37 results on '"Vult von Steyern F"'
Search Results
2. Giant-cell tumour of the knee: THE CONDITION OF THE CARTILAGE AFTER TREATMENT BY CURETTAGE AND CEMENTING
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Vult von Steyern, F., Kristiansson, I., Jonsson, K., Mannfolk, P., Heinegård, D., and Rydholm, A.
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- 2007
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3. Treatment of local recurrences of giant cell tumour in long bones after curettage and cementing: A SCANDINAVIAN SARCOMA GROUP STUDY
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Vult von Steyern, F., Bauer, H. C. F., Trovik, C., Kivioja, A., Bergh, P., Holmberg Jörgensen, P., Follerås, G., and Rydholm, A.
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- 2006
4. Protein secretion from mouse skeletal muscle: coupling of increased exocytotic and endocytotic activities in denervated muscle
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Vult von Steyern, F., Kanje, M., and Tågerud, S.
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- 1993
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5. Telomeric associations correlate with telomere length reduction and clonal chromosome aberrations in giant cell tumor of bone
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Gebre-Medhin, S., primary, Broberg, K., additional, Jonson, T., additional, Gorunova, L., additional, Vult von Steyern, F., additional, Brosjö, O., additional, Jin, Y., additional, Gisselsson, D., additional, Panagopoulos, I., additional, Mandahl, N., additional, and Mertens, F., additional
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- 2009
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6. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation
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Hallor, K H, primary, Staaf, J, additional, Jönsson, G, additional, Heidenblad, M, additional, Vult von Steyern, F, additional, Bauer, H C F, additional, IJszenga, M, additional, Hogendoorn, P C W, additional, Mandahl, N, additional, Szuhai, K, additional, and Mertens, F, additional
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- 2007
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7. Postnatal appearance of 5-HT2A receptors on fast flexor and slow extensor rat motor neurons
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Vult von Steyern, F., primary and Lømo, T., additional
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- 2005
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8. Rhodamine B, a fluorescent probe for acidic organelles in denervated skeletal muscle
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Vult von Steyern, F, Josefsson, J-O, Tågerud, Sven, Vult von Steyern, F, Josefsson, J-O, and Tågerud, Sven
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- 1996
9. Endocytotic activity of mouse skeletal muscle fibres after long-term denervation
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Vult von Steyern, F, Libelius, Rolf, Lawoko, G, Tågerud, Sven, Vult von Steyern, F, Libelius, Rolf, Lawoko, G, and Tågerud, Sven
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- 1994
10. Protein secretion from mouse skeletal muscle. Coupling of increased exocytotic and endocytotic activities in denervated muscle
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Vult von Steyern, F, Kanje, M, Tågerud, Sven, Vult von Steyern, F, Kanje, M, and Tågerud, Sven
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- 1993
11. Rhodamine B, a fluorescent probe for acidic organelles in denervated skeletal muscle.
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Vult von Steyern, F, primary, Josefsson, J O, additional, and Tågerud, S, additional
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- 1996
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12. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation.
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Hallor, K. H., Staaf, J., Jönsson, G., Heidenblad, M., Vult von Steyern, F., Bauer, H. C. F., IJszenga, M., Hogendoorn, P. C. W., Mandahl, N., Szuhai, K., Mertens, F., and Jönsson, G
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CHROMOSOMES ,CHORDOMA ,IN situ hybridization ,GENOMICS ,DNA ,KARYOTYPES - Abstract
The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development. [ABSTRACT FROM AUTHOR]
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- 2008
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13. Postnatal appearance of 5-HT2A receptors on fast flexor and slow extensor rat motor neurons
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Vult von Steyern, F. and Lømo, T.
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NEURONS , *NERVOUS system , *MOTOR ability , *COLLOIDS - Abstract
Abstract: Motor neurons to the slowly contracting extensor soleus muscle in behaving rats begin to fire tonically in the 2nd week after birth. In the adult, tonic firing becomes predominant and appears to arise from plateau potentials under monoaminergic control. In the present work, motor neurons to slowly contracting extensor soleus and rapidly contracting extensor digitorum longus, a physiological flexor muscle, were retrogradely labeled with fluorescent dextran and examined for immunoreactivity to 5-HT2A receptors in 1 and 2 week old and adult rats. No reactivity was detected at 1 week. At 2 weeks, reactivity was detected on 67% slowly contracting extensor soleus (16 of 24) and 19% extensor digitorum longus (11 of 57) motor neurons. In the adult, the intensity of staining was higher and the percentage of labeled motor neurons 79 for slowly contracting extensor soleus (34 of 43) and 31 for extensor digitorum longus (11 of 35). On slowly contracting extensor soleus motor neurons, labeling appeared more often on soma and dendrites than on dendrites only, whereas on extensor digitorum longus motor neurons, labeling appeared more often on dendrites only. These results are consistent with the hypothesis that serotonergic innervation contributes to the appearance and subsequent increase in tonic firing of rat slowly contracting extensor soleus motor neurons in postnatal development. [Copyright &y& Elsevier]
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- 2006
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14. Better referral of soft tissue sarcoma.
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Styring E, Rydholm A, and Vult von Steyern F
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- 2012
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15. Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features.
