214 resultados para Tumor antigen presentation
Resumo:
the (dis)orientation of thought in its encounter with art can be understood as the direct result of an encounter with indeterminacy as a lack in meaning. As an artist I am aware of how this indeterminacy impacts on the perceived value and authority of the artistic voice and in particular its value as a research voice. This paper explores this indeterminacy of meaning, as a profound and disturbing unknowing characteristic of the sublime and argues its value to advanced thought and for any methodological understanding of practice-led research. Lyotard described the sublime as an ‘understanding’ through which art and its associated practices may be able to resist an all too easy assimilation by the public as just a consumer commodity. His thought represents an attempt to both politically and philosophically understand art’s, and particularly abstract painting’s, affect as a state of profound and positive unknowing. To talk of the sublime in art is to speak of the suspension of any comfortable certainty in being and instead to engage with the real as a limit to meaning and knowing. It is to talk of the presentation of the unpresentable as a momentary but significant dissolution of representation. This understanding of the sublime is then further explored through the cultural phenomena of the monochrome painting and applied to the work of the two contemporary artists, Franz Erhard Walter and Günter Umberg. Initially the monochrome was understood as an attempt to go beyond traditional representation and present the unpresentable. In the one hundred years or so since that initial move this understanding has broadened. The monochrome now presents itself as a genre or even project within visual art but it still has much to teach us. In the concretely abstract and performative artworks of Franz Erhard Walter and Günter Umberg, traces of this ambition remain and their work can be seen to pose questions probing our understandings and experiences of artistic meaning, its value and the real.
Resumo:
On 16 July 2003 the Australian Government’s Treasurer, the Honourable Peter Costello, addressed the Sydney Institute on his vision for a tolerant Australian society. Drawing from Putnam’s research Costello argued that tolerance will flow from an active voluntary sector. However, Costello’s proposed model for a “tolerant” society fails to acknowledge that all behaviour is strategic and that voluntary association based on disinterested action is not possible. Ultimately, Treasurer Costello’s notion of tolerant society fuelled by an active voluntary sector may not lead to his desired end. Indeed, the promotion of voluntary association may contribute to the ongoing exclusion of citizens with low social capital. Amid the dynamism of the modern era some citizens such as ageing workers, slow or ineffective learners and women may be especially at risk. Accordingly, rather than advocating a policy approach that seeks to build inclusiveness through an active voluntary sector this paper recommends a policy approach that explores ways in which to strengthen learning and the wider involvement of individuals through both formal and informal means.
Resumo:
Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results:In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.
Resumo:
Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening. © 2010 Landes Bioscience.
Resumo:
Background: Clinical practice and clinical research has made a concerted effort to move beyond the use of clinical indicators alone and embrace patient focused care through the use of patient reported outcomes such as healthrelated quality of life. However, unless patients give consistent consideration to the health states that give meaning to measurement scales used to evaluate these constructs, longitudinal comparison of these measures may be invalid. This study aimed to investigate whether patients give consideration to a standard health state rating scale (EQ-VAS) and whether consideration of good and poor health state descriptors immediately changes their selfreport. Methods: A randomised crossover trial was implemented amongst hospitalised older adults (n = 151). Patients were asked to consider descriptions of extremely good (Description-A) and poor (Description-B) health states. The EQ-VAS was administered as a self-report at baseline, after the first descriptors (A or B), then again after the remaining descriptors (B or A respectively). At baseline patients were also asked if they had considered either EQVAS anchors. Results: Overall 106/151 (70%) participants changed their self-evaluation by ≥5 points on the 100 point VAS, with a mean (SD) change of +4.5 (12) points (p < 0.001). A total of 74/151 (49%) participants did not consider the best health VAS anchor, of the 77 who did 59 (77%) thought the good health descriptors were more extreme (better) then they had previously considered. Similarly 85/151 (66%) participants did not consider the worst health anchor of the 66 who did 63 (95%) thought the poor health descriptors were more extreme (worse) then they had previously considered. Conclusions: Health state self-reports may not be well considered. An immediate significant shift in response can be elicited by exposure to a mere description of an extreme health state despite no actual change in underlying health state occurring. Caution should be exercised in research and clinical settings when interpreting subjective patient reported outcomes that are dependent on brief anchors for meaning. Trial Registration: Australian and New Zealand Clinical Trials Registry (#ACTRN12607000606482) http://www.anzctr. org.au