High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.

Directory of Open Access Journals (Sweden)

Makoto Emori

Full Text Available Epithelioid sarcoma (ES is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high cells correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009. In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.

A general aspect on soft-tissue sarcoma and c-kit expression in primitive neuroectodermal tumor and Ewings sarcoma

International Nuclear Information System (INIS)

Kara, Ismail O.; Sahin, B.; Gonlusen, G.; Ergin, M.; Erdogan, S.

2005-01-01

Within soft-tissue sarcoma, primitive neuroectodermal tumors have been shown to cover a wide spectrum of small round cell sarcomas, including Ewings sarcomas (Es) and primitive neuroectodermal tumors (PET). The role of the stem cell factor/kit pathway has been investigated in different human tumors especially in chronic metallically leukemia and gastrointestinal stromal tumor and an autocrine loop has been assumed in small cell lung carcinoma, and recently in Es and PET. Our aim is to investigate the c-kit expression in Es and PET and also to assessed if c-kit has any role in disease process. We thoroughly searched the archives of the Department of Pathology, Faculty of Medicine, Cukurova University Turkey, between 2000 and 2004; and found 14 ES and 14 PNET paraffin embedded tissues. We carried out the detection of the c-kit expression by immunohistochemical staining. The patients median age was 23.7 +/-14.6 (12 male and 16 female). Five were diagnosed as metastatic disease whereas 23 were diagnosed as non-metastatic disease at admission. The mean follow up period was 38.9 +/- 22.3 months. The main localization of the disease was lower extremity (32.1%), and others were as follows: head and neck 25%, thorax and abdomen 14.3%, pelvic and upper extremity 7.1% (11 were localized skeletal and 17 were extraskeletal). According to treatment modalities, 10 were treated with surgery alone, 11 with surgery and chemotherapy, and 7 with surgery, radiation therapy and also with chemotherapy. The primary tumor was lower than 5 cm in its dimension in 21 patients. While in 5 patients, tumor was more than 5 cm but did not exceed 10 cm, it was >10 cm in 2 patients. The c-kit expression was positive in 7 patients both cytoplasmic and membranously, whereas 8 patients were positive cytoplasmically. In 5 PNET patients, c-kit expression were stained immunohistochemically in over 50% and in 3 of ES patients. There was no significant correlation between c-kit expression and gender

Procholecystokinin as marker of human Ewing sarcomas

DEFF Research Database (Denmark)

Reubi, Jean Claude; Koefoed, Pernille; Hansen, Thomas von O

2004-01-01

PURPOSE: Ewing sarcoma is a rapidly growing mesenchymal tumor in young adults. Although it was shown previously to express the cholecystokinin (CCK) gene, it is unknown whether CCK gene expression is detectable at protein level in Ewing sarcoma tumor cell lines, in tumor tissue, and in plasma from...... Ewing sarcoma patients, and, if so, whether CCK peptides might play a role as tumor markers. EXPERIMENTAL DESIGN: CCK gene expression was evaluated with in situ hybridization or reverse transcription-PCR in tumor tissue. CCK precursors and bioactive CCK were measured with specific RIAs in tumor tissue......, in cell culture medium, and in plasma of Ewing sarcoma patients before and after chemotherapy as well as after tumor recurrence. RESULTS: CCK mRNA was identified in 12 Ewing sarcoma biopsies sampled in two series and in four Ewing sarcoma cell lines but not in unrelated neoplasia. Immunoreactive pro...

Different Expression and Localization of Phosphoinositide Specific Phospholipases C in Human Osteoblasts, Osteosarcoma Cell Lines, Ewing Sarcoma and Synovial Sarcoma

Directory of Open Access Journals (Sweden)

V.Vasco

2017-06-01

Full Text Available Background: Bone hardness and strength depends on mineralization, which involves a complex process in which calcium phosphate, produced by bone-forming cells, was shed around the fibrous matrix. This process is strictly regulated, and a number of signal transduction systems were interested in calcium metabolism, such as the phosphoinositide (PI pathway and related phospholipase C (PLC enzymes. Objectives: Our aim was to search for common patterns of expression in osteoblasts, as well as in ES and SS. Methods: We analysed the PLC enzymes in human osteoblasts and osteosarcoma cell lines MG-63 and SaOS-2. We compared the obtained results to the expression of PLCs in samples of patients affected with Ewing sarcoma (ES and synovial sarcoma (SS. Results: In osteoblasts, MG-63 cells and SaOS-2 significant differences were identified in the expression of PLC δ4 and PLC η subfamily isoforms. Differences were also identified regarding the expression of PLCs in ES and SS. Most ES and SS did not express PLCB1, which was expressed in most osteoblasts, MG-63 and SaOS-2 cells. Conversely, PLCB2, unexpressed in the cell lines, was expressed in some ES and SS. However, PLCH1 was expressed in SaOS-2 and inconstantly expressed in osteoblasts, while it was expressed in ES and unexpressed in SS. The most relevant difference observed in ES compared to SS regarded PLC ε and PLC η isoforms. Conclusion: MG-63 and SaOS-2 osteosarcoma cell lines might represent an inappropriate experimental model for studies about the analysis of signal transduction in osteoblasts

A Case of Distal Epithelioid Sarcoma of the Thumb Expressing Podoplanin, TLE1 and Ca 125

Directory of Open Access Journals (Sweden)

George Karagkounis

2013-01-01

Full Text Available Distal epithelioid sarcoma is a rare and slowly growing tumor that usually develops in the upper extremities of young adults. Neoplastic cells have both spindle and epithelioid appearance and are characterized by the loss of the nuclear protein SMARCB1/INI1. We present the case of a distal epithelioid sarcoma arising in the thumb of a 14-year-old girl, which immunohistochemically was characterized by the loss of SMARCB1/INI1 protein as well as the expression of podoplanin (D2-40, TLE1, Glut1, and Ca 125; plus, we highlight the differential diagnosis of epithelioid sarcoma from its histological mimics.

Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

International Nuclear Information System (INIS)

Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

1988-01-01

Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

Visual Comparison of Multiple Gene Expression Datasets in a Genomic Context

Directory of Open Access Journals (Sweden)

Borowski Krzysztof

2008-06-01

Full Text Available The need for novel methods of visualizing microarray data is growing. New perspectives are beneficial to finding patterns in expression data. The Bluejay genome browser provides an integrative way of visualizing gene expression datasets in a genomic context. We have now developed the functionality to display multiple microarray datasets simultaneously in Bluejay, in order to provide researchers with a comprehensive view of their datasets linked to a graphical representation of gene function. This will enable biologists to obtain valuable insights on expression patterns, by allowing them to analyze the expression values in relation to the gene locations as well as to compare expression profiles of related genomes or of di erent experiments for the same genome.

Small-molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma.

Science.gov (United States)

Boro, Aleksandar; Prêtre, Kathya; Rechfeld, Florian; Thalhammer, Verena; Oesch, Susanne; Wachtel, Marco; Schäfer, Beat W; Niggli, Felix K

2012-11-01

Ewing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well-characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read-out system, we screened a small-molecule compound library enriched for FDA-approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit-list of nine well-known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes. Copyright © 2012 UICC.

EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing's Sarcoma.

Science.gov (United States)

Hossain, Mohammad Motarab; Ray, Swapan Kumar

2014-10-01

Ewing's sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing's sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing's sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing's sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing's sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing's sarcoma in cell culture and animal models.

Clinical and biological significance of hepatoma-derived growth factor in Ewing's sarcoma.

Science.gov (United States)

Yang, Yang; Li, Hui; Zhang, Fenfen; Shi, Huijuan; Zhen, Tiantian; Dai, Sujuan; Kang, Lili; Liang, Yingjie; Wang, Jin; Han, Anjia

2013-11-01

We sought to investigate the clinicopathological significance and biological function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and enhanced sensitization to serum starvation-induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Immunohistochemical expression of promyelocytic leukemia body in soft tissue sarcomas

Directory of Open Access Journals (Sweden)

Yasunaga Yuji

2008-11-01

Full Text Available Abstract Background The function of promyelocytic leukemia (PML bodies is not well known but plays an important role in controlling cell proliferation, apoptosis and senescence. This study was undertaken to analyze the clinical significance of PML body expression in primary tumor samples from malignant fibrous histiocytoma (MFH and liposarcoma patients. Methods We studied MFH and liposarcoma samples from 55 patients for PML bodies. Fluorescent immunostaining of PML bodies was performed in the paraffin-embedded tumor sections. Results PML body immunostaining was identified in 63.9% of MFH and 63.2% of liposarcoma samples. PML body expression rates of all sarcoma cells were 1.5 ± 1.8% (range: 0–7.0 in MFH and 1.3 ± 1.4% (0–5.2 in liposarcoma samples. PML body expression (p = 0.0053 and a high rate of PML body expression (p = 0.0012 were significantly greater prognostic risk factors for death than the other clinical factors in MFH patients. All liposarcoma patients without expression of PML were disease free at the end of the study. Conclusion Our study suggests that the presence of PML bodies may indicate a poor prognosis for MFH and liposarcoma patients.

Regulatory roles and therapeutic potential of microRNA in sarcoma.

Science.gov (United States)

Lim, Hui Jun; Yang, Jia-Lin

2016-01-01

MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in various biological processes, including cell differentiation and development. They play multiple key roles as tumour suppressors, oncogenes or both in particular cases. This review aims to summarise current findings of the expression of miRNAs and their role in clinical oncology. Current knowledge regarding the involvement of miRNAs in different sarcoma subtypes will be assessed, in conjunction with their potential application as therapeutic targets. Relevant articles in scientific databases were identified using a combination of search terms, including "microRNA," "deregulation," "sarcoma," and "targeted therapy". These databases included Medline, Embase, Cochrane Review, Pubmed and Scopus. Aberrant miRNA expression patterns have been identified in a range of sarcoma subtypes, and differences in miRNA expression profiles between malignant cells and their normal counterparts suggests that miRNAs play key roles in sarcoma development. The identification of unique miRNA patterns in individual tumour types could possibly be used as a diagnostic tool in sarcoma. Moreover, identification of these miRNAs provides novel targets for the development of therapeutic strategies in distinct sarcoma subtypes. miRNAs hold significant potential as diagnostic biomarkers, as well as therapeutic targets in sarcoma. Possible future clinical applications include the use of miRNA pathways as therapeutic targets or miRNA expression profiling as a means of patient selection. The involvement miRNAs will undoubtedly contribute to the advancement of future targeted therapeutic interventions in sarcoma, and further establishment of appropriate delivery systems is vital for their use in clinical settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Down-regulated E-cadherin expression is associated with poor five-year overall survival in bone and soft tissue sarcoma: results of a meta-analysis.

Directory of Open Access Journals (Sweden)

Ning Wang

Full Text Available To conduct a meta-analysis to evaluate the prognostic role of E-cadherin expression in bone and soft tissue sarcomas.The PubMed, EMBASE, and Web of Science databases were searched using terms related to E-cadherin, sarcoma, and prognosis for all articles published in English before March 2014. Pooled effect was calculated from the available data to evaluate the association between negative E-cadherin expression and 5-year overall survival and tumor clinicopathological features in sarcoma patients. Pooled odds ratios (OR and risk ratios (RR with 95% confidence intervals (CI were calculated using a fixed-effects model.Eight studies met the selection criteria and reported on 812 subjects. A total of 496 subjects showed positive E-cadherin expression (59.9%. Negative E-cadherin expression in bone and soft tissue sarcomas was correlated with lower 5-year overall survival (OR = 3.831; 95% CI: 2.246-6.534, and was associated with higher clinical stage (RR = 1.446; 95% CI: 1.030-2.028 and with male sex (RR = 0.678; 95% CI: 0.493-0.933.In the E-cadherin negative group, 5-year overall survival was significantly worse than in the E-cadherin positive group. However, further studies are required to confirm these results.

Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors

Directory of Open Access Journals (Sweden)

Skubitz Amy PN

2008-05-01

Full Text Available Abstract The heterogeneity that soft tissue sarcomas (STS exhibit in their clinical behavior, even within histological subtypes, complicates patient care. Histological appearance is determined by gene expression. Morphologic features are generally good predictors of biologic behavior, however, metastatic propensity, tumor growth, and response to chemotherapy may be determined by gene expression patterns that do not correlate well with morphology. One approach to identify heterogeneity is to search for genetic markers that correlate with differences in tumor behavior. Alternatively, subsets may be identified based on gene expression patterns alone, independent of knowledge of clinical outcome. We have reported gene expression patterns that distinguish two subgroups of clear cell renal carcinoma (ccRCC, and other gene expression patterns that distinguish heterogeneity of serous ovarian carcinoma (OVCA and aggressive fibromatosis (AF. In this study, gene expression in 53 samples of STS and AF [including 16 malignant fibrous histiocytoma (MFH, 9 leiomyosarcoma, 12 liposarcoma, 4 synovial sarcoma, and 12 samples of AF] was determined at Gene Logic Inc. (Gaithersburg, MD using Affymetrix GeneChip® U_133 arrays containing approximately 40,000 genes/ESTs. Gene expression analysis was performed with the Gene Logic Genesis Enterprise System® Software and Expressionist software. Hierarchical clustering of the STS using our three previously reported gene sets, each generated subgroups within the STS that for some subtypes correlated with histology, and also suggested the existence of subsets of MFH. All three gene sets also recognized the same two subsets of the fibromatosis samples that we had found in our earlier study of AF. These results suggest that these subgroups may have biological significance, and that these gene sets may be useful for sub-classification of STS. In addition, several genes that are targets of some anti-tumor drugs were found to

Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients

International Nuclear Information System (INIS)

Greither, Thomas; Taubert, Helge; Koser, Franziska; Kappler, Matthias; Bache, Matthias; Lautenschläger, Christine; Göbel, Steffen; Holzhausen, Hans-Jürgen; Wach, Sven; Würl, Peter

2012-01-01

Argonaute genes are essential for RNA interference, stem cell maintenance and differentiation. The Piwi-like genes, a subclass of the Argonaute genes, are expressed mainly in the germline. These genes may be re-expressed in tumors, and expression of the Piwi-like genes is associated with prognosis in several types of tumors. We measured the expression of Piwi-like mRNAs (Piwi-like 2–4) in 125 soft tissue sarcoma (STS) samples by qPCRs. Statistical tests were applied to study the correlation of expression levels with tumor-specific survival for STS patients. In multivariate Cox’s regression analyses, we showed that low Piwi-like 2 and Piwi-like 4 mRNA expression were significantly associated with a worse prognosis (RR = 1.87; p = 0.032 and RR = 1.82; p = 0.039). Low expression of both genes was associated with a 2.58-fold increased risk of tumor-related death (p = 0.01). Piwi-like 4 and combined Piwi-like 2 and 4 mRNA levels correlated significantly with prognosis (RR = 3.53; p = 0.002 and RR = 5.23; p = 0.004) only for female but not for male patients. However, combined low Piwi-like 2 and 3 transcript levels were associated with worse survival (RR = 5.90; p = 0.02) for male patients. In this study, we identified a significant association between the expression of Piwi-like 2 and 4 mRNAs and the tumor-specific survival of soft tissue sarcoma patients. Furthermore, a connection between sex and the impact of Piwi-like mRNA expressions on STS patients’ prognosis was shown for the first time

A novel dataset for real-life evaluation of facial expression recognition methodologies

NARCIS (Netherlands)

Siddiqi, Muhammad Hameed; Ali, Maqbool; Idris, Muhammad; Banos Legran, Oresti; Lee, Sungyoung; Choo, Hyunseung

2016-01-01

One limitation seen among most of the previous methods is that they were evaluated under settings that are far from real-life scenarios. The reason is that the existing facial expression recognition (FER) datasets are mostly pose-based and assume a predefined setup. The expressions in these datasets

Targeting the p53 Pathway in Ewing Sarcoma

Science.gov (United States)

Neilsen, Paul M.; Pishas, Kathleen I.; Callen, David F.; Thomas, David M.

2011-01-01

The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53. PMID:21197471

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

Directory of Open Access Journals (Sweden)

Patrick P. Lin

2011-01-01

Full Text Available The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC. Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further.

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

Science.gov (United States)

Lin, Patrick P.; Wang, Yongxing; Lozano, Guillermina

2011-01-01

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further. PMID:20953407

siRNA associated with immunonanoparticles directed against cd99 antigen improves gene expression inhibition in vivo in Ewing's sarcoma.

Science.gov (United States)

Ramon, A L; Bertrand, J R; de Martimprey, H; Bernard, G; Ponchel, G; Malvy, C; Vauthier, C

2013-07-01

Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles. Copyright © 2013 John Wiley & Sons, Ltd.

INI Expressing Epithelioid Sarcoma with Osteoclastic Giant Cells in a Child: A Case Report with Summary of Prior Published Cases.

Science.gov (United States)

Bhattacharyya, Riju; Ghosh, Ranajoy; Saha, Koushik; Chatterjee, Uttara

2017-08-01

Epithelioid sarcoma is a heterogeneous tumor with 2 subtypes, classic and proximal. The proximal variant is more aggressive and occurs in proximal location in young adults. We present a proximal epithelioid sarcoma in the leg of an 8 year old girl with rhabdoid morphology and scattered osteoclastic giant cells. Nuclear INI-1 was retained. Despite wide local excision, local recurrence occurred at 8 months. Following re-excision, she developed a chest wall metastasis after 9 months. Epithelioid sarcoma, proximal type with osteoclastic giant cells in the pediatric age group has not been reported previously and should be considered in the differential diagnoses of tumors with epithelioid cell morphology and scattered osteoclastic giant cells. Retained INI expression helped to differentiate this tumor from malignant rhabdoid tumor.

Multimedia Content Development as a Facial Expression Datasets for Recognition of Human Emotions

Science.gov (United States)

Mamonto, N. E.; Maulana, H.; Liliana, D. Y.; Basaruddin, T.

2018-02-01

Datasets that have been developed before contain facial expression from foreign people. The development of multimedia content aims to answer the problems experienced by the research team and other researchers who will conduct similar research. The method used in the development of multimedia content as facial expression datasets for human emotion recognition is the Villamil-Molina version of the multimedia development method. Multimedia content developed with 10 subjects or talents with each talent performing 3 shots with each capturing talent having to demonstrate 19 facial expressions. After the process of editing and rendering, tests are carried out with the conclusion that the multimedia content can be used as a facial expression dataset for recognition of human emotions.

Cyclin D1 and Ewing's sarcoma/PNET: A microarray analysis.

Science.gov (United States)

Fagone, Paolo; Nicoletti, Ferdinando; Salvatorelli, Lucia; Musumeci, Giuseppe; Magro, Gaetano

2015-10-01

Recent immunohistochemical analyses have showed that cyclin D1 is expressed in soft tissue Ewing's sarcoma/peripheral neuroectodermal tumor (PNET) of childhood and adolescents, while it is undetectable in both embryonal and alveolar rhabdomyosarcoma. In the present paper, microarray analysis provided evidence of a significant upregulation of cyclin D1 in Ewing's sarcoma as compared to normal tissues. In addition, we confirmed our previous findings of a significant over-expression of cyclin D1 in Ewing sarcoma as compared to rhabdomyosarcoma. Bioinformatic analysis also allowed to identify some other genes, strongly correlated to cyclin D1, which, although not previously studied in pediatric tumors, could represent novel markers for the diagnosis and prognosis of Ewing's sarcoma/PNET. The data herein provided support not only the use of cyclin D1 as a diagnostic marker of Ewing sarcoma/PNET but also the possibility of using drugs targeting cyclin D1 as potential therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma.

Science.gov (United States)

Nakayama, Robert; Zhang, Yi-Xiang; Czaplinski, Jeffrey T; Anatone, Alex J; Sicinska, Ewa T; Fletcher, Jonathan A; Demetri, George D; Wagner, Andrew J

2016-03-29

Selinexor is an orally bioavailable selective inhibitor of nuclear export that has been demonstrated to have preclinical activity in various cancer types and that is currently in Phase I and II clinical trials for advanced cancers. In this study, we evaluated the effects of selinexor in several preclinical models of various sarcoma subtypes. The efficacy of selinexor was investigated in vitro and in vivo using 17 cell lines and 9 sarcoma xenograft models including gastrointestinal stromal tumor (GIST), liposarcoma (LPS), leiomyosarcoma, rhabdomyosarcoma, undifferentiated sarcomas, and alveolar soft part sarcoma (ASPS). Most sarcoma cell lines were sensitive to selinexor with IC50s ranging from 28.8 nM to 218.2 nM (median: 66.1 nM). Selinexor suppressed sarcoma tumor xenograft growth, including models of ASPS that were resistant in vitro. In GIST cells with KIT mutations, selinexor induced G1- arrest without attenuation of phosphorylation of KIT, AKT, or MAPK, in contrast to imatinib. In LPS cell lines with MDM2 and CDK4 amplification, selinexor induced G1-arrest and apoptosis irrespective of p53 expression or mutation and irrespective of RB expression. Selinexor increased p53 and p21 expression at the protein but not RNA level, indicating a post-transcriptional effect. These results indicate that selinexor has potent in vitro and in vivo activity against a wide variety of sarcoma models by inducing G1-arrest independent of known molecular mechanisms in GIST and LPS. These studies further justify the exploration of selinexor in clinical trials targeting various sarcoma subtypes.

Biochemical characterization of cells transformed via transfection by feline sarcoma virus proviral DNA.

OpenAIRE

Rosenberg, Z F; Sahagan, B G; Snyder, H W; Worley, M B; Essex, M; Haseltine, W A

1981-01-01

Murine fibroblasts transformed by transfection with DNA from mink cells infected with the Snyder-Theilen strain of feline sarcoma virus and subgroup B feline leukemia virus were analyzed for the presence of integrated proviral DNA and the expression of feline leukemia virus- and feline sarcoma virus-specific proteins. The transformed murine cells harbored at least one intact feline sarcoma virus provirus, but did not contain feline leukemia virus provirus. The transformed murine cells express...

Gene expression profiling of low-grade endometrial stromal sarcoma indicates fusion protein-mediated activation of the Wnt signaling pathway.

Science.gov (United States)

Przybyl, Joanna; Kidzinski, Lukasz; Hastie, Trevor; Debiec-Rychter, Maria; Nusse, Roel; van de Rijn, Matt

2018-05-01

Low-grade endometrial stromal sarcomas (LGESS) harbor chromosomal translocations that affect proteins associated with chromatin remodeling Polycomb Repressive Complex 2 (PRC2), including SUZ12, PHF1 and EPC1. Roughly half of LGESS also demonstrate nuclear accumulation of β-catenin, which is a hallmark of Wnt signaling activation. However, the targets affected by the fusion proteins and the role of Wnt signaling in the pathogenesis of these tumors remain largely unknown. Here we report the results of a meta-analysis of three independent gene expression profiling studies on LGESS and immunohistochemical evaluation of nuclear expression of β-catenin and Lef1 in 112 uterine sarcoma specimens obtained from 20 LGESS and 89 LMS patients. Our results demonstrate that 143 out of 310 genes overexpressed in LGESS are known to be directly regulated by SUZ12. In addition, our gene expression meta-analysis shows activation of multiple genes implicated in Wnt signaling. We further emphasize the role of the Wnt signaling pathway by demonstrating concordant nuclear expression of β-catenin and Lef1 in 7/16 LGESS. Based on our findings, we suggest that LGESS-specific fusion proteins disrupt the repressive function of the PRC2 complex similar to the mechanism seen in synovial sarcoma, where the SS18-SSX fusion proteins disrupt the mSWI/SNF (BAF) chromatin remodeling complex. We propose that these fusion proteins in LGESS contribute to overexpression of Wnt ligands with subsequent activation of Wnt signaling pathway and formation of an active β-catenin/Lef1 transcriptional complex. These observations could lead to novel therapeutic approaches that focus on the Wnt pathway in LGESS. Copyright © 2018 Elsevier Inc. All rights reserved.

Bone sarcomas

International Nuclear Information System (INIS)

Mudry, P.

2008-01-01

Bone sarcomas are malignancies with peak incidence in adolescents and young adults. The most frequent are osteosarcoma and Ewing sarcoma/PNET, in an older adults are seen chondrosarcomas, other ones are rare. In general, biology of sarcomas is closely related to pediatric malignancies with fast growth, local aggressiveness, tendency to early hematogenic dissemination and chemo sensitivity. Diagnostics and treatment of bone sarcomas should be done in well experienced centres due to low incidence and broad issue of this topic. An interdisciplinary approach and staff education is essential in due care of patients with bone sarcoma. If these criteria are achieved, the cure rate is contemporary at 65 - 70 %, while some subpopulation of patients has chance for cure up to 90 %. Osteosarcoma and Ewing sarcoma/PNET are discussed below as types of most frequent bone sarcoma. (author)

Targeting protein kinases to reverse multidrug resistance in sarcoma.

