| 1. |
- Gustafsson Asting, Annika, et al.
(författare)
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EP1-4 subtype, COX and PPAR gamma receptor expression in colorectal cancer in prediction of disease-specific mortality
- 2007
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Ingår i: International journal of cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:2, s. 232-40
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Tidskriftsartikel (refereegranskat)abstract
- The importance of prostaglandins in tumor growth and progression is well recognized, including antineoplastic activities by cyclooxygenase (COX) inhibitors. Variation in treatment response to COX inhibition has questioned differences in expression of cell surface and nuclear membrane receptors among tumors with different disease progression. The purpose of this study was to evaluate whether EP(1-4) subtype, PPAR gamma receptor and COX-1/COX-2 expression in colorectal cancer are related to tumor-specific mortality. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to demonstrate expression and protein appearance in tumor tissue compared with normal colon tissue. EP(1) and EP(2) subtype receptor protein was highly present in tumor cells, EP(3) occurred occasionally and EP(4) was not visible. PPAR gamma, EP(2) and EP(4) mRNA were significantly higher in normal colon tissue compared with tumor tissue, without any distinct relationship to Dukes A-D tumor stage. Multivariate analyses indicated that increased tumor tissue EP(2) and COX-2 expression predicted poor survival (p<0.001). COX-1 expression was significantly higher than COX-2 expression in normal colon tissue. Average COX-2 mRNA was not increased in tumor tissue compared with normal colon. However, most tumor cells stained positive for COX-2 protein, which was low or undetectable in normal mucosa cells. COX-1 protein was preferentially visible in stroma. EP(1-4) subtype receptor mRNAs were generally positively correlated to both COX-1 and COX-2 in tumor tissue, but not in normal colon. Our results imply that both prostaglandin production (COX-2) and signaling via EP(1-4) subtype receptors, particularly EP(2), predict disease-specific mortality in colorectal cancer.
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| 2. |
- Gustafsson Asting, Annika, et al.
(författare)
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Prostanoid receptor expression in colorectal cancer related to tumor stage, differentiation and progression.
- 2007
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:8, s. 1107-12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Alterations in eicosanoid metabolism is well established in a variety of malignant tumors, particularly colorectal carcinoma. Recent studies in our laboratory have emphasized a role for EP subtype receptors in progression of colorectal cancer and disease specific mortality. Therefore, the aim of the present study was to extend our knowledge to include additional receptor expression (DP1, DP2, FP, IP, TP) for prostanoids (PGD2, TXA2, PGF2alpha, PGI2) in relationship to tumor stage, differentiation and progression of colorectal cancer. MATERIAL AND METHODS: Total RNA from 62 tumors and adjacent normal colon tissue (n = 48) was extracted. Quantification of receptor expression was performed by realtime PCR and related to the expression of an appropriate housekeeping gene (GAPDH). Tumors were assessed according to Dukes A-D (stage I-IV). RESULTS: DP1, DP2, FP and IP receptor subtypes displayed significantly reduced overall expression in tumor tissue compared to normal colon tissue, while the TP receptor subtype showed significantly higher expression in tumor tissue. Overall expression of the prostanoid receptors in tumor tissue was not related to clinical indexes as tumor stage and tumor cell differentiation evaluated by multivariate analyses. Cultured colorectal cancer cell lines with low (HT-29) and high (HCA-7) intrinsic PGE2 production at confluent state did not express DP1 and IP receptor subtypes, but displayed low expression of DP2, FP and TP receptor subtypes. CONCLUSION: The results in the present study indicate imbalanced expression of prostanoid receptors in colorectal cancer compared to normal colon tissue without clear cut relationship to disease progression. Therefore, future studies should be performed on defined cells within the tumor tissue compartment determining whether any prostanoid receptor(s) is useful as a molecular target in treatment or prevention of colorectal cancer.
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| 3. |
- Gustafsson Asting, Annika, et al.
(författare)
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Receptor and enzyme expression for prostanoid metabolism in colorectal cancer related to tumor tissue PGE2.
- 2010
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Ingår i: International journal of oncology. - 1791-2423. ; 36:2, s. 469-478
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Tidskriftsartikel (refereegranskat)abstract
- Prostaglandins support progression of colorectal cancer by several mechanisms. This conclusion is based on epidemiological and drug intervention long-term studies or retrieved from animal and cell culture experiments. The aim of the present study was to map receptor and enzyme expression for prostanoid metabolism in the presence of high or low PGE2 content within colon cancer tissue at primary tumor operation and after short-term preoperative provision of non-steroidal anti-inflammatory drug (NSAID). Twenty-three unselected patients with colon cancer were randomly selected to receive indomethacin (NSAID) or sham treatment for 3 days before surgery. Normal colon and tumor tissue were collected at operation for RNA extraction. Tissue PGE2 levels were measured by radioimmunoassay. Gene expression was quantified by microarray and real-time PCR. COX-1 expression increased proportionally to COX-2 expression in colon cancer tissue from untreated patients. Indomethacin reduced PGE2 content in normal and tumor tissue with subsequently decreased IP, HPGD and PPARgamma receptor expression in both tumor and normal colon tissue, while subtype EP1-4 receptors were not significantly influenced by indomethacin treatment. MPGES-1 expression was not related to overall PGE2 content in tumor and colon tissue, but decreased significantly in normal tissue during indomethacin exposure. Reduction of tumor tissue PGE2 was related to significant alteration in expression of several hundred genes indicating decreased cell cycling and increased apoptosis during indomethacin treatment, probably related to upregulation of acute phase reactants in tumor tissue. Increased prostanoid activity in colon cancer tissue is related to cross-talk between tumor and stroma cells.
