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- Jernberg-Wiklund, Helena, et al.
(author)
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Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I)
- 2007
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In: Advances in Cancer Research. - 0065-230X .- 2162-5557. ; 97, s. 139-165
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Research review (peer-reviewed)abstract
- Human multiple myeloma (MM) is characterized by the expansion of neoplastic plasmablasts/plasma cells with complex genetic aberrations and high dependence for survival and growth on cytokines produced in the bone marrow microenvironment. As tools in the study of MM about 80 authentic MM cell lines and a few relevant in vivo mouse models are available. The dependence on insulin-like growth factor receptor (IGF-IR) signaling in the development and maintenance of the malignant phenotype in a variety of cancers is a rationale for attempts to improve tumor treatment by selectively inhibiting the IGF-IR in malignant cells by neutralizing antibodies, dominant negative IGF-IR, and IGF-IR siRNA. Testing the hypothesis that abrogating IGF-IR-mediated signaling of survival should make MM cells more susceptible to apoptosis, our studies have so far provided proof-of-principle by the demonstration that inhibition of a signaling pathway stimulating survival renders cells susceptible to drug-induced apoptosis when the drug (dexamethasone) and inhibitor (rapamycin) converge on the same target, that is p70S6K. The recent publication of the three-dimensional structure of the IGF-IR kinase domain has facilitated the development of IGF-IR inhibitors of the cyclolignan family, that is picropodophyllin, with capacity to distinguish also in vivo between the IGF-IR and the insulin receptor. Studies in vitro and in vivo with picropodophyllin show promising effects, that is apoptosis induction and growth arrest, and have made it possible to evaluate the biological and therapeutic effects of inhibition of the IGF-IR signaling in MM.
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- Mougiakakos, D, et al.
(author)
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Regulatory T cells in cancer
- 2010
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In: Advances in cancer research. - 2162-5557. ; 107, s. 57-117
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Journal article (peer-reviewed)
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- Simpson, Melanie A, et al.
(author)
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Preface
- 2014
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In: Advances in Cancer Research. - 0065-230X .- 2162-5557. ; 123, s. xv-xvi
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Journal article (peer-reviewed)
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- van Leeuwen, I, et al.
(author)
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Sirtuins and p53
- 2009
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In: Advances in cancer research. - 2162-5557. ; 102, s. 171-195
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Journal article (peer-reviewed)
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- Östman, Arne, et al.
(author)
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Involvement of platelet-derived growth factor in disease : development of specific antagonists
- 2001
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In: Advances in Cancer Research. - 0065-230X .- 2162-5557. ; 80, s. 1-38
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Journal article (peer-reviewed)abstract
- Platelet-derived growth factor (PDGF) is a family of dimeric isoforms that stimulates, e.g., growth, chemotaxis and cell shape changes of various connective tissue cell types and certain other cells. The cellular effects of PDGF isoforms are exerted through binding to two structurally related tyrosine kinase receptors. Ligand binding induces receptor dimerization and autophosphorylation. This enables a number of SH2 domain containing signal transduction molecules to bind to the receptors, thereby initiating various signaling pathways. PDGF isoforms have important roles during the embryonic development, particularly in the formation of connective tissue in various organs. In the adult, PDGF stimulates wound healing. Overactivity of PDGF has been implicated in certain disorders, including fibrotic conditions, atherosclerosis, and malignancies. Different kinds of PDGF antagonists are currently being developed and evaluated in different animal disease models, as well as in clinical trials.
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| 19. |
- Östman, Arne, et al.
(author)
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PDGF receptors as targets in tumor treatment
- 2007
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In: Advances in Cancer Research. - San Diego : Academic Press. - 0065-230X .- 2162-5557. - 9780120066971 ; 97, s. 247-274
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Research review (peer-reviewed)abstract
- Signaling through platelet-derived growth factor (PDGF) receptors contributes to multiple tumor-associated processes. The recent introduction of clinically useful PDGF inhibitors have the last years validated PDGF receptors in malignant and stromal cells as relevant cancer drug targets. Mutational activation of PDGF receptor signaling in malignant cells has been described in some rare tumor types such as dermatofibrosarcoma protuberans, a subset of GISTs, and some hematologic malignancies. Furthermore, expression of PDGF receptors on pericytes is a common characteristic of solid tumors. The clinical efficacy of novel multikinase inhibitors, such as sunitimb and sorafemb, most likely involves targeting of PDGF receptor-dependent pericytes. Preclinical studies suggest that targeting of stromal PDGF receptors might also constitute a novel strategy to enhance tumor drug uptake. Finally, recent studies have implied both pro- and antimetastatic effects of PDGF receptors on malignant and stromal cells. The studies on the roles of PDGF receptors in cancer signaling are thus presently in a dynamic phase where collaborations between oncologists, pathologists, and tumor biologists are predicted to be highly productive.
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