| 1. |
- 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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| 2. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 3. |
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| 4. |
- Mellberg, Sofie, et al.
(författare)
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Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis.
- 2009
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Ingår i: The FASEB journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 23:5, s. 1490-1502
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Tidskriftsartikel (refereegranskat)abstract
- To define molecular events accompanying formation of the 3-dimensional (3D) vascular tube, we have characterized gene expression during vascular endothelial growth factor (VEGF)-induced tubular morphogenesis of endothelial cells. Microarray analyses were performed comparing gene induction in growth-arrested, tube-forming endothelial cells harvested from 3D collagen cultures to that in proliferating endothelial cells cultured on fibronectin. Differentially expressed genes were clustered and analyzed for specific endothelial expression through publicly available datasets. We validated the contribution of one of the identified genes, vascular endothelial protein tyrosine phosphatase (VE-PTP), to endothelial morphogenesis. Silencing of VE-PTP expression was accompanied by increased VEGF receptor-2 (VEGFR2) tyrosine phosphorylation and activation of downstream signaling pathways. The increased VEGFR2 activity promoted endothelial cell cycle progression, overcoming the G(0)/G(1) arrest associated with organization into tubular structures in the 3D cultures. Proximity ligation showed close association between VEGFR2 and VE-PTP in resting cells. Activation of VEGFR2 by VEGF led to rapid loss of association, which was resumed with time in parallel with decreased receptor activity. In conclusion, we have identified genes, which may serve critical functions in formation of the vascular tube. One of these, VE-PTP, regulates VEGFR2 activity thereby modulating the VEGF-response during angiogenesis.
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| 5. |
- 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, s. 951-956
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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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| 6. |
- 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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| 7. |
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| 8. |
- Raykova, Doroteya, 1986-, et al.
(författare)
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A method for Boolean analysis of protein interactions at a molecular level
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Determination of interactions between native proteins in cells is important for understanding function. Here the authors report MolBoolean as a method to detect interactions between endogenous proteins in subcellular compartments, using antibody-DNA conjugates for identification and signal amplification. Determining the levels of protein-protein interactions is essential for the analysis of signaling within the cell, characterization of mutation effects, protein function and activation in health and disease, among others. Herein, we describe MolBoolean - a method to detect interactions between endogenous proteins in various subcellular compartments, utilizing antibody-DNA conjugates for identification and signal amplification. In contrast to proximity ligation assays, MolBoolean simultaneously indicates the relative abundances of protein A and B not interacting with each other, as well as the pool of A and B proteins that are proximal enough to be considered an AB complex. MolBoolean is applicable both in fixed cells and tissue sections. The specific and quantifiable data that the method generates provide opportunities for both diagnostic use and medical research.
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| 9. |
- Song, Nguyen Van, et al.
(författare)
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Prevalence of cervical infection and genotype distribution of human Papilloma virus among females in Da Nang, Vietnam
- 2017
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:3, s. 1243-1247
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The goal of the present study was to determine the prevalence and distribution of high-risk human papilloma virus (HPV) genotypes in women from two districts in and around Da Nang city, Vietnam.Materials and Methods: All participants were randomly selected, 200 from the Hai Chau district and 200 from the Son Tra district. The detection and genotyping of HPV were performed by real-time polymerase chain reaction (PCR) technique.Results: Out of a total of 400 women, we found that 38 (9.5%) were infected with a high-risk HPV genotype, the most prevalent genotypes being 16, 18, 58 and 59. By assessment of the HPV findings in relation to sociodemographic characteristics, we found significant differences between the two study districts and between the age groups, as well as differences associated with occupation and the use of contraceptives.Conclusion: The proportion of high–risk genotypes other than 16 and 18 was relatively high, and since the HPV genotype distribution is known to vary greatly across populations, the information from this study can be used for planning of screening and vaccination programs in Da Nang.
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| 10. |
- Sun, Yi, et al.
(författare)
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Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:604
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Tidskriftsartikel (refereegranskat)abstract
- The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature. Both CD93 and IGFBP7 were up-regulated in tumor-associated endothelial cells. IGFBP7 interacted with CD93 via a domain different from multimerin-2, the known ligand for CD93. In two mouse tumor models, blockade of the CD93/IGFBP7 interaction by monoclonal antibodies promoted vascular maturation to reduce leakage, leading to reduced tumor hypoxia and increased tumor perfusion. CD93 blockade in mice increased drug delivery, resulting in an improved antitumor response to gemcitabine or fluorouracil. Blockade of the CD93 pathway triggered a substantial increase in intratumoral effector T cells, thereby sensitizing mouse tumors to immune checkpoint therapy. Last, analysis of samples from patients with cancer under anti-programmed death 1/programmed death-ligand 1 treatment revealed that overexpression of the IGFBP7/CD93 pathway was associated with poor response to therapy. Thus, our study identified a molecular interaction involved in tumor vascular dysfunction and revealed an approach to promote a favorable tumor microenvironment for therapeutic intervention.
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