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| 2. |
- Femel, Julia, 1986-, et al.
(författare)
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Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden
- 2022
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Nature. - 0340-7004 .- 1432-0851. ; 71:8, s. 2029-2040
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 is able to induce VEGF-like signaling, which contributes to tumor angiogenesis. Furthermore, several studies have demonstrated an immunosuppressive function of Gal1 through effects on both effector and regulatory T cells. Elevated Gal1 expression and secretion have been shown in many tumor types, and high Gal1 serum levels have been connected to poor prognosis in cancer patients. These findings suggest that therapeutic strategies directed against Gal1 would enable simultaneous targeting of angiogenesis, immune evasion and metastasis. In the current study, we have analyzed the potential of Gal1 as a cancer vaccine target. We show that it is possible to generate high anti-Gal1 antibody levels in mice immunized with a recombinant vaccine protein consisting of bacterial sequences fused to Gal1. Growth of Gal1 expressing melanomas was significantly impaired in the immunized mice compared to the control group. This was associated with improved perfusion of the tumor vasculature, as well as increased infiltration of macrophages and cytotoxic T cells (CTLs). The level of granzyme B, mainly originating from CTLs in our model, was significantly elevated in Gal1 vaccinated mice and correlated with a decrease in tumor burden. We conclude that vaccination against Gal1 is a promising pro-immunogenic approach for cancer therapy that could potentially enhance the effect of other immunotherapeutic strategies due to its ability to promote CTL influx in tumors.
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| 3. |
- Lee-Manion, M., et al.
(författare)
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In Vitro Antioxidant Activity and Antigenotoxic Effects of Avenanthramides and Related Compounds
- 2009
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 57:22, s. 10619-10624
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Tidskriftsartikel (refereegranskat)abstract
- Avenanthramides are substituted N-cinnamoylanthranilic acids, with hydroxycinnamic acid and anthranilic acid moieties. These alkaloid phenols, which are unique to oats, may confer health benefits via antioxidant or other mechanisms. Synthetic avenanthramides, hydroxycinnamic acids, Tranilast, and ascorbic acid were evaluated for antioxidant activity using two assays, DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant potential), and for antigenotoxicity using the Comet assay with stressed human adenocarcinoma colon cells. Of all the compounds tested, N-(3',4'-dihydroxy-(E)-cinnamoyl)-5-hydroxyanthranilic acid (2c), an abundant oat avenanthramide, generally had the highest activity in all three assays. The drug Tranilast showed antigenotoxic effects, but not antioxidant activity, suggesting that antigenotoxicity is not dependent on antioxidant effects. Overall, results show that avenanthramides exert antioxidant and antigenotoxic activities that are comparable to those of ascorbic acid and which have the potential to exert beneficial physiological effects.
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| 4. |
- Ogren, J, et al.
(författare)
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Prevalence of Dientamoeba fragilis, Giardia duodenalis, Entamoeba histolytica/dispar, and Cryptosporidium spp in Da Nang, Vietnam, detected by a multiplex real-time PCR
- 2016
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 1600-0463. ; 124:6, s. 529-533
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Sikkema, A. H., et al.
(författare)
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Vascular endothelial growth factor receptor 2 (VEGFR-2) signalling activity in paediatric pilocytic astrocytoma is restricted to tumour endothelial cells
- 2011
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 37:5, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Tumours depend on angiogenesis for enhanced tumour cell survival and progression. Vascular endothelial growth factor receptor (VEGFR) signalling plays a major part in this process. Previously, we evaluated tyrosine kinase activity in paediatric brain tumour tissue lysates using a peptide microarray containing 144 different tyrosine kinase peptide substrates. When applied to paediatric pilocytic astrocytoma tissue, this analysis revealed extensive phosphorylation of VEGFR-derived peptides. The aim of the current study was to validate this result and determine the presence of VEGFR-2 activity in paediatric pilocytic astrocytoma as the main VEGFR in terms of mitogenic signalling. In addition, the localization of VEGFR1-3 mRNA expression was assessed. Methods: VEGFR-2 phosphorylation was determined by adopting a proximity ligation assay approach. Enrichment of endothelial markers and VEGFRs in tumour endothelium was determined by quantitative polymerase chain reaction (qPCR) analysis of laser-microdissected blood vessels. Results: Proximity ligation assays on tumour cryosections showed the presence of phosphorylation of VEGFR-2, which primarily localized to vascular endothelium. qPCR analysis of endothelial markers and VEGFRs showed a 13.6-fold average enrichment of VEGFR-2 expression in the laser-microdissected endothelium compared to whole tumour. Also the expression of VEGFR-1 and -3 was highly enriched in the endothelium fraction with an average fold-enrichment of 16.5 and 50.8 respectively. Conclusions: Phosphorylated VEGFR-2 is detected on endothelial cells in paediatric pilocytic astrocytoma. Furthermore, endothelial cells are the main source of VEGFR1-3 mRNA expression. This suggests a crucial role for VEGF/VEGFR-induced angiogenesis in the progression and maintenance of these tumours.
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| 6. |
- Dandebo, Lovisa, et al.
