Prion diseases belong to a group of infectious, fatal neurodegenerative disorders. The conformational conversion of a cellular prion protein (PrP(C)) into an abnormal misfolded isoform (PrP(Sc)) is the key event in prion disease pathology. PrP106-126 resembles PrP(Sc) in some physicochemical and biological characteristics, such as apoptosis induction in neurons, fibrillar formation, and mediation of the conversion of native cellular PrP(C) to PrP(Sc). Numerous studies have been conducted to explore the inhibiting methods on the aggregation and neurotoxicity of prion neuropeptide PrP106-126. We showed that PrP106-126 aggregation, as assessed by fluorescence assay and atomic force microscopy, is inhibited by platinum complexes cisplatin, carboplatin, and Pt(bpy)Cl2. ESI-MS and NMR assessments of PrP106-126 and its mutant peptides demonstrate that platinum complexes bind to the peptides in coordination and nonbonded interactions, which rely on the ligand properties and the peptide sequence. In peptides, methionine residue is preferred as a potent binding site over histidine residue for the studied platinum complexes, implying a typical thiophile characteristic of platinum. The neurotoxicity induced by PrP106-126 is better inhibited by Pt(bpy)Cl2 and cisplatin. Furthermore, the ligand configuration contributes to both the binding affinity and the inhibition of peptide aggregation. The pursuit of novel platinum candidates that selectively target prion neuropeptide is noteworthy for medicinal inorganic chemistry and chemical biology.
Background
Previously, only six cases of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNENs) with squamous cell carcinoma (SCC) component have been described in the colorectum, and the molecular landscape of MiNENs is also poorly understood. Herein, we present a unique case in which the SCC developed as a component of a MiNEN in the rectum.
Case presentation
The patient was firstly diagnosed as rectal small cell neuroendocrine carcinoma (SCNEC) covered by tubulovillous adenoma, and then mixed SCNEC and SCC in the same site 6 months later. Representative samples from the three histologic subtypes were then sent for next-generation sequencing (NGS) separately. Multiple liver metastases occurred in the following month after the last surgery. The patient died of ketoacidosis 1 year after initial diagnosis of the tumor.
Conclusion
This is the first report of this exceedingly rare tumor type to include NGS of the 3 separate morphological entities. Our findings may expedite the understanding of combined tumors in the colorectum.
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