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Search Results: 1 - 10 of 448 matches for " Imre Kovesdi "
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Adenoviral Producer Cells
Imre Kovesdi,Susan J. Hedley
Viruses , 2010, DOI: 10.3390/v2081681
Abstract: Adenovirus (Ad) vectors, in particular those of the serotype 5, are highly attractive for a wide range of gene therapy, vaccine and virotherapy applications (as discussed in further detail in this issue). Wild type Ad5 virus can replicate in numerous tissue types but to use Ad vectors for therapeutic purposes the viral genome requires modification. In particular, if the viral genome is modified in such a way that the viral life cycle is interfered with, a specific producer cell line is required to provide trans-complementation to overcome the modification and allow viral production. This can occur in two ways; use of a producer cell line that contains specific adenoviral sequences incorporated into the cell genome to trans-complement, or use of a producer cell line that naturally complements for the modified Ad vector genome. This review concentrates on producer cell lines that complement non-replicating adenoviral vectors, starting with the historical HEK293 cell line developed in 1977 for first generation Ad vectors. In addition the problem of replication-competent adenovirus (RCA) contamination in viral preparations from HEK293 cells is addressed leading to the development of alternate cell lines. Furthermore novel cell lines for more complex Ad vectors and alternate serotype Ad vectors are discussed.
Genetic Incorporation of Human Metallothionein into the Adenovirus Protein IX for Non-Invasive SPECT Imaging
J. Michael Mathis,Shilpa Bhatia,Alok Khandelwal,Imre Kovesdi,Stephen J. Lokitz,Yoshi Odaka,Amol M. Takalkar,Tracee Terry,David T. Curiel
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016792
Abstract: As the limits of existing treatments for cancer are recognized, clearly novel therapies must be considered for successful treatment; cancer therapy using adenovirus vectors is a promising strategy. However tracking the biodistribution of adenovirus vectors in vivo is limited to invasive procedures such as biopsies, which are error prone, non-quantitative, and do not give a full representation of the pharmacokinetics involved. Current non-invasive imaging strategies using reporter gene expression have been applied to analyze adenoviral vectors. The major drawback to approaches that tag viruses with reporter genes is that these systems require initial viral infection and subsequent cellular expression of a reporter gene to allow non-invasive imaging. As an alternative to conventional vector detection techniques, we developed a specific genetic labeling system whereby an adenoviral vector incorporates a fusion between capsid protein IX and human metallothionein. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional metallothionein (MT) as a component of their capsid surface. We demonstrate the feasibility of 99mTc binding in vitro to the pIX-MT fusion on the capsid of adenovirus virions using a simple transchelation reaction. SPECT imaging of a mouse after administration of a 99mTc-radiolabeled virus showed clear localization of radioactivity to the liver. This result strongly supports imaging using pIX-MT, visualizing the normal biodistribution of Ad primarily to the liver upon injection into mice. The ability we have developed to view real-time biodistribution in their physiological milieu represents a significant tool to study adenovirus biology in vivo.
Dendritic Cell Based PSMA Immunotherapy for Prostate Cancer Using a CD40-Targeted Adenovirus Vector
Briana Jill Williams, Shilpa Bhatia, Lisa K. Adams, Susan Boling, Jennifer L. Carroll, Xiao-Lin Li, Donna L. Rogers, Nikolay Korokhov, Imre Kovesdi, Alexander V. Pereboev, David T. Curiel, J. Michael Mathis
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046981
Abstract: Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs) with prostate specific membrane antigen (PSMA) have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells). To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ). Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy.
The evaluation of possibilities of sustainable tourism and recreation in the Mrtva Tisa area near urug7
Na? Imre
Glasnik Srpskog Geografskog Dru?tva , 2008, DOI: 10.2298/gsgd0804081n
Abstract: The preserved parts of the nature or areas that are inteded to be protected and well-planned in terms of harmonizing the nature and tourist activities and recreation could become potential eco-tourist attractions. The Tisa meander near urug, the Dead Tisa, together with the fish pond 'Be ej', presents a natural, though somewhat manaffected, environment. The paper offers an analysis of the indicators of sustainability which has shown that with proper valorisation and prevention of potential forms of degradation of water and landscape this oasis could provide people with recreation and tourist activities on the water (e.g. rowing), bird watching, as well as numerous gastronomical treats typical of this area.
The Dynamics of Trade in Central and Eastern European Countries
Imre Ferto
Managing Global Transitions , 2007,
Abstract: The Dynamics of Trade in Central and Eastern European CountriesAbstract: We describe the evolving pattern of Central European countries’ trade using recently developed empirical procedures based around the classic Balassa index. Despite significant changes in Central European economies during transition to a market economy, the distribution of the indices did not change radically over the 1990s. Our results suggest that the trade pattern converged in Czech Republic, Hungary, Poland and Slovenia, while it polarised in Estonia Latvia, Lithuania and Slovakia over the period. For particular product groups, the indices display greater variation. They are stable for product groups with comparative disadvantage, but product groups with weak to strong comparative advantage show significant variation. At the product level different development can be observed in the changes of trade specialization. The comparative advantages are still based largely on primary and natural resource intensive product groups in the Baltic countries, while CEE5 countries show a successful upgrading process in technological and human capital intensive products.
