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Tombolan L.,University of Padua | Zampini M.,University of Padua | Casara S.,University of Padua | Boldrin E.,University of Padua | And 6 more authors.
PLoS ONE | Year: 2015

Background: Rhabdomyosarcomas (RMS) are rare but very aggressive childhood tumors that arise as a consequence of a regulatory disruption in the growth and differentiation pathways of myogenic precursor cells. According to morphological criteria, there are two major RMS subtypes: embryonal RMS (ERMS) and alveolar RMS (ARMS) with the latter showing greater aggressiveness and metastatic potential with respect to the former. Efforts to unravel the complex molecular mechanisms underlying RMS pathogenesis and progression have revealed that microRNAs (miRNAs) play a key role in tumorigenesis. Methodology/Principal Findings: The expression profiles of 8 different RMS cell lines were analyzed to investigate the involvement of miRNAs in RMS. The miRNA population from each cell line was compared to a reference sample consisting of a balanced pool of total RNA extracted from those 8 cell lines. Sixteen miRNAs whose expression discriminates between translocation-positive ARMS and negative RMS were identified. Attention was focused on the role of miR-27a that is up-regulated in the more aggressive RMS cell lines (translocation-positive ARMS) in which it probably acts as an oncogene. MiR-27a overexpressing cells showed a significant increase in their proliferation rate that was paralleled by a decrease in the number of cells in the G1 phase of the cell cycle. It was possible to demonstrate that miR-27a is implicated in cell cycle control by targeting the retinoic acid alpha receptor (RARA) and retinoic X receptor alpha (RXRA). Conclusions: Study results have demonstrated that miRNA expression signature profiling can be used to classify different RMS subtypes and suggest that miR-27a may have a therapeutic potential in RMS by modulating the expression of retinoic acid receptors. © 2015 Tombolan et al.


Zhang W.,Childrens Hospital of Hebei Province | Li F.,Childrens Hospital of Hebei Province | Yang Y.,Childrens Hospital of Hebei Province | Xue L.,Childrens Hospital of Hebei Province | And 2 more authors.
Journal of Cosmetic and Laser Therapy | Year: 2016

Background: Pulsed dye laser (PDL) treatment remains the standard of care for infantile hemangiomas (IHs). However, the use of PDL to treat IHs in neonates has been hardly reported. In this study, the PDL treatments of IHs between neonatal and non-neonatal patients were retrospectively investigated. Methods: All patients diagnosed with hemangiomas were treated by PDL. Their clinical data were collected, and the treatment outcomes and PDL parameters in neonates and non-neonates were analyzed using the Mann–Whitney U-rank test. Results: All patients reached good or excellent scale in the treatment efficiency assessment. Laser energy used per treatment session was significantly lower in neonatal group than in non-neonatal group (Z = −8.980, P < 0.001). Total laser energy used in neonates was also markedly lower than that in non-neonatal patients (Z = −3.065, P = 0.002). However, treatment session numbers in these two groups were not significantly different (Z = −1.725, P = 0.085). Additionally, we observed that after each treatment, the purpura disappeared faster in neonates (2–4 weeks) than in non-neonatal patients (4–6 weeks), indicating neonates might have greater recovery ability. Conclusions: PDL, with distinct parameters, was effective in the treatment of IHs in neonates. After each laser treatment, neonates recovered faster than non-neonatal patients. © 2016 Taylor & Francis Group, LLC


Wang Q.,Peoples Hospital of Xiangtan County | Dong J.,Institute of Pediatric Research | Zhu Y.,Children Hospital of Hunan Province
Journal of Pediatric Surgery | Year: 2012

Purpose: Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract in preterm infants, whereas probiotic supplementation might reduce NEC risk and potentially provide benefits to preterm infants. We performed an updated meta-analysis of all relevant randomized, controlled trials to assess the benefits of probiotic supplementation for preterm very low-birth-weight (VLBW) infants. Methods: We searched in PubMed, Embase, and Chinese BioMedical Literature Database (CBM) databases, and 20 randomized, controlled trials (a total of 3816 preterm VLBW infants) were finally included into this meta-analysis. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model depending on the heterogeneity of the included studies. Results: Probiotic supplement was associated with a significantly decreased risk of NEC in preterm VLBW infants (RR = 0.33; 95% confidence interval [CI], 0.24-0.46; P <.00001). Risk of death was also significantly reduced in the probiotic group (RR = 0.56; 95% CI, 0.43-0.73; P <.0001). There was no difference in the risk of sepsis between the probiotic group and placebo group (RR = 0.90; 95% CI, 0.71-1.15; P =.40). Conclusions: Probiotic supplement can reduce risk of NEC and mortality in preterm VLBW infants. However, the optimum type of probiotic supplement and the long-term effects need further study. © 2012 Elsevier Inc. All rights reserved.


