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- Naidu, R., et al.
(författare)
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Per- and poly-fluoroalkyl substances (PFAS) : Current status and research needs
- 2020
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Ingår i: Environmental Technology & Innovation. - : Elsevier BV. - 2352-1864. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- An expert workshop focusing on per- and poly-fluoroalkyl substances (PFAS) was held in Adelaide, South Australia, Australia in September 2019 following the 8th International Contaminated Site Remediation Conference — CleanUp 2019. The workshop was organised by the Cooperative Research Centre for Contamination and Remediation of the Environment (CRC CARE) and was chaired by Professor Ravi Naidu, CEO and Managing Director of CRC CARE and Director of the Global Centre for Environmental Remediation at the University of Newcastle, NSW. The purpose of the workshop, which was attended by more than 50 experts in the field of contaminated land assessment and management, was to discuss the current state of play and research needs relating to PFAS contaminated sites. This paper provides a summary of the discussions and conclusions and lists actions and needs that the expert group identified as critical for pursuing successful PFAS management and remedy approaches.This paper is intended to capture the shared information, comments, and current thinking related to PFAS challenges and research needs as identified by the group of expert participants; the write up is not intended to be a complete dissertation on the science and work that has been carried out. With a fast-evolving subject and increased government and public attention on PFAS presence in the environment, the group was convened with the objective of providing value in contributing to solutions to the PFAS challenges that are faced both in Australia and internationally. The text contained herein provides references to observations and methods that the experts drew on in their discussions and in support of their commentary; documentation of the original references was not provided, and the reader should consult the scientific literature if further information and confirmation of observations is required. Following a brief on the background to PFAS challenges, the paper focusses on research gaps identified by experts with focus on Australian soils and groundwater including climatic patterns, an overview of PFAS research in Australia with emphasis on:RegulatoryAnalytical considerationsEcological and Human Health RisksFate and TransportRemediation and Risk Management.
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| 2. |
- Xue, Y. H., et al.
(författare)
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An approach to suppress the evolution of resistance in BRAF(V600E)-mutant cancer
- 2017
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Ingår i: Nat Med. - : Springer Science and Business Media LLC. - 1078-8956. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAF(amp)) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or in combination with other ERK signaling inhibitors. Single-cell sequencing and multiplex fluorescence in situ hybridization analyses mapped the emergence of extra-chromosomal amplification in parallel evolutionary trajectories that arose in the same tumor shortly after treatment. The evolutionary selection of BRAF(amp) was determined by the fitness threshold, the barrier that subclonal populations need to overcome to regain fitness in the presence of therapy. This differed for inhibitors of ERK signaling, suggesting that sequential monotherapy is ineffective and selects for a progressively higher BRAF copy number. Concurrent targeting of the RAF, MEK and ERK kinases, however, imposed a sufficiently high fitness threshold to prevent the propagation of subclones with high-level BRAF(amp). When administered on an intermittent schedule, this treatment inhibited tumor growth in 11/11 PDXs of lung cancer or melanoma without apparent toxicity in mice. Thus, gene amplification can be acquired and expanded through parallel evolution, enabling tumors to adapt while maintaining their intratumoral heterogeneity. Treatments that impose the highest fitness threshold will likely prevent the evolution of resistance-causing alterations and, thus, merit testing in patients.
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