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Mitra S, Farswan A, Piccinelli P, Sydow S, Hesla A, Tsagkozis P, Vult von Steyern F, Almqvist M, Eriksson M, Magnusson L, Nilsson J, Pillay N, and Mertens F
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- Humans, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, DNA Copy Number Variations, Biomarkers, Tumor genetics, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms pathology, Gene Expression Regulation, Neoplastic, Genomics, Sweden, Fibrosarcoma genetics, Fibrosarcoma pathology, Transcriptome, Gene Expression Profiling methods, Sarcoma genetics, Sarcoma pathology, Mutation
- Abstract
Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
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- 2024
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16. The diagnostic utility of DNA copy number analysis of core needle biopsies from soft tissue and bone tumors.
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Köster J, Piccinelli P, Arvidsson L, Vult von Steyern F, Bedeschi Rego De Mattos C, Almquist M, Nilsson J, Magnusson L, and Mertens F
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- Biopsy, Large-Core Needle, DNA Copy Number Variations, Humans, Retrospective Studies, Bone Neoplasms diagnosis, Bone Neoplasms genetics, Soft Tissue Neoplasms diagnosis, Soft Tissue Neoplasms genetics
- Abstract
Morphologic and immunohistochemical analysis of preoperative core needle biopsies (CNB) is important in the management of patients with soft tissue and bone tumors (STBTs). Most SBTB subtypes have more or less extensive DNA copy number aberrations (CNA), potentially providing useful diagnostic information. To evaluate the technical feasibility of single nucleotide polymorphism (SNP) array analysis and the diagnostic usefulness of the copy number profiles, we studied CNBs from 171 patients with suspected STBTs. SNP array analysis could be performed on 168 (98%) of the samples. The CNA profile was compatible with the CNB diagnosis in 87% of the cases. Discrepant cases were dominated by false-negative results due to nonrepresentative material or contamination with normal cells. 70 genomic profiles were indicative of specific histopathologic tumor entities and in agreement with the corresponding CNB diagnoses in 83%. In 96 of the cases with aberrant CNA profiles, the SNP profiles were of sufficient quality for segmentation, allowing clustering analysis on the basis of the Jaccard similarity index. The analysis of these segment files showed three major CNA clusters, based on the complexity levels and the predominance of gains versus losses. For 43 of these CNB samples, we had SNP array data also from their corresponding surgical samples. In 33 of these pairs, the two corresponding samples clustered next to each other, with Jaccard scores ranging from 0.61 to 0.99 (median 0.96). Also, for those tumor pairs that did not cluster together, the Jaccard scores were relatively high (median 0.9). 10 cases showed discrepant results, mainly due to varying degrees of normal cell contamination or technical issues. Thus, the copy number profile seen in a CNB is typically highly representative of the major cell population in the tumor., (© 2022. The Author(s).)
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- 2022
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17. Late Local Recurrence and Metastasis in Soft Tissue Sarcoma of the Extremities and Trunk Wall: Better Outcome After Treatment of Late Events Compared with Early.
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von Konow A, Ghanei I, Styring E, and Vult von Steyern F
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- Extremities surgery, Humans, Margins of Excision, Neoplasm Recurrence, Local surgery, Retrospective Studies, Sarcoma surgery, Soft Tissue Neoplasms surgery
- Abstract
Background: Approximately 80% of soft tissue sarcoma (STS) recurrences, local and metastatic disease, are diagnosed within the first 3 years after primary diagnosis and treatment. Recurrences, however, can present after a longer period of remission. Our goal was to identify factors that may predict the risk of late recurrence., Methods: We identified 677 patients with STS of the extremities and trunk wall from a population-based sarcoma register. Of these, 377 patients were alive and event-free at 3 years and were included for analysis of possible risk factors for late recurrence., Results: Fifty-five of 377 (15%) patients developed late recurrence: 23 local recurrence, 21 metastasis, and 11 both manifestations. With R0 wide surgical margin as reference, R0 marginal (hazard ratio [HR] 2.6; p = 0.02) and R1 (HR 5.0; p = 0.005) margins were risk factors for late local recurrence. Malignancy grade (HR 8.3; p = 0.04) and R0 marginal surgical margin (HR 2.3; p = 0.04) were risk factors for late metastasis. We could not find a statistically significant correlation of late recurrence with many of the generally known risk factors for local recurrence and metastasis in STS. Outcome after treatment of late recurrences was better compared with outcome after treatment of early events., Conclusions: Late recurrences, albeit relatively rare, do occur. Outcome after treatment was good compared with outcome after early events. Long surveillance of all patients with high-grade STS, especially if R0 wide surgical margin is not achieved in the primary treatment, appear to be well justified., (© 2021. The Author(s).)
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- 2021
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18. High Recurrence Rate of Myxofibrosarcoma: The Effect of Radiotherapy Is Not Clear.
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Teurneau H, Engellau J, Ghanei I, Vult von Steyern F, and Styring E
- Abstract
Background: Myxofibrosarcoma (MFS) is one of the more common types of soft-tissue sarcoma (STS) in patients over 60 years of age. Local recurrence (LR) rates have been reported to be higher compared to other STS types., Patients and Methods: Using a population-based series from the southern Sweden health care region, 56 consecutive patients with MFS and localized disease at diagnosis were analyzed with respect to LR and distant metastases after surgery ± adjuvant treatment., Results: The overall local recurrence ( n = 15) and metastasis ( n = 13) rates were 27% and 21%, respectively; 6 patients had both. Surgical margin was the only statistically significant prognostic factor for LR. Patients operated with a marginal margin had an HR of 4.5 (CI 1.3-15.1, p =0.02) and those operated with an intralesional margin 9.4 (CI 2.0-43.5, p =0.004) compared to those operated with a wide surgical margin. There was no difference in the LR rate depending on radiotherapy or not, although the latter group had smaller and more superficial tumors. 23 patients received radiotherapy, 9 of whom developed LR, all within the irradiated field. A tumor size >5 cm and intralesional surgical margin were shown to be risk factors for distant metastases., Conclusions: The rate of LR for patients with myxofibrosarcoma was high. The impact of RT on local tumor control was unclear. The surgical margin was important for both local and distant tumor control. Large tumor size was a risk factor for distant metastasis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2019 Hjalmar Teurneau et al.)
