1,721,000 research outputs found
Proteomic approaches in colon cancer: promising tools for new cancer markers and drug targets discovery
No full textNovel technologies are needed from which to identify new and more efficient biomarkers and improved molecular targets for the expedient and accurate diagnosis and treatment of colorectal cancer. Many advances have been made in direct and virtual imaging for detection of polyps and malignant-type lesions. These require tissue verification before definitive intervention. Inclusion of a simple serum test, more accurate than CEA, especially for early cancer detection, would make virtual imaging much more successful. Proteomics, the study of the proteins and protein pathways involved in disease, is a new dimension in preclinical and clinical development. Mass spectrometric analysis of serum proteins has been shown to be a fast and simple approach yielding a large datastream of information to mine for biomarker patterns. Preliminary studies in a variety of cancers has shown this to be a promising direction. Protein arrays of tumor lysates allows assessment of expression and activation of proteins that may be specific colorectal cancer targets or targets that are shown to be universally important in cancer, such as those proteins involved in angiogenesis. Small quantities of tumor are needed for this technique and allow direct analysis of the biochemical events ongoing in the tumor and/or the stroma. This provides insight into the biology of the disease and can be used to identify targets for therapeutic intervention as well as to monitor the ability to successfully attack those targets. Together, these 2 technologies have been shown to advance the field and may be important new steps in diagnosis, prognosis, and treatment of colorectal cancer
L-asparaginase inhibits invasive and angiogenic activity and induces autophagy in ovarian cancer
Full text linkAbstract
Recent work identified L-asparaginase (L-ASP) as a putative therapeutic target for ovarian cancer. We suggest that L-ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cell—endothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human microvascular endothelial cells (HMVEC) were exposed to L-ASP at physiologically attainable concentrations and subjected to analyses of endothelial tube formation, invasion, adhesion and the assessment of sialylated proteins involved in matrix-associated and heterotypic cell adhesion. Marked reduction in HMVEC tube formation in vitro, HMVEC and ovarian cancer cell invasion, and heterotypic cell-cell and cell-matrix adhesion was observed (P < 0.05–0.0001). These effects were associated with reduced binding to ß1integrin, activation of FAK, and cell surface sialyl LewisX (sLex) expression. No reduction in HMVEC E-selectin expression was seen consistent with the unidirectional inhibitory actions observed. L-ASP concentrations were non-toxic to either ovarian cancer or HMVEC lines in the time frame of the assays. However, early changes of autophagy were observed in both cell types with induction of ATG12, beclin-1, and cleavage of LC-3, indicating cell injury did occur. These data and the known mechanism of action of L-ASP on glycosylation of nascent proteins suggest that L-ASP reduces of ovarian cancer dissemination and progression through modification of its microenvironment.
The reduction of ovarian cancer cell surface sLex inhibits interaction with HMVEC and thus HMVEC differentiation into tubes, inhibits interactio
Effetti sinergici dell’azione antitumorale dell’epigallocatechina-3-gallato in combinazione con il carboxyamido-triazole, un’inibitore dei canali del calcio voltaggio-indipendenti.
No full textExosomes released by k562 chronic myeloid leukemia cells promote endothelial cell tubular differentiation through uptake and cell-to-cell transfer
No full textExosomes, microvesicles of endocytic origin
released by normal and tumor cells, play an important role in cell-to-cell ommunication. Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human
umbilical endothelial cells (HUVECs). Fluorescent-labeled exosomes were nternalized by HUVECs during tubular
differentiation on Matrigel. Exosome localization was perinuclear early in differentiation, moving peripherally in cells
undergoing elongation and connection. Exosomes move within and between nanotubular structures connecting the remodeling endothelial cells. They stimulated angiotube
formation over a serum/growth factor-limited medium control,doubling total cumulative tube length (P = 0.003). Treatment of K562 cells with two clinically active tyrosine
kinase inhibitors, imatinib and dasatinib, reduced their total exosome release (P\0.009); equivalent concentrations of
drug-treated exosomes induced a similar extent of tubular differentiation. However, dasatinib treatment of HUVECs markedly inhibited HUVEC response to drug control CML
exosomes (P\0.002). In an in vivo mouse matrigel plug model angiogenesis was induced by K562 exosomes and abrogated by oral dasatinib treatment (P\0.01). K562 exosomes induced dasatinib-sensitive Src phosphorylation and activation of downstream Src pathway proteins in HUVECs.
Imatinib was minimally active against exosome
stimulation of HUVEC cell differentiation and signaling.
Thus, CML cell-derived exosomes induce angiogenic activity in HUVEC cells. The inhibitory effect of dasatinib on exosome production and vascular differentiation and
signaling reveals a key role for Src in both the leukemia and its microenvironment
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
Comparative protEome profiling and functional analysis of chronic myelogenous leucemia cell lines
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