Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel

Background: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. Aim: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. Methods: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT-PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. Results: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. Conclusion: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel.7 page(s

Sea-ice dynamics in an Arctic coastal polynya during the past 6500 years

The production of high-salinity brines during sea-ice freezing in circum-arctic coastal polynyas is thought to be part of northern deep water formation as it supplies additional dense waters to the Atlantic meridional overturning circulation system. To better predict the effect of possible future summer ice-free conditions in the Arctic Ocean on global climate, it is important to improve our understanding of how climate change has affected sea-ice and brine formation, and thus finally dense water formation during the past. Here, we show temporal coherence between sea-ice conditions in a key Arctic polynya (Storfjorden, Svalbard) and patterns of deep water convection in the neighbouring Nordic Seas over the last 6500 years. A period of frequent sea-ice melting and freezing between 6.5 and 2.8 ka BP coincided with enhanced deep water renewal in the Nordic Seas. Near-permanent sea-ice cover and low brine rejection after 2.8 ka BP likely reduced the overflow of high-salinity shelf waters, concomitant with a gradual slow down of deep water convection in the Nordic Seas, which occurred along with a regional expansion in sea-ice and surface water freshening. The Storfjorden polynya sea-ice factory restarted at ~0.5 ka BP, coincident with renewed deep water penetration to the Arctic and climate amelioration over Svalbard. The identified synergy between Arctic polynya sea-ice conditions and deep water convection during the present interglacial is an indication of the potential consequences for ocean ventilation during states with permanent sea-ice cover or future Arctic ice-free conditions

Inhibition of cancer cell invasion and metastasis by genistein

Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In particular, genistein has emerged as an important inhibitor of cancer metastasis. Consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein’s antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade. Reports have demonstrated that, at high concentrations, genistein can inhibit several proteins involved with primary tumor growth and apoptosis, including the cyclin class of cell cycle regulators and the Akt family of proteins. At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the transforming growth factor (TGF)-β signaling pathway. Several in vitro findings have been corroborated in both in vivo animal studies and in early-phase human clinical trials, demonstrating that genistein can both inhibit human cancer metastasis and also modulate markers of metastatic potential in humans, respectively. Herein, we discuss the variety of mechanisms by which genistein regulates individual steps of the metastatic cascade and highlight the potential of this natural product as a promising therapeutic inhibitor of metastasis

Invasive properties of cancer - a treatment target? : In vitro studies in human prostate cancer cell lines

Dr.philos.Dr.philos

Closing the loop Approaches to monitoring the state of the Arctic Mediterranean during the International Polar Year 20072008

During the 4th International Polar Year 2007–2009 (IPY), it has become increasingly obvious that we need to prepare for a new era in the Arctic. IPY occurred during the time of the largest retreat of Arctic sea ice since satellite observations started in 1979. This minimum in September sea ice coverage was accompanied by other signs of a changing Arctic, including the unexpectedly rapid transpolar drift of the Tara schooner, a general thinning of Arctic sea ice and a double-dip minimum of the Arctic Oscillation at the end of 2009. Thanks to the lucky timing of the IPY, those recent phenomena are well documented as they have been scrutinized by the international research community, taking advantage of the dedicated observing systems that were deployed during IPY. However, understanding changes in the Arctic System likely requires monitoring over decades, not years. Many IPY projects have contributed to the pilot phase of a future, sustained, observing system for the Arctic. We now know that many of the technical challenges can be overcome. The Norwegian projects iAOOS-Norway, POLEWARD and MEOP were significant ocean monitoring/research contributions during the IPY. A large variety of techniques were used in these programs, ranging from oceanographic cruises to animal-borne platforms, autonomous gliders, helicopter surveys, surface drifters and current meter arrays. Our research approach was interdisciplinary from the outset, merging ocean dynamics, hydrography, biology, sea ice studies, as well as forecasting. The datasets are tremendously rich, and they will surely yield numerous findings in the years to come. Here, we present a status report at the end of the official period for IPY. Highlights of the research include: a quantification of the Meridional Overturning Circulation in the Nordic Seas (“the loop”) in thermal space, based on a set of up to 15-year-long series of current measurements; a detailed map of the surface circulation as well as characterization of eddy dispersion based on drifter data; transport monitoring of Atlantic Water using gliders; a view of the water mass exchanges in the Norwegian Atlantic Current from both Eulerian and Lagrangian data; an integrated physical–biological view of the ice-influenced ecosystem in the East Greenland Current, showing for instance nutrient-limited primary production as a consequence of decreasing ice cover for larger regions of the Arctic Ocean. Our sea ice studies show that the albedo of snow on ice is lower when snow cover is thinner and suggest that reductions in sea ice thickness, without changes in sea ice extent, will have a significant impact on the arctic atmosphere. We present up-to-date freshwater transport numbers for the East Greenland Current in the Fram Strait, as well as the first map of the annual cycle of freshwater layer thickness in the East Greenland Current along the east coast of Greenland, from data obtained by CTDs mounted on seals that traveled back and forth across the Nordic Seas. We have taken advantage of the real-time transmission of some of these platforms and demonstrate the use of ice-tethered profilers in validating satellite products of sea ice motion, as well as the use of Seagliders in validating ocean forecasts, and we present a sea ice drift product – significantly improved both in space and time – for use in operational ice-forecasting applications. We consider real-time acquisition of data from the ocean interior to be a vital component of a sustained Arctic Ocean Observing System, and we conclude by presenting an outline for an observing system for the European sector of the Arctic Ocean