| 1. |
- Gustavsson, Helene, 1977, et al.
(author)
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ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors.
- 2010
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10
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Journal article (peer-reviewed)abstract
- Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this study was to investigate the function of ADAMTS1 in prostate tumors.
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| 2. |
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| 3. |
- Jennbacken, Karin, 1978, et al.
(author)
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The prostatic environment suppresses growth of androgen-independent prostate cancer xenografts: an effect influenced by testosterone.
- 2009
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In: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 69:11, s. 1164-75
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Journal article (peer-reviewed)abstract
- BACKGROUND: Interactions between prostate cancer cells and their surrounding stroma play an important role in the growth and maintenance of prostate tumors. To elucidate this further, we investigated how growth of androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 prostate tumors was affected by different microenvironments and androgen levels. METHODS: Tumor cells were implanted subcutaneously and orthotopically in intact and castrated immunodeficient mice. Orthotopic tumor growth was followed by magnetic resonance imaging (MRI). Gene expression in the tumors was evaluated by means of microarray analysis and microvessel density (MVD) was analyzed using immunohistochemistry. RESULTS: The results showed that LNCaP-19 tumors grew more rapidly at the subcutaneous site than in the prostate, where tumors were obviously inhibited. Castration of the mice did not affect ectopic tumors but did result in increased tumor growth in the prostatic environment. This effect was reversed by testosterone treatment. In contrast to LNCaP-19, the LNCaP cells grew rapidly in the prostate and castration reduced tumor development. Gene expression analysis of LNCaP-19 tumors revealed an upregulation of genes, inhibiting tumor growth (including ADAMTS1, RGS2 and protocadherin 20) and a downregulation of genes, promoting cell adhesion and metastasis (including N-cadherin and NRCAM) in the slow-growing orthotopic tumors from intact mice. CONCLUSIONS: The results show that the prostatic environment has a varying impact on AD and AI tumor xenografts. Data indicate that the androgen-stimulated prostatic environment limits growth of orthotopic AI tumors through induction of genes that inhibit tumor growth and suppression of genes that promote cell adhesion and metastasis.
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| 4. |
- Tesan, Tajana, 1977, et al.
(author)
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Differential expression of angiopoietin-2 and vascular endothelial growth factor in androgen-independent prostate cancer models
- 2008
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In: BJU. ; 102:8, s. 1034-9
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Journal article (peer-reviewed)abstract
- ABSTRACT To investigate the relationship between microvessel density (MVD), blood vessel morphology and the expression of angiopoietin (Ang)-1, Ang-2, tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Tie)-2, and vascular endothelial growth factor (VEGF) in androgen-dependent (AD) and androgen-independent (AI) prostate cancer models, to gain insight into the regulation of angiogenesis at different stages of prostate cancer. MATERIALS AND METHODS MVD and blood vessel morphology were evaluated by CD34 immunohistochemical staining. The mRNA and protein secretion of the Angs, Tie-2 and VEGF were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively, in LNCaP (AD) and LNCaP-19, C4-2, C4–2B4 and PC-3 (AI) prostate cancer xenografts in mice. RESULTS LNCaP, C4-2 and C4–2B4 xenografts had high expression of Ang-2 and VEGF, similar MVD and blood vessel morphology. However, the most angiogenic cell line LNCaP-19 expressed low levels of both factors and had different vessel morphology. PC-3 xenografts had a similar MVD to LNCaP, C4-2 and C4–2B4, but the Ang-2 and VEGF expression as well as the vessel morphology were similar to LNCaP-19. CONCLUSION The differences in MVD, blood vessel morphology and the expression of Ang-2 and VEGF show that prostate cancer cells display angiogenic heterogeneity, which indicates different roles of these factors in the regulation of angiogenesis in different stages of prostate cancer.
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| 5. |
- Tesan, Tajana, 1977, et al.
(author)
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A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma
- 2017
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Journal article (peer-reviewed)abstract
- Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5' gene fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I-BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway activation compared to BRAF WT. Comparing fusion detection methods, we found Fluorescence in situ hybridization with BRAF break apart probe as the most sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Moreover, the consistency and growing list of BRAF/RAF gene fusions suggests these rearrangements to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.
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| 6. |
- Tomic, Tajana Tesan, et al.
(author)
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Castration resistant prostate cancer is associated with increased blood vessel stabilization and elevated levels of VEGF and Ang-2.
- 2012
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In: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 72:7, s. 705-12
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Journal article (peer-reviewed)abstract
- Angiogenesis is important for the progression of prostate cancer and may be a target for treatment in castration resistant (CR) disease. This study was performed to investigate blood vessel stabilization and expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) in CR and hormone naïve (HN) prostate cancer. The effect of androgen deprivation therapy (ADT) on these parameters was also studied.
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| 7. |
- Welén, Karin, 1970, et al.
(author)
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Pericyte coverage decreases invasion of tumour cells into blood vessels in prostate cancer xenografts.
- 2009
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In: Prostate cancer and prostatic diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 12:1, s. 41-6
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Journal article (peer-reviewed)abstract
- Androgen-independent prostate cancer is an aggressive disease with high angiogenic and metastatic potential. Increased microvessel density and altered invasion properties have previously been described in LNCaP-19, an androgen-independent subline to LNCaP. To characterize the differences in angiogenesis and invasion, the vessels of these tumour xenografts were investigated with immunohistochemistry, and the influence of tumour cells on endothelial cell migration, proliferation and tube formation was studied in vitro. The blood vessels of LNCaP were found to be stabilized by pericytes more frequently than vessels in LNCaP-19. Further, tumour cell invasion was decreased in pericyte-covered blood vessels in both the tumour types. LNCaP-19 displayed an increased potential to induce endothelial cell migration in vitro. In conclusion, pericyte coverage seems to be important for the invasion of tumour cells into blood vessels. Further, LNCaP-19 has lower pericyte coverage and an increased potential to induce endothelial cell migration, which reflects its high microvessel density.
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