Science.gov (United States)

Chen, Hua; Shen, Jacson; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

2016-02-01

Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microsatellites with Macro-Influence in Ewing Sarcoma

Directory of Open Access Journals (Sweden)

Stephen L. Lessnick

2012-07-01

Full Text Available Numerous molecular abnormalities contribute to the genetic derangements involved in tumorigenesis. Chromosomal translocations are a frequent source of these derangements, producing unique fusion proteins with novel oncogenic properties. EWS/ETS fusions in Ewing sarcoma are a prime example of this, resulting in potent chimeric oncoproteins with novel biological properties and a unique transcriptional signature essential for oncogenesis. Recent evidence demonstrates that EWS/FLI, the most common EWS/ETS fusion in Ewing sarcoma, upregulates gene expression using a GGAA microsatellite response element dispersed throughout the human genome. These GGAA microsatellites function as enhancer elements, are sites of epigenetic regulation and are necessary for EWS/FLI DNA binding and upregulation of principal oncogenic targets. An increasing number of GGAA motifs appear to substantially enhance EWS/FLI-mediated gene expression, which has compelling biological implications as these GGAA microsatellites are highly polymorphic within and between ethnically distinct populations. Historically regarded as junk DNA, this emerging evidence clearly demonstrates that microsatellite DNA plays an instrumental role in EWS/FLI-mediated transcriptional regulation and oncogenesis in Ewing sarcoma. This unprecedented role of GGAA microsatellite DNA in Ewing sarcoma provides a unique opportunity to expand our mechanistic understanding of how EWS/ETS fusions influence cancer susceptibility, prognosis and transcriptional regulation.

Ewing's sarcoma of bone tumor cells produces MCSF that stimulates monocyte proliferation in a novel mouse model of Ewing's sarcoma of bone.

Science.gov (United States)

Margulies, B S; DeBoyace, S D; Damron, T A; Allen, M J

2015-10-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Ewing's Sarcoma of Bone Tumor Cells Produce MCSF that Stimulates Monocyte Proliferation in a Novel Mouse Model of Ewing's Sarcoma of Bone

Science.gov (United States)

Margulies, BS; DeBoyace, SD; Damron, TA; Allen, MJ

2015-01-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. PMID:26051470

Kaposi's Sarcoma

Science.gov (United States)

... Name: Category: Share: Yes No, Keep Private Kaposi’s Sarcoma Share | Kaposi’s sarcoma (KS) is a vascular neoplasm of the skin ... symptoms of HIV infection. This type of Kaposi's sarcoma progresses slowly, with new lesions appearing every few ...

Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets

Science.gov (United States)

Marchetto, Aruna; Gerke, Julia S.; Rubio, Rebeca Alba; Kiran, Merve M.; Musa, Julian; Knott, Maximilian M. L.; Ohmura, Shunya; Li, Jing; Akpolat, Nusret; Akatli, Ayse N.; Özen, Özlem; Dirksen, Uta; Hartmann, Wolfgang; de Alava, Enrique; Baumhoer, Daniel; Sannino, Giuseppina; Kirchner, Thomas; Grünewald, Thomas G. P.

2018-01-01

Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4-, BCOR-CCNB3-, EWSR1-NFATc2-, and EWSR1-ETS-translocated sarcomas are distinct entities, and revealed that ATP1A1, BCL11B, and GLG1 constitute specific markers for Ewing sarcoma. Their high expression was validated by immunohistochemistry and proved to depend on EWSR1-FLI1-binding to highly active proximal super-enhancers. Automated cut-off-finding and combination-testing in a tissue-microarray comprising 174 samples demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined strong BCL11B- and GLG1-immunoreactivity. Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple, and cost-efficient way to diagnose Ewing sarcoma by immunohistochemistry. These markers may significantly reduce the number of misdiagnosed patients, and thus improve patient care. PMID:29416716

Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma

International Nuclear Information System (INIS)

Greve, B.; Sheikh-Mounessi, F.; Ernst, I.; Eich, H.T.; Kemper, B.; Goette, M.

2012-01-01

Background and purpose: Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro. Material and methods: An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation. Results: Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation. Conclusion: Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma. (orig.)

Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma.

Science.gov (United States)

Greve, B; Sheikh-Mounessi, F; Kemper, B; Ernst, I; Götte, M; Eich, H T

2012-11-01

Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro. An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation. Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation. Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma.

[Primitive cutaneous Ewing's sarcoma: a diagnostic and therapeutic dilemma].

Science.gov (United States)

Delaplace, M; Mélard, P; Perrinaud, A; Goré, C; Vergier, B; Machet, L

2011-05-01

Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman. A 21-year-old woman presented with a scapular lesion that had been slowly developing for one year. The 1-cm lesion was removed and histological examination showed proliferation of small round cells in the dermis. Immunostaining revealed cytoplasmic membrane expression of CD99 and a negative immunoprofile for other small round-cell tumors. Ewing's sarcoma fusion gene transcripts were detected using fluorescence in situ hybridization (FISH). A staging examination revealed no other abnormalities. It was decided to treat the lesion as for osseous Ewing's sarcoma with wide resection followed by systemic adjuvant chemotherapy. Cutaneous Ewing's sarcoma raises concerns about diagnosis and treatment. Owing to the non-specificity of its clinical presentation, histology and immunoprofile, diagnosis of superficial Ewing's sarcoma is difficult and numerous differential diagnoses must be considered. When dealing with a surface tumour, the diagnosis of cutaneous Ewing's sarcoma must be considered. CD99 immunostaining and molecular testing for evidence of EWSR1 rearrangement are useful investigations to confirm the diagnosis. Furthermore, modalities of treatment must be carefully discussed. Cutaneous Ewing's sarcoma is currently treated in the same way as osseous Ewing's sarcoma (wide surgical excision, adjuvant radiotherapy when surgical margins are unsatisfactory, systemic adjuvant chemotherapy, and, in some cases, bone marrow transplant). However, some studies show a more favourable prognosis for cutaneous Ewing's sarcoma than for osseous Ewing's sarcoma. We may thus ask whether such aggressive multimodal treatment is needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Comprehensive comparison of large-scale tissue expression datasets

DEFF Research Database (Denmark)

Santos Delgado, Alberto; Tsafou, Kalliopi; Stolte, Christian

2015-01-01

a comprehensive evaluation of tissue expression data from a variety of experimental techniques and show that these agree surprisingly well with each other and with results from literature curation and text mining. We further found that most datasets support the assumed but not demonstrated distinction between......For tissues to carry out their functions, they rely on the right proteins to be present. Several high-throughput technologies have been used to map out which proteins are expressed in which tissues; however, the data have not previously been systematically compared and integrated. We present......://tissues.jensenlab.org), which makes all the scored and integrated data available through a single user-friendly web interface....

Matrix metalloproteinase 1: role in sarcoma biology.

Directory of Open Access Journals (Sweden)

Muhammad Umar Jawad

2010-12-01

Full Text Available In carcinomas stromal cells participate in cancer progression by producing proteases such as MMPs. The expression MMP1 is a prognostic factor in human chondrosarcoma, however the role in tumor progression is unknown. Laser capture microdissection and In Situ hybridization were used to determine cellular origin of MMP1 in human sarcomas. A xenogenic model of tumor progression was then used and mice were divided in two groups: each harboring either the control or a stably MMP1 silenced cell line. Animals were sacrificed; the neovascularization, primary tumor volumes, and metastatic burden were assessed. LCM and RNA-ISH analysis revealed MMP1 expression was predominantly localized to the tumor cells in all samples of sarcoma (p = 0.05. The percentage lung metastatic volume at 5 weeks (p = 0.08 and number of spontaneous deaths secondary to systemic tumor burden were lower in MMP1 silenced cell bearing mice. Interestingly, this group also demonstrated a larger primary tumor size (p<0.04 and increased angiogenesis (p<0.01. These findings were found to be consistent when experiment was repeated using a second independent MMP1 silencing sequence. Prior clinical trials employing MMP1 inhibitors failed because of a poor understanding of the role of MMPs in tumor progression. The current findings indicating tumor cell production of MMP1 by sarcoma cells is novel and highlights the fundamental differences in MMP biology between carcinomas and sarcomas. The results also emphasize the complex roles of MMP in tumor progression of sarcomas. Not only does metastasis seem to be affected by MMP1 silencing, but also local tumor growth and angiogenesis are affected inversely.

V-ATPase as an effective therapeutic target for sarcomas

Energy Technology Data Exchange (ETDEWEB)

Perut, Francesca, E-mail: francesca.perut@ior.it [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Avnet, Sofia; Fotia, Caterina; Baglìo, Serena Rubina; Salerno, Manuela [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Hosogi, Shigekuni [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Kusuzaki, Katsuyuki [Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Baldini, Nicola [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy)

2014-01-01

Malignant tumors show intense glycolysis and, as a consequence, high lactate production and proton efflux activity. We investigated proton dynamics in osteosarcoma, rhabdomyosarcoma, and chondrosarcoma, and evaluated the effects of esomeprazole as a therapeutic agent interfering with tumor acidic microenvironment. All sarcomas were able to survive in an acidic microenvironment (up to 5.9–6.0 pH) and abundant acidic lysosomes were found in all sarcoma subtypes. V-ATPase, a proton pump that acidifies intracellular compartments and transports protons across the plasma membrane, was detected in all cell types with a histotype-specific expression pattern. Esomeprazole administration interfered with proton compartmentalization in acidic organelles and induced a significant dose-dependent toxicity. Among the different histotypes, rhabdomyosarcoma, expressing the highest levels of V-ATPase and whose lysosomes are most acidic, was mostly susceptible to ESOM treatment. - Highlights: • Osteosarcoma, rhabdomyosarcoma, and chondrosarcoma survive in acidic microenvironment. • At acidic extracellular pH, sarcoma survival is dependent on V-ATPase expression. • Esomeprazole administration induce a significant dose-dependent toxicity.

Epidemic Kaposi Sarcoma

Science.gov (United States)

... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Classic Kaposi Sarcoma

Science.gov (United States)

... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

The Epidemiology of Sarcoma

Directory of Open Access Journals (Sweden)

Burningham Zachary

2012-10-01

Full Text Available Abstract Sarcomas account for over 20% of all pediatric solid malignant cancers and less than 1% of all adult solid malignant cancers. The vast majority of diagnosed sarcomas will be soft tissue sarcomas, while malignant bone tumors make up just over 10% of sarcomas. The risks for sarcoma are not well-understood. We evaluated the existing literature on the epidemiology and etiology of sarcoma. Risks for sarcoma development can be divided into environmental exposures, genetic susceptibility, and an interaction between the two. HIV-positive individuals are at an increased risk for Kaposi’s sarcoma, even though HHV8 is the causative virus. Radiation exposure from radiotherapy has been strongly associated with secondary sarcoma development in certain cancer patients. In fact, the risk of malignant bone tumors increases as the cumulative dose of radiation to the bone increases (p for trend

Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells.

Science.gov (United States)

Fisher, Jonathan P H; Flutter, Barry; Wesemann, Florian; Frosch, Jennifer; Rossig, Claudia; Gustafsson, Kenth; Anderson, John

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma. To explore the hypothesis that zoledronic acid, IL-2 and anti-GD2 antibodies will synergize in a therapeutic combination, we evaluated in vitro cytotoxicity and tumor growth inhibition in the GD2 expressing cancers neuroblastoma and Ewing's sarcoma. Vδ2 T cells exert ADCC against GD2-expressing Ewing's sarcoma and neuroblastoma cell lines, an effect which correlates with the brightness of GD2 expression. In an immunodeficient mouse model of small established GD2-expressing Ewing's sarcoma or neuroblastoma tumors, the combination of adoptively transferred Vδ2+ T cells, expanded in vitro with zoledronic acid and IL-2, with anti-GD2 antibody ch14.18/CHO, and with systemic zoledronic acid, significantly suppressed tumor growth compared to antibody or γδT cell-free controls. Combination treatment using ch14.18/CHO, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as neuroblastoma or Ewing's sarcoma both rational and feasible.

Sarcomas cutâneos primários Primary cutaneous sarcomas

Directory of Open Access Journals (Sweden)

Luiz Fernando Fróes Fleury Jr

2006-06-01

Full Text Available Os sarcomas com apresentação cutânea primária são tumores raros e de grande heterogeneidade histológica. Com a evolução da oncologia cutânea e da cirurgia dermatológica, os dermatologistas têm sido cada vez mais requisitados para o diagnóstico e orientação terapêutica de tumores menos freqüentes. Este artigo de revisão analisa os sarcomas cutâneos primários observando suas características clínicas, etiopatogênicas e histológicas, bem como aspectos do tratamento e evolução. Enfatiza os sarcomas de maior relevância para o dermatologista, como angiossarcoma, dermatofibrossarcoma protuberans, fibroxantoma atípico, leiomiossarcoma, lipossarcoma, tumor maligno de bainha de nervo periférico e sarcoma epitelióide. O sarcoma de Kaposi não é abordado devido a suas características individuais específicas.Soft tissue tumors represent a heterogeneous group of mesenchymal and neural lesions. The cutaneous presentation of these tumours is rare. With the evolution of dermatologic surgery and cutaneous oncology, dermatologists have emerged as specialists for skin cancer management. This article reviews primary cutaneous sarcomas with particular emphasis on the epidemiologic, clinical, and histological features of diagnosis, as well as treatment modalities and prognosis. The most frequent cutaneous sarcomas were reviewed, including angiosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, leiomyosarcoma, liposarcoma, malignant nerve sheath tumor, and epithelioid sarcoma. Kaposi's sarcoma, due to specific characteristics, was omitted from this review.

Kaposi's sarcoma

International Nuclear Information System (INIS)

Kirova, Y.M.; Belembaogo, E.; Frikha, H.; Yu, S.J.; Le Bourgeois, J.P.

1997-01-01

Moriz Kaposi was the first who, in 1872, described five patients presenting with 'sarcoma idiopathicum multiple hemorrhagicum'. In 1912 Sternberg termed this disease Kaposi's sarcoma. Since then various forms of this rare disease have been observed. In 1914 Hallenberg described the first cases of African or endemic Kaposi's sarcoma. In the 1960's the first reports discussing Kaposi's sarcoma following organ transplantation and immunosuppressive therapy were published. After 1981, the epidemic form associated with the acquired immunodeficiency syndrome (AIDS) was described. All these forms, their history, treatment methods and the role of radiation therapy in the management of this rare malignancy are discussed, and the literature is reviewed. (authors)

Copy Number Alterations and Methylation in Ewing's Sarcoma

Science.gov (United States)

Jahromi, Mona S.; Jones, Kevin B.; Schiffman, Joshua D.

2011-01-01

Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs) and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease. PMID:21437220

Copy Number Alterations and Methylation in Ewing's Sarcoma

Directory of Open Access Journals (Sweden)

Mona S. Jahromi

2011-01-01

Full Text Available Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease.

Targeted therapy for sarcomas

Directory of Open Access Journals (Sweden)

Forscher C

2014-03-01

Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

DR6 as a diagnostic and predictive biomarker in adult sarcoma.

Directory of Open Access Journals (Sweden)

Kun Yang

Full Text Available The Death Receptor 6 (DR6 protein is elevated in the serum of ovarian cancer patients. We tested DR6 serum protein levels as a diagnostic/predictive biomarker in several epithelial tumors and sarcomas.DR6 gene expression profiles were screened in publically available arrays of solid tumors. A quantitative immunofluorescent western blot analysis was developed to test the serum of healthy controls and patients with sarcoma, uterine carcinosarcoma, bladder, liver, and pancreatic carcinomas. Change in DR6 serum levels was used to assay the ability of DR6 to predict the response to therapy of sarcoma patients.DR6 mRNA is highly expressed in all tumor types assayed. Western blot analysis of serum DR6 protein demonstrated high reproducibility (r = 0.97. Compared to healthy donor controls, DR6 serum levels were not elevated in patients with uterine carcinosarcoma, bladder, liver, or pancreatic cancers. Serum DR6 protein levels from adult sarcoma patients were significantly elevated (p<0.001. This was most evident for patients with synovial sarcoma. Change in serum DR6 levels during therapy correlated with clinical benefit from therapy (sensitivity 75%, and positive predictive value 87%.DR6 may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.Diagnosis of sarcoma can be difficult and can lead to improper management of these cancers. DR6 serum protein may be a tool to aid in the diagnosis of some sarcomatous tumors to improve treatment planning. For patients with advanced disease, rising DR6 levels predict non-response to therapy and may expedite therapeutic decision making and reduce reliance on radiologic imaging.

BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.

Directory of Open Access Journals (Sweden)

Elizabeth T Wiles

Full Text Available The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines. BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing's sarcoma and contributes to the EWS/FLI repressed gene signature. BCL11B repressive activity is mediated by the NuRD co-repressor complex. We further demonstrate that re-expression of SPRY1, a repressed target of BCL11B, limits the transformation capacity of Ewing sarcoma cells. These data define a new pathway downstream of EWS/FLI required for oncogenic maintenance in Ewing sarcoma.

Intracardiac Low-grade Sarcoma Following Treatment for Ewing Sarcoma.

Science.gov (United States)

Ortiz, Michael V; Magnan, Heather; Slotkin, Emily K; Ambati, Srikanth R; Chou, Alexander J; Wexler, Leonard H; Meyers, Paul A; Walsh, Michael F; Heaton, Todd; Girardi, Leonard N; Wolden, Suzanne L; Price, Anita P; Kennedy, Jennifer A; Zehir, Ahmet; Hameed, Meera; Berger, Michael F; Kentsis, Alex; Shukla, Neerav

2017-11-01

A 16-year-old male was diagnosed with Ewing sarcoma of the ribcage with pulmonary metastases. Six months after completion of scheduled therapy, he was found to have a new intracardiac mass, presumed recurrent Ewing sarcoma. EWSR1 fusion was not detected by droplet digital polymerase chain reaction from blood plasma. After no improvement with salvage chemotherapy, he underwent surgical resection that identified a low-grade spindle cell sarcoma. Despite the near-synchronous presentation of 2 unrelated sarcomas, extensive genomic analyses did not reveal any unifying somatic or germline mutations nor any apparent cancer predisposition. This case also highlights the potential role of utilizing plasma cell-free DNA for diagnosing tumors in locations where biopsy confers high morbidity.

Artificial neural network inference (ANNI: a study on gene-gene interaction for biomarkers in childhood sarcomas.

Directory of Open Access Journals (Sweden)

Dong Ling Tong

Full Text Available OBJECTIVE: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI. METHOD: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. RESULTS: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS; FCGRT and OLFM1 in Ewing's sarcoma (EWS suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. CONCLUSIONS: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas.

CD133 expression in chemo-resistant Ewing sarcoma cells

Directory of Open Access Journals (Sweden)

Kovar Heinrich

2010-03-01

Full Text Available Abstract Background Some human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance. Methods Expression of the CD133-encoding PROM1 gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and in vivo tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl-5-(3-carboxy-methoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium assays. Results PROM1 expression was either absent or extremely low in most tumors. However, PROM1 was highly over-expressed in 4 of 48 cases. Two of the 4 patients with PROM1 over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of PROM1 in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny. Conclusions Up to 10% of ESFT express high levels of PROM1. In some tumors and cell

Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

Directory of Open Access Journals (Sweden)

Karacali Bilge

2007-10-01

Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

Ewing sarcoma

Science.gov (United States)

Bone cancer - Ewing sarcoma; Ewing family of tumors; Primitive neuroectodermal tumors (PNET); Bone neoplasm - Ewing sarcoma ... to the lungs and other bones. At the time of diagnosis, spread is seen in about one- ...

Investigating the gene expression profiles of metastasising sarcoma cells

Czech Academy of Sciences Publication Activity Database

Cavanna, T.; Pokorná, Eva; Veselý, Pavel; Zicha, D.

2005-01-01

Roč. 40, č. 1 (2005), s. 37 ISSN 0035-9017. [Cytokinematics 2004. International Symposium on Microscopy of Live Cells in the Post Genomics Era /8./. 05.09.2004-07.09.2004, Hradec Králové] Institutional research plan: CEZ:AV0Z5052915 Keywords : sarcoma * metastasis Subject RIV: EB - Genetics ; Molecular Biology

Kaposi’s Sarcoma-associated herpesvirus microRNAs

Directory of Open Access Journals (Sweden)

Eva eGottwein

2012-05-01

Full Text Available Kaposi’s Sarcoma-associated herpesvirus (KSHV is a human pathogenic -herpesvirus strongly associated with the development of Kaposi’s Sarcoma and B cell proliferative disorders, including primary effusion lymphoma (PEL. The identification and functional investigation of non-coding RNAs expressed by KSHV is a topic with rapidly emerging importance. KSHV miRNAs derived from 12 stem-loops located in the major latency locus have been the focus of particular attention. Recent studies describing the transcriptome-wide identification of mRNA targets of the KSHV miRNAs suggest that these miRNAs have evolved a highly complex network of interactions with the cellular and viral transcriptomes. Relatively few KSHV miRNA targets, however, have been characterized at a functional level. Here, our current understanding of KSHV miRNA expression, targets and function will be reviewed.

Cytogenetically confirmed primary Ewing's sarcoma of the pancreas.

Science.gov (United States)

Golhar, Ankush; Ray, Samrat; Haugk, Beate; Singhvi, Suresh Kumar

2017-05-04

Ewing's sarcoma is a highly aggressive malignant tumour most commonly affecting long bones in children and adolescents. It is part of the Ewing's sarcoma family of tumours (ESFTs) that also include peripheral primitive neuroectodermal tumour and Askin's tumours. ESFTs share common cytogenetic aberrations, antigenic profiles and proto-oncogene expression with an overall similar clinical course. In 99% of ESFTs, genetic translocation with molecular fusion involves the EWSR1 gene on 22q12. Approximately 30% of ESFTs are extraosseous, most commonly occurring in the soft tissues of extremities, pelvis, retroperitoneum and chest wall. Primary presentation in solid organs is very rare but has been described in multiple sites including the pancreas. Accurate diagnosis of a Ewing's sarcoma in a solid organ is critical in facilitating correct treatment. We report the case of a 17-year-old girl with cytogenetically confirmed primary pancreatic Ewing's sarcoma and provide a brief review of the published literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical practice guideline: 2006 update of recommendations for the radiotherapeutic management of patients with soft tissue sarcoma (sarcoma of the extremity, uterine sarcoma and retroperitoneal sarcoma)

International Nuclear Information System (INIS)

Le Pechoux, C.; Pautier, P.; Le Cesne, A.; Delannes, M.; Bui, B.N.; Blay, J.Y.; Bonichon, F.; Bonvalot, S.; Morice, P.; Chevalier-Place, A.; Taieb, S.; Coindre, J.M.; Ray-Coquard, I.; Stoeckle, E.

2006-01-01

Context. - The National French Federation of Comprehensive Cancer Centres (FNCLCC) initiated the update of clinical practice guideline for the management of patients with soft tissue sarcoma in collaboration with the French Sarcoma Group (GSF-GETO), specialists from French public universities, general hospitals and private clinics and with the French National Cancer Institute. This work is based on the methodology developed in the 'Standards, Options and Recommendations' (SOR) project. Objectives - To update SOR guidelines for the management of patients with oft tissue sarcoma previously validated in 1995. Methods. -The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. Results. - This article presents the updated recommendations for radiotherapeutic management. The main recommendations are: 1) irradiation before or after surgical treatment is the standard for soft tissue sarcoma of the extremity and uterine sarcoma; 2) no systematic irradiation should be done in case of retroperitoneal sarcoma. (author)

Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

International Nuclear Information System (INIS)

Sadri, Navid; Zhang, Paul J.

2013-01-01

Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression

Stages of Ewing Sarcoma

Science.gov (United States)

... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

The Danish Sarcoma Database

DEFF Research Database (Denmark)

Jørgensen, Peter Holmberg; Lausten, Gunnar Schwarz; Pedersen, Alma B

2016-01-01

AIM: The aim of the database is to gather information about sarcomas treated in Denmark in order to continuously monitor and improve the quality of sarcoma treatment in a local, a national, and an international perspective. STUDY POPULATION: Patients in Denmark diagnosed with a sarcoma, both...... skeletal and ekstraskeletal, are to be registered since 2009. MAIN VARIABLES: The database contains information about appearance of symptoms; date of receiving referral to a sarcoma center; date of first visit; whether surgery has been performed elsewhere before referral, diagnosis, and treatment; tumor...... of Diseases - tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System). Data quality and completeness are currently secured. CONCLUSION: The Danish Sarcoma Database is population based and includes sarcomas occurring...

