Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>This study was performed in order to determine whether monocyte <it>in vitro </it>function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease.</p> <p>Methods</p> <p>Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte <it>in vitro </it>interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis.</p> <p>Results</p> <p>All patients, as a group, had higher <it>in vitro </it>monocyte responsiveness in terms of IL-6 (AS) (<it>t </it>= 2.03; <it>p </it>< 0.05) and MCP-1 (SFM) (<it>t </it>= 2.49; <it>p </it>< 0.05) compared to controls. Increased <it>in vitro </it>monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05–4.88; <it>p </it>< 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03–6.92; <it>p </it>< 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (χ = 4.0; <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>In HNSCC patients, changed monocyte <it>in vitro </it>response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors.</p

Multiorgan Metastasis of Human HER-2+ Breast Cancer in Rag2−/−;Il2rg−/− Mice and Treatment with PI3K Inhibitor

In vivo studies of the metastatic process are severely hampered by the fact that most human tumor cell lines derived from highly metastatic tumors fail to consistently metastasize in immunodeficient mice like nude mice. We describe a model system based on a highly immunodeficient double knockout mouse, Rag2−/−;Il2rg−/−, which lacks T, B and NK cell activity. In this model human metastatic HER-2+ breast cancer cells displayed their full multiorgan metastatic potential, without the need for selections or additional manipulations of the system. Human HER-2+ breast cancer cell lines MDA-MB-453 and BT-474 injected into Rag2−/−;Il2rg−/− mice faithfully reproduced human cancer dissemination, with multiple metastatic sites that included lungs, bones, brain, liver, ovaries, and others. Multiorgan metastatic spread was obtained both from local tumors, growing orthotopically or subcutaneously, and from cells injected intravenously. The problem of brain recurrencies is acutely felt in HER-2+ breast cancer, because monoclonal antibodies against HER-2 penetrate poorly the blood-brain barrier. We studied whether a novel oral small molecule inhibitor of downstream PI3K, selected for its penetration of the blood-brain barrier, could affect multiorgan metastatic spread in Rag2−/−; Il2rg−/− mice. NVP-BKM120 effectively controlled metastatic growth in multiple organs, and resulted in a significant proportion of mice free from brain and bone metastases. Human HER-2+ human breast cancer cells in Rag2−/−;Il2rg−/− mice faithfully reproduced the multiorgan metastatic pattern observed in patients, thus allowing the investigation of metastatic mechanisms and the preclinical study of novel antimetastatic agents

Fear of predation drives stable and differentiated social relationships in guppies

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Social relationships can have important consequences for fitness in animals. Whilst numerous studies have shown that individuals often join larger groups in response to perceived predation risk (i.e. fear of predation), the importance of predation risk in driving the formation and stability of social relationships within groups has been relatively ignored. We experimentally tested how predation threat influenced fine-scale social network structure using Trinidadian guppies (Poecilia reticulata). When perceived predation risk was high, individuals developed stable and more differentiated social ties compared to when perceived risk was low. Intriguingly, social differentiation coincided with shoals being somewhat smaller under high-perceived risk, suggesting a possible conflict between forming stable social relationships and larger social groups. Individuals most at risk of predation (large and bold individuals) showed the most exaggerated responses in several social measures. Taken together, we provide the first experimental evidence that proximate risk of predation can increase the intensity of social relationships and fine-scale social structure in animal populations.DPC acknowledges funding from the National Environmental Research Council (NE/E001181/1) and Leverhulme Trust (RPG-175) and SKD and DPC acknowledge funding from The Danish Council for Independent Research (DFF – 1323-00105)

Excretion patterns of coccidian oocysts and nematode eggs during the reproductive season in Northern Bald Ibis (Geronticus eremita)

