bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Tumor Angiogenesis by the Matrix Metalloproteinase–Activated Anthrax Lethal Toxin in an Orthotopic Model of Anaplastic Thyroid Carcinoma
Authors: Alfano Randall W. , Leppla Stephen H. , Liu Shihui , Bugge Thomas H. , Ortiz Janelle M. , Lairmore Terry C. , Duesbery Nicholas S. , Mitchell Ian C. , Nwariaku Fiemu , Frankel Arthur E. 
Published: January 2010

Abstract
Patients with anaplastic thyroid carcinoma (ATC) typically succumb to their disease months after diagnosis despite aggressive therapy. A large percentage of ATCs have been shown to harbor the V600E B-Raf point mutation, leading to the constitutive activation of the mitogen-activated protein kinase pathway. ATC invasion, metastasis, and angiogenesis are in part dependent on the gelatinase class of matrix metalloproteinases (MMP). The explicit targeting of these two tumor markers may provide a novel therapeutic strategy for the treatment of ATC. The MMP-activated anthrax lethal toxin (LeTx), a novel recombinant protein toxin combination, shows potent mitogen-activated protein kinase pathway inhibition in gelatinase-expressing V600E B-Raf tumor cells in vitro. However, preliminary in vivo studies showed that the MMP-activated LeTx also exhibited dramatic antitumor activity against xenografts that did not show significant antiproliferative responses to the LeTx in vitro. Here, we show that the MMP-activated LeTx inhibits orthotopic ATC xenograft progression in both toxin-sensitive and toxin-resistant ATC cells via reduced endothelial cell recruitment and subsequent tumor vascularization. This in turn translates to an improved long-term survival that is comparable with that produced by the multikinase inhibitor sorafenib. Our results also indicate that therapy with the MMP-activated LeTx is extremely effective against advanced tumors with well-established vascular networks. Taken together, these results suggest that the MMP-activated LeTx-mediated endothelial cell targeting is the primary in vivo antitumor mechanism of this novel toxin. Therefore, the MMP-activated LeTx could be used not only in the clinical management of V600E B-Raf ATC but potentially in any solid tumor. Mol Cancer Ther; 9(1); 190–201
Astrocyte Elevated Gene-1: A Novel Target for Human Glioma Therapy
Authors: Emdad Luni , Sarkar Devanand , Lee Seok-Geun , Su Zhao Zhong , Yoo Byoung Kwon , Dash Rupesh , Yacoub Adly , Fuller Christine E. , Shah Khalid , Dent Paul , Bruce Jeffrey N. , Fisher Paul B. 
Published: January 2010

Abstract
Malignant gliomas including glioblastoma multiforme (GBM) and anaplastic astrocytomas are the most common primary brain tumors. Despite multimodal treatment including surgery, chemotherapy, and radiation, median survival for patients with GBMs is only 12 to 15 months. Identifying molecules critical for glioma progression is crucial for devising effective targeted therapy. In the present study, we investigated the potential contribution of astrocyte elevated gene-1 (AEG-1) in gliomagenesis and explored the possibility of AEG-1 as a therapeutic target for malignant glioma. We analyzed the expression levels of AEG-1 in 9 normal brain tissues and 98 brain tumor patient samples by Western blot analysis and immunohistochemistry. AEG-1 expression was significantly elevated in &gt;90% of diverse human brain tumor samples including GBMs and astrocytic tumors, and also in human glioma cell lines compared with normal brain tissues and normal astrocytes. Knockdown of AEG-1 by small interfering RNA inhibited cell viability, cloning efficiency, and invasive ability of U87 human glioma cells and 9L rat gliosarcoma cells. We also found that matrix metalloproteases (MMP-2 and MMP-9) are involved in AEG-1–mediated invasion of glioma cells. In an orthotopic nude mouse brain tumor model using primary human GBM12 tumor cells, AEG-1 small interfering RNA significantly suppressed glioma cell growth in vivo. Taken together, these provocative results indicate that AEG-1 may play a crucial role in the pathogenesis of glioma and that AEG-1 could represent a viable potential target for malignant glioma therapy. Mol Cancer Ther; 9(1); 79–88
DOC45, a Novel DNA Damage–Regulated Nucleocytoplasmic ATPase That Is Overexpressed in Multiple Human Malignancies
Authors: Sun Hong , Luo Xiuquan , Montalbano JoAnne , Jin Weixin , Shi Jingxue , Sheikh M. Saeed , Huang Ying 
Published: January 2010

