1,720,968 research outputs found
Recellularized colorectal patient-derived scaffold as in vitro pre-clinical 3D model for drug screening
Full text linkPurpose: Colorectal cancer (CRC), the third most common cancer diagnosed in both men and women shows a highly ineffective therapeutic management. In contrast, CRC is a rare pediatric tumor, representing only 1% of all pediatric malignancies, with an incidence of approximately 1 per million. In this context, an urgent needing not yet addressed is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III colon cancer patients, both young and adults, without any predictive factor of efficacy. Secondly, in the field of drug discovery the critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We purpose to develop a patient-derived 3D preclinical model useful for drug evaluation that can mimic in vitro the patient's disease.
Methods: Surgically resected healthy colon mucosa and matched CRC were decellularized by a detergent-enzymatic treatment (DET). DET scaffolds were recellularized with HT29 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences and DNA amount quantification. Chemosensitivity test was performed using increasing concentration of 5-Fluorouracil (5-FU), range 0.1 μM to 100 μM. In vivo studies were carried out using the zebrafish (Danio rerio) animal model. For cancer xenograft assays, HT29 cells were injected into the duct of Couvier and subsequently incubated in 96-well plates with different concentrations of 5-FU. Drug absorption and perfusion along fresh and DET tumor scaffolds were evaluated qualitative using autofluorescence of doxorubicin (doxo, 594nm) and quantitative calculated by Darcy’s law. Buffy coat-derived monocytes were cultured with DET scaffolds and macrophages
lineage markers were evaluated with flow cytometry.
Results: Decellularization protocol allowed the preservation of original structure and ultrastructure (SEM analysis). Five days after recellularization with HT29 cell line, the 3D CRC model exhibited reduced sensitivity to 5-FU treatments compared with conventional 2D culture. Calculated IC50 resulted in 11.5 μM and 1.3 μM of 5-FU, respectively. In the zebrafish transplantation model, HT29 extravasation was detected after 4 days post injection. Moreover, we obtained a 5-FU IC50 comparable with that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that doxorubicin diffuses through the volume of 3D CRC model and co-localize with the cell nuclei which repopulate the 3D CRC scaffold. Finally, we observed that monocytes exposed to tumor decellularized ECM differentiated towards a pro-tumoral anti-inflammatory macrophage-like profile.
Conclusion: 3D CRC model could be preclinical reliable tool to bridge the gap between in vitro, in vivo and ex vivo drug testing assays. The 3D CRC model, translated in the pediatric setting, could help clinicians and oncologists to identify the most suitable treatment for the patient
Preclinical three-dimensional colorectal cancer model: The next generation of in vitro drug efficacy evaluation
No full textColorectal cancer (CRC), the third most common cancer diagnosed in both men and women in the United States, shows a highly ineffective therapeutic management. In these years neither substantial improvements nor new therapeutic approaches have been provided to patients. Performing the early lead discovery phases of new cancer drugs in cellular models, resembling as far as possible the real in vivo tumor environment, may be more effective in predicting their future success in the later clinical phases. In this review, we critically describe the most representative bioengineered models for anticancer drug screening in CRC from the conventional two-dimensional models to the new-generation three-dimensional scaffold-based ones. The scaffold aims to replace the extracellular matrix, thus influencing the biomechanical, biochemical, and biological properties of cells and tissues. In this scenario, we believe that reconstitution of tumor condition is mandatory for an alternative in vitro methods to study cancer development and therapeutic strategies
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
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
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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