| 1. |
- Acedo, P, et al.
(författare)
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Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy in TP53 mutant pancreatic tumors
- 2019
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Ingår i: Future science OA. - : Future Science Ltd. - 2056-5623. ; 5:2, s. FSO366-
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Tidskriftsartikel (refereegranskat)abstract
- Aim: TAp73 is a tumor suppressor, which compensates for p53 loss and induces apoptosis in tumors in response to genotoxic stress or small-molecule treatments. Pancreatic ductal adenocarcinoma has a late onset of the disease, responds poorly to the existing therapies and has a very low survival rates. Result: Here, using drug-repurposing approach, we found that protoporphyrin IX (PpIX) and benzoporphyrin derivative (BPD) monoacid ring A activate TAp73 and induce apoptosis in pancreatic cancer cells. PpIX and BPD induce reactive oxygen species and inhibit thioredoxin reductase 1. Conclusion: Thus, PpIX and BPD target cancer cells’ vulnerabilities namely activate TAp73 tumor suppressor and inhibit oncogenic Trx1. Our findings may contribute to faster repurposing of PpIX and BPD to treat pancreatic tumors.
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| 2. |
- Aljabali, Alaa A. A., et al.
(författare)
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The viral capsid as novel nanomaterials for drug delivery
- 2021
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Ingår i: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 7:9
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Forskningsöversikt (refereegranskat)abstract
- The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging. Lay abstract: The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging. Here we performed a comprehensive database search to review findings in this area, demonstrating that viral nanostructures possess unique properties that make them ideal for applications in diagnostics, cell labeling, contrasting agents and drug delivery structures.
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| 3. |
- Arvidsson, Per I., et al.
(författare)
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Institutional profile : the national Swedish academic drug discovery & development platform at SciLifeLab
- 2017
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Ingår i: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 3:2
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.
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| 4. |
- Arvidsson, PI
(författare)
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On the bridge over the translational valley of death: interview with Per I Arvidsson
- 2017
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Ingår i: Future science OA. - : Future Science Ltd. - 2056-5623. ; 3:2, s. FSO183-
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Tidskriftsartikel (refereegranskat)abstract
- Per I Arvidsson speaks to Francesca Lake, Managing Editor: Per received his PhD in organic chemistry from Gothenburg University (Sweden) in 1999, where he continued as a lecturer for a short time. Following 2 years at the ETH Zurich (Switzerland) as a postdoctoral fellow, he went on to establish an independent research group at the Department of Biochemistry and Organic Chemistry at Uppsala University (Sweden). In 2006, he joined AstraZeneca R&D Södertälje (Sweden). After 1-year in-house training for future leaders in drug discovery and development, he became team leader in Medicinal Chemistry in 2007. In 2008, he was appointed Candidate Drug Delivery team leader with responsibility for preclinical drug discoveries in several CNS and pain projects. In 2010, he became Project Director at the innovative medicine unit for CNS & Pain research in Södertälje with responsibility from lead optimization to end of Phase II for projects in the neurodegeneration area. After joining AstraZeneca, he continued to pursue academic research as Adjunct Professor in bioorganic chemistry at the Department of Biochemistry and Organic Chemistry, Uppsala University (2007–2010), and the Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University (2010–2013). In 2010, he was appointed honorary professor in Pharmacy and Pharmacology at the University of KwaZulu Natal (South Africa). In 2013, he was recruited to the Karolinska Institute in Stockholm as Director of Drug Discovery & Development, to build up the National Swedish infrastructure for Drug Discovery & Development at the Science for Life Laboratory (SciLifeLab). Since 2013, he has been a part-time research professor at the College of Health Science at the University of KwaZulu Natal. He is named inventor on over 15 patent applications, and coauthor to over 100 publications, two of which have won ‘most cited papers’ awards.
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| 5. |
- Bäck, M
(författare)
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Omega-3 fatty acids in atherosclerosis and coronary artery disease
- 2017
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Ingår i: Future science OA. - : Future Science Ltd. - 2056-5623. ; 3:4, s. FSO236-
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Tidskriftsartikel (refereegranskat)abstract
- Omega-3 polyunsaturated fatty acids have emerged as possible protective factors associated with a decreased risk for myocardial infarction in populations with a high marine food intake, which may relate to effects on lipid metabolism, thrombosis and inflammation. Omega-3 fatty acids decrease triglyceride levels and also compete as substrates for enzymes involved in the biosynthesis of lipid mediators. The balance between omega-3-derived specialized proresolving mediators and pro-inflammatory lipid mediators from arachidonic acid metabolism can be measured as the resolvin-to-leukotriene ratio, which has been shown to predict subclinical atherosclerosis. The results of experimental, observational and randomized studies of omega-3 fatty acids are somewhat variable and should be interpreted in view of the models used and the populations studied.
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| 6. |
- El-Schich, Zahra, et al.
