bank intervention. As an illustration, we examine the Mexican devaluation of 1994. Contrary to what might have been expected given the alleged peso overvaluation, high‐net‐exporting firms outperformed the market beginning in late 1993. This pattern is, on the other hand, consistent with forward‐looking stock prices that assigned an increasing probability to a devaluation benefiting exporting firms. Copyright © 2002 John Wiley & Sons, Ltd.
Financial market integration in Europe: on the effects of EMU on stock markets
Authors: Fratzscher Marcel 
Published: August 2002

AbstractThis paper analyses the integration process of European equity markets since the 1980s. Its central focus is on the role that EMU, and specifically, changes in exchange rate volatility, has played in this process of financial integration. Building on an uncovered interest rate parity condition to measure financial integration, a trivariate GARCH model with time‐varying coefficients yields three key results: first, European equity markets have become highly integrated only since 1996. Second, the Euro area market has gained considerably in importance in world financial markets and has taken over from the USA as the dominant market in Europe. Third, the integration of European equity markets is in large part explained by the drive towards EMU, and in particular the elimination of exchange rate volatility and uncertainty in the process of monetary unification. Copyright © 2002 John Wiley & Sons, Ltd.
The determinants of birth intervals: a qualitative approach from Punjab, India
Authors: Huber Ulli S. 
Published: August 2002

AbstractThe determinants of birth intervals have been a focus of attention because of the strong relationship between birth intervals, mortality and fertility. This paper criticises the conventional hazard model approach to the determinants of birth intervals on the grounds of, first, the widespread assumption that birth intervals are planned and go according to plan, and secondly, a common failure to situate birth intervals within the social structures in which they take place. In‐depth interviews with four Punjabi couples about their birth interval related experiences are used to illustrate an alternative approach, which centres on an exploration of the roots of each action influencing birth intervals. This exploration takes into account that not all human actions are planned to maximise the actor's benefit, but that they can also be normative, habitual, or emotion‐driven; and it disentangles the two‐way relationship between birth interval related actions and social structures. Birth intervals are thought to be unlikely to develop according to a master plan because of their complexity, which stems from the considerable number of actions and actors involved in creating them. Copyright © 2002 John Wiley & Sons, Ltd.
Summarizing electronic discourse
Authors: Farrell Robert 
Published: August 2002

AbstractThe explosion of available information on the Internet has fueled the demand for automatic methods of text summarization. Existing approaches have primarily focused on abstracting documents such as news articles or technical papers. In this article, we examine how to create summaries of on‐line asynchronous communication, in particular, discussion groups. First, we provide background on the nature of discussions as informal communication, and then we give a short history of computer conferencing and discussion systems. We then explain our approach to the problem and a set of observations and experiments we have done, putting our work in the context of research on automatic text summarization. We then describe a hierarchical discourse summarization algorithm and its implementation in system called Interactive Discussion Summarizer (IDS). We close with discussion and conclusions. Copyright © 2002 John Wiley & Sons, Ltd.
Decadal variability of the Danube river flow in the lower basin and its relation with the North Atlantic Oscillation
Authors: Rîmbu Norel , Boroneanţ Constanţa , Buţă Carmen , Dima Mihai 
Published: August 2002

AbstractThe decadal variability (>5 years) of the Danube river flow in the lower basin and its connection with the North Atlantic Oscillation (NAO) is analysed for the period 1931–95. Associated linkages with precipitation (PP) in the European sector, global sea surface temperature (SST) and atmospheric circulation for the period 1931–81, and the 500 hPa geopotential heights (G500) over the Northern Hemisphere for the period 1948–95 are also investigated.The results show that there is an out‐of‐phase relationship between the time series of the Danube river flow anomalies and the NAO index. The time series of a PP index, defined as the average of normalized precipitation anomalies over a large area including the Danube basin, presents a time evolution similar to that of the river flow anomalies.The correlation maps between the river flow anomalies and global SST show coherent large‐scale patterns. High values of the Danube river flow are associated with a tripole‐like SST structure in the North Atlantic similar to that appearing during the negative phase of the NAO, and with negative SST anomalies in the central North Pacific and positive SST anomalies in the eastern and central tropical Pacific. Physically consistent sea level pressure and 500 hPa geopotential height are obtained. Copyright © 2002 Royal Meteorological Society.
Dependence between extreme sea surge, river flow and precipitation in eastern Britain
Authors: Svensson Cecilia , Jones David A. 
Published: August 2002

