3 resultados para Mitotic Catastrophe

em WestminsterResearch - UK


Relevância:

20.00% 20.00%

Publicador:

Resumo:

The institutionalization of Utopia Studies in the last decade is premised upon a specifically aesthetic reception of Ernst Bloch’s theory of the “utopian impulse” during the 1980s and 1990s. A postmodern uneasiness to both left and right formulations of the "End of History" during this period imposes a resistance to concepts of historical and political closure or totality, resulting in a "Utopianism without Utopia". For all the attractiveness of this pan-utopianism, its failure to consider the relation between historical representation and fulfillment renders it consummate with liberalism as a merely inverted conservatism. In contrast to this specific recuperation of a Bloch, the continuing importance of Walter Benjamin’s theory of the dialectical image and the speculative concept of historical experience which underlies it becomes apparent. The intrusion of the historical Absolute is coded throughout Benjamin’s thought as the eruptive and mortuary figure of catastrophe, which stands as the dialectical counterpart to the utopian wish images of the collective dream. Indeed, the motto under which the Arcades Project was to be constructed derives from Adorno: “Each epoch dreams of itself as annihilated by catastrophe”.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The slogan ‘capitalism is crisis’ is one that has recently circulated swiftly around the global Occupy movement. From Schumpeter to Marx himself, the notion that the economic cycles instituted by capitalism require periodic crises as a condition of renewed capital accumulation is a commonplace. However, in a number of recent texts, this conception of crisis as constituting the very form of urban capitalist development itself has taken on a more explicitly apocalyptic tone, exemplified by the Invisible Committee's influential 2007 book The Coming Insurrection, and its account of what it calls simply ‘the metropolis’. ‘It is useless to wait’, write the text's anonymous authors, ‘for a breakthrough, for the revolution, the nuclear apocalypse or a social movement.… The catastrophe is not coming, it is here.’ In considering such an apocalyptic tone, this paper thus situates and interrogates the text in terms both of its vision of the metropolis as a terrain of total urbanization and its effective spatialization of the present as itself a kind of ‘unnoticed’ apocalypse: the catastrophe which is already here. It does so by approaching this not only apropos its place within contemporary debates surrounding leftist politics and crisis theory but also via its imaginative intersection with certain post-1960s science fiction apocalyptic motifs. What, the paper asks, does it mean to think apocalypse as the ongoing condition of the urban present itself, as well as the opening up of political and cultural opportunity for some speculative exit from its supposedly endless terrain?

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Previous studies have associated the overexpression of histone deacetylase 2 (HDAC2) and the presence of TP53 mutations with the progression to advanced stage drug resistant colorectal cancer (CRC). However, the mechanistic link between HDAC2 expression and the TP53 mutational status has remained unexplored. Here, we investigated the function of HDAC2 in drug resistance by assessing the synergistic effects of DNA-targeted chemotherapeutic agents and HDAC inhibitors (HDACis) on two TP53-mutated colorectal adenocarcinoma CRC cell lines (SW480 and HT-29) and on the TP53-wild type carcinoma cell line (HCT116 p53+/+) and its TP53 deficient sub-line (HCT116 p53-/-). We showed that in the untreated SW480 and HT-29 cells the steady-state level of HDAC2 was low compared to a TP53-wild type carcinoma cell line (HCT116 p53+/+). Increased expression of HDAC2 correlated with drug resistance, and depletion by shRNA sensitised the multi-drug resistance cell line HT-29 to CRC chemotherapeutic drugs such as 5-fluorouracil (5-FU) and oxaliplatin (Oxa). Combined treatment with the HDACi suberoylanilide hydroxamic acid plus 5-FU or Oxa reduced the level of HDAC2 expression, modified chromatin structure and induced mitotic cell death in HT-29 cells. Non-invasive bioluminescence imaging revealed significant reductions in xenograft tumour growth with HDAC2 expression level reduced to <50% in treated animals. Elevated levels of histone acetylation on residues H3K9, H4K12 and H4K16 were also found to be associated with resistance to VPA/Dox or SAHA/Dox treatment. Our results suggest that HDAC2 expression rather than the p53 mutation status influences the outcome of combined treatment with a HDACi and DNA-damaging agents in CRC.