1,720,983 research outputs found
Abstract 35: Chemo-radiotherapy induces tolerogenic STAT3 signaling in circulating myeloid-derived suppressor cells in patients with head and neck squamous cell carcinoma (HNSCC)
No full textAbstract
Background and Objectives: While radiation therapy (RT) and certain types of chemotherapy are potentially immunogenic, they rarely generate antitumor immune responses. Our previous studies in mice showed that effects of RT on solid tumors are limited by the activation of tumor-promoting and immunosuppressive protein STAT3 in tumor-associated myeloid cells. Current study focused on determining whether STAT3 plays similar role in promoting immune evasion and therapeutic resistance in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemo-radiation therapy.
Patients, Materials, and Methods: 15 patients with stage III-IV HNSCC who received CRT with curative intent consented to collect blood and tissue biopsy (IRB#14255). Before and during week 2 of RT, tissue biopsies were collected of a cancer-involved lymph node that received full dose radiation. Blood specimens were collected from patients before and during RT on weeks 1, 2, 4, 6, and 7, as well as 6-12 weeks after treatment completion. After isolation, PBMCs and plasma samples were cryopreserved and stored in liquid nitrogen for no longer than 12 months. For flow-cytometric analysis, PBMC were thawed in 37°C water bath, washed and pre-incubated in RPMI1640 media supplemented with 20% of autologous plasma for 2 h. Cells were then stained with fluorescently-labeled antibodies specific for CD14, CD15, CD33, and HLA-DR (eBioscience). For intracellular staining of phosphorylated-STAT3 (pSTAT3), cells were fixed, permeablized and then stained with fluorescently-labeled antibodies specific to tyrosine 705-phosphorylated STAT3 (pSTAT3; BD Biosciences) or an isotype control. mRNA was isolated from PBMC from baseline and Week 2 draw during RT from 6 patients. Expression of 730 genes selected for immune profiling was evaluated by nCounter Immune Cell Profiling Assay (Nanostring) and data was analyzed using nSolver software (Nanostring).
Results: CRT resulted in the accumulation of potently immunosuppressive polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs; HLA-DRloCD14-CD15+) in circulation of HNSCC patients. The PMN-MDSCs had high levels of activated STAT3, which correlated with the expression of immune checkpoint inhibitor, programmed death-ligand 1 (PD-L1). The analysis of gene expression in patients' PBMC indicated increased expressions of multiple protein mediators that promote immune suppression and MDSC functions such as IL-1β (20.7 fold, p=1.59E-5), IDO (3.6 fold, p=0.1) and VEGF (13.2 fold, p=7.97E-6) during RT. Pathway analysis using KEGG data base predicted that RT enhanced NF-κB signaling in PBMC. In contrast, number of circulating CD3+ T cell was significantly reduced and expression of genes involved in T-cell cytotoxicity including Granzymes A/K/M and Perforin-1 were decreased by greater than twice (p<0.05) during RT. In addition, significant increase in expression of immune checkpoint molecules; PD-L1 (2.7 fold, p=0.05) and TIM-3 (10.7 fold, p=2.45E-6), was observed.
Conclusion: The data suggest that RT induces accumulation of PMN-MDSC in circulation and activation of STAT3 which positively regulates suppressive function of MDSC. Correspondingly, the percentage of T cells in circulation and the expression level of genes regulating cytotoxic functions were significantly reduced during RT. Taken together, the results suggest that RT could induce tolerogenic effects in HNSCC patients. Our further studies will test the feasibility of using the TLR9-targeted STAT3 inhibitors, alone or combination with checkpoint inhibitors, to overcome immune suppression and improve RT efficacy in syngeneic mouse models of HNSCC.
Citation Format: Haejung Won, Sagus Sampath, Erminia Massarelli, Ellie Maghami, Marcin Kortylewski. Chemo-radiotherapy induces tolerogenic STAT3 signaling in circulating myeloid-derived suppressor cells in patients with head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 35.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Abstract 36: Changes in cellular and molecular immune markers in the peripheral blood of patients undergoing chemotherapy and radiation for squamous cell carcinoma of head and neck: A prospective pilot study
No full textAbstract
Objective: In order to help further development of novel immunotherapeutic targets related to signal-transducer and activator of transcription-3 (STAT3) in squamous cell carcinoma of head and neck (SCCHN), data are needed to help understand changes in immune-mediated signaling during treatment. The purpose of this study was to analyze changes in the mRNA or protein expression of inflammatory or immunosuppressive mediators in peripheral blood mononuclear cells (PBMC) or plasma, in SCCHN patients receiving concurrent chemotherapy and radiation therapy (CRT).
Methods: This was a prospective biospecimen collection study of 15 patients with stage III-IV SCCHN who received CRT with curative intent. Blood specimens were obtained before, during weeks 1, 2, 4, 6, and 7 of CRT, and 6-12 weeks after treatment completion. Plasma and PBMC were separated from patients' blood using Vacutainer CPT tubes (BD Bioscience) within 2 hours after collection by centrifugation at 1800×g for 20 min at room temperature and stored in -80°C. Plasma samples were analyzed for 30 human cytokines and chemokines using Luminex FLEXMAP 3D system at the Clinical Immunobiology Correlative Studies (CICSL) core at City of Hope. mRNA was isolated from PBMCs acquired at the baseline and at the second week draw during RT from 6 patients and expression of 730 genes selected for immune profiling was evaluated using nCounter Immune Cell Profiling Assay, and data were analyzed using nSolver software (Nanostring).
Results: Among the plasma level of 30 cytokines tested by Luminex Assay, IL-6 showed cumulative increase during RT (one-way ANOVA, p=0.046). At 6 week post RT, IL-6 level decreased comparable to baseline level. Plasma level of IFN-gamma was significantly increased at 2 week of RT and the level remained unchanged until 12 week post CRT (p=0.0004). In contrast, we observed pro-inflammatory cytokine IL-12 was significantly decreased during CRT (p=0.0004). Plasma level of a tumor promoting cytokine HGF was significantly increased during and 12 week post CRT (p=0.0035). Comparison of gene expression profiles in PBMC from 6 patients between baseline and the second week of CRT indicates that mRNA expression of 335 immune-regulators are differentially expressed (p&lt;0.05) among 740 tested. Consistent with the plasma cytokine analysis, mRNA level of IL-6 in PBMC was 13.9 fold increased (p=0.003). Subsequently, increase in STAT3 expression was observed (1.7 fold, p=0.002) since IL-6 stimulates Janus kinase (JAK)-STAT pathway. In addition, mRNA expression of Th2 cytokines including IL-10, IL-5, and TGFb1 were significantly increased by greater than 2 folds (p&lt;0.05).
Conclusion: These results suggest CRT affects immune activation in SCCHN patients systemically, which may contribute to immune suppression and disease relapse after treatment. Our data provide an impetus for investigating STAT3-targeted therapies in SCCHN.
Citation Format: Sagus Sampath, Hae Jung Won, Ellie Maghami, Erminia Massarelli, Nayana Vora, Lalit Vora, Marcin Kortylewski. Changes in cellular and molecular immune markers in the peripheral blood of patients undergoing chemotherapy and radiation for squamous cell carcinoma of head and neck: A prospective pilot study [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 36.</jats:p
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
