1,721,066 research outputs found
Identification and Targeting of Stem Cell-Activated Pathways in Cancer Therapy
Get PDFThe hierarchical organization and heterogeneity that are present within malignancies have been recently attributed to stem cell-like subset of tumor cells. Cancer Stem Cells (CSCs) have gained an exclusive interest as they are identified to push tumor growth and seed metastasis and are responsible for therapy failure and tumor resistance [1]. The molecular mechanism that drives the CSC population
has started to emerge, and the identification and origin of factors that maintain or even induce a CSC phenotype remain an intense area of research. This special issue contains seven articles, four reviews, and three original studies, highlighting the recent advances in CSC-activated pathways, with particular emphasis on the cross-talk between the CSC and the tumor microenvironment (TME). The studies presented here also highlighted compounds (e.g., epi-drugs) that are described to modulate CSCs and TME-activated pathways and thus can be subsequently exploited for therapeutic use. P. Gener et al., in a review article, discussed the overlapping phenotype between CSC and mesenchymal cancer cells, in terms of origin, activated pathways, and the implication for cancer treatment. Indeed, similarly to CSC, a link between epithelial to mesenchymal transition of cancer cells and metastasis as well as resistance to anticancer agents has been proposed [2]. Although other reports suggested that EMT is not necessary for metastasis, but rather it is the tumor microenvironment that regulate epithelial or mesenchymal state, still agent able to target common pathways regulating both CSC and EMT (e.g., TGF-β and NF-κβ signaling) showed antimetastatic potential and improved anticancer treatments. However, the authors also suggested that the strategies to prevent tumor remission by targeting the highlighted pathways should include integrated combining approach that take in account the intrinsic dynamism characterizing, within the tumor, the interconversion capacity of non-CSCs to new CSCs and mesenchymal cells, via EMT activation. As suggested above, several evidences demonstrated a critical role of the microenvironment in regulating CSC and their involvement in tumor progression. In this regard C. Ciardiello et al. reviewed the bidirectional communication mechanisms between the CSC and the microenvironment,
mediated by extracellular vesicles (EVs). EVs are considered as one of the most effective vehicles of information among cells, and recent findings demonstrated that they play an important role in cancer development and progression, by transferring information between cancer cells as well as between cancer cells and tumor microenvironment, at both paracrine and systemic level [3]. EVs are highly heterogeneous;however, they can be classified in two major classes: the shed microvesicles, formed through the direct budding of the plasma membrane, and the exosomes, small size vesicles (30-150 nm) generated through the classical endosome-multivesicular body pathway [3]. The specific role of this latter class of vesicles was reviewed by J. Xu et al. They speculate that exosomes play a role in maintaining homeostasis between non-CSCs and CSCs within the tumor. The authors described how exosomes can regulate both EMT and CSC phenotype activating Hindawi Stem Cells International Volume 2019, Article ID 8549020, 2 pages https://doi.org/10.1155/2019/8549020
stem-related signaling pathways (e.g., Wnt, Notch, or Hedgehog pathways) by docking on cancer cell receptors and/or transferring their cargo inside the cells. Epigenetic alterations play an important role in the initiation
and progression of several cancers. Moreover, since epigenetic alterations are dynamic and generally reversible, epigenetic manipulation has emerged as an attractive novel anticancer treatment. Increasing evidences support the significance of epigenetic regulation in CSC features [4]. DNA methylation and histone acetylation are two epigenetic modifications that participate in the modulation of many gene expressions, which regulate important cellular activity such as proliferation, differentiation, and migration [5]. While the role of DNA methylation in CSCs is relatively well established, the role of histone and nonhistone protein acetylation is still not completely clear [4]. In this context, different hematological and solid tumors are characterized by deregulation of the protein acetylation pattern as a result of genetic or epigenetic changes [6]. Protein acetylation is catalyzed by acetyltransferases and deacetylases, through the addition and removal of acetyl groups to lysine residues, respectively [5]. Small molecule inhibitors of both acetyltransferases and deacetylases are in clinical trials, and four deacetylase inhibitors have been approved by FDA for the treatment of hematological malignancies [6]. In this issue, D. Trisciuoglio et al. reviewed the physiological and pathological roles of acetyltransferase enzymes as well as their involvement in the regulation of stem cell renewal and differentiation in both normal and cancer cell population. The authors also discussed the potential of acetyltransferase inhibitors as novel anticancer drugs. Two additional epi-drugs, 5-azacytidine (AZA) and 5-aza- 2 ′-deoxycytidine (DAC), have been also approved by FDA in hematological tumors, and several studies have shown their
therapeutic potential also in solid tumors [5]. Here, K. Agrawal et al. demonstrated for the first time the influence of stromal cells and of their secretome on cancer cell response to AZA and DAC. In details, considering that in metastatic setting the interactions between colorectal cancer cells (CRCs) and stroma at the distant metastatic sites are important, the authors investigated the effects of colonunassociated normal human foreskin and lung fibroblasts, of their radiation-induced senescent counterparts and of their conditioned medium, on CRC cell response to AZA and DAC. Interestingly, although opposite effects of fibroblasts and of their conditioning medium on AZA and DAC antitumor effects were reported and discussed, the authors suggested the potential of the tumor-stroma ratio in predicting the outcome of DNA-demethylating epigenetic cancer therapy.
Finally, this special issue contains two additional original studies on two interesting topics. The first study by Q.-Y. Liu et al. deals with the potential of human normal mesenchymal stem cells (MSCs). MSCs can be isolated from multiple sources including bone marrow, fat, umbilical cord, and menstrual blood and hold a great potential in regenerative medicine and in cell-based therapies in different clinical applications [7]. Interestingly, the authors presented several evidences, both in vitro and in vivo xenograft model, demonstrating that human menstrual blood-derived stem cells can inhibit cervical cancer cell growth and thus suggesting an original novel cell-therapy anticancer approach. The second study by F. Basit et al. evaluated the expression of the Myc oncogenes and Mxd antagonists in hematopoietic stem cell and myeloid progenitor populations in the Flt3-ITD-knockin myeloproliferative mouse model. Indeed, mutations in the FLT3 gene have been reported in acute myeloid leukemia (AML) and were associated with poor prognosis, while Myc dysregulation has been reported in
hematological malignancies. The authors, by highlighting a cross-talk between the FLT3 receptor and Myc, suggested the potential of combination therapies with tyrosine kinase inhibitors and Myc antagonists in treating AML
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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