| 1. |
- Vinnakota, Katyayni, et al.
(författare)
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M2-like macrophages induce colon cancer cell invasion via matrix metalloproteinases
- 2017
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541. ; 232:12, s. 3468-3480
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Tidskriftsartikel (refereegranskat)abstract
- The inflammatory milieu plays an important role in colon cancer development and progression. Previously, we have shown that tumor-associated macrophages (TAMs), an important component of the tumor microenvironment, are enriched in tumors compared with normal tissue and confer a poorer prognosis. In the present study, we found that matrix metallopeptidase-9 (MMP-9), which degrades extracellular matrix proteins, was increased in biopsies from colon cancer patients and in mouse xenografts with SW480 cell-derived tumors. SW480 colon cancer cells exposed to M2-like macrophage-conditioned medium (M2-medium) exhibited increased MMP-9 mRNA, protein expression and gelatinase activity. A similar effect was obtained by the addition of tumor necrosis factor-α (TNFα) and leukotriene D4 (LTD4). MMP-9 expression and activity were reduced by a TNFα blocking antibody adalimumab and a cysteinyl leukotriene receptor 1 (CysLTR1, the receptor for LTD4) antagonist montelukast. M2-medium also induced changes in the epithelial-mesenchymal transition (EMT) markers E-cadherin, β-catenin, vimentin, and snail in SW480 cells. We also found that both M2-medium and TNFα and LTD4 induced stabilization/nuclear translocation of β-catenin. Furthermore, we also observed an elongated phenotype that may indicate increased invasiveness, as confirmed in a collagen I invasion assay. M2-medium increased the invasive ability, and a similar effect was also obtained by the addition of TNFα and LTD4. The specific MMP inhibitor I or adalimumab and montelukast reduced the number of invasive cells. In conclusion, our findings show that M2-medium enriched in TNFα and LTD4 promote colon cancer cell invasion via MMP-9 expression and activation and the induction of EMT.
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| 2. |
- Savari, Sayeh, et al.
(författare)
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Cysteinyl leukotriene 1 receptor influences intestinal polyp incidence in a gender-specific manner in the ApcMin/+ mouse model
- 2016
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 37:5, s. 491-499
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Tidskriftsartikel (refereegranskat)abstract
- There is emerging literature emphasizing the role of inflammatory eicosanoids, including prostaglandins and leukotrienes, in cancer development. Increased expression of both the cysteinyl leukotriene receptor 1 (CysLTR1) and the enzyme responsible for the production of leukotrienes, 5-lipoxygenase (5-LOX), is associated with poor prognosis in patients with colorectal adenocarcinomas. Apc mutation is an early event in the development of sporadic and hereditary (FAP) colorectal cancer. We utilized the Apc(Min/+) mouse model of FAP/sporadic colorectal cancer to investigate the role of CysLTR1 in intestinal tumorigenesis by crossing Apc(Min/+) mice with mice lacking the Cysltr1 gene. We could observe a reduced tumor burden in the small intestine of double-mutant female (Cysltr1(-/-) Apc(Min/+)) but not double-mutant male mice, compared to gender-matched single-mutant (Cysltr1(+/+) Apc(Min/+)) mice. This reduction was in a Cysltr1 dependent manner, female double mutant mice having significantly reduced tumor formation compared to control littermates. The female double-mutant phenotype was accompanied with decreased systemic inflammation, as evidenced by significantly reduced serum levels of PGE2 and CysLTs, as well as increased CD3(+)CD8(+) T cell tumor infiltration. Furthermore, the reduced formation of polyps in double-mutant (Cysltr1(-/-) Apc(Min/+)) female mice could in part be explained by the cytotoxic action of CD3(+)CD8(+) T cells in the polyp and reduced nuclear accumulation of β-catenin in the epithelium of small intestinal polyps. Our results stress the important role that CysLTR1 plays in colorectal cancer and its potential as a therapeutic target in cancer therapy.
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| 3. |
- Linnskog, Rickard, et al.
(författare)
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Interleukin-6 drives melanoma cell motility through p38α-MAPK-dependent up-regulation of WNT5A expression.