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- 2019
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19. Different patterns of clonal evolution among different sarcoma subtypes followed for up to 25 years.
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Hofvander J, Viklund B, Isaksson A, Brosjö O, Vult von Steyern F, Rissler P, Mandahl N, and Mertens F
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- Chromosome Aberrations, Chromosome Banding, Chromosomes ultrastructure, Follow-Up Studies, Gene Fusion, Humans, Mutation, Nucleotides chemistry, Oncogene Proteins, Fusion genetics, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Transcription Factor CHOP genetics, Clonal Evolution, Liposarcoma genetics, Liposarcoma, Myxoid genetics, Neoplasm Recurrence, Local, Sarcoma genetics
- 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.
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- 2018
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20. Inflammatory leiomyosarcoma is a distinct tumor characterized by near-haploidization, few somatic mutations, and a primitive myogenic gene expression signature.
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Arbajian E, Köster J, Vult von Steyern F, and Mertens F
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- Adolescent, Adult, Female, Gene Expression Profiling, Humans, Inflammation genetics, Inflammation pathology, Leiomyosarcoma pathology, Male, Mutation, Polymorphism, Single Nucleotide, Soft Tissue Neoplasms pathology, Transcriptome, Young Adult, Leiomyosarcoma genetics, Soft Tissue Neoplasms genetics
- Abstract
Inflammatory leiomyosarcoma is a soft-tissue tumor resembling conventional leiomyosarcoma, but with a prominent intrinsic inflammatory component. Previous studies have suggested that inflammatory leiomyosarcoma differs genetically from leiomyosarcoma, but in-depth analyses are lacking. Here we provide a comprehensive picture of the genome and transcriptome of inflammatory leiomyosarcoma by combining cytogenetic, single-nucleotide polymorphism array, mRNA-sequencing, and whole-exome sequencing data. The results show that inflammatory leiomyosarcoma has a specific genetic profile characterized by near-haploidization with or without subsequent whole-genome doubling. Consistently, both parental copies of chromosomes 5 and 22 are preserved. Apart from recurrent mutation of the NF1 gene, additional somatic events that could serve as driver mutations were not found at either the nucleotide or the genome level. Furthermore, no fusion transcripts were identified. Global gene expression profiling revealed particularly prominent differential expression of genes, including ITGA7, MYF5, MYF6, MYOD1, MYOG, and PAX7, involved in muscle development and function, providing strong argument for grouping inflammatory leiomyosarcoma with myogenic sarcomas, rather than with myofibroblastic lesions. Combined with previously published data, there are now 10 cases of inflammatory leiomyosarcoma with confirmed near-haploid genotype. These patients differ from leiomyosarcoma patients in being younger (median 41 years), showing a male predominance (9:1), and few relapses (1 of 8 informative patients). Thus, the clinical, morphological, and genetic data provide compelling support for inflammatory leiomyosarcoma being a distinct subtype of myogenic tumors.
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- 2018
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21. The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma.
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Trovik C, Bauer HCF, Styring E, Sundby Hall K, Vult Von Steyern F, Eriksson S, Johansson I, Sampo M, Laitinen M, Kalén A, Jónsson H Jr, Jebsen N, Eriksson M, Tukiainen E, Wall N, Zaikova O, Sigurðsson H, Lehtinen T, Bjerkehagen B, Skorpil M, Egil Eide G, Johansson E, and Alvegard TA
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- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Child, Child, Preschool, Extremities, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local epidemiology, Referral and Consultation statistics & numerical data, Registries, Sarcoma diagnosis, Sarcoma epidemiology, Sarcoma pathology, Sarcoma secondary, Scandinavian and Nordic Countries epidemiology, Soft Tissue Neoplasms diagnosis, Soft Tissue Neoplasms epidemiology, Soft Tissue Neoplasms pathology, Torso, Sarcoma therapy, Soft Tissue Neoplasms therapy
- Abstract
Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.
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- 2017
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22. Radiation-associated angiosarcoma after breast cancer: improved survival by excision of all irradiated skin and soft tissue of the thoracic wall? A report of six patients.
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Styring E, Klasson S, Rydholm A, and Vult von Steyern F
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- Adult, Aged, Breast Neoplasms radiotherapy, Female, Humans, Middle Aged, Thoracic Wall, Hemangiosarcoma surgery, Neoplasms, Radiation-Induced surgery, Skin pathology, Subcutaneous Tissue surgery
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- 2015
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23. Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma.
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Hofvander J, Tayebwa J, Nilsson J, Magnusson L, Brosjö O, Larsson O, Vult von Steyern F, Mandahl N, Fletcher CD, and Mertens F
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- Abnormal Karyotype, Humans, In Situ Hybridization, Fluorescence, Mediator Complex genetics, Real-Time Polymerase Chain Reaction, Repressor Proteins genetics, Reverse Transcriptase Polymerase Chain Reaction, Trans-Activators genetics, DNA-Binding Proteins genetics, Gene Fusion genetics, Sarcoma genetics, Soft Tissue Neoplasms genetics, Transcription Factors genetics
- Abstract
Purpose: Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about one third. No tumor-specific rearrangement has been identified, and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions., Experimental Design: RNA-Seq, FISH, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas., Results: Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3' partner and either MED12 or CITED2 as the 5' partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before., Conclusions: Our results suggest that PRDM10 fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS., (©2014 American Association for Cancer Research.)
