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Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy. In recent years, targeting epigenetic pathways has emerged as a promising approach to overcome tumor immunosuppression and cancer progression. Moreover, the progress in nanotechnology has provided new opportunities for enhancing the efficacy of conventional and epigenetic drugs. Nano-based drug delivery systems (NDDSs) offer several advantages, including improved drug pharmacokinetics, enhanced tumor penetration, and reduced systemic toxicity. Smart NDDSs enable precise targeting of stromal components and augment the effectiveness of immunotherapy through multiple drug delivery options. This review offers an overview of the latest nano-based approaches developed to achieve superior therapeutic efficacy and overcome drug resistance. We specifically focus on the TME and epigenetic-targeted therapies in the context of PDAC, discussing the advantages and limitations of current strategies while highlighting promising new developments. By emphasizing the immense potential of NDDSs in improving therapeutic outcomes in PDAC, our review paves the way for future research in this rapidly evolving field.
Elsevier
2023
2010
Nanomaterial grouping: Existing approaches and future recommendations
The physico-chemical properties of manufactured nanomaterials (NMs) can be fine-tuned to obtain different functionalities addressing the needs of specific industrial applications. The physico-chemical properties of NMs also drive their biological interactions. Accordingly, each NM requires an adequate physico-chemical characterization and potentially an extensive and time-consuming (eco)toxicological assessment, depending on regulatory requirements. Grouping and read-across approaches, which have already been established for chemicals in general, are based on similarity between substances and can be used to fill data gaps without performing additional testing. Available data on “source” chemicals are thus used to predict the fate, toxicokinetics and/or (eco)toxicity of structurally similar “target” chemical(s). For NMs similar approaches are only beginning to emerge and several challenges remain, including the identification of the most relevant physico-chemical properties for supporting the claim of similarity. In general, NMs require additional parameters for a proper physico-chemical description. Furthermore, some parameters change during a NM's life cycle, suggesting that also the toxicological profile may change.
This paper compares existing concepts for NM grouping, considering their underlying basic principles and criteria as well as their applicability for regulatory and other purposes. Perspectives and recommendations based on experiences obtained during the EU Horizon 2020 project NanoReg2 are presented. These include, for instance, the importance of harmonized data storage systems, the application of harmonized scoring systems for comparing biological responses, and the use of high-throughput and other screening approaches. We also include references to other ongoing EU projects addressing some of these challenges.
Elsevier
2019
2009
1999
2007
Målinger og beregninger av luftforurensning i Øvre Årdal. 2. Spredning ved normal drift. NILU OR
NILU ¿ Norsk institutt for luftforskning har på oppdrag fra Norsk Hydro ASA utført spredningsberegninger for utslipp til luft av SO2, fluorid, svevestøv og tungmetaller fra aluminiumverket i Øvre Årdal. Beregningene ble kjørt for et referanseår (2010) med vanlige utslippsforhold. Grenseverdier og luftkvalitetskriterier er overholdt for alle komponenter.
Maksimum timemiddelkonsentrasjon i modellområdet er 200 µg/m3 (EU grenseverdi 350 µg/m3), høyeste årsmiddelet er 8 µg/m3 (EU grenseverdi 20 µg/m3).
Årsmiddelkonsentrasjoner for svevestøv, gassformig fluorid og de fleste tungmetaller er langt under grense- og målsettingsverdiene, med unntak av nikkel dets årsmiddelkonsentrasjon bare er litt lavere enn målsettingsverdien.
2012
Målinger og beregninger av luftforurensning i Øvre Årdal. 1. Oppfølging av SO2 i ombyggingsperioden. NILU OR
NILU ¿ Norsk institutt for luftforskning har på oppdrag fra Norsk Hydro ASA utført målinger av SO2 under ombyggingen av renseanlegget til aluminiumverket i Øvre Årdal i perioden 11. mai ¿ 21. oktober 2011. Det ble også utført spredningsberegninger for utslipp til luft av SO2, fluorid, svevestøv og tungmetaller for 3 utslipp/meteorologi-scenarier.
Målingene med passive prøvetakere ved 20 steder i Øvre Årdal ga ikke noen overskridelse av Klifs anbefalte luftkvalitetkriterium eller EUs grenseverdi for økosystemer. Høyeste halvårsmiddelkonsentrasjonen var 14,9 µg/m3 i umiddelbar nærhet av anlegget.
Beregninger for ombyggingsperioden (scenario 1) ga overskridelse av EUs grenseverdi for timemiddel (350 µg/m3), som tillates overskredet 24 ganger per kalenderår. Høyeste halvårsmiddelkonsentrasjon i Øvre Årdal ble beregnet på 17 µg/m3, som er lavere enn gjeldende grenseverdier. For vanlige utslippsforhold og meteorologi fra ombyggingsperioden (scenario 2) overholdes alle grenseverdier og luftkvalitetskriterier. Resultatene for scenario 3 (vanlige utslippsforhold for en referanseperiode) er beskrevet i separat rapport.
2012