1,720,958 research outputs found
Synergic interaction of chemotherapy and PDT by co-delivery of DTX and photosensitizers in nanoparticles
Full text linkThe combinations of two or more drugs/treatment modalities are increasingly considered very useful tools to increase efficacy and reduce side effects of anticancer therapies. To this aim, photodynamic therapy (PDT) is being widely investigated in combination with established therapeutic modalities including chemotherapy. In this connection, the progresses in the field of nanomedicine led to the production of nanocarriers offering opportunities to ameliorate the control of drug concentration ratios that is a prerequisite for obtaining synergic effects in combination therapy.
In this PhD thesis, PLGA-PEI hyaluronic acid (HA)-targeted nanoparticles (NPs) and keratin NPs were used for the co-delivery to cancer cells in vitro of the chemotherapeutic docetaxel (DTX) in combination with the PDT photosensitizers meso-tetraphenyl chlorin disulphonate (TPCS2a) or chlorin e6 (Ce6). To improve tumor selectivity, in the design of PLGA-PEI NPs, HA was selected for the active targeting of CD44 receptor overexpressed by cancer cells. PLGA-PEI NPs co-loaded with DTX and TPCS2a at fixed drug ratios were tested in DTX –sensitive (HeLa, MDA-MB-231 and MCF-7) and –resistant (HeLa-R) cells grown in 2D and 3D cultures. As 3D cultures, spheroids and mammospheres were used as avascular tumor models and cultures enriched of cancer stem cells (CSCs), respectively. In HeLa and MDA-MB-231 monolayers the highest synergism, evaluated by the Combination index (CI), between chemotherapy and PDT was found at DTX/TPCS2a ratio of 1:35 and co-loaded in the same NP (DTX/TPCS2a-NPs). Interestingly, strong synergism of chemotherapy and PDT was found also in the DTX -resistant cells where the dose of chemotherapeutic could be reduced by ~100 times with DTX/TPCS2a-NPs with respect to monotherapy. In spheroids, the DTX/TPCS2a-NPs at 1:35 ratio gave a strong antagonism (CI >1), while, in these 3D tumor cell models, DTX/TPCS2a ratios 1:3 and 1:5 gave synergism. In spheroids generated from DTX –resistant cells the 1:3 concentration ratio was significantly better in terms of synergism as shown by lower CI values. Combination treatments with DTX and TPCS2a co-loaded in the same NP suppressed also sphere formation, due to the presence of CSCs. Different results were obtained with mammospheres generated from MDA-MB-231 and MCF-7 breast cancer cells, very likely because of the different percentages of CSCs in the two culture models. Based on these results, we demonstrated the advantage of using HA-targeted layer-by-layer NPs as carriers of DTX and TPCS2a to finely control the drug ratio inside the NPs and to precisely deliver the payloads in cancer cells.
Combination of chemotherapy and PDT was also performed co-encapsulating DTX and Ce6 in keratin-based NPs (DTX/Ce6-KNP) prepared by the aggregation method and with a ratio 1.8:1. The cytotoxic effects of combined chemotherapy and PDT, in comparison with monotherapies, and CI analysis were investigated in HeLa and HeLa-R cells in monolayers as well as 3D tumor spheroids. Combination therapy using DTX/Ce6-KNP caused only slight synergism in DTX –sensitive cell monolayers while clear synergism was found in drug resistant cells. Notably, the combination of free drugs caused antagonism. The efficacy of DTX/Ce6-KNP was also assessed in spheroids of DTX -sensitive and -resistant cells where strongest synergism and highest reduction of spheroid volume were observed. In conclusion, these results highlight that: i) the co-delivery of PSs for PDT and chemotherapeutics in NPs allows the control of drug concentration ratios for obtaining synergic interactions; ii) optimized drug ratios determined in 2D cell tumor models do not reproduce synergic interactions in the 3D models and poses the question of the most reliable in vitro models for screening combination therapy; iii) combination of chemotherapy and PDT appears particularly useful for treating drug-resistant tumors
Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids
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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
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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