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- 2015
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24. Oral contraceptive use, parity, and constitutional characteristics in soft tissue sarcoma: a Swedish population-based case-control study 1988-2009.
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Wagner P, Alvegård T, Ranstam J, Rydholm A, Vult von Steyern F, and Olsson H
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- Adult, Aged, Body Composition, Case-Control Studies, Contraceptives, Oral adverse effects, Female, Histiocytoma epidemiology, Histiocytoma etiology, Humans, Leiomyosarcoma epidemiology, Leiomyosarcoma etiology, Liposarcoma epidemiology, Liposarcoma etiology, Middle Aged, Nerve Sheath Neoplasms epidemiology, Nerve Sheath Neoplasms etiology, Odds Ratio, Parity, Pregnancy, Risk Factors, Sarcoma etiology, Surveys and Questionnaires, Sweden epidemiology, Young Adult, Contraceptives, Oral administration & dosage, Sarcoma epidemiology
- Abstract
Purpose: The study was designed to investigate the influence of surrogate factors associated with sex (SH) and growth hormones (GH) on the risk of developing soft tissue sarcomas (STS)., Background and Methods: The etiology of soft tissue sarcoma is largely unknown. We have studied the effect of hormone related factors on STS in the Swedish population between 1988 and 2009 using a population-based matched case-control design., Results: Our study is the largest on this topic to date, including 634 cases in a primary matched analysis and 855 cases in an unmatched sensitivity analysis. We identified protective effects connected to constitutional characteristics, hormonal and reproductive factors. Being shorter than your peers at age 11 was associated with an odds ratio (OR) of 0.51 (0.36-0.74). Having used oral contraceptives (OC), OR 0.75 (0.49-1.15), and high parity, OR 0.16 (0.04-0.63), comparing three or more children to two or less, also appeared to reduce the risk of STS. The risk was further reduced with the duration of OC use (p = 0.01), comparing use for 11 years or more to use for 3 years or less yielded an OR of 0.10 (0.02-0.41). No effect was observed for ever having had perimenopausal hormone therapy OR 1.02 (0.70-1.47). The effect of BMI varied significantly with subtype (p = 0.03) and tumor location (p < 0.001)., Conclusions: We observed surrogates of SH, GH, and insulin-like growth factor 1 to be associated with STS development. These findings are important as they may connect STSs to the group of hormone-dependent tumors, potentially revealing common treatment and prevention targets.
- Published
- 2014
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25. Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma.
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Płaszczyca A, Nilsson J, Magnusson L, Brosjö O, Larsson O, Vult von Steyern F, Domanski HA, Lilljebjörn H, Fioretos T, Tayebwa J, Mandahl N, Nord KH, and Mertens F
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- Adult, Carrier Proteins genetics, Carrier Proteins isolation & purification, Chromosome Banding, Endosomes genetics, Endosomes pathology, Female, Histiocytoma, Benign Fibrous pathology, Humans, In Situ Hybridization, Fluorescence, Intracellular Signaling Peptides and Proteins, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins isolation & purification, Membrane Proteins isolation & purification, Middle Aged, Oncogene Proteins, Fusion isolation & purification, Polymorphism, Single Nucleotide, Protein Kinase C beta isolation & purification, Protein Kinase C-delta isolation & purification, Signal Transduction, Tetraspanin 30 genetics, Tetraspanin 30 isolation & purification, Histiocytoma, Benign Fibrous genetics, Membrane Proteins genetics, Oncogene Proteins, Fusion genetics, Protein Kinase C beta genetics, Protein Kinase C-delta genetics
- Abstract
Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs in the skin (so-called dermatofibroma), but may also appear in soft tissues (so-called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The origin of BFH is unknown, and it has been questioned whether it is a true neoplasm. Chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs were found to harbor recurrent fusions of genes encoding membrane-associated proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C (PKC) isoforms PRKCB and PRKCD. PKCs are serine-threonine kinases that through their many phosphorylation targets are implicated in a variety of cellular processes, as well as tumor development. When inactive, the amino-terminal, regulatory domain of PKCs suppresses the activity of their catalytic domain. Upon activation, which requires several steps, they typically translocate to cell membranes, where they interact with different signaling pathways. The detected PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or LAMTOR1 and the entire catalytic domain of the PKC. This novel pathogenetic mechanism should result in constitutive kinase activity at an ectopic location. The results show that BFH indeed is a true neoplasm, and that distorted PKC activity is essential for tumorigenesis. The findings also provide means to differentiate BFH from other skin and soft tissue tumors. This article is part of a Directed Issue entitled: Rare cancers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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26. Integrative genome and transcriptome analyses reveal two distinct types of ring chromosome in soft tissue sarcomas.
