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- Fridberg, Marie, et al.
(författare)
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Modifying effect of gender on the prognostic value of clinicopathological factors and Ki67 expression in melanoma : a population-based cohort study
- 2012
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Ingår i: Biology of Sex Differences. - : Springer Science and Business Media LLC. - 2042-6410. ; 3, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignant melanoma is the most deadly form of skin cancer. Female sex is known to have a protective effect on incidence, tumour characteristics, and mortality from melanoma. However, the potentially modifying effect of sex on the prognostic significance of clinicopathological and investigative factors is generally not taken into consideration in biomarker studies. In this study, we compared the sex-specific distribution and prognostic value of established tumour characteristics and Ki67 expression in 255 cases of incident primary melanoma in a prospective, population-based cohort study.METHODS: The study included 255 incident cases of melanoma, 132 females and 123 males, in the Malmö Diet and Cancer Study. Tumours from 226 (88.6%) cases had been assembled in tissue microarrays. Clinicopathological factors and immunohistochemical Ki67 expression were assessed and correlated with disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier analysis, log rank test and univariable and multivariable Cox regression analyses, stratified for gender. Effect of gender on melanoma-specific survival (MSS) after first recurrence was also analysed.RESULTS: Women were significantly younger at diagnosis than men (p = 0.012). The most common tumour sites were the legs in women (37.5%) and the dorsal trunk in men (37.8%). Kaplan-Meier analysis revealed that tumour location had no prognostic impact in women, but in men, location to the frontal trunk was significantly associated with a reduced DFS compared with all other locations combined and location to the dorsal trunk was significantly associated with a prolonged OS. High Ki67 expression was significantly associated with a reduced DFS and OS in men but not in women, also when adjusted for other factors. In men, but not in women, ulceration was an independent prognostic factor for both DFS and OS. MSS after first local, regional or distant recurrence was significantly shorter for men than for women.CONCLUSIONS: The results from this study demonstrate that the prognostic value of tumour location, Ki67 expression and ulceration in melanoma differs according to gender. These findings need to be validated in future studies, as they may help improve prognostication in patients with melanoma. Moreover, our findings demonstrate that sex-stratified analyses add valuable information to biomarker studies.
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| 2. |
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| 3. |
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| 4. |
- Fridberg, Marie, et al.
(författare)
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The role of science in Swedish pre-schools : children’s collaborative learning scaffolded by iPads
- 2014
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Konferensbidrag (refereegranskat)abstract
- To extend current understanding of how emerging technologies, i.e. iPads, can be used in pre-schools to support collaborative learning of real-life science phenomena. Research on the potential of web-based technologies to support collaborative inquiry-based science learning in schools (Redfors et al. 2013) is continued by investigating the role of stop-motion animations (Fleer, 2013, Hoban, 2007) in developing children’s understanding of science phenomena, by synthesising the two domains defined by Eshach (2006) for kids’ science learning, content and investigations. The theoretical framework is primarily based on phenomenography focusing on developmental pedagogy (Marton & Booth, 1997, Pramling Samuelsson & Asplund Carlsson, 2008). Design-based research (Barab & Squire, 2004) is used to bridge the worlds of academia and theory with the realities, complexities, and constraints of educational practice, and foster viable practices. A mixed-methods approach, including video and qualitative and quantitative data measures is used. The research adheres to the ethical guidelines of the Swedish Research Council. All participants and children’s caregivers are informed and agree to voluntary and anonymous participation with a right to abandon participation. In this paper we report on the first phase of the project where videos of children’s work with constructing and discussing time-lapse and stop motion sequences of science phenomena have been analysed within our theoretical framework. Stop-motion animations (Fleer 2013) help children, teachers and students to more consciously consider concepts. We see a great potential in work where teachers, students and researchers jointly develop, enact and evaluate learning processes supported by ubiquitous technologies in pre-school.
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| 5. |
- Fridberg, Marie, et al.
