1,720,968 research outputs found
Selection and validation of miR-1280 as a suitable endogenous normalizer for qRT-PCR Analysis of serum microRNA expression in Hepatocellular Carcinoma
Full text linkNormalization procedures for the qRT-PCR analysis of miRNA in biological samples are recommended to reduce the variability caused by pre-analytical factors. Since there is no universal standardized normalization strategy for miRNA qRT-PCR studies, we conducted a throughout study to evaluate a panel of small non-coding RNAs (sncRNAs) as reference gene candidate for biomarker studies in serum samples of patients with hepatocellular carcinoma (HCC). Five sncRNAs (miR-1280, miR-1275, SNORD-116, SNORD-68, and U6) were chosen as candidate of reference genes. This study included 122 patients with HCC and was organized into a "pilot phase" consisting of 20 serum samples of HCC patients, and a "validation phase" of 102 patients. Expression level of these candidates were analyzed by qRT-PCR. Assessment of gene stability was performed using four different integrative platforms (geNorm NormFinder, Bestkeeper, and the Delta Ct method). To determine the gene stability during the follow-up of the patient, we extend the analysis of the validation cohort at T1 (1 month after treatment) and T2 (6 month after treatment). MiR-1280 was identified as the most stably expressed reference gene in both pilot and validation phase also during the follow-up. MiR-1280 appears a reliable reference gene candidate in biomarker studies
A comparative characterization of the circulating miRNome in whole blood and serum of HCC patients
Full text linkmiRNAs are considered promising non-invasive biomarkers. Serum represents the major source of biomarkers, being readily accessible for many analytical tests. Recently, whole blood has drawn increasing interest in biomarker studies due to the presence of cancer-interacting cells and circulating cancer cells. Although Hepatocellular Carcinoma (HCC) is the seventh most frequent cancer worldwide, fragmented information exists regarding the miRNome characterization in blood and serum. We profiled the circulatory miRNome of paired serum and blood samples from 20 HCC patients, identifying 274 miRNA expressed in serum and 670 in blood, most of them still uncharacterized. 157 miRNA significantly differ between the two biofluids with 28 exclusively expressed in serum. Six miRNA clusters significantly characterize the two compartments, with the cluster containing miR-4484, miR-1281, miR-3178, miR-3613-3p, miR-4532, miR-4668-5p, miR-1825, miR-4487, miR-455-3p, miR-940 having the highest average expression in serum compared to blood. The ontological analysis revealed a role of these miRNAs in cancer progression, vascular invasion and cancer immune surveillance thought the regulation of DUSP1, PD-L1 and MUC1. Taken together, these results provide the most comprehensive contribution to date towards a complete miRNome profile of blood and serum for HCC patients. We show a consistent portion of circulatory miRNAs being still unknown
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
Circulatory mirna as a biomarker for therapy response and disease-free survival in hepatocellular carcinoma
Full text linkThe clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD). The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p=0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC
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
- …