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Nord KH, Macchia G, Tayebwa J, Nilsson J, Vult von Steyern F, Brosjö O, Mandahl N, and Mertens F
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- Adult, Aged, Aged, 80 and over, Cyclin-Dependent Kinase 4 genetics, Female, Gene Amplification, Gene Expression Profiling, Genetic Association Studies, Genome, Human, HMGA2 Protein genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-mdm2 genetics, Proto-Oncogene Proteins c-mdm2 metabolism, Retinoblastoma Protein genetics, Sarcoma metabolism, Sarcoma mortality, Soft Tissue Neoplasms metabolism, Soft Tissue Neoplasms mortality, Ring Chromosomes, Sarcoma genetics, Soft Tissue Neoplasms genetics, Transcriptome
- Abstract
Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their content varies considerably between and within tumors. Partly due to this extensive variation, the genetic content of many ring-containing tumors remains poorly characterized. Ring chromosomes are particularly prevalent in specific subtypes of sarcoma. Here, we have combined fluorescence in situ hybridization (FISH), global genomic copy number and gene expression data on ring-containing soft tissue sarcomas and show that they harbor two fundamentally different types of ring chromosome: MDM2-positive and MDM2-negative rings. While the former are often found in an otherwise normal chromosome complement, the latter seem to arise in the context of general chromosomal instability. In line with this, sarcomas with MDM2-negative rings commonly show complete loss of either CDKN2A or RB1 -both known to be important for genome integrity. Sarcomas with MDM2-positive rings instead show co-amplification of a variety of potential driver oncogenes. More than 100 different genes were found to be involved, many of which are known to induce cell growth, promote proliferation or inhibit apoptosis. Several of the amplified and overexpressed genes constitute potential drug targets.
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- 2014
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27. Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors of the Wnt/beta-catenin signaling pathway.
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Nord KH, Nilsson J, Arbajian E, Vult von Steyern F, Brosjö O, Cleton-Jansen AM, Szuhai K, and Hogendoorn PC
- Subjects
- Adolescent, Adult, Child, Cluster Analysis, DNA Copy Number Variations, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Mutation, Polymorphism, Single Nucleotide, Young Adult, Bone Neoplasms genetics, Bone Neoplasms metabolism, Chromosome Deletion, Chromosomes, Human, Pair 22, Osteoblastoma genetics, Osteoblastoma metabolism, Wnt Signaling Pathway
- Abstract
Osteoblastoma is a bone forming tumor with histological features highly similar to osteoid osteoma; the discrimination between the tumor types is based on size and growth pattern. The vast majority of osteoblastomas are benign but there is a group of so-called aggressive osteoblastomas that can be diagnostically challenging at the histopathological level. The genetic aberrations required for osteoblastoma development are not known and no genetic difference between conventional and aggressive osteoblastoma has been reported. In order to identify recurrent genomic aberrations of importance for tumor development we applied cytogenetic and/or SNP array analyses on nine conventional and two aggressive osteoblastomas. The conventional osteoblastomas showed few or no acquired genetic aberrations while the aggressive tumors displayed heavily rearranged genomes. In one of the aggressive osteoblastomas, three neighboring regions in chromosome band 22q12 were homozygously deleted. Hemizygous deletions of these regions were found in two additional cases, one aggressive and one conventional. In total, 10 genes were recurrently and homozygously lost in osteoblastoma. Four of them are functionally involved in regulating osteogenesis and/or tumorigenesis. MN1 and NF2 have previously been implicated in the development of leukemia and solid tumors, and ZNRF3 and KREMEN1 are inhibitors of the Wnt/beta-catenin signaling pathway. In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma.
- Published
- 2013
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28. A novel GTF2I/NCOA2 fusion gene emphasizes the role of NCOA2 in soft tissue angiofibroma development.
- Author
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Arbajian E, Magnusson L, Mertens F, Domanski HA, Vult von Steyern F, and Nord KH
- Subjects
- Adult, Base Sequence, Chromosome Breakage, Chromosomes, Human, Pair 7, Female, Humans, Oncogene Proteins, Fusion genetics, Angiofibroma genetics, Nuclear Receptor Coactivator 2 genetics, Transcription Factors, TFII genetics
- Published
- 2013
- Full Text
- View/download PDF
29. Recurrent rearrangement of the PHF1 gene in ossifying fibromyxoid tumors.
- Author
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Gebre-Medhin S, Nord KH, Möller E, Mandahl N, Magnusson L, Nilsson J, Jo VY, Vult von Steyern F, Brosjö O, Larsson O, Domanski HA, Sciot R, Debiec-Rychter M, Fletcher CD, and Mertens F
- Subjects
- Adult, Aged, Aged, 80 and over, Base Sequence, Bone Neoplasms pathology, Cell Shape, Chromosome Breakage, Chromosomes, Human genetics, Cytogenetic Analysis, Female, Fibroma, Ossifying pathology, Humans, In Situ Hybridization, Fluorescence, Male, Metaphase, Middle Aged, Molecular Sequence Data, Paraffin Embedding, Polycomb-Group Proteins, Polymerase Chain Reaction, Polymorphism, Single Nucleotide genetics, Recurrence, Bone Neoplasms genetics, DNA-Binding Proteins genetics, Fibroma, Ossifying genetics, Gene Rearrangement genetics, Transcription Factors genetics
- Abstract
Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor of unknown lineage. Although most cases are histologically and clinically benign, some show malignant morphological features and local recurrences are not uncommon; a few may even metastasize. In the present study, cytogenetic analysis identified different structural rearrangements of chromosome band 6p21 in tumor cells from three cases of OFMT, including one with typical, one with atypical, and one with malignant morphological features. Mapping of the 6p21 breakpoint by fluorescence in situ hybridization (FISH) indicated that the PHF1 gene was rearranged in all three cases. Further FISH, 5'-rapid amplification of cDNA ends, and RT-PCR analyses disclosed an EP400/PHF1 fusion transcript in one of the cases. Interphase FISH on tumor sections from 13 additional cases of OFMT showed rearrangement of the PHF1 locus in four of four typical, two of three atypical, and one of six malignant lesions. Thus, the PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of OFMTs, irrespective of whether they are diagnosed as typical, atypical, or malignant lesions. The PHF1 protein interacts with the polycomb-repressive complex 2 (PRC2), which, in turn, regulates the expression of a variety of developmental genes. Thus, the results indicate that deregulation of PRC2 target genes is crucial for OFMT development., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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30. Complications and survival after surgical treatment of 214 metastatic lesions of the humerus.
