1,720,967 research outputs found
Identification of Molecular Determinants of Tumor Sensitivity and Resistance to Anticancer Drugs
No full textResistance to drugs is a major problem in cancer chemotherapy. Various cellular mechanisms of drug resistance have been identified in cultured tumor cell lines selected for growth in the presence of sublethal concentrations of various anticancer drugs. They involve drug transport and detoxification, qualitative or quantitative alterations of the drug target, repair of drug-induced DNA lesions, and alterations in signaling or execution of apoptosis. More recently, the possibility to simultaneously analyze the expression of thousands of genes using DNA microarrays has allowed exploring the relationships between gene expression and sensitivity to several anticancer drugs. A number of studies using microarrays for identifying genes governing tumor chemosensitivity focused on tumor cell lines. Some clinical studies have also been carried out to investigate whether tumor gene expression patterns could predict clinical response to chemotherapy. Results of these studies are encouraging, indicating that individualization of drug treatment based on multigenic response-predictive markers is feasible
Delivery of methoxymorpholinyl doxorubicin by interleukin 2-activated NK cells: effect in mice bearing hepatic metastases
Full text linkThe possibility of using interleukin 2 (IL-2)-activated natural killer cells
(A-NK) to carry methoxymorpholinyl doxorubicin (MMDX; PNU 152243) to
liver-infiltrating tumours was explored in mice bearing 2-day established M5076
reticulum cell sarcoma hepatic metastases. In vitro, MMDX was 5.5-fold more
potent than doxorubicin against M5076 tumour cells. MMDX uptake by A-NK cells
correlated linearly with drug concentration in the incubation medium [correlation
coefficient (r) = 0.999]; furthermore, as MMDX incorporation was readily
reproducible in different experiments, the amount of drug delivered by A-NK cells
could be modulated. In vivo experiments showed that intravenous (i.v.) injection
of MMDX-loaded A-NK cells exerted a greater therapeutic effect than equivalent or
even higher doses of free drug. The increase in lifespan (ILS) following A-NK
cell delivery of 53 microg kg(-1) MMDX, a dosage that is ineffective when
administered in free form, was similar to that observed in response to 92 microg
kg(-1) free drug, a dosage close to the 10% lethal dose (ILS 42% vs. 38%
respectively). These results correlated with pharmacokinetic studies showing that
MMDX encapsulation in A-NK cells strongly modifies its organ distribution and
targets it to tissues in which IL-2 activated lymphocytes are preferentially
entrapped after i.v. injection
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
Pentoxifylline and its major oxidative metabolites exhibit different pharmacological properties
No full textPrevious investigations indicate that some of the metabolites of the hemorheological agent pentoxifylline (PTX), namely 1-(5-hydroxyhexyl)-3,7-dimethylxanthine (M1), 1-(4-carboxybutyl)-3,7-dimethylxanthine (M4) and 1-(3-carboxypropyl)-3,7-dimethylxanthine (M5), concur to some of the biological effects of the drug. However, information on the bioactivity of the major circulating oxidative metabolites of PTX (M4 and M5) is scanty. Here, we compared the effects of M4 and M5 with that of PTX and its major reductive metabolite, M1, on TNF-alpha production and cytotoxicity, endothelial cell proliferation and on the ATPase activity related to some ATP-binding cassette (ABC) transporters. Unlike PTX and M1, M4 and M5 poorly inhibited lipopolysaccaride-stimulated tumor necrosis factor-alpha (TNF-alpha) release by RAW 264.7 murine macrophages, and did not affect at all cell proliferation and upregulation of TNF-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) in H5V endothelioma cells. By contrast, M4 and M5 were more effective than PTX and M1 in protecting WC/1 murine fibrosarcoma cells from TNF-alpha cytotoxicity. Moreover, results from ATP hydrolase assays indicated that neither PTX nor its tested metabolites interacted significantly with the human multidrug resistance transporters p-glycoprotein/multidrug resistance 1 (MDR1), multidrug resistance-related protein 1 (MRP1), and breast cancer resistance protein (BCRP). Based on these results and literature data, M5, retaining some of the PTX effects but lacking in significant inhibition of TNF-alpha production, may be a promising candidate drug for certain pathologic conditions
- …
