13 research outputs found
Update on cervical disc arthroplasty: where are we and where are we going?
Despite the very good results of anterior cervical discectomy and fusion, there are concerns of adjacent level degeneration. For this reason, interest has grown in the potential for motion sparing alternatives. Cervical disc arthroplasty is thus evolving as a potential alternative to fusion. Specific design characteristic and implants will be reviewed and outcomes summarized
Regional differences in prostaglandin Eā metabolism in human colorectal cancer liver metastases
Background: Prostaglandin (PG) Eā plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGEā catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGEā content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGEā in human CRC cells in vitro. Methods: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGEā levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) Ī². Results: PGEā levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGEā. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.Conclusions: There is significant intra-tumoral heterogeneity in PGEā content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGEā metabolism should be targeted for novel treatment of advanced CRC