Anti-SYP monoclonal antibody, clone TZQ13

Solid papillary carcinoma (SPC) is a histological subtype of breast carcinomas. At least 50% of SPC show neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a transcription factor now employed as a useful neuroendocrine marker. It is suppressed by the Notch signaling pathway in other neuroendocrine tumors. However, the usefulness of INSM1 as a neuroendocrine marker and the relationships between INSM1 and NOTCH receptors in SPC of the breast currently remain unclear. To clarify the usefulness of INSM1 as a neuroendocrine marker and the relationships between INSM1 and NOTCH receptors in SPC, we performed immunohistochemistry using 19 tissue specimens of SPC of the breast. We complementarily analyzed public RNA sequencing data on breast carcinomas. Immunohistochemical examinations revealed that the staining intensity of INSM1 was significantly higher in the neuroendocrine group than in the non-neuroendocrine group. Positive correlations were observed between INSM1 and synaptophysin (SYP), or chromogranin-A (CHGA). In all cases, NOTCH 2 and 3 were positive, while NOTCH 1 and 4 were negative. According to public RNA data analyses, there were positive correlations between INSM1 and SYP, or CHGA, and negative correlations between INSM1 and NOTCH1-3. INSM1 is useful as a diagnostic marker for SPC with neuroendocrine differentiation in the breast.

Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 30 (GSK-3 beta)/beta-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3 beta/beta-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippo campus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment, whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3 beta activity, with decreased inactive phosphorylated GSK-3 beta levels and increased GSK-3 beta, the active form of the kinase. Correspondingly, downstream beta-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus beta-catenin status and the higher dose of NaF also reduced cytoplasmic beta-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3 beta/beta-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3 beta/beta-catenin signaling in the fluoride-induced neurotoxicity. (C) 2018 Published by Elsevier Ltd.