Validation of MIMGO: a method to identify differentially expressed GO terms in a microarray dataset

Directory of Open Access Journals (Sweden)

Yamada Yoichi

2012-12-01

Full Text Available Abstract Background We previously proposed an algorithm for the identification of GO terms that commonly annotate genes whose expression is upregulated or downregulated in some microarray data compared with in other microarray data. We call these “differentially expressed GO terms” and have named the algorithm “matrix-assisted identification method of differentially expressed GO terms” (MIMGO. MIMGO can also identify microarray data in which genes annotated with a differentially expressed GO term are upregulated or downregulated. However, MIMGO has not yet been validated on a real microarray dataset using all available GO terms. Findings We combined Gene Set Enrichment Analysis (GSEA with MIMGO to identify differentially expressed GO terms in a yeast cell cycle microarray dataset. GSEA followed by MIMGO (GSEA + MIMGO correctly identified (p Conclusions MIMGO is a reliable method to identify differentially expressed GO terms comprehensively.

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

Science.gov (United States)

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-07-16

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Gene expression profile of AIDS-related Kaposi's sarcoma

International Nuclear Information System (INIS)

Cornelissen, Marion; Kuyl, Antoinette C van der; Burg, Remco van den; Zorgdrager, Fokla; Noesel, Carel JM van; Goudsmit, Jaap

2003-01-01

Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages

Imaging Ewing's sarcoma

International Nuclear Information System (INIS)

Henk, C.B.; Grampp, S.; Kainberger, F.; Breitenseher, M.; Imhof, H.; Mostbeck, G.H.

1998-01-01

Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and 201 thallium scanning has been shown to be sensitive in the monitoring of treatment response. Today, computed tomography is not longer used to image the tumor site; however, spiral CT of the lungs plays a central role as a staging and follow-up tool. (orig.) [de

Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma.

Science.gov (United States)

Ban, J; Jug, G; Mestdagh, P; Schwentner, R; Kauer, M; Aryee, D N T; Schaefer, K-L; Nakatani, F; Scotlandi, K; Reiter, M; Strunk, D; Speleman, F; Vandesompele, J; Kovar, H

2011-05-05

EWS-FLI1 is a chromosome translocation-derived chimeric transcription factor that has a central and rate-limiting role in the pathogenesis of Ewing's sarcoma. Although the EWS-FLI1 transcriptomic signature has been extensively characterized on the mRNA level, information on its impact on non-coding RNA expression is lacking. We have performed a genome-wide analysis of microRNAs affected by RNAi-mediated silencing of EWS-FLI1 in Ewing's sarcoma cell lines, and differentially expressed between primary Ewing's sarcoma and mesenchymal progenitor cells. Here, we report on the identification of hsa-mir-145 as the top EWS-FLI1-repressed microRNA. Upon knockdown of EWS-FLI1, hsa-mir-145 expression dramatically increases in all Ewing's sarcoma cell lines tested. Vice versa, ectopic expression of the microRNA in Ewing's sarcoma cell lines strongly reduced EWS-FLI1 protein, whereas transfection of an anti-mir to hsa-mir-145 increased the EWS-FLI1 levels. Reporter gene assays revealed that this modulation of EWS-FLI1 protein was mediated by the microRNA targeting the FLI1 3'-untranslated region. Mutual regulations of EWS-FLI1 and hsa-mir-145 were mirrored by an inverse correlation between their expression levels in four of the Ewing's sarcoma cell lines tested. Consistent with the role of EWS-FLI1 in Ewing's sarcoma growth regulation, forced hsa-mir-145 expression halted Ewing's sarcoma cell line growth. These results identify feedback regulation between EWS-FLI1 and hsa-mir-145 as an important component of the EWS-FLI1-mediated Ewing's sarcomagenesis that may open a new avenue to future microRNA-mediated therapy of this devastating malignant disease.

Human Sarcoma growth is sensitive to small-molecule mediated AXIN stabilization.

Directory of Open Access Journals (Sweden)

Alessandra De Robertis

Full Text Available Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.

Science.gov (United States)

Tanaka, Miwa; Yamazaki, Yukari; Kanno, Yohei; Igarashi, Katsuhide; Aisaki, Ken-ichi; Kanno, Jun; Nakamura, Takuro

2014-07-01

Ewing's sarcoma is a highly malignant bone tumor found in children and adolescents, and the origin of this malignancy is not well understood. Here, we introduced a Ewing's sarcoma-associated genetic fusion of the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ) of long bones collected from late gestational murine embryos. EWS-ETS fusions efficiently induced Ewing's sarcoma-like small round cell sarcoma formation by these cells. Analysis of the eSZ revealed a fraction of a precursor cells that express growth/differentiation factor 5 (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS-ETS-dependent tumor induction. Genes downstream of the EWS-ETS fusion protein were quite transcriptionally active in eSZ cells, especially in regions in which the chromatin structure of the ETS-responsive locus was open. Inhibition of β-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewing's sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewing's sarcoma and provide clues to the histogenesis of Ewing's sarcoma in bone.

Kaposi sarcoma

Science.gov (United States)

... please enable JavaScript. Kaposi sarcoma is a cancerous tumor of the connective tissue, and is often associated with HIV/AIDS . Causes Before the HIV/AIDS epidemic, Kaposi sarcoma was seen mainly in older Italian ... this group, the tumors developed slowly. In people with HIV/AIDS, the ...

Uterine sarcoma Part II—Uterine endometrial stromal sarcoma: The TAG systematic review

Directory of Open Access Journals (Sweden)

Huann-Cheng Horng

2016-08-01

Full Text Available Endometrial stromal tumors are rare uterine tumors (<1%. Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS, and uterine undifferentiated sarcoma (UUS. This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS. Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

Directory of Open Access Journals (Sweden)

Dirksen Uta

2010-07-01

Full Text Available Abstract Background Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor. Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. Methods HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. Results 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Conclusions Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Efficacy of Wnt-1 monoclonal antibody in sarcoma cells

International Nuclear Information System (INIS)

Mikami, Iwao; Koizumi, Kiyoshi; Jablons, David M; You, Liang; He, Biao; Xu, Zhidong; Batra, Sonny; Lee, Amie Y; Mazieres, Julien; Reguart, Noemi; Uematsu, Kazutsugu

2005-01-01

Sarcomas are one of the most refractory diseases among malignant tumors. More effective therapies based on an increased understanding of the molecular biology of sarcomas are needed as current forms of therapy remain inadequate. Recently, it has been reported that Wnt-1/β-catenin signaling inhibits apoptosis in several cancers. In this study, we investigated the efficacy of a monoclonal anti-Wnt-1 antibody in sarcoma cells. We treated cell lines A-204, SJSA-1, and fresh primary cultures of lung metastasis of sarcoma with a monoclonal anti-Wnt-1 antibody. Wnt-1 siRNA treatment was carried out in A-204. We assessed cell death using Crystal Violet staining. Apoptosis induction was estimated by flow cytometry analysis (Annexin V and PI staining). Cell signaling changes were determined by western blotting analysis. We detected Wnt-1 expression in all tissue samples and cell lines. Significant apoptosis induction was found in monoclonal anti-Wnt-1 antibody treated cells compared to control monoclonal antibody treated cells (p < 0.02). Similarly, we observed increased apoptosis in Wnt-1 siRNA treated cells. Blockade of Wnt-1 signaling in both experiments was confirmed by analyzing intracellular levels of Dishevelled-3 and of cytosolic β-catenin. Furthermore, the monoclonal anti-Wnt-1 antibody also induced cell death in fresh primary cultures of metastatic sarcoma in which Wnt-1 signaling was active. Our results indicate that Wnt-1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells. These data suggest that Wnt-1 may be a novel therapeutic target for the treatment of a subset of sarcoma cells in which Wnt-1/β-catenin signaling is active

Epidemiology and therapies for metastatic sarcoma

Directory of Open Access Journals (Sweden)

Amankwah EK

2013-05-01

Full Text Available Ernest K Amankwah,1 Anthony P Conley,2 Damon R Reed2 1Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Sarcoma Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma, adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. Keywords: chemotherapy, pediatric sarcoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, synovial sarcoma

An efficient annotation and gene-expression derivation tool for Illumina Solexa datasets.

Science.gov (United States)

Hosseini, Parsa; Tremblay, Arianne; Matthews, Benjamin F; Alkharouf, Nadim W

2010-07-02

The data produced by an Illumina flow cell with all eight lanes occupied, produces well over a terabyte worth of images with gigabytes of reads following sequence alignment. The ability to translate such reads into meaningful annotation is therefore of great concern and importance. Very easily, one can get flooded with such a great volume of textual, unannotated data irrespective of read quality or size. CASAVA, a optional analysis tool for Illumina sequencing experiments, enables the ability to understand INDEL detection, SNP information, and allele calling. To not only extract from such analysis, a measure of gene expression in the form of tag-counts, but furthermore to annotate such reads is therefore of significant value. We developed TASE (Tag counting and Analysis of Solexa Experiments), a rapid tag-counting and annotation software tool specifically designed for Illumina CASAVA sequencing datasets. Developed in Java and deployed using jTDS JDBC driver and a SQL Server backend, TASE provides an extremely fast means of calculating gene expression through tag-counts while annotating sequenced reads with the gene's presumed function, from any given CASAVA-build. Such a build is generated for both DNA and RNA sequencing. Analysis is broken into two distinct components: DNA sequence or read concatenation, followed by tag-counting and annotation. The end result produces output containing the homology-based functional annotation and respective gene expression measure signifying how many times sequenced reads were found within the genomic ranges of functional annotations. TASE is a powerful tool to facilitate the process of annotating a given Illumina Solexa sequencing dataset. Our results indicate that both homology-based annotation and tag-count analysis are achieved in very efficient times, providing researchers to delve deep in a given CASAVA-build and maximize information extraction from a sequencing dataset. TASE is specially designed to translate sequence data

General Information about Kaposi Sarcoma

Science.gov (United States)

... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Immunosuppressive Therapy-Related Kaposi Sarcoma

Science.gov (United States)

... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Uterine sarcoma – current perspectives

Directory of Open Access Journals (Sweden)

Benson C

2017-08-01

Full Text Available Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade, undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. Keywords: sarcoma, leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyoma

Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma.

Science.gov (United States)

Liu, Tang; Shen, Jacson K; Li, Zhihong; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

2016-04-01

Sarcomas include some of the most aggressive tumors and typically respond poorly to chemotherapy. In recent years, specific gene fusion/mutations and gene over-expression/activation have been shown to drive sarcoma pathogenesis and development. These emerging genomic alterations may provide targets for novel therapeutic strategies and have the potential to transform sarcoma patient care. The RNA-guided nuclease CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein-9 nuclease) is a convenient and versatile platform for site-specific genome editing and epigenome targeted modulation. Given that sarcoma is believed to develop as a result of genetic alterations in mesenchymal progenitor/stem cells, CRISPR-Cas9 genome editing technologies hold extensive application potentials in sarcoma models and therapies. We review the development and mechanisms of the CRISPR-Cas9 system in genome editing and introduce its application in sarcoma research and potential therapy in clinic. Additionally, we propose future directions and discuss the challenges faced with these applications, providing concise and enlightening information for readers interested in this area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma.

Science.gov (United States)

Haga, Ayako; Ogawara, Yoko; Kubota, Daisuke; Kitabayashi, Issay; Murakami, Yasufumi; Kondo, Tadashi

2013-06-01

Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synovial sarcoma

Directory of Open Access Journals (Sweden)

Sucari S.C. Vlok

2014-12-01

Full Text Available Synovial sarcoma is a malignant, predominantly juxta-articular, soft-tissue tumour representing approximately 10% of all soft-tissue sarcomas. Frequently initially incorrectly diagnosed as a benign lesion, it should be considered as a diagnosis when a young adult patient presents with a calcified juxta-articular soft-tissue mass of insidious onset.

Clinical management of soft tissue sarcomas

International Nuclear Information System (INIS)

Pinedo, H.M.; Verweij, J.

1986-01-01

This book is concerned with the clinical management of soft tissue sarcomas. Topics covered include: Radiotherapy; Pathology of soft tissue sarcomas; Surgical treatment of soft tissue sarcomas; and Chemotherapy in advanced soft tissue sarcomas

Soft Tissue Sarcoma

Science.gov (United States)

... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.

Directory of Open Access Journals (Sweden)

Marisa R Buchakjian

Full Text Available Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection. Luciferase expression measured by real-time bioluminescence imaging increases over time, with an initial robust increase following viral injection, followed by a steady rise over the next several weeks as primary tumors develop and grow. Intramuscular injections were more commonly associated with evidence of systemic viral distribution than subcutaneous injections. All mice developed soft tissue sarcomas at the primary injection site, with histological examination identifying 93% of tumors as invasive pleomorphic sarcomas based on microscopic morphology and immunohistochemical expression of sarcoma markers. A lymphocytic infiltrate was present in 64% of the sarcomas in this immunocompetent model and 71% of tumors expressed PD-L1. This is the first report of a viral-Cre mediated Trp53/Pten mouse model of undifferentiated pleomorphic sarcoma. The bioluminescence imaging feature, along with high penetrance of the model and its immunological characteristics, makes it suited for pre-clinical studies of soft tissue sarcoma.

Junction region of EWS-FLI1 fusion protein has a dominant negative effect in Ewing's sarcoma in vitro.

Science.gov (United States)

Jully, Babu; Vijayalakshmi, Ramshankar; Gopal, Gopisetty; Sabitha, Kesavan; Rajkumar, Thangarajan

2012-11-12

Ewing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein. In-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251-343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251-280 ectopically in Ewing's sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed. Our modelling analysis indicated that Junction region (aa 251-343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing's sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect. Junction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing's Sarcoma.

General Information about Ewing Sarcoma

Science.gov (United States)

... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

Neutrality of miniSTR D22S1045 marker by Ewing's sarcoma phenotype.

Science.gov (United States)

Silva, Deborah S B S; Raimann, Paulo E; Moro, Tatiane; Picanço, Juliane B; Abujamra, Ana L; de Farias, Caroline B; Roesler, Rafael; Brunetto, Algemir L; Alho, Clarice S

2013-11-01

Neutrality investigations of markers with forensic use are important to see if a phenotypic trait is being expressed in relation to the alleles of the marker. MiniSTR marker D22S1045 (locus 22q12.3) is localized near the breakpoint region of the EWS gene (22q12.2), which leads to the development of Ewing's Sarcoma. Analyzing allele frequencies and linkage disequilibrium in Ewing's sarcoma patients and non-affected populations, we found that the marker mD22S1045 was neutral when related to Ewing's Sarcoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

Directory of Open Access Journals (Sweden)

Sonja Koopal

2007-09-01

Full Text Available Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV-infected tumor cells that express endothelial cell (EC markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

Treatment Option Overview (Ewing Sarcoma)

Science.gov (United States)

... Ewing Sarcoma Treatment Osteosarcoma Treatment Research Ewing Sarcoma Treatment (PDQ®)–Patient Version General Information About Ewing Sarcoma ... started or in another part of the body. Treatment Option Overview Key Points There are different types ...

Epidemiology and therapies for metastatic sarcoma

Science.gov (United States)

Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

2013-01-01

Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival.

Science.gov (United States)

Giebler, Maria; Staege, Martin S; Blauschmidt, Sindy; Ohm, Lea I; Kraus, Matthias; Würl, Peter; Taubert, Helge; Greither, Thomas

2018-01-01

A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients' prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated ( r S = 0.5; p = 6.4 × 10 -9 ; Spearman's rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival ( p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients' prognosis.

RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism.

Directory of Open Access Journals (Sweden)

For Yue Tso

2018-01-01

Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the etiologic agent of Kaposi's sarcoma (KS. It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment. Our approach is to characterize and compare the gene expression profile in KS lesions versus non-cancer tissues from the same individual. Such comparisons could identify pathways critical for KS formation and maintenance. This is the first study that utilized high throughput RNA-seq to characterize the viral and cellular transcriptome in tumor and non-cancer biopsies of African epidemic KS patients. These patients were treated anti-retroviral therapy with undetectable HIV-1 plasma viral load. We found remarkable variability in the viral transcriptome among these patients, with viral latency and immune modulation genes most abundantly expressed. The presence of KSHV also significantly affected the cellular transcriptome profile. Specifically, genes involved in lipid and glucose metabolism disorder pathways were substantially affected. Moreover, infiltration of immune cells into the tumor did not prevent KS formation, suggesting some functional deficits of these cells. Lastly, we found only minimal overlaps between our in vivo cellular transcriptome dataset with those from in vitro studies, reflecting the limitation of in vitro models in representing tumor lesions. These findings could lead to the identification of diagnostic and therapeutic markers for KS, and will provide bases for further mechanistic

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

Science.gov (United States)

Viollet, Coralie; Davis, David A.; Tekeste, Shewit S.; Reczko, Martin; Pezzella, Francesco; Ragoussis, Jiannis

2017-01-01

Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases. PMID:28046107

Efficacy of ATR inhibitors as single agents in Ewing sarcoma

DEFF Research Database (Denmark)

Nieto-Soler, Maria; Morgado-Palacin, Isabel; Lafarga, Vanesa

2016-01-01

Ewing sarcomas (ES) are pediatric bone tumors that arise from a driver translocation, most frequently EWS/FLI1. Current ES treatment involves DNA damaging agents, yet the basis for the sensitivity to these therapies remains unknown. Oncogene-induced replication stress (RS) is a known source...... efficacy in ES xenografts as single agents. Expression of EWS/FLI1 or EWS/ERG oncogenic translocations sensitizes non-ES cells to ATR inhibitors. Our data shed light onto the sensitivity of ES to genotoxic agents, and identify ATR inhibitors as a potential therapy for Ewing Sarcomas....

The Danish Sarcoma Database

Directory of Open Access Journals (Sweden)

Jorgensen PH

2016-10-01

Full Text Available Peter Holmberg Jørgensen,1 Gunnar Schwarz Lausten,2 Alma B Pedersen3 1Tumor Section, Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, 2Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Aim: The aim of the database is to gather information about sarcomas treated in Denmark in order to continuously monitor and improve the quality of sarcoma treatment in a local, a national, and an international perspective. Study population: Patients in Denmark diagnosed with a sarcoma, both skeletal and ekstraskeletal, are to be registered since 2009. Main variables: The database contains information about appearance of symptoms; date of receiving referral to a sarcoma center; date of first visit; whether surgery has been performed elsewhere before referral, diagnosis, and treatment; tumor characteristics such as location, size, malignancy grade, and growth pattern; details on treatment (kind of surgery, amount of radiation therapy, type and duration of chemotherapy; complications of treatment; local recurrence and metastases; and comorbidity. In addition, several quality indicators are registered in order to measure the quality of care provided by the hospitals and make comparisons between hospitals and with international standards. Descriptive data: Demographic patient-specific data such as age, sex, region of living, comorbidity, World Health Organization's International Classification of Diseases – tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System. Data quality and completeness are currently secured. Conclusion: The Danish Sarcoma Database is population based and includes sarcomas occurring in Denmark since 2009. It is a valuable tool for monitoring sarcoma incidence and quality of treatment and its improvement, postoperative

[Demographic Analysis of Patients with Osteosarcoma, Chonddrosarcoma, Ewing's Sarcoma from one Sarcoma Center in Switzerland].

Science.gov (United States)

Hodel, Sandro; Seeli, Franziska; Fuchs, Bruno

2015-06-17

Retrospective analysis of presentation, diagnosis and outcome of patients with osteosarcoma, chondrosarcoma and Ewing's sarcoma was performed for a single Sarcoma Center in Zurich at the University Hospital Balgrist. 201 patients were included. Overall survival at five and ten years were 74 ± 6%, 69 ± 7% for osteosarcoma (n = 85, since 2000), 85 ± 7%, 80 ± 9% for Ewing's sarcoma (n = 43, since 1990) and 86 ± 5%, 78 ± 9% for chondrosarcoma (n = 73, since 2000). The here presented overall survival rates from a single Sarcoma Center in Switzerland appear to be equivalent to other large international monocenter studies. The presentation and epidemiology of these patients are in accordance with large multicenter epidemiological studies. A nationwide sarcoma database (SwissSARCOS; www.sarcoma.ch) seems indispensable for more detailed analysis and quality management in such rare diseases.

Junction region of EWS-FLI1 fusion protein has a dominant negative effect in Ewing’s Sarcoma in vitro

International Nuclear Information System (INIS)

Jully, Babu; Vijayalakshmi, Ramshankar; Gopal, Gopisetty; Sabitha, Kesavan; Rajkumar, Thangarajan

2012-01-01

Ewing’s sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein. In-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251–343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251–280 ectopically in Ewing’s sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed. Our modelling analysis indicated that Junction region (aa 251–343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing’s sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect. Junction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing’s Sarcoma

Primary Intradural Extraosseous Ewing's Sarcoma

OpenAIRE

Kim, Seok Won; Shin, Ho

2009-01-01

Ewing's sarcoma usually arises from skeletal bone, but rarely may have an extraskeletal origin. However, Ewing's sarcoma that originates around the spinal column, especially, the intradural extramedullary type is extremely rare. We report a rare case of primary intraspinal extraskeletal Ewing's sarcoma.

Epigenetic silencing of apoptosis-inducing gene expression can be efficiently overcome by combined SAHA and TRAIL treatment in uterine sarcoma cells.

Directory of Open Access Journals (Sweden)

Leopold F Fröhlich

Full Text Available The lack of knowledge about molecular pathology of uterine sarcomas with a representation of 3-7% of all malignant uterine tumors prevents the establishment of effective therapy protocols. Here, we explored advanced therapeutic options to the previously discovered antitumorigenic effects of the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA by combined treatment with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2L. In addition, we investigated the uterine sarcoma cell lines, MES-SA and ESS-1, regarding the underlying molecular mechanisms of SAHA and TRAIL-induced apoptosis and their resistance towards TRAIL. Compared to single SAHA or TRAIL treatment, the combination of SAHA with TRAIL led to complete cell death of both tumor cell lines after 24 to 48 hours. In contrast to single SAHA treatment, apoptosis occured faster and was more pronounced in ESS-1 cells than in MES-SA cells. Induction of SAHA- and TRAIL-induced apoptosis was accompanied by upregulation of the intrinsic apoptotic pathway via reduction of mitochondrial membrane potential, caspase-3, -6, and -7 activation, and PARP cleavage, but was also found to be partially caspase-independent. Apoptosis resistance was caused by reduced expression of caspase-8 and DR 4/TRAIL-R1 in ESS-1 and MES-SA cells, respectively, due to epigenetic silencing by DNA hypermethylation of gene promoter sequences. Treatment with the demethylating agent 5-Aza-2'-deoxycytidine or gene transfer therefore restored gene expression and increased the sensitivity of both cell lines against TRAIL-induced apoptosis. Our data provide evidence that deregulation of epigenetic silencing by histone acetylation and DNA hypermethylation might play a fundamental role in the origin of uterine sarcomas. Therefore, tumor growth might be efficiently overcome by a cytotoxic combinatorial treatment of HDAC inhibitors with TRAIL.

Uterine sarcoma - current perspectives.

Science.gov (United States)

Benson, Charlotte; Miah, Aisha B

2017-01-01

Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases.

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

International Nuclear Information System (INIS)

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-01-01

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas

Standardizing evaluation of sarcoma proliferation- higher Ki-67 expression in the tumor periphery than the center

DEFF Research Database (Denmark)

Fernebro, J; Engellau, J; Persson, A

2007-01-01

Soft tissue sarcomas often present as large and histopathologically heterogenous tumors. Proliferation has repeatedly been identified as a prognostic factor and immunostaining for Ki-67 represents the most commonly used proliferation marker. There is, however, a lack of consensus on how to evaluate...... of proliferation in soft tissue sarcomas should be standardized for clinical application of Ki-67 as a prognostic marker....

Sarcomas: etiología y síntomas Sarcomas: etiology and symptoms

Directory of Open Access Journals (Sweden)

Roberto Gabriel Albín Cano

2012-07-01

Full Text Available Debido a la amplia diversidad de sarcomas, casi son inexistentes los textos que incluyen todas las variedades de este tipo de cáncer. Generalmente, su descripción y revisión se incluyen en las del sistema de órganos afectados específicamente, y la literatura que los aborda está muy fragmentada en las diferentes especialidades médicas. Se realiza una revisión bibliográfica sobre la etiología y síntomas de la mayor parte de los diferentes tipos de sarcomas. Es objetivo de esta revisión, lograr unir la información más actual disponible acerca de la etiología y síntomas de los sarcomas. Se han identificado diferentes factores de riesgo y factores etiológicos, tanto genéticos, infecciosos, como ambientales. Los grandes descubrimientos en relación con los mecanismos genéticos involucrados en los diferentes tipos de sarcoma, han abierto un camino de inestimable valor para introducir nuevos tratamientos, que incluyen ensayos con anticuerpos monoclonales y nuevos fármacos de terapia génica.

