1,720,977 research outputs found
Einfluss des HPV-Status und der Strahlentherapie auf den immunogenen Phänotyp von Kopf-Hals-Tumorzelllinien
Get PDFWhile the treatment of squamous cell carcinoma of the head and neck (HNSCC) with radiotherapy (RT) is complemented more and more by immunotherapy in clinical trials, little is known about the impact of the human papillomavirus (HPV) status or the applied RT scheme on the immune phenotype of the tumor cells. Therefore, we aimed to examine the impact of the HPV status of four human HNSCC cell lines on cell death and the expression of immune checkpoint molecules (ICMs) after RT with either hypofractionation irradiation (5x3.0Gy) or a high single dose (1x19.3Gy) via multicolor flow cytometry and quantitative PCR at an early time point after therapy. In our study, 5x3.0Gy RT induced high numbers of early and late apoptotic cells independent of the HPV status, but necrosis was only increased in the HPV-positive UM-Scc-47 cells. Generally, the immune stimulatory ICMs (CD70, CD137-L, ICOS-L) were less affected by RT compared to the immune suppressive ones (PD-L1, PD-L2, and the herpesvirus entry mediator (HVEM)). A significant higher surface expression of the analyzed ICMs was found after hypofractionated RT compared to a single high dose; however, regardless of the HPV status, with the exception of ICOS-L. Here, HPV-positive HNSCC tumor cells showed a stronger response to 5x3.0Gy than HPV-negative ones. On the RNA level, only minor alterations of ICMs were observed following RT, with the exception of the HPV negative cell line CAL33 treated with 5x3.0Gy, where PD-L2, HVEM and CD70 were significantly increased. We conclude that the HPV status may not distinctly predict immunological responses following RT, and thus cannot be used as a single predictive marker for therapy responses in HNSCC. In contrast, the patient-specific individual expression of ICMs following RT is preferable for the targeted patient selection for immune therapy directed against distinct ICM
Influence of Low Dose-Radiotherapy on the Phenotype of Fibroblast-like Synoviocytes in Dependence of Initial Inflammatory Status, Gender, and Irradiation Frequency
Get PDFBackground
Many inflammatory musculoskeletal diseases, such as rheumatoid arthritis (RA), are char
acterized by a painful swelling of joints, bone erosion, and cartilage reduction. Fibroblast-like
synoviocytes (FLS) are the key effector cells that perpetuate inflammation within the synovium.
In the inflammatory regions, hyperplasia takes place and FLS have a significantly lower rate
of apoptosis. FLS produce components of the synovial fluid that maintain the joint homeostasis
in healthy tissue. Low-dose radiotherapy (LD-RT) is known to ameliorate inflammation. It re
duces bone and cartilage loss by increasing apoptosis of the FLS and reducing their growth
rate in the human tumor necrosis factor-α transgenic (hTNFα tg) mice, which is an animal
model of RA. The hTNF-α tg mouse model is characterized by an overexpression of TNF-α
that results in the classical symptoms seen in RA patients. It has been shown that both the
dose and frequency of irradiation have an impact on cells; however, the exact underlying mech
anisms in LD-RT are mostly unknown. There are currently effective medications for RA, but
unfortunately there are still patients who do not react to it accordingly. Therefore, LD-RT could
potentially be a good additive therapy because it has been well-tested in clinical settings. Fur
thermore, as females are more susceptible to RA and the gender-dependent sensitivity of ra
diation is currently highly discussed, we also investigated whether there are gender effects for
LD-RT. The results were compared to healthy, wild type (C57Bl/6) littermates to understand
the impact of the initial inflammatory status on the radiation response of FLS.
Methods
The FLS of the female and male hTNFα tg and C57Bl/6 mice were isolated from the hind
paws and were cultivated. 24 hours after seeding, the cells were irradiated with varying X-ray
doses and frequencies (1x/2x), whereby the total dose was always 0; 0.1; 0.5; 1.0 or 2.0 Gray
(Gy). The gene expression (Cxcl-1, hTNF-α, Il-6, Mmp-13, Mmp-9, Opg, Tgf-β, Cdh11, Mmp
3, Rank-l and Vcam-1) and cytokine release (hTNF-α, CXCL-1, TGF-β and IL-6) of the FLS
from the mice were analysed using quantitative polymerase chain reaction (qPCR) analyses
and by investigating the FLS supernatants (SN) via enzyme linked immunosorbent assay
(ELISA), respectively.
Results
Our data showed that the untreated FLS pools display differences in terms of their cytokine
release, but that these differences are dependent on the sex and the inflammatory status. In
an inflammatory set-up, male-derived FLS pools secreted significantly higher properties of
hTNF-α than females. Furthermore, we were able to provide a broad overview of the gene
expressions of FLS after exposure to single or fractionated X-ray doses. Genes associated
with osteoclastogenesis, cartilage degrading enzymes and Tgf-β appeared to be particularly
impacted.
Conclusion
Given that we were able to demonstrate that female and male FLS pools significantly dif
fered in their cytokine milieu prior to any irradiation, it has become clear how important it is to
base future research upon this knowledge. It might offer a new perspective on gender-person
alised treatment options, but future research would be required to further verify and validate
these findings. There were no changes in gene expression or cytokine release in all healthy
FLS pools when applying X-ray doses lower than 2x1.0Gy, such as 2x0.05 Gy, 2x0.25 Gy or
2x0.5 Gy, irrespective of gender. We conclude that irradiation with those doses may not cause
harm to healthy surrounding FLS
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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