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  • 1201.
    Ydreborg, Berit
    et al.
    Department of Community Medicine and Public Health, Örebro County Council, Örebro, Sweden / National Centre for Work and Rehabilitation, Department of Health and Society, Linköping University, Linköping, Sweden.
    Ekberg, Kerstin
    National Centre for Work and Rehabilitation, Department of Health and Society, Linköping University, Linköping, Sweden.
    Nilsson, Kerstin
    University of Skövde, School of Life Sciences.
    Swedish social insurance officers' experiences of difficulties in assessing applications for disability pensions: an interview study2007In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 7, p. 128-Article in journal (Refereed)
    Abstract [en]

    Background

    In this study the focus is on social insurance officers judging applications for disability pensions. The number of applications for disability pension increased during the late 1990s, which has resulted in an increasing number of disability pensions in Sweden. A more restrictive attitude towards the clients has however evolved, as societal costs have increased and governmental guidelines now focus on reducing costs. As a consequence, the quantitative and qualitative demands on social insurance officers when handling applications for disability pensions may have increased. The aim of this study was therefore to describe the social insurance officers' experiences of assessing applications for disability pensions after the government's introduction of stricter regulations.

    Methods

    Qualitative methodology was employed and a total of ten social insurance officers representing different experiences and ages were chosen. Open-ended interviews were performed with the ten social insurance officers. Data was analysed with inductive content analysis.

    Results

    Three themes could be identified as problematic in the social insurance officers' descriptions of dealing with the applications in order to reach a decision on whether the issue qualified applicants for a disability pension or not: 1. Clients are heterogeneous. 2. Ineffective and time consuming waiting for medical certificates impede the decision process. 3. Perspectives on the issue of work capacity differed among different stakeholders. The backgrounds of the clients differ considerably, leading to variation in the quality and content of applications. Social insurance officers had to make rapid decisions within a limited time frame, based on limited information, mainly on the basis of medical certificates that were often insufficient to judge work capacity. The role as coordinating actor with other stakeholders in the welfare system was perceived as frustrating, since different stakeholders have different goals and demands. The social insurance officers experience lack of control over the decision process, as regulations and other stakeholders restrict their work.

    Conclusion

    A picture emerges of difficulties due to disharmonized systems, stakeholder-bound goals causing some clients to fall between two stools, or leading to unnecessary waiting times, which may limit the clients' ability to take an active part in a constructive process. Increased communication with physicians about how to elaborate the medical certificates might improve the quality of certificates and thereby reduce the clients waiting time.

  • 1202.
    Yildirimman, Reha
    et al.
    Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany .
    Brolén, Gabriella
    Cellartis AB, SE-41346 Gothenburg, Sweden .
    Vilardell, Mireia
    Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany .
    Eriksson, Gustav
    Cellartis AB, SE-41346 Gothenburg, Sweden .
    Synnergren, Jane
    University of Skövde, School of Life Sciences.
    Gmuender, Hans
    Genedata AG, CH-4053 Basel, Switzerland .
    Kamburov, Atanas
    Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany .
    Ingelman-Sundberg, Magnus
    Karolinska Inst, Dept Physiol & Pharmacol, Pharmacogenet Sect, S-17177 Stockholm, Sweden .
    Castell, Jose
    Univ Valencia, Fac Med, Dept Biochem & Mol Biol, E-46009 Valencia, Spain / Univ Hosp La Fe Valencia, Unit Expt Hepatol, E-46009 Valencia, Spain .
    Lahoz, Agustin
    Univ Hosp La Fe Valencia, Unit Expt Hepatol, E-46009 Valencia, Spain .
    Kleinjans, Jos
    Maastricht Univ, Dept Toxicogen, NL-6229 ER Maastricht, Netherlands.
    van Delft, Joost
    Maastricht Univ, Dept Toxicogen, NL-6229 ER Maastricht, Netherlands.
    Bjorquist, Petter
    Cellartis AB, SE-41346 Gothenburg, Sweden .
    Herwig, Ralf
    Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany .
    Human Embryonic Stem Cell Derived Hepatocyte-Like Cells as a Tool for In Vitro Hazard Assessment of Chemical Carcinogenicity2011In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 124, no 2, p. 278-290Article in journal (Refereed)
    Abstract [en]

