1,720,959 research outputs found
The NPM1 wild-type OCI-AML2 and the NPM1-mutated OCI-AML3 cell lines carry DNMT3A mutations.
No full textRole of microRNAs in the activity of new therapeutic inhibitors of Src kinases in CD133+ colorectal cancer cells
No full textColorectal cancer (CRC) is the second most common cause of cancer-related death (after lung cancer) and, recently CRC stem cells have been identified as CD133+ CRC cells and isolated. In CRC cells, a significant increase of cellular Src kinase activity over that observed in the adjacent normal mucosa, with its activation being linked to malignant potential has been observed. Based on this background, our hypothesis is that a strong inhibition of Src kinase in CD133+ CRC cells can be beneficial for the therapy of this type of cancer. To this purpose new inhibitors of Src phosphorilation were utilized in order to study and inhibit the progression of CRC at the level of CD133+ CRC cells.
Decrease of HT-29 colon cancer cell number after treatment with different novel Src inhibitors.
The novel Src kinase inhibitors SI34 - SI83 - S7 - S13, from pyrazol [3,4,d-] pyrimidine derivatives, have been tested on the CD133+ in HT-29 cell line (about 98% CD133+ cells). The dose response curves have been performed by using the concentrations of 2 - 10 - 25 - 50 μM and measuring the effect in terms of total cell number after 24 and 48 hours of treatment. Whereas SI34 e SI83 are effective at concentrations of 25 μM after 48 hours of treatment, S7 e S13 are more potent since determined a decrease in cell number at lower concentrations (10 μM after the first 24 hours of treatment, with a maximum of significant decrease reached with the S13 compound.
Cell cycle and proliferation analysis of S13-treated HT-29 colon cancer cells.
The cytofluorimetry analysis of HT-29 cells showed that 24 hours treatment with 10 μM S13 inhibits the progression of cell cycle. S13-treated cells undergo to a consistent apoptosis after 72 hours of treatment. Moreover,[3H]thymidine uptake assay demonstrated that S13 Src kinase inhibitor significantly inhibited the proliferation of HT-29 cells after 24 and 48 h of culture.
MicroRNA expression induced by S13 in HT-29 colon cancer cells.
Total RNA was extracted from untreated HT-29 cells and from HT-29 cells after 6h and 12h of treatment with 10 μM of S13 and RNA quality control analysis was performed.
High definition Agilent 15K miRNA microarray based on Sanger miRbase12 was hybridised with total RNA and treated cells showed altered expression of several miRNAs.
Among these, has-miR-494 displayed up-regulation in HT-29 cells after 6h of treatment with increased expression at 12h (> 2-fold).
In order to validate the microarray results, the expression levels of 3 most differentially up-regulated miRNAs and 2 most differentially down-regulated miRNAs were examined by qRT-PCR using an All-in-OneTM miRNA qRT-PCR Detection Kit (GeneCopoeia, Rockville, MD, USA) and was performed by 7900HT instrument (Applied Biosystems, USA).
Our results showed that the expression levels of hsa-miR-1225, mir-197-3p, and hsa-miR-574-3p were not proven to be significant and not in line with the microarray results, whereas hsa-miR-494, hsa-miR-1207-5p were significantly increased in agreement with microarray data.
These reported preliminary results strongly support the starting hypothesis since 1) the new Src inhibitors inhibited the growth of CD133+ HT-29 CRC cells; 2) they significantly promoted HT-29 apoptosis and inhibited its proliferation; and 3) One of these new Src inhibitors significantly modulated the expression of different miRNAs in HT-29 cells.
Further studies are required to confirm our preliminary data, to clarify the function of miR-494 in HT-29 CRC cells via transfection experiments and its role in transduction pathway downstream of src kinases.
The goal of this study is to identify new drug targets useful for diagnostic and therapeutic purposes in CRC.
Acknowledgment: Supported in part by “Fondazione Cassa di Risparmio di Terni”
Anti-rheumatoid arthritis activity of decoction from the leaves of the tree Artocarpus tonkinensis used in Vietnamese traditional medicine
No full textThe decoction of the leaves of the tree Artocarpus Tonkinensis (AT) is used in traditional Vietnamese medicine for the treatment of rheumatoid arthritis and backache by the ethnic minority called Black Hmong.
In order to scientifically validate the traditional utilization of this ancient Vietnamese remedy, collagen-induced arthritis, a widely accepted experimental mouse model of autoimmune arthritis, has been used.
DBA/1 mice treated with collagen plus Freund adjuvant at day-0, were concomitantly given the decoction of the leaves of At ad libitum, whereas the control group were given water. After 28 days, mice were re-challenged with collagen plus Freund adjuvant. In the following two weeks, 50% of control mice developed arthritis clinically evaluated by joint swelling. The scoring system for subjective evaluation of arthritis severity gave the maximum score of 4, whereas no mice in the At treated group developed a clinical evident arthritis (0 score). Histology of joints evidenced a wide cartilage destruction and an intense cell inflammatory infiltration in control mice, whereas cartilage was normal and either no or very mild cell inflammatory infiltration was observed in At-treated mice. The gene expression, evaluated by the mouse inflammatory response & autoimmunity plate of the Qiagen RT2 profiler PCR array profile, of joints evidenced that 39 genes involved in autoimmune diseases were modulated in At-treated mice compared to controls. Of them, 23 genes were up-regulated whereas 16 genes down-regulated in At-treated mice compared to controls. Additionally, analysis of lymph nodes showed that the number of cells were doubled in At-treated mice compared to controls. Real-time PCR analysis and ELISA experiments are currently under way to validate gene expression profile results.
In conclusion, our experiments validated the traditional therapeutic uses of At decoction and showed that different autoimmunity and inflammatory genes are involved in its therapeutic mechanism.
Acknoledgment: This work was supported in part by a project of Ministero degli Esteri e della Cooperazione Internazionale
Integration of Traditional and Western Medicine in Vietnamese Populations: A Review of Health Perceptions and Therapies
No full textIn Vietnam, two types of traditional medicine (TM) are practiced: Thuoc nam, medicine of the South, and thuoc bac, medicine of the North, both of which are largely based on herbal drugs used by different Vietnamese ethnic groups. This review presents recently published information from various databases regarding TM, especially herbal drugs, and its integration with Western medical practices outside and inside Vietnam. We first discuss the integration of traditional and modern health concepts by Vietnamese immigrants living outside Vietnam. Next, we describe native and emigrated health education and practices of pharmacy students, health professionals, and citizens living in Vietnam. Finally, we report the recent biological validation of medicinal plants and non-herbal therapies emerging from Vietnamese TM and their current and potential medical uses as identified by Western approaches. The main example described here involves utilization of the tree Artocarpus tonkinensis by the ethnic minority of Black Hmong in northern Vietnam, who use a decoction of its leaves to treat arthritis and backache without apparent adverse effects. Our comprehensive review emphasizes that, although Vietnam has a very rich collection of TM practices (particularly the use of herbal drugs), these therapies should be biologically and clinically validated with modern Western methods for optimal integration of Western and traditional medicine in global populations
The gene mutation landscape of acute myeloid leukemia cell lines and its exemplar use to study the BCOR tumor suppressor
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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
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