5 research outputs found
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
Longitudinal river zonation in the tropics: examples of fish and caddisflies from endorheic Awash river, Ethiopia
Primary Research PaperSpecific concepts of fluvial ecology are
well studied in riverine ecosystems of the temperate
zone but poorly investigated in the Afrotropical
region. Hence, we examined the longitudinal zonation
of fish and adult caddisfly (Trichoptera) assemblages
in the endorheic Awash River (1,250 km in length),
Ethiopia. We expected that species assemblages are
structured along environmental gradients, reflecting
the pattern of large-scale freshwater ecoregions. We
applied multivariate statistical methods to test for differences in spatial species assemblage structure and
identified characteristic taxa of the observed biocoenoses
by indicator species analyses. Fish and
caddisfly assemblages were clustered into highland
and lowland communities, following the freshwater
ecoregions, but separated by an ecotone with highest
biodiversity. Moreover, the caddisfly results suggest
separating the heterogeneous highlands into a forested
and a deforested zone. Surprisingly, the Awash
drainage is rather species-poor: only 11 fish (1
endemic, 2 introduced) and 28 caddisfly species (8
new records for Ethiopia) were recorded from the
mainstem and its major tributaries. Nevertheless,
specialized species characterize the highland forests, whereas the lowlands primarily host geographically
widely distributed species. This study showed that a
combined approach of fish and caddisflies is a
suitable method for assessing regional characteristics
of fluvial ecosystems in the tropicsinfo:eu-repo/semantics/publishedVersio