1,721,030 research outputs found
L'enzima nicotinamide N-Metiltrasferasi: un nuovo marker diagnostico e target terapeutico nel carcinoma orale
Full text linkIl carcinoma squamocellulare (OSCC) rappresenta la lesione neoplastica più frequente nella cavità orale. Nonostante i progressi effettuati in campo sia chirurgico sia terapeutico, la sopravvivenza media a 5 anni si mantiene ancora al di sotto del 50%. La ricerca di marcatori molecolari coinvolti nella progressione neoplastica risulta essere quindi di primaria importanza.
In relazione a studi precedentemente condotti, che hanno portato all’identificazione dell’enzima Nicotinamide N-metiltrasferasi (NNMT) quale potenziale marker di alcune tipologie di tumore, è risultato interessante intraprendere uno studio dell’espressione dell’NNMT nel carcinoma orale squamocellulare. Tale analisi è stata condotta su campioni di tessuto orale sano e canceroso relativi a pazienti affetti da OSCC, affrontando uno studio sia a carico del mRNA mediante RT-PCR e Real-Time PCR, sia a carico della proteina mediante Western blot, analisi immunoistochimiche e saggio di attività enzimatica. Allo scopo di esplorare il coinvolgimento dell’NNMT nel metabolismo della cellula tumorale, sono stati successivamente effettuati esperimenti di silenziamento dell’enzima in una linea cellulare di carcinoma orale; le cellule trasfettate e quelle di controllo sono state in seguito inoculate in topi nudi.
I risultati ottenuti hanno consentito di osservare un aumento significativo dell’espressione dell’NNMT (tessuto tumorale vs mucosa sana) nella maggior parte dei soggetti privi di metastasi, mentre nei casi che presentavano metastasi linfonodali l’NNMT non sembrava subire marcate alterazioni della sua espressione. L’analisi immunoistochimica ha confermato l’overespressione della proteina nei campioni di OSCC rispetto ai campioni di mucosa sana dove il segnale era quasi o del tutto assente. Inoltre l’aumento di espressione dell’NNMT risultava più marcato nei campioni di tumore moderatamente o ben differenziato rispetto ai campioni di tumore indifferenziato.
I risultati ottenuti mediante saggio di attività catalitica hanno indicato un aumento dei livelli di attività dell’enzima nel tessuto tumorale nella quasi totalità dei campioni esaminati.
Il silenziamento dell’NNMT effettuato su cellule di carcinoma orale ha comportato una diminuzione della crescita cellulare e della capacità di formare colonie in assenza di adesione al substrato. Gli esperimenti condotti sui topi atimici hanno mostrato come l’inoculo delle cellule trasfettate nelle quali il gene NNMT era stato silenziato determinava la formazione di masse tumorali di dimensioni marcatamente ridotte rispetto a quelle ottenute in seguito all’inoculo delle cellule di controllo.
L’elevata espressione dell’NNMT nel carcinoma squamocellulare sembrerebbe indicare che l’enzima possa svolgere una funzione importante nel processo di oncogenesi orale. L’esistenza di una correlazione inversa tra i livelli di espressione dell’NNMT in OSCC (tumore versus mucosa sana) e la presenza di metastasi supporta l’ipotesi secondo la quale l’enzima possa svolgere un importante ruolo nell’invasione neoplastica, candidandolo a potenziale marcatore prognostico di tale neoplasia. L’identificazione di una correlazione inversa tra i livelli di espressione dell’NNMT e il grado istologico suggerisce un possibile ruolo dell’enzima nelle fasi iniziali dell’oncogenesi. I risultati delle analisi di attività enzimatica consentono inoltre di candidare l’NNMT quale possibile marcatore diagnostico di tale tipologia neoplastica. I risultati ottenuti in seguito agli esperimenti di silenziamento ed analisi in vivo evidenziano un coinvolgimento dell’enzima NNMT nella proliferazione cellulare. Il silenziamento di tale enzima comporta infatti una riduzione della capacità proliferativa e del potenziale tumorigenico della cellula neoplastica; la sua inibizione potrebbe quindi rappresentare un possibile approccio molecolare alla terapia del carcinoma orale.Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. In recent 50 years, despite the advances in surgery and adjuvant therapies, the 5-year mortality rate of oral cancer is about 50% around the world. Up to now, reliable biomarkers for OSCC are still lacking. Therefore, it is necessary to identify target molecules for effective therapy and for early diagnosis of OSCC.