AbstractFlooding in estuaries may be caused by both high river flows and by high sea levels. In order to investigate whether these tend to occur simultaneously in eastern Britain, the dependence between high sea surge (observed sea level minus predicted astronomical tide), river flow and precipitation was studied using a measure of dependence specially developed for extremal dependence. Extreme events were interpreted using meteorological maps. This new analysis found that the strongest flow–surge dependence occurs between river flow on the north shore of the Firth of Forth and sea surge at Aberdeen, Wick and Lerwick. In contrast to most other catchments in eastern Britain, the area to the north of the Firth of Forth is not sheltered from south‐westerly winds by any major topographical barrier. Therefore, precipitation from this direction may be orographically enhanced as it encounters the hills on the northern side of the firth, and high river flows may ensue. Events resulting in both high river flow and surge in the northern part of the study area were found to be caused by cyclones travelling north‐eastward to the north of Scotland. High surge events, only, were associated with similar storm tracks, but without much precipitation from the fronts. High river flows, only, were associated with rain‐bearing east–west‐directed fronts over northern Britain, with slow‐moving depressions located over or to the west of the British Isles where they are unable to generate a strong surge in the North Sea. The dependence between river flow and surge was found to be stronger during winter than summer, and a lagged analysis revealed that the dependence is strongest when flow and surge occur on the same day, but was also strong for lags of plus and minus 1 day. For precipitation, the dependence with both flow and surge is strongest when precipitation precedes them by 1 day. Copyright © 2002 Royal Meteorological Society.
The contribution of a discursive view to understanding and managing organizational change
Authors: Heracleous Loizos 
Published: August 2002

Abstract

Effective change management is not just about the ‘hard’ structural aspects of organizations; it requires an in‐depth appreciation of the cultural, human aspects of organizations, and taking actions based on this understanding.

Organizational discourse can provide access to this conceptual world of organizations and can also be used as an avenue for influencing it.

Recent empirical research is used to illustrate the above points.

Use of metaphor by change agents is then discussed as a prime example of how discourse can help to achieve effective organizational change.

Copyright © 2002 John Wiley & Sons, Ltd.
Enterprise resource planning systems and organizational change: transforming work organization?
Authors: Hall Richard 
Published: August 2002

Abstract

Enterprise Resource Planning Systems (ERPs) are computer‐based technologies that integrate data across an organization and impose standardized procedures on the input, use and dissemination of that data.

This paper argues that ERPs are an increasingly important source of organizational change with major implications for the organization and management of work.

ERPs are potentially associated with the following changes in the organization of work: downsizing and delayering of organizations; decentralizing responsibilities for various tasks while further concentrating control; increasing the range and depth of skills for some jobs while deskilling and routinizing the tasks inherent in other jobs; and the intensification of work in many jobs within the organization.

ERP implementations, therefore, need to be managed carefully.

Copyright © 2002 John Wiley & Sons, Ltd.
Changing the language of change: how new contexts and concepts are challenging the ways we think and talk about organizational change
Authors: Marshak Robert J. 
Published: August 2002

Abstract

This article proposes that our current terminology and conceptual language for organizational change make it difficult to address the range of changes confronting contemporary organizations.

Difficulties discussed include ambiguous and imprecise ways of talking about organizational change, changing organizational contexts that require new ways to think and talk about change, and dealing with implicit assumptions about change that may not be relevant in a world of continual change.

A matrix of change scenarios is presented and the term ‘morphing’ is introduced to describe continuous whole‐system change in hyperactive business environments.

Concepts, assumptions and metaphors associated with ‘altered consciousness’ and self‐organizing ‘complex adaptive systems’ are also discussed as alternative ways to think and talk about transformational change.

Implications discussed include the need to be specific and self‐reflective when thinking and talking about organizational change, and to rethink a possible over‐reliance on mechanistic, engineering or planned movement concepts, metaphors and word imagery.

Copyright © 2002 John Wiley & Sons, Ltd.
Building visitor attractions in peripheral areas—Can uniqueness overcome isolation to produce viability?
Authors: Prideaux Bruce 
Published: August 2002

AbstractAttractions are a major component of the tourism industry and often exert considerable influence over individual travel priorities. In peripheral areas the uniqueness of attractions becomes an issue of greater significance than in the core, as visitors must allocate additional time and finances to travel greater distances to participate in the experiences on offer vis à vis competing attractions located nearer to the core. This paper considers a range of issues that affect the construction and operation of visitor attractions in the periphery. Issues that are of particular importance are location and access factors, the community, supporting tourism infrastructure and viability. As the isolation factor increases, the scale of the attraction must increase as must its uniqueness factor if it is to achieve and maintain viability. The significance of these factors is illustrated by considering the development of Burra as a heritage tourism attraction located in the near periphery of Adelaide, South Australia. Copyright © 2002 John Wiley & Sons, Ltd.
Rediscovering the imagination: investigating active and passive visitor experience in the 21st century
Authors: Voase Richard 
Published: August 2002

AbstractThe experiential nature of visits to cultural and heritage attractions is theorised. Contemporary discourses posit the emergence of a ‘thoughtful’ consumer and a paradoxical ‘dumbing‐down’ of culture. The discursive links between ‘active’ consumption and thought/learning, and of ‘passive’ consumption with dumbness/fun, are argued to be fallacious; the meanings of ‘active’ and ‘passive’ are in need of re‐evaluation. ‘Dumbing‐down’ is suggested to be a discursive term for the lowering of the threshold of engagement by cultural producers, implying neither ‘dumb’ content nor ‘dumb’ consumers. Postmodernisation has eroded the protocols governing access to culture, producing two simultaneous effects: the augmentation of opportunities for ‘thoughtful’ engagement, and increasing commodification giving rise to a ‘smart’ consumer with an initial focus on transaction. A popular threshold of engagement is a recommended and rational strategy for attracting and engaging both ‘thoughtful’ and ‘smart’ consumers. Copyright © 2002 John Wiley & Sons, Ltd.