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| 4. |
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| 5. |
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| 6. |
- Kodeda, Karl, et al.
(författare)
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Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure.
- 2012
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Ingår i: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 41:4, s. 1397-1404
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Tidskriftsartikel (refereegranskat)abstract
- Several factors determine overall outcome and possible local recurrence after curative surgery for rectal carcinoma. Surgical performance is usually believed to be the most pertinent factor, followed by adjuvant oncological treatment and tumor histopathology. However, chromosomal instability is common in colorectal cancer and tumor clones are assumed to differ in aggressiveness and potential of causing local recurrence. The aim of this study was, therefore, to evaluate if genetic alterations in primary rectal carcinoma are predictive of local recurrences. A large clinical database with linked bio-bank allowed for careful matching of two patient groups (R0) resected for rectal carcinoma. One group had developed early, isolated local recurrences and the other group seemed cured after 93months follow-up. DNA from the primary tumors was analysed with array-CGH (comparative genomic hybridization) including 55,000 genomic probes. DNA from all primary tumors in both groups displayed previously reported and well-recognised DNA aberrations in colorectal carcinoma. Significant copy number gains were confirmed in the 4q31.1-31.22 region in DNA from tumors with subsequent local recurrence. Twenty-two affected genes in this region code for products with high relevance in tumor biology (p53 regulation, cell cycle activity, transcription). DNA from rectal carcinoma displayed well-known aberrations as described for colon carcinoma with no obvious prediction of local rectal recurrence. Gains in the 4q31.1-31.22 DNA region are highly potential for local recurrence despite R0 resection to be confirmed in larger patient materials.
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| 7. |
- Lagerstedt, Kristina, 1976, et al.
(författare)
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Genes with relevance for early to late progression of colon carcinoma based on combined genomic and transcriptomic information from the same patients.
- 2010
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Ingår i: Cancer informatics. - 1176-9351. ; 9, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. METHODS: Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. RESULTS: Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A-D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. CONCLUSIONS: Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes.
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| 8. |
- Lönnroth, Christina, 1946, et al.
(författare)
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Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer.
- 2014
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Ingår i: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 45:6, s. 2208-2220
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical data, and an increasing list of clinical investigations, show anti‑inflammatory agents to favourably influence the biology of colorectal tumor. We have earlier reported on re‑expression of activated immune cells after three days preoperative treatment of patients with colorectal carcinoma, randomized to receive oral NSAID(indomethacin or celebrex). Antisecretory prophylaxis(esomeprasol) was provided to all patients and served as sham treatment. Concomittant to MHC locus activation, Prominin1/CD133, a marker associated with stemness and poor prognosis in several solid tumors, was downregulated. The aim of the present study was to evaluate expression of additional regulators belonging to the stem cell niche, OCT4, SOX2 and BMP7, aswellas some microRNAs, reported to act as tumor suppressors or oncomiRs. Peroperative tumor biopsies were analyzed by microarrays, quantitative real‑time PCR and immunohistochemistry(IHC). The stem cell master regulator SOX2 was increased by NSAIDs(p<0.01), aswellas the tumor suppressor miR‑630(p<0.01), while BMP7, a marker for poor prognosis in CRC, was downregulated by NSAID(indomethacin, p<0.02). The upregulation of SOX2, but not of its heterodimer binding partner OCT4, could imply a negative feed‑back loop, with a switch‑off for stemness preservation of tumor cells. This is supported by the overall evaluation of gene expression profiles with subsequent events, indicating less aggressive tumors following NSAID treatment.
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| 9. |
- Fransson, Göran, 1968-, et al.
(författare)
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Becoming a teacher – an introduction to the book.
- 2008
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Ingår i: Newly Qualified Teachers in Northern Europe. - Gävle : Gävle University Press. - 9789197489331 ; , s. 11-26
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Fransson, Göran, et al.
(författare)
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Summary, conclusions and future perspective
- 2008
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Ingår i: Newly Qualified Teachers in Northern Europe. - Gävle : Gävle University Press. - 9789197489331 ; , s. 167-192
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Gustafsson Asting, Annika, et al.
(författare)
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COX-2 Gene Expression in Colon Cancer Tissue related to Regulating Factors and Promoter Methylation Status
- 2011
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.
