| 1. |
- Claesson-Welsh, Lena
(författare)
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Blood vessels as targets in tumor therapy
- 2012
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 117:2, s. 178-186
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Forskningsöversikt (refereegranskat)abstract
- The landmark papers published by Judah Folkman in the early 1970s on tumor angiogenesis and therapeutic implications promoted the rapid development of a very dynamic field where basic scientists, oncologists, and pharmaceutical industry joined forces to determine the molecular mechanisms in blood vessel formation and find means to exploit this knowledge in suppressing tumor vascularization and growth. A wealth of information has been collected on angiogenic growth factors, and in 2004 the first specific blood vessel-targeted cancer therapy was introduced: a neutralizing antibody against vascular endothelial growth factor (VEGF). Now (2011) we know that suppression of tumor angiogenesis may be a double-edged sword and that the therapy needs to be further refined and individualized. This review describes the hallmarks of tumor vessels, how different angiogenic growth factors exert their function, and the perspectives for future development of anti-angiogenic therapy.
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| 2. |
- Claesson-Welsh, Lena
(författare)
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Oxygen sensing : a stunningly elegant molecular machinery highjacked in cancer
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:3, s. 205-210
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Forskningsöversikt (refereegranskat)abstract
- Oxygen is of fundamental importance for most living organisms, and the maintenance of oxygen homeostasis is a key physiological challenge for all large animals. Oxygen deprivation, hypoxia, is a critical component of many human diseases including cancer, heart disease, stroke, vascular disease, and anaemia. The discovery of oxygen sensing provides fundamental knowledge of a stunningly elegant molecular machinery; it also promises development of new therapeutics for serious diseases such as cancer. As a result of their impressive contributions to our understanding of the mechanisms by which cells sense oxygen and signal in hypoxia, Gregg Semenza, Peter Ratcliffe, and William Kaelin were awarded the Nobel Prize in 2019.
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| 3. |
- Claesson-Welsh, Lena, et al.
(författare)
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Permeability of the Endothelial Barrier : Identifying and Reconciling Controversies
- 2021
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Ingår i: Trends in Molecular Medicine. - : Elsevier. - 1471-4914 .- 1471-499X. ; 27:4, s. 314-331
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Forskningsöversikt (refereegranskat)abstract
- Leakage from blood vessels into tissues is governed by mechanisms that control endothelial barrier function to maintain homeostasis. Dysregulated endothelial permeability contributes to many conditions and can influence disease morbidity and treatment. Diverse approaches used to study endothelial permeability have yielded a wealth of valuable insights. Yet, ongoing questions, technical challenges, and unresolved controversies relating to the mechanisms and relative contributions of barrier regulation, transendothelial sieving, and transport of fluid, solutes, and particulates complicate interpretations in the context of vascular physiology and pathophysiology. Here, we describe recent in vivo findings and other advances in understanding endothelial barrier function with the goal of identifying and reconciling controversies over cellular and molecular processes that regulate the vascular barrier in health and disease.
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| 4. |
- Claesson-Welsh, Lena
(författare)
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Vascular permeability - the essentials
- 2015
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:3, s. 135-143
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Forskningsöversikt (refereegranskat)abstract
- The vasculature, composed of vessels of different morphology and function, distributes blood to all tissues and maintains physiological tissue homeostasis. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and hyperpermeable vessels with poor blood flow, which further promotes hypoxia and disease propagation. Chronic vessel permeability may also facilitate metastatic spread of cancer. Thus, there is a strong incentive to learn more about an important aspect of vessel biology in health and disease: the regulation of vessel permeability. The current review aims to summarize current insights into different mechanisms of vascular permeability, its regulatory factors, and the consequences for disease.
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| 5. |
- Claesson-Welsh, Lena
(författare)
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VEGF receptor signal transduction - A brief update
- 2016
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Ingår i: Vascular pharmacology. - : Elsevier BV. - 1537-1891 .- 1879-3649. ; 86, s. 14-17
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Forskningsöversikt (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) signal transduction through receptor tyrosine lcinases VEGF receptor 1, -2 and -3 is of crucial importance for monocytes/macrophages, blood vascular endothelial and lymphatic endothelial cells both in physiology and in a number of pathologies notably cancer. This brief review summarizes the current status of VEGF receptor signaling with emphasis on in vivo data.
