| 1. |
|
|
| 2. |
- Brune, Jan Claas, et al.
(författare)
-
Mesenchymal stromal cells from primary osteosarcoma are non-malignant and strikingly similar to their bone marrow counterparts.
- 2011
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 129, s. 319-330
-
Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSC) are multipotent cells that can be isolated from a number of human tissues. In cancer, MSC have been implicated with tumor growth, invasion, metastasis, drug resistance and were even suggested as possible tumor-initiating cells in osteosarcoma (OS). However, MSC from OS and their possible tumor origin have not yet been thoroughly investigated. Therefore, primary OS mesenchymal progenitors and OS-derived MSC were studied. OS samples contained very high frequencies of mesenchymal progenitor cells as measured by the CFU-F assay (median: 1,117 colonies per 10(5) cells, range: 133 - 3,000, n=6). This is considerably higher compared to other human tissues such as normal bone marrow (1.3 ± 0.2 colonies per 10(5) cells, n=8). OS-derived MSC (OS-MSC) showed normal MSC morphology and expressed the typical MSC surface marker profile (CD105/CD73/CD90/CD44/HLA-classI/CD166 positive, CD45/CD34/CD14/CD19/HLA-DR/CD31 negative). Furthermore, all OS-MSC samples could be differentiated into the osteogenic lineage, and all but one sample into adipocytes and chondrocytes. Genetic analysis of OS-MSC as well as OS-derived spheres showed no tumor-related chromosomal aberrations. OS-MSC expression of markers related to tumor-associated fibroblasts (fibroblast surface protein, alpha-smooth muscle actin, vimentin) was comparable to bone marrow MSC and OS-MSC growth was considerably affected by tyrosine kinase inhibitors. Taken together, our results demonstrate that normal, non-malignant mesenchymal stroma cells are isolated from OS when MSC culture techniques are applied. OS-MSC represent a major constituent of the tumor microenvironment, and they share many properties with bone marrow-derived MSC. © 2010 UICC.
|
|
| 3. |
|
|
| 4. |
- Carneiro, Ana, et al.
(författare)
-
A prognostic model for soft tissue sarcoma of the extremities and trunk wall based on size, vascular invasion, necrosis, and growth pattern.
- 2011
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; Dec, s. 1279-1287
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: In soft tissue sarcoma, better distinction of high-risk and low-risk patients is needed to individualize treatment and improve survival. Prognostic systems used in clinical practice identify high-risk patients based on various factors, including age, tumor size and depth, histological type, necrosis, and grade. METHODS:: Whole-tumor sections from 239 soft tissue sarcomas of the extremities were reviewed for the following prognostic factors: size, vascular invasion, necrosis, and growth pattern. A new prognostic model, referred to as SING (Size, Invasion, Necrosis, Growth), was established and compared with other clinically applied systems. RESULTS:: Size, vascular invasion, necrosis, and peripheral tumor growth pattern provided independent prognostic information with hazard ratios of 2.2-2.6 for development of metastases in multivariate analysis. When these factors were combined into the prognostic model SING, high risk of metastasis was predicted with a sensitivity of 74% and a specificity of 85%. Moreover, the prognostic performance of SING compared favorably with other widely used systems. CONCLUSIONS:: SING represents a promising prognostic model, and vascular invasion and tumor growth pattern should be considered in soft tissue sarcoma prognostication. Cancer 2010. © 2010 American Cancer Society.
|
|
| 5. |
- Dimitrijevic, Ivan, et al.
(författare)
-
Increased angiotensin II type 1 receptor expression in temporal arteries from patients with giant cell arteritis.
- 2009
-
Ingår i: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 116:5, s. 990-996
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Currently, giant cell arteritis (GCA) is primarily treated with corticosteroids or immunomodulating agents, but there is interest in identifying other noncorticosteroid alternatives. Similarities exist in the injury pathways between GCA and atherosclerosis. Angiotensin II is a vasoactive peptide involved in vessel inflammation during atherosclerosis, and angiotensin II receptor inhibitors are effective in preventing atherosclerosis. The present study was performed to elucidate the role of angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors in GCA. DESIGN: Experimental retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: Ten patients with GCA and 10 control patients, who were clinically suspected of having GCA but were diagnosed as not having GCA, were included. METHODS: Immunohistochemistry, using anti-AT(1) and anti-AT(2) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries. MAIN OUTCOME MEASURES: AT(1) and AT(2) receptor immunostaining intensity was quantified. RESULTS: Hematoxylin-eosin-stained sections of temporal arteries from patients with GCA showed intimal hyperplasia, internal elastic lamina degeneration, and band-shaped infiltrates of inflammatory cells, including lymphocytes, histocytes, and multinucleated giant cells. AT(1) receptor staining was primarily observed in the medial layer of the temporal arteries and was higher in the patients with GCA than in the control patients. This was a result of increased AT(1) receptor immunostaining of both vascular smooth muscle cells and infiltrating inflammatory cells. Only faint immunostaining was seen for AT(2) receptors, primarily in the endothelial cells, and to a lesser extent on the smooth muscle cells. Immunostaining with antibodies for the AT(2) receptor was similar in the patients with GCA and in controls. CONCLUSIONS: These results suggest that AT(1) receptors play a role in the development of GCA. Inhibition of the angiotensin system may thus provide a noncorticosteroid alternative for the treatment of GCA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
|
|
| 6. |
- Dimitrijevic, Ivan, et al.
(författare)
-
Increased Tissue Endothelin-1 and Endothelin-B Receptor Expression in Temporal Arteries from Patients with Giant Cell Arteritis.
