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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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- Smythe, Tristan A., et al.
(författare)
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Metabolic transformation of environmentally-relevant brominated flame retardants in Fauna : A review
- 2022
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 161
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Forskningsöversikt (refereegranskat)abstract
- Over the past few decades, production trends of the flame retardant (FR) industry, and specifically for brominated FRs (BFRs), is for the replacement of banned and regulated compounds with more highly brominated, higher molecular weight compounds including oligomeric and polymeric compounds. Chemical, biological, and environmental stability of BFRs has received some attention over the years but knowledge is currently lacking in the transformation potential and metabolism of replacement emerging or novel BFRs (E/NBFRs). For articles published since 2015, a systematic search strategy reviewed the existing literature on the direct (e.g., in vitro or in vivo) non-human BFR metabolism in fauna (animals). Of the 51 papers reviewed, and of the 75 known environmental BFRs, PBDEs were by far the most widely studied, followed by HBCDDs and TBBPA. Experimental protocols between studies showed large disparities in exposure or incubation times, age, sex, depuration periods, and of the absence of active controls used in in vitro experiments. Species selection emphasized non-standard test animals and/or field-collected animals making comparisons difficult. For in vitro studies, confounding variables were generally not taken into consideration (e.g., season and time of day of collection, pollution point-sources or human settlements). As of 2021 there remains essentially no information on the fate and metabolic pathways or kinetics for 30 of the 75 environmentally relevant E/BFRs. Regardless, there are clear species-specific and BFRspecific differences in metabolism and metabolite formation (e.g. BDE congeners and HBCDD isomers). Future in vitro and in vivo metabolism/biotransformation research on E/NBFRs is required to better understand their bioaccumulation and fate in exposed organisms. Also, studies should be conducted on well characterized lab (e. g., laboratory rodents, zebrafish) and commonly collected wildlife species used as captive models (crucian carp, Japanese quail, zebra finches and polar bears).
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