1,720,962 research outputs found
Neuropilin 2 role in the regulation of disseminated tumour cells dormancy and metastasis in breast and head and neck cancer
Get PDFPrograma de Doctorat en Biomedicina / Tesi realitzada a l'Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - Fundació ClínicMetastases are considered the last stage of tumour progression and the main cause of death associated to solid tumours. There are no effective treatments for metastasis which remain non- curable with more than 90% of patients dying from metastatic disease. They derive from disseminated tumour cells (DTCs) that can remain occult in a dormant state while adapting to the new microenvironment. By mechanisms that are still unclear, dormant DTCs can re-activate and become proliferative giving rise to metastatic outgrowth. Therefore, understanding the mechanisms by which metastases are formed is essential to face one of the most important problems in clinical oncology. Metastasis development depends on DTCs survival in circulation as well as on their ability to colonize new microenvironments. Therefore, we propose that the tumour microenvironment regulates the fate and survival of DTCs in secondary organs, hence regulating metastases.
This project has been developed in order to decipher the role of the nervous system in breast cancer (BrCa) and head and neck cancer (HNSCC) progression and metastasis. Particularly, we have investigated whether the neurogene neuropilin 2 (NRP2) has a crucial role in regulating DTCs biology and in remodelling the metastatic niche generating a favourable microenvironment for the survival and proliferation of the DTCs, all stimulating metastasis. As classical partners of NRPs, we have also studied the effect of class 3 semaphorins (SEMA3s) and their receptors, plexins (PLXNs), on tumour cells biology.
On one hand, we have shown that SEMA3F has an anti-tumour effect in vivo increasing quiescence markers expression and inducing a switch in primary tumours behaviour to a more dormant phenotype. We have also shown that it diminishes cell dissemination to secondary organs, which makes SEMA3F a potential good prognosis factor in BrCa and HNSCC. On the other hand, our results suggest that PLXNA2 inhibits tumour growth as well as prevents cell migration and invasion while it might modulate cell stemness. Moreover, we have also found that PLXNA3 might restrain tumour growth in oestrogen receptor (ER)-positive breast tumours and that the oestrogen signalling up- regulates PLXNA3 expression, associating PLXNA3 with longer dormancy periods of ER-positive breast tumours.
Finally, we have mainly focused on deciphering the role of NRP2 in regulating DTCs biology and lung metastases. Here, we have shown that NRP2 positively regulates BrCa and HNSCC cells proliferation, adhesion, migration, invasion and survival in vitro and in vivo. NRP2 deletion clearly inhibits tumour growth in vivo as well as decreases the number and size of lung metastases. Moreover, NRP2 is essential for lung DTCs proliferative phenotype, hence promoting lung metastases growth in vivo. Highlighting the role of the microenvironment, we have shown that the lung microenvironment up- regulates NRP2 expression partly by macrophages and fibroblasts-derived TGFβ1. Altogether, this thesis contributes to a better understanding of DTCs biology describing TGFβ1-NRP2 axis as a dormancy inhibitor pathway, promoting DTCs re-awakening and lung metastases development. The negative correlation of NRP2 expression with metastasis free survival in BrCa and HNSCC patients’ and our results emphasizing the metastatic role of NRP2, suggest that NRP2 could be a bad prognosis biomarker and a good target to design new drugs against metastasis.Les metàstasis, principal causa de mortalitat associada a tumors sòlids que provoquen la mort de més del 90% dels pacients, no disposen d’un tractament efectiu. Les metàstasis deriven de cèl·lules tumorals disseminades (CTDs) que escapen del tumor primari i, després d’un període d’adaptació al nou microambient, proliferen donant lloc a la metàstasi. Durant aquest període d’adaptació, les CTDs entren en un estat de latència que es caracteritza per una parada del cicle cel·lular, fet que les fa invisibles davant de les teràpies actuals. Mitjançant mecanismes parcialment desconeguts, les CTDs es reactiven i proliferen generant la metàstasi. Per tant, és imprescindible millorar el coneixement sobre la biologia de les CTDs per fer front a un dels principals problemes de l’oncologia clínica actual. Per tal que es generi una metàstasi, es requereix la supervivència de les CTDs tant en circulació com al nou microambient que colonitzaran. Tenint tot això en compte, proposem que el microambient tumoral influencia el fenotip i la supervivència de les CTDs, regulant així la formació de metàstasis.
Aquesta tesi ha tingut com a objectiu l’estudi de la influència de factors neuronals en el desenvolupament del tumor i la metàstasi als càncers de mama i de cap i coll. Concretament, hem estudiat el paper de la Neuropilina 2 (NRP2) en la regulació de la biologia i supervivència de les CTDs, així com en la modulació del microambient tumoral, afavorint la formació de metàstasis. Així mateix, hem analitzat l’efecte i la contribució de les semaforines de classe 3 (SEMA3s) i els seus receptors, les plexines (PLXNs), als càncers de mama i de cap i coll.
D’una banda, hem posat de manifest la funció anti-tumoral de la SEMA3F en augmentar l’expressió de marcadors de latència, a més de reduir la disseminació tumoral i d’induir fenotips menys proliferatius a les CTDs in vivo. D’altra banda, els nostres resultats suggereixen que la PLXNA2 semblaria inhibir el creixement de tumors de mama receptor d’estrogen (ER)-negatius, disminuint la migració i invasió cel·lular. Altrament, l’expressió de la PLXNA3 està regulada per la via dels estrògens, associant la seva expressió als períodes de latència més perllongats en tumors de mama ER-positius. Finalment, el nostre estudi s’ha centrat a determinar la funció de la NRP2 a les CTDs i al desenvolupament de metàstasis al pulmó. En concret, hem demostrat la relació de l’expressió de NRP2 amb una major proliferació, adhesió, migració, invasió i supervivència cel·lular in vitro i in vivo. En concordança, hem mostrat que la inhibició de NRP2 redueix tant el creixement del tumor primari com la formació de metàstasis als pulmons in vivo. Finalment, destacant el paper del microambient tumoral als pulmons, hem vist que el TGFβ1 secretat pels macròfags i fibroblasts pulmonars augmenta l’expressió de NRP2 a les cèl·lules tumorals.
En definitiva, aquesta tesi contribueix a un major coneixement de les CTDs descrivint l’eix TGFβ1- NRP2 com a inhibidor de la latència cel·lular i promotor de les metàstasis pulmonars. Tenint en compte la correlació de l’expressió de NRP2 en pacients de càncer de mama i de cap i coll amb una major incidència de metàstasis, definim la NRP2 com a marcador de mala prognosi contra la qual generar possibles noves eines terapèutiques per a millorar els tractaments de la malaltia metastàtic
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
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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