(författare)
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The impact of a road safety policy implementation within an international organization
- 2021
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Ingår i: Journal of Public Health-Heidelberg. - : Springer Science and Business Media LLC. - 2198-1833 .- 1613-2238. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Aim This study was performed within an international organization (IO), headquartered in Washington, D.C. The employees are facing great risks during their missions abroad, where developing countries are the most common travel destination. The IO conducted a staff road safety survey in 2008 and based a road safety policy on the results of this survey. In 2017, a follow-up survey investigated the impact of the policy implementation. The aim of this study was to investigate the effect of that policy. Subjects and methods This study is based on two cross-sectional road safety surveys conducted by the IO's Staff Road Safety Task Force. The study population consisted of both regular employees and consultants based at country offices (CO) worldwide. The number of reported road traffic crashes and near-crashes (nearly had a crash), as well as road safety behavior, was compared between these two surveys. The analysis was performed from a gender perspective. High-risk countries were identified based on the number of reported road traffic crashes and near-crashes. Results Over a period of nine years, the incidence rates had dropped from 1.6 to 0.7 road traffic crashes per 1000 travel days and from 14 to 8.9 near-crashes per 1000 travel days. Seat belt usage had increased from 70% to 80%. There were no major differences between male and female respondents. Developing countries had the highest travel adjusted event rates. Conclusion The findings of this study suggest that the policy had a positive impact on road safety among CO staff within the IO.
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| 7. |
- Dimberg, J, et al.
(författare)
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Decreased levels of precursor transforming growth factor beta(1) in human colorectal cancer
- 2001
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Ingår i: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 7:6, s. 597-601
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor (TGF) beta (1) is a growth factor with wide-ranging effects on proliferation, differentiation, immunosuppression, apoptosis and matrix remodelling. TGF beta (1) seems to have an antitumorigenic role in the gastrointestinal tract but may also be associated with the development of colorectal cancer. Initially, TGF beta (1) is produced in a latent (precursor) form in epithelial cells and then is activated by a not clearly understood multistep process. In this study, we analysed precursor TGF beta (1) protein expression (n=40) and TGF beta (1) gene expression (n=49) in human colorectal adenocarcinomas and 49 normal adjacent tissue. Out of these 49 normal tissues 40 were matched. Western blot analysis revealed that the precursor TGF beta (1) protein levels were generally lower in colorectal cancerous tissue compared to adjacent noncancerous tissue (P <0.001). Furthermore, with real-time PCR our results cannot reflect a statistically significant difference in TGF beta (1) gene expression between the tumour tissue and normal tissue. These finds indicate that it is likely that there are mechanisms which control precursor TGF beta (1) protein expression by factor(s) at the level of pre-translation of the TGF beta (1) transcript and/or at the level of post-translation of the TGF beta (1) protein in the tumours. This process may be related to carcinogenesis and poses the question whether the suppression of the precursor TGF beta (1) is an early event, in vivo, in the human colorectal adenoma-carcinoma sequence.
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| 8. |
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| 9. |
- Dimberg, Peter H., 1985-, et al.
(författare)
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A Comparison Between Regression Models and Genetic Programming for Predictions of Chlorophyll-a Concentrations in Northern Lakes
- 2016
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Ingår i: Environmental Modelling and Assessment. - : Springer Science and Business Media LLC. - 1420-2026 .- 1573-2967. ; 21:2, s. 221-232
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Tidskriftsartikel (refereegranskat)abstract
- Chlorophyll-a (chl-a) concentrations are often used as a proxy for water quality problems as well as phytoplankton blooms. Available chl-a models range from simple phosphorus loading models to complex regression and dynamic models. A comparison of multiple regression models was made with genetic programming (GP) techniques to predict chl-a concentrations over a large range of 104 Swedish lakes. Independent variables used were lake area, mean depth, iron, latitude, ammonium, nitrogen + nitrate, pH, phosphate, secchi depth, silicon, temperature, total phosphorus, total nitrogen and total organic carbon. GP is a method based on the Darwinian evolution theory. This implies that a program will be able to test different mathematical equations, iterating and improving each equation using fundamental ideas from evolution theory to increase the predictive power. A good correspondence was found between the multiple regression and the GP modelling approach. No significant improvement of the predictive power was found using GP, and it is therefore recommended that multiple regression methods should be preferred when predicting chl-a concentrations as these models tend to be less complex and the modelling approach is easier to use. Results from GP were in some cases more accurate compared to multiple regressions; however, the best model was created by multiple regressions which used concentrations of total phosphorus, total nitrogen and latitude as independent variables. These findings will be an important note for limnologists and modelling managers when developing future models of chl-a concentrations in lakes.
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| 10. |
- Dimberg, Y, et al.
(författare)
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Effects of low-dose X-irradiation on mouse-brain aggregation cultures
- 1992
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 61:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- Biochemical and morphological differentiation in reaggregating mouse-brain cell cultures after low-dose radiation (0.5 Gy) in vitro was studied. Cells were irradiated on culture day 2, corresponding to embryonic day 15-16, and different glial and neuronal markers were followed through development to postnatal day 40. The shape and size of irradiated aggregates were more irregular and smaller compared with controls. Total amounts of DNA and protein were significantly lower in irradiated aggregates than in controls between days 8 and 20. After 30 days in culture activities of the glial markers glutamine synthetase (GS) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) were lower in X-irradiated aggregates than in controls. However, after 40 days the CNP activity in irradiated aggregates increased to levels above those of the controls. Irradiated and control aggregates did not differ significantly in neuronal marker enzyme activities, i.e. choline acetyltransferase (ChAT), acetylcholine esterase (AChE) and glutamic acid decarboxylase (GAD) measured on a per mg protein basis. On days 20 and 30 the amount of nerve growth factor (NGF) was two-fold higher in irradiated aggregates compared with non-irradiated ones, suggesting that, after irradiation, surviving cells in culture were induced to produce more NGF. After 40 days the amount of NGF in irradiated aggregates had decreased to the level found in the control aggregates.
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