50 research outputs found

    Retargeted adenoviruses for radiation-guided gene delivery

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    The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

    Strategic communication and the entrepreneurial role of the corporate communication officer

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    Considering the recent evolution of the communication/PR profession in large organizations both private and public, many scholars agree that a process of institutionalization is occurring. In other words, communication’s importance has been growing, reaching in recent years a strategic position as a lever for companies’ governance. A first objective of this chapter is to describe, looking at management and communication/PR literature, how and to what extent communication has become strategic. The main hypothesis is that communication has become strategic within companies’ governance in order to help each organization to develop consistently – mainly in terms of values – within its environment. A second objective is to describe, looking at the entrepreneurial organization theory and communication/PR literature, another side of the strategic evolution of communication, which is to help each organization to develop – mainly in terms of services, products and reputation – as a different, or preferably unique, entity as compared to the other organizations. The evolution of the strategic contribution of communication/PR within organizations’ decision-making has a strong impact on the role that corporate communication officers (CCOs) play in organizations both on the isomorphic and on the entrepreneurial–innovative sides of the communicational activity they carry out to support the evolution of their organizations

    Strategies to Target Tumor Immunosuppression

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    The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

    Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential

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