1,721,209 research outputs found
Natural Regulatory T Cells and Persistent Viral Infection
No full textShuo Li, Eric J. Gowans, Claire Chougnet, Magdalena Plebanski, and Ulf Dittme
Immunomodulatory effects of cyclophosphamide: optimising treatment for improved efficacy in patients with refractory gynaecological cancers
No full textAbstract withheld by author
Investigation of early dendritic cell lineage for potential application in immunotherapy and vaccine development
No full textDendritic cells (DCs) are an important component of the innate immune system, which modulate the adaptive immune response. As a professional APC, DCs are often targeted in vaccine research and immunotherapeutic development. Most studies mass-produce mature DCs in late-phase in vitro cultures using mainly GM-CSF. However, DC-based therapy, especially for cancer, has largely been unsuccessful. Furthermore, the use of GM-CSF for DC generation can also produce myeloid derived suppressor cells (MDSCs). The presence of these cells may have contributed to the lack of response from the in vitro DCs. In this thesis, we investigated the properties, such as phenotype, endocytosis, activation and functionality, of early GM-CSF and GM-CSF + IL-4 derived DCs and MDSCs. We also attempted to explore the possible use of the early GM-CSF derived DCs in cancer therapy by exposing them to in vitro cancer cell lines. Whilst the results from this study revealed several promising aspects of the early GM-CSF derived culture, these findings still warrant further research before they can be integrated into the development of future vaccine and immunotherapeutic treatments
The role of TNFR2+ regulatory T cells in human cancers
No full textCancer is currently the leading cause of death worldwide. Almost all human cancers present with high numbers of regulatory T cells (Tregs) within their tumor microenvironment. Regulatory T cells are a subset of T cells that have detrimental effects within cancer patients as they can dampen anti-tumor immunity and enable cancer progression. Additionally, most cancer patients have high levels of the pro-inflammatory cytokine, tumor necrosis factor (TNF), which can induce TNF Receptor 2 (TNFR2) on Tregs. TNFR2+ Tregs represent a highly potent Treg subset, and depletion of these cells results in tumor eradication within murine mesothelioma models. As there are currently no studies on TNFR2+ Tregs in human cancers, this PhD aimed to investigate the role of TNFR2+ Tregs in ovarian cancer and in acute myeloid leukemia (AML). The results demonstrate that TNFR2+ Tregs are indeed present at elevated levels within the tumor microenvironment (ascites) of newly diagnosed ovarian cancer patients, and within the peripheral blood as well as the tumor microenvironment (bone marrow) of newly diagnosed AML patients. Additionally, these cells were also present at elevated levels within the peripheral blood of AML patients at clinical remission, suggesting that they are resistant to current standard induction chemotherapy. Elevated levels within the tumor microenvironment were partly attributed to the selective migration of TNFR2+ Tregs from the peripheral blood into the tumor microenvironment, for both ovarian cancer as well as AML patients. These Tregs were significantly more suppressive in function within ascites when compared to those from the peripheral blood of ovarian cancer patients, while they had a similar functional phenotype when comparing the peripheral blood and the bone marrow of newly diagnosed AML patients. The novel combined therapy of the chemotherapeutic drugs, panobinostat and azacitidine, when administered to newly diagnosed AML patients as an induction therapy, was able to selectively reduce TNFR2+ Treg proportions within the peripheral blood of all patients. This reduction was, however, observed within the bone marrow of only a proportion of the patients who did clinically better, demonstrating that TNFR2+ Treg proportions within the bone marrow of newly diagnosed AML patients are correlated with disease outcome. In vitro studies suggested that panobinostat may be responsible for the observed reduction of TNFR2+ Tregs. Furthermore, administration of the chemotherapeutic drug lenalidomide, a TNF inhibitor, along with azacitidine to AML patients at clinical remission as a maintenance therapy, was also able to reduce TNFR2 levels on CD4 T cells, as well as TNFR2+ Treg levels within the peripheral blood of a proportion of the patients who did clinically better. In vitro studies suggested that lenalidomide may be responsible for the reduction of TNFR2 levels, however this was not via its ability to inhibit TNF production, indicating a novel mechanism. Collectively, the results demonstrate that TNFR2+ Tregs are present at elevated levels within human ovarian cancer and AML patients and that a number of chemotherapeutic drugs can selectively reduce the proportion of TNFR2+ Tregs, with this reduction being correlated with a better clinical outcome. Targeting TNFR2+ Tregs therefore appears to be a promising strategy to further improve the current poor prognosis of cancer patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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