| 1. |
- Ekman, Simon, et al.
(författare)
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Activation of growth factor receptors in esophageal cancer : implications for therapy
- 2007
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 12:10, s. 1165-1177
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Forskningsöversikt (refereegranskat)abstract
- Esophageal cancer is a highly aggressive disease and is the seventh most common cause of cancer-related death in the western world. Worldwide, it ranks as the sixth most frequent cause of cancer death. Despite advances in surgical techniques and treatment, the prognosis of esophageal cancer remains poor, with very few long-term survivors. The need for novel strategies to detect esophageal cancer earlier and to improve current therapy is urgent. It is well established that growth factors and growth factor receptor-mediated signaling pathways are important components of the transformation process in many forms of cancer, including esophageal cancer. With the recent advances in drug development, there are emerging possibilities to use growth factor signal transduction pathways in targeted therapy. This review provides a summary of the role of growth factors and their receptors in esophageal cancer and discusses their potential roles as biomarkers and as targets in therapy.
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| 2. |
- Heldin, Carl-Henrik
(författare)
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Autocrine PDGF stimulation in malignancies
- 2012
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 117:2, s. 83-91
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Forskningsöversikt (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) isoforms are important mitogens for different types of mesenchymal cells, which have important functions during the embryonal development and in the adult during wound healing and tissue homeostasis. In tumors, PDGF isoforms are often over-expressed and contribute to the growth of both normal and malignant cells. This review focuses on tumors expressing PDGF isoforms together with their tyrosine kinase receptors, thus resulting in autocrine stimulation of growth and survival. Patients with such tumors could benefit from treatment with inhibitors of either PDGF or PDGF receptors.
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| 3. |
- Heldin, Carl-Henrik
(författare)
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Development and possible clinical use of antagonists for PDGF and TGF-beta
- 2004
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 109:3, s. 165-178
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are examples of signaling molecules which control the growth, survival motility and differentiation of cells. PDGF stimulates the growth mainly of connective tissue cells, whereas TGF-beta inhibits the growth of most cell types. PDGF and TGF-beta exert their cellular effects by binding to receptors equipped with tyrosine and serine/threonine kinase activities, respectively. Both factors have important roles e.g. during the embryonal development and in wound healing. Overactivity of PDGF or PDGF receptors contributes to the development of certain diseases characterized by excessive cell growth including fibrotic disorders, atherosclerosis and malignancies. Overactivity of TGF-beta also contributes to fibrotic conditions, since TGF-beta promotes accumulation of extracellular matrix molecules. In cancer, TGF-beta is initially a tumor suppressor due to its ability to inhibit cell growth, however, at later stages of tumor progression TGF-beta has tumor promoting activity by enhancing the invasive properties of tumor cells and by suppressing the immune system and promoting angiogenesis. The involvement of PDGF in TGF-beta in serious diseases makes clinically useful antagonists highly desirable. A low molecular weight receptor kinase inhibitor of the PDGF receptor kinase is now tested clinically, and TGF-beta antagonists are under development. The present review discusses the development and possible clinical use of antagonsts for PDGF and TGF-beta.
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| 4. |
- Heldin, Carl-Henrik
(författare)
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Growth factor regulation of kinases
- 2001
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Ingår i: Ernst Schering Res Found Workshop. - 0947-6075. ; :34, s. 1-18
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Forskningsöversikt (populärvet., debatt m.m.)
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| 5. |
- Heldin, Carl-Henrik, 1952-, et al.
