39 research outputs found

    Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review

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    Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation

    Emotional work as a necessity: a psychosocial analysis of low-carbon energy collaboration stories

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    The urgent challenges of climate change and encouraging (more) sustainable consumption call for effective collaborations between stakeholders. However political and professional contexts often prioritise delivery of outcomes (the ‘what’) over process (the ‘how’). Indeed, even when external engagement or internal communication processes are carefully planned the actually ‘doing’ of them may still be hard, and at times emotionally intensive, work. This is where psychosocial theories offer significant insight; however, to date, they have been primarily brought to bear on caring and health professions rather than sustainability. Through a psychosocial analysis of collaboration stories gathered within a major project on low-carbon energy challenges across Europe, this chapter explores this emotional work. Results will be of practical interest to those looking to understand, encourage and undertake collaborative working for sustainability

    An Immunogenic Model of KRAS-Mutant Lung Cancer Enables Evaluation of Targeted Therapy and Immunotherapy Combinations.

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    Mutations in oncogenes such as KRAS and EGFR cause a high proportion of lung cancers. Drugs targeting these proteins cause tumor regression but ultimately fail to elicit cures. As a result, there is an intense interest in how to best combine targeted therapies with other treatments, such as immunotherapies. However, preclinical systems for studying the interaction of lung tumors with the host immune system are inadequate, in part due to the low tumor mutational burden in genetically engineered mouse models. Here we set out to develop mouse models of mutant KRAS-driven lung cancer with an elevated tumor mutational burden by expressing the human DNA cytosine deaminase, APOBEC3B, to mimic the mutational signature seen in human lung cancer. This failed to substantially increase clonal tumor mutational burden and autochthonous tumors remained refractory to immunotherapy. However, establishing clonal cell lines from these tumors enabled the generation of an immunogenic syngeneic transplantation model of KRAS-mutant lung adenocarcinoma that was sensitive to immunotherapy. Unexpectedly, antitumor immune responses were not directed against neoantigens but instead targeted derepressed endogenous retroviral antigens. The ability of KRASG12C inhibitors to cause regression of KRASG12C -expressing tumors was markedly potentiated by the adaptive immune system, highlighting the importance of using immunocompetent models for evaluating targeted therapies. Overall, this model provides a unique opportunity for the study of combinations of targeted and immunotherapies in immune-hot lung cancer. SIGNIFICANCE: This study develops a mouse model of immunogenic KRAS-mutant lung cancer to facilitate the investigation of optimal combinations of targeted therapies with immunotherapies

    International corporate entrepreneurship of Chinese exporters : an empirical study

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    Market orientation, corporate entrepreneurship and learning orientation are relevant and important organizational capabilities determining performance particularly for exporters who face an increasingly complex environment. A survey was undertaken in China to investigate their inter-relationships as well as their impact on performance. Results show that learning orientation is the major cultural precursor instrumental to market orientation and entrepreneurship development. It was also found that corporate entrepreneurship is a perfect mediator between learning- and market orientation-performance relationships. Chinese exporters are advised to cultivate themselves in developing a learning culture which can help them become more market oriented and entrepreneurial, and thus outperform in foreign countries
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