| 1. |
- Brekke, Helge R., et al.
(författare)
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Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors
- 2009
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 11:5, s. 514-528
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to identify new prognostic biomarkers with clinical impact in malignant peripheral nerve sheath tumor (MPNST), a highly aggressive malignancy for which no consensus therapy exists besides surgery. We have used tissue microarrays (TMAs) to assess in situ expression of 14 cell-cycle-regulating proteins in 64 well-characterized MPNST patients: 36 sporadic and 28 with neurofibromatosis type 1 (NF1). We developed a new software application for evaluation and logistics of the TMA images and performed a literature survey of cell cycle proteins in MPNST. For NF1-associated patients, there was a clear association between nuclear expression of p53 and poor survival (p = 0.004). Among the other proteins analyzed, we also found significant associations between survival and clinical variables, but none were as strong as that for p53. For the total series of MPNSTs, p53 was shown to be an independent predictor of survival, and patients without remission, with tumor size larger than 8 cm, and with positive p53 expression had a 60 times greater risk of dying within the first 5 years compared with the remaining patients (p = 0.000002). This is the most comprehensive study of in situ protein expression in MPNST so far, and expressed p53 was found to be a strong surrogate marker for outcome. Patients in complete remission with a primary p53-positive MPNST diagnosis may be considered in a high-risk subgroup and candidates for adjuvant treatment. Neuro-Oncology 11, 514-528, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00271, January 30, 2009.)
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| 2. |
- Bruun, Jarle, et al.
(författare)
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Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer
- 2015
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 21:16, s. 3759-3770
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 50 UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical highrisk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (greater than 75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (C) 2015 AACR.
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| 3. |
- Haglund, Kaisa, et al.
(författare)
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Cindr interacts with anillin to control cytokinesis in Drosophila melanogaster
- 2010
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 20:10, s. 944-950
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Tidskriftsartikel (refereegranskat)abstract
- Cytokinesis, the final step of cell division, conventionally proceeds to cell separation by abscission, or complete cytokinesis [1, 2], but may in certain tissues be incomplete, yielding daughter cells that are interconnected in syncytia by stable intercellular bridges [3]. The mechanisms that determine complete versus incomplete cytokinesis are not known. Here we report a novel in vivo role of the Drosophila CD2AP/CIN85 ortholog Cindr in both complete and incomplete cytokinesis. We also show evidence for the presence of persistent intercellular bridges in the major larval imaginal disc epithelia. During conventional division of both cultured and embryonic cells, Cindr localizes to cleavage furrows, intercellular bridges, and midbodies. Moreover, in cells undergoing incomplete cytokinesis in the female germline and the somatic ovarian follicle cell and larval imaginal disc epithelia, Cindr localizes to arrested cleavage furrows and stable intercellular bridges, respectively. In these structures, Cindr colocalizes with the essential cytokinesis regulator Anillin. We show that Cindr interacts with Anillin and that depletion of either Cindr or Anillin gives rise to binucleate cells and fewer intercellular bridges in vivo. We propose that Cindr and Anillin cooperate to promote intercellular bridge stability during incomplete cytokinesis in Drosophila melanogaster.
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| 4. |
- Holland, Petter, et al.
(författare)
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HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1-and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes. We propose that HS1BP3 regulates autophagy by modulating the PA content of the ATG16L1-positive autophagosome precursor membranes through PLD1 activity and localization. Our findings provide key insights into how autophagosome formation is regulated by a novel negative-feedback mechanism on membrane lipids.
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| 5. |
- Holter, Oystein Gullvåg, et al.
