Search

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas, characterized by complex karyotypes. The molecular bases of such malignancy are poorly understood and efficient targeted molecular therapies are currently lacking. Here we describe a novel zebrafish model of MPNSTs, represented by the transgenic mutant line Tg(-8.5nkx2.2a:GFP)ia2. ia2 homozygous animals displayed embryonic lethality by 72 hpf, while the heterozygotes develop visible tumor masses with high frequency in adulthood. Histological and immunohistochemical examination revealed aggressive tumors with either mesenchymal or epithelial features. The former (54% of the cases) arose either in the abdominal cavity, or as intrathecal/intraspinal lesions and is composed of cytokeratin-negative spindle cells with fascicular/storiform growth pattern consistent with zebrafish MPNSTs. The second histotype was composed by polygonal or elongated cells, immunohistochemically positive for the pan-cytokeratin AE1/AE3. The overall histologic and immunohistochemical features were consistent with a malignant epithelial neoplasm of possible gastrointestinal/pancreatic origin. With an integrated approach, based on microsatellite (VNTR) and STS markers, we showed that ia2 insertion, in Tg(-8.5nkx2.2a:GFP)ia2 embryos, is associated with a deletion of 15.2 Mb in the telomeric portion of chromosome 1. Interestingly, among ia2 deleted genes we identified the presence of the 40S ribosomal protein S6 gene that may be one of the possible drivers for the MPNSTs in ia2 mutants.Thanks to the peculiar features of zebrafish as animal model of human cancer (cellular and genomic similarity, transparency and prolificacy) and the GFP tag, the Tg(-8.5nkx2.2a:GFP)ia2 line provides a manageable tool to study in vivo with high frequency MPNST biology and genetics, and to identify, in concert with the existing zebrafish MPNST models, conserved relevant mechanisms in zebrafish and human cancer development.

Siki (Centroscymnus coelolepis) hydrolysates may contain calcitonin gene-related peptide (CGRP)-like molecules. These CGRP-like molecules have attracted attention from the food industry due to their promising applications in the field of functional foods. These CGRP-like molecules were purified and sequenced, and found to show homology to fragments of fish and human collagen. The effect on plasma CGRP-levels of daily gavage with siki hydrolysate containing CGRP-like molecules was further studied in male Wistar rats. The plasma CGRP-levels in rats force fed with the siki hydrolysate were significantly higher than those of the control group. The siki hydrolysate included immunoreactive-CGRP molecules which resisted simulated protein digestion. They were able to cross the intestinal barrier intact and could be responsible for the increase in plasma CGRP levels. This increment in plasma CGRP levels was insufficient to affect body weight or food intake. However, it could lead to other beneficial effects on health. © 2012 Elsevier Ltd.

Fish protein hydrolysates (FPH) have good and well documented functional properties. Peptides obtained from various fish protein hydrolysates have also shown bioactive and antioxidative activities. The aim of this study was to evaluate how storage and preparation of cod (Gadus morhua) backbones influence the yield, functionality, bioactivity (CGRP and gastrin/CCK related molecules) and antioxidative properties of fish protein hydrolysates. A series of hydrolysis trials have been carried out using backbones from cod that were initially fresh or frozen and further hydrolysed for different times (10, 25, 45 and 60 min). Use of fresh raw material significantly increased yield of dry FPH, gave lighter and less yellow powders with better emulsification properties. Longer time of hydrolysis gave higher FPH yield, increased degree of hydrolysis and decreased water holding capacity of the powders. Among the hydrolysis times tested, 25 and 45 min hydrolysis demonstrated the best emulsification properties. FPH have potential to enhance product stability by preventing oxidative deterioration. The DPPH scavenging activity showed that antioxidative activity of hydrolysates could be due to the ability to scavenge lipid radicals. The ability of hydrolysates to inhibit iron induced lipid oxidation was not influenced by time of hydrolysis. This work also shows that it is possible to obtain bioactive molecules from cod backbones by protein hydrolysis. The content of bioactive peptides (gastrin/CCK- and CGRP-like peptides) could make the cod hydrolysates useful for incorporation in functional foods.

Fish protein hydrolysates (FPH) may have potential as bioactive components in functional foods as nutraceuticals. This study focused on the identification of calcitonin gene-related peptide (CGRP) molecules in FPH. CGRP is a neuropeptide belonging to the calcitonin/CGRP family and is known as potent arterial and venous vasodilator in humans. Hydrolysates of industrial origin were prepared from siki (Centroscymnus coelolepsis) heads and were analyzed for the presence of CGRP-like molecules using specific radioimmunoassays and radioreceptorassays. The biological activity of the CGRP-related molecules was assessed by their ability to stimulate the adenylate cyclase activity in rat liver membranes. They were finally purified using gel exclusion chromatography and high-performance liquid chromatography (HPLC). These molecules presented a molecular weight around 1500-2500 Da and were obtained with a purification factor of 79. The incorporation of FPH with CGRP-like molecules in functional foods could lead to the development of new useful products for health and nutrition markets. © 2007 American Chemical Society.