| 1. |
- 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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| 2. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 3. |
- Thijssen, Victor L. J. L., et al.
(författare)
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Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth
- 2018
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 246:4, s. 447-458
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Tidskriftsartikel (refereegranskat)abstract
- Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types. (c) 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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| 4. |
- Wentink, Madelon Q., et al.
(författare)
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Vaccination approach to anti-angiogenic treatment of cancer
- 2015
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Ingår i: Biochimica et Biophysica Acta. CR. Reviews on Cancer. - : Elsevier BV. - 0304-419X .- 1879-2561. ; 1855:2, s. 155-171
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Forskningsöversikt (refereegranskat)abstract
- Improvement of patient survival by anti-angiogenic therapy has proven limited. A vaccination approach inducing an immune response against the tumor vasculature combines the benefits of immunotherapy and anti-angiogenesis, and may overcome the limitations of current anti-angiogenic drugs. Strategies to use whole endo: thelial cell vaccines and DNA- or protein vaccines against key players in the VEGF signaling axis, as well as specific markers of tumor endothelial cells, have been tested in preclinical studies. Current clinical trials are now testing the promise of this specific anti-cancer vaccination approach. This review will highlight the state-of-the-art in this exciting field of cancer research.
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| 5. |
- Aanhane, Ed, et al.
(författare)
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Different angioregulatory activity of monovalent galectin-9 isoforms
- 2018
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Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 0969-6970 .- 1573-7209. ; 21:3, s. 545-555
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-9 consists of two peptide-linked carbohydrate recognition domains (CRDs), but alternative splicing and proteolytic processing can give rise to multiple galectin-9 isoforms. Some of these consist of a single CRD and can exert different functions in cell biology. Here, we explored the role of these galectin-9 isoforms in endothelial cell function and angiogenesis. For this, we compared the effects of the two separate CRDs (Gal-9N and Gal-9C) with the tandem repeat galectin-9M on endothelial cell proliferation, migration, sprouting and tube formation in vitro as well as on angiogenesis in vivo using the chicken chorioallantoic membrane (CAM) assay. Galectin-9 isoforms significantly affected proliferation in quiescent endothelial cells and migration in activated endothelial cells. Interestingly, both monovalent gal-9 CRDs displayed opposite effects compared to gal-9M on proliferation and migration. Sprouting was significantly inhibited by gal-9C, while all isoforms appeared to stimulate tube formation. Angiogenesis in vivo was hampered by all three isoforms with predominant effects on vessel length. In general, the isoforms induced only subtle concentration-dependent effects in vitro as well as in vivo. Collectively, the effects of different galectin-9 isoforms in endothelial cell biology depend on the cellular activation status. While opposing effects can be observed on a cellular level in vitro, all galectin-9 isoforms hamper angiogenesis in vivo. This warrants further investigation of the regulatory mechanisms that underlie the diverging roles of galectin-9 isoforms in endothelial cell biology since this could provide therapeutic opportunities.
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| 6. |
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| 7. |
- 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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| 8. |
- Huijbers, Elisabeth J. M, 1979-
(författare)
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Development of a Cancer Vaccine Targeting Tumor Blood Vessels
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A treatment strategy for cancer is the suppression of tumor growth by directing an immune response to the tumor vessels, which will destroy the tissue.In this thesis we describe the development of a vaccine that targets antigens expressed around angiogenic vasculature in most solid tumors. These antigens are alternative spliced extra domains of glycoproteins present in the extracellular matrix; e.g. the extra domain-B (ED-B) and extra domain-A (ED-A) of fibronectin and the C-domain of tenascin-C (TNCC).We show that it is possible to break self-tolerance and induce a strong antibody response against ED-B by vaccination. Furthermore, tumor growth was inhibited and the changes observed in the tumor tissue were consistent with an attack of the tumor vasculature by the immune system.For clinical development of therapeutic vaccines, targeting self-molecules like ED-B, a potent but non-toxic biodegradable adjuvant is required. The squalene-based Montanide ISA 720 (M720) in combination with CpG DNA fulfilled these requirements and induced an equally strong anti-self immune response as the preclinical golden standard Freund’s adjuvant. We have further characterized the immune response against ED-B generated with the adjuvant M720/GpG. The ED-B vaccine also inhibited tumor growth in a therapeutic setting in a transgenic mouse model of pancreatic insulinoma in which tumorigenesis was already initiated. Furthermore, antibodies against ED-A and TNCC could be induced in mice and rabbits. We analyzed the expression of ED-A in breast tumors of transgenic MMTV-PyMT mice, a metastatic breast cancer model, with the aim to use this model to study the effect of an ED-A vaccine on metastasis. We also detected ED-B in canine mammary tumor tissue. Therefore vascular antigens might also represent potential therapeutic targets in dogs. All together our preclinical data demonstrate that a vaccine targeting tumor blood vessels is a promising new approach for cancer treatment.
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| 9. |
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| 10. |
- Salomonsson, Emma, et al.
(författare)
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The anti-angiogenic peptide anginex greatly enhances Galectin-1 binding affinity for glycoproteins
- 2011
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 286:16, s. 13801-13804
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is a key event in cancer progression and therefore a promising target in cancer treatment. Galectin-1, a β-galactoside binding lectin, is up-regulated in the endothelium of tumors of different origin and has been shown to be the target for anginex, a powerful anti-angiogenic peptide with anti-tumor activity. Here we show that when bound to anginex, galectin-1 binds various glycoproteins with hundred-to thousand-fold higher affinity. Anginex also interacts with galectin-2,-7,-8N, and-9N but not with galectin-3,-4, or-9C.
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