Escaping NK cells and recruiting neutrophils: How Morgana/NF-κB signaling promotes metastasis

Cancer cells escape immune surveillance and induce immune cell aberrant activation to support tumour growth and progression. We recently reported that Morgana/NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling in breast cancer cells is responsible for NK (Natural Killer) cell inactivation and neutrophil recruitment in the primary tumour and in the lung pre-metastatic niche

Structural Priming and the Mental Representation of Agentive and Temporal by-Phrase Constructions: An Eye-Tracking Study

The phenomenon in psycholinguistics known as structural priming happens, during language comprehension, when a prime sentence facilitates the processing speed of a target sentence, when both bear the same syntactic structure. In the present study, two specific passive constructions were investigated, the agentive by-phrase and the temporal by-phrase, to evaluate whether these structures primes each other or whether they prime themselves. On-line sentence processing measured by eye-tracking data in the form of duration of fixations within the AOIs (areas of interest) as well as fixation regressions to those AOIs corresponding to the prepositional by-phrases, the NP (det N), and the VP (aux V) respectively. The study yielded significant findings for priming of agentive targets with agentive primes and a failure to find priming in all other combinations of agentive and temporal prime and target conditions. The implications of these findings for an understanding of the mental representation of syntax of these constructions are discussed

The double face of Morgana in tumorigenesis

Morgana is a chaperone protein able to bind to ROCK I and II and to inhibit their kinase activity. Rho kinases are multifunctional proteins involved in different cellular processes, including cytoskeleton organization, centrosome duplication, cell survival and proliferation. In human cancer samples Morgana appears to be either downregulated or overexpressed, and experimental evidence indicate that Morgana behaves both as an oncosuppressor and as a proto-oncogene. Our most recent findings demonstrated that if on the one hand low Morgana expression levels, by inducing ROCK II hyperactivation, cause centrosome overduplication and genomic instability, on the other hand, Morgana overexpression induces tumor cell survival and chemoresistance through the ROCK I-PTEN-AKT axis. Therefore, Morgana belongs to a new class of proteins, displaying both oncogenic and oncosuppressor features, depending on the specific cellular context

PhoNoCMap: An application mapping tool for photonic networks-on-chip

While providing a promising solution for high-performance on-chip communication, photonic networks-on-chip suffer from insertion loss and crosstalk noise, which may severely constrain their scalability. In this paper, we introduce a methodology and a related tool, PhoNoCMap, for the design space exploration of optical NoCs mapping solutions, which automatically assigns application tasks to the nodes of a generic photonic NoC architecture such that the worst-case either insertion loss or crosstalk noise are minimized. The experimental results show significant benefits in terms of insertion loss and crosstalk noise, allowing improved network scalability

P03.25 Neutralizing extracellular CHP-1 impairs tumor growth and metastasis formation

Background Found in the extracellular compartment, Heat Shock Proteins (HSPs) are actively secreted proteins that modulate the tumor behavior. Extracellular HSPs play a unique role as extracellular chaperones and receptors-binding molecules, favoring the establishment and maintenance of different cancer hallmarks, including immune modulation and evasion. CHP-1, is a ubiquitously expressed protein with chaperone activity and its high expression correlates with high tumor grade and lymph node positivity in different breast and lung cancer subtypes. In addition, CHP-1 is actively and uncanonically secreted by cancer cells in the tumor microenvironment (TME). Materials and Methods Sera cancer patients were analyzed for the presence of CHP-1. To assess the role of extracellular CHP-1 (eCHP-1) in the TME, in vitro experiments on different cell populations have been performed. To dissect the molecular mechanisms, through which eCHP-1 induces cancer progression, have been analyzed specific signaling pathways in cancer and immune cells. Immune cell composition in presence of eCHP-1 in tumors has been identified using flow-cytometry. The characterization of eCHP-1 inhibition as therapeutic approach has been conducted in breast and colon cancer pre-clinical models. Results eCHP-1 activates an autocrine signaling through TLR2, TLR4 and LRP1, promoting tumor progression and metastasis formation in different pre-clinical models. Moreover, eCHP-1 can modulate the immune composition of the TME, making interesting the analysis of its inhibition in cancer immunotherapy. Conclusions eCHP-1 represents a easy accessible protein for diagnosis and targeting in very aggressive canncers. Disclosure Information L. Secli: None. F. Fusella: None. M. Brancaccio: None

OD26 - Inverse consistency error as a validation metric for deformable image registration: preliminary implementation research

The aim of this work is to develop a novel automatic voxel-based quantitative measurement approach to evaluate the registration accuracy of a Deformable Image Registration (DIR) algorithm in clinical practice. As the Inverse Consistency Error (ICE) can be computed directly from the deformation vector field (DVF) generated by the Treatment Planning System (TPS), it appears to be a valid surrogate of standard quality assurance metrics to assess the spatial error in the registration process