- 2014
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 8:8, s. 1365-1378
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Tidskriftsartikel (refereegranskat)abstract
- Extensive research has demonstrated a tumor-promoting role of increased WNT5A expression in malignant melanoma. However, very little light has been shed upon how WNT5A expression is up-regulated in melanoma. A potential regulator of WNT5A expression is the pro-inflammatory cytokine Interleukin (IL)-6, which shares the ability of WNT5A to increase melanoma cell invasion. Here, we investigate whether IL-6 can promote melanoma cell motility through an increased expression of WNT5A. We clearly demonstrate that the WNT5A-antagonistic peptide Box5 could inhibit IL-6-induced melanoma cell migration and invasion. Furthermore, IL-6 stimulation of the human melanoma cell lines HTB63 and A375 increased the expression of WNT5A in a dose-dependent manner. To identify the signaling mechanism responsible for this up-regulation, we explored the involvement of the three main signals induced by IL-6; STAT3, Akt and ERK 1/2. Of these, only STAT3 was activated by IL-6 in the melanoma cell lines tested. However, the STAT3 inhibitor S3I-201 failed to inhibit IL-6-induced WNT5A up-regulation in HTB63 and A375 cells. Nor did STAT3 siRNA silencing affect the expression of WNT5A. In search of an alternative signaling mechanism, we detected IL-6-induced activation of p38-MAPK in HTB63 and A375 cells. The p38-MAPK inhibitor SB203580 abolished the IL-6-induced WNT5A up-regulation and blocked IL-6-induced melanoma cell invasion. The latter effect could be rescued by the addition of recombinant WNT5A. Notably, immunoprecipitation analysis revealed that only the p38α-MAPK isoform was activated by IL-6, and subsequent siRNA silencing of p38α-MAPK abolished the IL-6-induced up-regulation of WNT5A. Taken together, we demonstrate a novel link between the two melanoma pro-metastatic agents IL-6 and WNT5A explaining how IL-6 can increase melanoma cell invasion and thus promote the metastatic process. This finding provides a basis for future therapeutic intervention of melanoma progression.
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| 4. |
- Bengtsson, Astrid, et al.
(författare)
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The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-induced differentiation of colon cancer cells
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT(1)R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT(2)R) is lost. Further, our previous data indicate that patients with high CysLT(1)R and low CysLT(2)R expression have a poor prognosis. In this study, we examined whether the balance between CysLT(1)R and CysLT(2)R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA). Methods: To determine the effect of ATRA on CysLT(2)R promoter activation, mRNA level, and protein level, we performed luciferase gene reporter assays, real-time polymerase chain reactions, and Western blots in colon cancer cell lines under various conditions. Results: ATRA treatment induces CysLT(2)R mRNA and protein expression without affecting CysLT(1)R levels. Experiments using siRNA and mutant cell lines indicate that the up-regulation is retinoic acid receptor (RAR) dependent. Interestingly, ATRA also up-regulates mRNA expression of leukotriene C-4 synthase, the enzyme responsible for the production of the ligand for CysLT(2)R. Importantly, ATRA-induced differentiation of colorectal cancer cells as shown by increased expression of MUC-2 and production of alkaline phosphatase, both of which could be reduced by a CysLT(2)R-specific inhibitor. Conclusions: This study identifies a novel mechanism of action for ATRA in colorectal cancer cell differentiation and demonstrates that retinoids can have anti-tumorigenic effects through their action on the cysteinyl leukotriene pathway.
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| 5. |
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| 6. |
- Sandvik, Ann-Helen, et al.
(författare)
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Sjuksköterskestudenters erfarenheter av sin första kliniska utbildningsperiod : en nordisk kvantitativ studie
- 2012
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Ingår i: Vård i Norden. - 0107-4083 .- 1890-4238. ; 32:1, s. 20-25
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in quality of clinical education and support to students occur and there are demands for a unification of higher education in Europe.Aim: The aim of the study was to describe the nursing students’ experiences of their first clinical education period in relation to learning and professional development.Methods: The sample consisted of 139 nursing students from Finland and Sweden. The data was collected by questionnaire and analyzed statistically.Findings: Students’ experiences of clinical competence were examined from four perspectives: clinical preception, learning, learning objectives and reflection. Overall, students rated highly, however there were statistically significant differences among the students concerning nationality and length of clinical education. Students did not always get a clear picture of what was expected of them in clinical education and there were deficits in continuing feedback. Students’ clinical learning was associated with the length of clinical education.Conclusions: Clinical preceptoring as a catalyst in student's understanding and learning is central. Students rated learning of tasks and skills higher than abilities that require more reflection and consideration, which may indicate a more task-centered preception. A conscious didactic approach would help students to reflect and develop into professionals in nursing and caring science.
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| 7. |
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| 8. |
- Abukhader, Sajed, et al.
(författare)
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Getting supply chain strategies involved in “E-commerce & Environment” - a research potentioal for LCA case studies
- 2004
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Konferensbidrag (refereegranskat)abstract
- Based on a previous content analysis work, there is nowadays a need for assessing a list of strategies related to the management of supply chains and logistics discipline, such as postponement, customisation, centralisation/decentralisation, etc. The need for environmental assessment of these strategies stems from the challenging necessity for bridging two fields: logistics/supply chain management field, and the environmental field. Equally important, a cumulating experience from performing such assessments would hopefully enhance the ability of assessing complex issues such as E-commerce within a framework of a recent, novel model of assessment – ‘the horizontal assessment’. The ultimate purpose of this paper is to discuss the windows of opportunities of environmental assessment of these strategies. One idea is: to acquire the experience of LCA case studies and Energy analysis studies as an input for this model. Research methods of literature survey, case survey and concept development are conducted to discuss and model the aspects and elements of this idea.
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