| 1. |
- 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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| 2. |
- Eskilsson, Anna, 1977-
(författare)
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På plats i historien : Studier av hembygsföreningar på 2000-talet
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Local heritage societies were established in Sweden for about a hundred years ago. The societies responded to the large changes of industrialisation, emigration and urbanisation during that time. Today there are about 2 000 societies with almost half a million members altogether. Why do people turn to local heritage societies today? The image of them, associated with folklore costumes and quaint old cottages, is not consistent with the extensive activity in the 21st century. That raises questions that have not been clarified in previous research. The aim of this thesis is to find out what today's local heritage societies do, as well as to investigate what their meanings are for people and the local society. Thereby the intention is to contribute to an understanding of their present extent and endurance over time.The activities of three local heritage societies in and around the city of Linköping are mapped out in this thesis. The survey shows extensive and very broad activities that are well adjusted to present time. The traditional image has become rigid, but in parts it is accurate since the activities are still dominated by local use of history., which also contributes to their extent and continuity. Place and history as common ground is something universal: The need for people to be oriented in time and space contributes to the persistence of the local heritage societies. At the same time there seems to be something strong in society today which contributes to their extent.The thesis shows that the societies can have knowledge-generating, ideological, existential and social meaning. Through the local heritage society people can learn about, evaluate and gain feelings for the place. The society also contributes to strengthening the power of togetherness in the local community as a part of the civilian society. The multifaceted meaning of the activities makes it possible for the societies to keep or even strengthen their attraction, especially among the large group of retired people.
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| 3. |
- Lundmark, Peter, 1982-, et al.
(författare)
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Industrial Challenges within the Remanufacturing System
- 2009
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Ingår i: Proceedings of the 3rd Swedish Production Symposium, Stockholm, Sweden. - 9789163360060 ; , s. 132-138
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Konferensbidrag (refereegranskat)abstract
- This paper is a literature review of challenges within the remanufacturing system. Thechallenges in the remanufacturing system has been categorised in a collection phase, aremanufacturing process phase and a redistribution phase which the challenges havebeen presented according to. The causes and effects of each challenge have beenexplored and are presented in this paper. The final result is a compilation figure with thechallenges for the whole remanufacturing system. In general uncertainties and complexitycan be seen as the main characteristics for the challenges within the remanufacturingsystem.
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| 4. |
- Nilsson, Johan, et al.
(författare)
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Paracetamol analogues conjugated by FAAH induce TRPV1-mediated antinociception without causing acute liver toxicity
- 2021
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 213
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio.
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