1,721,037 research outputs found
Caratteristiche molecolari e stato di metilazione del cancro colorettale ad insorgenza precoce (≤ 40 anni di età)
No full textIntroduzione: Pressochè sconosciuta fino a 3 o 4 decenni fa, la genetica del cancro ha portato a rilevanti avanzamenti della nostra conoscenza sullo sviluppo tumorale. Molte sindromi sono state identificate seguendo la legge dell’ereditarietà Mendeliana per cui la patologia era trasmessa da una generazione all’altra.
Il cancro colorettale è una patologia che insorge ad età avanzata in entrambi i sessi ed aumenta con l’avanzare dell’età. L’età media alla diagnosi degli individui affetti si aggira intorno ai 70 anni. Tuttavia una piccola frazione di pazienti sviluppa il cancro colorettale più precocemente. Le ragioni per cui alcuni individui sviluppano cancro colorettale ad un’età insolita sono ancora sconosciute.
Scopo: L’obiettivo di questo studio è quello di comparare le caratteristiche molecolari e lo stato di metilazione dei cancri colorettali che insorgono precocemente con i tumori ad età più avanzata, per individuare possibili meccanismi patogenetici che intervengono nella carcinogenesi dei tumori giovanili.
Metodi: Nel nostro studio abbiamo incluso 33 pazienti con tumori insorti prima di 40 anni di età e un gruppo di controllo composto da 41 pazienti con tumori insorti dopo i 60 anni. Il gruppo di controllo è stato selezionato tenendo in considerazione le caratteristiche principali dei casi giovanili: preponderanza di sesso maschile, stadio di Dukes C e D e localizzazione tumorale nel colon sinistro. Tutti i tumori sono stati indagati per il test di Instabilità dei Microsatelliti, l’analisi immunoistochimica dei geni del Mismatch Repair (MMR) e l’identificazione delle mutazioni a livello somatico dei geni K-RAS e BRAF. La ricerca delle mutazioni germinali dei geni del MMR è stata eseguita nei casi con test di screening positivi. L’analisi del gene APC è stata condotta in tutti i pazienti con sospetto clinico di Poliposi Familiare, mentre il gene MUTYH è stato indagato in tutti i casi giovanili. Infine, abbiamo valutato il ruolo della metilazione aberrante del DNA (ipermetilazione e ipometilazione) in tutti i 74 carcinomi colorettali. In particolare l’ipermetilazione è stata ricercata con la metodica MS-MLPA usando tre differenti kit della MRC-Holland (ME001, ME002, e ME011), mentre l’ipometilazione delle LINE-1 è stata valutata con il trattamento del bisulfito mediante l’analisi con il pirosequenziamento.
Risultati: I cancri colorettali ad insorgenza precoce mostravano un’alta incidenza di forme ereditarie (6 casi, di cui 5 di Sindrome di Lynch e 1 di Poliposi Familiare, 18%) e delle mutazioni somatiche del gene K-RAS (33% contro 7%, p<0.005). Le mutazioni somatiche del gene BRAF sono state ritrovate solamente in 4 tumori colorettali ad età avanzata con perdita dell’espressione della proteina MLH1 e instabilità dei microsatelliti. Il numero medio dei geni metilati nei cancri colorettali ad insorgenza precoce era di 3.4 mentre nei cancri colorettali ad insorgenza tardiva era di 5.22 e questa differenza era statisticamente significativa (p< 0.005). L’ipermetilazione dei geni GATA-5, WT1 e ESR1 era un evento ugualmente frequente nei carcinomi giovanili e nei controlli. Inoltre i carcinomi giovanili in assenza dei casi con Sindrome di Lynch mostravano un’elevata frequenza di ipometilazione delle sequenze LINE-1.
