Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors.

The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples.

Human adipose-derived mesenchymal stem cells accelerate decellularized neobladder regeneration.

Decellularized natural bladder matrices (neobladders) represent an exciting means to regenerate the bladder following bladder cancer-associated cystectomy. In this study, we compare the evolution of decellularized matrices with recellularized matrices by seeding it with human adipose-derived mesenchymal stem cells (ADSC) after implantation following partial cystectomy in rats. We discovered significant anatomical differences since 10 days after neobladder implantation with the ADSC-containing matrices promoting a significant recovery of mature p63- and cytokeratin 7-positive urothelium.

Insulin resistance disrupts epithelial repair and niche-progenitor Fgf signaling during chronic liver injury.

Insulin provides important information to tissues about feeding behavior and energy status. Defective insulin signaling is associated with ageing, tissue dysfunction, and impaired wound healing. In the liver, insulin resistance leads to chronic damage and fibrosis, but it is unclear how tissue-repair mechanisms integrate insulin signals to coordinate an appropriate injury response or how they are affected by insulin resistance.

Imbalance of immunological synapse-kinapse states reflects tumor escape to immunity in glioblastoma.

Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells.

Prognostic Significance of Cyclins A2, B1, D1, and E1 and Numerical Aberrations in Oral Squamous Cell Carcinomas.

We analysed the expression of cyclins A2, B1, D1, and E1 by immunohistochemistry and numerical aberrations in gene by fluorescence in situ hybridization technique in 67 primary oral squamous cell carcinomas (OSCC). Cyclin A2 expression was observed in 54 (83.1%) tumours, cyclin D1 in 58 (89.

Human Suprapatellar Fat Pad-Derived Mesenchymal Stem Cells Induce Chondrogenesis and Cartilage Repair in a Model of Severe Osteoarthritis.

Cartilage degeneration is associated with degenerative bone and joint processes in severe osteoarthritis (OA). Spontaneous cartilage regeneration is extremely limited. Often the treatment consists of a partial or complete joint implant.

Opposite Effects of Mechanical Action of Fluid Flow on Proangiogenic Factor Secretion From Human Adipose-Derived Stem Cells With and Without Oxidative Stress.

Mechanical forces, hypoxia, and oxidative stress contribute to skin renewal, perfusion, and wound healing, but how are they regulating subcutaneous adipose-derived stem cells (ASCs) in the inflammatory microenvironment associated to skin repair and disorders is unknown. In this study, ASCs were isolated from lipoaspirate samples from plastic surgery patients, primary cultured and their differentiation and secretion of a panel of cytokines with pronounced effects on skin repair and angiogenesis were studied under mechanical stimulation by intermittent fluid flow, 1% hypoxia and oxidative stress by glutathione (GSH) depletion with buthionine sulfoximine (BSO) treatment. Mechanical action of fluid flow did not alter mesenchymal phenotype of CD90 /CD29 /CD44 /CD34 /CD106 /CD45 ASCs; however, it remarkably induced ASC secretion of human umbilical vein endothelial cell (HUVEC) migration-stimulating factors.

Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy.

Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic reticulum (ER) Ca2+, likely in association with an abnormal distribution of the mitochondrial network.

Cryoplasty versus angioplasty in the treatment of arterial restenosis in an experimental model of atherosclerosis in rabbits.

Cryoplasty may reduce the incidence of post-angioplasty restenosis in peripheral atherosclerotic arteries. Our study is looking to investigate the mid-term effects (4 weeks) of an FDA-approved cryoplasty catheter (PolarCath(®), Boston Scientific) compared to a conventional angioplasty catheter using a hypercholesterolemic rabbit model of arterial restenosis based on diet plus vessel injury. Thirty-six normolipidemic, 3-month old male New Zealand White rabbits were used.

Ultrastructural pathology of anaplastic and grade II ependymomas reveals distinctive ciliary structures--electron microscopy redux.

Ependymoma tumors likely derive from the ependymal cells lining the CNS ventricular system. In grade II ependymomas, tumor cells resemble typical ependymocytes, while anaplastic ependymomas are poorly differentiated. We studied three grade II and one anaplastic ependymoma, focusing on the ciliary structures.

Family history and breast cancer hormone receptor status in a Spanish cohort.

Background: Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women.

Materials And Methods: A population-based study was conducted in the city of Santiago de Compostela, Spain.

Influence of on-site cytopathology evaluation on the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic masses.

Objectives: The aim of this study was to evaluate the influence of on-site cytopathological evaluation on the diagnostic yield of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) for the differential diagnosis of solid pancreatic masses in an unselected series of consecutive patients.

Methods: Patients undergoing EUS-guided FNA of solid pancreatic lesions over a 2-year study period were included. Samples were either evaluated on site by a cytopathologist or processed by the endoscopist and sent to the pathology department for evaluation.

[Laryngeal adenocarcinoma: case report].

Laryngeal adenocarcinomas are extremely unusual (only 0.35 %-0.5 % of all laryngeal malignancies).

Clinicopathological and immnuohistochemical findings in a series of folliculosebaceous cystic hamartoma.

Background: Folliculo-sebaceous cystic hamartoma (FSCH) is an uncommon skin condition presenting as a slow-growing papulo-nodular lesion, in or around the nose. Most cases are not clinically suspected and only histopathological examination allows the diagnosis. Pathological features include a dermal-located infundibulo-cystic structure with sebaceous glands radiating around, a stromal component encircling the epithelial structures, with clefts between the lesional epithelial and stromal parts, as well as between this and the adjacent dermis.

Controversial origin of Pseudomyxoma peritonei.

Pseudomyxoma peritonei describes the accumulation of mucinous material in the abdominal cavity. The main diagnostic problem appears when the primary site of origin could be appendix or ovary. In this paper describe clinicopathological features and biological markers that support appendiceal origin.

Immunohistochemical expression of HIF-1alpha in response to early myocardial ischemia.

This study aims to evaluate the effects of ischemia on the myocardial fibers and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor-1 alpha (HIF-1alpha) in human heart specimens. We have prospectively analyzed the HIF-1alpha expression in human ischemic hearts with the ABC-inmunohistochemistry technique and amplification by biotinylated tyramide. The relationship between the expression of HIF-1alpha and the temporal evolution of ischemia has also been evaluated.