1,720,974 research outputs found
The IGF-I receptor in cell growth, transformation and apoptosis
No full textThe following brief summary is based on a recent
review by Rubin and Baserga w1x, and the reader is
referred to that review for extended references. A
simplified representation of the IGF system includes
3 receptors, 3 ligands and 6 IGF binding proteins
.IGFBPs.. The ligands are the mature IGF-I.70
aminoacids., the mature IGF-II.67 aminoacids. and
insulin. The receptors are the type I insulin-like
growth factor receptor.IGF-IR., the insulin receptor
.IR. and the IGF-II receptor .IGF-IIR.. In terms of
cellular proliferation, the IGF-IR is the most active of
the 3 receptors.see below.: it is activated by all 3
ligands, and, although it has several functional features
in common with the IR w2x, the b subunit of the
IGF-IR is 10 times more mitogenic than the beta
subunit of the IR w3x. Insulin at supraphysiological
concentrations also activates the IGF-IR; this is an
important point to remember, because when insulin is
used at mg concentrations, it exerts its mitogenic
stimulation through the IGF-IR w4x. Under appropriate
conditions, the IR is mitogenic
Rhabdomyosarcomas are potential target of MAGE-specific immunotherapies.
No full textThe search for alternative strategies of therapy remains a major issue for most
neoplastic diseases. The expression of several tumor antigens makes human
rhabdomyosarcomas, which are the most frequent form of soft tissue tumor in
children, a good candidate for tumor-specific immunotherapy. To assess the
feasibility of this approach, we evaluated the ability of rhabdomyosarcoma cell
lines to process and present the MAGE-A tumor antigens to effectors of the
immune system. To this end, we investigated recognition of MAGE-A-positive
rhabdomyosarcoma cells by HLA-B*3701-restricted T cells specific for a
MAGE-A-derived peptide. Low level of HLA expression impaired recognition of the
tumor cells. Therefore, to obtain HLA expression avoiding the use of IFN-gamma
and TNF-alpha, which could affect the proteasome activity, a rhabdomyosarcoma
line was transduced by a retroviral vector encoding the HLA-B*3701 allele.
Recognition of the infected cells was then observed also in the absence of
IFN-gamma and TNF-alpha treatment, thus demonstrating that rhabdomyosarcoma
cells were indeed able to naturally process and present the MAGE-A antigens.
These results demonstrate that rhabdomyosarcoma cells expressing MAGE-A can be
targets of tumor-specific effectors, suggesting the feasibility of clinical
protocols of specific immunotherapy also for the treatment of rhabdomyosarcom
P53 GENE POINT MUTATIONS IN RELATION TO P53 NUCLEAR-PROTEIN ACCUMULATION IN COLORECTAL CANCERS
No full textIt is known that structural alterations of the p53 tumour suppressor gene cause malignant transformation and tumour progression in colorectal mucosa. In this study, 38 colorectal cancers were analysed for mutations detected in the p53 gene by single-strand conformational polymorphism and DNA sequence analysis, and the results were compared with p53 protein expression detected by immunohistochemistry. A very strict association (P<0.0001) was found between genetic alterations and protein accumulation, as detected by the PAb 1801 monoclonal antibody. p53 expression and gene mutations were more frequent in rectal than in colonic cancers. No relation was observed with Dukes' stage, even though most of the mutations were at exon 7 in Dukes' A-B cancers and almost all mutations at exon 8 were observed in Dukes' C-D cancers. DNA ploidy was not generally associated with p53 protein expression or gene mutations. However, 83 per cent of cases with exon 5 and 6 mutations were diploid or near-diploid and 71 per cent of cases with mutations at exons 7 and 8 were aneuploid. Tumours with p53 gene mutations at exon 5 had a higher median [H-3]thymidine labelling index (17 per cent) than those with mutations at exons 6, 7, and 8 (11.8 per cent)
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
NGR-TNF, a novel vascular-targeting agent, does not induce cytokine recruitment of proangiogenic bone marrow-derived cells.
No full textThe tumor vessel targeting agent NGR-TNF controls the different stages of the tumorigenic process in transgenic mice by distinct mechanisms.
No full textNGR-TNF is a vascular targeting agent in advanced clinical development, coupling tumor necrosis factor-a (TNF) with the CNGRCG peptide, which targets a CD13 isoform specifically expressed by angiogenic vessels. Antitumor efficacy of NGR-TNF has been described in different transplantation tumor models. Nevertheless, the mechanism underlying its activity is not fully understood. In the wild type and in the immunodeficient (RAG¡/¡) RIP1-Tag2 models of multistage pancreatic carcinogenesis, we demonstrate that CD13 is highly expressed on endothelial cells of hyperplastic and angiogenic islets, whereas its expression is down regulated in tumors where it partially colocalize with pericytes. In vivo
CNGRCG peptides coupled to fluorescent nanoparticles (quantum dots) bind to CD13 and colocalize with anti-CD31, in pancreatic islets. At early stage, low doses of NGR-murine (m)TNF have a direct cytotoxic effect inducing endothelial cell apoptosis, reducing vessel density and eventually inhibiting the development of angiogenic islets. At a later stage, NGRmTNF is able to reduce tumor growth inducing vascular normalization, exclusively when treatment is carried out in the immunocompetent mice. Interestingly, NGR-mTNF-treated tumors from these mice are characterized by CD8C T cell infiltration. At molecular level, overexpression of genes involved in vessels normalization was detected only in NGRmTNF- treated tumors from immunocompetent mice. These findings identified a new mechanism of action of NGR-mTNF, providing support for the development of new therapeutic strategies combining chemotherapy or active/adoptive immunotherapies to low dose NGR-TNF treatment
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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