Due to the wide diversity of sarcomas, almost no texts include all varieties of this type of cancer. Generally, their description and review is included in those of the specifically affected organ system, and the literature containing that information is very fragmented in different medical specialties. We performed a literature review on the etiology and symptoms of most types of sarcomas. It is aimed at achieving a recompilation of most current information available on the causes and symptoms of sarcomas. Different risks and etiologic factors have been identified regarding genetics, infections, and environment. The great discoveries regarding genetic mechanisms involved in different types of sarcomas, have opened an invaluable way to introduce new treatments, including monoclonal antibodies and new drugs of gene therapy.

Radiosensitivity of soft tissue sarcomas

International Nuclear Information System (INIS)

Hirano, Toru; Iwasaki, Katsuro; Suzuki, Ryohei; Monzen, Yoshio; Hombo, Zenichiro

1989-01-01

The correlation between the effectiveness of radiation therapy and the histology of soft tissue sarcomas was investigated. Of 31 cases with a soft tissue sarcoma of an extremity treated by conservative surgery and postoperative radiation of 3,000-6,000 cGy, local recurrence occurred in 12; 5 out of 7 synovial sarcomas, 4 of 9 MFH, one of 8 liposarcomas, none of 4 rhabdomyosarcomas and 2 of 3 others. As for the histological subtyping, the 31 soft tissue sarcomas were divided into spindle cell, pleomorphic cell, myxoid and round cell type, and recurrence rates were 75%, 33.3%, 16.7% and 0%, respectively. From the remarkable difference in recurrent rate, it was suggested that round cell and myxoid type of soft tissue sarcomas showed a high radiosensitivity compared to the spindle cell type with low sensitivity. Clarifying the degree of radiosensitivity is helpful in deciding on the management of limb salvage in soft tissue sarcomas of an extremity. (author)

Sarcoma Immunotherapy: Past Approaches and Future Directions

Science.gov (United States)

D'Angelo, S. P.; Tap, W. D.; Schwartz, G. K.; Carvajal, R. D.

2014-01-01

Sarcomas are heterogeneous malignant tumors of mesenchymal origin characterized by more than 100 distinct subtypes. Unfortunately, 25–50% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease. PMID:24778572

Postirradiation sarcoma in retinoblastoma. Induction or predisposition

International Nuclear Information System (INIS)

Schwarz, M.B.; Burgess, L.P.; Fee, W.E. Jr.; Donaldson, S.S.

1988-01-01

An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods.13 references

Genome-wide gene expression dataset used to identify potential therapeutic targets in androgenetic alopecia

Directory of Open Access Journals (Sweden)

R. Dey-Rao

2017-08-01

Full Text Available The microarray dataset attached to this report is related to the research article with the title: “A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in androgenetic alopecia” (Dey-Rao and Sinha, 2017 [1]. Male-pattern hair loss that is induced by androgens (testosterone in genetically predisposed individuals is known as androgenetic alopecia (AGA. The raw dataset is being made publicly available to enable critical and/or extended analyses. Our related research paper utilizes the attached raw dataset, for genome-wide gene-expression associated investigations. Combined with several in silico bioinformatics-based analyses we were able to delineate five strategic molecular elements as potential novel targets towards future AGA-therapy.

Targeted therapies for bone sarcomas

International Nuclear Information System (INIS)

Mudry, P.

2011-01-01

Therapy success in bone sarcoma is significantly better compared to history cohorts with 60 - 70 % overall survival to date. Unfortunately, there is yet no shift and movement in better survival of patients with relapsed and refractory bone sarcomas during last twenty years. This article reviews targeted therapeutics for bone sarcomas which are under investigation and which could give chance to patients suffering from relapsed and chemo resistant bone sarcomas. Majority of the targeted drugs are given as part of phase 1 or 2 studies. (author)

Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

Science.gov (United States)

Gill, Sonja J; Travers, Jon; Pshenichnaya, Irina; Kogera, Fiona A; Barthorpe, Syd; Mironenko, Tatiana; Richardson, Laura; Benes, Cyril H; Stratton, Michael R; McDermott, Ultan; Jackson, Stephen P; Garnett, Mathew J

2015-01-01

Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.

Postradiation sarcomas: importance of surgery

International Nuclear Information System (INIS)

Lagrange, J.L.; Ramaioli, A.; Chateau, M.C.; Pignol, J.P.; Marchal, C.; Resbeut, M.; Richaud, P.; Rambert, P.; Tortechaux, J.; Seng, S.H.; La Fontan, B. de; Reme-Saumon, M.; Roullet, B.; Bof, J.; Coindre, J.M.

1997-01-01

Purpose: To evaluate the role of surgery in the treatment of Post-radiation sarcomas Materials. Post-radiation sarcomas is a rare entity and large series have rarely been reported. In order to improve knowledge about this entity the Radiotherapist group of the French Cancer Centres (FNCLCC) decided to collect retrospectively the cases treated in their institutions. In order to be sure of the histology, all the cases were reviewed by a panel of pathologists of the FNCLCC Pathologist group. A total of 129 cases of sarcomas, and 108 were reviewed; analysis of 8 is in progress, and no material was obtained in the other 11 cases. The diagnosis of sarcomas was confirmed in 80 cases. All patients (60 F, 20 M) have received radiation therapy (median dose 50 Gy; 9-110 Gy) for the treatment of the primary tumor. At this time the age was 44 years (6-83 y). Diagnoses included: breast C. 42%, Lymphomas 11.5%, gynaecological C. 10% benign lesions 5% miscellaneous. Sarcomas developed after a mean interval of 12 years (3-64 y), in bone in 30% of the cases and in soft tissue in 70%. The majority of lesions (90%) developed in the irradiated field (dose received was between 50 Gy and 60 Gy). Histologically there were 29% Malignant HistiocytofibroSarcomas, 19% OsteoSarcomas, 15% FibroSarcomas, 9% LipoSarcomas, 6% LeiomyoSarcomas, miscellaneous sarcomas 22%. Treatment included: Surgery 28 cases, Surgery+Chemotherapy 17 cases, Chemotherapy only 16 cases, Radiation therapy only 1 case, surgery + Radiation therapy 5 cases, Radiation therapy +chemotherapy 6 cases, Surgery + Radiation therapy + Chemotherapy 7 cases, no treatment 5 cases. Results. The outcome is known for all but 3 patients. 51 patients have died (44 of their sarcoma, 4 of the primary tumour, 2 of other cause and 1 iatrogenic). Median survival is 23 months (95% confidence interval 16-29 mo) but 9 patients survived 5 yr or more. Median survival was 43 mo for patients treated by surgery (28p), 6 mo for chemotherapy group (16 p

Ewing sarcoma

International Nuclear Information System (INIS)

Hamanoue, Satoshi; Makimoto, Atsushi

2007-01-01

Ewing sarcoma is the second most frequent primary bone cancer affecting children or young adults. Advances in molecular biology have revealed common chromosomal translocations such as EWS-FLI1 among Ewing sarcoma and related diseases such as primitive neuroectodermal tumor (PNET), so these are considered as Ewing sarcoma family tumor (ESFT). Although fewer than 10% of patients with ESFT survived before establishment of modern multiagent chemotherapy, the multimodal therapeutic regimens including combination chemotherapy, radiotherapy, and surgery can cure 60% of patients with localized disease, due to the collaborative research in European-American or the international trials. The standard chemotherapy for localized ESFT now comprises vincristine, actinomycin D, cyclophosphamide and doxorubicin (VACD) in Europe or vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC-IE) in North America. Meanwhile, those with metastatic disease have a much worse outcome with an approximately 10-30% 5-year event-free survival rate. New American-European collaborative trials such as EURO-E.W.I.N.G. 99 are in progress for further improvement of the cure rate in localized and metastatic ESFT. In Japan, Japan Ewing Sarcoma Study Group (JESS) phase II clinical trial for localized ESFT, and some clinical trials including new drugs are ongoing and waiting for results. (author)

Primary renal synovial sarcoma

Directory of Open Access Journals (Sweden)

Girish D. Bakhshi

2012-03-01

Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

Primary clear cell sarcoma of bone

International Nuclear Information System (INIS)

Choi, J.H.; Gu, M.J.; Kim, M.J.; Bae, Y.K.; Choi, W.H.; Shin, D.S.; Cho, K.H.

2003-01-01

Clear cell sarcoma is a rare soft tissue sarcoma of young adults with melanocytic differentiation. It occurs predominantly in the soft tissue of extremities, typically involving tendons and aponeuroses. Primary clear cell sarcoma of bone is extremely rare. We report a case of primary clear cell sarcoma of the right first metatarsal in a 48-year-old woman and provide a literature review of the entity. (orig.)

Radio-induced sarcomas in survivors of Ewing sarcoma

International Nuclear Information System (INIS)

Boriani, S.; Sudanese, A.; Toni, A.; Monesi, M.; Ciaroni, D.; Mancini, A.; Frezza, G.; Barbieri, E.; Picci, P.; Bacci, G.

1988-01-01

Of 255 cases of Ewing's sarcoma recorded at the Bone Tumor Center of the Rizzoli Orthopaedic Institute, 78 patients (irradiated and with a follow-up of longer than3 years) were considered ''at risk'' for the development of a second radio-induced sarcoma (RIS). Three of the 78 patients developed an RIS in the irradiated field. Theoretical and statistical analyses were carried out considering different modalities of local treatment. Statistically, the only significant factor was related to the irradiation dose. Surgical resection seems to prevent RIS

Lymphangiectatic Kaposi's sarcoma in a patient with AIDS Sarcoma de Kaposi linfangiectásico em paciente com Aids

Directory of Open Access Journals (Sweden)

Mônica Santos

2013-04-01

Full Text Available Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma.O sarcoma de Kaposi é uma neoplasia originária do endotélio linfatico, que apresenta um amplo espectro de manifestações, com quatro formas clínicas: sarcoma de Kaposi clássico, endêmico, iatrogêncio e epidêmico ou associado ao HIV. Em pacientes imunocompetentes, a doença é tipicamente limitada às extremidades. Porém em pacientes imunideprimidos, o sarcoma de Kaposi é uma doença sistêmica multifocal. Apresenta cursos clínicos diferentes, desde simples lesões cutâneas isoladas até lesões agressivas e difusas, com ou sem envolvimento sistêmico. Lesões avançadas de sarcoma de Kaposi, principalmente as localizadas nas extremidades, podem apresentar linfedema. Neste trabalho, reportamos caso de paciente com forma rara de Sarcoma de Kaposi associado a Aids, chamada de sarcoma de Kaposi linfangiectásico.

Radiographic appearance of Ewing sarcoma of the hands and feet: report from the Intergroup Ewing Sarcoma Study

International Nuclear Information System (INIS)

Reinus, W.R.; Gilula, L.A.; Shirley, S.K.; Askin, F.B.; Siegal, G.P.

1985-01-01

Review of current data from the Intergroup Ewing Sarcoma Study (IESS) shows that Ewing sarcoma is rare in bones of the hands and feet. The 12 patients from the IESS protocols with hand or foot Ewing sarcoma are comparable to those already reported in the literature. With the exception of lesions in the calcaneus, the prognosis for disease-free survival is excellent. The radiographic features of hand and foot Ewing sarcoma are generally those of classic Ewing sarcoma: permeation, soft-tissue mass, and often, associated sclerotic reaction. However, with the exception of sclerosis, features suggesting bone reaction and slow tumor growth in these patients were distinctly uncommon compared with Ewing sarcoma in general. Apparently location of the lesion is important, since in the reported cases in the literature and in this series, lesions of the calcaneus fared poorly. The importance of this set of patients therefore relates to awareness and early recognition of an unusual appearance and location of Ewing sarcoma

EWS-FLI1 inhibits TNFα-induced NFκB-dependent transcription in Ewing sarcoma cells

International Nuclear Information System (INIS)

Lagirand-Cantaloube, Julie; Laud, Karine; Lilienbaum, Alain; Tirode, Franck; Delattre, Olivier; Auclair, Christian; Kryszke, Marie-Helene

2010-01-01

Research highlights: → EWS-FLI1 interferes with TNF-induced activation of NFκB in Ewing sarcoma cells. → EWS-FLI1 knockdown in Ewing sarcoma cells increases TNF-induced NFκB binding to DNA. → EWS-FLI1 reduces TNF-stimulated NFκB-dependent transcriptional activation. → Constitutive NFκB activity is not affected by EWS-FLI1. → EWS-FLI1 physically interacts with NFκB p65 in vivo. -- Abstract: Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NFκB) is a tightly regulated transcription factor controlling cell survival, proliferation and differentiation, as well as tumorigenesis. NFκB activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NFκB activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NFκB basal activity, but impairs TNF-induced NFκB-driven transcription, at least in part through inhibition of NFκB binding to DNA. We detected an in vivo physical interaction between the fusion protein and NFκB p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NFκB.

Radiation-induced soft-tissue and bone sarcoma

International Nuclear Information System (INIS)

Kim, J.H.; Chu, F.C.; Woodard, H.Q.; Melamed, R.; Huvos, A.; Cantin, J.

1978-01-01

From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed

Gene expression response to EWS–FLI1 in mouse embryonic cartilage

Directory of Open Access Journals (Sweden)

Miwa Tanaka

2014-12-01

Full Text Available Ewing's sarcoma is a rare bone tumor that affects children and adolescents. We have recently succeeded to induce Ewing's sarcoma-like small round cell tumor in mice by expression of EWS–ETS fusion genes in murine embryonic osteochondrogenic progenitors. The Ewing's sarcoma precursors are enriched in embryonic superficial zone (eSZ cells of long bone. To get insights into the mechanisms of Ewing's sarcoma development, gene expression profiles between EWS–FLI1-sensitive eSZ cells and EWS–FLI1-resistant embryonic growth plate (eGP cells were compared using DNA microarrays. Gene expression of eSZ and eGP cells (total, 30 samples was evaluated with or without EWS–FLI1 expression 0, 8 or 48 h after gene transduction. Our data provide useful information for gene expression responses to fusion oncogenes in human sarcoma.

A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.

Science.gov (United States)

Leacock, Stefanie W; Basse, Audrey N; Chandler, Garvin L; Kirk, Anne M; Rakheja, Dinesh; Amatruda, James F

2012-01-01

Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

Proof of radiation-induced tumour TNF-α expression in Ewing sarcoma cell line RM-82 following clinically relevant in vitro fractionated irradiation and in vivo one-time irradiation

International Nuclear Information System (INIS)

Litzenberger, K.; Ruebe, C.E.; Erren, M.; Liu, L.; Valen, F. van; Palm, J.; Yang, K.; Ruebe, C.

2004-01-01

The purpose of the present study was to investigate the influence of fractionated irradiation on TNF-α expression in Ewing sarcoma cell line RM-82 in vitro and following its establishment as a xenograft tumour in the nude mouse in vivo [de

Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?

DEFF Research Database (Denmark)

Carneiro, Ana; Francis, Princy; Bendahl, Pär-Ola

2009-01-01

Soft tissue sarcoma (STS) diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC arrays and gene expression profiling to 18 extremity soft tissue LMS and...

Promiscuous partnerships in Ewing's sarcoma.

Science.gov (United States)

Sankar, Savita; Lessnick, Stephen L

2011-07-01

Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing's sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing's sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing's sarcoma. However, in recent years there have been reports of rare fusions in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing's sarcoma and Ewing's-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

[Update on soft tissue sarcomas].

Science.gov (United States)

Bui, Binh Nguyen; Tabrizi, Reza; Dagada, Corinne; Trufflandier, Nathalie; St ckle, Eberhard; Coindre, Jean-Michel

2002-01-01

Important refinements have taken place in the diagnosis of soft tissue sarcoma with extensive use of immuno-histochemistry. New entities have been described, while malignant histiocytofibroma, the most diagnosed sarcoma type during the last two decades, has been dismembered. As for prognosis, the new UICC classification is effectively more discriminating in the definition of prognostic groups; but the usefullness of new biological or genetic markers remains to be assessed. Several breakthrough have taken place in the last years in the treatment of soft tissue sarcoma. Isolated limb perfusion with TNF, hyperthermia and melphalan have proven its efficacy, and is now an alternative to preoperative chemotherapy and/or radiotherapy for limb sparing treatment of the primary tumor site or to amputation. For systemic treatments, novel cytostatic drugs have been shown to be active in sarcomas, including ecteinascidine (ET743) and Glivec (STI571). This last drug has been shown to be remarkably active in c-kit+ stromal sarcoma of the gastro-intestinal tract. It can hopefully regarded as an example for targeted therapies, which may come with a better understanding of the molecular mechanisms triggered by the fundamental, specific genetic alterations shown in sarcoma.

Kaposi’s Sarcoma in Film

Directory of Open Access Journals (Sweden)

Richard F. WAGNER

2016-04-01

Full Text Available Kaposi’s sarcoma, a historically rare, indolent cutaneous malignancy of elderly men emerged as a frequent and easily recognizable cutaneous manifestation of Acquired Immunodeficiency Syndrome in the 1980s. Since these tumors were often visible to the public, Kaposi’s sarcoma quickly became a stigmatizing marker for those infected, and predicted the high mortality risk from comorbid opportunistic infections. English language films released from 1985-2008 are analyzed for their depictions of Kaposi’s sarcoma, and the role(s it played in these films. With the advent of highly active antiretroviral therapy for those with HIV infection, Kaposi’s sarcoma has once again become relatively rare.

The MetabolomeExpress Project: enabling web-based processing, analysis and transparent dissemination of GC/MS metabolomics datasets

Directory of Open Access Journals (Sweden)

Carroll Adam J

2010-07-01

Full Text Available Abstract Background Standardization of analytical approaches and reporting methods via community-wide collaboration can work synergistically with web-tool development to result in rapid community-driven expansion of online data repositories suitable for data mining and meta-analysis. In metabolomics, the inter-laboratory reproducibility of gas-chromatography/mass-spectrometry (GC/MS makes it an obvious target for such development. While a number of web-tools offer access to datasets and/or tools for raw data processing and statistical analysis, none of these systems are currently set up to act as a public repository by easily accepting, processing and presenting publicly submitted GC/MS metabolomics datasets for public re-analysis. Description Here, we present MetabolomeExpress, a new File Transfer Protocol (FTP server and web-tool for the online storage, processing, visualisation and statistical re-analysis of publicly submitted GC/MS metabolomics datasets. Users may search a quality-controlled database of metabolite response statistics from publicly submitted datasets by a number of parameters (eg. metabolite, species, organ/biofluid etc.. Users may also perform meta-analysis comparisons of multiple independent experiments or re-analyse public primary datasets via user-friendly tools for t-test, principal components analysis, hierarchical cluster analysis and correlation analysis. They may interact with chromatograms, mass spectra and peak detection results via an integrated raw data viewer. Researchers who register for a free account may upload (via FTP their own data to the server for online processing via a novel raw data processing pipeline. Conclusions MetabolomeExpress https://www.metabolome-express.org provides a new opportunity for the general metabolomics community to transparently present online the raw and processed GC/MS data underlying their metabolomics publications. Transparent sharing of these data will allow researchers to

Proximal-type epithelioid sarcoma - Case report Sarcoma epitelióide tipo proximal - Relato de caso

Directory of Open Access Journals (Sweden)

Luciana Mendes dos Santos

2013-06-01

Full Text Available Epithelioid sarcoma, first described by Enzinger in 1970, is a rare soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in distal portions of the extremities of adolescents and young adults. In 1997, Guillou et al. described a different type of epithelioid sarcoma, called proximal-type epithelioid sarcoma, which is found mostly in the pelvic and perineal regions and genital tracts of young to middle-aged adults. It is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. In this paper we present a case of proximal-type epithelioid sarcoma with an aggressive clinical course, including distant metastasis and death nine months after diagnosis.O sarcoma epitelióide, primeiramente descrito por Enzinger, em 1970, é uma neoplasia de partes moles que ocorre principalmente nas extremidades distais de adolescentes e adultos jovens. Em 1997, Guillou e cols. descreveram um tipo diferente de sarcoma epitelióide, que afetava frequentemente a região pélvica, períneo e áreas genitais de pacientes de média idade, com exame histológico caracterizado pela proliferação de células com aspecto epitelióide. Neste trabalho, descreve-se caso de paciente que apresentava há três meses duas lesões na região glútea, cujo exame histológico confirmou diagnóstico de sarcoma epitelioide do tipo proximal, já com presença de metástases pulmonares e cerebrais e que foi a óbito nove meses após o diagnóstico.

Evaluation of c-kit expression in classic Kaposi's sarcoma in a cohort of Egyptian patients

International Nuclear Information System (INIS)

Hussein, T.M.; El-Sabaa, B.M.; Hanafy, N.F.

2012-01-01

Kaposis sarcoma (KS) is in angio proliferative disorder associated with human herpes virus 8 infection. Classic Ks is the most prevalent type of KS in countries of the Mediterranean basin including Egypt. Several in vitro studies have detected C-kit expression in AIDS related-KS however, only a few studies addressed this Issue In the classic type with no data on the ethnicity of studied cases. The prospect of installing targeted anti-c-kit treatment to KS patients presents a promising avenue in KS therapeutics. Aim: To elucidate the expression of c-kit in classic KS cases and study possible relations with expression of HHV8 latency-associated nuclear antigen-1 (LANA-1) and other clinico pathological parameters. Methods: Twenty four cases of classic KS of the plaque and nodular stages in the lower limb were studied. Immunohistochemical detection of HHV8-LANA-1 and c-kit was carried out on archival paraffin embedded tissue, possession of the pathology and dermatology Departments, Alexandria School Of Medicine, Egypt. Statistical analysis of possible reltions between both antigen and clinico pathological parameters (patient age and gender and histological stage) was performed. Results: HHV8 expression was detected in 100% of cases while c-kit immunoreactivity was found in 54.2% of cases. There was no correlation between c-kit and HHV8 immunoreactivity or any of the studied clinico pathological parameters. Conclusions: This is the first report of c-kit expression in classic KS in an ethnically homogeneous cohort of arabs of the Mediterranean region. We detected c-kit expression in about half the cases with no relationship to HHV8 LANA expression or clinico pathological parameters

Simultaneous lymph node involvement by Castleman disease and Kaposi sarcoma

Directory of Open Access Journals (Sweden)

Luciana Wernersbach Pinto

2011-02-01

Full Text Available Both multicentric Castleman disease and Kaposi sarcoma are more frequently observed in HIV infected patients. The coexistence of these Human herpesvirus 8 related lesions, in the same tissue, has been observed, but literature reports are scant. On the other hand, the expression of HHV-8-LANA-1 is easily demonstrable by immunohistochemistry. This has been shown to be a powerful tool for the diagnosis of these entities. The aim of this report is to communicate our experience with a case of multicentric Castleman disease occurring in the setting of HIV infection, which demonstrated microscopic Kaposi sarcoma in the same lymph node during the pathological work-up

Sarcoma risk after radiation exposure

Directory of Open Access Journals (Sweden)

Berrington de Gonzalez Amy

2012-10-01

Full Text Available Abstract Sarcomas were one of the first solid cancers to be linked to ionizing radiation exposure. We reviewed the current evidence on this relationship, focusing particularly on the studies that had individual estimates of radiation doses. There is clear evidence of an increased risk of both bone and soft tissue sarcomas after high-dose fractionated radiation exposure (10 + Gy in childhood, and the risk increases approximately linearly in dose, at least up to 40 Gy. There are few studies available of sarcoma after radiotherapy in adulthood for cancer, but data from cancer registries and studies of treatment for benign conditions confirm that the risk of sarcoma is also increased in this age-group after fractionated high-dose exposure. New findings from the long-term follow-up of the Japanese atomic bomb survivors suggest, for the first time, that sarcomas can be induced by acute lower-doses of radiation (

Uterine sarcoma – current perspectives

Science.gov (United States)

Benson, Charlotte; Miah, Aisha B

2017-01-01

Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. PMID:28919822

PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells.

Directory of Open Access Journals (Sweden)

Diana Marklein

Full Text Available We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX. We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.

EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewing's sarcoma.

