| 1. |
- Alanazi, Sultan, et al.
(författare)
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Histone Methyltransferase Inhibition Has a Cytotoxic Impact on Transformed Mast Cells : Implications for Mastocytosis
- 2020
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 40:5, s. 2525-2536
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Mast cell transformation, as manifested in mastocytosis, can be a serious condition for which there are limited therapeutic options. Mastocytosis cells can be sensitive to histone deacetylase (HDAC) inhibitors, but their sensitivity to other histone-modifying enzymes has not been assessed. Here we addressed this issue.Materials and Methods: Inhibitors of histone methyl transferases, histone demethylases, histone acetyl transferases and HDACs were tested for their effects on growth, viability, caspase-3 activation and annexin V/DRAQ7 staining in transformed mast cells.Results: Transformed mast cells underwent cell death in response to histone methyl transferase and HDAC inhibition, but were not sensitive to histone demethylase or histone acetyl transferase inhibition. Histone methyl transferase inhibition led to cell death with characteristics of apoptosis, as judged by caspase-3 activation. However, DNA fragmentation was not apparent and Annexin V+/DRAQ7(-) cells were not predominant, suggesting a type of cell death differing from classical apoptosis.Conclusion: Histone methyl transferase inhibition could be developed as a novel regimen for targeting mastocytosis.
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| 2. |
- Engström, Wilhelm
(författare)
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Effects of Insulin-like Growth Factor Binding Protein 7 on Apoptosis in Human Teratocarcinoma Cells In Vitro
- 2010
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30, s. 911-914
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Tidskriftsartikel (refereegranskat)abstract
- Human teratocarcinoma cells (Tera-2) deprived of serum undergo programmed cell death which can be counteracted by simultaneous addition of IGF-II. This protective effect of IGF-II was specific in the sense that addition of IGF-binding protein 7 (IGFBP-7) resulted in an increased apoptotic rate almost comparable to that of the classical IGFBPs. Autoradiographic analysis of incorporated tritiated thymidine indicated that the proportion of S-phase cells was comparable, irrespective of total cell numbers. This further suggests that IGF-II rescues cells from apoptosis and that IGFBP-7 is a specific antagonist.
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| 3. |
- Engström, Wilhelm, et al.
(författare)
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Epigenic regulation of the IGF2/H19 locus
- 2014
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 5895-5895
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Engström, Wilhelm
(författare)
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Expression of JNK-interacting Protein JIP-1 and Insulin-like Growth Factor II in Wilms Tumour Cell Lines and Primary Wilms Tumours
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29, s. 2467-2472
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Tidskriftsartikel (refereegranskat)abstract
- JNK-interacting protein 1 (JIP-1) is an important scaffolding protein in the JNK signalling pathway. It is also believed to play a role in the mediation of mitogenic messages from the plasma membrane to the cell interior. Previous studies suggest that the JIP-gene is co-regulated with the insulin-like growth factor II (IGF II) gene, thereby contributing to the growth stimulatory effects of this potent growth factor. The striking coexpression of these two genes was found in murine fetuses as well as in primary human embryonic tumours. When six primary Wilms tumours were examined, the two genes showed a high degree of co-variation in the sense that high expression of IGF II was followed by high expression of JIP-1 and vice versa. However, when the human Wilms tumour cell line WCCS-1 was examined, a very modest intrinsic expression of IGF 11 was accompanied by a moderate expression of JIP-1. When exogenous IGF H was added, which has previously been shown to induce apoptosis in this cell line, the JIP-1 expression increased. These data suggest that JIP-1 has a more complex role in the regulation of proliferation as well as programmed cell death.
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| 5. |
- Engström, Wilhelm
(författare)
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The Expression of the Insulin-like Growth Factor II, JIP-1 and WT1 Genes in Porcine Nephroblastoma
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29, s. 4999-5003
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Tidskriftsartikel (refereegranskat)abstract
- c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1) is an important scaffolding protein in the JNK signalling pathway. It is also believed to play a role in the mediation of mitogenic messages from the plasma membrane to the cell interior. Previous studies have suggested that the JIP gene is co-regulated with the insulin-like growth factor II (IGF-II) gene, thereby contributing to the growth stimulatory effects of this potent growth factor. The striking co-expression of these two genes has been found in murine foetuses as well as in primary human embryonic tumours. When six primary Wilms tumours (nephroblastomas) from pig were examined, the two genes showed a high degree of co-variation in the sense that high or low expression of IGF-II and high or low expression of JIP-1 ocurred together. By contrast the expression of a third Wilms tumour related gene, WT1, was completely uncorrelated to the expression of IGF-II and JIP. In this respect, porcine nephroblastomas resemble human Wilms tumours. This further suggests that JIP-1 may play a role in the regulation of IGF-II-driven tumour cell proliferation.
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| 6. |
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| 7. |
- Engström, Wilhelm
(författare)
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The RECK Gene and Biological Malignancy-Its Significance in Angiogenesis and Inhibition of Matrix Metalloproteinases
- 2014
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 3867-3873
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Forskningsöversikt (refereegranskat)abstract
- The RECK (reversion-inducing cysteine-rich protein with Kazal motifs) gene is a relatively newly discovered gene with important implications in cancer biology. RECK is normally expressed in all cells of the body and has an important role in the balance between destructive and constructive features of the extracellular matrix (ECM). The RECK protein is a membrane-bound glycoprotein that inhibits matrix metalloproteinases with the function of breaking-down the ECM. There is a significant correlation between RECK gene expression and the formation of new vessels, presumably via the mediation of vascular endothelial growth factor (VEGF), which is an important and powerful inducer of angiogenesis.. Research has shown that down-regulation of RECK is caused by the rat sarcoma oncogene (RAS), which is also a common cause of tumor development in the early stages. For a tumor to progress and gain characteristics that classifies it as malignant, the degradation of the ECM and mobilization of new blood vessels are essential functions. If the tumor is inhibited with respect to these functions, it will cease to grow. RECK is, therefore, a potential tumor inhibitor but also a prognostic marker available at early clinical stages.
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