The aim was to evaluate sentinel node detection capacity by means of a magnetic probe in 11 patients with oral squamous cell carcinoma at stages T1‐T2 received submucosal injections of a superparamagnetic iron oxide contrast agent (SPIO). A magnetic probe was used for sentinel node biopsy. The use of SPIO and magnetic probes in the early stages of oral cancer may offer an alternative to conventional radioisotope techniques and/or elective neck dissection.

Early diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of dysplasia could greatly improve the outcome of affected patients. For the first time we compared the mutational landscape of non-progressing dysplasia (NPD; n = 42) with progressing dysplasia (PD; n = 24), along with patient-matched LSCC biopsies; a total of 90 samples. Using targeted next-generation sequencing identified non-synonymous mutations in six genes (PIK3CA, FGFR3, TP53, JAK3, MET, FBXW7), and mutations were validated by Sanger sequencing and/or qPCR. Analysis was extended in silico to 530 head and neck (HNSCC) cases using TCGA data. Mutations in PIK3CA and FGFR3 were detected in PD and LSCC cases, as well as other HNSCC cases, but absent in NPD cases. In contrast, mutations in JAK3, MET and FBXW7 were found in NPD cases but not PD, LSCC or other HNSCC cases. TP53 was the most frequently mutated gene in both PD and NPD cases. With the exception of R248W, mutations were mutually exclusive. Moreover, five of seven PD mutations were located in motif H2 of p53, whereas none of the NPD mutations were. In summary, we propose that the mutational profile of laryngeal dysplasia has utility for the early detection of patients at risk of progression.

The left atrial appendage (LAA) is a small muscular extension that grows from the anterolateral wall of the left atrium, in the proximity of the left pulmonary veins. The presence of a membrane in the LAA is a rare clinical entity whose origin is not known. Its clinical implication in the genesis of atrial arrhythmias and thromboembolic risk remains unknown. We report a case of an obstructive membrane located at the base of the LAA, found incidentally in a young patient who was initially undergoing a transesophageal echocardiogram prior to an invasive treatment for atrial fibrillation.

Neuroblastoma is a type of cancer intimately related with early development and differentiation of neuroendocrine cells, and constitutes one of the pediatric cancers with higher incidence and mortality. Protein tyrosine phosphatases (PTPs) are key regulators of cell growth and differentiation by their direct effect on tyrosine dephosphorylation of specific protein substrates, exerting major functions in the modulation of intracellular signaling during neuron development in response to external cues driving cell proliferation, survival, and differentiation. We review here the current knowledge on the role of PTPs in neuroblastoma cell growth, survival, and differentiation. The potential of PTPs as biomarkers and molecular targets for inhibition in neuroblastoma therapies is discussed.

Introduction Osteosarcoma (OS) is the most common primary bone sarcoma that mainly occurs in children and adolescents. The existence of drug resistant cancer stem cells (CSCs) with progenitor properties is responsible for OS relapse and metastasis. Thus, development of specific therapies targeting OS-CSCs is necessary to increase the long-term survival rate. Although ascorbic acid (AA) has controversial history as anticancer agent, recently it has been re-evaluated revealing more cytotoxic effect to cancer than normal cells. The aim of the study was to analyse AA as potential therapeutic for selective targeting of OS-CSCs. Material and methods To establish primary tumour cultures, tumour samples were mechanically dissected and enzymatically digested. Sarcosphere assay was used to isolate OS-CSCs. The cytotoxic effect of AA was determined by MTT assay as well as relationship between cell concentration and AA. OS-CSCs were treated with different concentrations of AA (2.5-55 mg/ ml) during 72 hour. Concentrations of AA used for further experiments were 30 mg/ml and 40 mg/ml, respectively. Effect of AA on sarcosphere-forming ability was measured under low-attachment condition during 28 days. Cell death type was determined by Annexin V/PI staining using flow cytometry. Levels of GAPDH were determined by western blot while ROS were measured by DCFH-DA assay. Seahorse XF analyzer was used to measure glycolysis and oxidative phosphorylation. Results and discussions While AA did not have any effect on hMSCs, U2OS and Hek 293, respectively, AA efficiently induced dose-dependent viability reduction of OS-CSCs. Further, it can be concluded that IC 50 values of AA depend on the number of seeded OS-CSCs. AA successfully reduced sarcosphere formation on 6th day. High cytotoxicity of AA was further confirmed by Annexin V/PI staining. Prevalent death mode induced by AA was apoptotic since more than 70% of Annexin V-positive cells were detected. In addition, AA inhibited the activity of the key glycolytic enzyme GAPDH and induced ROS levels. Following the treatment with AA, extracellular acidification rate as a measure of glycolysis, was reduced significantly. Moreover, AA increased metabolic potential of OS-CSCs implying cells' ability to meet an energy demand via respiration and glycolysis. Conclusion Based on the obtained results, it can be concluded that AA selectively targets OS-CSCs. The death mechanism is based on the blockage of glycolytic cycle and increased intracellular levels of ROS. Introduction The female mammary gland is a very dynamic organ that undergoes continuous tissue remodelling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy increase the risk of breast cancer, the reasons are unclear. Clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy and that miR-424 (322)/503...