Clinical significance of STEAP1 extracellular vesicles in prostate cancer.

BACKGROUND: Extracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance. METHODS: STEAP1 was identified on EVs in prostate cancer patient plasma. EVs were validated using electron microscopy, Western blot, nanoparticle tracking analysis, and nanoscale flow cytometry. STEAP1-positive EVs were quantified for 121 males with prostate cancer and 55 healthy age-matched control males. An evaluation of STEAP1 in prostate cancer tissue was also performed using established prostate cancer cohort data (TCGA, MSKCC, and SU2C/PCF Dream Team). RESULTS: Evaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. However, no association was found between total STEAP1 EV levels and disease recurrence or overall survival. Cohort data from prostate cancer tissue also found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified. CONCLUSIONS: STEAP1 is known to be enriched on the cells of the prostate with potential clinical significance in prostate cancer. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer.

Microscopic indicators of axe and hatchet trauma in fleshed and defleshed mammalian long bones.

The characterization of wounds in bone caused by chopping weapons has been based on either semi-fleshed or defleshed specimens. This approach has not been adequately justified as reflecting actual cases involving fleshed bone. Likewise, the histological appearance of features in chopping wounds also deserves further attention. We used 11 fresh pig (Sus scrofa) articulated hind limbs, including the femur, tibia, and fibula with contiguous surrounding flesh (including an intact epidermal layer), to receive wounds using two axes and two hatchets. Scanning electron microscopy analysis of these wounds exhibited osteon pullouts in the fracture surfaces of fleshed specimens, suggesting the attenuation of force by the surrounding flesh. Lamellar separation was also exhibited at the impact sites and fracture surfaces of both fleshed and defleshed specimens. A consistently rough morphology is characteristic of fracture surfaces while impact surfaces are smooth and yielded evidence of striations from each implement.

Macroscopic analysis of axe and hatchet trauma in fleshed and defleshed mammalian long bones.

Recently, the authors have noted that many studies involving the characterization of chopping weapon wounds have used either semi-fleshed or defleshed bones (e.g., J Forensic Sci 2001; 46: 228). As these types of specimens do not reflect the full range of actual cases of postmortem dismemberment or perimortem trauma, 11 fresh pig (Sus scrofa) articulated hind limbs, with contiguous surrounding flesh, were inflicted with wounds using two axes and two hatchets. Defleshed humeri and femora were subjected to the same treatment. While there were no great differences found between the fleshed and defleshed specimens, characteristics observed including entrance site width and the presence of chattering were inconsistent with some aspects of Humphrey and Hutchinson's study (J Forensic Sci 2001; 46: 228). Further, it was found that curve transverse and spiral fractures were prevalent in femora, while longitudinal fractures were prevalent in fibulae. Hence, fracture types may play a role in characterizing some wounds caused by chopping weapons.