Conclusioni: Abbiamo riscontrato differenze nel “make-up” genetico tra i carcinomi ad insorgenza precoce rispetto a quelli ad insorgenza tardiva. I tumori giovanili mostrano maggiori alterazioni costituzionali e somatiche del Sistema del Mismatch Repair, più frequenti mutazioni del gene K-RAS ed un minor numero di geni metilati. L’ipermetilazione dei geni ESR1, GATA5, WT1 potrebbe suggerire il possibile utilizzo di questi geni come marcatori nella diagnosi precoce del cancro del colon.Background: Almost unknown until 3 to 4 decades ago, cancer genetics led to the most relevant advancements of our understanding in tumor development. Many syndromes have been identified in which the disease is transmitted from generation to generation following Mendelian inheritance.
Colorectal cancer (CRC) is usually considered a disease of the elderly in both sexes and increases with advancing age. So the mean age of affected individuals is around 70 years. However a small fraction of patients develops colorectal cancer earlier. The reasons whereby some individuals develop CRC at an unusual age are poorly understood.
Aim: Despite the clinical suspicion of a genetic origin (Lynch Syndrome and Familial Adenomatous Polyposis), the purpose of this study is to compare biomolecular features and methylation status of early onset CRC with those from tumors of elderly patients in order to elucidate possible pathogenetic mechanisms that onset in young individuals.
Methods: In the study we included 33 patients with disease ≤40 years of onset and a control group composed of 41 patients with disease at ≥60 age, matched for the three characteristics of preponderance of male sex, C and D stages of Dukes and site of tumor especially in distal colon. All tumors were investigated for Microsatellite Instability (MSI) test and Mismatch Repair (MMR) immunohistochemistry analyses, identification of K-RAS and BRAF somatic mutations.
Detection of MMR genes germline mutations was performed only in cases with positive screening tests. APC gene mutations were investigated in patients with a clinical suspect of Familial Polyposis, whereas MUTYH gene was detected in the 33 young cases. Finally, we explored the role of aberrant DNA methylation (hypermethylation and hypomethylation) of all 74 colorectal carcinomas. In particular hypermethylation was investigated by MS-MLPA method using three different kits from MRC-Holland (ME001, ME002, and ME011) and hypomethylation of long interspersed element 1 (LINE-1) was evaluated by bisulfite DNA treatment and pyrosequencing assay.
Results: Early onset CRC showed an high incidence of hereditary forms (6 cases, 5 Lynch Syndrome and 1 Familial Adenomatous Polyposis, 18%) and K-RAS somatic mutations (33% versus 7%, p60 years. Moreover early onset CRC, excluding Lynch Syndrome cases, showed high hypomethylation frequency of LINE-1 sequences.
Conclusion: We have found differences in the genetic make-up of carcinomas from young and elderly patients. Early onset tumors showed constitutional and somatic defective of Mismatch Repair System, more frequent K-RAS somatic mutations and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis
La riflessione interlinguistica nella Gramatica española di J. F. Perles y Campos (1689)
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
Radial versus femoral approach in STEMI: what do we know so far?
No full textRadial approach has been used since 1989 to perform coronary angiography as an alternative to femoral access. During past decades, the development of dedicated equipment has led to high efficacy also in complex procedures. ST elevation myocardial infarction (STEMI) is known to be a high bleeding risk setting and in turn bleeding events can negatively impact on outcomes. Observational studies have demonstrated feasibility, efficacy and safety of radial approach when compared to femoral access in STEMI patients, with benefit in bleeding rates. These advantages have also been described in specific populations such as in the elderly and in patients with cardiogenic shock. Some large randomized trials have been conducted to assess outcomes of transradial access versus transfemoral access, with RIVAL and MATRIX representing the largest two studies. The RIVAL documented a significant reduction in access site-related complications in the global population of acute coronary syndrome (ACS) patients, with also lower mortality and net clinical adverse events (NACE), mainly driven by significant reduction of bleeding and all-cause mortality, in the STEMI sub-group. Overall, the MATRIX trial confirmed that radial access decreased bleeding and all-cause death thus reducing the rate of NACE and supporting the transradial access as the one to be preferred in ACS patients. Clinical advantages of radial access have been also tested in smaller randomized trials corroborating the evidence of radial access as a highly recommendable alternative to femoral access in the setting of primary percutaneous coronary intervention (p-PCI). The current evidence suggests that radial access should become the default access for patients with ACS undergoing invasive management
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
- …
