1,240 research outputs found

    “Omics” of HER2-Positive Breast Cancer

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    HER2/neu amplification/overexpression is the only somatic mutation widely considered to be a marker of disease outcome and response to treatment in breast cancer. Pathologists have made large efforts to achieve accuracy in characterizing HER2/neu status. The introduction of transtuzumab contributed to development of additional measures to identify sensitive and resistant subclasses of HER2/neu-positive tumors. In this article, we describe the latest advances in HER2/neu status diagnostic assessment and the most relevant research emerging from ‘‘Omics’’ (genomics, epigenetics, transcriptomics, and proteomics) studies on HER2/neu-positive breast cancer. A large quantity of biomarkers from different studies highlighted HER2/neu-positive specific proliferation, cell cycle arrest, and apoptosis mechanisms, as well as immunological and metabolic behavior. Major driver genes of tumor progression have had a candidate status (GRB7, MYC, CCND1, EGFR, etc.), even though the main role for HER2/neu is largely recognized. Nonetheless, existing omics data and HER2/neupositive molecular profiles seem to suggest that few proteogenomic alterations in HER2, EGFR, and PI3K networks could significantly affect the effectiveness of transtuzumab. The systematic search of molecular alterations in and across these pathways can help to select the most appropriate drug for a given patient based on in-depth understanding of complexity in tumor biology

    Gene Expression Profiling of Epithelial–Mesenchymal Transition in Primary Breast Cancer Cell Culture

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    Background/Aim: Epithelial–mesenchymal transition (EMT) is a process co-opted by cancer cells to invade and form metastases. In the present study we analyzed gene expression profiles of primary breast cancer cells in culture in order to highlight genes related to EMT. Materials and Methods: Microarray expression analysis of primary cells isolated from a specimen of a patient with an infiltrating ductal carcinoma of the breast was performed. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) analyses validated microarray gene expression trends. Results: Thirty-six candidate genes were selected and used to generate a molecular network displaying the tight relationship among them. The most significant Gene Ontology biological processes characterizing this network were involved in cell migration and motility. Conclusion: Our data revealed the involvement of new genes which displayed tight relationships among them, suggesting a molecular network in which they could contribute to control of EMT in breast cancer. This study may offer a basis for understanding complex mechanisms which regulate breast cancer progression and for designing individualized anticancer therapies

    Remnants and Revenants: politics and violence in the work of Agamben and Derrida

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    This is the peer reviewed version of the following article: Frazer, Elizabeth, and Kimberly Hutchings. "Remnants and revenants: politics and violence in the work of Agamben and Derrida." The British Journal of Politics & International Relations 13.2 (2011): 127-144, which has been published in final form at http://dx.doi.org/10.1111/j.1467-856X.2010.00428.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Jacques Derrida and Giorgio Agamben both consider the question of whether there can be politics without violence, offering contrasting responses. In the case of Agamben, the remnant (that which remains) is disruptive and destabilising of present institutions; in the case of Derrida the revenant, the spectre, promises a future that is open. This reading of the two theories suggests that Derrida's response to the question of politics and violence is more persuasive than Agamben's. But the abstraction of his argument, like the tensions and contradictions in Agamben's, means that we are not hereby furnished with the resources to think politically about violence

    Inflammatory Response to a High Radiation Dose in Breast Cancer

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    Background: Radiation therapy (RT) is an essential treatment modality used for breast cancer (BC) care. Radiations can stimulate the immune system via the early activation of cytokine cascades, which can greatly affect cellular radio-sensitivity. Our aim is to analyze inflammatory response induced by high ionizing radiation (IR) doses, generated by intraoperative radiotherapy (IORT) treatment, to identify several potential targets that may influence cell radio-response. Methods: MCF10, MCF7 and MDA-MB231 BC cell lines have been exposed to high IR (23 Gray and 9 Gray), delivered by IORT treatments. Conditioned media (CM) were assayed at the time points: 0’, 30’, 1, 3, 6, 24, 48, and 72 hours, for production of cytokines, chemokines and growth factors by using Luminex technology. Results: We observed a very low cytokine concentration in MCF7 CM and a greater expression, of TH1 and TH2 cytokines, IL-7, G-CSF and MCP-1 in MCF10A CM. MDA-MB231 CM showed a reduced expression of TH1 and TH2 cytokines, IL-7, G-CSF, MCP-1 and an up-regulation of GM-CSF, IL-6 and IL-8 factors. Conclusions: Our results indicate that cytokine production in most cases is dose independent and time and cell type dependent. In particular, an over production at 24 hours after IORT treatment was observed. In addition, we speculate that MCF10A cells potentially exhibit an increased capacity to activate the immune system after IR exposure, and that MDAMB231 cells could have a role in radio-resistance phenotype through IL-6 and IL-8 high production activated by IR

    Brisures du romaneque: 'La Malédiction de la Madone', ou d'une pratique ironique du docufiction.

