1,720,981 research outputs found
PRECLINICAL PET IMAGING FOR TUMOUR CHARACTERIZATION: FOCUS ON HYPOXIA AND INFLAMMATION
Get PDFImaging molecular techniques including PET, CT, MRI allow to detect and to monitor normal and pathological conditions non-invasively in clinic. The recent development of dedicated small animal instruments together to the availability of appropriate animal models of disease has allowed the use of these methods in preclinical research with the possibility to transfer directly the obtained results in clinic.
In this thesis’s work we characterized two preclinical oncology models through the use of an animal PET instrument focusing on two processes correlated to tumour growth such as hypoxia and inflammation.
Tissue hypoxia is considered as a negative prognostic factor both for answer to pharmacological and radiant therapy and for tumour progression and invasiveness. Consequently, identification and localization of hypoxic areas within the tumour have an important interest in clinical diagnostic. To this aim, BALB/c nu/nu mice were inoculated with murine cells of mammary adenocarcinoma (EMT-6) and with human cells of prostate adenocarcinoma (PC-3) and pharingeal cancer (FaDu). Animals were monitored using two hypoxic radiopharmaceutical recently developed, [18F]FAZA and [64Cu]ATSM at two different times, using PET and autoradiography. In parallel, an in vitro evaluation of specific hypoxic markers such as carbonic anhydrase IX and cupper transporters (Ctr-1 and ATP7B) was performed. In FaDu model we confirmed the same [64Cu]ATSM distribution at the two analyzed times, that is similar to that of [18F]FAZA. On the contrary, EMT-6 and PC-3 models showed a time-dependent [64Cu]ATSM uptake, with a distribution at late time (24hrs post injection) similar to that of [18F]FAZA. The different distribution of [64Cu]ATSM can be only partially explained by the different cupper pumps localization observed in vitro. Other factors such red-ox and cellular pH may influence [64Cu]ATSM uptake. PET imaging is an interesting method to identify and monitor tumour hypoxia in a non invasive way but it needs further studies that associate metabolic changes to proteomic pattern changes.
Positron Emission Tomography (PET) imaging with [18F]2-fluoro-2-deoxy-D-glucose-PET ([18F]FDG-PET) is widely used in neoplastic patients for disease assessment and evaluation of treatment efficacy. Results interpretation must take into account the contribution of inflammatory cells that infiltrate growing tumours for [18F]FDG uptake. In this work, we established a preclinical model of peritoneal carcinomatosis to verify the actual contribution of macrophages to signals obtained with [18F]FDG-PET. Groups of mice with peritoneal carcinosis were longitudinally evaluated with [18F]FDG-PET. Intraperitoneal depletion of macrophages was achieved by an approach that proved to be safe and effective, i.e. administration of clodronate encapsulated into liposomes. Sham-liposomes were used in control animal cohorts. Using [18F]FDG-PET we detected and monitored peritoneal lesions’ growth, with a good correlation between the real neoplastic lesions extension and that measured using [18F]FDG-PET. Macrophage depleted animals showed a substantial drop in tumour growth. In conclusion, [18F] FDG-PET imaging allows the non-invasive detection of peritoneal adenocarcinoma lesions and macrophages are directly and indirectly involved in [18F]FDG uptake by promoting tumour growth and spreading in the peritoneal cavity
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
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
Effects of hormonal therapy on [18F]FDG and [11C]choline in vitro uptake on several prostatic cell lines
No full textIntroduction: Androgens influence prostate cancer (PC) cell growth by acting on cell cycle and hormones ablation is the first line of therapeutic intervention until the tumour became hormone refractory. Anti-androgen therapy is based on the blockade of ARs (Androgen Receptors) through the administration of AR[1] antagonist or the reduction of androgen levels through the activation of GnRH receptors[2]. [11C]Choline-PET imaging is extensively used in clinical practice for patients restaging following an increase in PSA levels[3]. However, androgen effects on tracer uptake has been poorly investigated. We studied the effect of the androgen Dihidrotestosterone (DHT), Triptorelin (GnRH agonist), Bicalutamide (AR antagonist) on [11C]Choline and [18F]FDG uptake on two different PC cell lines: human androgen sensitive LNCaP cells and androgen independent, AR positive murine cells TRAMP-C1.
Methods: PC cells were divided in several groups of treatment as follows: a) DHT 10-9M, Triptorelin 10–7M alone or in combination with DHT 10-9M and a control group; b) DHT 10-9M, Bicalutamide 10-4 or 10-5M alone or in combination with DHT 10-9M and a control group. Cells were incubated with [18F]FDG (1μCi/ml) for 60 min or with [11C]Choline (4μCi/ml) for 30 min. Radiotracers uptake was expressed as % Uptake= (radioactivity in the cells/total radioactivity added) x 100 and normalized to total protein content. In parallel a MTS assay was performed to evaluate the toxicity of treatments.
Results: DHT increased [18F]FDG and [11C]Choline uptake in LNCaP and TRAMP-C1 cells. In addition it increased cell growth in LNCaP cells as showed by MTS assay. Triptorelin increased [18F]FDG uptake only in LNCaP. Treatment with Bicalutamide had not effect on radiotracers uptake in LNCaP cells, whereas in doses of 10-4M it significantly inhibited cell growth, effect that was not inhibited by DHT co-treatment. In TRAMP-C1 cells Bicalutamide particularly in dose of 10-4M increased [18F]FDG uptake. As observed in LNCaP cells, Bicalutamide 10-4M inhibited significantly cell growth in TRAMP-C1 cells.
Conclusions: As expected radiotracers uptake was modulated by DHT in both cell lines. Contrary to what expected, treatment with the AR antagonist Bicalutamide didn’t modulate tracers uptake in androgen sensitive cells (LNCaP), whereas it increased [18F]FDG uptake in androgen-independent AR positive cells (TRAMP-C1) although reducing cell growth. Finally Triptorelin treatment increased [18F]FDG uptake in LNCaP, but not in TRAMP-C1. Results of our study indicated that radiotracers uptake is influenced by AR receptors as indicated by DHT effects. These effects were not inhibited by the administration of the AR antagonist Bicalutamide that when it was administered alone, surprisingly increased the relative uptake of [18F]FDG in residual cells. Finally Triptorelin effect observed in LNCaP but not in TRAMP-C1 may be due to different expression or function of GnRH in the two types of PC cell lines.
References:
[1] Gelman EP; J Clin Oncl 20:3001-15 (2002)
[2] Dondi D et al; Cancer Res 54:4091-4095 (1994)
[3] Algan O et al; Radiat Res 146(3):267-75 (1996
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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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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