- 2010
-
Ingår i: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 117, s. 628-636
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Endothelin (ET)-1 has been implicated in the atherosclerotic process and during inflammation. Similarity in the development process of giant cell arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have been developed, principally to target cardiovascular disease states. High doses of corticosteroids currently are used in the treatment of GCA, whereas other treatments are not as reliably effective. The present study was performed to elucidate the role for ET-1, ET(A), and ET(B) receptors in GCA. DESIGN: Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: The study included 10 patients with GCA and 10 control patients with clinically suspected GCA but diagnosed not to have GCA. METHODS: Immunohistochemistry, with anti ET-1, anti-ET(A), and anti-ET(B) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries. MAIN OUTCOME MEASURES: Endothelin-1, ET(A), and ET(B) receptor immunostaining intensities were quantified. RESULTS: Temporal arteries from the patients with GCA showed the typical histologic features, including intimal thickening, disruption or loss of the elastic lamina, and inflammatory infiltrates of lymphocytes, macrophages, and multinucleated giant cells. These features were associated with increased ET-1 and ET(B) receptor immunoreactivity in the medial layer of the temporal arteries and endothelial cells in patients with GCA compared with the controls. The increased ET-1 and ET(B) receptor immunoreactivity occurred in vascular smooth muscle cells (SMCs) and multinucleated giant cells. The ET-1 and ET(B) receptor immunoreactivity correlated with the degree of systemic inflammation. No changes were observed in ET(A) receptor expression in SMCs or endothelial cells compared with controls. CONCLUSIONS: The results suggest a role for ET-1 and ET(B) receptors in GCA. Inhibiting the ET system may provide a corticosteroid-sparing alternative in the treatment of GCA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
|
|
| 7. |
- Dimitrijevic, Ivan, et al.
(författare)
-
Reduced expression of angiotensin II and angiotensin receptor type 1 and type 2 in resistance arteries from nasal lesions in granulomatosis with polyangiitis (Wegener's granulomatosis).
- 2011
-
Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 40, s. 448-452
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Angiotensin II (ANGII) is involved in vessel inflammation and is important in the development of cardiovascular disorders such as atherosclerosis. During active disease, patients with granulomatosis with polyangiitis (GPA; Wegener's granulomatosis) have accelerated atherosclerosis and ANGII inhibitors are recommended to these patients to reduce atherosclerosis. We assessed the hypothesis that the expression of ANGII and its receptors in arteries in granulomatous lesions change in GPA. Methods: ANGII and angiotensin receptors were quantified in vessels from granulomatous lesions from patients with GPA using immunohistochemistry. Anti- ANGI type 1 (AT1) and type 2 (AT2) antibodies were applied on formalin-fixed and paraffin-embedded biopsies from nasal mucous membranes from eight patients with GPA and eight controls. Results: ANGII expression was localized to the endothelial cells (ECs) in arteries and sparsely to vascular smooth muscle cells (VSMCs) in nasal biopsies. AT1 receptor (AT1R) staining was intense and located in the VSMCs in the medial layer of the control arteries. AT2 receptor (AT2R) immunostaining was faint and was located only in the ECs. Patients with GPA showed marked down-regulation of positively immunostained ECs for ANGII or AT2R, and a reduced number of AT1R in VSMCs. ANGII, AT1R, and AT2R staining was persistent on infiltrating leucocytes. Conclusions: These results suggest down-regulation of the angiotensin system in arteries in granulomatous nasal lesions in GPA. Inhibition of the angiotensin system may prove less efficient in inhibiting the vascular inflammation process in GPA.
|
|
| 8. |
|
|
| 9. |
- Engellau, Jacob, et al.
(författare)
-
Identification of low-risk tumours in histological high-grade soft tissue sarcomas
- 2007
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 43:13, s. 1927-1934
-
Tidskriftsartikel (refereegranskat)abstract
- In more than one-third of patients with a histological high-grade malignant soft tissue sarcoma metastasis develops despite local control of the primary tumour. Hence, adjuvant chemotherapy is increasingly used for these relatively chemoresistant tumours which requires improved prognostication to exclude low-risk patients from overtreatment. We assessed the value of stepwise prognostication in a series of 434 histological high-grade STS of the extremity and trunk wall. Vascular invasion was used as the first discriminator whereafter the risk factors tumour necrosis, size (>8 cm) and infiltrating growth pattern were used to discriminate high- and low-risk tumours. We identified a high-risk group with a cumulative incidence of metastasis >0.4 at 5 years, and a low-risk group, comprising half of the tumours, with a cumulative incidence of metastasis <0.15. The model was validated in an independent material of 175 patients. This model improved prognostication in STS and is of value for identifying patients who probably should not receive adjuvant chemotherapy. (C) 2007 Elsevier Ltd. All rights reserved.
|
|
| 10. |
- Hofvander, Jakob, et al.
(författare)
-
Different patterns of clonal evolution among different sarcoma subtypes followed for up to 25 years
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3662-
-
Tidskriftsartikel (refereegranskat)abstract
- To compare clonal evolution in tumors arising through different mechanisms, we selected three types of sarcoma—amplicon-driven well-differentiated liposarcoma (WDLS), gene fusion-driven myxoid liposarcoma (MLS), and sarcomas with complex genomes (CXS)—and assessed the dynamics of chromosome and nucleotide level mutations by cytogenetics, SNP array analysis and whole-exome sequencing. Here we show that the extensive single-cell variation in WDLS has minor impact on clonal key amplicons in chromosome 12. In addition, only a few of the single nucleotide variants in WDLS were present in more than one lesion, suggesting that such mutations are of little significance in tumor development. MLS displays few mutations other than the FUS-DDIT3 fusion, and the primary tumor is genetically sometimes much more complex than its relapses, whereas CXS in general shows a gradual increase of both nucleotide- and chromosome–level mutations, similar to what has been described in carcinomas.
|
|
