18 research outputs found
Characterisation of the Cell Line HC-AFW1 Derived from a Pediatric Hepatocellular Carcinoma
Current treatment of paediatric hepatocellular carcinoma (HCC) is often inefficient due to advanced disease at diagnosis and resistance to common drugs. The aim of this study was to generate a cell line derived from a paediatric HCC in order to expand research in this field. We established the HC-AFW1 cell line from a liver neoplasm of a 4-year-old boy through culturing of primary tumor specimens. The cell line has been stable for over one year of culturing and has a doubling time of 40 h. The tumour cells have an epithelial histology and express HCC-associated proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin, CD10, CD326, HepPar1 and Vimentin. Forty-nine amino acids in exon 3 of β-Catenin that involve the phosphorylation sites of GSK3 were absent and β-Catenin is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. Several alterations of gene copy numbers were detected by genome-wide SNP array. Among the different drugs tested, cisplatin and irinotecan showed effective inhibition of tumour cell growth in a proliferation assay at concentrations below 5 µg/ml. Subcutaneous xenotransplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growing dedifferentiated tumours with high levels of serum AFP. Histological analyses of the primary tumour and xenografts included national and international expert pathological review. Consensus reading characterised the primary tumour and the HC-AFW1-derived tumours as HCC. HC-AFW1 is the first cell line derived from a paediatric HCC without a background of viral hepatitis or cirrhosis and represents a valuable tool for investigating the biology of and therapeutic strategies for childhood HCC
Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy
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Vegetation refugia can inform climate-adaptive land management under global warming
Natural resource managers need information about the risks associated with climate change to provide guidance on where to implement various management practices on natural lands. The spatial variation of projected impacts within a vegetation type can be used to target climate-adaptive management actions because different locations will be exposed to different levels of climatic stress. Vegetation refugia are areas that retain non-stressful climate conditions under future climates. Consensus vegetation refugia – areas retaining suitable climates under both wetter and drier future projections – represent only 14.6% of California's natural vegetation. One state and one federal government agency have incorporated vegetation refugia maps into conservation planning for 522 vertebrate species and for post-wildfire reforestation. Monitoring how vegetation responds to management actions at sites within vegetation refugia can improve the conservation of plants subjected to a changing climate
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The influence of model frameworks in spatial planning of regional climate-adaptive connectivity for conservation planning
Landscape connectivity improves species’ capacity to adapt to climate change. These models are increasingly needed and available for climate-change conservation planning. However, their relative strengths and weaknesses are unclear. We asked how well do the spatial outputs from four connectivity models intended to support climate change conservation agree? To understand the implications of selecting one or several approaches, we compared various combinations of four connectivity models for ecoregions in California, U.S.A. Two models are based on landscape structure, Land Facet Corridors and Omniscape, while two other models, Meta-Corridor Approach and Network Flow Analysis (NFA), use focal species’ range dynamics to determine connectivity. We also describe how each approach integrates climate-adaptive connectivity concepts. Variation in modeling methods, objectives, inputs, and landscape representations strongly affects the modeled connectivity patterns. For the region where all four models were run, almost three quarters of the landscape was selected by one or more models, but three or more agree for only 9.5% of the area, all of which is riparian. This emphasizes the importance of riparian areas for climate adaptation. We found NFA prioritized connections close to protected areas, while Meta-Corridor avoided higher cost agricultural and developed areas. The structural models agreed in areas with low human impact but Omniscape avoided areas of low topographic diversity and Land Facet Corridors avoided connections in areas with no protected areas. Connectivity models should be selected based on the conservation objectives, such as spatial scale to be implemented, and a combination of models may be best