(författare)
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The role of science in Swedish pre-schools : children’s collaborative learning scaffolded by iPads
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To extend current understanding of how emerging technologies, i.e. iPads, can be used in pre-schools to support collaborative learning of real-life science phenomena. Research on the potential of web-based technologies to support collaborative inquiry-based science learning in schools (Redfors et al. 2013) is continued by investigating the role of stop-motion animations (Fleer, 2013, Hoban, 2007) in developing children’s understanding of science phenomena, by synthesising the two domains defined by Eshach (2006) for kids’ science learning, content and investigations. The theoretical framework is primarily based on phenomenography focusing on developmental pedagogy (Marton & Booth, 1997, Pramling Samuelsson & Asplund Carlsson, 2008). Design-based research (Barab & Squire, 2004) is used to bridge the worlds of academia and theory with the realities, complexities, and constraints of educational practice, and foster viable practices. A mixed-methods approach, including video and qualitative and quantitative data measures is used. The research adheres to the ethical guidelines of the Swedish Research Council. All participants and children’s caregivers are informed and agree to voluntary and anonymous participation with a right to abandon participation. In this paper we report on the first phase of the project where videos of children’s work with constructing and discussing time-lapse and stop motion sequences of science phenomena have been analysed within our theoretical framework. Stop-motion animations (Fleer 2013) help children, teachers and students to more consciously consider concepts. We see a great potential in work where teachers, students and researchers jointly develop, enact and evaluate learning processes supported by ubiquitous technologies in pre-school.
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| 6. |
- Larsson, Anna H, et al.
(författare)
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Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 12, s. 282-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. Method: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). Results: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. Conclusions: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.
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| 7. |
- Nodin, Björn, et al.
(författare)
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Discovery of Dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer
- 2012
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Ingår i: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 5:1, s. 6-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Dachshund homolog 2 (DACH2) gene has been implicated in development of the female genital tract in mouse models and premature ovarian failure syndrome, but to date, its expression in human normal and cancerous tissue remains unexplored. Using the Human Protein Atlas as a tool for cancer biomarker discovery, DACH2 protein was found to be differentially expressed in epithelial ovarian cancer (EOC). Here, the expression and prognostic significance of DACH2 was further evaluated in ovarian cancer cell lines and human EOC samples. Methods: Immunohistochemical expression of DACH2 was examined in tissue microarrays with 143 incident EOC cases from two prospective, population-based cohorts, including a subset of benign-appearing fallopian tubes (n = 32). A nuclear score (NS), i.e. multiplier of staining fraction and intensity, was calculated. For survival analyses, cases were dichotomized into low (NS < = 3) and high (NS > 3) using classification and regression tree analysis. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the impact of DACH2 expression on survival. DACH2 expression was analysed in the cisplatin sensitive ovarian cancer cell line A2780 and its cisplatin resistant derivative A2780-Cp70. The specificity of the DACH2 antibody was tested using siRNA-mediated silencing of DACH2 in A2780-Cp70 cells. Results: DACH2 expression was considerably higher in the cisplatin resistant A2780-Cp70 cells compared to the cisplatin-sensitive A2780 cells. While present in all sampled fallopian tubes, DACH2 expression ranged from negative to strong in EOC. In EOC, DACH2 expression correlated with several proteins involved in DNA integrity and repair, and proliferation. DACH2 expression was significantly higher in carcinoma of the serous subtype compared to non-serous carcinoma. In the full cohort, high DACH2 expression was significantly associated with poor prognosis in univariable analysis, and in carcinoma of the serous subtype, DACH2 remained an independent factor of poor prognosis. Conclusions: This study provides a first demonstration of DACH2 protein being expressed in human fallopian tubes and EOC, with the highest expression in serous carcinoma where DACH2 was found to be an independent biomarker of poor prognosis. Future research should expand on the role of DACH2 in ovarian carcinogenesis and chemotherapy resistance.
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| 9. |
- Nodin, Björn, et al.