(författare)
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Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:1, s. 16-44
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Forskningsöversikt (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) isoforms and their receptors have important roles during embryogenesis, particularly in the development of various mesenchymal cell types in different organs. In the adult, PDGF stimulates wound healing and regulates tissue homeostasis. However, overactivity of PDGF signalling is associated with malignancies and other diseases characterized by excessive cell proliferation, such as fibrotic conditions and atherosclerosis. In certain tumours, genetic or epigenetic alterations of the genes for PDGF ligands and receptors drive tumour cell proliferation and survival. Examples include the rare skin tumour dermatofibrosarcoma protuberance, which is driven by autocrine PDGF stimulation due to translocation of a PDGF gene, and certain gastrointestinal stromal tumours and leukaemias, which are driven by constitute activation of PDGF receptors due to point mutations and formation of fusion proteins ofthe receptors, respectively. Moreover, PDGF stimulates cells in tumour stroma and promotes angiogenesis as well as the development of cancer-associated fibroblasts, both of which promote tumour progression. Inhibitors of PDGF signalling may thus be of clinical usefulness in the treatment of certain tumours.
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| 6. |
- Heldin, Carl-Henrik, et al.
(författare)
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Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition
- 2009
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Ingår i: Current Opinion in Cell Biology. - : Elsevier Ltd.. - 0955-0674 .- 1879-0410. ; 21:2, s. 166-176
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Forskningsöversikt (refereegranskat)abstract
- Members of the transforming growth factor-beta (TGF-beta) family have important roles during embryogenesis, as well as in the control of tissue homeostasis in the adult. They exert their cellular effects via binding to serine/threonine kinase receptors. Members of the Smad family of transcription factors are important intracellular messengers, and recent studies have shown that the ubiquitin ligase TRAF6 mediates other specific signals. TGF-beta signaling is tightly controlled by post-translational modifications, which regulate the activity, stability, and subcellular localization of the signaling components. The aim of this review is to summarize some of the recent findings on the mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition.
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| 7. |
- Heldin, Carl-Henrik
(författare)
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Platelet-derived growth factor : an introduction
- 2004
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Ingår i: Cytokine & growth factor reviews. - : Elsevier BV. - 1359-6101 .- 1879-0305. ; 15:4, s. 195-196
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Heldin, Carl-Henrik, et al.
(författare)
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Regulation of EMT by TGFβ in cancer
- 2012
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 586:14, s. 1959-1970
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Forskningsöversikt (refereegranskat)abstract
- Transforming growth factor-beta (TGF beta) suppresses tumor formation since it inhibits cell growth and promotes apoptosis. However, in advanced cancers TGF beta elicits tumor promoting effects through its ability to induce epithelial-mesenchymal transition (EMT) which enhances invasiveness and metastasis; in addition, TGF beta exerts tumor promoting effects on non-malignant cells of the tumor, including suppression of immune surveillance and stimulation of angiogenesis. TGF beta promotes EMT by transcriptional and posttranscriptional regulation of a group of transcription factors that suppresses epithelial features, such as expression of components of cell junctions and polarity complexes, and enhances mesenchymal features, such as production of matrix molecules and several cytokines and growth factors that stimulate cell migration. The EMT program has certain similarities with the stem cell program. Inducers and effectors of EMT are interesting targets for the development of improved diagnosis, prognosis and therapy of cancer.
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| 9. |
- Heldin, Carl-Henrik, 1952-, et al.
(författare)
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Role of Smads in TGFβ signaling
- 2012
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 347:1, s. 21-36
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Forskningsöversikt (refereegranskat)abstract
- Transforming growth factor-β (TGFβ) is the prototype for a large family of pleiotropic factors that signal via heterotetrameric complexes of type I and type II serine/threonine kinase receptors. Important intracellular mediators of TGFβ signaling are members of the Smad family. Smad2 and 3 are activated by C-terminal receptor-mediated phosphorylation, whereafter they form complexes with Smad4 and are translocated to the nucleus where they, in cooperation with other transcription factors, co-activators and co-repressors, regulate the transcription of specific genes. Smads have key roles in exerting TGFβ-induced programs leading to cell growth arrest and epithelial-mesenchymal transition. The activity and stability of Smad molecules are carefully regulated by a plethora of post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation and poly(ADP)-ribosylation. The Smad function has been shown to be perturbed in certain diseases such as cancer.
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| 10. |
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