Abstract
In this article, we report the characterization of a novel DNA damage–regulated gene, named DNA damage–regulated overexpressed in cancer 45 (DOC45). Our results indicate that DNA damage–inducing agents, including doxorubicin (adriamycin), etoposide, and ionizing and UV radiation, strongly downregulate DOC45 expression, whereas endoplasmic reticulum stress–inducing agents do not. Our results also indicate that DOC45 is overexpressed in several human malignancies, including cancers of the colon, rectum, ovary, lung, stomach, and uterus. DOC45 harbors conserved nucleotide triphosphate–binding motifs and is capable of ATP hydrolysis, findings that highlight its function as a novel ATPase. Although predominantly cytoplasmic, DOC45 exhibits a characteristic nucleocytoplasmic distribution and, on inhibition of nuclear export, predominantly accumulates in the nucleoli. These results suggest that DOC45 may shuttle between nucleus and cytoplasm to carry out its function. Our results also indicate that DOC45 expression is enhanced during oncogenic Ras-mediated transformation and that its expression is linked to phosphoinositide 3-kinase signaling pathway. Furthermore, short hairpin RNA–mediated knockdown of DOC45 in human colon cancer cells inhibits their proliferation and enhances cellular sensitivity to doxorubicin-induced cell death, suggesting that DOC45 plays an important role in cell proliferation and survival. Collectively, our results indicate that DOC45 is a novel ATPase that is linked to cellular stress response and tumorigenesis, and may also serve as a valuable tumor marker. Mol Cancer Res; 8(1); 57–66
A critique of John Holloway's Change The World Without Taking Power
Authors: McNaughton Colm 
Published: January 2010

John Holloway's Change the World Without Taking Power is an attempt to translate the Zapatista experience into Marxist categories—an undertaking fraught with many difficulties. This review interrogates the four key issues addressed by Holloway: the state, the nature of power, commodity fetishism and the meaning and relevance of revolution. Born in Dublin and now living and working in Mexico City, John Holloway is one of a small group of intellectual—activists whose work emerges from and contributes to an autonomist reading of Marxism. Holloway's work within this milieu has largely been concerned with revitalising a Marxist comprehension of the state—that is, until January 1994, when the masked Zapatistas of Chiapas, Mexico, burst onto the global scene. After this, he became a commentator on the role and impact of the Zapatistas on the resistance to exclusive forms of globalisation. Indeed, his most recent work, Change The World Without Taking Power, is an attempt to translate the Zapatista experience into Marxist categories. Holloway is often criticised for focusing so heavily on the Zapatistas, but in his defence, they do seem to constitute a significant shift within the emancipatory imagination and, as such, their contribution warrants further scrutiny and reflection. In examining Holloway's contribution, I will address four key issues: the state, the nature of power, commodity fetishism and the meaning and relevance of revolution.
Capital, Fractions of Capital and the State: ‘Neo-Marxist’ Analysis of the South African State
Authors: Clarke Simon 
Published: January 2010

This paper examines what has been called the ‘neo-Marxist’ or, more unkindly, the ‘vulgar Poulantzian’, approach to the state. The typical feature of this approach is a formulation of the relation between capital and the state in terms of the struggle between ‘fractions of capital’ to establish the position of ‘hegemonic fraction’ within the ‘power bloc’. The state then represents the unity of capital in relation to the proletariat and the dominance of the hegemonic fraction in relation to the other fractions of capital. Research which is guided by this view of the state tends, therefore, to examine state activity in relation to the policies proposed by various political parties and pressure groups which are said to be the ‘representatives’ of particular fractions of capital. This examination is usually complemented by an account of the particular ‘interests’ of the fractions in play. The policy actually adopted by the state is then explained by reference to the supposed ‘hegemony’ of the fraction in whose interest the policy is said to be. This paper aims to develop a critique of this ‘fractionalist’ approach to the state through a critique of its conceptions of class, of class fractions and of the state. It is argued that the ‘fractionalist’ approach is ‘overpoliticised’ in seeing the state as condensation of the social, at the same time as being ‘economistic’ in directly identifying the state with capital. The critique is developed with reference to the best ‘neo-Marxist’ work on the state that has blossomed in recent years, that on the South African state. It is hoped, however, that the critique will have a wider relevance.(1)
The New Information Technologies: Is there an ‘alternative strategy’?
Authors: Negrine Ralph 
Published: January 2010

The Conservative government has adopted a market-led and entertainment-led approach to the development of IT generally. It has privatised BT, established a competitor and has pursued a distinctive market philosophy towards the development of the new media. One of these media, cable systems, has attracted much interest because it contains within it the possibility of the creation of a so-called ‘national grid’, marrying communications and culture, business and entertainment in an intricate and complex way. But because all these developments have taken place in the private sector, the Left has been quick to criticise the government's approach and have pointed out the many consequences: in terms of employment, impact on culture, diminishing the public domain, reducing acountability and so on. However, this article suggests that these critiques are by no means as complete as first appears since they themselves lack any coherent ‘alternative strategy’ that is ‘realistic’, plausible or meaningful. This, the article goes on to argue, will present a future socialist government with a serious problem. What will its own approach be and how much can it learn from these critiques?
Company Takeovers and the Australian Equity Market
Authors: Dodd Peter 
Published: January 2010