Directory of Open Access Journals (Sweden)

Leah A Owen

2008-04-01

Full Text Available EWS/FLI is a master regulator of Ewing's sarcoma formation. Gene expression studies in A673 Ewing's sarcoma cells have demonstrated that EWS/FLI downregulates more genes than it upregulates, suggesting that EWS/FLI, and/or its targets, function as transcriptional repressors. One critical EWS/FLI target, NKX2.2, is a transcription factor that contains both transcriptional activation and transcriptional repression domains, raising the possibility that it mediates portions of the EWS/FLI transcriptional signature. We now report that microarray analysis demonstrated that the transcriptional profile of NKX2.2 consists solely of downregulated genes, and overlaps with the EWS/FLI downregulated signature, suggesting that NKX2.2 mediates oncogenic transformation via transcriptional repression. Structure-function analysis revealed that the DNA binding and repressor domains in NKX2.2 are required for oncogenesis in Ewing's sarcoma cells, while the transcriptional activation domain is completely dispensable. Furthermore, blockade of TLE or HDAC function, two protein families thought to mediate the repressive function of NKX2.2, inhibited the transformed phenotype and reversed the NKX2.2 transcriptional profile in Ewing's sarcoma cells. Whole genome localization studies (ChIP-chip revealed that a significant portion of the NKX2.2-repressed gene expression signature was directly mediated by NKX2.2 binding. These data demonstrate that the transcriptional repressive function of NKX2.2 is necessary, and sufficient, for the oncogenic phenotype of Ewing's sarcoma, and suggest a therapeutic approach to this disease.

Imaging Primary Mouse Sarcomas After Radiation Therapy Using Cathepsin-Activatable Fluorescent Imaging Agents

Energy Technology Data Exchange (ETDEWEB)

Cuneo, Kyle C. [Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Mito, Jeffrey K.; Javid, Melodi P. [Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Ferrer, Jorge M. [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Kim, Yongbaek [Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul (Korea, Republic of); Lee, W. David [The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Bawendi, Moungi G. [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts (United States); Brigman, Brian E. [Department of Orthopedic Surgery, Duke University School of Medicine, Durham, North Carolina (United States); Kirsch, David G., E-mail: david.kirsch@duke.edu [Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States)

2013-05-01

Purpose: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. Methods and Materials: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activated fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. Results: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. Conclusions: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.

Classical NF-κB Metabolically Reprograms Sarcoma Cells Through Regulation of Hexokinase 2

Directory of Open Access Journals (Sweden)

Priya Londhe

2018-04-01

Full Text Available BackgroundMetabolic reprogramming has emerged as a cancer hallmark, and one of the well-known cancer-associated metabolic alterations is the increase in the rate of glycolysis. Recent reports have shown that both the classical and alternative signaling pathways of nuclear factor κB (NF-κB play important roles in controlling the metabolic profiles of normal cells and cancer cells. However, how these signaling pathways affect the metabolism of sarcomas, specifically rhabdomyosarcoma (RMS and osteosarcoma (OS, has not been characterized.MethodsClassical NF-κB activity was inhibited through overexpression of the IκBα super repressor of NF-κB in RMS and OS cells. Global gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0, and data were interpreted using gene set enrichment analysis. Seahorse Bioscience XFe24 was used to analyze oxygen consumption rate as a measure of aerobic respiration.ResultsInhibition of classical NF-κB activity in sarcoma cell lines restored alternative signaling as well as an increased oxidative respiratory metabolic phenotype in vitro. In addition, microarray analysis indicated that inhibition of NF-κB in sarcoma cells reduced glycolysis. We showed that a glycolytic gene, hexokinase (HK 2, is a direct NF-κB transcriptional target. Knockdown of HK2 shifted the metabolic profile in sarcoma cells away from aerobic glycolysis, and re-expression of HK2 rescued the metabolic shift induced by inhibition of NF-κB activity in OS cells.ConclusionThese findings suggest that classical signaling of NF-κB plays a crucial role in the metabolic profile of pediatric sarcomas potentially through the regulation of HK2.

Genome-wide mRNA and miRNA expression data analysis to screen for markers involved in sarcomagenesis in human chondrosarcoma cell lines

Directory of Open Access Journals (Sweden)

Biju Issac

2014-12-01

Full Text Available Genes and miRNAs involved in sarcomagenesis related pathways are unknown and therefore signaling events leading to mesenchymal cell transformation to sarcoma are poorly elucidated. Exiqon and Illumina microarray study on human chondrosarcoma JJ012 and chondrocytes C28 cell lines to compare and analyze the differentially expressed miRNAs and their gene targets was recently published in the Journal Tumor Biology in 2014. Here we describe in details the contents and quality controls for the miRNA and gene expression data associated with the study that is relevant to this dataset.

A zebrafish transgenic model of Ewing’s sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis

Directory of Open Access Journals (Sweden)

Stefanie W. Leacock

2012-01-01

Ewing’s sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing’s sarcoma family tumors (ESFTs, which include peripheral primitive neuroectodermal tumors (PNETs, are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing’s sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing’s sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing’s sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

An enhanced topologically significant directed random walk in cancer classification using gene expression datasets

Directory of Open Access Journals (Sweden)

Choon Sen Seah

2017-12-01

Full Text Available Microarray technology has become one of the elementary tools for researchers to study the genome of organisms. As the complexity and heterogeneity of cancer is being increasingly appreciated through genomic analysis, cancerous classification is an emerging important trend. Significant directed random walk is proposed as one of the cancerous classification approach which have higher sensitivity of risk gene prediction and higher accuracy of cancer classification. In this paper, the methodology and material used for the experiment are presented. Tuning parameter selection method and weight as parameter are applied in proposed approach. Gene expression dataset is used as the input datasets while pathway dataset is used to build a directed graph, as reference datasets, to complete the bias process in random walk approach. In addition, we demonstrate that our approach can improve sensitive predictions with higher accuracy and biological meaningful classification result. Comparison result takes place between significant directed random walk and directed random walk to show the improvement in term of sensitivity of prediction and accuracy of cancer classification.

Chemokines in Ewing sarcoma

NARCIS (Netherlands)

Sand, L.G.L.

2016-01-01

Ewing sarcoma is an aggressive primary malignant bone tumor with high degree of tumor vascularization and is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. To identify novel therapies and

CYP3A isoforms in Ewing's sarcoma tumours: an immunohistochemical study with clinical correlation.

Science.gov (United States)

Zia, Hamid; Murray, Graeme I; Vyhlidal, Carrie A; Leeder, J Steven; Anwar, Ahmed E; Bui, Marilyn M; Ahmed, Atif A

2015-04-01

Ewing's sarcoma is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P Ewing's sarcoma tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Ewing`s Sarcoma

Directory of Open Access Journals (Sweden)

Agnieszka Budny

2017-06-01

Full Text Available Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Clinical presentation is usually dominated by local bone pain and a mass. Magnetic resonance best defines the extent of the lesion. Patients diagnosed with Ewing's sarcoma within  last years show a improving  survival rate . Rehabilitation seems to be a crucial part of multimodal therapy.

Quantitative PCR and immunohistochemical analyses of HMGB1 and RAGE expression in canine disseminated histiocytic sarcoma (malignant histiocytosis).

Science.gov (United States)

Sterenczak, Katharina A; Kleinschmidt, Sven; Wefstaedt, Patrick; Eberle, Nina; Hewicker-Trautwein, Marion; Bullerdiek, Jörn; Nolte, Ingo; Murua Escobar, Hugo

2011-05-01

Disorders of histiocytic origin affecting humans and dogs share various similarities. Canine disseminated histiocytic sarcoma (DHS) (formerly known as malignant histiocytosis) is an aggressive neoplasm of interstitial dendritic cells (DCs). The receptor for glycation end products (RAGE) and the high mobility group box1 protein (HMGB1) have been shown to be required for the maturation and migration of DCs. Thus, deregulation of the expression of these genes could have a major effect on the progression of histiocytic disorders. Neoplastic canine DHS samples and non-neoplastic control samples were analysed immunohistochemically and via real-time PCR. Significant down-regulation of RAGE in the lung tumour samples and down-regulation of HMGB1 in the lung, lymph node and spleen tumour samples were detected compared to their non-neoplastic counterparts. RAGE and HMGB1 expression down-regulation in canine DHS points to a role in the progression of histiocytic disorders.

Sarcoma de Kaposi clássico fatal Fatal outcome in classic Kaposi's sarcoma

Directory of Open Access Journals (Sweden)

Eugênia Maria Damásio N. Ohe

2010-06-01

Full Text Available Descrito em 1872, o sarcoma de Kaposi é neoplasia multicêntrica rara originária de células endoteliais com manifestação cutânea e extracutânea. A forma clássica é muito mais frequente em homens idosos, com evolução prolongada e boa resposta a quimioterapia e radioterapia. Apresentaremos um caso de sarcoma de Kaposi clássico com comprometimento cutâneo e visceral em paciente do sexo feminino com rápida evolução fatal.First described in 1872, Kaposi's sarcoma is defined as a rare multifocal tumor that originates in the endothelial cells and presents with cutaneous and extracutaneous manifestations. The classic form is most common in elderly men and progression is slow. This tumor responds well to chemotherapy and radiotherapy. This report describes a classic case of Kaposi's sarcoma in a woman with skin and visceral manifestations in whom the disease rapidly progressed to a fatal outcome.

Technetium scanning in Kaposi's sarcoma and its simulators

International Nuclear Information System (INIS)

Gunnoe, R.; Kalivas, J.

1982-01-01

The clinical picture of ulcerated purple plaques on the legs often suggests several diagnoses: Kaposi's sarcoma, stasis dermatitis, atrophie blanche (livedoid vasculitis), and a poorly understood condition called acroangiodermatitis of Favre-Chaix (pseudo-Kaposi's sarcoma). Even the skin biopsy may not always be conclusive. We describe our experience with three patients with pseudo-Kaposi's sarcoma, one with true Kaposi's sarcoma and two with atrophie blanche. Clinical and histopathologic similarities among these three conditions pointed up the need for additional confirmatory studies, i.e., isotope scanning. The technetium scan was positive in both Kaposi's sarcoma and pseudo-Kaposi's sarcoma but negative in atrophie blanche

Synovial sarcoma of the abdominal wall

International Nuclear Information System (INIS)

Matushita, J.P.K.; Matushita, J.S.

1989-01-01

A case report of synovial sarcoma arising in the abdominal wall is presented. A brief review of the clinical and radiological features of synovial sarcoma is made. Pre-operative diagnosis of an abdominal wall synovial sarcoma is virtually impossible, but should be considered when a soft tissue swelling is found to show amorphous stippled calcification X-ray. (author) [pt

Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

Science.gov (United States)

Herrero-Martin, David; Fourtouna, Argyro; Niedan, Stephan; Riedmann, Lucia T.; Schwentner, Raphaela; Aryee, Dave N. T.

2011-01-01

Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease. PMID:22135504

Roentgenologic examination in Kaposi's sarcoma

International Nuclear Information System (INIS)

Kossovoj, A.L.

1990-01-01

Review of roentgenologic investigations into Kaposi's sarcoma is presented. It is shown that Kaposi's sarcoma is a disease injuring skin, osteal system, lungs and mediastinum, gastroeuteric tract and lymphatic nodes. Roentgenologic changes of soft tissues of limbs, osteal system, chest and gastroenteric tract organs are described. Manifestations of a tumor of any localization are quite different which makes it more difficult to perform roentgenologic diagnosis. An increase of Kaposi's sarcoma occurrence in patients suffering from aids as the disease increases is indicated

Penile epithelioid sarcoma: MR imaging findings

Energy Technology Data Exchange (ETDEWEB)

Sirikci, A.; Bayram, M.; Demirci, M. [Department of Radiology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey); Bakir, K. [Department of Pathology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey); Sarica, K. [Department of Urology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey)

1999-10-01

Magnetic resonance imaging findings of a 38-year-old man with epithelioid sarcoma of the penis is presented. It started as a firm, painless and slowly growing nodule at the base of his penis 6 months previously which caused pain radiating to the testis during coitus. It has been well known that sarcomas may well mimic reactive processes. Initial presentation of epithelioid sarcoma may provoke considerable diagnostic difficulty, and its differentiation from benign lesions, such as Peyronie`s disease and chronic inflammation, may be a clinical problem. In our present report the MR findings are compared with those of the epithelioid sarcomas of various locations reported in the literature and differential diagnosis of the entity is discussed. To our knowledge, this is the first report regarding the MR findings of the epithelioid sarcoma of penis. (orig.) With 3 figs., 16 refs.

Synovial sarcoma: MR evaluation in 23 patients

International Nuclear Information System (INIS)

Galant, J.; Marti-Bonmati, L.; Lafuente, J.; Hernandez, L.; Soler, R.; Saez, F.

1997-01-01

The synovial sarcoma is one of the most common soft tissue sarcomas. MR is the technique of choice to determine to local extension of malignant soft tissue tumors. To assess the clinical and MR imaging parameters associated with synovial sarcomas that aid in establishing their diagnosis. We review the clinical findings and images of 23 histologically confirmed synovial sarcomas that were studied by MR. Synovial sarcomas usually develop in young adults as soft tissue tumors, preferentially in the deep tissues of an extremity in close proximity to a joint. They are characterized as having a lobulated contour and septa, frequently infiltrating neighboring tissues at some point, and are heterogeneous. The presence of hemorrhage, as well as infiltration of the fascia in subcutaneous tumors, suggests the diagnosis of synovial sarcoma. The development of perilesional edema is not uncommon. Although, logically, the clinical and radiological features of synovial sarcomas can overlap with those of other soft tissue tumors, the findings described here are fairly characteristic of these lesions: thus, when present, they should serve to orient the diagnostic process. (Author) 16 refs

Breast sarcomas. Literature review

Directory of Open Access Journals (Sweden)

D. A. Ryabchikov

2014-01-01

Full Text Available The article presents an overview of the literature about breast sarcomas (nonepithelial malignances. Primary sarcomas are extremely rare, with less than 1 % of all malignant tumors of the breast. Breast carcinomas cause an increased interest of the scientists due to their unique clinical and pathological features and unpredictable prognosis.

Autophagy as a potential target for sarcoma treatment.

Science.gov (United States)

Min, Li; Choy, Edwin; Pollock, Raphael E; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

2017-08-01

Autophagy is a constitutively active, evolutionary conserved, catabolic process for maintaining homeostasis in cellular stress responses and cell survival. Although its mechanism has not been fully illustrated, recent work on autophagy in various types of sarcomas has demonstrated that autophagy exerts an important role in sarcoma cell growth and proliferation, in pro-survival response to therapies and stresses, and in therapeutic resistance of sarcoma. Thus, the autophagic process is being seen as a possibly novel therapeutic target of sarcoma. Additionally, some co-regulators of autophagy have also been investigated as promising biomarkers for the diagnosis and prognosis of sarcoma. In this review, we summarize contemporary advances in the role of autophagy in sarcoma and discuss the potential of autophagy as a new target for sarcoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment Option Overview (Kaposi Sarcoma)

Science.gov (United States)

... Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

LGR5 is expressed by Ewing sarcoma and potentiates Wnt/β-catenin signaling

Directory of Open Access Journals (Sweden)

Christopher A Scannell

2013-04-01

Full Text Available Ewing sarcoma (ES is an aggressive bone and soft tissue tumor of putative stem cell origin that predominantly occurs in children and young adults. Although most patients with localized ES can be cured with intensive therapy, the clinical course is variable and up to one third of patients relapse following initial remission. Unfortunately, little is yet known about the biologic features that distinguish low-risk from high-risk disease or the mechanisms of ES disease progression. Recent reports have suggested that putative cancer stem cells exist in ES and may contribute to an aggressive phenotype. The cell surface receptor LGR5 (leucine-rich repeat-containing G-protein coupled receptor 5 is a somatic stem cell marker that functions as an oncogene in several human cancers, most notably colorectal carcinoma. LGR5 is a receptor for the R-spondin (RSPO family of ligands and RSPO-mediated activation of LGR5 potentiates Wnt/β-catenin signaling, contributing to stem cell proliferation and self-renewal. Given its presumed stem cell origin, we investigated whether LGR5 contributes to ES pathogenesis. We found that LGR5 is expressed by ES and that its expression is relatively increased in cells and tumors that display a more aggressive phenotype. In particular, LGR5 expression was increased in putative cancer stem cells. We also found that neural crest-derived stem cells express LGR5, raising the possibility that expression of LGR5 may be a feature of ES cells of origin. LGR5-high ES cells showed nuclear localization of ß-catenin and robust activation of TCF-reporter activity when exposed to Wnt ligand and this was potentiated by RSPO. However, modulation of LGR5 or exposure to RSPO had no impact on proliferation confirming that Wnt/ β-catenin signaling in ES cells does not recapitulate signaling in epithelial cells. Together these studies show that the RSPO-LGR5-WNT- β-catenin axis is present and active in ES and may contribute to tumor pathogenesis.

[Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors].

Science.gov (United States)

Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

2012-09-01

The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

Directory of Open Access Journals (Sweden)

David Herrero-Martin

2011-01-01

Full Text Available Ewing's sarcoma family tumors (ESFT are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease.

Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with fibroblasts.

Science.gov (United States)

Aoki, Mikiko; Koga, Kaori; Hamasaki, Makoto; Egawa, Nagayasu; Nabeshima, Kazuki

2017-06-01

Emmprin (extracellular matrix metalloproteinase inducer, CD147) is a glycosylated transmembrane protein, consisting of two immunoglobulin domains, that stimulates the production of matrix metalloproteinases (MMPs) by tumor-associated fibroblasts. These effects play important roles in tumor invasion and metastasis. However, the precise mechanisms by which emmprin acts on fibroblasts have not been fully elucidated, especially in sarcoma cells. Previously, we demonstrated that emmprin, expressed in conditioned medium collected from the epithelioid sarcoma cell line (FU-EPS-1), stimulates MMP-2 production via interactions with fibroblasts. In this study, we used microvesicles derived from sarcoma cells, and determined whether emmprin exists in the microvesicles, which enhance the production of MMP-2 via fibroblasts. Microvesicles released from FU-EPS-1 cells were shown to contain full-length emmprin, identified as a 45-kDa protein characterized by polylactosamine glycosylation. Microvesicles collected from FU-EPS-1 cells transfected with emmprin-specific siRNA or transduced with shRNA displayed significantly reduced MMP-2 production by fibroblasts compared with those from control-transfected cells. Our findings show that emmprin is released through microvesicle shedding in sarcoma cells, and emmprin in microvesicles regulates MMP-2 production by influencing the activity of fibroblasts located at sites distant from the tumor cells.

Radiation induced sarcomas of bone following therapeutic radiation

International Nuclear Information System (INIS)

Kim, J.H.; Chu, F.C.H.; Woodward, H.Q.; Huvos, A.

1983-01-01

Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed

TFG-MET fusion in an infantile spindle cell sarcoma with neural features.

Science.gov (United States)

Flucke, Uta; van Noesel, Max M; Wijnen, Marc; Zhang, Lei; Chen, Chun-Liang; Sung, Yun-Shao; Antonescu, Cristina R

2017-09-01

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials. © 2017 Wiley Periodicals, Inc.

Kaposi's sarcoma-associated herpesvirus-like DNA sequences (KSHV/HHV-8) in oral AIDS-Kaposi's sarcoma: a PCR and clinicopathologic study.

Science.gov (United States)

Flaitz, C M; Jin, Y T; Hicks, M J; Nichols, C M; Wang, Y W; Su, I J

1997-02-01

Recently, a new human herpesvirus (KSHV/HHV-8) has been identified in classic, transplant, endemic, and AIDS Kaposi's sarcoma that may be involved in the pathogenesis of Kaposi's sarcoma. The purpose of this study was to evaluate oral AIDS-Kaposi's sarcoma for detection of KSHV/HHV-8 DNA. DNA extracted from 54 oral AIDS-Kaposi's sarcoma lesions (47 initial, 7 postvinblastine treated), 5 non-Kaposi's sarcoma HIV-positive lesions, and 3 non-Kaposi's sarcoma HIV-negative lesions was evaluated by polymerase chain reaction (KS330(233bp)amplicon) for KSHV/HHV-8. The AIDS-Kaposi's sarcoma study population consisted of 52 patients (51:1, men:woman; 92% men having sex with men, 8% heterosexual; mean age, 38 years; mean, CD4 59/mm3) Opportunistic infections occurred in 88% (candidiasis, 65%; Pneumocystis carinii pneumonia, 31%; nonoral Kaposi's sarcoma, 25%; mycobacterium avium-intracellulare (MAI), 16%; cytomegalovirus, 14%; herpes simplex virus, 14%). Sexually transmitted diseases occurred in 73% (gonorrhea, 37%; syphilis, 23%; condyloma, 22%; HSV, 16%). Most frequent lesion sites were palate (74%) and gingiva (17%). Most common lesion types were purple nodular (48%) and macular (42%). Histopathologic subtypes were nodular (71%), plaque (27%), and patch (2%). Polymerase chain reaction analysis detected KSHV/HHV-8 DNA in 53 of 54 AIDS-Kaposi's sarcoma lesions (47 of 47 initial, 6 of 7 postvinblastine treatment). KSHV/HHV-8 DNA was not detected in non-Kaposi's sarcoma lesions in HIV-positive or HIV-negative persons. KSHV/HHV-8 DNA sequence is present in a high proportion of oral AIDS-Kaposi's sarcoma lesions. Whether KSHV/HHV-8 is an etiologic agent or a cofactor in the development of this vascular neoplasm is uncertain and remains to be proven. Polymerase chain reaction analysis for KSHV/HHV-8 DNA sequence detection may be helpful in identifying Kaposi's sarcoma in early vascular proliferations, when the characteristic histopathologic features are not present.

Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors

International Nuclear Information System (INIS)

Massardo, Teresa; Jofre, Maria Josefina; Sierralta, Maria Paulina; Canessa, Jose; Castro, Gabriel; Berrocal, Isabel; Gallegos, Ivan

2012-01-01

Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. Results: FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. Conclusions: PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control

Inhibition of SOX2 induces cell apoptosis and G1/S arrest in Ewing's sarcoma through the PI3K/Akt pathway.

Science.gov (United States)

Ren, Chongmin; Ren, Tingting; Yang, Kang; Wang, Shidong; Bao, Xing; Zhang, Fan; Guo, Wei

2016-03-11

Ewing's sarcoma is an aggressive bone and soft tissue tumor with a high incidence in children and adolescents. Due to its high malignancy and poor prognosis, identification of novel biomarkers for intervention therapies is necessary to improve outcome. The EWS/FLI1 fusion gene is a characteristic of Ewing's sarcoma in most cases. Sex determining region Y-box 2 (SOX2) is a primary target of EWS/FLI1. It has been identified as an oncogene and linked to apoptotic resistance in several types of cancer. However, its role and regulatory mechanisms in Ewing's sarcoma are largely unknown. We systematically investigated the role of SOX2 in Ewing's sarcoma cell lines, human tissue samples and xenograft models. The expression of SOX2 was detected in Ewing's sarcoma samples by WB and IHC. siRNAs were used to knockdown EWS/FLI1 and SOX2 in A673 and RD-ES cell lines with the efficiencies tested by qRT-PCR and WB. The effect of SOX2 on cell cycle and apoptosis was determined by Flow cytometric and TUNEL assays. Akt overexpression was performed with plasmid. The protein expression of the corresponding factors was examined by WB analysis. Inhibition of SOX2 in vivo was performed by siRNA against SOX2 in xenograft models, and the protein expression of the regulators testified in vitro was examined in xenograft tumors by IHC and WB. The results confirmed that SOX2 was highly expressed in Ewing's sarcoma and was the target of EWS/FLI1. SOX2 advanced Ewing's sarcoma cell survival and proliferation by regulating p21, p27 and cyclin-E to facilitate G1/S phase transition and mediating caspase-3, PARP via both extrinsic (Fas and caspase-8) and intrinsic (caspase-9, Bad, Bcl-2 and XIAP) apoptotic pathways to restrain cell apoptosis. Additionally, SOX2 regulated the cell-cycle progression and apoptosis via activation of the PI3K/Akt signaling pathway. The mechanisms were proved both in vitro and in vivo. The results demonstrate that SOX2 played a central role in promoting Ewing's sarcoma

Molecular dissection of the mechanism by which EWS/FLI expression compromises actin cytoskeletal integrity and cell adhesion in Ewing sarcoma

Science.gov (United States)

Chaturvedi, Aashi; Hoffman, Laura M.; Jensen, Christopher C.; Lin, Yi-Chun; Grossmann, Allie H.; Randall, R. Lor; Lessnick, Stephen L.; Welm, Alana L.; Beckerle, Mary C.

