| 1. |
- Barman, Linda, 1972-, et al.
(författare)
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Interactions in online discussion forums - an underutilized resource for learning?
- 2019
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Ingår i: 2019 IEEE Frontiers in Education Conference (FIE). - Covington, KY, USA : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 1-5
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Konferensbidrag (refereegranskat)abstract
- This work-in progress research paper addresses how the discussion forums in online courses are made useful to promote students' learning. This qualitative study investigates the interactions between learners, as well as between learners and teachers in MOOCs. Community of Inquiry was used as an analytical framework to unveil how the discussions made in the online environment may connect to the course participants' learning processes. Preliminary findings indicate that the interactions taking place in the discussion forums primarily concerns issues regarding course structure. Very few posts concern challenging reasoning or, conversations that may support learners to deepen their understanding of the subject matter at hand.
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| 2. |
- Jansson, Malin, et al.
(författare)
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Expression and Circulating Levels of Perlecan in Breast Cancer : Implications for Oestrogen Dependent Stromal Remodeling
- 2020
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Ingår i: Journal of mammary gland biology and neoplasia. - : Springer Science and Business Media LLC. - 1083-3021 .- 1573-7039. ; 25, s. 69-77
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Tidskriftsartikel (refereegranskat)abstract
- Localised breast cancer can be cured by surgery and adjuvant treatments, but mortality remains high as some tumours metastasize early. Perlecan is a basement membrane (BM) protein involved in tumour development and progression. Here, mRNA and protein expression of perlecan, and mRNA expression of matrix degrading enzymes were studied in normal breast and invasive breast cancer, and correlated to prognostic risk factors, in particular oestrogen status. Moreover, plasma levels of perlecan were measured in patients with breast cancer and compared with controls. mRNA data was extracted from the Cancer Genome Atlas database. Perlecan protein expression was visualized using immunofluorescence and plasma levels measured by ELISA assay. Perlecan mRNA levels were twice as high in normal breast compared with breast cancer tissue. A strong correlation was found between mRNA expression of perlecan and several matrix-degrading enzymes in oestrogen receptor positive (ER+) tumours. Perlecan protein was localized to both epithelial and vascular BMs, but absent in the stroma in normal breast. In breast cancer, the expression of perlecan in epithelial BM was fragmented or completely lost, with a marked upregulation of perlecan expression in the stroma. Significantly higher levels of perlecan were found in plasma of ER+ patients when compared with ER- patients. This study shows that perlecan expression and degradation in breast cancer may be linked to the ER status of the tumour.
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| 3. |
- Jansson, Malin, et al.
(författare)
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MiR-155-mediated loss of C/EBP beta shifts the TGF-beta response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer
- 2013
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 32:50, s. 5614-5624
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Tidskriftsartikel (refereegranskat)abstract
- During breast cancer progression, transforming growth factor-beta (TGF-beta) switches from acting as a growth inhibitor to become a major promoter of epithelial-mesenchymal transition (EMT), invasion and metastasis. However, the mechanisms involved in this switch are not clear. We found that loss of CCAAT-enhancer binding protein beta (C/EBP beta), a differentiation factor for the mammary epithelium, was associated with signs of EMT in triple-negative human breast cancer, and in invasive areas of mammary tumors in MMTV-PyMT mice. Using an established model of TGF-beta-induced EMT in mouse mammary gland epithelial cells, we discovered that C/EBP beta was repressed during EMT by miR-155, an oncomiR in breast cancer. Depletion of C/EBP beta potentiated the TGF-beta response towards EMT, and contributed to evasion of the growth inhibitory response to TGF-beta. Furthermore, loss of C/EBP beta enhanced invasion and metastatic dissemination of the mouse mammary tumor cells to the lungs after subcutaneous injection into mice. The mechanism by which loss of C/EBP beta promoted the TGF-beta response towards EMT, invasion and metastasis, was traced to a previously uncharacterized role of C/EBP beta as a transcriptional activator of genes encoding the epithelial junction proteins E-cadherin and coxsackie virus and adenovirus receptor. The results identify miR-155-mediated loss of C/EBP beta as a mechanism, which promotes breast cancer progression by shifting the TGF-beta response from growth inhibition to EMT, invasion and metastasis.
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| 4. |
- Jansson, Malin, et al.
(författare)
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Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
- 2022
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with in situ and small invasive breast cancers (<= 15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated (p = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis (p = 0.002). In an external validation cohort (n = 1,104), high type IV collagen mRNA expression was significantly (p = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers.