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    La Malédiction de la Madone, pubblicato nel 2022, è il primo romanzo in cui Philippe Vilain, scrittore tra i maggiori rappresentanti dell’autofinzione, ab- bandona la narrazione in prima persona per un “docufiction” in terza persona basato sulla vita della camorrista Pupetta Maresca. questo cambio di rotta, an- cor più sorprendente per un autore come Vilain che aveva sempre vilipeso que- sto genere letterario, è occasione di mettere in questione le sue concezioni del romanzo e della letteratura. Ne vien fuori una narrazione tesa tra l’aspirazione a far corpo unico con la sua precedente produzione letteraria e le condizioni im- poste dalla “docufinzionalizzazione” della storia. La Malédiction de la Madone diventa così un vero e proprio laboratorio letterario dove la sperimentazione più fine e pensosa svela inattese punte d’ironia.La Malédiction de la Madone, published in 2022, is the first novel in which Philippe Vilain, a writer among the greatest representatives of autofiction, abandons the first-person narration for a third-person “docufiction” based on the life of the camorrist Pupetta Maresca. This change of course, even more surprising for an author like Vilain who had always vilified this literary genre, is an opportunity to question his conceptions of the novel and of literature. The result is a narrative tended between the aspiration to merge with his previous literary pro- duction and the conditions imposed by “docufictionalization” of the history. The Malédiction de la Madone thus becomes a real literary laboratory where the finest and most thoughtful experimentation reveals unexpected hints of irony

    FP-INJECTIVE SEMIRINGS, SEMIGROUP RINGS AND LEAVITT PATH ALGEBRAS

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    In this paper we give characterisations of FP-injective semirings (previously termed “exact” semirings in work of the first author). We provide a basic connection between FP-injective semirings and P-injective semirings, and establish that FP-injectivity of semirings is a Morita invariant property. We show that the analogue of the Faith-Menal conjecture (relating FP-injectivity and self-injectivity for rings satisfying certain chain conditions) does not hold for semirings. We prove that the semigroup ring of a locally finite inverse monoid over an FP-injective ring is FP-injective and give a criterion for the Leavitt path algebra of a finite graph to be FP-injective

    Alive-FP: Automated Verification of Floating Point Based Peephole Optimizations in LLVM

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    Peephole optimizations optimize and canonicalize code to enable other optimizations but are error-prone. Our prior research on Alive, a domain-specific language for specifying LLVM’s peephole optimizations, automatically verifies the correctness of integer-based peephole optimizations and generates C++ code for use within LLVM. This paper proposes Alive-FP, an automated verification and code generation framework for floating point based peephole optimizations in LLVM. Alive-FP handles bit precise floating point optimizations and a class of fast-math optimizations involving signed zeros, not-a-number, and infinities. This paper provides multiple encodings for various floating point operations to account for the various kinds of undefined behavior and under-specification in the LLVM’s language reference manual. We have translated all optimizations that belong to this category into Alive-FP. In this process, we have discovered seven wrong optimizations in LLVM.Technical report DCS-TR-72

    Portrait of inflammatory response to ionizing radiation treatment

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    Ionizing radiation (IR) activates both pro-and anti-proliferative signal pathways producing an imbalance in cell fate decision. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular radiation-dependent response. Radiation therapy can modulate anti-tumour immune responses, modifying tumour and its microenvironment. In this review, we report how IR could stimulate inflammatory factors to affect cell fate via multiple pathways, describing their roles on gene expression regulation, fibrosis and invasive processes. Understanding the complex relationship between IR, inflammation and immune responses in cancer, opens up new avenues for radiation research and therapy in order to optimize and personalize radiation therapy treatment for each patient
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