1,721,109 research outputs found
Cancer Stem Cells: From Birth to Death
No full textAbstract Conspicuous investigations have proven the role of cancer stem cells (CSCs) in the onset and progression of a plethora of liquid and solid neoplasms.
CSCs are endowed with the capability of initiating tumor growth and becoming dormant at distant organ sites just waiting for optimal conditions amenable for metastatic outgrowth. This cancer subpopulation is inherently resistant to anticancer therapeutics, and its targeting could avoid metastatic disease, which is largely incurable, and clinical relapses. CSCs are considered the Achilles heel of cancer. However, many efforts are necessary to identify univocal CSC markers as well as specific CSC biomarkers of therapeutic response.
Here, we summarize CSCs’ peculiarities and highlight novel anticancer compounds coping with the hallmarks of CSCs, comprising the resistance to cell death,
their quiescent state, the immune suppression, the epithelial to mesenchymal transition (EMT), and their metabolic adaptation to a hostile microenvironment
Designing an Intelligent Cyber-Biological System for Enhanced Analysis and Monitoring of Organoids
No full textOrganoids replicate key aspects of organ function and present a microcosmic representation of the in-vivo state, offering unprecedented opportunities for disease modeling, drug testing, and personalized medicine. However, the complexity of these heterogeneous biological models requires innovative approaches to optimize the analysis and monitoring. This work outlines an Intelligent Cyber-Biological System (ICBS) with a multi-layered MAPE-K structure for enhanced analysis and real-time organoid monitoring. Starting with the Laboratory Layer, the ICBS harnesses real-time data from organoid cultures, which the Data Layer processes and archives for insight extraction. The Intelligence Layer employs advanced machine learning (ML) models for pattern recognition and predictive analytics, identifying critical development stages and treatment responses. In the Decision Layer, perceptions derived from ML-generated guide strategic decision-making for culture condition adjustments and further examinations. The ICBS framework engages researchers in its findings, fostering decision implementation and a responsive feedback system. Its real-world application in the intestinal organoid case study demonstrates the feasibility and effectiveness of the proposed solution, increasing the efficiency of experimental processes and the predictive accuracy of treatment outcomes
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
The C-X-C Motif Chemokine Ligand 1 Sustains Breast Cancer Stem Cell Self-Renewal and Promotes Tumor Progression and Immune Escape Programs
Full text linkBreast cancer (BC) mortality is mainly due to metastatic disease, which is primarily driven by cancer stem cells (CSC). The chemokine C-X-C motif ligand-1 (CXCL1) is involved in BC metastasis, but the question of whether it regulates breast cancer stem cell (BCSC) behavior is yet to be explored. Here, we demonstrate that BCSCs express CXCR2 and produce CXCL1, which stimulates their proliferation and self-renewal, and that CXCL1 blockade inhibits both BCSC proliferation and mammosphere formation efficiency. CXCL1 amplifies its own production and remarkably induces both tumor-promoting and immunosuppressive factors, including SPP1/OPN, ACKR3/CXCR7, TLR4, TNFSF10/TRAIL and CCL18 and, to a lesser extent, immunostimulatory cytokines, including IL15, while it downregulates CCL2, CCL28, and CXCR4. CXCL1 downregulates TWIST2 and SNAI2, while it boosts TWIST1 expression in association with the loss of E-Cadherin, ultimately promoting BCSC epithelial-mesenchymal transition. Bioinformatic analyses of transcriptional data obtained from BC samples of 1,084 patients, reveals that CXCL1 expressing BCs mostly belong to the Triple-Negative (TN) subtype, and that BC expression of CXCL1 strongly correlates with that of pro-angiogenic and cancer promoting genes, such as CXCL2-3-5-6, FGFBP1, BCL11A, PI3, B3GNT5, BBOX1, and PTX3, suggesting that the CXCL1 signaling cascade is part of a broader tumor-promoting signaling network. Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC
Meeting the Challenge of Targeting Cancer Stem Cells
Full text linkNotwithstanding cancer patients benefit from a plethora of therapeutic alternatives, drug resistance remains a critical hurdle. Indeed, the high mortality rate is associated with metastatic disease, which is mostly incurable due to the refractoriness of metastatic cells to current treatments. Increasing data demonstrate that tumors contain a small subpopulation of cancer stem cells (CSCs) able to establish primary tumor and metastasis. CSCs are endowed with multiple treatment resistance capabilities comprising a highly efficient DNA damage repair machinery, the activation of survival pathways, enhanced cellular plasticity, immune evasion and the adaptation to a hostile microenvironment. Due to the presence of distinct cell populations within a tumor, cancer research has to face the major challenge of targeting the intra-tumoral as well as inter-tumoral heterogeneity. Thus, targeting molecular drivers operating in CSCs, in combination with standard treatments, may improve cancer patients' outcomes, yielding long-lasting responses. Here, we report a comprehensive overview on the most significant therapeutic advances that have changed the known paradigms of cancer treatment with a particular emphasis on newly developed compounds that selectively affect the CSC population. Specifically, we are focusing on innovative therapeutic approaches including differentiation therapy, anti-angiogenic compounds, immunotherapy and inhibition of epigenetic enzymes and microenvironmental cues
Colorectal Cancer Stem Cells: From the Crypt to the Clinic
Full text linkSince their first discovery, investigations of colorectal cancer stem cells (CSCs) have revealed some unexpected properties, including a high degree of heterogeneity and plasticity. By exploiting a combination of genetic, epigenetic, and microenvironmental factors, colorectal CSCs metastasize, resist chemotherapy, and continually adapt to a changing microenvironment, representing a formidable challenge to cancer eradication. Here, we review the current understanding of colorectal CSCs, including their origin, relationship to stem cells of the intestine, phenotypic characterization, and underlying regulatory mechanisms. We also discuss limitations to current preclinical models of colorectal cancer and how understanding CSC plasticity can improve the development of clinical strategies
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
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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