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Caratteristiche molecolari dei tumori primari del fegato: associazione con l'esito del trattamento e relazione con il sesso
No full textIl carcinoma epatocellulare (HCC) è il tumore epatico primario più comune e la seconda causa di morte per cancro a livello mondiale. L’HCC presenta un'eterogeneità clinica e biologica, che dipende da vie quali la neo-angiogenesi e la linfangiogenesi. Una caratteristica costante è il rapporto maschi/femmine sbilanciato verso il sesso maschile. Il trattamento curativo (come il trapianto di fegato, LT) può essere offerto a una minoranza di soggetti, poiché molto spesso l'HCC, già alla presentazione, non può essere sottoposto a LT. Per i pazienti che presentano un HCC non resecabile e multifocale alla diagnosi, le terapie sistemiche (farmaci inibitori della tirosin-chinasi [TKI] o la combinazione inibitori del checkpoint/ farmaci antiangiogenici) sono il miglior potenziale trattamento. Ciò che è chiaro, ma non ancora ben definito in letteratura, è il reale impatto delle caratteristiche molecolari sul comportamento del tumore in termini di decorso della malattia e risposta al trattamento.
L'obiettivo principale di questo studio è stato quello di analizzare le caratteristiche biologiche e istopatologiche dei pazienti affetti da HCC trattati con TKI, ovvero i farmaci finora più utilizzati, per determinare se le differenze di risposta possano essere attribuite a specifiche caratteristiche molecolari del tumore e se il sesso possa essere un ulteriore modificatore rilevante della risposta. Abbiamo quindi analizzato i preparati istologici di 23 pazienti trattati con TKI (18 maschi e 5 femmine) mediante immunoistochimica per quantificare l'espressione di angiopoietina-2 (Ang2), podoplanina e C-type Lectin Domain Family 2 (CLEC-2) (fattori rilevanti coinvolti nella neoangiogenesi e linfangiogenesi).
Il secondo obiettivo di questo studio è stato quello di analizzare le caratteristiche cliniche, biologiche e istopatologiche dei pazienti affetti da HCC con recidiva post-LT, al fine di identificare ciò che la determina.
Abbiamo esplorato le correlazioni della recidiva post-LT confrontando l'espressione di Ang2, podoplanina e CLEC-2 nei fegati espiantati di 140 pazienti (70 pazienti con HCC ricorrente dopo il trapianto e 70 pazienti senza). Ci siamo concentrati sulla possibile relazione tra il livello di espressione di queste molecole e la crescita e l'aggressività del tumore. Come coorte di validazione, abbiamo studiato una serie di pazienti del Centro Trapianti di Fegato di Bologna (30 pazienti con recidiva post-LT e 30 pazienti senza).
Infine, il terzo obiettivo di questo studio riguardava il confronto biologico e istopatologico tra HCC e colangiocarcinoma intraepatico (iCCA). Nonostante sia meno frequente, l'iCCA è il secondo tipo più frequente di tumore del fegato, rappresentando il 10-20% dei casi. Sebbene HCC e iCCA rappresentino gruppi biologicamente eterogenei, potrebbero non mostrare differenze così marcate quando si esaminano sottogruppi ben caratterizzati di ciascun tumore. Gli HCC più aggressivi tendono a presentare caratteristiche clinicamente comparabili agli iCCA. Pertanto, abbiamo valutato mediante immunoistochimica l'espressione delle proteine Ang2, podoplanina, CLEC-2, CD34, Lyve-1 e VEGF in 90 preparati istologici su tissue array (45 HCC; 45 iCCA).
L'analisi dei due segmenti iniziali dello studio ha determinato che Ang2, podoplanina e CLEC-2 sono associati all'aggressività biologica dell'HCC. L’associazione risulta evidente nel contesto delle differenze legate al sesso tra i pazienti sottoposti a terapia con TKI, nonché nella manifestazione delle recidive dopo il trapianto di fegato.
Nel progetto incentrato sui tissue array, l'analisi comparativa dei marcatori identificati ha rivelato che l'iCCA presenta spesso caratteristiche simili a quelle osservate nell'HCC, nonostante il profilo linfangiogenico sia risultato più marcato.Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second leading cause of cancer death worldwide. HCC presents clinical and biological heterogeneity, depending on pathways such as neo-angiogenesis and lymphangiogenesis. A constant feature is the male/female ratio unbalanced towards the male sex. Curative treatment (e.g. liver transplant, LT) can be offered to a minority of subjects, as very often HCC already at presentation is not amenable to LT. For patients who have unresectable and multifocal HCC at presentation, targeted therapies (tyrosine kinase-inhibitor drugs [TKIs] or the combination checkpoint inhibitors/antiangiogenic drugs) are the best potential treatment. What is clear but still not well defined in the literature is the real impact of molecular features on tumor behavior in term of course of disease and response to treatment.
Main objective of this study was to analyze the biological and histopathological characteristics of HCC patients treated with TKIs, i.e. the drugs that have been most used so far, to determine whether differences in response can be attributed to specific molecular features of the tumor and whether sex could be an additional relevant modifier of response. We thus analyzed the histological preparations of 23 TKI-treated patients (18 males and 5 females) by immunohistochemistry to quantify the expression of Angiopoietin-2 (Ang2), podoplanin and C-type Lectin Domain Family 2 (CLEC-2) (relevant factors involved in neoangiogenesis and lymphangiogenesis).
Second objective of this study was to analyze the clinical, biological and histopathological characteristics of HCC patients with HCC recurrence after LT, in order to identify what determines recurrence.
We explored the correlations with recurrence after LT by comparing the expression of Ang2, podoplanin and CLEC-2 in the explanted livers of 140 patients (70 patients with recurrent HCC post-transplantation and 70 patients without recurrence). We focused on the possible relationship between level of expression of these molecules and tumor growth and aggressiveness. As validation cohort, we studied a series of patients from Liver Transplant Centre of Bologna (30 patients with recurrence after LT and 30 patients without recurrence).
Finally, the third objective of this study concerned the biological and histopathological comparison between HCC and intrahepatic cholangiocarcinoma (iCCA). Indeed, although less frequent, iCCA is the second most frequent type of liver cancer, accounting for 10-20% of cases. Although HCC and iCCA represent biologically heterogeneous groups, they may not show such marked differences when examining well-characterized subgroups of each tumor. The most aggressive HCCs tend to present clinically comparable features to iCCA. Therefore, we evaluated by immunohistochemistry the expression of Ang2, podoplanin, CLEC-2, CD34, Lyve-1 and VEGF proteins in 90 histological preparations on tissue array (45 HCC; 45 iCCA).
Analysis of the initial two segments of the study allowed for the determination that Ang2, podoplanin, and CLEC-2 are associated with the biological aggressiveness of HCC. This association was evident in the context of sex-related differences among patients undergoing TKI therapy, as well as in the manifestation of recurrence post-liver transplantation.
In the project that focused on tissue arrays, the comparative analysis of the identified markers revealed that iCCA often exhibits characteristics similar to those observed in HCC, even though the lymphangiogenic profile is more marked
Dynamic Angiopoietin-2 Serum Level as Endothelial Damage Marker and Potential Therapeutic Target
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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
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