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Role of paraoxonase-2 in bladder cancer: effect of gene silencing and overexpression on cell proliferation, migration and chemoresistance.
Get PDFRUOLO DELLA PARAOXONASI-2 NEL TUMORE DELLA VESCICA: EFFETTO DEL SILENZIAMENTO E DELLA OVERESPRESSIONE DELLA PON2 SULLA PROLIFERAZIONE, MIGRAZIONE E CHEMORESISTENZA
SCOPO: Nella popolazione mondiale, il tumore della vescica occupa il 5° posto tra i tumori più frequenti. Lo scopo di questo studio è quello di comprendere il coinvolgimento della Paraoxonasi-2 (PON2) nella carcinogenesi dello stesso. Le cellule T24 (linea cellulare di carcinoma della vescica umana) sono state trasfettate utilizzando i plasmidi pcDNA3 e plKO.1 per indurre rispettivamente l’overespressione o il silenziamento del gene PON2.
MATERIALI E METODI: L’influenza della PON2 sulla migrazione cellulare è stata analizzata mediante il test di rimarginazione delle ferite in vitro. Le cellule T24 overespresse e silenziate per il gene della PON2, sono state trattate per 24 ore con Cisplatino e Gemcitabina e mediante il saggio colorimetrico MTT e l’utilizzo della 2,7-diclorofluoresceina diacetato. (DCFH-DA) sono state valutate, rispettivamente, la proliferazione cellulare e la suscettibilità allo stress ossidativo. Per comprendere l’implicazione della PON2 nell’apoptosi sono state valutate l’attività della Caspasi-3 e Caspasi-8.
RISULTATI: l’overespressione della PON2 ha determinato, nelle cellule T24 trattate con chemioterapici, un aumento della proliferazione cellulare, dei livelli intracellulari dei ROS e della Caspasi-3 e Caspasi-8. Al contrario, il silenziamento della PON2 ha portato ad una riduzione della vitalità cellulare delle cellule T24 dopo trattamento chemioterapico. Infine si è osservato un aumento della produzione di ROS ed un'attivazione di entrambe le Caspasi 3 ed 8.
CONCLUSIONI: sebbene questi risultati richiedano ulteriori conferme per comprendere appieno le potenziali implicazioni fisiopatologiche della PON2 nel cancro della vescica, i nostri dati propongono l'enzima PON2 quale biomarker utile per il monitoraggio della crescita tumorale e dei fenomeni di chemioresistenza.ROLE OF PARAOXONASE-2 IN BLADDER CANCER: EFFECT OF GENE SILENCING AND OVEREXPRESSION ON CELL PROLIFERATION, MIGRATION AND CHEMORESISTANCE.
Purpose: Bladder cancer (BC) represents the 7th most common neoplasm in men and the 17th most common in women, worldwide. The identification of reliable biomarkers becomes essential for both early diagnosis and effective therapy of BC. Paraoxonase-2 (PON2) exhibits anti-oxidant and anti-apoptotic activity. Therefore, the aim of this study was to explore the involvement of PON2 in BC cell metabolism. To analyze the potential role of PON2 enzyme in the physiopathology of bladder cancer, we transfected T24 cells (human bladder cancer cell lines) by using pcDNA3 and plKO.1 plasmid to induce the overexpression or the silencing of PON2 gene, respectively.
Materials and methods: we tested the PON2 biological influence on cell migration by monolayer wound healing assay. Subsequently, T24 transfected cells were treated for 24 h with cisplatin and gemcitabine and then we measured the cell proliferation by MTT colorimetric assay and susceptibility to oxidative stress. In the harvested cells, we also investigated the activity levels of both Caspase-3 and Caspase-8 as key regulators of the apoptotic response.
Results: the PON2 overexpression was responsible for an increased T24 cell viability against chemotherapy agents that resulted also in a ROS production and Caspases activation lower than the control. Conversely, the PON2 silenced gene reduced the strength of T24 cells to the chemotherapy treatment. The decreased cell viability was correlated to an increased production of ROS and to an activation of Caspases higher compared to the control.
Conclusions: although these results require further confirmations to fully understand the potential implications of PON2 modulation in BC our data define the PON2 enzyme as a strong and novel molecular approach to control the tumor growth and its susceptibility to chemotherapeutics
Predictors of cord blood unit cell content in a volume unrestricted large series collections: a chance for a fast and cheap multiparameter selection model
No full textBACKGROUND: Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. METHODS: Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. RESULTS: Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie’s gender and birth weight have a positive correlation with CB TNC content. The babie’s birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie’s, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 10(8) (group A) have a significant higher CD34+ content than group B (female babie’s, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 10(6), while no CBUs with high concentration of CD34+ were detect in group B. CONCLUSION: This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries
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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