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| 12. |
- Gustafsson Asting, Annika, et al.
(författare)
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Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer.
- 2014
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Ingår i: Journal of Cancer Therapy. - : Scientific Research Publishing, Inc.. - 2151-1934 .- 2151-1942. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer; these DNA alterations may have been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.
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| 13. |
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| 14. |
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| 15. |
- Gustafsson, Christina, 1945-
(författare)
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Degree project in higher education.
- 2008
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Ingår i: Examining Praxis. - Rotterdam : Sense Publishers. - 9789087906047 - 9789087906054 ; , s. 17-34
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 16. |
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| 18. |
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| 19. |
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| 20. |
- Gustafsson, Christina, 1945-
(författare)
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Introduktion till boken och dess teman
- 2012
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Ingår i: Kvalificerad som lärare?. - Gävle : Gävle University Press. - 9789197489348 ; , s. 7-20
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 21. |
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| 22. |
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| 23. |
- Gustafsson, Christina, 1945-
(författare)
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Maria Montessori
- 2020
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Ingår i: The SAGE Encyclopedia of Children and Childhood Studies. - Thousand Oaks : Sage Publications. - 9781473942929
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Bokkapitel (refereegranskat)
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| 24. |
- Gustafsson, Christina, 1945-
(författare)
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Montessori Education
- 2018. - 1
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Ingår i: International Handbook of Early Childhood Education. - Dordrecht : Springer. - 9789402409277 - 9789402409253 ; , s. 1439-1456
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Bokkapitel (refereegranskat)abstract
- This chapter is a compressed presentation of Maria Montessori’s life, about her pedagogy and its theoretical basis, and how the Montessori Method developed and gained geographic spread over more than 100 years. One aim has been to put in Montessori and her activities in a context in order to understand how her thinking evolved. Another aim has been to lay a theoretical perspective on the issues primarily associated with the Montessori Method – the prepared environment and the didactic material. These two key aspects are related to the role of the Montessori teacher and Montessori’s idea of the conditions for children’s learning and development. A third aim has been to discuss, with a critical but respectful approach, what parts of the Montessori Method has survived and what ought to survive in the twenty-first century in a society where we talk about gender/equality, multiculturalism and sustainable development. In short, it was an intention to raise the question how it is possible, in the light of the history to utilize basic ideas in the spirit of Montessori’s pedagogy and at the same time develop teaching and learning to suit the child and society a number of decades to come.
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| 25. |
- Gustafsson, Christina, 1945-
(författare)
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Montessori Schools
- 2020
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Ingår i: The SAGE Encyclopedia of Children and Childhood Studies. - Thousand Oaks : Sage Publications. - 9781473942929
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Bokkapitel (refereegranskat)
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| 26. |
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| 33. |
- Hofsten, Anna, et al.
(författare)
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Case seminars open doors to deeper understanding : Nursing students’ experiences of learning
- 2010
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Ingår i: Nurse Education Today. - : Elsevier BV. - 0260-6917 .- 1532-2793. ; 30:6, s. 533-538
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The Case Method is a teaching method in which cases from real life inspire students to actively seek knowledge that they discuss in structured seminars. Case seminars in health education have been evaluated, compared and discussed, but descriptions that can help us understand how students learn in the seminars have not previously been published. In a Swedish nursing programme, where case seminars have been used for several years, students were asked to write about their experiences of learning in the seminars. The aim of the present study was to describe this learning process from the students' point of view.METHOD:Written data were analysed using content analysis.FINDINGS:A theme concerning how the Case Method opens doors to deeper understanding was identified as a thread running through different codes and categories. Students described the importance of new perspectives and their wish to participate in discussions with other students. The students indicated that the structure, which involved pre-prepared cases and writing on the white board, positioned their own knowledge in a wider context and that the learning atmosphere enabled everyone to participate.CONCLUSIONS:The Case Method seems to involve students in a way that deepens their understanding and critical thinking.
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| 34. |
- Löfmark, Anna, et al.
(författare)
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Student nurses' ability to perform pain assessment.
- 2003
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Ingår i: Nurse Education in Practice. - 1471-5953 .- 1873-5223. ; 3:3, s. 133-43
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate student nurses' ability to handle a pain assessment situation. A systematic way of working based on knowledge within the area is emphasised in nursing education today. The performance of 32 student nurses at a university college in Sweden took place in an arranged assessment situation that closely simulated clinical practice. The conversation between the student and the patient (a voluntary patient) was videotaped and analysed with content analysis according to predetermined components of pain assessment. The results showed that one-third of the students had performed adequately based on the requirements for pain assessment in the curriculum for nursing education. Two-thirds of the group did not handle the situation systematically and also showed a lack of knowledge of pain assessment, and among these was a group of students whose performance was inadequate. The results indicate that during their education it is very important for student nurses to obtain experience and guidance in how to work systematically and to have their knowledge and skills in pain assessment evaluated.
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