(författare)
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High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma
- 2012
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Ingår i: Diagnostic Pathology. - : Springer Science and Business Media LLC. - 1746-1596. ; 7:1, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malignant melanoma is the most lethal form of skin cancer with a variable clinical course even in patients with thin melanomas and localized disease. Despite increasing insights into melanoma biology, no prognostic biomarkers have yet been incorporated into clinical protocols. Reduced expression of the RNA binding motif protein 3 (RBM3) has been shown to correlate with tumour progression and poor prognosis in melanoma and several other cancer forms. In ovarian cancer, an inverse association was found between expression of RBM3 and the minichromosome maintenance 3 (MCM3) gene and protein. In melanoma, gene expression analysis and immunohistochemical validation has uncovered MCM3 as a putative prognostic biomarker. The aim of the present study was to examine the associations of MCM3 expression with clinical outcome and RBM3 expression in a prospective, population-based cohort of melanoma. Methods: Immunohistochemical MCM3 expression was examined in 224 incident cases of primary melanoma from the Malmo Diet and Cancer Study, previously analysed for RBM3 expression. Spearman's Rho and Chi-Square tests were used to explore correlations between MCM3 expression, clinicopathological factors, and expression of RBM3 and Ki67. Kaplan Meier analysis, the log rank test, and univariable and multivariable Cox proportional hazards modelling were used to assess the impact of MCM3 expression on disease-free survival (DFS) and melanoma-specific survival (MSS). Results: High MCM3 expression was significantly associated with unfavourable clinicopathological features and high Ki67 expression. A significant inverse correlation was seen between expression of MCM3 and RBM3 (p = 0.025). High MCM3 expression was associated with a reduced DFS (HR = 5.62) and MSS (HR = 6.03), and these associations remained significant in multivariable analysis, adjusted for all other factors (HR = 5.01 for DFS and HR = 4.96 for MSS). RBM3 expression remained an independent prognostic factor for MSS but not DFS in the multivariable model. Conclusions: These findings provide validation of the utility of MCM3 expression as an independent biomarker for prognostication of patients with primary melanoma. Moreover, the inverse association and prognostic impact of MCM3 and RBM3 expression indicate a possible interaction of these proteins in melanoma progression, the functional basis for which merits further study.
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| 10. |
- Redfors, Andreas, 1961-, et al.
(författare)
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On the potential of mobile and ubiquitous technologies to support collaborative processes with a science content in pre-schools
- 2014
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Konferensbidrag (refereegranskat)abstract
- We will present on a project that sets out to extend current understanding of how emerging technologies can be used by children and their pre-school teachers as socio-cognitive tools to support collaboration and reflection in investigating complex, real-life problems. The research group LISMA has previously been involved in work situated at the intersection of new information and communication technologies (ICTs), social cognition, and learning with research focused on examining the potential of web-based technologies to support social and psychological processes which are at the centre of learning, with a special interest in inquiry-based science learning to support active involvement, collaboration, cognitive flexibility, reflective and critical thinking, and the development of adaptive expertise (Redfors et al. 2013). Hence, we will synthesise the two domains defined by Eshach (2006) for kids’ science learning; content (concepts, explanatory models) and investigations (hypothesis, problematizing, questions, experiments). With this project we will take this line of work further and focus on the role of ubiquitous technologies in pre-schools. The project methodology is based on the idea of design-based research (Barab & Squire, 2004). This approach seeks to bridge the often disconnected worlds of academia and theory with the realities, complexities, and constraints of educational practice. Design-based research is the most suitable methodological approach to the goals of this project, since its iterative, participatory, and evidence-based philosophy can foster the development of viable, empirically tested practices. The collaborative activities that we will create will be iteratively tested and refined, first as pilot projects, then during local implementations, and finally during implementations and synthesis work at a global level. This approach can ensure that the outcomes of such work can be used in other similar learning contexts. In the context of this approach, we will follow a mixed-methods approach, which will include qualitative and quantitative data collection measures. We will report on the first phase of the project where we will work with pre- and in-service pre-school teachers developing Slowmations (Fleer, 2013; Hoban, 2007) to develop their own and children’s understanding of science phenomena. Slowmations (“SlowAnimation”) are software generated simple stop-motion animations played slowly at two frames per second. Children photograph objects, creating a sequence of photographic images, which they put together as a video clip, with self-generated narration to explain the phenomena. Research suggests that slowmations (Fleer 2013) helps children to more consciously consider concepts. Teachers and students (during VFU) will in collaboration with researchers in a design-based process develop, enact and evaluate slow-mations. Through a future international group we will be able to identify the critical attributes, the important constraints and the crucial characteristics of successful research-based activities.
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