- Author
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Wedin R, Hansen BH, Laitinen M, Trovik C, Zaikova O, Bergh P, Kalén A, Schwarz-Lausten G, Vult von Steyern F, Walloe A, Keller J, and Weiss RJ
- Subjects
- Adult, Aged, Aged, 80 and over, Analysis of Variance, Bone Nails, Bone Neoplasms surgery, Bone Plates, Cohort Studies, Confidence Intervals, Disease-Free Survival, Female, Fracture Fixation, Internal mortality, Fractures, Spontaneous diagnostic imaging, Fractures, Spontaneous mortality, Humans, Humeral Fractures diagnostic imaging, Humeral Fractures mortality, Humerus surgery, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Neoplasm Invasiveness pathology, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Neoplasm Staging, Postoperative Complications mortality, Postoperative Complications physiopathology, Postoperative Complications surgery, Prognosis, Proportional Hazards Models, Prostheses and Implants, Radiography, Registries, Reoperation, Retrospective Studies, Risk Assessment, Survival Analysis, Sweden, Bone Neoplasms mortality, Bone Neoplasms secondary, Fracture Fixation, Internal methods, Fractures, Spontaneous surgery, Humeral Fractures surgery, Humerus pathology
- Abstract
Background: The humerus is the second most common long-bone site of metastatic bone disease. We report complications, risk factors for failure, and survival of a large series of patients operated on for skeletal metastases of the humerus., Materials and Methods: This study was based on 208 patients treated surgically for 214 metastatic lesions of the humerus. Reconstructions were achieved by intramedullary nails in 148, endoprostheses in 35, plate fixation in 21, and by other methods in 10., Results: The median age at surgery was 67 years (range, 29-87 years). Breast cancer was the primary tumor in 31%. The overall failure rate of the surgical reconstructions was 9%. The reoperation rate was 7% in the proximal humerus, 8% in the diaphysis, and 33% in the distal part of the bone. Among 36 operations involving an endoprosthesis, 2 were failures (6%) compared with 18 of 178 osteosynthetic devices (10%). In the osteosynthesis group, intramedullary nails failed in 7% and plate fixation failed in 22%. Multivariate Cox regression analysis showed that prostate cancer was associated with an increased risk of failure after surgery (hazard ratio, 7; P < 0.033). The cumulative survival after surgery was 40% (95% confidence interval [CI] 34-47) at 1 year, 21% (95% CI, 15-26) at 2 years, and 16% (95% CI, 12-19) at 3 years., Conclusions: Our method of choice is the cemented hemiprosthesis for pathologic proximal humeral fractures and interlocked intramedullary nail for lesions in the diaphysis. Pathologic fractures in the distal humerus are uncommon and associated with a very high reoperation rate., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
31. Radiation-associated angiosarcoma after breast cancer: high recurrence rate and poor survival despite surgical treatment with R0 resection.
- Author
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Seinen JM, Styring E, Verstappen V, Vult von Steyern F, Rydholm A, Suurmeijer AJ, and Hoekstra HJ
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms mortality, Breast Neoplasms surgery, Combined Modality Therapy, Female, Follow-Up Studies, Hemangiosarcoma etiology, Hemangiosarcoma surgery, Humans, Middle Aged, Neoplasm Recurrence, Local etiology, Neoplasm Recurrence, Local surgery, Neoplasm Staging, Neoplasms, Radiation-Induced etiology, Neoplasms, Radiation-Induced surgery, Prognosis, Radiotherapy mortality, Retrospective Studies, Survival Rate, Tertiary Care Centers, Breast Neoplasms radiotherapy, Hemangiosarcoma mortality, Mastectomy mortality, Neoplasm Recurrence, Local mortality, Neoplasms, Radiation-Induced mortality, Radiotherapy adverse effects
- Abstract
Background: Secondary angiosarcoma of the breast is a rare but severe long-term complication of breast cancer treated with breast-conserving surgery and radiotherapy. We characterized a population-based cohort of patients with secondary angiosarcomas from two tertiary hospitals to investigate this complication with respect to surgical treatment and outcome., Methods: We identified 35 patients with a history of radiation for breast cancer that developed angiosarcoma in the irradiated field from 1990 to 2009. Of these, 31 underwent surgery and were included for analysis., Results: Angiosarcoma developed after median 7 years (range 3-25 years). R0 resection was obtained in 23 of 31 patients after primary treatment. Local recurrence developed in 19 patients after median 6 months (range 1-89 months). Regional and distant metastases occurred in 13 patients after median 17 months (range 2-50 months); nine which also had local recurrence. Patients whose local recurrence could be operated on had a better survival after treatment than those who were not considered for surgical treatment, median 34 months (range 6-84 months) compared with 6 months (range 5-24 months). The median disease-free survival and disease-specific survival was 16 and 37 months, respectively., Conclusions: Despite R0 resection, two-thirds of the patients developed a local recurrence. Survival among those with local recurrence was better if the patient could be treated with surgery. Overall, the prognosis was dismal and median DSS was just over 3 years.