2014-01-01

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised. PMID:25057021

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.

Directory of Open Access Journals (Sweden)

Xin Huang

Full Text Available Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR T cells targeting the type I insulin-like growth factor receptor (IGF1R or tyrosine kinase-like orphan receptor 1 (ROR1 molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15 and ROR1 (11/15 were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.

Radiological Findings of Primary Retroperitoneal Ewing Sarcoma

Energy Technology Data Exchange (ETDEWEB)

Ulusan, S.; Koc, Z.; Tuba Canpolat, E.; Colakoglu, T. [Depts. of Radiology, Pathology, and General Surgery, Baskent Univ. Faculty of Medicine, Adana (Turkey)

2007-09-15

Ewing sarcomas are most commonly located in bone, while extra skeletal involvement of the retroperitoneum is extremely rare. We describe the radiologic and pathological findings in an adult patient with retroperitoneal extra skeletal Ewing sarcoma. Keywords: Color Doppler ultrasound; computed tomography; extra skeletal Ewing sarcoma; magnetic resonance imaging; ultrasound.

Radiological Findings of Primary Retroperitoneal Ewing Sarcoma

International Nuclear Information System (INIS)

Ulusan, S.; Koc, Z.; Tuba Canpolat, E.; Colakoglu, T.

2007-01-01

Ewing sarcomas are most commonly located in bone, while extra skeletal involvement of the retroperitoneum is extremely rare. We describe the radiologic and pathological findings in an adult patient with retroperitoneal extra skeletal Ewing sarcoma. Keywords: Color Doppler ultrasound; computed tomography; extra skeletal Ewing sarcoma; magnetic resonance imaging; ultrasound

Kaposi`s sarcoma; Sarcome de Kaposi

Energy Technology Data Exchange (ETDEWEB)

Kirova, Y M; Belembaogo, E; Frikha, H; Yu, S J; Le Bourgeois, J P [Hopital Henri-Mondor, 94 - Creteil (France)

1997-09-01

Moriz Kaposi was the first who, in 1872, described five patients presenting with `sarcoma idiopathicum multiple hemorrhagicum`. In 1912 Sternberg termed this disease Kaposi`s sarcoma. Since then various forms of this rare disease have been observed. In 1914 Hallenberg described the first cases of African or endemic Kaposi`s sarcoma. In the 1960`s the first reports discussing Kaposi`s sarcoma following organ transplantation and immunosuppressive therapy were published. After 1981, the epidemic form associated with the acquired immunodeficiency syndrome (AIDS) was described. All these forms, their history, treatment methods and the role of radiation therapy in the management of this rare malignancy are discussed, and the literature is reviewed. (authors)

Therapeutic applications of histone deacetylase inhibitors in sarcoma.

Science.gov (United States)

Tang, Fan; Choy, Edwin; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

2017-09-01

Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory.

Science.gov (United States)

Li, Wen-Xing; Dai, Shao-Xing; Liu, Jia-Qian; Wang, Qian; Li, Gong-Hua; Huang, Jing-Fei

2016-01-01

Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases.

Adrenal Ewing's Sarcoma in an Elderly Man.

Science.gov (United States)

Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

2018-02-15

Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

Cross-Dataset Analysis and Visualization Driven by Expressive Web Services

Science.gov (United States)

Alexandru Dumitru, Mircea; Catalin Merticariu, Vlad

2015-04-01

. The application offers a set of features to visualize and cross-compare the datasets. Users can select a region of interest in space and time on which an aerosol map layer is plotted. Hovmoeller time-latitude and time-longitude profiles can be displayed by selecting orthogonal cross-sections on the globe. Statistics about the selected dataset are also displayed in different text and plot formats. The datasets can also be cross-compared either by using the delta map tool or the merged map tool. For more advanced users, a WCPS query console is also offered allowing users to process their data with ad-hoc queries and then choose how to display the results. Overall, the user has a rich set of tools that can be used to visualize and cross-compare the aerosol datasets. With our application we have shown how the NASA WorldWind framework can be used to display results processed efficiently - and entirely - on the server side using the expressiveness of the OGC WCPS web-service. The application serves not only as a proof of concept of a new paradigm in working with large geospatial data but also as an useful tool for environmental data analysts.

Current State of Pediatric Sarcoma Biology and Opportunities for Future Discovery: A Report from the Sarcoma Translational Research Workshop

Science.gov (United States)

Hingorani, Pooja; Janeway, Katherine; Crompton, Brian D.; Kadoch, Cigall; Mackall, Crystal L.; Khan, Javed; Shern, Jack F.; Schiffman, Joshua; Mirabello, Lisa; Savage, Sharon A.; Ladanyi, Marc; Meltzer, Paul; Bult, Carol J.; Adamson, Peter C.; Lupo, Philip J.; Mody, Rajen; DuBois, Steven G.; Parsons, D. Williams; Khanna, Chand; Lau, Ching; Hawkins, Douglas S.; Randall, R. Lor; Smith, Malcolm; Sorensen, Poul H.; Plon, Sharon E.; Skapek, Stephen X.; Lessnick, Stephen; Gorlick, Richard; Reed, Damon R.

2017-01-01

Sarcomas are a rare subgroup of pediatric cancers comprised of a variety of bone and soft-tissue tumors. While significant advances have been made in improving outcomes of patients with localized pediatric sarcomas since the addition of systemic chemotherapy to local control many decades ago, outcomes for patients with metastatic and relapsed sarcoma remain poor with few novel therapeutics identified to date. With the advent of new technologies to study cancer genomes, transcriptomes and epigenomes, our understanding of sarcoma biology has improved tremendously in a relatively short period of time. However, much remains to be accomplished in this arena especially with regard to translating all of this new knowledge to the bedside. To this end, a meeting was convened in Philadelphia, PA on April 18, 2015 sponsored by the QuadW foundation, Children’s Oncology Group and CureSearch for Children’s Cancer that brought together sarcoma clinicians and scientists from North America to review the current state of pediatric sarcoma biology and ongoing/planned genomics based clinical trials in an effort to identify and bridge knowledge gaps that continue to exist at the current time. At the conclusion of the workshop, three key objectives that would significantly further our understanding of sarcoma were identified and a proposal was put forward to develop an all-encompassing pediatric sarcoma biology protocol that would address these specific needs. This review summarizes the proceedings of the workshop. PMID:27132463

Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo

Directory of Open Access Journals (Sweden)

Petru Edgar

2010-03-01

Full Text Available Abstract Background Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat on MES-SA uterine sarcoma cells in vitro and in vivo. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21WAF1 and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma in vivo. Results Vorinostat efficiently suppressed MES-SA cell growth at a low dosage (3 μM already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 μM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. HDACs class I (HDAC2 and 3 as well as class II (HDAC7 were preferentially affected by this treatment. Vorinostat significantly increased p21WAF1 expression and apoptosis. Nude mice injected with 5 × 106 MES-SA cells were treated for 21 days with vorinostat (50 mg/kg/day and, in comparison to placebo group, a tumor growth reduction of more than 50% was observed. Results obtained by light- and electron-microscopy suggested pronounced activation of apoptosis in tumors isolated from vorinostat-treated mice. Conclusions Our data strongly indicate the high therapeutic potential of vorinostat in uterine sarcomas.

Sarcoma-The standard-bearer in cancer discovery.

Science.gov (United States)

Potter, Jared W; Jones, Kevin B; Barrott, Jared J

2018-06-01

Sarcoma is a rare tumor type that occurs most frequently in connective tissue. Despite its uncommon occurrence, sarcoma research has provided the means for groundbreaking research that has advanced our understanding of general cancer mechanisms. It is through sarcoma research that the pioneering efforts of cancer immunotherapy were explored, that we understand the inherent genetic nature of cancer mutations, and that we appreciate the subclassification of general cancer types to make more accurate prognoses. This review explores the brief history of sarcoma research and what sarcomas can still teach us about the future of cancer research, especially in regard to novel immunotherapy targets, the role of epigenetics in disease progression and chemoresistance, and the benefits of more focused clinical trials. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Angiography of histopathologic variants of synovial sarcoma

International Nuclear Information System (INIS)

Lois, J.F.; Fischer, H.J.; Mirra, J.M.; Gomes, A.S.; California Univ., Los Angeles

1986-01-01

Synovial sarcomas are rare soft tissue tumors which histopathologically can be divided into monophasic, biphasic and mixed variants. As part of a protocol for intra-arterial chemotherapy 12 patients with biopsy proven synovial sarcoma underwent angiography. The angiograms on these patients were reviewed to determine whether synovial sarcomas and their variants demonstrated a characteristic angiographic appearance. Synovial sarcomas appeared angiographically as soft tissue masses which showed a fine network of tumor vessels with an inhomogeneous capillary blush. Their degree of vascularity varied according to their histopathology. Monophasic synovial sarcomas demonstrated in general a higher degree of neovascularity than the biphasic form. This finding was also suggested by histopathologic analysis of the vessels in the tumor. Although angiography did not show a distinctive vascular pattern it may be useful to evaluate tumor size and vascularity. (orig.)

Postradiation sarcoma involving the spine

International Nuclear Information System (INIS)

Sundaresan, N.; Huvos, A.G.; Krol, G.; Hughes, J.E.; Cahan, W.G.

1986-01-01

Postradiation sarcomas arising many years after treatment of cancer are long term sequelae of therapy. We describe the clinical features, radiographic findings, and results of treatment in 13 patients with such sarcomas encountered over a 6-year period. Of these patients, 9 had bone sarcomas and the remaining 4 had paraspinal tumors arising from adjacent soft tissue and nerve. The primary cancer for which radiation was given included Hodgkin's disease (4 patients), breast cancer (2 patients), cervix cancer (2 patients), and a variety of others (5 patients). The latent interval to the occurrence of the second neoplasm varied from 6 to 30 years (median, 10 years) after treatment of the original tumor. Despite aggressive treatment, the overall prognosis was poor. The median survival was 8 months, with only 3 surviving more than 2 years. Although rare, postradiation sarcoma should be considered in the differential diagnosis of patients presenting with late onset of spinal pain or neurological symptoms after clinical remission of an original cancer

Ewing's sarcoma of the patella.

Science.gov (United States)

Gorelik, Natalia; Dickson, Brendan C; Wunder, Jay S; Bleakney, Robert

2013-05-01

Ewing's sarcoma is a relatively rare malignancy, occurring mainly between 4 and 25 years of age. It usually arises from the pelvis, followed by the femur, tibia, and remainder of both the long bones of the extremities and flat bones of the axial skeleton. To the best of our knowledge, Ewing's sarcoma of the patella has never been reported previously. Patellar tumors occur infrequently and represent an uncommon etiology of anterior knee pain. We describe the rare case of a 41-year-old man who presented with a 3-4 month history of escalating right anterior knee pain and swelling. Imaging demonstrated an aggressive patellar tumor with an adjacent soft tissue mass. The diagnosis of Ewing's sarcoma was confirmed by pathology. Physicians should be aware of atypical locations for Ewing's sarcoma and, conversely, of rare tumors arising in the patella and accounting for anterior knee pain. Early recognition of such malignancies allows prompt initiation of treatment, hence improving prognosis.

Differential roles of SS18-SSX fusion gene and insulin-like growth factor-1 receptor in synovial sarcoma cell growth

International Nuclear Information System (INIS)

Toernkvist, Maria; Natalishvili, Natalia; Xie Yuntao; Girnita, Ada; D'Arcy, Padraig; Brodin, Bertha; Axelson, Magnus; Girnita, Leonard

2008-01-01

Recently we demonstrated that the synovial sarcoma specific fusion gene SS18-SSX is crucial for cyclin D1 expression and is linked to cell proliferation. In this report we explore the role of SS18-SSX and IGF-1R for their potential functions in cellular proliferation and survival in cultured synovial sarcoma cells. We found that targeting of SS18-SSX mRNA by antisense oligonucleotide treatment drastically and rapidly decreased cell proliferation but caused only a slight increase of apoptosis. The synovial sarcoma cells were confirmed to express IGF-1R, and treatment with an IGF-1R inhibitor resulted in substantially reduced cell viability by inducing apoptosis in these cells. Conversely, inhibition of the IGF-1R resulted only in a slight to moderate decrease in DNA synthesis. In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells. Whereas SS18-SSX maintains cyclin D1 and cell proliferation, IGF-1R protects from apoptosis

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.

Science.gov (United States)

Tawbi, Hussein A; Burgess, Melissa; Bolejack, Vanessa; Van Tine, Brian A; Schuetze, Scott M; Hu, James; D'Angelo, Sandra; Attia, Steven; Riedel, Richard F; Priebat, Dennis A; Movva, Sujana; Davis, Lara E; Okuno, Scott H; Reed, Damon R; Crowley, John; Butterfield, Lisa H; Salazar, Ruth; Rodriguez-Canales, Jaime; Lazar, Alexander J; Wistuba, Ignacio I; Baker, Laurence H; Maki, Robert G; Reinke, Denise; Patel, Shreyaskumar

2017-11-01

Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC). Patients with soft-tissue sarcoma had to be aged 18 years or older to enrol; patients with bone sarcoma could enrol if they were aged 12 years or older. Patients had histological evidence of metastatic or surgically unresectable locally advanced sarcoma, had received up to three previous lines of systemic anticancer therapy, had at least one measurable lesion according to the Response Evaluation Criteria In Solid Tumors version 1.1, and had at least one lesion accessible for biopsy. All patients were treated with 200 mg intravenous pembrolizumab every 3 weeks. The primary endpoint was investigator-assessed objective response. Patients who received at least one dose of pembrolizumab were included in the safety analysis and patients who progressed or reached at least one scan assessment were included in the activity analysis. Accrual is ongoing in some disease cohorts. This trial is registered with ClinicalTrials.gov, number NCT02301039. Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). Median follow-up was 17·8 months (IQR 12·3-19·3). Seven (18%) of 40 patients with soft-tissue sarcoma had an objective response, including four (40%) of ten patients with undifferentiated pleomorphic sarcoma, two (20%) of ten patients with liposarcoma, and one (10%) of ten patients

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

Science.gov (United States)

Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

Directory of Open Access Journals (Sweden)

Fengchun Ye

2011-01-01

Full Text Available The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS. The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

Is There a Predisposition Gene for Ewing's Sarcoma?

Directory of Open Access Journals (Sweden)

R. L. Randall

2010-01-01

Full Text Available Ewing's sarcoma is a highly malignant tumor of children and young adults. The molecular mechanisms that underlie Ewing's Sarcoma development are beginning to be understood. For example, most cases of this disease harbor somatic chromosomal translocations that fuse the EWSR1 gene on chromosome 22 with members of the ETS family. While some cooperative genetic events have been identified, such as mutations in TP53 or deletions of the CDKN2A locus, these appear to be absent in the vast majority of cases. It is therefore uncertain whether EWS/ETS translocations are the only consistently present alteration in this tumor, or whether there are other recurrent abnormalities yet to be discovered. One method to discover such mutations is to identify familial cases of Ewing's sarcoma and to then map the susceptibility locus using traditional genetic mapping techniques. Although cases of sibling pairs with Ewing's sarcoma exist, familial cases of Ewing's sarcoma have not been reported. While Ewing's sarcoma has been reported as a 2nd malignancy after retinoblastoma, significant associations of Ewing's sarcoma with classic tumor susceptibility syndromes have not been identified. We will review the current evidence, or lack thereof, regarding the potential of a heritable condition predisposing to Ewing's sarcoma.

Is There a Predisposition Gene for Ewing's Sarcoma?

Science.gov (United States)

Randall, R. L.; Lessnick, S. L.; Jones, K. B.; Gouw, L. G.; Cummings, J. E.; Cannon-Albright, L.; Schiffman, J. D.

2010-01-01

Ewing's sarcoma is a highly malignant tumor of children and young adults. The molecular mechanisms that underlie Ewing's Sarcoma development are beginning to be understood. For example, most cases of this disease harbor somatic chromosomal translocations that fuse the EWSR1 gene on chromosome 22 with members of the ETS family. While some cooperative genetic events have been identified, such as mutations in TP53 or deletions of the CDKN2A locus, these appear to be absent in the vast majority of cases. It is therefore uncertain whether EWS/ETS translocations are the only consistently present alteration in this tumor, or whether there are other recurrent abnormalities yet to be discovered. One method to discover such mutations is to identify familial cases of Ewing's sarcoma and to then map the susceptibility locus using traditional genetic mapping techniques. Although cases of sibling pairs with Ewing's sarcoma exist, familial cases of Ewing's sarcoma have not been reported. While Ewing's sarcoma has been reported as a 2nd malignancy after retinoblastoma, significant associations of Ewing's sarcoma with classic tumor susceptibility syndromes have not been identified. We will review the current evidence, or lack thereof, regarding the potential of a heritable condition predisposing to Ewing's sarcoma. PMID:20300555

Advances in sarcoma gene mutations and therapeutic targets.

Science.gov (United States)

Gao, Peng; Seebacher, Nicole A; Hornicek, Francis; Guo, Zheng; Duan, Zhenfeng

2018-01-01

Sarcomas are rare and complex malignancies that have been associated with a poor prognostic outcome. Over the last few decades, traditional treatment with surgery and/or chemotherapy has not significantly improved outcomes for most types of sarcomas. In recent years, there have been significant advances in the understanding of specific gene mutations that are important in driving the pathogenesis and progression of sarcomas. Identification of these new gene mutations, using next-generation sequencing and advanced molecular techniques, has revealed a range of potential therapeutic targets. This, in turn, may lead to the development of novel agents targeted to different sarcoma subtypes. In this review, we highlight the advances made in identifying sarcoma gene mutations, including those of p53, RB, PI3K and IDH genes, as well as novel therapeutic strategies aimed at utilizing these mutant genes. In addition, we discuss a number of preclinical studies and ongoing early clinical trials in sarcoma targeting therapies, as well as gene editing technology, which may provide a better choice for sarcoma patient management. Published by Elsevier Ltd.

A Challenging Case of Metastatic Intra-Abdominal Synovial Sarcoma with Unusual Immunophenotype and Its Differential Diagnosis

Directory of Open Access Journals (Sweden)

Yi-Che Changchien

2012-01-01

Full Text Available The primary and metastatic gastrointestinal synovial sarcoma is rare with a wide differential diagnosis. It usually expresses cytokeratins EMA, BCL2 with an occasional CD99, and S100 positivity but not desmin. We present a case of metastatic synovial sarcoma with unusual immunophenotype causing diagnostic challenges. The tumor cells showed focal cytokeratin, EMA, and, unexpectedly, desmin positivity. Additional intranuclear TLE-1 positivity and negativity for CD34 and DOG-1 were also identified. A diagnosis of monophasic synovial sarcoma was confirmed by using FISH break-apart probe. RT-PCR revealed the SYT-SSX1 fusion gene. Intra-abdominal synovial sarcoma, either primary or metastatic, with unusual desmin positivity raises the diagnostic challenge, since a wide range of differential diagnoses could show a similar immunophenotype (leiomyosarcoma, desmoid tumor, myofibroblastic tumor, and rarely GIST etc.. Typical morphology and focal cytokeratin/EMA positivity should alert to this tumor, and FISH and RT-PCR remain the gold standard for the confirmation.

Delays in the management of retroperitoneal sarcomas

DEFF Research Database (Denmark)

Seinen, Jojanneke; Almquist, Martin; Styring, Emelie

2010-01-01

Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal...... sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care...... at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers...

Imaging characteristics of primary cranial Ewing sarcoma

International Nuclear Information System (INIS)

Li, Wai-Yung; Saunders, Dawn E.; Brock, Penelope

2005-01-01

Ewing sarcoma accounts for 10-15% of all childhood malignant bone tumours and is second in prevalence to osteosarcoma. The skull bones are an unusual site of origin of primary Ewing sarcoma in children. Previous reports concentrate on the neurosurgical aspects and relatively good outcome compared to other bone tumours of the calvarium. Reported cases mainly describe the imaging characteristics on CT. To describe the MRI and CT features of primary cranial Ewing sarcoma. The neuroimaging of three cases of primary cranial Ewing sarcoma are reviewed. Our three cases show an extra-axial mass that is high attenuation on CT and low signal on T2-weighted MRI. Haemorrhagic components, dural extension and contrast enhancement are also characteristic features. CT attenuation and magnetic resonance signal characteristics reflect sheets of densely packed cells seen in Ewing sarcoma. (orig.)

Arsenic trioxide inhibits Ewing's sarcoma cell invasiveness by targeting p38(MAPK) and c-Jun N-terminal kinase.

Science.gov (United States)

Zhang, Shuai; Guo, Wei; Ren, Ting-Ting; Lu, Xin-Chang; Tang, Guo-Qing; Zhao, Fu-Long

2012-01-01

Ewing's sarcoma is the second most frequent primary malignant bone tumor, mainly affecting children and young adults. The notorious metastatic capability of this tumor aggravates patient mortality and remains a problem to be overcome. We investigated the effect of arsenic trioxide (As₂O₃) on the metastasis capability of Ewing's sarcoma cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide assays to choose appropriate concentrations of As₂O₃ for the experiments. Migration, invasion, and adhesion assays were performed to assess the effect of As₂O₃ on the metastasis of Ewing's sarcoma. Immunofluorescent staining was used to observe cytoskeleton reorganization in Ewing's sarcoma cells treated with As₂O₃. Changes in matrix metalloproteinase-9 expression and the mitogen-activated protein kinase (MAPK) pathway were investigated using western blot. Inhibitors of p38(MAPK) (sb202190) and c-Jun NH₂-terminal kinase (JNK, sp600125) were used in invasion assays to determine the effect of p38(MAPK) and JNK. We found that As₂O₃ may markedly inhibit the migration and invasion capacity of Ewing's sarcoma cells with structural rearrangements of the actin cytoskeleton. The expressions of matrix metalloproteinase-9, phosphor-p38(MAPK), and phosphor-JNK were suppressed by As₂O₃ treatment in a dose-dependent manner. The inhibitors of p38(MAPK) (sb202190) and JNK (sp600125) enhanced the inhibition induced by As₂O₃, which was counteracted by anisomycin, an activating agent of p38(MAPK) and JNK. Taken together, our results demonstrate that As₂O₃ can inhibit the metastasis capability of RD-ES and A-673 cells and may have new therapeutic value for Ewing's sarcoma.

Soft tissue sarcoma - diagnosis and treatment

International Nuclear Information System (INIS)

Ruka, W.; Rutkowski, P.; Krzakowski, M.

2009-01-01

Significant progress in the treatment of soft tissue sarcoma (STS), both primary tumor and local recurrences/metastatic disease, has been achieved in recent years. Surgery is essential modality, but the use of combined treatment (standard combination of surgery with adjuvant radiotherapy, chemotherapy in selected cases and perioperative rehabilitation) in highly-experienced centers increased possibility of cure and limitations of extent of local surgery. Current combined therapy together with the use of reconstructive methods allows for limb-sparing surgery in majority of soft tissue sarcoma patients (amputation in 10% of cases as compared to approximately 50% in the 1960 - 70s). The slow, but constant, increase of rate of soft tissue sarcoma patients with long-term survival has been observed. Contemporary 5-year overall survival rate in patients with extremity soft tissue sarcomas is 55 -78%. In case of diagnosis of metastatic disease the prognosis is still poor (survival of approximately 1 year). Good results of local therapy may be expected only after planned (e.g., after preoperative biopsy - tru - cut or incisional) radical surgical excision of primary tumor with pathologically negative margins (R0 resection). Following appropriate diagnostic check-up, adjuvant radiotherapy is necessary in the majority of patients treated with radical surgery need, as well as long-term rehabilitation and follow-up examinations in treating center are needed for at least 5 years. The progress is due to the introduction of targeted therapy acting on molecular or genetic cellular disturbances detected during studies on etiopathogenetic mechanisms of sarcoma subtypes. In view of rarity of sarcomas and necessity of multidisciplinary therapy, the crucial issue is that management of these tumors should be hold in experienced oncological sarcoma centers. (authors)

Radiological findings of pulmonary Kaposi's sarcoma. Manifestaciones radiologicas del sarcoma de Kaposi pulmonar

Energy Technology Data Exchange (ETDEWEB)

Rosello, J A; Hernandez, S; Arranz, M; Jareo, J; Ancoechea, J

1994-01-01

Kaposi's sarcoma (KS) is the most common neoplasm in AIDS patients. The incidence of pulmonary involvement is approximately 20%. The radiological findings are reported in plain chest x-ray and computed tomography (CT) in 15 patients diagnosed as having pulmonary Kaposi's sarcoma, in whom concomitant pulmonary infection was ruled out. The most common radiological pattern was that of bilateral perihilar interstitial involvement (86%), while poorly defined multiple nodules seldom presented (13%). In 40% of cases, the pulmonary parenchymal lesion was accompanied by pleural effusion. This sign is useful in the differential diagnosis involving opportunistic P. carinii pneumonia, a very common process in these patients which rarely presents with pleural effusion. The chest CT finding that was most characteristic of pulmonary Kaposi's sarcoma was bilateral perihilar peribronchovascular enlargement. (Author)

Testicular myeloid sarcoma: case report.

