| 1. |
- Bümming, Per, 1965, et al.
(författare)
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Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:3, s. 460-4
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Tidskriftsartikel (refereegranskat)abstract
- Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.
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| 2. |
- Engström, Katarina, 1956
(författare)
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Clinical and molecular studies of liposarcoma
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims: (1) To analyse clinicopathological characteristics, treatment and outcome of liposarcoma, and to determine whether, and how, the Scandinavian Sarcoma Group (SSG) treatment guidelines were followed; (2) to analyse tumour volume and morphology response after radiotherapy in myxoid/round cell liposarcoma (MLS/RCLS); (3) to examine the role of the MLS-specific fusion gene FUS-DDIT3 in development of liposarcomas; and (4) to analyse expression patterns of cell cycle regulating proteins in MLS. Methods: (1) A total of 319 liposarcomas reported between 1986?1998 to the SSG Register were reviewed. Altogether 237 patients without metastasis were analyzed for local recurrences in relation to surgical margins and radiotherapy, metastasis and survival. (2) Thirty-three primary or metastatic MLSs/RCLSs were treated with radiotherapy. Tumour size was measured by MRI or CT. Histopathology was performed of both non-irradiated and irradiated lesions. (3) The fibrosarcoma cell line HT1080 was transfected with the recombinant vectors pFUS-DDIT3-EGFP, pDDIT3-EGFP and pFUSa-EGFP. The tranfectants and the HT1080 cell line were injected into SCID mice, followed by histopathology. The transfected and non-transfected cells were cultured with adipogenic induction medium and microarray-based expression comparison of the different cell lines was performed. (4) Cell cycle controlling factors were analysed by immunohistochemistry and Western blotting in non-irradiated and irradiated MLSs/RCLSs. Results: (1) Altogether 78% were primarily operated at a sarcoma centre, 45% with wide margins. Only 58% of high-grade (Grades III-IV) lesions with non-wide surgery had postoperative radiotherapy. The risk of local recurrence in this group was 47%, if not irradiated. The estimated 10-year local recurrence-free and metastasis-free survival in the low-grade (Grades I-II) group was 87% and 95% respectively, while in the high-grade group it was 75% and 61%, respectively. Independent adverse prognostic factors for local recurrence were surgery outside a sarcoma centre and dedifferentiated liposarcoma. For metastases, they were old age, large tumour size, high grade and histological type MLS /RCLS. (2) Irradiated MLS/RCLS showed median tumour volume reduction of 52% in 23 tumours. The morphology showed paucicellularity, hyalinization and lipoma-like appearance. There were no obvious differences in volume reduction or morphologic response in MLSs/RCLSs in comparison with MLSs. (3) Cells expressing FUS-DDIT3 and DDIT3 grew in SCID mice as liposarcomas and the capillary network was similar to that found in MLSs/RCLSs. Cells transfected with DDIT3 responded in vitro to adipogenic factors by accumulation of fat, and microarray-based comparison showed that the DDIT3 and FUS-DDIT3 transfected variants shifted toward an MLS/RCLS-like expression pattern. (4) High expression of cyclin D1 and E, their kinases and kinase-inhibitors P16, P27 and P57 was observed, together with low Ki67 and normal cyclin A. Conclusion: Liposarcoma should be treated at specialized centres and postoperative radiotherapy is indicated for high-grade lesions, at least after non-wide surgery. Low-grade MLSs have high radio-responsiveness, and radiotherapy is indicated after non-wide surgery or in a preoperative setting. The fusion oncogene FUS-DDIT3 and DDIT3 may induce a liposarcoma phenotype, with DDIT3 being the tumour type-determining part of the fusion oncogene. Deregulation of G1-controlling proteins is common and indicates that MLS cells accumulate in late G1 phase.
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| 3. |
- Engström, Katarina, 1956, et al.
(författare)
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Irradiation of myxoid/round cell liposarcoma induces volume reduction and lipoma-like morphology
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:6, s. 838-845
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate the clinical and morphological effects of radiotherapy in the treatment of myxoid/round cell liposarcoma (MLS/RCLS). Thirty-three primary and metastatic MLS/RCLS tumours in 15 patients were treated with radiation therapy. Twenty-seven of the 33 tumours were surgically removed after preoperative radiation (34-46 Gy) while six tumours were treated with radiotherapy alone (44-60 Gy). The pretreatment diagnosis was established in all 15 patients based on fine needle aspirates or histological findings. Tumour size was measured by CT or MRI before and after radiotherapy in 30 tumours. Thirteen tumours from 11 patients were genetically characterised before and/or after radiation therapy. Twenty-three of 30 irradiated tumours showed a median reduction in tumour volume of 52% and seven lesions a median progression of 36%. All 27 surgically removed tumours revealed histological features of radiation response. The most striking morphological changes were lipoma-like appearance, paucicellularity and hyalinisation. Twelve of 13 tumours analysed before and/or after radiation therapy showed the FUS-DDIT3 translocation. Radiation therapy of MLS/RCLS induces histopathologic accumulation of mature lipoma-like areas and tumour volume reduction that may facilitate resectability.
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| 4. |
- Engström, Katarina, 1956, et al.
(författare)
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Liposarcoma: outcome based on the Scandinavian Sarcoma Group register.
- 2008
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 113:7, s. 1649-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to study the clinicopathological characteristics, treatment, and outcome of liposarcoma in an unselected, population-based patient sample, and to establish whether treatment was according to the Scandinavian Sarcoma Group (SSG) treatment guidelines. METHODS: The SSG Pathology Board reviewed 319 liposarcoma cases reported between 1986 and 1998. After the review, 237 patients without metastasis were analyzed for local recurrence rate in relation to surgical margins, radiotherapy, occurrence of metastasis, and survival. RESULTS: Seventy-eight percent of the patients were primarily operated on at a sarcoma center, 45% with wide margins. All patients operated on outside the center had nonwide margins. Low-grade lesions constituted 67% of cases. Despite nonwide surgery, only 58% of high-grade lesions were treated with postoperative radiotherapy. The risk of local recurrence after nonwide surgery, without irradiation, was 47% for high-grade lesions. The estimated 10-year, local recurrence-free and metastasis-free survival in the low-grade group was 87% and 95%, respectively. In the high-grade group, it was 75% and 61%, respectively. Independent adverse prognostic factors for local recurrence were surgery outside a sarcoma center and histological type dedifferentiated liposarcoma. For metastases, they were old age, large tumor size, high grade, and histological type myxoid liposarcoma with a round cell component. Radiotherapy showed significant effect on local recurrence rate for the same grade and margin. CONCLUSIONS: Patients with liposarcoma should be treated at specialized centers. Postoperative radiotherapy decreases the local recurrence rate. To maintain quality and provide support for further trials, reporting to quality registers is crucial.
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| 5. |
- 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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| 6. |
- Engström, Per, et al.
(författare)
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Loss evasion and tax aversion
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this paper is to study if taxpayers behave in a loss averse manner when filing their tax returns. This is important for tax design but also for understanding human behavior in general. The predictions of prospect theory can be contrasted to those of expected utility theory. We use data for 3.6 million Swedish taxpayers for the income year 2006. Our research method is quasi-experimental using a regression kink and discontinuity approach. We also use an alternative instrumental-variables approach. There is strong evidence of loss aversion. We estimate the coefficient of loss aversion using actual behavior and the instrument-variables approach. Our estimate is very close to the estimates reported in the experimental literature.
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| 7. |
- Hanson, Ellen, et al.
(författare)
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Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmö Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach. The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample ≤70 years. We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals.
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| 8. |
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| 9. |
- 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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| 10. |
- 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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