- Published
- 2012
- Full Text
- View/download PDF
32. Changing clinical presentation of angiosarcomas after breast cancer: from late tumors in edematous arms to earlier tumors on the thoracic wall.
- Author
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Styring E, Fernebro J, Jönsson PE, Ehinger A, Engellau J, Rissler P, Rydholm A, Nilbert M, and Vult von Steyern F
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms pathology, Cohort Studies, Edema epidemiology, Edema pathology, Female, Hemangiosarcoma epidemiology, Hemangiosarcoma pathology, Humans, Middle Aged, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local pathology, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary pathology, Prognosis, Arm, Breast Neoplasms therapy, Edema etiology, Hemangiosarcoma etiology, Neoplasm Recurrence, Local etiology, Neoplasms, Second Primary etiology, Thoracic Wall pathology
- Abstract
Angiosarcoma is a rare complication of breast cancer treatment. In order to define predictors, clinical presentation, and outcome, we characterized a population-based 50-year cohort of angiosarcomas after breast cancer. Clinical data were collected from all females with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008 in the Southern Swedish health care region. In total, 31 angiosarcomas developed at a median age of 71 years. The patients formed two distinct groups; 14 females treated for breast cancer with radical mastectomy and radiotherapy 1949-1988 developed angiosarcomas in edematous arms (Stewart-Treves syndrome) after median 11 years, and 17 females treated by segmental resection, anti-hormonal treatment and radiotherapy 1980-2005 developed angiosarcomas in the irradiated field on the thoracic wall after median 7.3 years. The clinical presentations were heterogeneous and included hematoma-like lesions, multiple bluish-reddish nodules, and asymptomatic lumps. The overall 5-year survival was 16%. In this population-based cohort, the early angiosarcomas developed in edematous arms after radical mastectomies, whereas more recent cases occurred after a shorter time period in the irradiated fields following breast conserving surgery. We conclude that the clinical presentation of angiosarcomas has changed, parallel with altered treatment principles for breast cancer.
- Published
- 2010
- Full Text
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33. Cytogenetic analysis of 101 giant cell tumors of bone: nonrandom patterns of telomeric associations and other structural aberrations.
- Author
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Gorunova L, Vult von Steyern F, Storlazzi CT, Bjerkehagen B, Follerås G, Heim S, Mandahl N, and Mertens F
- Subjects
- Adolescent, Adult, Aged, Chromosome Breakage, Cytogenetic Analysis methods, Female, Giant Cell Tumor of Bone diagnosis, Humans, In Situ Hybridization, Fluorescence methods, Karyotyping, Male, Middle Aged, Prognosis, Statistics, Nonparametric, Tumor Cells, Cultured, Chromosome Aberrations, Giant Cell Tumor of Bone genetics, Telomere genetics
- Abstract
Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor with metastatic potential. We performed cytogenetic analysis on 101 GCTB from 92 patients. Karyotypes were obtained from 95 tumors, 47 of which had clonal aberrations. The majority of the cytogenetically abnormal GCTB had multiple, up to 28 per tumor, clones. Clonal telomeric associations (tas) and other structural and numerical changes were found in about 70, 60, and 30%, respectively, of clonally abnormal tumors. Forty-seven aberrations were recurrent, of which 35 are novel. The vast majority of the recurrent aberrations were tas, confirming the important role of telomeric fusions in the development of GCTB. The frequency of tas in GCTB cultures increased with passaging, suggesting a selective advantage of tas-positive cells in vitro. The termini most frequently involved in tas were 22p, 13p, 15p, 21p, 14p, 19q, 1q, 12p, 11p, and 20q. The frequency of tas (irrespective of their clonality) was significantly higher in tumors carrying clonal changes, indicating that tas are precursors of other types of aberrations. In line with this assumption, the chromosomes preferentially involved in tas in a given tumor were also the ones most often affected by other rearrangements. We did not find the previously reported amplicon in 20q11.1, assessed by fluorescence in situ hybridization in 10 tumors. Nor did we find any association between cytogenetic features and adverse clinical outcome. Thus, local recurrences probably depend more on the adequacy of surgical treatment than on the intrinsic biology of the tumors.
- Published
- 2009
- Full Text
- View/download PDF
34. Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.
- Author
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Hallor KH, Staaf J, Bovée JV, Hogendoorn PC, Cleton-Jansen AM, Knuutila S, Savola S, Niini T, Brosjö O, Bauer HC, Vult von Steyern F, Jonsson K, Skorpil M, Mandahl N, and Mertens F
- Subjects
- Cyclin-Dependent Kinase Inhibitor p16 genetics, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Female, Gene Dosage genetics, Gene Expression Profiling, Humans, Male, Metalloproteases genetics, Metalloproteases metabolism, Middle Aged, N-Acetylglucosaminyltransferases genetics, N-Acetylglucosaminyltransferases metabolism, Sequence Deletion genetics, Bone Neoplasms genetics, Bone Neoplasms pathology, Chondrosarcoma genetics, Chondrosarcoma pathology, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 8 genetics
- Abstract
Purpose: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification., Experimental Design: The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were obtained in a subset of the tumors., Results: Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Several apparently distinctive aberrations affecting conventional central and peripheral tumors, respectively, were identified. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1, and EXT2 genes. The chromosomal imbalances in two distinct groups of predominantly near-haploid and near-triploid tumors, respectively, support the notion that polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of chondrosarcoma progression. Increasing patient age as well as tumor grade were associated with adverse outcome, but no copy number imbalance affected metastasis development or tumor-associated death., Conclusion: Despite similarities in the overall genomic patterns, the present findings suggest that some regions are specifically altered in conventional central and peripheral tumors, respectively.