    Hepatocyte-like cells derived from the differentiation of human embryonic stem cells (hES-Hep) have potential to provide a human relevant in vitro test system in which to evaluate the carcinogenic hazard of chemicals. In this study, we have investigated this potential using a panel of 15 chemicals classified as noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured whole-genome transcriptome responses with gene expression microarrays. We applied an ANOVA model that identified 592 genes highly discriminative for the panel of chemicals. Supervised classification with these genes achieved a cross-validation accuracy of > 95%. Moreover, the expression of the response genes in hES-Hep was strongly correlated with that in human primary hepatocytes cultured in vitro. In order to infer mechanistic information on the consequences of chemical exposure in hES-Hep, we developed a computational method that measures the responses of biochemical pathways to the panel of treatments and showed that these responses were discriminative for the three toxicity classes and linked to carcinogenesis through p53, mitogen-activated protein kinases, and apoptosis pathway modules. It could further be shown that the discrimination of toxicity classes was improved when analyzing the microarray data at the pathway level. In summary, our results demonstrate, for the first time, the potential of human embryonic stem cell--derived hepatic cells as an in vitro model for hazard assessment of chemical carcinogenesis, although it should be noted that more compounds are needed to test the robustness of the assay.

  • 1203.
    Zeijlon, Jessika
    et al.
    University of Skövde, School of Life Sciences.
    Lidestam, Magdalena
    University of Skövde, School of Life Sciences.
    Vad förebygger depression bland äldre: en litteraturstudie2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Late-life depression is a major public health problem which causes emotional suffering among individuals and their relatives, and also leads to increased health care costs. In Sweden the prevalence of late-life depression is approximately 12-15 % among those aged 65 and older. The aim of this literature review was to compile and examine previous research considering late-life depression-preventive factors. Literature searches were made in the databases LibHub, PubMed and Cinahl using the keywords: prevention, depression, depressive symptoms, elderly, old and old people. Twelve scientific articles were selected and analyzed. Five main themes were identified. Theme activity showed conflicting results, dietary supplements were effective in one of two studies and social support was an important factor in preventing depression and counteracts the negative effects of stressful life events and economic stress. Cognitive strategies such as “positive restructuring” and CBT treatment were found to have an effect on depression symptoms. An intervention program including training of nursery care staff had significant effect, especially in nursing homes with a high prevalence of depression. Conclusion: Further literature studies and further deepening of the different themes are needed to draw accurate conclusions. There is a need for more research in this area, larger studies and longer follow-up is needed.

  • 1204.
    Zhang, Hong
    et al.
    University of Skövde, School of Life Sciences.
    Sun, Xiao-Feng
    Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Synnerstad, Ingrid
    Division of Dermatology, Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Rosdahl, Inger
    Division of Dermatology, Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Importance of FAS-1377, FAS-670 and FASL-844 Polymorphisms in Tumor Onset, Progression and Pigment Phenotypes of Swedish Patients With Melanoma: A Case-Control Analysis2007In: The Cancer Journal, ISSN 1528-9117, E-ISSN 1540-336X, Vol. 13, no 4, p. 233-237Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Human skin melanoma at later stages usually has an extremely poor prognosis. It is of importance to search for biologic markers to identify and monitor individuals at risk for melanoma for early diagnosis and to avoid tumor progression. The FAS gene and its natural ligand (FASL) gene initiate the death signal cascade, playing a central role in the apoptotic signaling pathway and tumor growth and metastasis. PATIENTS AND METHODS: In this study, we analyzed polymorphisms in 229 patients with melanoma and 351 age- and gender-matched tumor-free individuals. Genomic DNAs were isolated from mononuclear cells in peripheral vein blood, and the polymorphisms were examined with polymerase chain reaction-restriction fragment length polymorphism techniques. Frequency in distribution of the polymorphisms was compared between the patients with melanoma and the healthy control subjects, and associations with patients' pigment phenotypes, age at diagnosis, and melanoma characteristics were analyzed. RESULTS AND CONCLUSIONS: The FAS-1377, FAS-670, and FASL-844 polymorphisms were not found to be markers of melanoma risk (P > 0.05). In patients with melanoma, frequencies of the FAS-1377, FAS-670, and FASL-844 polymorphisms were different between the patients aged <50 and > or =50 years (P < or = 0.025, P < or = 0.025, and P < or = 0.01). Moreover, the FAS-670 polymorphism correlated with tumor Breslow thickness (P < or = 0.01) and Clark level (P < or = 0.001) and was associated with tumors developing in sun-exposed locations (P < or = 0.001). FAS and FASL were not markers for melanoma risk but might be important in the development and progression of sun-induced melanoma independently of skin type.

