26 research outputs found
Frondoside A suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis
A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 mu M of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1-0.5 mu M) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer
Onderzoek naar de trekvissoorten in het Schelde-estuarium. Voortplantings-en opgroeihabitat van rivierprik en fint
Migratory fish such as river lamprey and twaite shad are important indicators of ecosystem functioning. Over the past century, most migratory fish have disappeared from the river Scheldt due to human impacts. The previous study on migratory fishes in the Scheldt showed however that most species show the first signs of recovery (Stevens et al., 2009). For both river lamprey and twaite shad there are strong indications that they reproduce in the Scheldt. However, the spawning and nursery habitats of both species are unknown and it is unclear whether the preconditions for a sustainable recovery are met. The spawning and nursery habitat of river lamprey can be located through targeted sampling of the larvae in the sediment. Sampling with fyke nets showed that adult river lamprey migrate mainly to the Bovenschelde and Zwalmbeek. In both rivers a number of locations were selected, which are, according to the literature, expected to be suitable habitats for the larvae of river lamprey. Wadable sites were sampled with a specially designed sediment pump and the deeper sites with a Van Veen grab. In neither of these rivers, however, river lamprey larvae could be found and no spawning sites could be identified. Possible reasons for the lack of larvae in the samples are (1) that no suitable larval habitat is present in the studied areas, (2) that the larval density in the investigated habitats is low and hence sampling frequency should be increased, (3) that the River Bovenschelde and the River Zwalm are not the main spawning grounds for river lamprey in the Scheldt. Telemetry of adult river lamprey could be a possible solution to locate the spawning grounds. In order to improve the reproduction and survival of river lamprey in the River Bovenschelde, the migration barriers in the Scheldt and its tributaries should be cleared and sufficient larval habitat should be availability. Larval habitat could be created in the River Zwalm and other tributaries through the restoration of natural banks. In addition, mud and sand banks in the Bovenschelde should be protected as much as possible as potential larval habitat.The population of twaite shad in the Scheldt is too small to identify the critical habitats by sampling in the field. Therefore, a habitat suitability model for spawning and larval shad was constructed based on literature data. Hereto, we first selected the environmental variables that determine habitat suitability. Next, for each variable the tolerance range was determined. Finallly, the variables were combined using fuzzy logic in order to determine the degree of suitability of a habitat. The model predicts the presence of suitable spawning habitat in the Upper Zeeschelde, upstream of the River Durme. Later in the season, when the water temperature rises, suitable spawning habitat is also present in the Rivers Kleine Nete and Grote Nete. Suitable habitat for larval shad is located mainly in the Upper Zeeschelde upstream Rupelmonde and in the River Rupel. Spawning of twaite shad takes place in the main channel and during their ontogeny the larvae migrate to the edges of the main channel and to side channels.Therefore, in areas with suitable spawning and larval habitat, both the main and side channels need protection. In particular mudflats, sand flats and subtidal low dynamic habitats should be safeguarded. Dredging of these habitats thus mortgages the recovery of the twaite shad population in the Scheldt. The oxygen concentration in the estuary has been greatly improved in recent years.However, in summer a low-oxygen zone in the freshwater area persists, comprising the upstream migration of adults and the survival of larvae. Periodic hypoxic conditions should therefore be avoided and a minimum oxygen content of 5 mg / l is essential for both adults and larvae. During the last century, hydrodynamics in the estuary has increased markedly. As a result, larvae have more difficulties in maintaining their position in suitable habitat. Actions that increase the river/tidal flow or eliminate local retention areas should therefore be avoided