- Published
- 2009
- Full Text
- View/download PDF
35. The homeodomain transcription factors Islet 1 and HB9 are expressed in adult alpha and gamma motoneurons identified by selective retrograde tracing.
- Author
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Vult von Steyern F, Martinov V, Rabben I, Njå A, de Lapeyrière O, and Lømo T
- Subjects
- Animals, Dextrans, Female, Fluorescent Dyes, Gene Expression physiology, Homeodomain Proteins genetics, Male, Mice, Mice, Inbred Strains, Motor Neurons classification, Muscle, Skeletal innervation, Rats, Rats, Wistar, Homeodomain Proteins metabolism, Motor Neurons metabolism, Trans-Activators metabolism, Transcription Factors metabolism
- Abstract
To study gene expression in differentiated adult motoneuron subtypes, we used fluorescent dextrans for both anterograde and retrograde axonal tracing in adult rat and mouse. Application of these dyes to the cut distal and proximal ends of small extramuscular nerve branches revealed both the peripheral ramifications and the cell bodies of subsets of motoneurons. We show that the soleus muscle is innervated by two nerve branches, one of which contains gamma motor and sensory axons but no alpha motor axons. By retrograde tracing of this branch, we selectively labelled gamma motoneurons. In adult rat, the nerves innervating the soleus and extensor digitorum longus muscles contain almost exclusively axons innervating slow (type I) and fast (type 2) muscle fibres, respectively. We selectively labelled slow and fast type motoneurons by retrograde tracing of these nerves. With immunocytochemistry we show that adult motoneurons express several homeodomain genes that are associated with motoneuron differentiation during early embryonic development. Combining selective retrograde labelling with immunocytochemistry we compared the expression patterns in alpha and gamma motoneurons. The homeodomain transcription factors Islet 1 and HB9 were expressed in slow and fast alpha motoneurons and in soleus gamma motoneurons. Motoneurons in each population varied in their intensity of the immunostaining, but no factor or combination of factors was unique to any one population.
- Published
- 1999
- Full Text
- View/download PDF
36. Secretion of plasminogen activator and lysosomal enzymes from mouse skeletal muscle: effect of denervation.
- Author
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Vult von Steyern F and Josefsson JO
- Subjects
- Animals, Brefeldin A, Cold Temperature, Cyclopentanes pharmacology, Glucuronidase metabolism, Male, Mannans pharmacology, Mice, beta-Galactosidase metabolism, Lysosomes enzymology, Muscle Denervation, Muscles enzymology, Plasminogen Activators metabolism, Urokinase-Type Plasminogen Activator metabolism
- Abstract
Levels of hydrolytic enzymes increase in skeletal muscle after denervation and their activities in the extracellular matrix appear to be important for interaction between muscle and nerve. Using enzymatic assays for beta-glucuronidase, beta-galactosidase, and plasminogen activator, we show that secretion of these enzymes from mouse skeletal muscle increases after denervation and that drugs interfering with the secretory pathway or the reuptake of enzymes modulate this release. Thus, brefeldin A inhibited secretion of plasminogen activator activity and mannan increased secreted amounts of beta-glucuronidase, but not of beta-galactosidase, in denervated muscle. In innervated muscle, brefeldin A decreased secreted activity of plasminogen activator, but mannan had no effect on secretion of either beta-glucuronidase or beta-galactosidase. Furthermore, secretion of plasminogen activator was temperature dependent. These observations, together with previous studies, suggest that secretion of hydrolytic enzymes from adult skeletal muscle may be of physiological significance in nerve-muscle communication.
- Published
- 1995
- Full Text
- View/download PDF
37. Endocytotic activity of mouse skeletal muscle fibres after long-term denervation.
- Author
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Vult von Steyern F, Libelius R, Lawoko G, and Tågerud S
- Subjects
- Animals, Horseradish Peroxidase, Lysosomes physiology, Male, Mice, Mice, Inbred Strains, Microscopy, Electron, Models, Biological, Motor Endplate ultrastructure, Muscles ultrastructure, Nerve Regeneration, Phrenic Nerve injuries, Phrenic Nerve physiology, Endocytosis, Muscle Denervation, Muscles physiopathology
- Abstract
The endocytotic activity of skeletal muscle fibres and its relation to the denervated endplate region has been studied using horseradish peroxidase (HRP) as marker for endocytosis. In muscles denervated for a short time period (10-20 days) HRP-uptake occurred in small segments of the muscle fibres near the centre of the muscle (endplate region). After long-term denervation (6-12 months) similar segments with high endocytotic activity were seen preferentially in more peripheral parts of the muscle fibres. Ultrastructural characteristics of segments with high endocytotic activity from long-term denervated muscle fibres include a proliferating transverse tubular system, HRP-containing bodies of different sizes with some very large vacuoles extending over several sarcomeres. These characteristics are similar to those described previously for HRP-uptake in the endplate region of short-term denervated muscle (Tågerud et al., J. Neurol. Sci., 75 (1986) 141) except that no recognizable endplate structures were observed in the present study. The results are discussed in relation to the fate of the denervated endplate and the receptive capacity for synapse formation in long-term denervated muscle.
- Published
- 1994
- Full Text
- View/download PDF
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