  • 1205.
    Zhang, Hong
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Wang, Da-Wei
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Department of Stomatology, The Third Hospital of Hebei Medical University, Hebei, China.
    Adell, Gunnar
    Department of Oncology, Karolinska University Hospital, Karolinska, Sweden.
    Sun, Xiao-Feng
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Heath Science, Linköping University, Sweden .
    WRAP53 is an independent prognostic factor in rectal cancer- a study of Swedish clinical trial of preoperative radiotherapy in rectal cancer patients2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. 294-Article in journal (Refereed)
    Abstract [en]

    Background: Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors. Methods: We examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival. The WRAP53 protein was examined by immunohistochemistry in normal mucosa, primary tumors and lymph node metastases from 143 rectal cancer patients participated in a Swedish clinical trial of preoperative radiotherapy. Results: Frequency of WRAP53 protein expression was increased in primary rectal cancer compared to the normal mucosa (p < 0.05). In non-radiotherapy group positive WRAP53 in primary tumors (p = 0.03, RR, 3.73, 95% CI, 1.13-11.89) or metastases (p = 0.01, RR, 4.11, 95% CI, 1.25-13.14), was associated with poor prognosis independently of stages and differentiations. In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival (p = 0.04). An interaction analysis showed that the correlations of WRAP53 with the prognostic significance with and without radiotherapy in the metastasis differed (p = 0.01). In the radiotherapy group, expression of WRAP53 in metastases gave a better outcome (p = 0.02, RR, 0.32, 95% CI, 0.13-0.84), and an interaction analysis showed significance between the two groups (p = 0.01). Conclusion: WRAP53 may be a new biomarker used to predict prognosis and to select suitable patients for preoperative radiotherapy.

  • 1206.
    Zhang, Hong
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Widegren, Emma
    Linkoping Univ, Dept Oncol, Inst Clin & Expt Med, Linkoping, Sweden .
    Wang, Da-Wei
    Hebei Med Univ, Hosp 3, Dept Stomatol, Shijiazhuang, Peoples R China.
    Sun, Xiao-Feng
    Linkoping Univ, Dept Oncol, Inst Clin & Expt Med, Linkoping, Sweden .
    SPARCL1: a potential molecule associated with tumor diagnosis, progression and prognosis of colorectal cancer2011In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 32, no 6, p. 1225-1231Article in journal (Refereed)
    Abstract [en]

    We investigated whether SPARCL1 played an essential role in tumor initiation, formation and progression of colorectal carcinomas. In this study, we examined expression of SPARCL1 protein in the normal colorectal mucosa, adjacent normal mucosa and primary and lymph node metastases from colorectal cancer patients. In matched patients, we found that SPARCL1 was negative in the distant normal colorectal mucosa, weakly expressed in the adjacent normal mucosa, strongly expressed in primary colorectal adenocarcinomas and slightly expressed in their lymph node metastases. A similar pattern was observed in the SPARCL1 expression from our series of non-matched colorectal cancer patients. The strongest expression and highest frequency of the SPARCL1 protein were found in the primary cancers. Interestingly, in the primary tumors, the frequency of SPARCL1 expression was significantly increased from the Dukes' A to Dukes' B tumors and then decreased gradually from the Dukes' B to C and D tumors. There was no difference in the intensity of SPARCL1 expression between the central areas and invasion margins of the primary tumors. Moreover, the SPARCL1 protein was more strongly expressed in the highly differentiated tumors than the lower differentiated ones. The patients with positive expression of SPARCL1 in their tumors had worse prognosis than the patients with SPARCL1-negative ones, even after the analyses by Multivariate and Interaction method. Expression of SPARCL1 protein might be a valuable biomarker for early diagnosis in colorectal cancers and further predicting patients' prognosis.