In the present study, we focused on the expression of Nicotinamide N-Methyltransferase (NNMT), which catalyses the N-methylation of nicotinamide, pyridines and other structural analogs, playing an important role in the biotransformation and detoxification of many xenobiotics. Several tumours have been associated with abnormal NNMT expression. However its role in tumour development remains largely unknown. To explore the involvement of NNMT in OSCC, we analysed the enzyme expression in tumour and non-tumour oral tissues obtained at surgery by RT-PCR, Real-Time PCR, Western blot, immunoistochemical analysis and catalytic activity assay. We also evaluated the effect of shRNA-mediated inhibition of NNMT on the proliferative potential of an oral cancer cell line. Transfected and normal oral cells were injected into athymic mices in order to evaluated the effect of NNMT silencing on tumour growth.
The results showed a significant increase of NNMT expression (tumour tissue vs normal mucosa) in most of the favourable OSCCs (N0), while no marked NNMT expression alteration between tumour and normal mucosa was detected in most of metastatic tissues (N+). Immunohistochemical analyses performed on paraffin-embedded samples of oral cancer and normal mucosa indicated a significant NNMT upregulation in the examined OSCCs, that was more evident in well- and moderately-differentiated cases than in undifferentiated ones. Consistent with the results of immunoistochemistry, NNMT specific activity values were significantly higher in OSCCs than in control samples. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, showing an inhibition rates around 70%, observed at both the mRNA and protein levels. Down-regulation of NNMT significantly inhibited cell proliferation and decreased colony formation ability on soft agar. In athymic mices NNMT silencing effectively induced a drastic reduction in tumour volume, suggesting the involvement of the enzyme in cancer development.
The present data support the hypothesis that NNMT plays a role in oral carcinogenesis and represents a highly promising marker for early detection of oral cancer. The results obtained from silencing and in vivo experiments seem to suggest that NNMT is involved in cell proliferation and its inhibition could represent a possible molecular approach to the treatment of oral cancer
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
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
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
Catecholamine O-Methyltransferase as a Promising Diagnostic and Therapeutic Target in Oral Squamous Cell Carcinoma
No full textOral squamous cell carcinoma (OSCC), which constitutes over 90% of all oral cancers, is the most prevalent malignancy affecting the oral cavity and is marked by high aggressive behavior and high recurrence rate. Although significant progress has been made in therapeutic strategies, the overall prognosis for OSCC patients remains poor, primarily due to the common occurrence of late-stage diagnosis and the frequent development of metastases. Therefore, implementing effective early detection methods alongside the development of targeted therapies is essential to significantly enhance clinical outcomes and long-term survival rates in affected individuals. In this experimental study, we focused on Catecholamine OMethyltransferase (COMT), a key enzyme involved in the metabolic breakdown of catecholamines such as dopamine, epinephrine, and norepinephrine. COMT regulates neurotransmitter levels and oxidative stress, and its polymorphisms have been linked to cancer susceptibility, progression, and therapeutic response. COMT expression levels were assessed at both mRNA and protein level in OSCC specimens compared to adjacent healthy tissue. Our findings demonstrated a significant overexpression of COMT in cancerous tissues, suggesting its potential role as a diagnostic marker. Ongoing functional analyses are being performed using gene knockdown approaches to elucidate the role of the enzyme in OSCC phenotype
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