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| 5. |
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| 6. |
- Jansson, Malin, 1978-, et al.
(författare)
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Stromal Type I Collagen in Breast Cancer: Correlation to Prognostic Biomarkers and Prediction of Chemotherapy Response
- 2024
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Ingår i: CLINICAL BREAST CANCER. - : Elsevier. - 1526-8209 .- 1938-0666. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- Type I collagen is involved in the development and progression of breast cancer. Here, type I collagen mRNA and protein expression were analysed in 2509 and 1395 breast cancer patients, respectively. Results show that low type I collagen expression is a marker of more aggressive breast cancer, and also a predictive biomarker of response to adjuvant chemotherapy. Introduction: Fibrillar collagens accumulate in the breast cancer stroma and appear as poorly defined spiculated masses in mammography imaging. The prognostic value of tissue type I collagen remains elusive in treatment-na & iuml;ve and chemotherapy-treated breast cancer patients. Here, type I collagen mRNA and protein expression were analysed in 2 large independent breast cancer cohorts. Levels were related to clinicopathological parameters, prognostic biomarkers, and outcome. Method: COL1A1 mRNA expression was analysed in 2509 patients with breast cancer obtained from the cBioPortal database. Type I collagen protein expression was studied by immunohistochemistry in 1395 women diagnosed with early invasive breast cancer. Results: Low COL1A1 mRNA and protein levels correlated with poor prognosis features, such as hormone receptor negativity, high histological grade, triple-negative subtype, node positivity, and tumour size. In unadjusted analysis, high stromal type I collagen protein expression was associated with improved overall survival (OS) (HR = 0.78, 95% CI = 0.61-0.99, p = .043) and trended towards improved breast cancer-specific survival (BCSS) (HR = 0.65, 95% CI = 0.42-1.01, P = 0.053), although these findings were lost after adjustment for other clinical variables. In unadjusted analysis, high expression of type I collagen was associated with better OS (HR = 0.70, 95% CI = 0.55-0.90, P = .006) and BCSS (HR = 0.55, 95% CI = 0.34-0.88, P = .014) among patients not receiving chemotherapy. Strikingly, the opposite was observed among patients receiving chemotherapy. There, high expression of type I collagen was instead associated with worse OS (HR = 1.83, 95% CI = 0.65-5.14, P = .25) and BCSS (HR = 1.72, 95% CI = 0.54-5.50, P = .357). Conclusion: Low stromal type I collagen mRNA and protein expression are associated with unfavourable tumour characteristics in breast cancer. Stromal type I collagen might predict chemotherapy response.
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| 7. |
- Jansson, Malin, 1978-
(författare)
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The role of stroma-derived substances in breast cancer progression and their function as tumour markers
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In 2020, more than 2,260,000 women were diagnosed with breast cancer. Most patients are cured with surgery and adjuvant treatment, but despite that, approximately 700,000 women die of the disease every year. The historical focus on breast cancer progression has been on the malignant epithelial cell. However, cancer cells do not grow in isolation. In recent years, the importance of the tumour microenvironment in cancer progression has been highlighted. Perlecan and type IV collagen are basement membrane (BM) proteins in the normal mammary gland, and type I collagen is the main fibrillar collagen in the interstitial extracellular matrix (ECM). In cancer development, perlecan and type IV collagen have multifunctional roles and when degraded from the BM, bioactive substances and other fragments are released in the circulation. Significant ECM changes also occur that lead to an accumulation of fibrillar collagens. Given their abundance in the ECM; perlecan, type IV and type I collagen are of interest for breast cancer progression and may be of importance as new biomarkers to monitor disease, predict patient outcome and the treatment effect.Aim: In this thesis, the protein and mRNA expression of perlecan, type IV and I collagen in breast cancer tissue is studied. The aim is to characterize the expression pattern of these proteins in breast cancer tissue and to see whether there is a correlation to known prognostic biomarkers and to the patient prognosis. Moreover, to evaluate circulating perlecan and type IV collagen as diagnostic and prognostic biomarkers in breast cancer patients.Methods: In this thesis project, eight different patient cohorts were used. In freshly frozen normal breast and breast cancer tissue, perlecan protein expression was visualized using immunofluorescence. Type IV and I collagen protein expression were studied with immunohistochemistry in formalin-fixed, paraffin embedded primary breast cancer tissue, and type IV collagen in metastatic breast cancer tissue. For gene expression analysis, mRNA and clinicopathological data were extracted from the Cancer Genome Atlas and cBioportal database. Circulating plasma levels of perlecan were analysed in breast cancer patients and controls, circulating levels of CA15-3 and type IV collagen in patients with