  • 1207.
    Zhang, Zhi-Yong
    et al.
    Linkoping Univ, Inst Clin & Expt Med, Dept Oncol, S-58185 Linkoping, Sweden / Tangshan Gongren Hosp, Dept Pathol, Tangshan, Peoples R China / Hebei Med Univ, Hosp 1, Lab Ctr, Shijiazhuang, Peoples R China.
    Zhang, Hong
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Adell, Gunnar
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
    Sun, Xiao-Feng
    Linkoping Univ, Inst Clin & Expt Med, Dept Oncol, S-58185 Linkoping, Sweden.
    Endosialin expression in relation to clinicopathological and biological variables in rectal cancers with a Swedish clinical trial of preoperative radiotherapy2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. Artikelnr 89-Article in journal (Refereed)
    Abstract [en]

    Background: The importance of changes in tumour-associated stroma for tumour initiation and progression has been established. Endosialin is expressed in fibroblasts and pericytes of blood vessels in several types of tumours, and is involved in the progression of colorectal cancer. In order to see whether endosialin was related to radiotherapy (RT) response, and clinicopathological and biological variables, we investigated endosialin expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative RT. Methods: Endosialin was immunohistochemically examined in normal mucosa, including distant (n = 72) and adjacent (n = 112) normal mucosa, and primary tumours (n = 135). Seventy-three of 135 patients received surgery alone and 62 received additional preoperative RT. Results: Endosialin expression in the stroma increased from normal mucosa to tumour (p < 0.0001) both in RT and non-RT group. In the RT group, endosialin expression in the stroma was positively associated with expression of cyclooxygenase-2 (Cox-2) (p = 0.03), p73 (p = 0.01) and phosphates of regenerating liver (PRL) (p = 0.002). Endosialin expression in the tumour cells of both in the RT group (p = 0.01) and the non-RT group (p = 0.06) was observed more often in tumours with an infiltrative growth pattern than in tumours with an expansive growth pattern. In the RT group, endosialin expression in tumour cells was positively related to PRL expression (p = 0.02), whereas in the non-RT group, endosialin expression in tumour cells was positively related to p73 expression (p = 0.01). Conclusions: Endosialin expression may be involved in the progression of rectal cancers, and was related to Cox-2, p73 and PRL expression. However, a direct relationship between endosialin expression and RT responses in patients was not found.

  • 1208.
    Zichner, Thomas
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Lubovac, Zelmina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Temporal analysis of oncogenesis using microRNA expression data2008In: Proc. Ger. Conf. Bioinformatics, GCB, Bonn: Gesellschaft für Informatik , 2008, p. 128-137Conference paper (Refereed)
    Abstract [en]

    MicroRNAs (miRNAs) have rapidly become the focus of many cancer research studies. These small non-coding RNAs have been shown to play important roles in the regulation of oncogenes and tumor suppressors. It has also been demonstrated that miRNA expression profiles differ significantly between normal and cancerous cells, which indicates the possibility of using miRNAs as markers for cancer diagnosis and prognosis. However, not much is known about the regulation of miRNA expression. One of the issues worth investigating is whether deregulations of miRNA expression in cancer cells occur according to some pattern or in a random order. We therefore selected two approaches, previously used to derive graph models of oncogenesis using chromosomal imbalance data, and adapted them to miRNA expression data. Applying the adapted algorithms to a breast cancer data set, we obtained results indicating the temporal order of miRNA deregulations during tumor development. When analyzing the specific deregulations appearing at different time points in the derived model, we found that several of the deregulations identified as early events could be supported through literature studies.

  • 1209.
    Åberg, Cecilia
    University of Skövde, School of Life Sciences.
    Att stödja föräldrar på Barnavårdscentralen (BVC): En kvalitativ intervjustudie om BVC-sjuksköterskors erfarenheter2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Becoming a parent is an overwhelming experience. It is important to have support available for those who need it in order for parents to safely meet the needs of their child, and to strengthen the development of their child. The Child Health Nurse has a central role in supporting parents with childen aged 0-6 years. The aim of this study was to describe Child Health Nurses experiences of supporting parents. The method being used was a qualitative content analysis with an inductive approach described by Lundman and Hällgren Graneheim. The data was collected through interviews with four Child Health Nurses. The result shows that the Child Health Nurses experienced that parenting support was something which took place each time they met with the parents. By being there for the family and by strengthening the own resources of the parents, she could support their parenting. A changed society demanded a change in child health care and the conditions given influenced the support available for parents.