Stock market prices are investigated around the dates of takeover offers. The 242 companies in the sample of takeover offers are classified firstly as offerors and offerees, and secondly as to whether or not the takeover was achieved. The study employs the two parameter asset pricing model and allows for shifts in risk. Any gains arising from takeovers are won by the acquired firm at the expense of the acquiring firm. The stock market reaction to takeover offers is generally consistent with the Efficient Markets Hypothesis with one notable exception. Alternative interpretations of this anomaly are considered.
Formalisation and Organisational Effectiveness in Hospitals
Authors: Hetherington Robert W. 
Published: January 2010

This study tests four propositions concerning the relationship between formalisation and organisational performance. The propositions are based on Hage's axiomatic theory, wherein formalisation is inversely associated with worker satisfaction and organisational adaptation, and positively associated with efficiency and production. Data were collected by questionnaire from 348 respondents from 92 units of eight hospitals, measuring formalisation, complexity, coördination, climate for change, quality of care and worker satisfaction. Propositions were tested on data aggregated to the unit level. Findings strongly indicate the need for careful respecification of the Hage model in terms of subconcepts of structural and performance measures. Confirmations are reported for four of the five propositions examined, and specified in terms of the subconcepts involved. Unexpected reversals are also found, however, suggesting that formalisation under some circumstances is beneficial for adaptation and morale, but conducive to inefficiencies under other circumstances.
Social dialogue in Hungary and its influence on EU accession
Authors: Boda Dorottya , Neumann László 
Published: January 2010

The paper reviews the positions of the Hungarian social partners on the labour issues relating to EU accession. In addition to the topics dealt with in the 'Social Policy and Employment' chapter in the accession negotiations, the paper also discusses unions' and employers'views on labour migration, as well as how the adaptation of EU regulations in various sectors is likely to affect employment prospects. The paper argues that, on the one hand, social dialogue on EU accession can become more meaningful if employers and unions develop a co-ordinated strategy. On the other hand, appropriate back-up by experts is also required, because social partners ought to influence the complex system of negotiations being conducted, by experts of both the EU Commission and the Hungarian government, behind the scenes of high-level political negotiations. The authors also analyse the operation of social dialogue fora dedicated to EU accession issues. Hungary was the first East European candidate country to establish a joint committee with the Economic and Social Council (ESC), and within the country labour-related issues of accession have been delegated to the newly founded European Integration Council. In these fora the behaviour of trade unions is largely a consequence of the frustration over the fact that the current right-wing coalition government does not wish to go any further than formally observe the unions' consulting rights on major issues. At the same time organisational weakness and internal divisions still exist on the trade union side.
The European social dialogue in the 1990s: institutional innovations and new paradigms
Authors: Goetschy Janine 
Published: January 2010

This article describes the major changes undergone by social dialogue in the 1990s. Two distinct periods are covered. The first, following in the wake of the Maastricht Social Agreement annexed to the Maastricht Treaty (1992), did not produce the expected new impetus and results. The novel institutional device of ‘collective bargaining in the shadow of the law’, though an advantage in some respects, was also a source of weakness for the social dialogue. The most striking feature of the second period, covering the later part of the 1990s, is the impressive diversification of institutional forms of social dialogue, a development that ought to multiply its chances of success, even if the new forms tend to be rather less ambitious. Four main new developments are described: • Diversification of the forums for discussion; • Increase in the number and type of topics covered; • Use of OMC tools in the context of the social dialogue; • Search for new ways of establishing connections between different forms and levels of social dialogue. Whether this proliferation of ‘entry points’, arenas and discussion topics will serve to strengthen the actors and improve the results of the European social dialogue remains an open question.
Flexible employment practices and working time patterns: the potential for and limits of ecological impact
Authors: Garcia Ernest , La Roca Francese , Hildebrandt Eckart , Kühleis Christoph 
Published: January 2010