Science.gov (United States)

Zago, Luzia Beatriz Ribeiro; Ladeia, Antônio Alexandre Lisbôa; Etchebehere, Renata Margarida; de Oliveira, Leonardo Rodrigues

2013-01-01

Myeloid sarcomas are extramedullary solid tumors composed of immature granulocytic precursor cells. In association with acute myeloid leukemia and other myeloproliferative disorders, they may arise concurrently with compromised bone marrow related to acute myeloid leukemia, as a relapsed presentation, or occur as the first manifestation. The testicles are considered to be an uncommon site for myeloid sarcomas. No therapeutic strategy has been defined as best but may include chemotherapy, radiotherapy and/or hematopoietic stem cell transplantation. This study reports the evolution of a patient with testicular myeloid sarcoma as the first manifestation of acute myeloid leukemia. The patient initially refused medical treatment and died five months after the clinical condition started.

Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors; Utilidad del estudio PET con FDG en la evaluacion de sarcomas de diverso origen y de tumores no sarcoma-no epiteliales

Energy Technology Data Exchange (ETDEWEB)

Massardo, Teresa [Seccion Medicina Nuclear, Departamento de Medicina, Hospital Clinico Universidad de Chile, Santiago (Chile); Jofre, Maria Josefina; Sierralta, Maria Paulina; Canessa, Jose [Centro PET de imagenes moleculares, Hospital Militar de Santiago, Santiago (Chile); Castro, Gabriel; Berrocal, Isabel [Seccion Medicina Nuclear, Departamento de Medicina, Hospital Clinico Universidad de Chile, Santiago (Chile); Gallegos, Ivan [Departamento Anatomia Patologica, Hospital Clinico Universidad de Chile, Santiago (Chile)

2012-07-01

Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. Results: FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. Conclusions: PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

Magnetic resonance imaging features of extremity sarcomas of uncertain differentiation

International Nuclear Information System (INIS)

Stacy, G.S.; Nair, L.

2007-01-01

The purpose of this review is to illustrate the pertinent clinical and imaging features of extremity sarcomas of uncertain differentiation, including synovial sarcoma, epithelioid sarcoma, clear-cell sarcoma, and alveolar soft part sarcoma. These tumours should be considered in the differential diagnosis when a soft-tissue mass is encountered in the extremity of an adolescent or young adult

Immunotherapy of childhood Sarcomas

Directory of Open Access Journals (Sweden)

Stephen S Roberts

2015-08-01

Full Text Available Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing’s family of tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with localized stage are curable with surgery and/or chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New therapies for these patients are urgently needed. Immunotherapy is an established treatment modality for both liquid and solid tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In the past, immunomodulatory agents such as interferon, interleukin-2, and Liposomal-muramyl  tripeptide phosphatidyl-ethanolamine (L-MTP have been tried, with some activity seen in subsets of patients; additionally, various cancer vaccines have been studied with possible benefit. Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA4 and PD-1 are being actively explored in pediatric sarcomas. Building on the success of adoptive T cell therapy for EBV-related lymphoma, strategies to redirect T cells using chimeric antigen receptors and bispecific antibodies are rapidly evolving with potential for the treatment of sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and tumor vaccines. The future integration of antibody based and cell based therapies into an overall treatment strategy of sarcoma will be discussed.

Ewing's Sarcoma Localized in the Mandible: A Case Report

OpenAIRE

Akbayram, S; Başaranoglu, M; Kaya, A; Açıkgöz, M; Üstyol, L; Taşkın, GA; Dogan, M

2015-01-01

Ewing's sarcoma is one of the most aggressive primary bone tumours. Ewing's sarcoma arising from the bones of the head and neck region is extremely rare; only 4–9% of all Ewing's sarcoma originate in this region. We report a case of Ewing's sarcoma localized in the mandible because of its unusual presentation.

Second malignancies after treatment for Ewing's sarcoma

International Nuclear Information System (INIS)

Ahrens, Susanne; Dunst, Juergen; Ruebe, Christian; Paulussen, Michael; Hoffmann, Christine; Juergens, Herbert

1997-01-01

Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated

Second malignancies after treatment for Ewing's sarcoma

Energy Technology Data Exchange (ETDEWEB)

Ahrens, Susanne; Dunst, Juergen; Ruebe, Christian; Paulussen, Michael; Hoffmann, Christine; Juergens, Herbert

1997-07-01

Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated

Synovial sarcoma: a rare presentation of parapharyngeal mass.

Science.gov (United States)

Shaariyah, Mohd Mokhtar; Mazita, Ami; Masaany, Mansor; Razif, Mohd Yunus; Isa, Mohamed Rose; Asma, Abdullah

2010-06-01

Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and received adjuvant radiotherapy.

New Therapeutic Targets in Soft Tissue Sarcoma

Science.gov (United States)

Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C.; Lazar, Alexander J

2012-01-01

Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

Ewing's Sarcoma of the Adrenal Gland.

Science.gov (United States)

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Intraneural synovial sarcoma of the median nerve

Directory of Open Access Journals (Sweden)

Rahul Kasukurthi

2010-06-01

Full Text Available Synovial sarcomas are soft-tissue malignancies with a poor prognosis and propensity for distant metastases. Although originally believed to arise from the synovium, these tumors have been found to occur anywhere in the body. We report a rare case of synovial sarcoma arising from the median nerve. To our knowledge, this is the twelfth reported case of intraneural synovial sarcoma, and only the fourth arising from the median nerve. Because the diagnosis may not be apparent until after pathological examination of the surgical speci­men, synovial sarcoma should be kept in mind when dealing with what may seem like a benign nerve tumor.

Synovial sarcoma with relevant immunocytochemistry and special emphasis on the monophasic fibrous variant

Directory of Open Access Journals (Sweden)

Kottu Radhika

2010-01-01

Full Text Available Background: Monophasic fibrous synovial sarcoma (SS is the most common variant of SS. Only a few cytological studies are available on this entity. Bcl-2 protein expression has been described as a characteristic marker of SS and is useful for its differentiation from other sarcomas. Cytokeratin and CD99 are also used in detecting SS. Aims: To evaluate synovial sarcoma and its variants cytomorphologically. Materials and Methods: During a period of 10 years 7 months, i.e. from January 1998 to July 2008, 12 cytologic specimens diagnosed as synovial sarcoma were reviewed. Ten cases were diagnosed as SS on aspiration alone but two cases required ancillary technique i.e., immunocytochemistry staining with bcl-2 and cytokeratin. The smears were stained with Papanicolaou and May-Grόnwald-Giemsa stains. Results: All cytologic specimens in our study had similar appearance. Most smears were highly cellular and were made up of densely packed tri-dimensional groups and singly scattered round to oval cells. Cellular monomorphism and vascular channels within the cell groups were the remarkable findings. Only one case showed cytologic evidence of epithelial differentiation. Bcl-2, cytokeratin, CD99 positivity was seen on immunohistochemistry staining. Results were categorized according to age, sex and morphologic variants. Conclusions: Although cytomorphologic features of synovial sarcomas are characteristic enough to permit its recognition, clinical correlation is necessary for accurate diagnosis. Monophasic variant is the most common entity observed in the present study.

Characteristics of 64 sarcoma patients referred to a sarcoma center after unplanned excision.

Science.gov (United States)

Dyrop, Heidi Buvarp; Safwat, Akmal; Vedsted, Peter; Maretty-Kongstad, Katja; Hansen, Bjarne Hauge; Jørgensen, Peter Holmberg; Baad-Hansen, Thomas; Keller, Johnny

2016-02-01

Unplanned excision of sarcoma before referral to specialist centers can affect prognosis and surgical outcome. The diagnostic pathway of these patients is uncertain and needs to be reviewed. We aimed to describe patient and tumor characteristics, initial symptoms, initial and final diagnosis, and explore reasons for unplanned excision in this patient group. From a previous study on 258 sarcoma patients, we identified 64 patients referred after surgery. Medical records were reviewed. The majority were soft tissue sarcomas, most often with thoracic location. Leiomyosarcoma was the most frequent final diagnosis, lipoma, and fibroma/dermatofibroma the most frequent initial diagnoses. Fifty percent were superficial small tumors, and 60.9% had not received diagnostic imaging before surgery. Fifty percent were referred from public surgical departments, and 1/3 from private specialists. Twenty-three patients had initial presence of alarm symptoms registered before surgery, the remaining 2/3 fell outside referral criteria or alarm symptoms were not discovered. Patients referred after unplanned excision often have small superficial tumors and the majority fall outside of defined referral criteria. Referral criteria are not a guarantee for detection of all sarcomas and surgeons should always be aware of the possibility of malignancy when removing a tumor. © 2016 Wiley Periodicals, Inc.

[{sup 18}F]FMISO and [{sup 18}F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression

Energy Technology Data Exchange (ETDEWEB)

Rajendran, J.G.; Peterson, L.M.; Grierson, J.R.; Eary, J.F. [Division of Nuclear Medicine, Department of Radiology, University of Washington Medical Center, Box 356113, WA 98195, Seattle (United States); Wilson, D.C. [Radiation Oncology, British Columbia Cancer Control Agency, Vancouver, BC (Canada); Conrad, E.U.; Bruckner, J.D. [Department of Orthopedic Surgery, University of Washington Medical Center, Seattle, Washington (United States); Rasey, J.S.; Chin, L.K.; Hofstrand, P.D. [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States); Krohn, K.A. [Division of Nuclear Medicine, Department of Radiology, University of Washington Medical Center, Box 356113, WA 98195, Seattle (United States); Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

2003-05-01

Hypoxia imparts resistance to radiotherapy and chemotherapy and also promotes a variety of changes in tumor biology through inducible promoters. The purpose of this study was to evaluate the use of positron emission tomography (PET) imaging with fluorine-18 fluoromisonidazole (FMISO) in soft tissue sarcomas (STS) as a measure of hypoxia and to compare the results with those obtained using [{sup 18}F]fluorodeoxyglucose (FDG) and other known biologic correlates. FDG evaluates energy metabolism in tumors while FMISO uptake is proportional to tissue hypoxia. FMISO uptake was compared with FDG uptake. Vascular endothelial growth factor (VEGF) expression was also compared with FMISO uptake. Nineteen patients with STS underwent PET scanning with quantitative determination of FMISO and FDG uptake prior to therapy (neo-adjuvant chemotherapy or surgery alone). Ten patients receiving neo-adjuvant chemotherapy were also imaged after chemotherapy but prior to surgical resection. Standardized uptake value (SUV) was used to describe FDG uptake; regional tissue to blood ratio ({>=}1.2 was considered significant) was used for FMISO uptake. Significant hypoxia was found in 76% of tumors imaged prior to therapy. No correlation was identified between pretherapy hypoxic volume (HV) and tumor grade (r=0.15) or tumor volume (r=0.03). The correlation of HV with VEGF expression was 0.39. Individual tumors showed marked heterogeneity in regional VEGF expression. The mean pixel-by-pixel correlation between FMISO and FDG uptake was 0.49 (range 0.09-0.79) pretreatment and 0.32 (range -0.46-0.72) after treatment. Most tumors showed evidence of reduced uptake of both FMISO and FDG following chemotherapy. FMISO PET demonstrates areas of significant and heterogeneous hypoxia in soft tissue sarcomas. The significant discrepancy between FDG and FMISO uptake seen in this study indicates that regional hypoxia and glucose metabolism do not always correlate. Similarly, we did not find any relationship

DNA Methylation and Gene Expression Profiling of Ewing Sarcoma Primary Tumors Reveal Genes That Are Potential Targets of Epigenetic Inactivation

Directory of Open Access Journals (Sweden)

Nikul Patel

2012-01-01

Full Text Available The role of aberrant DNA methylation in Ewing sarcoma is not completely understood. The methylation status of 503 genes in 52 formalin-fixed paraffin-embedded EWS tumors and 3 EWS cell lines was compared to human mesenchymal stem cell primary cultures (hMSCs using bead chip methylation analysis. Relative expression of methylated genes was assessed in 5-Aza-2-deoxycytidine-(5-AZA-treated EWS cell lines and in a cohort of primary EWS samples and hMSCs by gene expression and quantitative RT-PCR. 129 genes demonstrated statistically significant hypermethylation in EWS tumors compared to hMSCs. Thirty-six genes were profoundly methylated in EWS and unmethylated in hMSCs. 5-AZA treatment of EWS cell lines resulted in upregulation of expression of hundreds of genes including 162 that were increased by at least 2-fold. The expression of 19 of 36 candidate hypermethylated genes was increased following 5-AZA. Analysis of gene expression from an independent cohort of tumors confirmed decreased expression of six of nineteen hypermethylated genes (AXL, COL1A1, CYP1B1, LYN, SERPINE1, and VCAN. Comparing gene expression and DNA methylation analyses proved to be an effective way to identify genes epigenetically regulated in EWS. Further investigation is ongoing to elucidate the role of these epigenetic alterations in EWS pathogenesis.

Novel exon-exon breakpoint in CIC-DUX4 fusion sarcoma identified by anchored multiplex PCR (Archer FusionPlex Sarcoma Panel).

Science.gov (United States)

Loke, Benjamin Nathanael; Lee, Victor Kwan Min; Sudhanshi, Jain; Wong, Meng Kang; Kuick, Chik Hong; Puhaindran, Mark; Chang, Kenneth Tou En

2017-08-01

We describe the clinical and pathological features and novel genetic findings of a case of CIC-DUX4 sarcoma occurring in the thigh of a 35-year-old man. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was used to identify the novel fusion breakpoints of this CIC-DUX4 sarcoma using formalin-fixed and paraffin-embedded tumour material. This CIC-DUX4 sarcoma has a novel fusion breakpoint between exon 20 of the CIC gene and exon 1 of the DUX4 gene. This case report describes an additional case of CIC-DUX4 sarcoma with a novel fusion breakpoint, and demonstrates the value of this next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) in both diagnosis for patient care and in identification of a novel fusion breakpoint in this tumour type. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

AIDS-related Kaposi sarcoma: findings on thallium-201 scintigraphy

International Nuclear Information System (INIS)

Lee, V.W.; Rosen, M.P.; Baum, A.; Cohen, S.E.; Cooley, T.P.; Liebman, H.A.

1988-01-01

No simple, noninvasive method is available for evaluating extracutaneous Kaposi sarcoma in AIDS patients or for following the tumor's response to treatment. We report our preliminary experience with thallium-201 scintigraphy in nine AIDS patients with proved Kaposi sarcoma. Eight of the nine had abnormal uptake of the radionuclide in skin, lymph nodes, oral cavity, vagina, and lungs. Only four of the nine had cutaneous Kaposi sarcoma at the time of scanning. All cutaneous and mucosal lesions were thallium avid. Two of the six patients with thallium-avid nodes underwent nodal biopsy. Both biopsies confirmed the diagnosis of Kaposi sarcoma. Cutaneous Kaposi sarcoma developed later in one of these patients, showing the efficacy of thallium scintigraphy for the early detection of extracutaneous lesions. These preliminary results show thallium avidity in Kaposi sarcoma involving the skin and various extracutaneous sites (lymph nodes, lung, mucosa, and vagina). Thallium scintigraphy is a potentially useful procedure for detecting extracutaneous Kaposi sarcoma in AIDS patients

NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

Science.gov (United States)

Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

2017-07-01

CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

The frequency of p53, Ki67, CD99 and Fli-1 protein expression in paraffin-embedded tissue blocks in Ewing’s sarcoma

Directory of Open Access Journals (Sweden)

Bagheri Hossein-Abadi Z

2011-06-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ewing sarcoma family tumors (ESFTs are among the most malignant tumors in children and young adults. ESFTs include Ewing sarcoma (ES and peripheral primitive neuroectodermal tumors (pPNETs. As there seemed to be few studies on the molecular biology of ESFTs, we investigated the frequency of CD99, Ki67, p53 and Fli-1 protein expression in 15 Iranian patients with ESFTs. In addition, the correlation between expression rate of these proteins and various clinical factors, including age, sex and survival was computed."n"nMethods: The expression of the aforesaid proteins was studied by immunohisto-chemistry in formalin-fixed and paraffin-embedded blocks of 15 ESFTs specimens. Stained sections were classified according to the percentage of stained tumor cells."n"nResults: The results showed the membrane expression of CD99 protein in all of the specimens. The nuclear expression of Fli-1 protein was observed in 86.7% and the over-expression of p53 nuclear protein was seen in 53.3% of the specimens. The expression rate of Ki67 protein was 60%. Although a significant correlation was not shown between the expression levels of Ki67, p53 or Fli-1 proteins with age, sex or survival of the patients, there was a significant

Dural metastasis of Ewing's sarcoma.

Science.gov (United States)

Ben Nsir, Atef; Boughamoura, Mohamed; Maatouk, Mezri; Kilani, Mohamed; Hattab, Nejib

2013-01-01

Metastatic Ewing's sarcoma to the central nervous system is an uncommon condition and debate concerning the true origin of its metastases is still up to date. To the best of our knowledge, only two cases of dural metastatic Ewing's sarcoma have been published in the English medical literature. We present an additional case in a 24-year-old female and discuss the pathogenesis of these unusual tumors with review of the relevant literature concerning their treatment and outcome. A 24-year-old female with previous history of pelvis Ewing's sarcoma and recently discovered lung metastases, presented with moderate headache for the past 2 weeks and weakness in her left leg for the past 2 days. Computed tomography scan and magnetic resonance imaging revealed an extra-axial right frontoparietal mass invading the superior sagittal sinus but with clear delineation with brain parenchyma. Imaging features were suggestive of a meningioma as no abnormalities in the skull abutting to the tumor were noted. The patient underwent surgical removal of her tumor. Near total resection was achieved and histological examination showed evidence of metastatic Ewing's sarcoma. Postoperative adjuvant radiation and chemotherapy were administered. The patient improved well postoperatively with full recovery of her motor weakness. She is symptom free with no signs of progression, at most recent follow-up, 8 months after surgery. Despite its rarity, metastatic Ewing's sarcoma must be considered in the differential diagnosis of extra-axial dural masses particularly meningiomas.

An Interaction with Ewing's Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer.

Science.gov (United States)

Kedage, Vivekananda; Selvaraj, Nagarathinam; Nicholas, Taylor R; Budka, Justin A; Plotnik, Joshua P; Jerde, Travis J; Hollenhorst, Peter C

2016-10-25

More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing's sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing's sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing's sarcoma. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Uterine sarcoma

Science.gov (United States)

... Livingstone; 2014:chap 88. Crum CP, Laury AR, Hirsch MS, Quick CM, Peters WA. Undifferentiated uterine sarcoma. ... Crum CP, Quick CM, Laury AR, Peters WA, Hirsch MS, eds. Gynecologic and Obstetric Pathology . Philadelphia, PA: ...

Sarcoma Immunotherapy

Energy Technology Data Exchange (ETDEWEB)

Gouw, Launce G., E-mail: launce.gouw@hsc.utah.edu [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Jones, Kevin B. [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Sharma, Sunil [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Randall, R. Lor [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States)

2011-11-10

Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.

Sarcoma Immunotherapy

International Nuclear Information System (INIS)

Gouw, Launce G.; Jones, Kevin B.; Sharma, Sunil; Randall, R. Lor

2011-01-01

Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis

Testicular granulocytic sarcoma without systemic leukemia

NARCIS (Netherlands)

Lagerveld, B. W.; Wauters, C. A. P.; Karthaus, H. F. M.

2005-01-01

This case report describes a unilateral testicular granulocytic sarcoma or chloroma. Because of the relatively immature nature of the tumor cells, the histological diagnosis can be difficult. Granulocytic sarcomas are well known in patients with systemic leukemia and can sometimes precede a systemic

Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

Directory of Open Access Journals (Sweden)

Michela Pasello

2011-01-01

Full Text Available Recent studies have indicated that targeting glutathione-S-transferase (GST isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthiohexanol (NBDHEX has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST. NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

Ewing's Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue.

Science.gov (United States)

Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C

2016-04-30

The molecular mechanism responsible for Ewing's Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

Granulocytic sarcoma masquerading as Ewing′s sarcoma: A diagnostic dilemma

Directory of Open Access Journals (Sweden)

Haresh Kunhi

2008-01-01

Full Text Available An eleven-year-old boy presented with a swelling in his left elbow. Radiologically the features were that of an Ewing′s sarcoma involving the ulna. Histopathology showed small round cell tumor strongly positive for Monoclonal Imperial Cancer research fund 2 (MIC2 antigen. Similar cells in the bone marrow were involved with MIC2 positivity. The patient developed skin lesions, which on biopsy were found to be chloromas. The initial biopsies were reevaluated with special stains revealing granulocytic sarcomas in acute myeloid leukemia masquerading as Ewing′s due to its MIC2 positivity. The possibility of myeloid neoplasms should be considered routinely with known MIC2 positive round cell tumors.

Optimal management of primary retroperitoneal sarcoma: an update.

Science.gov (United States)

Miah, Aisha B; Hannay, Jonathan; Benson, Charlotte; Thway, Khin; Messiou, Christina; Hayes, Andrew J; Strauss, Dirk C

2014-05-01

Soft tissue sarcomas are a group of heterogeneous neoplasms with more than 50 histological subtypes exhibiting major differences in terms of pathogenesis, genetic alterations and clinical behavior. Sarcomas represent approximately 1% of malignancies with retroperitoneal sarcomas representing 10-15% of all soft tissue sarcomas. Surgery is currently the only modality which offers the chance of cure. Surgery for retroperitoneal sarcomas presents specific challenges due their location in a complex space surrounded by vital structures and visceral organs often prohibiting resection with wide margins. Furthermore, even after complete resection local recurrence is common and the leading cause of death. In this article the authors describe the initial investigations, prognostic factors and optimal surgical management. The evidence and current research as regards the role of multimodality treatment is reviewed and discussed.

Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

Science.gov (United States)

2013-06-20

Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Synovial sarcoma with radiological appearances of primitive neuroectodermal tumour/Ewing sarcoma: differentiation by molecular genetic studies

International Nuclear Information System (INIS)

O'Donnell, P.; Diss, T.C.; Whelan, J.; Flanagan, A.M.

2006-01-01

Synovial sarcoma (SS) arises in soft tissues but may invade adjacent bone. We describe a case of SS presenting as aggressive lysis of the proximal ulna, the imaging of which suggested a primary bone lesion. Needle biopsy showed a 'small round blue cell tumour', and a primitive neuroectodermal tumour (PNET)/Ewing sarcoma was suggested on the basis of the imaging appearances. The definitive diagnosis of synovial sarcoma was made following molecular genetic studies, which demonstrated a fusion product incorporating the genes SYT and SSX1. The importance of correct diagnosis to guide appropriate management, and, therefore, the necessity for molecular genetic studies, is discussed. (orig.)

Osteogenic sarcoma of the skull. A clinicopathologic study of 19 patients

International Nuclear Information System (INIS)

Huvos, A.G.; Sundaresan, N.; Bretsky, S.S.; Butler, A.

1985-01-01

The authors studied 19 patients with well documented osteogenic sarcomas arising in the skull, which represent 1.6% of all osteogenic sarcomas registered during a 60-year period (1921-1981). Ten sarcomas were primary, de novo tumors. Nine others developed secondary osteogenic sarcomas; among these, six arose as a complication of Paget's disease, two followed irradiation, and one was associated with pre-existent fibrous dysplasia. The sarcomas arose in equal proportion in both sexes with the men being much older (mean age, 44 years) as compared to the women (mean age, 31 years). Patients with de novo osteogenic sarcomas were considerably younger than those with secondary lesions. Osteoblastic osteogenic sarcoma was by far the most common histologic variant in both the primary and the Paget's sarcomas. None of the patients with Paget's sarcoma lived longer than 1 year; the median survival here was 4 months. Patients with de novo osteogenic sarcomas fared much better and there are four long-term survivors (longer than 3 years) who are currently disease-free

Physiotherapy management of patients with HIV-associated Kaposi's sarcoma.

