| 1. |
- Engström, Wilhelm, et al.
(författare)
-
The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling
- 2015
-
Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 36, s. S38-S60
-
Forskningsöversikt (refereegranskat)abstract
- The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.
|
|
| 2. |
- Eriksson, Staffan, et al.
(författare)
-
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
- 2015
-
Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 36, s. S254-S296
-
Forskningsöversikt (refereegranskat)abstract
- Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
|
|
| 3. |
- Engström, Wilhelm, et al.
(författare)
-
Epigenic regulation of the IGF2/H19 locus
- 2014
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 5895-5895
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
| 4. |
- Engström, Wilhelm
(författare)
-
Role of fibroblast growth factors in elicitation of cell responses
- 2014
-
Ingår i: Cell Proliferation. - : Wiley. - 0960-7722 .- 1365-2184. ; 47, s. 3-11
-
Tidskriftsartikel (refereegranskat)abstract
- Fibroblast growth factors (FGFs) are signalling peptides that control important cell processes such as proliferation, differentiation, migration, adhesion and survival. Through binding to different types of receptor on the cell surface, these peptides can have different effects on a target cell, the effect achieved depending on many features. Thus, each of the known FGFs elicits specific biological responses. FGF receptors (FGFR 1-5) initiate diverse intracellular pathways, which in turn lead to a variety of results. FGFs also bind the range of FGFRs with a series of affinities and each type of cells expresses FGFRs in different qualitative and quantitative patterns, which also affect responses. To summarize, cell response to binding of an FGF ligand depends on type of FGF, FGF receptor and target cell, all interacting in concert. This review aims to examine properties of the FGF family and its members receptors. It also aims to summarize features of intracellular signalling and highlight differential effects of the various FGFs in different circumstances.
|
|
| 5. |
|
|
| 6. |
- Engström, Wilhelm
(författare)
-
The RECK Gene and Biological Malignancy-Its Significance in Angiogenesis and Inhibition of Matrix Metalloproteinases
- 2014
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34, s. 3867-3873
-
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.
|
|
| 7. |
- Engström, Wilhelm
(författare)
-
The WT1 Gene - Its Role in Tumourigenesis and Prospects for Immunotherapeutic Advances
- 2014
-
Ingår i: In Vivo. - 0258-851X. ; 28, s. 675-681
-
Forskningsöversikt (refereegranskat)abstract
- The Wilms Tumour 1 (WT1) gene is a complex gene which was originally linked to suppression of cancer in kidneys. Studies of WT1-knockout mice confirmed the important role of WT1 in the pathogenesis of Wilms' tumour, a tumour which accounts for 95% of all childhood renal tumours. In such cases, the WT1 gene acts as a tumour-suppressor gene. Subsequent research has shown that the WT1 gene in many other cases acts as an oncogene, most prominently in leukaemia and lung cancer (even though these cancer forms can emerge as a result of many other aetiological factors). Since WT1 acts as an oncogene in many different organs, it is of great importance to evaluate how and when the WT1 gene and protein act. This information can then be used to develop immunotherapy to stabilize and treat different malignant diseases. Both phase I and phase II studies have been carried out on candidate vaccines with varying but overall promising results. The immune response does not always correlate with the clinical response, however, and the efficacy of the treatment is often limited. Further development is, therefore, needed to understand how vaccines can be improved, so that they, can hopefully fulfil a clinical role in the future.
|
|
| 8. |
- Nordin, Matilda, et al.
(författare)
-
Epigenetic regulation of the Igf2/H19 gene cluster
- 2014
-
Ingår i: Cell Proliferation. - : Wiley. - 0960-7722 .- 1365-2184. ; 47, s. 189-199
-
Tidskriftsartikel (refereegranskat)abstract
- Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals; they are expressed unevenly from the two parental alleles. Igf2 is a growth factor expressed in most normal tissues, solely from the paternal allele. H19 gene is transcribed (but not translated to a protein) from the maternal allele. Igf2 protein is a growth factor particularly important during pregnancy, where it promotes both foetal and placental growth and also nutrient transfer from mother to offspring via the placenta. This article reviews epigenetic regulation of the Igf2/H19 gene-cluster that leads to parent-specific expression, with current models including parental allele-specific DNA methylation and chromatin modifications, DNA-binding of insulator proteins (CTCFs) and three-dimensional partitioning of DNA in the nucleus. It is emphasized that key genomic features are conserved among mammals and have been functionally tested in mouse. The enhancer competition model', the boundary model' and the chromatin-loop model' are three models based on differential methylation as the epigenetic mark responsible for the imprinted expression pattern. Pathways are discussed that can account for allelic methylation differences; there is a recent study that contradicts the previously accepted fact that biallelic expression is accompanied with loss of differential methylation pattern.
|
|
| 9. |
- Bergman, Daniel, et al.
(författare)
-
Insulin-Like Growth Factor 2 in Development and Disease: A Mini-Review
- 2013
-
Ingår i: Gerontology. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 59, s. 240-249
-
Forskningsöversikt (refereegranskat)abstract
- Background: Insulin-like growth factor 2 (IGF2) is a protein hormone known to regulate cell proliferation, growth, migration, differentiation and survival. The gene is parentally imprinted in the sense that transcripts are almost exclusively derived from the paternal allele. Loss of imprinting of the IGF2 gene is a recurrent observation in growth disorders that combine overgrowth with a variety of malignant tumours. Moreover, IGF2 has been proposed to play a role in the development of a variety of seemingly unrelated cancers that play an important role in geriatric medicine, e.g. breast cancer, colon cancer and lung cancer. Finally, IGF2 has been implicated in cardiovascular disease, since, for example, IGF2 has been shown to influence the size of atherosclerotic lesions. Objective: To summarize current knowledge about IGF2, its interactions with binding proteins and receptors and connections with key diseases. Methods: The contents of this paper were based on reviews of existing literature within the field. Results: There is a substantial amount of research linking IGF2 to growth disorders, cancer and to a much lesser degree cardiovascular disease. Some of the studies on IGF2 and tumour growth have yielded conflicting results, for instance regarding its effect on apoptosis. Conclusion: Today, our knowledge on how IGF2 is composed and interacts with receptors has come a long way. However, there is comparatively little information on how IGF2 affects tumour growth and cardiovascular diseases such as atherosclerosis. Thus, further research will be needed to elucidate the impact of IGF2 on key diseases. Copyright (C) 2012 S. Karger AG, Basel
|
|
| 10. |
|
|
