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Poly(ethylene glycol)–avidin bioconjugates: suitable candidates for tumor pretargeting
No full textAvidin-poly(ethylene glycol) (PEG) conjugates were obtained by derivatization of about 10% of the protein amino groups (four amino groups per protein molecule) with linear 5 kDa PEG or branched 10 or 20 kDa PEGs. Circular dichroism analysis showed that the polymer conjugation neither altered the protein structure nor the environment of the aromatic amino acids which are present at the level of the biotin binding site. Spectroscopic studies were carried out to evaluate the biotin recognition activity of the conjugates either in terms of number of biotin binding sites or avidin/biotin affinity. Avidin-PEG 5 kDa and avidin-PEG 10 kDa displayed over 90% of the native protein biological activity while a reduction in the recognition of biotinylated antibodies of about 25% was found with PEG 20 kDa. In vivo studies demonstrated that the protein immunogenicity was in the order: wild type avidin>avidin-PEG 5 kDa>avidin-PEG 10 kDa>avidin-PEG 20 kDa. By intravenous injection into mice bearing a solid tumor, all conjugates displayed prolonged permanence in the circulation with respect to the native protein. The area under the curve values of avidin-PEG 5 kDa, avidin-PEG 10 kDa and avidin-PEG 20 kDa were about 3-, 7- and 30-times higher than the wild type avidin with reduced accumulation in kidneys and liver. Interestingly, all conjugates accumulated significantly in the tumor mass. In particular, in the case of avidin-PEG 20 kDa, 8% of the injected dose (ID)/g of tissue accumulated in the tumor after 5 h from the administration and over 6% of the ID/g was maintained throughout 72 h
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Author Correction: A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions (Scientific Reports, (2019), 9, 1, (5623), 10.1038/s41598-019-42014-2)
No full text: An amendment to this paper has been published and can be accessed via a link at the top of the paper
Pretargeting strategies for radio-immunoguided tumour localisation and therapy
No full textThe selective recognition of tumour cells by monoclonal antibodies, labelled with radioactive isotopes, for use in diagnosis and treatment, forms the basis of immunoscintigraphy, radio-immunoguided surgery and radio-immunotherapy. Research into the application of these systems has encountered multiple difficulties, most notably a low tumour to non-tumour ratio of radioactivity. The development of pretargeting systems, separating the individual steps of tumour cell targeting and the introduction of the radioactive label, have led to significant increments in tumour to non-tumour ratios and an improvement in diagnostic accuracy. Before pretargeting strategies are applied clinically, a thorough understanding of these systems is required and forms the backbone of this report. Clinical examples of early trials have already confirmed many of the theoretical advantages of pretargeting systems and new protocols are already being investigated
Receptor-mediated radionuclide therapy with 90Y-DOTA-D-Phe1-Tyr3- Octreotide: Preliminary report in cancer patients
No full textRecent advances in receptor mediated tumor imaging led to the development of a new somatostatin analogue DOTA-D-Phe1-Tyr3-Octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, stable labeling with yttrium-90 (90Y) and favourable biodistribution in patients. The aim of this work was to evaluate acute and late toxicity and the response rate in cancer patients administered 90YDOTATOC. Twenty patients received three equal i.v. injections of 90Y- DOTATOC. Cohorts of 5 patients were treated starting with 1.1 GBq per cycle in escalating dosage (0.4 GBq increments) in subsequent groups. No patients showed acute or delayed major adverse reactions up to the dose of 22 GBq of 90Y-DOTATOC per cycle (6.6 GBq total). Maximum tolerated dose has not been determined yet. One patient, after 4.4 GBq total dose, developed delayed kidney grade II toxicity. Complete and partial tumor mass reduction (CR and PR) was measured in 25% of patients along with 55% showing stable disease (SD) and 20% progressive disease (PD). These results indicate that high activities of 90Y-DOTATOC can be administered with low risk of myelotoxicity, although the radiation doses to the kidneys require careful consideration. Tumor doses were high enough in most cases to obtain objective therapeutic responses
Variations on the Author
Get PDF“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
AvidinPEGylation by active site protection
No full textAimed at investigating new approaches for protein PEGylation with low chemical modification of the active recognition site, avidin was PEGylated emploing a soluble macromolecular active site protecting agent prepared by biotinilation of branched PEG 20 kDa
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
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