Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy.

OBJECTIVES: Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy. METHODS: From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration. RESULTS: Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20+ B-lymphocytes, followed by CD68+ macrophages, CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), and T-bet+ Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells. CONCLUSIONS: Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.

Effects of parasitic freshwater mussels on their host fishes: a review.

Freshwater mussels in the order Unionida are highly adapted to parasitize fish for the primary purpose of dispersal. The parasitic larval stage affixes itself to the gills or fins of the host where it becomes encysted in the tissue, eventually excysting to develop into a free-living adult. Research on the parasitic interactions between unionids and their host fishes has garnered attention recently due to the increase in worldwide preservation efforts surrounding this highly endangered and ecologically significant order. With the exception of heavy infestation events, these mussels cause minor effects to their hosts, typically only observable effect in combination with other stressors. Moreover, the range of effect intensities on the host varies greatly with the species involved in the interaction, an effect that may arise from different evolutionary strategies between long- and short-infesting mussels; a distinction not typically made in conservation practices. Lower growth and reduced osmotic potential in infested hosts are commonly observed and correlated with infestation load. These effects are typically also associated with increases in metabolic rate and behaviour indicative of stress. Host fish seem to compensate for this through a combination of rapid wound healing in the parasitized areas and higher ventilation rates. The findings are heavily biased towards Margaritifera margaritifera, a unique mussel not well suited for cross-species generalizations. Furthermore, the small body of molecular and genetic studies should be expanded as many conclusions are drawn from studies on the ultimate effects of glochidiosis rather than proximate studies on the underlying mechanisms.

Temperature and predator-mediated regulation of plasma cortisol and brain gene expression in juvenile brown trout (Salmo trutta).

BACKGROUND: Temperature affects many aspects of performance in poikilotherms, including how prey respond when encountering predators. Studies of anti-predator responses in fish mainly have focused on behaviour, whereas physiological responses regulated through the hypothalamic-pituitary-interrenal axis have received little attention. We examined plasma cortisol and mRNA levels of stress-related genes in juvenile brown trout (Salmo trutta) at 3 and 8 °C in the presence and absence of a piscivorous fish (burbot, Lota lota). RESULTS: A redundancy analysis revealed that both water temperature and the presence of the predator explained a significant amount of the observed variation in cortisol and mRNA levels (11.4 and 2.8%, respectively). Trout had higher cortisol levels in the presence than in the absence of the predator. Analyses of individual gene expressions revealed that trout had significantly higher mRNA levels for 11 of the 16 examined genes at 3 than at 8 °C, and for one gene (retinol-binding protein 1), mRNA levels were higher in the presence than in the absence of the predator. Moreover, we found interaction effects between temperature and predator presence for two genes that code for serotonin and glucocorticoid receptors. CONCLUSIONS: Our results suggest that piscivorous fish elicit primary stress responses in juvenile salmonids and that some of these responses may be temperature dependent. In addition, this study emphasizes the strong temperature dependence of primary stress responses in poikilotherms, with possible implications for a warming climate.

Substrate-size choice in European eel (Anguilla anguilla) elvers is not altered by piscivore chemical cues.

The European eel Anguilla anguilla Linnaeus 1758 is critically endangered with recruitment estimated at 5-10% of historical levels. Enhancing survival of recruits is pivotal for conservation, and restoration should consider habitat choice of elvers ascending river systems. We experimentally show that newly ascended elvers choose small pebble habitat over finer and larger substrates, regardless of the presence or absence of piscivore chemical cues, indicating no predator-induced change in substrate choice. Enriching habitats with this substrate fraction should enhance eel recruitment as well as biodiversity at large.

Structural complexity in the hatchery rearing environment affects activity, resting metabolic rate and post-release behaviour in brown trout Salmo trutta.

The effects of structural enrichment in the hatchery rearing environment of brown trout Salmo trutta was linked to post-release performance. Enrichment resulted in reduced swimming activity scored in an open field test and reduced movement in a natural river after release. Also, enrichment increased resting metabolic rates, which correlated positively with overwinter growth.

Ice cover affects the growth of a stream-dwelling fish.

Protection provided by shelter is important for survival and affects the time and energy budgets of animals. It has been suggested that in fresh waters at high latitudes and altitudes, surface ice during winter functions as overhead cover for fish, reducing the predation risk from terrestrial piscivores. We simulated ice cover by suspending plastic sheeting over five 30-m-long stream sections in a boreal forest stream and examined its effects on the growth and habitat use of brown trout (Salmo trutta) during winter. Trout that spent the winter under the artificial ice cover grew more than those in the control (uncovered) sections. Moreover, tracking of trout tagged with passive integrated transponders showed that in the absence of the artificial ice cover, habitat use during the day was restricted to the stream edges, often under undercut banks, whereas under the simulated ice cover condition, trout used the entire width of the stream. These results indicate that the presence of surface ice cover may improve the energetic status and broaden habitat use of stream fish during winter. It is therefore likely that reductions in the duration and extent of ice cover due to climate change will alter time and energy budgets, with potentially negative effects on fish production.