1,721,020 research outputs found
TARGETING PEPTIDES CONTAINING SUPRAMOLECULAR AGGREGATES TOWARD CANCER CELLS
Full text linkMultimodal supramolecular compounds that combine imaging and therapeutic capabilities are the focus of intensive research for applications in the growing field of nanomedicine. These compounds offer the prospect to increase diagnostic accuracy and therapeutic effectiveness, while minimizing side effects from treatment. Nanoparticles with a micellar or liposomal structure obtained by assembling amphiphilic compounds are promising candidates for such multifunctional therapeutic platforms.
Selective target of these nanoparticles for cancer cells can be obtained by labeling supramolecular aggregates with peptides able to recognize transmembrane receptors overexpressed in many human tumors. Examples of peptide that can be used to drive selectively the nanoparticle on the cancer cells are the octreotide (analog of the somatostatin), [7-14] bombesin and CCK8 peptides. To reach this result, new amphiphilic monomers were designed, synthesized and structurally characterized. Amphiphilic monomers are functionalized with polydentate chelating agent (such as DOTA, DTPA and DTPAGlu) able to coordinate radioactive or paramagnetic metals for diagnostic applications, or with bioactive molecules able to recognize the cellular target. These molecules are able to auto assemble or to aggregate in mixed micelles or liposomes in aqueous solution.
All monomers were synthesized in solid-phase following an Fmoc strategy. The aggregates formulated are investigated by physical chemical methods like Small Angle Neutron Scattering (SANS) and Dynamic Light Scattering (DLS), relaxivity measurement and spectroscopy techniques (fluorescence and UV-Vis). These studies have allowed selecting the best systems for shape and size with relation to relaxivity parameters and aggregation stability. To validate the specificity and the citotoxicity of the delivery systems in vitro and in vivo studies were also performed.
The monomers containing the chelating agent, (C18)2DOTA, (C18)2DTPA and (C18)2DTPAGlu are able to auto assemble. Moreover in mixed aggregates they showed to drive the aggregation process. Aggregates fuctionalized with octreotide were investigated as promising target-selective contrast agent for MRI (Magnetic Resonance Imaging). The high relaxivity values, associated with the supramolecular aggregates, confirm the obtainment of a more rigid contrast agent able to carry numerous gadolinium ions on target cells.
In vitro binding assays on bombesin labeled liposomes allowed to select (C18)2DOTA/(C18)2-L5-bombesin as the lead compound. In these supramolecular aggregate, the peptidic monomer contains the more appropriate spacer of the length between the peptide and the hydrophobic moiety. In vivo studies confirmed the specificity towards to the receptor of the bombesin labeled liposome with respect to the liposome exposing a scrambled peptide sequence.Aggregates fuctionalized with CCK8 peptide were investigated as target-selective drug delivery systems.
The drug delivery of chemioterapeutics (i.e. doxorubicin) was studied on A431 cells overexpressing CCK receptors. The loading and release of the drug were carried out in (C18)2DOTA/(C18)2-L5-CCK8 liposome. The results obtained show the specificity and the efficacy of the system on cellular target, compared with control aggregate. In conclusion this research has permitted the achievement of new supramolecular systems containing a bioactive molecule and a chelating agent able to target tumor cells, as possible of diagnostic and therapeutic
Localisation d'in insulinome bénin par imagerie des récepteurs du glucagon-like peptide-1
No full text
Synthesis and characterization of DOTA-coupled dimeric Y1 receptors antagonists for breast cancer targeting
No full text
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
- …