Individual reproductive success largely depends on the ability to optimize behaviour, immune function and the physiological stress response. We have investigated correlations between behaviour, faecal steroid metabolites, immune parameters, parasite excretion patterns and reproductive output in a critically endangered avian species, the Northern Bald Ibis (Geronticus eremita). In particular, we related haematocrit, heterophil/lymphocyte ratio, excreted immune-reactive corticosterone metabolites and social behaviour with parasite excretion and two individual fitness parameters, namely, number of eggs laid and number of fledglings. We found that the frequency of excretion of parasites’ oocysts and eggs tended to increase with ambient temperature. Paired individuals excreted significantly more samples containing nematode eggs than unpaired ones. The excretion of nematode eggs was also significantly more frequent in females than in males. Individuals with a high proportion of droppings containing coccidian oocysts were more often preened by their partners than individuals with lower excretion rates. We observed that the more eggs an individual incubated and the fewer offspring fledged, the higher the rates of excreted samples containing coccidian oocysts. Our results confirm that social behaviour, physiology and parasite burden are linked in a complex and context-dependent manner. They also contribute background information supporting future conservation programmes dealing with this critically endangered species

Culture and Personal Epistemology: U.S. and Middle Eastern Students’ beliefs about Scientific Knowledge and Knowing

Middle Eastern (Omani) and Western (U.S.) students’ beliefs about knowledge and knowing in the sciences were compared on four dimensions of personal epistemology proposed by Hofer and Pintrich ( Review of Educational Research (1997), 67 , 88–140). As predicted, given their experiences with comparatively traditional political and religious institutions, Omani more so than U.S. college students were more likely to accept scientific authorities as the basis of scientific truth. Furthermore, Omani men were more accepting of authorities than were Omani women, but there was no gender difference among U.S. students. Omani more than U.S. students also believed that knowledge in the sciences was simpler and more certain, which is consistent with comparisons between U.S. and Asian students (e.g., Qian & Pan, 2002, A comparision of epistemological beliefs and learning from science text between American and Chinese high school students. In B. K. Hofer & P. R. Pintrich (Eds.), Personal epistomology: The psychology of beliefs about knowledge and knowing (pp. 365–385), Mahwah, NJ: Erlbaum). Students in the two countries did not differ, however, in whether their beliefs were based on personal opinions versus systematic evidence. Suggestions for further research included directly assessing experiences with, and attitudes toward, authorities in academic and other areas of students’ lives.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43812/1/11218_2005_Article_1826.pd

Understanding first year university students: personal epistemology and learning

Whilst participation in higher education has increased dramatically over the last two decades, many universities are only now beginning to pay more attention to the learning experiences of first year students. It is important for universities to understand how first year students conceive of learning and knowing in order to promote effective approaches to learning. Even though an extensive body of research demonstrates that beliefs about learning and knowing influence student approaches to learning and learning outcomes, there has been no Australian research that has investigated this critical learner characteristic across first year university students. This paper reports on preliminary data from an ongoing longitudinal study designed to investigate first year students’ beliefs about knowing and learning (epistemological beliefs). Students from teacher education and creative industry faculties in two Australian universities completed the Epistemological Beliefs Survey (EBS) in the first week of their first semester of study. A series of one-way ANOVA using key demographics as independent variables and the EBS factor scores as dependent variables showed that epistemological beliefs were related to the course of study, previous post-school education experience, family experience at University, gender and age. These data help us to understand students’ beliefs about learning and knowing with a view to informing effective learning in higher education

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ABSTRACT Most organisms, including ourselves, are exposed to environmental stressors at various points during life, and responses to such stressors have been optimised by evolution to give the best fitness outcomes. It is expected that environmental change will substantially increase long-term stress exposure in many animal groups in the coming decades. A major challenge for biologists is to understand and predict how this will influence individuals, populations and ecosystems, and over what time scale such effects will occur. This requires a multi-disciplinary approach, combining studies of mechanisms with studies of fitness consequences for individuals and their descendants. In this review, I discuss the positive and negative fitness consequences of responses to stressful environments, particularly during early life, and with an emphasis on studies in birds. As many of the mechanisms underlying stress responses are highly conserved across the vertebrate groups, the findings from these studies have general applicability when interpreted in a life history context. One important route that has recently been identified whereby chronic stress exposure can affect health and longevity over long time frames is via effects on telomere dynamics. Much of this work has so far been done on humans, and is correlational in nature, but studies on other taxa, and experimental work, are increasing. I summarise the relevant aspects of vertebrate telomere biology and critically appraise our current knowledge with a view to pointing out important future research directions for our understanding of how stress exposure influences life histories