240 research outputs found
My life of the other: the exchange of identities in Dora Bruder, by Patrick Modiano
No full textAnálise do embaralhamento identitário em Dora Bruder, de Patrick Modiano. Após leitura da nota de desaparecimento de Dora Bruder publicada em um jornal parisiense em 1941, o narrador inominado em primeira pessoa – a quem se interpõe a figura do próprio Modiano – busca saber quem foi essa adolescente judia, as circunstâncias de seu desaparecimento e seu destino. Diante da escassez de vestígios sobre ela, o narrador mobiliza interessadamente sua própria memória pessoal num jogo de espelhamento sob o pano de fundo do trauma da Ocupação nazista na França. Este trabalho ambiciona escrutinar esse processo, tanto em sua singularidade quanto nas intrincadas relações que tece com a vasta obra do autor. Para tanto, mobiliza discussões sobre a escrita de si, a memória, o surrealismo e a narrativa policialAnalysis of identity scrambling in Dora Bruder, by Patrick Modiano. After reading the disappearance note o f O ora Bruder published in a Parisian newspaper in 1941, the narrator with no name in first person – to whom the figure of Modiano himself stands – seeks to know who this J ewish teenager was, the circumstances o f her disappearance and her fate. Faced with rhe scarcity o f traces o f her, the narrator interestedly mobilizes his own personal memory in a mirroring game with the nazi occupation in France as a backdrop. This work aims to scrutinize this process, both in its singularity and in its intricate relationships with the vast work o f rhe author. To this end, ir mobilizes discussions about the writing o f oneself, memory, surrealism and the crime fictio
The German Occupation in recent French fiction : an analysis of the literary “mode retro”
No full textThis thesis attempts to analyse and characterise the mode rétro, the remarkable renewal of interest in the German Occupation of France, which is coloured by an extensive re-evaluation of the period's significance. An introduction places this fashion in its literary, social and historical context, revealing how, from 1940 to 1969, a collective and predominantly Gaullist 'myth' of the Resistance became established, with the result that the national response to invasion was accepted to be one of wide-spread heroism and revolt. Part I studies the reaction to such résistancialisme, showing how this orthodox interpretation of events was undermined and, for many, discredited, and offering explanations of the timing and direction of the new view. Part II focuses on the fiction, memoirs, autobiographies and biographies of the younger authors, those who have no direct adult experience of the années noires. It is suggested that their obvious obsession with absent parent-figures reflects their awareness that the past has been misrepresented and their heritage rendered problematic. Their sole means of escape from this predicament, their only source of emotional relief is seen to lie in the creation of a personal account of the early 1940s running contrary to the prevalent orthodoxy, the fabrication of a 'counter-myth'. It is thus the notion of myth which links the various sections of the survey, and so gives the thesis its overall unity
Abstract 817: Unbiased discovery of exosome-associated biomarkers using xenograft models
No full textAbstract
We developed a novel, genome-wide method for biomarker discovery that is able to separate intrinsic markers of disease from markers of host response. Specifically, we implanted cell lines derived from two primary canine osteosarcoma tumors with different biological behavior into the tibiae of athymic nude mice. Both cell lines formed orthotopic tumors, and each recapitulated the biological behavior of the original primary tumor in terms of growth rate and metastatic potential (1,2). We also developed a cross-species hybrid genome that allowed us to identify separate canine and mouse transcripts in tumor xenografts (2). In other words, we were able to determine the contribution of canine mRNA sequences (derived from the implanted tumor cells) and mouse mRNA sequences (derived from infiltrating stroma) to define tumor-intrinsic features and host-specific features that contribute to osteosarcoma progression. When we applied this analysis method to exosome-derived mRNAs, we found canine-derived transcripts that were only present in exosomes of tumor-bearing mice that were associated with functions such as protein kinase A (PKA) and actin cytoskeleton signaling, and with upstream transcriptional regulators such as FOXF1, ESR1, and TP53. We also found tumor-specific, canine-derived transcripts that were associated with functions such as caveolae-derived endocytosis, energy utilization and metabolism, immune interactions, and G-coupled receptor signaling, and with upstream transcriptional regulators such as HNF1A, ESR1, NIPR1, and HNF4A. This method has the potential to reduce the statistical uncertainty that arises from the use of pre-selected molecules among the background of thousands of genomic features in patient samples. Using genome-wide analyses, we are able to combine multiple, highly correlated genes to manage this problem, increase markers' robustness, and avoid random correlations. In conclusion, this technology is useful to identify nucleic acids that serve as cancer biomarkers with high precision, and inter-species sequence conservation can be used to further improve its predictions.
References
1. Scott MC, Sarver AL, Tomiyasu H, Cornax I, Van Etten J, Varshney J, et al. Aberrant Retinoblastoma (RB)-E2F Transcriptional Regulation Defines Molecular Phenotypes of Osteosarcoma. J Biol Chem 2015;290(47):28070-83.
2. Scott MC, Tomiyasu H, Garbe JR, Cornax I, Amaya C, O'Sullivan MG, et al. Heterotypic models of osteosarcoma recapitulate tumor heterogeneity and biological behavior. Disease Models & Mechanisms 2016, doi: 10.1242/dmm.026849.
Citation Format: Milcah C. Scott, John R. Garbe, Hirotaka Tomiyasu, Alicia Donnelly, Brad A. Bryan, Subbaya Subramanian, Jaime F. Modiano. Unbiased discovery of exosome-associated biomarkers using xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 817. doi:10.1158/1538-7445.AM2017-817</jats:p
Progress in Adaptive Immunotherapy for Cancer in Companion Animals: Success on the Path to a Cure
No full textHarnessing the ability of the immune system to eradicate cancer has been a long-held goal of oncology. Work from the last two decades has finally brought immunotherapy into the forefront for cancer treatment, with demonstrable clinical success for aggressive tumors where other therapies had failed. In this review, we will discuss a range of therapies that are in different stages of clinical or preclinical development for companion animals with cancer, and which share the common objective of eliciting adaptive, anti-tumor immune responses. Even though challenges remain, manipulating the immune system holds significant promise to create durable responses and improve outcomes in companion animals with cancer. Furthermore, what we learn from this process will inform and accelerate development of comparable therapies for human cancer patients
The cytokine storm—An appropriate, over‐reactive response to SARS‐CoV‐2 or the wrong immune pathway?
No full textClues to immune function and oncogenesis provided by events that activate the cell cycle machinery in normal human T cells
No full textAbstract
A common feature seen in states of decreased immune competence or immunosuppression and in diseases of the blood, such as lymphohematopoietic cancers, is the disruption of the normal pathways of cell cycle control. In lymphocytes a series of nonlinear biochemical cascades leads to cellular proliferation and also controls the production of cytokines that provide immunologic help (i.e., aid in B and T cell proliferation, maturation, and differentiation). These two distinct outcomes can be dissociated, as stimuli that incite production of cytokines need not lead to cell division, and conversely, exogenously provided cytokines may promote lymphocyte proliferation. The signals that induce production of cytokines, particularly interleukin-2, have been extensively characterized. It also is known that the fidelity of cell cycle progression is dependent on a regulatory network whose key components include cyclin-dependent kinases and cyclins. This review describes the current state of knowledge linking the antigen receptor response pathways and the activation of the cell cycle machinery in T cells.</jats:p
Stage-specific embryonic antigen: determining expression in canine glioblastoma, melanoma, and mammary cancer cells
No full textAbstract PO-29: Conserved and unique transcriptional programs in human and canine non-Hodgkin lymphomas inform the judicious applications for the spontaneous canine model of disease
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