(författare)
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Erfaringer i akademia - en ny kartlegging
- 2021. - 1
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Ingår i: Likestilling i akademia - fra kunnskap til endring. - Oslo : Cappelen Damm Akademisk. ; , s. 119-152
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Bokkapitel (refereegranskat)abstract
- The chapter provides a summarizing review of the main findings of the FRONT project with respect to gender and equality at different career levels. The review is based on quantitative surveys together covering 269 variables and 1,056 respondents. Among students, negative experiences are significantly more common for women than men, particularly when it comes to social treatment. Among employees, women experience markedly more challenges involving factors such as negative scrutiny, unwanted sexual attention or partners whose careers were given priority. The data reveal differences also in several other factors, but these were often moderate. Thus, it is typically a complex process with many components that results in an “accumulated disadvantage” for women. The differences were found at all career levels, but with a clear tendency towards more challenges for women at higher career levels. The observations from FRONT are discussed in light of other studies, a main conclusion being that the situation is surprisingly similar in different countries.
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| 6. |
- Holter, Øystein Gullvåg, et al.
(författare)
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Bøygen-modellen: Hypotesen om akkumulering av ulempe
- 2021. - 1
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Ingår i: Likestilling i akademia - fra kunnskap til endring. - Oslo : Cappelen Damm Akademisk. ; , s. 157-192
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Bokkapitel (refereegranskat)abstract
- Material from the FRONT project shows significant gendered differences in how the working environment and organizational culture are experienced. It is not a single factor that negatively affects women, but a complex process involving many components over time – with different causes and modes of action – together giving an accumulated disadvantage. These processes and their effects are summarized in a model called“Bøygen”, after the creature who creates obstacles and counter-forces to Peer Gynt in Ibsen’s play. The academic version of Bøygen operates partly through an “accumulation” of disadvantages throughout the academic career, and partly through experiences that tend to cause loss of self-confidence and motivation. External resistance and lack of support translates into inner doubt. The Bøygen model is discussed in relation to international research on the effects of barriers to women in academia. The model is the first of three theoretical contributions to the project (chapters 7, 8 and 9) based on the empirical content in chapters 1–6. [G1]inte säker på vad som menas här: approaches?
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| 7. |
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| 8. |
- Snickare, Lotta, et al.
(författare)
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Experiences in Academia : A New Survey Study
- 2022
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Ingår i: Gender Equality in Academia. - Oslo : Cappelen Akademisk Forlag. ; , s. 129-164
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Bokkapitel (refereegranskat)abstract
- The chapter provides a summarizing review of the main findings of the FRONT project with respect to gender and gender equality on different career levels. The review is based on two surveys, an employee survey with 190 variables and 843 respondents, and a student survey with 79 variables and 213 respondents. Among students, negative experiences are significantly more common for women than men, particularly when it comes to social treatment. Among employees, women experience markedly more challenges involving factors such as negative scrutiny, unwanted sexual attention or partners whose careers were given priority. The data also reveal differences in several other factors, but these were often moderate. Thus, it is typically a complex process with many components, resulting in an “accumulated disadvantage” for women. The differences were found on all career levels but with a clear tendency towards more challenges for women on higher levels. The observations from FRONT are discussed in light of other studies, a main conclusion being that the situation is surprisingly similar in different countries.
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| 9. |
- Snickare, Lotta, et al.
(författare)
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Menn, maskulinitet og faghierarki
- 2021. - 1
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Ingår i: <em>Likestilling i akademia – fra kunnskap til endring</em>. - Oslo : Cappelen Damm Akademisk. ; , s. 49-74
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Bokkapitel (refereegranskat)abstract
- Research on gender equality in academia only addresses men’s experiences to a limited extent, and the significance of masculine norms is also poorly elucidated. In this chapter, we present our results on the effects of male dominance in the Faculty of Mathematics and Natural Sciences. We first discuss whether it is an advantage to be a man at the faculty. The simple answer, based on our data, is “yes”. However, although we could not identify a specific “male” pattern of problems, a significant proportion of men experience problems – some feel “as affected as women” and oppose specific measures for women. There are also indications of informal communities of men, a poorly-considered majority position, the notion that an academic career is incompatible with family and caregiving – not just for women, but for men too – and tendencies toward an unyielding connection between men, masculinity and professional hierarchies.
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