| 1. |
- Ekerhult, Teresa, et al.
(författare)
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Sclerosis as a predictive factor for failure after bulbar urethroplasty: a prospective single-centre study.
- 2018
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 52:4, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess whether sclerosis in histology following bulbar urethroplasty is a predictive factor for failure of surgery.Resected stricture specimens from 45 patients undergoing open urethroplasty with excision and anastomosis were collected prospectively during 2011-2014. Histopathological characteristics, including fibrosis (grade I-III), inflammation and sclerosis, were evaluated using different routine staining. These specimens were compared to normal urethral resection specimens from patients undergoing sex-correction surgery. The uropathologist who conducted the analyses was blinded to the study design.The outcomes of the histological classifications were as follows: 19 patients had grade I fibrosis, of whom three had failures; 13 patients had grade II fibrosis, without any failures; and the most severe fibrosis, grade III, including sclerosis, was found in 13 patients (11 with sclerosis), with failure in eight. Sclerosis was a significant risk factor for restricture when comparing patients with sclerosis and those without sclerosis, and likewise when adjusting for age, inflammation and stricture length.Histological findings of sclerosis in the resected urethral stricture specimen indicate a significantly higher risk for restricture after urethroplasty surgery.
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| 2. |
- Engström, Katarina, 1956, et al.
(författare)
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The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
- 2006
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Ingår i: The American journal of pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 168:5, s. 1642-53
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.
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| 3. |
- Kåbjörn-Gustafsson, Christina, et al.
(författare)
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Biopsy retrieval, tissue handling, morphology and histophatologic characteristics
- 2012
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Ingår i: Bladder pain syndrome-a clinical guide. eds.Nordling, Boucheloche, Cervigni, Fall, van der Merwe, Wyndale.. - New York, USA : Springer Verlag. - 9781441969293
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Kåbjörn-Gustafsson, Christina, et al.
(författare)
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Cell Senescence in Myxoid/Round Cell Liposarcoma
- 2014
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2014:Article ID 208786
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round cell liposarcoma (MLS/RCLS) is the second most common liposarcoma type and characterized by the fusion oncogenes FUS-DDIT3 or EWSR1-DDIT3. Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases and their inhibitors but very few cells progressing through the G1/S boundary. Here, we extend the investigation to proteins involved in cell senescence in an immunohistochemistry based study of 17 MLS/RCLS cases. Large subpopulations of tumor cells expressed the RBL2 pocket protein and senescence associated heterochromatin 1γ and IL8 receptor β. We conclude that MLS/RCLS tissues contain major populations of senescent tumor cells and this may explain the slow growth rate of this tumor type.
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| 5. |
- Kåbjörn-Gustafsson, Christina, et al.
(författare)
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DDIT3 Expression in Liposarcoma Development
- 2014
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2014
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Tidskriftsartikel (refereegranskat)abstract
- Liposarcomas are mesenchymal tumors containing variable numbers of lipoblasts or adipocytes. The most common entities, well differentiated/dedifferentiated liposarcoma (WDLS/DDLS) and myxoid/round cell liposarcoma (MLS/RCLS), are both characterized by genetic rearrangements that affect the expression of the transcription factor DDIT3. DDIT3 induces liposarcoma morphology when ectopically expressed in a human fibrosarcoma. The role of DDIT3 in lipomatous tumors is, however, unclear. We have analyzed the expression of DDIT3 in 37 cases of liposarcoma (WDLS/DDLS n = 10, MLS/RCLS n = 16, and pleomorphic liposarcomas (PLS) n = 11) and 11 cases of common benign lipomas. Major cell subpopulations of WDLS/DDLS and MLS/RCLS tumors were found to express DDIT3 or the derived fusion protein, whereas PLS cases showed only a few positive cells. The lipomas contained large subpopulations expressing DDIT3. No correlation between numbers of DDIT3 expressing cells and numbers of lipoblasts/adipocytes was found. In vitro adipogenic treatment of two DDIT3 expressing cell lines induced lipid accumulation in small subpopulations only. Our results suggest a dual, promoting and limiting, role for DDIT3 in the formation of lipoblasts and liposarcoma morphology.