primary and metastatic breast cancer as well as controls. Perlecan and type IV collagen were measured with ELISA assays, and CA15-3 were using an electrochemiluminescence immunoassay.Results: In breast cancer tissue, perlecan and type IV collagen protein expression in the epithelial BM was fragmented or completely lost, and perlecan and type IV collagen was expressed to varying extent in the tumour stroma. The mRNA analysis confirmed that type IV collagen mRNA was expressed in primary breast cancer tissue and highly expressed in metastatic tissue. Type I collagen was mostly highly expressed in the tumour stroma. Low type I collagen protein and mRNA expression correlated with biomarkers for aggressive breast cancer, but no effect on survival could be seen. Among patients receiving chemotherapy, low stromal type I collagen protein expression was associated with better survival compared to high expression, even after adjusting for other relevant factors. There was no correlation of perlecan or type IV collagen protein expression to clinically used prognostic biomarkers, but an oestrogen receptor dependent correlation between mRNA expression of perlecan and several matrix-degrading enzymes were found. Survival analysis showed that high stromal type IV collagen protein and mRNA expression in the primary tumour was significantly associated with a poorer survival, and high protein expression with a risk of developing distant metastasis. Metastatic breast cancer patients had higher levels of circulating type IV collagen compared to healthy controls and patients with primary breast cancer. High circulating type IV collagen levels correlated with poorer survival in metastatic breast cancer patients, and was superior to CA15-3 at detecting metastatic breast cancer.Conclusions: The protein expression pattern of perlecan, type IV collagen and type I collagen become abnormal during breast cancer development. Stromal type IV collagen protein and mRNA in the primary tumour correlates to poorer prognosis, most likely due to a higher risk of developing metastatic disease. Circulating type IV collagen can function as a biomarker for detecting metastatic disease in patients with primary breast cancer and is prognostic in patients with metastatic breast cancer. Low stromal type I collagen is a marker for an aggressive breast cancer disease and can predict chemotherapy response.
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| 8. |
- Lager, Susanne, 1978, et al.
(författare)
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Perinatal lack of maternal IL-6 promotes increased adiposity during adulthood in mice.
- 2011
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 152:4, s. 1336-46
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Tidskriftsartikel (refereegranskat)abstract
- The perinatal environment appears important in establishing metabolic phenotypes in adulthood. Mice deficient in IL-6 (IL-6(-/-)) tend to develop mature-onset obesity, but it is unknown whether perinatal exposure to IL-6 produced by the dam influences the metabolism of adult offspring. To address this issue, we monitored IL-6(-/-) offspring of IL-6(-/-) or IL-6(+/-) dams, as well as wild-type (WT) mice. At adult age, IL-6(-/-) mice weighed significantly more and had more body fat than WT mice, regardless of maternal genotype, and had lower insulin sensitivity. This phenotype was more pronounced in IL-6(-/-) offspring of IL-6(-/-) dams, because they gained weight significantly faster than IL-6(-/-) offspring of IL-6(+/-) dams and had more body fat and higher serum leptin levels at an earlier age. The leptin content was 2-fold higher in milk from IL-6(-/-) than WT dams. However, cross-fostering IL-6(-/-) mice with WT dams did not alter body weight, body composition, or adipocyte size at adult age compared with IL-6(-/-) mice fostered by IL-6(-/-) dams. Conversely, WT mice fostered by IL-6(-/-) dams weighed significantly more than those fostered by WT dams and had more body fat, larger adipocytes, and altered hypothalamic gene expression. We conclude that body fat of adult mice can be increased by perinatal exposure to factors affected by lack of maternal IL-6.
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| 9. |
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| 10. |
- Lyth, Johan, 1980-, et al.
(författare)
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Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men
- 2015
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Ingår i: British Journal of Dermatology. - : Wiley-Blackwell. - 0007-0963 .- 1365-2133. ; 172:3, s. 700-706
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium.Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011.Methods: This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM 1997-2011. The patients were followed through 2012 in the national Cause-of-Death Register.Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site, and health care region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P = 0·0008) and the CMM-specific survival significantly improved in men diagnosed 2007-2011 compared to men diagnosed 1997-2001 (hazard ratio=0·81; 95% CI 0·72-0·91, P = 0·0009) while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared to those diagnosed earlier 1997-2001 and later 2007-2011.Conclusion: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.
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