Tumorangiogenese und Immunsuppression: Strategische Angriffspunkte für neue Therapieansätze beim Plattenepithelkarzinom der Mundhöhle (HNSCC)

Zusammenfassung: Hintergrund: Die Tumorangiogenese und tumorassoziierte Immunsuppression sind Grundvoraussetzung für eine erfolgreiche Tumorevolution. Unsere bisherigen Analysen zeigen, dass Mundhöhlenkarzinomzellen über eine Produktion von TGF-β1 ("transforming growth factor-beta1") und MCP-1 ("monocyte chemoattractant protein-1") die Makrophageninfiltration in den Tumor stimulieren. Die angelockten Makrophagen produzieren den angiogenetischen sowie immunsupprimierenden Wachstumsfaktor VEGF ("vascular endothelial growth factor") und induzieren zudem die Produktion dieses Faktors über Interleukin (IL)-1α in den Tumorzellen. Neuere In-vitro-Studien zeigen, dass Retinsäure (VitaminA) die TGF-β1- und MCP-1-Produktion der Tumorzellen hemmt. Deshalb wurde in der vorliegenden Studie der Einfluss von Retinsäure auf die Makrophageninfiltration und VEGF-Produktion im Mausmodell analysiert. Material und Methoden: Mäusen der AJ-Linie (10Mäuse pro Gruppe) wurden Polyethylenschwämme (5×2mm3) mit humanen HNSCC-Zellen (450.000-150.0000/10μl RPMI) subkutan eingepflanzt. Mäuse mit Tumoren von mindestens 0,7-1 cm3 Durchmesser wurden täglich mit Retinsäure (160µg/kg) i.p. behandelt. Nach 21Tagen wurden die Schwämme entnommen und immunhistologisch nach VEGF-A, MCP-1, CD68 und CD31 untersucht. Die Bestimmung der Serumwerte von VEGF-A und MCP-1 erfolgte mit dem ELISA. Die Organe wurden entnommen und nach Makro- und- Mikrometastasen untersucht. Ergebnisse: Bei allen mit Retinsäure behandelten Tieren kam es zur vollständigen Tumorregression. Die Mäuse wiesen keinen Metastasenbefall auf (p=0,00) und die Makrophageninfiltration in den Tumor konnte blockiert werden (p=0,007). Alle behandelten Tiere regulierten die MCP-1- (0pg/ml) und VEGF-A-Serumwerte (12pg/ml) herunter (p=0,001). Schlussfolgerung: Die Ergebnisse zeigen, dass die Blockierung der Makrophageninfiltration in den Tumor mit VitaminA ein möglicher Therapieansatz ist, um die Induktion der zwei wichtigsten Überlebensstrategien des Tumors, Immunsuppression und Angiogenese, zu hemme

T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs) while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy

Unique Continuation for Schr\"odinger Evolutions, with applications to profiles of concentration and traveling waves

We prove unique continuation properties for solutions of the evolution Schr\"odinger equation with time dependent potentials. As an application of our method we also obtain results concerning the possible concentration profiles of blow up solutions and the possible profiles of the traveling waves solutions of semi-linear Schr\"odinger equations.Comment: 23 page

Distributed-Pair Programming can work well and is not just Distributed Pair-Programming

Background: Distributed Pair Programming can be performed via screensharing or via a distributed IDE. The latter offers the freedom of concurrent editing (which may be helpful or damaging) and has even more awareness deficits than screen sharing. Objective: Characterize how competent distributed pair programmers may handle this additional freedom and these additional awareness deficits and characterize the impacts on the pair programming process. Method: A revelatory case study, based on direct observation of a single, highly competent distributed pair of industrial software developers during a 3-day collaboration. We use recordings of these sessions and conceptualize the phenomena seen. Results: 1. Skilled pairs may bridge the awareness deficits without visible obstruction of the overall process. 2. Skilled pairs may use the additional editing freedom in a useful limited fashion, resulting in potentially better fluency of the process than local pair programming. Conclusion: When applied skillfully in an appropriate context, distributed-pair programming can (not will!) work at least as well as local pair programming

Why We Read Wikipedia

Wikipedia is one of the most popular sites on the Web, with millions of users relying on it to satisfy a broad range of information needs every day. Although it is crucial to understand what exactly these needs are in order to be able to meet them, little is currently known about why users visit Wikipedia. The goal of this paper is to fill this gap by combining a survey of Wikipedia readers with a log-based analysis of user activity. Based on an initial series of user surveys, we build a taxonomy of Wikipedia use cases along several dimensions, capturing users' motivations to visit Wikipedia, the depth of knowledge they are seeking, and their knowledge of the topic of interest prior to visiting Wikipedia. Then, we quantify the prevalence of these use cases via a large-scale user survey conducted on live Wikipedia with almost 30,000 responses. Our analyses highlight the variety of factors driving users to Wikipedia, such as current events, media coverage of a topic, personal curiosity, work or school assignments, or boredom. Finally, we match survey responses to the respondents' digital traces in Wikipedia's server logs, enabling the discovery of behavioral patterns associated with specific use cases. For instance, we observe long and fast-paced page sequences across topics for users who are bored or exploring randomly, whereas those using Wikipedia for work or school spend more time on individual articles focused on topics such as science. Our findings advance our understanding of reader motivations and behavior on Wikipedia and can have implications for developers aiming to improve Wikipedia's user experience, editors striving to cater to their readers' needs, third-party services (such as search engines) providing access to Wikipedia content, and researchers aiming to build tools such as recommendation engines.Comment: Published in WWW'17; v2 fixes caption of Table

Maximising transparency in a doctoral thesis: The complexities of writing about the use of QSR*NVIVO within a grounded theory study

This paper discusses the challenges of how to provide a transparent account of the use of the software programme QSR*NVIVO (QSR 2000) within a Grounded Theory framework (Glaser and Strauss 1967; Strauss and Corbin 1998). Psychology students are increasingly pursuing qualitative research projects such to the extent that the UK Economic and Social Research Council (ESRC) advise that students should have skill in the use of computer assisted qualitative data analysis software (CAQDAS) (Economic and Social Research Council 2001). Unlike quantitative studies, rigid formulae do not exist for writing-up qualitative projects for doctoral theses. Most authors, however, agree that transparency is essential when communicating the findings of qualitative research. Sparkes (2001) recommends that evaluative criteria for qualitative research should be commensurable with the aims, objectives, and epistemological assumptions of the research project. Likewise, the use of CAQDAS should vary according to the research methodology followed, and thus researchers should include a discussion of how CAQDAS was used. This paper describes how the evolving process of coding data, writing memos, categorising, and theorising were integrated into the written thesis. The structure of the written document is described including considerations about restructuring and the difficulties of writing about an iterative process within a linear document