| 1. |
- Campbell, Diahnn, et al.
(författare)
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Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D, L-lactic-co-glycolic) acid nanoparticles nanoparticles
- 2015
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Ingår i: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 17:48
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as potent immune adjuvant. Method In this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2) positive breast cancer. Results Free peptide did not significantly augment immune responses but, when delivered in poly(D, L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2 specific T cells was observed in vitro. Vaccination of HER2NEU transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91 loaded PLGA-NPs enhanced the activation of HER2 specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival. Conclusion Taken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine.
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| 2. |
- Saenz, Rebecca, et al.
(författare)
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TLR4-dependent activation of dendritic cells by an HMGB1-derived peptide adjuvant
- 2014
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Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 12:211
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Tidskriftsartikel (refereegranskat)abstract
- High mobility group box protein 1 (HMGB1) acts as an endogenous danger molecule that is released from necrotic cells and activated macrophages. We have previously shown that peptide Hp91, whose sequence corresponds to an area within the B-Box domain of HMGB1, activates dendritic cells (DCs) and acts as an adjuvant in vivo. Here we investigated the underlying mechanisms of Hp91-mediated DC activation. Hp91-induced secretion of IL-6 was dependent on clathrin-and dynamin-driven endocytosis of Hp91 and mediated through a MyD88- and TLR4-dependent pathway involving p38 MAPK and NF kappa B. Endosomal TLR4 has been shown to activate the MyD88-independent interferon pathway. Hp91-induced activation of pIRF3 and IL-6 secretion was reduced in IFN alpha beta R knockout DCs, suggesting an amplification loop via the IFN alpha beta R. These findings elucidate the mechanisms by which Hp91 acts as immunostimulatory peptide and may serve as a guide for the future development of synthetic Th1-type peptide adjuvants for vaccines.
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| 3. |
- Carson, Dean Bradley, 1970-, et al.
(författare)
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Creating 'good' hospital to home transfers in the rural north of Sweden : informal workarounds and opportunities for improvement
- 2024
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Ingår i: Home Health Care Services Quarterly. - : Routledge. - 0162-1424 .- 1545-0856. ; 43:1, s. 18-38
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Tidskriftsartikel (refereegranskat)abstract
- Hospital to home transfers for older people require effective communication, coordination and collaboration across multiple service settings. Rural Nursing Theory and the Beyond Periphery model explain why this is particularly difficult in rural areas, but there are few examples of how rural services respond. This paper presents a case study of the district of Tärnaby in the inland north of Sweden. Data are drawn from interviews with health and care staff in Tärnaby, observations, and experiences of the researchers. Data were analyzed thematically, with four main themes emerging–role clarity, communication, geography, and understanding of the rural context. Responses to challenges included increasing opportunities for communication between service providers and improving documentation. The paper concludes that informal "workarounds" run the risk of further disconnecting rural service settings from "the city". Rather, the aim needs to be to improve contextual understanding through formally incorporating "the rural" in service design.
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