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| 6. |
- Kåbjörn-Gustafsson, Christina
(författare)
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Liposarcomas - proliferation, senescence and the role of DDIT3
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipomatous tumors comprise benign and malignant forms called lipomas and liposarcomas. Myxoid/round cell liposarcoma (MLS/RCLS) is the second most common liposarcoma and is characterized by the fusion oncogenes FUS-DDIT3 or EWSR1-DDIT3. To understand the morphology of MLS we investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in immune-deficient mice. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, the fusion gene and normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line. MLS/RCLS may develop from cell types other than preadipocytes. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene. Further immunohistochemical investigation of the expression of the DDIT3 protein showed that major cell subpopulations of well differentiated tumors and MLS/RCLS tumors were found to express DDIT3 or the derived fusion protein. Our results suggest a dual, promoting and limiting, role for DDIT3 in formation of lipoblasts and liposarcoma morphology. Most liposarcoma types are characterized by genomic instability caused by impaired TP53 function. Further analysis of TP53 in MLS/RCLS with mass spectrometry, immunoblotting and immunohistochemistry show that a normal TP53 protein is produced in three of four MLS cell lines. This shows that the TP53 system is functional in the majority of MLS cases. MLS/RCLS tumors express proteins involved in cell senescence. In a study of 17 MLS/RCLS cases, large subpopulations of tumor cells expressed the RBL2 pocket protein together with senescence-associated heterochromatin binding protein 1γ and IL8 receptor β. The expression pattern suggests that MLS/RCLS tumors contain large subpopulations of senescent cells compatible with the slow growth of this tumor type.
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| 7. |
- Langenskiöld, Marcus, 1972, et al.
(författare)
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Intestinal mucosal MMP-1 - a prognostic factor in colon cancer.
- 2013
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:5, s. 563-569
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. There is evidence that transforming growth factor-β1 (TGF-β1) and matrix metalloproteinases (MMPs) play an important role in tumor invasion and progression in colorectal cancer. The aim of this study was to assess their utility in prediction of cancer-specific survival (CSS). Materials and methods. 136 patients undergoing curative surgery for colorectal carcinoma were prospectively included. Samples were taken from tumor and tumor-free intestinal mucosa and ELISA was used to assess protein levels in the tissues. Patients were followed for CSS. The median follow-up time for all included patients was 65 months (range: 45-92). The main outcome measure was CSS. Results. T stage, lymph node involvement and high levels of MMP-1 as well as MMP-9 in tumor-free mucosa tissue were significantly associated with CSS in colon cancer in univariate analysis. This prognostic strength was maintained for MMP-1 and N-status in multivariate analysis. Conclusions. The results indicate that MMP-1 is independently associated with CSS in patients with colon cancer. Furthermore, a possible clinical implication is that MMP-1 protein expression in tumor-free mucosa could identify colon cancer patients with poor CSS in need of more intensified adjuvant treatment.
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| 8. |
- Logadottir, Yr, et al.
(författare)
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Clinical characteristics differ considerably between phenotypes of bladder pain syndrome/interstitial cystitis.
- 2012
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Ingår i: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599. ; 46:5, s. 365-70
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Bladder pain syndrome/interstitial cystitis (BPS/IC) is one of the most bothersome conditions in urological practice. This syndrome includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated European Society for the Study of Interstitial Cystitis (ESSIC) type 3C, the non-Hunner type of BPS/IC appears different concerning demographic, endoscopic and histological findings, as well as the response to all forms of treatment. The objective of this study was to determine whether there are additional dissimilarities in clinical presentation between the main phenotypes of BPS/IC. Material and methods. In total, 393 BPS/IC patients (210 type 3C and 183 non-Hunner), diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases and ESSIC criteria, were studied by surveying the clinical records including micturition diaries. Results. In this clinical material, BPS/IC ESSIC type 3C accounted for 55% of cases. Patients with non-Hunner disease were on average 20 years younger at the time of diagnosis. Furthermore, there was a marked and significant difference in bladder capacity under general anaesthesia (p < 0.0001). Conclusions. The findings in the present series, together with previously published reports by this group and by others, confirm the striking differences between the main forms of BPS/IC and underline the indispensability of adequate subtyping in clinical studies.
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| 9. |
- Ståhlberg, Anders, 1975, et al.
(författare)
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Normal and Functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry few or no additional cytogenetic changes. There are conflicting reports concerning the status and role of TP53 in MLS/RCLS. Here we analysed four MLS/RCLS derived cell lines for TP53 mutations, expression and function. Three SV40 transformed cell lines expressed normal TP53 proteins. Irradiation caused normal posttranslational modifications of TP53 and induced P21 expression in two of these cell lines. Transfection experiments showed that the FUS-DDIT3 fusion protein had no effects on irradiation induced TP53 responses. Ion Torrent AmpliSeq screening, using the Cancer Hotspot panel, showed no dysfunctional or disease associated alleles/mutations. In conclusion, our results suggest that most MLS/RCLS cases carry functional TP53 genes and this is consistent with the low numbers of secondary mutations observed in this tumor entity.
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