The discussion about the relationship between employment policy and environment policy has been predominantly about the extent to which environmental issues can be brought into industrial relations policy. Environmental problems are perceived as additional factors of influence, which have an impact on job security and working conditions, and which have so far not been adequately taken into account in standards and rules. From the current viewpoint of union representatives, conservation of the environment is being brought into discussion in the form of an "employment policy extended to include the environment". Progress made in this field in recent years is increasingly undermined by radical changes in the labour market. The current phase is being determined by high and rising rates of unemployment, growing numbers of casual and temporary jobs and stagnating pay levels. The strategies of management focus on increasing the flexibility of the workforce, in the form of flexible employment conditions, and more flexible use of laboúr. These changes in the crucial framework conditions for paid employment are bound to have a significant influence on the attitudes and behaviour of employees with regard to conservation of the environment. In the following article, we shall be looking at two aspects: Garcia and La Roca (1) deal with the increase in casual and temporary jobs, and Hildebrandt and Kühleis (2) deal with new patterns of working hours. This different emphasis relates to different aspects of "increased flexibility" . On the one hand, flexibility can be seen as a sign of increasing job insecurity, with the consequence that the scope for sustainable attitudes and behaviour is less than before. If, on the other hand, increased flexibility is seen as an opportunity for negotiating more leisure time and power for workers to allocate their time as they want - as in the German case - the room for manoeuvre is greater and it opens up possibilities for a sustainable way of life. The remarks in the first section deal with a representative survey of current attitudes in Spain, and lead to predominantly ' negative results. The second section deals with new models of working hours, and in this context, it examines the conditions and opportunities for positive changes in the lifestyle of employees. The approaches in the first and second section are not directly comparable, but they do provide insight into possible consequences of new management strategies for ecological commitment among employees in their working and leisure time.
Pension systems in the European Union and aspects of socio-economic change
Authors: Döring Diether 
Published: January 2010

The European Union has different traditions concerning the main concept of social security in general, and of retirement and pension benefits. Different political decisions dictate the range of personal coverage, how benefits are calculated and how the systems are financed. Within this paper, the author will try to distinguish the different types of core systems and will present a rough grouping of twelve national systems. The systems that provide social protection in old age have entered a period of massive socioeconomic change. This includes changes in the structure of employment, and of family life. At the same time, most European countries have become countries of immigration. The author does not intend to make a detailed analysis of these changes themselves, but rather to select elements of them, and examine different types of old age security systems within these changes.
Classical and/or alternative NF-κB pathway activation in multiple myeloma
Authors: Demchenko Yulia N. , Glebov Oleg K. , Zingone Adriana , Keats Jonathan J. , Bergsagel P. Leif , Kuehl W. Michael 
Published: January 2010

Abstract
Mutations involving the nuclear factor-κB (NF-κB) pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCLs). These mutations, which are apparent progression events, enable MM tumors to become less dependent on bone marrow signals that activate NF-κB. Studies on a panel of 51 MMCLs provide some clarification of the mechanisms through which these mutations act and the significance of classical versus alternative activation of NF-κB. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, and TACI) selectively activate the classical pathway. However, most mutations affecting NF-κB–inducing kinase (NIK) levels (NIK, TRAF2, TRAF3, cIAP1&2, and CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteasomal degradation of NIK in MM. Third, using transfection to selectively activate the classical or alternative NF-κB pathways, we show virtually identical changes in gene expression in one MMCL, whereas the changes are similar albeit nonidentical in a second MMCL. Our results suggest that MM tumors can achieve increased autonomy from the bone marrow microenvironment by mutations that activate either NF-κB pathway.
Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia transformations
Authors: Comar Jurandir F , Suzuki-Kemmelmeier Fumie , Constantin Jorgete , Bracht Adelar 
Published: January 2010

AbstractBackgroundGlutaminase predominates in periportal hepatocytes and it has been proposed that it determines the glutamine-derived nitrogen flow through the urea cycle. Glutamine-derived urea production should, thus, be considerably faster in periportal hepatocytes. This postulate, based on indirect observations, has not yet been unequivocally demonstrated, making a direct investigation of ureogenesis from glutamine highly desirable.MethodsZonation of glutamine metabolism was investigated in the bivascularly perfused rat liver with [U-14C]glutamine infusion (0.6 mM) into the portal vein (antegrade perfusion) or into the hepatic vein (retrograde perfusion).ResultsAmmonia infusion into the hepatic artery in retrograde and antegrade perfusion allowed to promote glutamine metabolism in the periportal region and in the whole liver parenchyma, respectively. The results revealed that the space-normalized glutamine uptake, indicated by14CO2production, gluconeogenesis, lactate production and the associated oxygen uptake, predominates in the periportal region. Periportal predominance was especially pronounced for gluconeogenesis. Ureogenesis, however, tended to be uniformly distributed over the whole liver parenchyma at low ammonia concentrations (up to 1.0 mM); periportal predominance was found only at ammonia concentrations above 1 mM. The proportions between the carbon and nitrogen fluxes in periportal cells are not the same along the liver acinus.ConclusionsIn conclusion, the results of the present work indicate that the glutaminase activity in periportal hepatocytes is not the rate-controlling step of the glutamine-derived nitrogen flow through the urea cycle. The findings corroborate recent work indicating that ureogenesis is also an important ammonia-detoxifying mechanism in cells situated downstream to the periportal region.