1,721,082 research outputs found
Abstract 1622: The role of the CCL-2 on lymphopenia-induced myeloid derived suppressor cells
No full textAbstract
The induction of lymphopenia prompts the expansion of CD11b+Ly6ChiLy6G- monocytic MDSCs (M-MDSCs) and CD11b+Ly6C+Ly6G+ polymorphonuclear MDSCs (PMN-MDSCs). Patients receiving adoptive cell therapy (ACT) require nonmyeloablative chemotherapy to induce lymphopenia and support anti-tumor immunity. However, the role of MDSCs in the setting of ACT is not fully understood. As high levels of CCL-2 can be measured in lymphopenic mice, in this study we investigate the role of CCL-2 in the expansion and function of lymphopenia-induced MDSCs using CCR2KO mouse models. Lymphopenia was induced in melanoma-bearing C57BL/6 (WT) and CCR2KO mice by 600rad of total body irradiation or combination therapy with cyclophosphamide and fludarabine. We first evaluated the percentages of splenic MDSCs in WT and CCR2KO mice after the induction of lymphopenia. At day 14, the expansion of total MDSCs were similar in WT (279% of normal) and CCR2KO (241% of normal). However, the mean percentages of M-MDSCs (3.5%) and PMN-MDSCs (30.3%) in CCR2KO mice were altered compared to M-MDSCs (22.2%) and PMN-MDSCs (21.7%) in WT mice. In addition, M-MDSCs in B16 tumors grown in CCR2KO mice were decreased compared to intratumoral M-MDSCs in WT mice (p<0.001). In contrast, the percentages of M-MDSCs and PMN-MDSCs were unchanged in the bone marrow (BM). To investigate the suppressive capacity of lymphopenia-induced MDSCs, OVA antigen-specific CD8+ T cells were co-cultured with OVA peptide in the presence of MDSCs purified from the spleens of CCR2KO and WT mice. Both CCR2KO and WT MDSCs potently suppressed T cell proliferation as measured by 3H thymidine incorporation. CCR2KO and WT MDSCs had significant arginase activity and production of nitrites. To investigate the efficacy of ACT, B16 tumor-bearing CCR2KO and WT mice were lymphodepleted and gp100 antigen-specific Thy1.2+CD8+ T cells were adoptively transferred followed by 3 days of IL-2 treatment. We found that donor T cell tumor infiltration was similar and no difference in tumor growth was observed between CCR2KO and WT mice. Collectively, these results suggest that the role of CCL-2 is important for the egress of lymphopenia-induced M-MDSCs from the BM, but has no effect on the expansion or function of PMN-MDSCs in the setting of lymphopenia. These data suggest that factors besides CCL-2 play an important role in the expansion and function of MDSCs after the induction of lymphopenia.
Citation Format: Pasquale P. Innamarato, Amy Weber, Shari Pilon-Thomas. The role of the CCL-2 on lymphopenia-induced myeloid derived suppressor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1622. doi:10.1158/1538-7445.AM2017-1622</jats:p
Abstract 2695: Role of tumor generated acidity in immune stromal interactions during prostate carcinogenesis
No full textAbstract
Insufficiency in tumor perfusion and high rate glycolysis combine to reduce the pH of tumor microenvironment. In a TRAMP model of prostate cancer, we had shown that carcinogenesis is associated with increasing acidification of the microenvironment and that neutralization of this acidity can prevent cancer emergence or metastases. Carcinogenesis in the TRAMP model is also associated with increased fibrosis and immune cells infiltration. We thus sought to determine if fibrosis drives immune infiltration in early tumorigenesis or vice-versa; and whether this dynamics is affected by tumor acidity. To investigate this, we harvested prostates from TRAMP mice or their matching non-transgenic controls at different time points and stained serial prostate tissue sections with F4/80 (macrophages), SMA (cancer-associated fibroblasts, CAFs), and Masson’s Trichome (collagen). Quantitative image analysis reveals that increase in fibrosis occur prior to macrophage infiltration and that both events preceded tumor development. However, the relative amount of collagen fibers was unchanged across all time points. Notably, neither fibrosis nor macrophage infiltration occurred in mice treated with buffer, suggesting an involvement of acidity in this immune stromal interactions. Interestingly, macrophages isolated from latter time points in the untreated group as well as macrophages co-cultured with prostate tumor cells at acidic pH, possessed an M2-like phenotype by expressing immunosuppressive genes (e.g. Arginase 1, Arg1) and a range of scavenging receptors (e.g. mannose receptor, Cd206), as well as releasing more angiogenic factors (e.g. VEGF and MMPs). Similar results were recapitulated when M2 macrophages were stimulated at acidic pH by showing enhanced Cd206 and Arg1 expression. On the functional level, macrophages activated at acidic pH had a higher ability to uptake fluorescently labelled ovalbumin and collagen, as examples of mannosylated ligands that prevail the fibrotic microenvironment. In summary, these results suggest that tumor acidity may promote fibrosis, with subsequent macrophage infiltration and phenotypic switching, leading to increased collagen turnover. It is suspected that this extracellular matrix remodeling may be permissive for tumor progression.
Citation Format: Asmaa El-Kenawi, Jasreman Dhillon, Arig Ibrahim-Hashim, Dominique Abrahams, Shari Pilon-Thomas, Brian Ruffell, Robert Gatenby, Robert Gillies. Role of tumor generated acidity in immune stromal interactions during prostate carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2695. doi:10.1158/1538-7445.AM2017-2695</jats:p
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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