| 1. |
- Andersson, Mattias K, 1979, et al.
(författare)
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Proliferation of Ewing sarcoma cell lines is suppressed by the receptor tyrosine kinase inhibitors gefitinib and vandetanib
- 2008
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Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Tyrosine kinase inhibitors (TKIs) have gained much attention in recent years as targeted agents for the treatment of a wide range of human cancers. We have investigated the effect of the TKIs gefitinib and vandetanib on tumor cell lines derived from Ewing sarcoma, a highly malignant tumor affecting bone and soft tissue in children and young adults. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR) and vandetanib selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2) with additional activity against VEGFR-3, EGFR and RET kinase receptors. RESULTS: Two Ewing sarcoma cell lines investigated showed high levels of nuclear EGFR expression as well as moderate expression in plasma membrane and cytoplasm. When treated with concentrations of 5 muM and more of either gefitinib or vandetanib, we observed a significant decrease in cell proliferation. However, there were no detectable changes in p44/42 MAPK and Akt-1 phosphorylation, or in the expression of cyclin D1 or c-Myc following gefitinib or vandetanib treatment. CONCLUSION: We conclude that Ewing sarcoma tumor cell proliferation is not highly sensitive to inhibition of EGFR signaling alone or the simultaneous inhibition of VEGFR receptors, EGFR and RET kinase. Decreased tumor cell proliferation could be achieved with gefitinib and vandetanib, but only at higher doses where non-specific effects of the compounds may be overriding. As Ewing tumor cells do not seem to depend on EGFR and VEGFR pathways for survival, other key factors in the cellular signaling of Ewing sarcoma should be targeted in order to obtain a potent therapeutic response.
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| 2. |
- Karlsson, Sandra, et al.
(författare)
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Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model
- 2009
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Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; 9, s. Article Number: 12-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women. Initial symptoms are often vague and may be confused with several other conditions or disorders. Thus, there is a need for an easy and reliable diagnostic tool. The objective of this work was to identify a gene expression signature specific for endometrial adenocarcinomas to be used for testing potential endometrial biomarkers.Results: Changes in expression between endometrial adenocarcinomas and non-/pre-malignant endometrium from the BDII EAC rat model were compared in cDNA microarray assays. By employing classification analysis (Weka) on the expression data from approximately 5600 cDNA clones and TDT analysis on genotype data, we identified a three-gene signature (Gpx3, Bgn and Tgfb3). An independent analysis of differential expression, revealed a total of 354 cDNA clones with significant changes in expression. Among the 10 best ranked clones, Gpx3, Bgn and Tgfb3 were found. Conclusion: Taken together, we present a unique data set of genes with different expression patterns between EACs and non-/pre-malignant endometrium, and specifically we found three genes that were confirmed in two independent analyses. These three genes are candidates for an EAC signature and further evaluations of their involvement in EAC tumorigenesis will be undertaken.
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| 3. |
- Monazzam, Azita, et al.
(författare)
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A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids
- 2005
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Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; :5, s. 32-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Considering the width and importance of using Multicellular Tumor Spheroids (MTS) in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further confirmation.RESULTS:SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining.CONCLUSION:The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments.
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| 4. |
- Monazzma, Azita, et al.
(författare)
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Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring
- 2006
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Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 6, s. 6-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn order to explore a pre-clinical method to evaluate if [18F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS) without and with treatment with five routinely used chemotherapy agents in breast cancer.MethodsThe response to each anticancer treatment was evaluated by measurement of the [18F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment.ResultsThe effect of Paclitaxel and Docetaxel on [18F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease) than in MCF-7 (up to 25% decrease).Doxorubicin reduced the [18F]FDG uptake per viable volume more noticeable in MCF-7 (25%) than in BT474 MTSs.Tamoxifen reduced the [18F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 μM.No effect of Imatinib was observed.ConclusionMTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur.The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response.In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs.
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| 5. |
- Lindmark, Ulrika, et al.
(författare)
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Food selection associated with sense of coherence in adults.
- 2005
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 28:4, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Favorable dietary habits promote health, whereas unfavorable habits link to various chronic diseases. An individual's "sense of coherence" (SOC) is reported to correlate with prevalence of some diseases to which dietary habits are linked. However, understanding what determines an individual's dietary preferences and how to change his/her behavior remains limited. The aim of the present study was to evaluate associations between dietary intake and SOC in adults. METHODS: Diet intake was recorded by an 84-item semi-quantitative food frequency questionnaire and SOC was measured by the 13-item Antonovsky questionnaire in 2,446 men and 2,545 women (25-74 years old) from the population based northern Sweden MONICA screening in 1999. RESULTS: Intakes of energy, total and saturated fat, ascorbic acid, sucrose, and servings of fruits, vegetables, cereals, and sweets correlated with SOC among women, whereas intakes of total and saturated fat, ascorbic acid, fiber, and alcohol, and servings of fruits, vegetables, bread, bread and cereals, fish, and potatoes correlated with SOC among men. With a few exceptions, intakes of these nutrients/foods were significantly explained by SOC quartile scores in linear GLM models. Both women and men classified into the highest SOC quartile had significantly higher age-BMI-education standardized mean intakes of vegetables than those in the lowest quartiles. Women in the highest SOC quartile also had higher intake of fruits but lower intakes of energy, total and saturated fat, sucrose, and sweets. Projection to latent structures (PLS) multivariate modeling of intakes of the 84 food items and food aggregates simultaneously on SOC scores supported low SOC to coincide with a presumably less health promoting dietary preference, e.g. intake of pizza, soft drinks, candies, sausages for main course, hamburgers, mashed potato, chips and other snacks, potato salad, French fries, whereas men and women with high SOC scores were characterized by e.g. high intake of rye crisp whole meal bread, boiled potato, vegetables, berries, and fruits. CONCLUSION: Both men and women in the highest, as compared with the lowest, SOC score quartile reported more "healthy" food choices. Dietary habits for individuals in the lowest SOC quartile therefore may render a higher risk for various endemic diseases.
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