The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the ‘off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers.

Pop-up satellite archival tags (PSATs) have recently been applied in attempts to follow the oceanic spawning migration of the European eel. PSATs are quite large, and in all likelihood their hydraulic drag constitutes an additional cost during swimming, which remains to be quantified, as does the potential implication for successful migration. Silver eels (LT = 598.6±29 mm SD, N = 9) were subjected to swimming trials in a Steffensen-type swim tunnel at increasing speeds of 0.3–0.9 body lengths s−1, first without and subsequently with, a scaled down PSAT dummy attached. The tag significantly increased oxygen consumption (MO2) during swimming and elevated minimum cost of transport (COTmin) by 26%. Standard (SMR) and active metabolic rate (AMR) as well as metabolic scope remained unaffected, suggesting that the observed effects were caused by increased drag. Optimal swimming speed (U opt) was unchanged, whereas critical swimming speed (U crit) decreased significantly. Swimming with a PSAT altered swimming kinematics as verified by significant changes to tail beat frequency (f), body wave speed (v) and Strouhal number (St). The results demonstrate that energy expenditure, swimming performance and efficiency all are significantly affected in migrating eels with external tags.

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Establishing relationships between parasite infection and physiological condition of the host can be difficult and therefore are often neglected when describing factors causing population declines. Using the parasite–host system between the parasitic nematode Contracaecum osculatum and the Eastern Baltic cod Gadus morhua, we here shed new light on how parasite load may relate to the physiological condition of a transport host. The Eastern Baltic cod is in distress, with declining nutritional conditions, disappearance of the larger fish, high natural mortality and no signs of recovery of the population. During the latest decade, high infection levels with C. osculatum have been observed in fish in the central and southern parts of the Baltic Sea. We investigated the aerobic performance, nutritional condition, organ masses, and plasma and proximate body composition of wild naturally infected G. morhua in relation to infection density with C. osculatum. Fish with high infection densities of C. osculatum had (i) decreased nutritional condition, (ii) depressed energy turnover as evidenced by reduced standard metabolic rate, (iii) reduction in the digestive organ masses, and alongside (iv) changes in the plasma, body and liver composition, and fish energy source. The significantly reduced albumin to globulin ratio in highly infected G. morhua suggests that the fish suffer from a chronic liver disease. Furthermore, fish with high infection loads had the lowest Fulton’s condition factor. Yet, it remains unknown whether our results steam from a direct effect of C. osculatum, or because G. morhua in an already compromised nutritional state are more susceptible towards the parasite. Nevertheless, impairment of the physiological condition can lead to reduced swimming performance, compromising foraging success while augmenting the risk of predation, potentially leading to an increase in the natural mortality of the host. We hence argue that fish–parasite interactions must not be neglected when implementing and refining strategies to rebuild deteriorating populations.

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The reformed European Common Fisheries Policy introduced a discard ban, with a possibility of exempting species where a high discard survival can be demonstrated. This necessitates a validation of the methods used for estimating the discard mortality of candidate species. In this study, we assess whether reflex impairment can predict short-term mortality in commercially trawled European plaice upon landing and after air exposure of up to 90 min. Sub-lethal stress was assessed by a suite of physiological variables. Over a 10-day period, mortality was monitored for a total of 199 plaice following trawl and air exposure of varying duration, and for 50 control fish scored for reflex impairment on board the vessel. Mortality was only observed in fish exposed to air for >60 min, and averaged 11.1% (95% CI = 7.1–16.3%). Reflex impairment was found to be a significant (P < 0.001) predictor of mortality in a generalized linear model, excluding other initially included variables by using a stepwise method. Plasma cortisol, haematocrit, and plasma osmolality all indicated a profound and increasing level of stress with air exposure, accompanied by a near depletion of muscle phosphocreatine and nucleotides. Fishing site had an unexpected, but significant (p < 0.05) effect on stress levels, which was also reflected in reflex impairment and mortality. Based on these findings, a possible exemption from the discard ban should include considerations on the duration of air exposure.