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| 6. |
- Claesson-Welsh, Lena, et al.
(författare)
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VEGFA and tumour angiogenesis
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 273:2, s. 114-127
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Forskningsöversikt (refereegranskat)abstract
- In this review we summarize the current understanding of signal transduction downstream of vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2, and the relationship between these signal transduction pathways and the hallmark responses of VEGFA, angiogenesis and vascular permeability. These physiological responses involve a number of effectors, including extracellular signal-regulated kinases (ERKs), Src, phosphoinositide 3 kinase (PI3K)/Akt, focal adhesion kinase (FAK), Rho family GTPases, endothelial NO and p38 mitogen-activated protein kinase (MAPK). Several of these factors are involved in the regulation of both angiogenesis and vascular permeability. Tumour angiogenesis primarily relies on VEGFA-driven responses, which to a large extent result in a dysfunctional vasculature. The reason for this remains unclear, although it appears that certain aspects of the VEGFA-stimulated angiogenic milieu (high level of microvascular density and permeability) promote tumour expansion. The high degree of redundancy and complexity of VEGFA-driven tumour angiogenesis may explain why tumours commonly develop resistance to anti-angiogenic therapy targeting VEGFA signal transduction.
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| 7. |
- Jakobsson, Lars, et al.
(författare)
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Building blood vessels- Stem cell models in vascular biology
- 2007
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 177:5, s. 751-755
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Forskningsöversikt (refereegranskat)abstract
- Spheroids of differentiating embryonic stem cells, denoted embryoid bodies, constitute a high-quality model for vascular development, particularly well suited for loss-of-function analysis of genes required for early embryogenesis. This review examines vasculogenesis and angiogenesis in murine embryoid bodies and discusses the promise of stem cell–based models for the study of human vascular development.
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| 8. |
- Koch, Sina, et al.
(författare)
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Signal transduction by vascular endothelial growth factor receptors
- 2011
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 437, s. 169-183
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Forskningsöversikt (refereegranskat)abstract
- VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling.
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| 9. |
- Li, Xiujuan, et al.
(författare)
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Embryonic stem cell models in vascular biology
- 2009
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:Suppl. 1, s. 53-56
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Forskningsöversikt (refereegranskat)abstract
- Embryonic stem cells have become an established tool in vascular biology to study the details of vasculogenesis as well as angiogenesis. There is also a future potential in using embryonic stem cell-derived endothelial cells for therapeutic purposes. It is important to evaluate this model by comparing features of endothelial cells derived from differentiating stem cells and their responsiveness to external stimuli to those of primary endothelial cells and to in vivo models. Through culture of mouse embryonic stem cell we discovered that differentiating stem cells are highly amenable to analyzing biochemical and cell biologic processes that are independent of flow. Endothelial cell function can be studied in the context of mutations or deletions that are embryonically lethal in vivo. Many, if not all, of the features of sprouting angiogenesis in differentiating stem cells closely mimic the in vivo process.
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| 10. |
- Sainz-Jaspeado, Miguel, et al.
(författare)
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Cytokines regulating lymphangiogenesis
- 2018
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Ingår i: Current Opinion in Immunology. - : CURRENT BIOLOGY LTD. - 0952-7915 .- 1879-0372. ; 53, s. 58-63
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Forskningsöversikt (refereegranskat)abstract
- Lymphatic vessels are established by differentiation of lymphendothelial progenitors during embryogenesis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing ones is rare in the healthy adult but takes place during pathological conditions such as inflammation, tissue repair and tumor growth. Conditions of dysfunctional lymphatics exist after surgical interventions or in certain genetic diseases. A key lymphangiogenic stimulator is vascular endothelial growth factor-C (VEGFC) acting on VEGF receptor-3 (VEGFR3) expressed on lymphendothelial cells. Other cytokines may act directly to regulate lymphangiogenesis positively or negatively, or indirectly by inducing expression of VEGFC. This review describes different known lymphangiogenic cytokines, their mechanism of action and role in lymphangiogenesis in health and disease.
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