D'Angelo E.,University of Padua | D'Angelo E.,Institute of Pediatric Research | Fassan M.,University of Padua | Maretto I.,University of Padua | And 8 more authors.
Oncotarget | Year: 2016

Background: Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradiotherapy (pCRT) followed by surgery. However, after pCRT the complete pathological response is approximately 20%, whereas in 20 to 40% of patients the response is poor or absent. Methods: Cancer biopsy specimens (n= 38) and serum samples (n= 34) obtained before pCRT from 38 LARC patients were included in the study. Patients were classiied in responders (R, tumor regression grade [TRG] 1-2; n= 16) and non-responders (NR, TRG 3-5; n= 22) according to the pathological response observed upon surgery. We performed miRNA microarrays analysis on biopsy specimens, and validated the selected candidates both by qRT-PCR (tissue and serum) and by in situ hybridization (tissue, miR-125b) analyses. Results: Eleven miRNAs were signiicantly different between R and NR (miR-154, miR-409-3p, miR-127-3p, miR-214*, miR-299-5p and miR-125b overexpressed in NR; miR-33a, miR-30e, miR-338-3p, miR-200a and miR-378 decreased). In particular, miR-125b resulted to be the best candidate to discriminate the two groups (AUC of 0.9026; 95% CI, 0.7618-1.043). Additionally, miR-125b serum levels were signiicantly overexpressed in NR patients compared to R (p-value=0.0087), with an excellent discriminating power (AUC of 0.782; 95% CI, 0.6123-0.9518). Conclusions: The obtained results further support the clinical impact of miRNA analysis. High miR-125b expression in tissue and serum were associated with a poor treatment response in LARC patients, therefore miR-125b could be considered as a possible novel non-invasive biomarker of response in LARC treatment.


Sikora K.,University of Verona | Bedin C.,University of Padua | Vicentini C.,University of Verona | Malpeli G.,University of Verona | And 11 more authors.
International Journal of Biological Markers | Year: 2015

Background: Currently, no reliable blood-based assay for early detection of pancreatic ductal adenocarcinoma (PDAC) is available. Cell-free DNA (cfDNA) quantitation in patients’ plasma has been recently applied in monitoring several cancer types. This study evaluates the diagnostic potential of cfDNA in PDAC patients. Methods: Plasma cfDNA levels and integrity ratio were assayed using quantitative real-time PCR of Alu-repeat amplicons in patients with pancreatic ductal adenocarcinoma (n=50), pancreatic neuroendocrine tumor (n=23), and chronic pancreatitis (n=20), as well as in healthy volunteers without evidence of pancreatic disease (n=23). Results: The total load of cfDNA, obtained by Alu83 quantitation, was the highest in PDAC patients than in any of the other patient groups (Welch t test; p<0.001) and was an average predictor of PDAC disease (AUC=0.664; CI, 0.56-0.77). A nonlinear association between Alu83 levels and subjects’ age was detected (Spearman’s rho=0.35; p<0.001) in the overall population, as well as within the PDAC patients’ group (Spearman’s rho=0.47; p<0.001). Necrosis-derived cfDNA fragments, quantitated with the Alu244 amplicon, were barely detectable in any of the samples and, in that respect, comparable between the different subject groups. CfDNA integrity estimation (Alu244/Alu83 ratio) was significantly affected by the limited detectability of plasma Alu244 levels. Conclusion: The lack of detectable levels of necrosis-derived cfDNA in pancreatic pathologies considerably affects the clinical use of such biomarker in PDAC patients. Different methods of analysis should be applied in the evaluation of the cfDNA diagnostic value in pancreas pathology. © 2014 Wichtig Publishing - eISSN 1724-6008.

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