(författare)
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Interfacing antibody-based microarrays and digital holography enables label-free detection for loss of cell volume
- 2015
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Ingår i: Future Science OA. - : Future Science Group. - 2056-5623. ; 1:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: We introduce the combination of digital holographic microscopy (DHM) and antibody microarrays as a powerful tool to measure morphological changes in specifically antibody-captured cells. The aim of the study was to develop DHM for analysis of cell death of etoposide-treated suspension cells. Result/Methodology: We demonstrate that the cell number, mean area, thickness, and volume were non-invasively measured by using DHM. The cell number was stable over time, but the two cell lines showed changes of cell area and cell irregularity after treatment. The cell volume in etoposide-treated cells was decreased, whereas untreated cells showed stable volume. Conclusions: Our results provide proof of concept for using DHM combined with antibody-based microarray technology for detecting morphological changes in captured cells.
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| 7. |
- Kjellman, Pontus, et al.
(författare)
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Size-dependent lymphatic uptake of nanoscale-tailored particles as tumor mass increases
- 2015
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Ingår i: Future science OA. - : Future Science Ltd. - 2056-5623. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the size-dependent lymphatic uptake of nanoparticles in mice with rapidly growing syngeneic tumors.MATERIALS & METHODS: Mice were inoculated subcutaneously with EL4 lymphoma cells and on day 5 or day 6 of tumor growth, injected peritumorally with either 29 nm or 58 nm of ultra-small superparamagnetic iron oxide nanoparticles. Twenty-four hours later the animals were imaged using MRI.RESULTS & CONCLUSION: The larger of the two particles can only be detected in the lymph node when injected in animals with 6-day-old tumors while the 29 nm ultra-small superparamagnetic iron oxide nanoparticle is observed on both time points. Tumor mass greatly impacts the size of particles that are transported to the lymph nodes.
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| 8. |
- Loureiro, J. A., et al.
(författare)
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Immunoliposomes doubly targeted to transferrin receptor and to α-synuclein
- 2015
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Ingår i: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The present study was designed to test the cellular uptake of PEGylated liposomes targeted to transferrin receptor and to alpha-synuclein by a cell model of the blood-brain barrier (BBB). Materials & methods: PEGylated immunoliposomes were prepared with anti-transferrin receptor OX26 and anti-alpha-synuclein LB509 antibodies to overcome the BBB in Parkinson's disease. Results: The doubly targeted immunoliposomes bind to transferrin receptor and to alpha-synuclein protein, as assessed by ELISA assays. We establish that 40% of an encapsulated tested drug (epigallocatechin-3-gallate) is released in a time frame of 44 h, which is reasonable for sustained release. The cellular uptake of doubly targeted immunoliposomes in cultured brain endothelial cells hCMEC/D3 was two-times more efficient than that of PEGylated liposomes. Conclusion: Immunoliposomes targeted to BBB receptors and to alpha-synuclein could potentially enable the transport of drugs across the BBB and reach one of the drug targets in Parkinson's disease. The blood-brain barrier (BBB) prevents the distribution of drugs into the brain, making the development of new treatments for brain disorders such as Parkinson's disease difficult. This is due to the presence of tight cell-cell junctions within the brain capillary endothelium. Nanocarriers that transport drugs across the BBB enable noninvasive modes of drug delivery (e.g., oral, systemic routes) to the brain. In the present study, we developed vesicles targeted with antibodies to BBB receptors and to a biological target of Parkinson's disease. This technology, known as Trojan horse technology, uses endogenous molecules that are able to cross the BBB through receptors present in the brain capillary endothelium.
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| 9. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial.
- 2020
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Ingår i: Future science OA. - London, United Kingdom : Future Science Ltd. - 2056-5623. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D).64 patients (T1D since <4months, age 10-17.99, fasting sC-peptide ≥0.12nmol/l, GADA-positive) were randomized intoDay(D) 1-90 400mg/day Ibuprofen, D1-450 vitamin D 2000IU/day, D15, 45 sc. 20μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40μg GAD-alum D15, 45; placebo.Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24h with change in C-peptide AUC at 15months (r=-0.776, p<0.0001).Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov).
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| 10. |
- Undin, Torgny, et al.
(författare)
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MS for investigation of time-dependent protein adsorption on surfaces in complex biological samples
- 2015
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Ingår i: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study aims at developing a nondestructive way for investigating proteinadsorption on surfaces such as biomaterials using mass spectrometry. Methods: Ventricular cerebrospinal fluid in contact with poly carbonate membranes were usedas adsorption templates and on-surface enzymatic digestion was applied to desorbproteins and cleave them into peptides. Mass spectrometric analysis provided bothprotein identification and determination of protein specific adsorption behavior. Results: In general, the adsorption increased with incubation time but also proteinspecifictime-resolved adsorption patterns from the complex protein solutionwere discovered. Conclusion: The method developed is a promising tool for thecharacterization of biofouling, which sometimes causes rejection and encapsulationof implants and can be used as complement to other surface analytical techniques.One problem associated with artificial materials in the body is that proteins in thebody interact with the surface, which sometimes causes rejection of the implant.In this study, a method for investigating the time-dependent protein adsorptionon a surface originating from a complex biological protein solution was developed.Compared with other surface analyses, this method can identify what proteins thatadsorbs on the surface. In addition, determination of protein-specific adsorptionbehavior in relation to incubation was possible
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