Marxist Literary Criticism, Then and Now
Imre Szeman
Mediations , 2009,
Abstract: Is there such a thing as a Marxist literary criticism? Imre Szeman argues that, despite the fact that Marxism has long privileged literature as an object of analysis and critique, there is no unitary methodology or set of considerations that distinguish a “Marxist” approach to literature from others. Here, Szeman provides a historicization and structural analysis of what he identifies as the three primary modes of Marxist literary criticism. At the same time, this essay also points to a fourth, as yet unnamed, possibility for Marxist literary critique that seeks to sublate the assumed “impasse” created by the limiting choice between “ideological” and “anti-ideological” culture, an impasse that, according to Szeman, bears witness to a profound historical shift.
The Left and Marxism in Eastern Europe: An Interview with Gáspár Miklós Tamás
Imre Szeman
Mediations , 2009,
Abstract: Imre Szeman interviews the political philosopher, journalist, and writer, Gáspár Miklós Tamás. Describing his own political move to the Left in relation to local post-Soviet politics in Hungary and global structures of contemporary capitalism, Tamás discusses the dangers of attaching hopes for greater rights and liberties to both free market structures and nostalgic forms of leftism. What answers can Marxism offer in response to the sociopolitical and philosophical pressures of the current conjuncture in which the free market agenda has become structurally and politically untenable? How must we re-think Marxism itself in a context in which solutions to the political impasses of the present can no longer be found in a return to Party politics of the past? How might Marxist political philosophy deal with pressing contradictions such as rising forms of ultranationalism? Addressing these and other questions, Tamás demonstrates how recent political developments in Hungary, and throughout Eastern Europe more generally, provide lessons for the Left throughout the globe.
Literature on the periphery of capitalism: Brazilian theory, Canadian culture Literature on the periphery of capitalism: Brazilian theory, Canadian culture
Imre Szeman
Ilha do Desterro , 2008,
Abstract: Any attempt to theorize the surprising similarities between Brazilian and Canadian cultural and literary history has to begin by openly acknowledging the vast and irrecoverable differences between them—differences of history, culture, economics, geography, and so on. Indeed, there seem to be so many differences that one might be inclined to see the points of connection as mere coincidence: the cultural circumstances and expressions of both countries might appear similar in outward appearance (or at least, might seem so in many cases), but their inner logic emerges out of entirely different material circumstances that cannot be passed over in silence. Any attempt to theorize the surprising similarities between Brazilian and Canadian cultural and literary history has to begin by openly acknowledging the vast and irrecoverable differences between them—differences of history, culture, economics, geography, and so on. Indeed, there seem to be so many differences that one might be inclined to see the points of connection as mere coincidence: the cultural circumstances and expressions of both countries might appear similar in outward appearance (or at least, might seem so in many cases), but their inner logic emerges out of entirely different material circumstances that cannot be passed over in silence.
Marxism after Marxism
Imre Szeman
Mediations , 2008,
Abstract: Imre Szeman reviews G ran Therborn’s From Marxism to Post-Marxism? The title is posed as a question, but the book leaves little doubt about the necessity of such a move. But would “post-Marxism” involve the abandonment of the insights of Marx and of the dialectic, or would it be better thought of as the refocusing of these very traditions on our own “bad new days”?
Literature on the periphery of capitalism: Brazilian theory, Canadian culture Literature on the periphery of capitalism: Brazilian theory, Canadian culture
Imre Szeman
Ilha do Desterro , 2008,
Abstract: In order to get past the blind spots that have developed in contemporary postcolonial theory, it is essential to seek out complementarities and solidarities in different national situations and in different modernities. This essay undertakes this task by exploring the homologous situations faced in Brazil and Canada in their respective attempts to create genuine national cultures. As in many postcolonial situations, the problem of creating an authentic culture is directly related to the sense that postcolonial culture is necessarily imitative and belated. In Misplaced Ideas, Roberto Schwarz exposes the hidden class character of the problem of cultural authenticity in Brazil, and in so doing, shows that the trauma of national-cultural identity merely reflects the contradictory structural position of Brazil’s postcolonial elite. Using Schwarz’s insights to explore the Canadian situation, the author shows that the same forces are at work in Canada. Though the crisis of a lack of an authentic Canadian culture has recently been surmounted as a result of the apparent international success of Canadian culture (especially literary fiction), that author cautions that this “success” story hides the class basis of Canadian culture in both its belated and isochronic phases (the latter being the moment when cultural belatedness is overcome). Making use of Brazilian theory to examine problems in Canadian culture allows us to see that Canadian modernity, long thought to be simply a derivative of the UK and USA, has similarities with Brazilian modernity that are essential to understanding the space and place Canada occupies in globalization. In order to get past the blind spots that have developed in contemporary postcolonial theory, it is essential to seek out complementarities and solidarities in different national situations and in different modernities. This essay undertakes this task by exploring the homologous situations faced in Brazil and Canada in their respective attempts to create genuine national cultures. As in many postcolonial situations, the problem of creating an authentic culture is directly related to the sense that postcolonial culture is necessarily imitative and belated. In Misplaced Ideas, Roberto Schwarz exposes the hidden class character of the problem of cultural authenticity in Brazil, and in so doing, shows that the trauma of national-cultural identity merely reflects the contradictory structural position of Brazil’s postcolonial elite. Using Schwarz’s insights to explore the Canadian situation, the author shows that the same forces are at w
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