  • 1210. Ådin, Hanna
    et al.
    Ekstrand, Maria
    Hammarlund, Kina
    University of Skövde, School of Life Sciences.
    Oskönt, krångligt, plastigt2009In: Insikt, ISSN 1104-0912, no 4, p. 8-9Article in journal (Other (popular science, discussion, etc.))
  • 1211.
    Åström, Stina
    University of Skövde, School of Life Sciences.
    Bränning som alternativ skötselmetodi gräsmarker2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    When the large-scale and nitrogen-intensive agriculture gained land many naturalpastures and meadows started to overgrow. This led to that many species dependent onopen land decreased or totally disappeared. To grow or re-colonize land many speciesneed some form of disturbance. Burning can be one of such disturbances. Burningincrease the light inlet and decrease the amount of nitrogen in the soil. Both of thesechanges will favor the open-land species.The aim of this study was to explore if burning could be a complement or alternative tograzing and mowing for preserving the biological diversity among plants in grasslands.The different kinds of grasslands that were inventoried include hard shoulders, meadows,field slopes and natural pastures. Both burned and control areas were inventoried at 11places. All of them were located in different habitats in Östergötland, Sweden.Three different diversity-indexes have been used to answer the question if diversity washigher on the burned areas than on the control surface. The result showed that both thediversity was higher and the distribution in species spread more evenly on the burnedareas. Species dependent on open land had a notably larger spreading on the burned areasthan on the control areas. This confirms the hypothesis that burning has a positive effecton open-land species and can be a complement or replacement for grazing or mowing inpreserving the biological diversity of plants in grasslands. The future care could bedifferent combinations of burning, grazing and mowing.To the conservation, this knowledge can have a great impact for both state and privatelandowners. Knowing that this method will favor the open-land species, more areas canbe burned. To burn, instead of mowing or grazing, can lead to that larger areas can havethe proper maintenance it requires, without changes in the financial budget of thelandowner.

  • 1212.
    Öhlén, Joakim
    et al.
    Institute of Health Care Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Furåker, Carina
    Institute of Health Care Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Jakobsson, Eva
    Institute of Health Care Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Bergh, Ingrid
    University of Skövde, School of Life Sciences.
    Hermansson, Evelyn
    Institute of Health Care Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Impact of the Bologna process in Bachelor nursing programmes: The Swedish case2011In: Nurse Education Today, ISSN 0260-6917, E-ISSN 1532-2793, Vol. 31, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    The higher education reform in Europe known as the “Bologna Process” implies further harmonisation and integration of nursing programmes into the higher education system. This study explores this process in Sweden, where the development of nursing education into an undergraduate programme started in 1977. The aim of this study was to analyse characteristics of the major subject and its relationship to other subject areas, such as medical sciences and social sciences, in Bachelor level nursing programmes in Sweden following initial implementation of the Bologna process. A constructivist approach and descriptive content analysis were employed to analyse the 2008 nursing curricula and syllabi of 27 undergraduate programmes at 26 Swedish universities and university colleges. The results revealed variation in terms and concepts used for the major subject as well as its scientific foundation, demarcation between the major subject and other subjects included in the study programmes and its relationship to the profession. These variations are linked to the variety of research orientations under debate in the Scandinavian countries: Nursing Science and Caring Science; representing different knowledge domains, focus, challenges and visions for the discipline. Potential implications of basing curricula on a major subject other than Nursing Science in a Bachelor level nursing programme are highlighted.

