Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer.

BACKGROUND: Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS: Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS: Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21% contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50% cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS: Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted.

Identifying the characteristics of children with pressure ulcers.

AIM: To identify the characteristics of children with pressure ulceration so that those at risk may be identified in future. METHOD: A multicentre survey was undertaken in 11 hospitals to ascertain the incidence, severity and position of pressure ulcers in paediatric inpatients. RESULTS: The most frequently reported ulcer grade involved blistering of the skin or a superficial skin break. The most frequent site was the sacrum or buttocks, heel, thigh, ear, occipital scalp, malleolus and spine. In 50 per cent (n=27) of children, pressure ulcers could be associated with equipment pressing or rubbing on the skin. CONCLUSION: Risk assessment tools designed specifically for children are needed, and more research should be undertaken to confirm the characteristics that increase children's risk of pressure ulceration and to establish the significance of individual characteristics.