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- Iacopetta, B, et al.
(författare)
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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
- 2006
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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| 2. |
- Harvey, B. P., et al.
(författare)
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Evolution of marine organisms under climate change at different levels of biological organisation
- 2014
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Ingår i: Water. - : MDPI AG. - 2073-4441. ; 6:11, s. 3545-3574
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Tidskriftsartikel (refereegranskat)abstract
- Research to date has suggested that both individual marine species and ecologicalprocesses are expected to exhibit diverse responses to the environmental effects of climatechange. Evolutionary responses can occur on rapid (ecological) timescales, and yet studiestypically do not consider the role that adaptive evolution will play in modulating biologicalresponses to climate change. Investigations into such responses have typically been focusedat particular biological levels (e.g., cellular, population, community), often lackinginteractions among levels. Since all levels of biological organisation are sensitive to globalclimate change, there is a need to elucidate how different processes and hierarchicalinteractions will influence species fitness. Therefore, predicting the responses ofcommunities and populations to global change will require multidisciplinary efforts acrossmultiple levels of hierarchy, from the genetic and cellular to communities and ecosystems.Eventually, this may allow us to establish the role that acclimatisation and adaptation willplay in determining marine community structures in future scenarios.
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| 3. |
- Turner, Lucy M., et al.
(författare)
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Energy metabolism and cellular homeostasis trade-offs provide the basis for a new type of sensitivity to ocean acidification in a marine polychaete at a high-CO2 vent: adenylate and phosphagen energy pools versus carbonic anhydrase
- 2015
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 218:14, s. 2148-2151
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Tidskriftsartikel (refereegranskat)abstract
- Species distributions and ecology can often be explained by their physiological sensitivity to environmental conditions. Whilst we have a relatively good understanding of how these are shaped by temperature, for other emerging drivers, such as P-CO2 we know relatively little. The marine polychaete Sabella spallanzanii increases its metabolic rate when exposed to high P-CO2 conditions and remains absent from the CO2 vent of Ischia. To understand new possible pathways of sensitivity to CO2 in marine ectotherms, we examined the metabolic plasticity of S. spallanzanii exposed in situ to elevated P-CO2 by measuring fundamental metabolite and carbonic anhydrase concentrations. We show that whilst this species can survive elevated P-CO2 conditions in the short term, and exhibits an increase in energy metabolism, this is accompanied by a significant decrease in carbonic anhydrase concentration. These homeostatic changes are unlikely to be sustainable in the longer term, indicating S. spallanzanii may struggle with future high P-CO2 conditions.
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| 4. |
- Turner, Lucy M., et al.
(författare)
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Metabolic responses to high pCO2 conditions at a CO2 vent site in juveniles of a marine isopod species assemblage
- 2016
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 163:10
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Tidskriftsartikel (refereegranskat)abstract
- We are starting to understand the relationship between metabolic rate responses and species’ ability to respond to exposure to high pCO2. However, most of our knowledge has come from investigations of single species. The examination of metabolic responses of closely related species with differing distributions around natural elevated CO2 areas may be useful to inform our understanding of their adaptive significance. Furthermore, little is known about the physiological responses of marine invertebrate juveniles to high pCO2, despite the fact they are known to be sensitive to other stressors, often acting as bottlenecks for future species success. We conducted an in situ transplant experiment using juveniles of isopods found living inside and around a high pCO2 vent (Ischia, Italy): the CO2 ‘tolerant’ Dynamene bifida and ‘sensitive’ Cymodoce truncata and Dynamene torelliae. This allowed us to test for any generality of the hypothesis that pCO2 sensitive marine invertebrates may be those that experience trade-offs between energy metabolism and cellular homoeostasis under high pCO2 conditions. Both sensitive species were able to maintain their energy metabolism under high pCO2 conditions, but in C. truncata this may occur at the expense of [carbonic anhydrase], confirming our hypothesis. By comparison, the tolerant D. bifida appeared metabolically well adapted to high pCO2, being able to upregulate ATP production without recourse to anaerobiosis. These isopods are important keystone species; however, given they differ in their metabolic responses to future pCO2, shifts in the structure of the marine ecosystems they inhabit may be expected under future ocean acidification conditions. © 2016, The Author(s).
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