This work supports further investigation into the use of MSC secretome for priming TCs toward a more differentiated phenotype, and it promotes the tissue engineering strategy as a promising modality to help improve treatment outcomes for chronic MRCTs.

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Mesenchymal stem cell secretome decreases the characteristic muscle degeneration associated with chronic rotator cuff tears.

Peritoneal dissemination is a particular form of metastasis typically observed in ovarian cancer and the major cause for poor patient's outcome. Identification of the molecular players involved in ovarian cancer dissemination can offer an approach to develop treatment strategies to improve clinical prognosis. Here, we identified mesothelin (MSLN) as a crucial protein in the multistep process of peritoneal dissemination of ovarian cancer. We demonstrated that MSLN is overexpressed in primary and matched peritoneal metastasis of high-grade serous carcinomas (HGSC). Using several genetically engineered ovarian cancer cell lines, resulting in loss or gain of function, we found that MSLN increased cell survival in suspension and invasion of tumor cells through the mesothelial cell layer in vitro. Intraperitoneal xenografts established with MSLN high ovarian cancer cell lines showed enhanced tumor burden and spread within the peritoneal cavity. These findings provide strong evidences that MSLN is a key player in ovarian cancer progression by triggering peritoneal dissemination and provide support for further clinical investigation of MSLN as a therapeutic target in HGSC.

The present study has been able to establish an animal model that disclosed the hallmarks of MRCT. This can now be used as a valuable, cost-effective, pre-clinical instrument to assist in the development of advanced tissue engineered strategies. Moreover, this animal model overcomes some of the limitations of those that have been reported so far and thus represents a more reliable source for the assessment of future therapeutic strategies with potential clinical relevance.

PurposePatients with Fanconi anaemia (FA), a rare DNA repair genetic disease, exhibit chromosome fragility, bone marrow failure, malformations and cancer susceptibility. FA molecular diagnosis is challenging since FA is caused by point mutations and large deletions in 22 genes following three heritability patterns. To optimise FA patients’ characterisation, we developed a simplified but effective methodology based on whole exome sequencing (WES) and functional studies.Methods68 patients with FA were analysed by commercial WES services. Copy number variations were evaluated by sequencing data analysis with RStudio. To test FANCA missense variants, wt FANCA cDNA was cloned and variants were introduced by site-directed mutagenesis. Vectors were then tested for their ability to complement DNA repair defects of a FANCA-KO human cell line generated by TALEN technologies.ResultsWe identified 93.3% of mutated alleles including large deletions. We determined the pathogenicity of three FANCA missense variants and demonstrated that two FANCA variants reported in mutations databases as ‘affecting functions’ are SNPs. Deep analysis of sequencing data revealed patients’ true mutations, highlighting the importance of functional analysis. In one patient, no pathogenic variant could be identified in any of the 22 known FA genes, and in seven patients, only one deleterious variant could be identified (three patients each with FANCA and FANCD2 and one patient with FANCE mutations)ConclusionWES and proper bioinformatics analysis are sufficient to effectively characterise patients with FA regardless of the rarity of their complementation group, type of mutations, mosaic condition and DNA source.

Wilms' Tumour (WT) is the most common kidney tumour in childhood, this fact and the embryonic complexity of WT create, whenever one of its three classical components predominates in cytologic smears, difficulties in the differential diagnoses with other less common entities. In the present study, we review the cytological and immunohistochemical characteristics of three children renal tumours, a Clear Cell Sarcoma of the Kidney (CCSK-case1), a Cellular Mesoblastic Nephroma (CMN-case2) and a Metanephric Adenoma (MA-case3) and compare them, for differential diagnostic purposes, with smears of blastematous, mesenchymal and epithelial predominant WTs, previously diagnosed in our Department. In all cases a mass was detected in the abdomen (2 and 8 year old children-cases 1 and 3, respectively), and pre-birth in case 2 (the tumour was detected during pregnancy). Fine needle biopsy was performed followed by routine cytologic examination. The presence of moderate amount of blue pale cytoplasm in neoplastic cells (case1), the presence of tightly cohesive, bland, spindle tumour cells (case2) and the identification of small, well differentiated epithelial tubules with psammoma bodies in case 3, were the main morphologic characteristics that we think represent the most important elements for distinguishing our cases from a WT. Immunoreactivity was only helpful in case 1 as we found a characteristic dot-like pattern positivity for vimentin, in the absence of immunoreactivity for the other markers that are usually positive in WT. Summing up, these three cases demonstrate that cytopathologists should be aware of the occurrence of uncommon renal neoplasms in childhood and should be acquainted with their characteristics, in order to avoid false diagnoses.

We describe a new approach for decreasing the characteristic muscle degeneration associated with chronic rotator cuff tears. This strategy is particularly important for patients whose tendon healing after later surgical repair could be compromised by the progressing degenerative changes. In addition, both precise intramuscular local injection and multiple systemic secretome injections have been shown to be promising delivery forms for preventing muscle degeneration.