AGO2-RIP-Seq reveals miR-34/miR-449 cluster targetome in sinonasal cancers.

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.

Biomolecular alterations temporally anticipate microarchitectural modifications of collagen in oral tongue squamous cell carcinoma.

High resolution analysis of collagen bundles could provide information on tumor onset and evolution. This study was focused on the microarchitecture and biomolecular organization of collagen bundles in oral tongue squamous cell carcinoma (OTSCC). Thirty-five OTSCC biopsy samples were analyzed by synchrotron-based phase-contrast microcomputed tomography and Fourier transform infrared imaging (FTIRI) spectroscopy. PhC-microCT evidenced the presence of reduced and disorganized collagen in the tumor area compared to the extratumoral (ExtraT) one. FTIRI also revealed a reduction of folded secondary structures in the tumor area, and highlighted differences in the peritumoral (PeriT) areas in relation with the OTSCC stage, whereby a significantly lower amount of collagen with less organized fibers was found in the PeriT stroma of advanced-OTSCC stages. Interestingly, no significant morphometrical mismatches were detected in the same region by PhC-microCT analysis. These results suggest that biomolecular alterations in the OTSCC stroma temporally anticipate structural modifications of collagen bundle microarchitecture.

A Novel Use of Autologous Fibrin by Intracatheter Injection in Persistent Postoperative Biliary Defects: Technical Note on a Preliminary Experience.

PURPOSE: To introduce percutaneous selective injection of autologous platelet-rich fibrin as a novel technique for persistent bile leakage repair and sharing the results of our preliminary experience. MATERIALS AND METHODS: Seven patients (57.1% females; mean age 69.6 ± 8 years) with the evidence of persistent bile leak secondary to hepatobiliary surgery and ineffective treatment with percutaneous transhepatic biliary drainage were submitted to fibrin injection. Platelet-rich fibrin, a dense fibrin clot promoting tissue regeneration, was obtained from centrifuged patient's venous blood. Repeated percutaneous injections through a catheter tip placed in close proximity to the biliary defect were performed until complete obliteration at fistulography. Technical and clinical success were evaluated. RESULTS: Bile leaks followed pancreaticoduodenectomy in five and major hepatectomy in two patients. Technical success defined as fibrin injection at BD site was achieved in all seven patients, and clinical success defined as a complete healing of the BD at fistulography was achieved in six patients. The median time to BD closure was 76.7 ± 40.5 days and the average procedure number was 3 ± 1 per patient. In one patient, defect persistance after four treatments required gelatin sponge injection. No major complications occurred. One case of post-procedural transitory hyperpirexia was registered. CONCLUSION: In persistent biliary defects, despite prolonged biliary drainage stay, percutaneous injection of autologous platelet-rich fibrin appears as a readily available and feasible emergent technique in promoting fistulous tracts obliteration still mantaining main ducts patency.

A pilot study to evaluate the expression of microRNA­let­7a in patients with intestinal­type sinonasal adenocarcinoma.

Despite its histological resemblance to colorectal adenocarcinoma, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITAC). The present study investigated the possible role and clinical value of microRNA (miR)-let-7a, a head and neck squamous cell carcinoma-related miR, in a well-characterized and homogeneous cohort of patients with ethmoidal ITAC associated with occupational exposure, treated by primary surgery. miR-let-7a expression levels were analyzed in 23 pairs of ethmoidal ITAC and adjacent normal formalin-fixed paraffin-embedded tissues by reverse transcription-quantitative PCR. The expression was evaluated in tumor and healthy tissues according to: Tumor grade (G) of differentiation and extension, and pTNM stage, and presence/absence of recurrence. Comparisons within and between groups were performed using two-tailed Student's paired t-test and one-way ANOVA with Tukey's post hoc test. P<0.05 was considered to indicate a statistically significant difference. miR-let-7a expression in ethmoidal ITAC tissues was significantly lower than that in adjacent normal tissues (P<0.05; mean expression level ± SD, 1.452707±1.4367189 vs. 4.094017±2.7465375). miR expression varied with pT stage. miR-let-7a was downregulated (P<0.05) in advanced stages (pT3-pT4) compared with earlier stages (pT1-pT2). Furthermore, downregulation of miR-let-7a in ITAC was associated with poorly-differentiated (G3) cancer (P<0.05). No other associations were observed between miR-let-7a expression and the other clinicopathological parameters, including disease-free survival. In conclusion, downregulation of miR-let-7a in ITAC was associated with advanced-stage (pT3 and pT4) and poorly-differentiated (G3) disease, suggesting that the mutation of this gene, combined with additional genetic events, could serve a role in ITAC pathogenesis.

Linfoma malt primario de la lengua / Primary malt limphoma of the tongue

Los linfomas derivados de los tejidos linfoides asociados a las mucosas (MALT) primarios de la lengua son infrecuentes. Se documenta el caso de una paciente de 80 años de edad, con un tumor en el dorso de la lengua filiado histológicamente como linfoma extranodal de células B. Se sugiere como posible origen del linfoma un proceso reactivo de origen desconocido, al presentar las glándulas salivales menores adyacentes al tumor un cuadro compatible con una sialadenitis mioepitelial (AU)

Primitive malignant lymphoma mucosa associated lymphoid tissue (MALT) on the tongue are rare entities. We report here a case of an old woman (80 years old) with a tumor in the dorsum of the tongue, which was histologically diagnosed as an extra-nodal marginal B cell lymphoma. An inflammatory reaction resembling myoepithelial sialoadenitis was observed in the minor salivary glands adjacent at the tumour, suggesting a possible derivation of the lymphoma from a previous reactive process of unknown origin (AU)