  • 1213.
    Östensson, Malin
    et al.
    Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Montén, Caroline
    Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Bacelis, Jonas
    Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Gudjonsdottir, Audur H.
    Queen Silvia Children’s Hospital, Sahlgrenska Academy at the University of Gothenburg, Department of Pediatrics, Gothenburg, Sweden.
    Adamovic, Svetlana
    Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Ek, Johan
    Buskerud Central Hospital, Department of Pediatrics, Drammen, Norway.
    Ascher, Henry
    Sahlgrenska Academy at the University of Gothenburg, Department of Public Health and Community Medicine, Unit of Social Medicine, Gothenburg, Sweden.
    Pollak, Elisabet
    Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Arnell, Henrik
    Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital and Division of Pediatrics, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
    Browaldh, Lars
    Department of Clinical Science and Education, Karolinska Institutet Södersjukhuset, Stockholm, Sweden.
    Agardh, Daniel
    Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Wahlström, Jan
    Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Staffan
    Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Torinsson-Naluai, Åsa
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, article id e70174Article in journal (Refereed)
    Abstract [en]

    Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component.

  • 1214.
    Österberg, Lovisa
    et al.
    University of Gothenburg.
    Levan, Kristina
    University of Gothenburg.
    Partheen, Karolina
    University of Gothenburg.
    Dalle, Ulla
    University of Gothenburg.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Sundfeldt, Karin
    University of Gothenburg.
    Horvath, György
    University of Gothenburg.
    Specific Copy Number Alterations Associated with Docetaxel/Carboplatin Response in Ovarian Carcinomas2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 11, p. 4451-4458Article in journal (Refereed)
    Abstract [en]

    Background: The continued high recurrence and mortality rate in ovarian cancer is a significant problem and the major obstacle in the treatment of ovarian cancer patients is chemotherapy resistance. Thus, finding predictive markers of chemoresistance and elucidating resistance mechanisms is crucial for individualising treatment and improving survival of ovarian cancer patients. Materials and Methods: Using array comparative genomic hybridisation (CGH), this pilot study analysed the tumour genomes of patients treated with docetaxel/carboplatin as first-line chemotherapy (6 resistant versus 24 sensitive cases). This is the first array CGH study of  such  material.  Results:  The  study  identified  genetic alterations specific to chemoresistant (gains in 9p13.2-13.1, 9q21.2-21.32,  9q21.33,  9q22.2-22.31,  9q22.32-22.33  and 9q33.1-34.11) and chemosensitive (losses in 8p23.3-23.1 and 8p22) disease. Additionally, when comparing the results to previously analysed tumour material from patients treated with paclitaxel/carboplatin, the two datasets identified different genetic  alteration  profiles.  Conclusion:  Specific  genetic alterations were identified and associated with chemotherapy response in ovarian cancer. It will be interesting to investigate these exciting data further in larger independent series of ovarian   tumours,   and   hopefully   will   contribute   to   the establishment of predictive markers.

  • 1215.
    Österberg, Lovisa
    et al.
    University of Gothenburg.
    Levan, Kristina
    University of Gothenburg.
    Partheen, Karolina
    University of Gothenburg.
    Delle, Ulla
    University of Gothenburg.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Horvath, Karin
    University of Gothenburg.
    Potential predictive markers of chemotherapy resistance ovarian serous carcinomas2009In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 9, p. 368-Article in journal (Refereed)
    Abstract [en]

    Background Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers.

    Methods To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level.

    Results We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group.

    Conclusion In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series.

  • 1216.
    Özdogan, Alper
    University of Skövde, School of Life Sciences.
    Clustering Genes by Using Different Types of Genomic Data and Self-Organizing Maps2008Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of the project was to identify biologically relevant novel gene clusters by using combined genomic data instead of using only gene expression data in isolation. The clustering algorithm based on self-organizing maps (Kasturi et al., 2005) was extended and implemented in order to use gene location data together with the gene expression and the motif occurrence data for gene clustering. A distance function was defined to be used with gene location data. The algorithm was also extended in order to use vector angle distance for gene expression data. Arabidopsis thaliana is chosen as a data source to evaluate the developed algorithm. A test data set was created by using 100 Arabidopsis genes that have gene expression data with seven different time points during cold stress condition, motif occurrence data which indicates the occurrence frequency of 614 different motifs and the chromosomal location data of each gene. Gene Ontology (http://www.geneontology.org) and TAIR (http://arabidopsis.org) databases were used to find the molecular function and biological process information of each gene in order to examine the biological accuracy of newly discovered clusters after using combined genomic data. The biological evaluation of the results showed that using combined genomic data to cluster genes resulted in new biologically relevant clusters.

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