Science.gov (United States)

Harris-Love, Michael O; Shrader, Joseph A

2004-01-01

Kaposi's sarcoma is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although Kaposi sarcoma lesions may contribute to significant physical impairments, there is a lack of scientific literature detailing the role of physiotherapy in the treatment of HIV-associated Kaposi's sarcoma. The present Case Report includes two males, aged 36 and 39 years, seropositive for HIV with invasive Kaposi's sarcoma. Patient A was evaluated for bilateral foot pain caused by plantar surface Kaposi s sarcoma lesions that rendered him unable to walk. He progressed to walking 400feet after a treatment regimen of gait training with the use of custom plastazote sandals. Patient B was evaluated for right lower extremity lymphoedema secondary to invasive Kaposi's sarcoma. He experienced an 18% reduction in limb volume, a 38% reduction in pain and a 20 degrees increase in terminal knee flexion after therapeutic exercise and the use of compressive bandaging and garments. This Case Report suggests that physiotherapy interventions may be valuable in the conservative management of patients with HIV-associated Kaposi s sarcoma.

[Molecular biology for sarcoma: useful or necessary?].

Science.gov (United States)

Neuville, Agnès; Coindre, Jean-Michel; Chibon, Frédéric

2015-01-01

Sarcomas are a heterogeneous group of tumors. Their diagnosis is based on morphology and immunohistochemical profile, with categories of tumors according to the type of tissue that they resemble. Nevertheless, for several tumors, cellular origin is unknown. Molecular analysis performed in recent years allowed, combining histophenotype and genomics, better classifying such sarcomas, individualizing new entities and grouping some tumors. Simple and recurrent genetic alterations, such as translocation, mutation, amplification, can be identified in one of two sarcomas and appear as new diagnostic markers. Their identification in specialized laboratories in molecular pathology of sarcomas is often useful and sometimes necessary for a good diagnosis, leading to a heavy and multidisciplinary multi-step treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Ewing's sarcoma of the head and neck

Directory of Open Access Journals (Sweden)

Adriano Santana Fonseca

2000-11-01

Full Text Available CONTEXT: Ewing's sarcoma is a rare neoplasm, which usually arises in long bones of the limbs and in flat bones of the pelvis, with the involvement of head and neck bones being very unusual. CASE REPORT: a case of Ewing's sarcoma occurring in the mandible of a 35-year-old female. Pain and swelling of the tumor were the main complaints. The early hypothesis was an undifferentiated malignant neoplasm, possibly a sarcoma. The CT scan depicted an expansive lesion, encapsulated, with septa and characteristics of soft tissue, involving the left side of the mandible and extending to the surrounding tissues. The patient underwent surgical excision of the lesion, the definitive diagnosis of Ewing's sarcoma was established, and the patient commenced on radiotherapy.

Extrauterine Low-Grade Endometrial Stromal Sarcoma

Directory of Open Access Journals (Sweden)

Yu-Ju Chen

2005-12-01

Conclusions: Low-grade endometrial stromal sarcoma typically has an indolent clinical course and favorable prognosis. Surgical resection is the primary therapeutic approach, and adjuvant therapy with radiotherapy, chemotherapy, or progesterone therapy should be considered for the management of residual or recurrent low-grade endometrial stromal sarcomas.

Hemipelvectomy with laparoscopic abdominoperineal excision for epithelioid sarcoma treatment

Directory of Open Access Journals (Sweden)

Daniel Paulino Santana

2017-07-01

Full Text Available The epithelioid sarcoma (ES is an unusual variant of the sarcoma, not reaching 1% of all soft tissue sarcomas. Initially reported in 1970, it has a more aggressive variant, which was classified as the “proximal-type” in 1997. These are aggressive tumors with high rates of distant metastasis and local relapses. Isolated radio and chemotherapy responses are poor and free-margin surgical resection is the treatment of choice.This is the case report of a 25-year-old male patient diagnosed with “proximal-type” ES in the perineal region. He underwent surgical resection in another institution and was later admitted to our institution with local recurrence with rectal and left thigh muscle invasion. Neoadjuvant radio-chemotherapy was performed, followed by laparoscopic abdominoperineal rectal resection and partial left hemipelvectomy associated with left lower-limb amputation. The patient had no postoperative complications and is currently undergoing outpatient follow-up. The anatomopathological analysis showed tumor-free margins.The “proximal-type” ES is a rare soft-tissue sarcoma subtype. High local recurrence, as well as the metastasis rates, makes its treatment a challenging task. Resumo: O sarcoma epitelióide (SE é um subtipo incomum de sarcoma, não chegando a 1% dos sarcomas de partes moles. Foi inicialmente descrito em 1970, sendo que em 1997 uma variante mais agressiva foi classificada como “tipo proximal”. São tumores agressivos, com altas taxas de metástases e recidiva local, com resposta pobre à quimioterapia e radioterapia isoladas. A ressecção cirúrgica com margens livres é o tratamento padrão.Apresentamos o caso de um paciente de 25 anos com SE tipo proximal avançado em região perineal, submetido a ressecção em outro serviço, evoluindo com recidiva local com invasão do canal anal e musculatura da coxa esquerda. Foi realizado tratamento radioquimioterápico neoadjuvante seguido de ressecção cirúrgica com

Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors

OpenAIRE

Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

2012-01-01

Background: The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. Aim: To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Material and Methods: Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sa...

Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells treated with melatonin

Science.gov (United States)

García-Santos, G; Martin, V; Rodríguez-Blanco, J; Herrera, F; Casado-Zapico, S; Sánchez-Sánchez, A M; Antolín, I; Rodríguez, C

2012-01-01

Background: Despite recent advances in cancer therapy, the 5-year survival rate for Ewing's sarcoma is still very low, and new therapeutic approaches are necessary. It was found previously that melatonin induces cell death in the Ewing's sarcoma cell line, SK-N-MC, by activating the extrinsic apoptotic pathway. Methods: Melatonin actions were analysed by metabolic viability/survival cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein activation/expression and electrophoretic mobility shift assay for transcription factor activation. Results: Melatonin increases the expression of Fas and its ligand Fas L, this increase being responsible for cell death induced by the indolamine. Melatonin also produces a transient increase in intracellular oxidants and activation of the redox-regulated transcription factor Nuclear factor-kappaB. Inhibition of such activation prevents cell death and Fas/Fas L upregulation. Cytotoxic effect and Fas/Fas L regulation occur in all Ewing's cell lines studied, and do not occur in the other tumour cell lines studied where melatonin does not induce cell death. Conclusion: Our data offers new insights in the study of alternative therapeutic strategies in the treatment of Ewing's sarcoma. Further attention deserves to be given to the differences in the cellular biology of sensitive tumours that could explain the cytotoxic effect of melatonin and the increase in the level of free radicals caused by this molecule, in particular cancer types. PMID:22382690

Primary clear cell sarcoma of rib

International Nuclear Information System (INIS)

Hersekli, Murat Ali; Ozkoc, Gurkan; Akpinar, Sercan; Ozalay, Metin; Tandogan, Reha N.; Bircan, Sema; Tuncer, Ilhan

2005-01-01

Clear cell sarcoma (malignant melanoma of soft tissues) is a very rare soft tissue neoplasm. It generally arises in tendons and aponeuroses. Although metastasis of malignant melanoma to bone is not uncommon, primary clear cell sarcoma of bone is an extremely rare neoplasm. To our knowledge five cases have been reported in the English literature. We present a case of primary clear cell sarcoma of bone in a 28-year-old woman arising in the left ninth rib. We treated the patient with total excision of the mass and postoperative radiotherapy. The patient is alive and well without local recurrence or distant metastasis at 33 months after surgery. (orig.)

Ewing's sarcoma mimicking a meningioma in radiological findings: a case report

International Nuclear Information System (INIS)

Kwon, Hee Jin; Choi, Sun Seob

2007-01-01

Ewing's sarcoma is an uncommon primary bone tumor. Primary Ewing's sarcoma of the cranium is extremely rare and constitutes only 1% of all Ewing's sarcoma cases. Usually, primary Ewing's sarcoma of the carnium manifests as an expansile osteolytic malignant bone tumor with or without intracranial extension. We report here the radiological findings of a case of Ewing's sarcoma mimicking a meningioma in an 18-year-old man

Orbital Epithelioid Sarcoma: A Case Report

NARCIS (Netherlands)

Jurdy, Lama L.; Blank, Leo E.; Bras, Johannes; Saeed, Peerooz

2016-01-01

Epithelioid sarcoma is a rare but often aggressive malignancy of soft tissue that usually occurs in young adults as a superficial lesion in the distal upper limbs. To date, there are only 4 case reports of epithelioid sarcoma primarily occurring in the orbit. Two of these patients were treated with

Radiological findings of pulmonary Kaposi's sarcoma. Manifestaciones radiologicas del sarcoma de Kaposi pulmonar

Energy Technology Data Exchange (ETDEWEB)

Rosello, J.A.; Hernandez, S.; Arranz, M.; Jareo, J.; Ancoechea, J.

1994-01-01

Kaposi's sarcoma (KS) is the most common neoplasm in AIDS patients. The incidence of pulmonary involvement is approximately 20%. The radiological findings are reported in plain chest x-ray and computed tomography (CT) in 15 patients diagnosed as having pulmonary Kaposi's sarcoma, in whom concomitant pulmonary infection was ruled out. The most common radiological pattern was that of bilateral perihilar interstitial involvement (86%), while poorly defined multiple nodules seldom presented (13%). In 40% of cases, the pulmonary parenchymal lesion was accompanied by pleural effusion. This sign is useful in the differential diagnosis involving opportunistic P. carinii pneumonia, a very common process in these patients which rarely presents with pleural effusion. The chest CT finding that was most characteristic of pulmonary Kaposi's sarcoma was bilateral perihilar peribronchovascular enlargement. (Author)

Olaratumab for advanced soft tissue sarcoma.

Science.gov (United States)

Tobias, Alexander; O'brien, Michael P; Agulnik, Mark

2017-07-01

Olaratumab is a humanized IgG1 monoclonal antibody that blocks the platelet-derived growth factor receptor alpha (PDGFRα). Its antagonistic behavior inhibits the receptor's tyrosine kinase activity, thereby, turning off the downstream signaling cascades responsible for soft tissue sarcoma tumorigenesis. In October 2016, olaratumab received Food and Drug Administration (FDA) approval for its use in combination with doxorubicin for treatment of advanced soft tissue sarcoma. Areas covered: This drug profile takes a comprehensive look at the clinical studies leading to FDA approval of olaratumab as well as its safety and efficacy as a front-line treatment option for sarcoma patients. The literature search was primarily conducted using PubMed. Expert commentary: The combination of olaratumab plus doxorubicin has provided a new front-line therapeutic option for soft tissue sarcoma patients. An open-label phase Ib and randomized phase II trial in patients with advanced soft tissue sarcoma demonstrated that the addition of olaratumab to doxorubicin prolonged progression-free survival by 2.5 months and overall survival by 11.8 months when compared to doxorubicin alone. Of importance, this clinically meaningful increase in overall survival did not come at the expense of a significantly greater number of toxicities. A phase III confirmatory trial (ClinicalTrials.gov Identifier NCT02451943) will be completed in 2020.

Ewing?s Sarcoma of the Adrenal Gland

OpenAIRE

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing’s sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing’s sarcoma is very rare. Here we report a case of Ewing’s sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five mon...

PNET Ewing's sarcoma: a case report of a 8-year-old child presenting with PNET Ewing sarcoma

International Nuclear Information System (INIS)

Bauskar, Pratibha; Bhalavat, Rajendra; Chandra, Manish; Bauskar, Dipak

2016-01-01

PNET (Primitive Neuro-Ectodermal) mostly present in younger children. PNET Ewing sarcoma Ewing's sarcomas are rare, aggressive tumors, growth from undeveloped brain cells, with a tendency towards recurrence. We report the case of a 8-year-old girl who presented with a one year history of pain in her lower neck region with single episode of un-consciousness associate with left side upper and lower limb weakness. Magnetic resonance imaging demonstrated an abnormal marrow changes involving C5 vertebra and involvement of posterior elements showing expansive changes. Biopsy showed malignant small round cell tumor identifying as PNET Ewing sarcoma. Laminectomy and Decompression of cervical tumor. (author)

Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas

OpenAIRE

Chan, Sock Hoai; Lim, Weng Khong; Ishak, Nur Diana Binte; Li, Shao-Tzu; Goh, Wei Lin; Tan, Gek San; Lim, Kiat Hon; Teo, Melissa; Young, Cedric Ng Chuan; Malik, Simeen; Tan, Mann Hong; Teh, Jonathan Yi Hui; Chin, Francis Kuok Choon; Kesavan, Sittampalam; Selvarajan, Sathiyamoorthy

2017-01-01

Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13....

Considerations for the long term treatment of pediatric sarcoma survivors

Directory of Open Access Journals (Sweden)

Kurt R Weiss

2018-01-01

Full Text Available Sarcomas are primary malignancies of the connective tissues. They are exceedingly rare in adults, but much more common in children. The historically recent advent of cytotoxic chemotherapy for pediatric sarcomas has revolutionized the treatment of these diseases and dramatically improved their prognoses. There is thus a population of pediatric sarcoma survivors that are “coming of age” as adults. However, this progress is not without consequences. Due to aggressive treatment protocols that include various combinations of surgery, chemotherapy, and radiation therapy, pediatric sarcoma survivors are at risk of myriad physical, medical, and psychological difficulties as they enter adulthood. These include but are not limited to physical disabilities, chemotherapy-induced cardiac issues, second malignancies, and anxiety. These patients pose unique challenges to their adult primary care physicians. One possible solution to these challenges is multidisciplinary sarcoma survivorship clinics. By paying greater attention to the unique issues of pediatric sarcoma survivors, involved physicians can maximize the physical and emotional health of pediatric sarcoma survivors.

Feline injection-site sarcoma / Sarcoma de aplicação felino

Directory of Open Access Journals (Sweden)

Julia Maria Matera

2008-08-01

Full Text Available The feline injection-site sarcoma (FIS is a challenge for the veterinarian and the affected cat’s owner. The injectable applications (vaccines, medications seems to be the reason for that neoplasia, more specifically, the inflammation caused by injury of given drugs or antigens to the health tissue. Generally the FIS presents a more aggressive behavior when compared to sarcoma not associated to application. The most effective treatment has not been established yet, but it is believed that a multimodality of therapies, surgery, radiotherapy, and chemotherapy would be the most indicated option. The knowledge of the illness in all of its aspects will supply to professionals colleges subsidies in relation to the best way to approach its diagnosis and treatment.O sarcoma de aplicação felino (SAF é atualmente um grande desafio para o médico veterinário e também para o proprietário do felino acometido. Aplicações injetáveis por via subcutânea ou intramuscular, como vacinas e medicações, aparecem como iniciadoras do processo de neogênese dessa neoplasia, mais precisamente a inflamação persistente, causada pela lesão ao tecido sadio decorrente do fármaco ou antígeno administrado. Geralmente o SAF apresenta comportamento mais agressivo quando comparado ao sarcoma não associado à aplicação. O tratamento mais eficaz ainda não está estabelecido, mas acredita-se que a multimodalidade de terapias, cirurgia, radioterapia e quimioterapia seja a opção mais indicada. O conhecimento da afecção em todos os seus aspectos irá fornecer aos colegas profissionais subsídios em relação a melhor maneira de abordá-la em termos de diagnóstico, tratamento e prevenção.

Wiki-Based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma: A New Paradigm in Sarcoma Evidence

Science.gov (United States)

Neuhaus, S. J.; Thomas, D.; Desai, J.; Vuletich, C.; von Dincklage, J.; Olver, I.

2015-01-01

In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community. PMID:25784832

Genetic susceptibility to bone and soft tissue sarcomas: a field synopsis and meta-analysis.

Science.gov (United States)

Benna, Clara; Simioni, Andrea; Pasquali, Sandro; De Boni, Davide; Rajendran, Senthilkumar; Spiro, Giovanna; Colombo, Chiara; Virgone, Calogero; DuBois, Steven G; Gronchi, Alessandro; Rossi, Carlo Riccardo; Mocellin, Simone

2018-04-06

The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases. To evaluate result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Integrative analysis of genetic and eQTL (expression quantitative trait locus) data was coupled with network and pathway analysis to explore the hypothesis that specific cell functions are involved in sarcoma predisposition. We retrieved 90 eligible studies comprising 47,796 subjects (cases: 14,358, 30%) and investigating 1,126 polymorphisms involving 320 distinct genes. Meta-analysis identified 55 single nucleotide polymorphisms (SNPs) significantly associated with disease risk with a high (N=9), moderate (N=38) and low (N=8) level of evidence, findings being classified as noteworthy basically only when the level of evidence was high. The estimated joint population attributable risk for three independent SNPs (rs11599754 of ZNF365/EGR2 , rs231775 of CTLA4 , and rs454006 of PRKCG ) was 37.2%. We also identified 53 SNPs significantly associated with sarcoma risk based on single studies.Pathway analysis enabled us to propose that sarcoma predisposition might be linked especially to germline variation of genes whose products are involved in the function of the DNA repair machinery. We built the first knowledgebase on the evidence linking DNA variation to sarcomas susceptibility, which can be used to generate mechanistic hypotheses and inform future studies in this field of oncology.

The Ewing sarcoma secretome and its response to activation of Wnt/beta-catenin signaling.

Science.gov (United States)

Hawkins, Allegra G; Basrur, Venkatesha; da Veiga Leprevost, Felipe; Pedersen, Elisabeth; Sperring, Colin; Nesvizhskii, Alexey I; Lawlor, Elizabeth R

2018-01-31

Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta-catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic

Uterine sarcomas-Recent progress and future challenges

International Nuclear Information System (INIS)

Seddon, Beatrice M.; Davda, Reena

2011-01-01

Uterine sarcomas are a group of rare tumours that provide considerable challenges in their treatment. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made post-operatively. Current staging systems have been unsatisfactory, although a new FIGO staging system specifically for uterine sarcomas has now been introduced, and may allow better grouping of patients according to expected prognosis. While the mainstay of treatment of early disease is a total abdominal hysterectomy, it is less clear whether routine oophorectomy or lymphadenectomy is necessary. Adjuvant pelvic radiotherapy may improve local tumour control in high risk patients, but is not associated with an overall survival benefit. Similarly there is no good evidence for the routine use of adjuvant chemotherapy. For advanced leiomyosarcoma, newer chemotherapy agents including gemcitabine and docetaxel, and trabectedin, offer some promise, while hormonal therapies appear to be more useful in endometrial stromal sarcoma. Novel targeted agents are now being introduced for sarcomas, and uterine sarcomas, and show some indications of activity. Non-pharmacological treatments, including surgical metastatectomy, radiofrequency ablation, and CyberKnife radiotherapy, are important additions to systemic therapy for advanced metastatic disease.

Sarcomas associated with hereditary nonpolyposis colorectal cancer: broad anatomical and morphological spectrum

DEFF Research Database (Denmark)

Nilbert, Mef; Therkildsen, Christina; Nissen, Anja

2009-01-01

-register to identify HNPCC families in which sarcomas had been diagnosed. Fourteen sarcomas were identified in families with mutations in MSH2, MSH6, and MLH1. The median age at sarcoma diagnosis was 43 (15-74) years. Soft tissue sarcomas predominated followed by uterine sarcomas and eight histopathological subtypes...

Histology and imaging of soft tissue sarcomas.

Science.gov (United States)

Kind, Michèle; Stock, Nathalie; Coindre, Jean Michel

2009-10-01

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Histology and imaging of soft tissue sarcomas

International Nuclear Information System (INIS)

Kind, Michele; Stock, Nathalie; Coindre, Jean Michel

2009-01-01

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Histology and imaging of soft tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Kind, Michele [Departement d' Imagerie Medicale, Institut Bergonie, 229 cours de l' Argonne, 33076 Bordeaux Cedex (France)], E-mail: kind@bergonie.org; Stock, Nathalie; Coindre, Jean Michel [Departement de Pathologie, Institut Bergonie, 229 cours de l' Argonne, 33076 Bordeaux Cedex (France); Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France)

2009-10-15

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype

Directory of Open Access Journals (Sweden)

Shingo Sato

2016-07-01

Full Text Available The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

Primary clear cell sarcoma of bone: a unique site of origin

International Nuclear Information System (INIS)

Gelczer, R.K.; Wenger, D.E.; Wold, L.E.

1999-01-01

Clear cell sarcoma is a rare soft tissue neoplasm, accounting for less than 1% of soft tissue sarcomas. We are presenting a case of a clear cell sarcoma of bone which, to our knowledge, is the only report of a primary clear cell sarcoma of bone. (orig.)

Subcentimeter Pulmonary Nodules Detected in Patients with Sarcoma

Directory of Open Access Journals (Sweden)

Michelle S. Ginsberg

2000-01-01

Full Text Available Background. Subcentimeter pulmonary nodules are being detected with increasing frequency in patients with sarcoma due to the greater use of chest CT, the advent of helical (spiral CT scanning and multidetector scanners, and the attendant decrease in image section thickness.Assessing the clinical significance of these pulmonary nodules is of particular importance in sarcoma patients, due to the frequent occurrence of pulmonary metastasis from sarcomas.

Sarcoma cutáneo mixto radioinducido Radiation-induced mixed cutaneous sarcoma

Directory of Open Access Journals (Sweden)

Isidoro Rubio-Correa

2012-06-01

Full Text Available Introducción: Los sarcomas son tumores malignos poco frecuentes, siendo raros en cabeza y cuello. En su etiología se involucran factores como agentes químicos, radiación, inmunosupresión y síndromes y anomalías genéticas. Caso clínico: Varón de 64 años, que presenta lesión en piel de mejilla derecha de un año de evolución, localización en la que presentó hace veinte años un carcinoma basocelular tratado con radioterapia. Tras descartar existencia de metástasis, se realizó exéresis de la lesión con márgenes de seguridad y reconstrucción con colgajo de Mustardé. Se complementó el tratamiento con radioterapia. Discusión: El diagnóstico es anatomopatológico, siendo fundamental descartar afectación metastásica. Para mejorar la supervivencia y disminuir su elevada tasa de recidiva, deberían tratarse de forma multidisciplinar (cirugía, radioterapia y/o quimioterapia. Conclusión: A pesar de su baja frecuencia, los sarcomas deben estar presentes en el diagnóstico diferencial de toda lesión que aparezca en zonas radiadas previamente, especialmente en la piel facial.Introduction: Sarcomas are malignant tumors that are infrequent, being rare in the head and neck. Factors such as chemical agents, radiation, immunosuppression, and genetic syndromes and abnormalities are involved in their etiology. Case report: A 64-year-old man developed a skin lesion on the right cheek one year earlier at the site where he had presented a basal cell carcinoma 20 years earlier that was treated with radiation therapy. After ruling out the existence of metastasis, the lesion was treated by surgical resection with safety margins and reconstruction with the Mustardé flap. Treatment was supplemented with radiation therapy. Discussion: The diagnosis of sarcomas is histopathologic and it is essential to rule out metastasis. To improve survival and reduce the high rate of recurrence, a multidisciplinary approach to treatment should be used (surgery

Protein complexes associated with the Kaposi's sarcoma-associated herpesvirus-encoded LANA

International Nuclear Information System (INIS)

Kaul, Rajeev; Verma, Subhash C.; Robertson, Erle S.

2007-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA is known to modulate viral and cellular gene expression. We report here on some initial proteomic studies to identify cellular proteins associated with the amino and carboxy-terminal domains of LANA. The results of these studies show an association of known cellular proteins which support LANA functions and have identified additional LANA-associated proteins. These results provide new evidence for complexes involving LANA with a number of previously unreported functional classes of proteins including DNA polymerase, RNA helicase and cell cycle control proteins. The results also indicate that the amino terminus of LANA can interact with its carboxy-terminal domain. This interaction is potentially important for facilitating associations with other cell cycle regulatory proteins which include CENP-F identified in association with both the amino and carboxy-termini. These novel associations add to the diversity of LANA functions in relation to the maintenance of latency and subsequent transformation of KSHV infected cells

Newly Characterized Murine Undifferentiated Sarcoma Models Sensitive to Virotherapy with Oncolytic HSV-1 M002

Directory of Open Access Journals (Sweden)

Eric K. Ring

2017-12-01

Full Text Available Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45 and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1. Both models expressed high levels of the primary HSV entry molecule nectin-1 (CD111 and were susceptible to killing by interleukin-12 (IL-12 producing HSV-1 M002 in vitro and in vivo. M002 resulted in a significant intratumoral increase in effector CD4+ and CD8+ T cells and activated monocytes, and a decrease in myeloid-derived suppressor cells (MDSCs in immunocompetent mice. Compared to parent virus R3659 (no IL-12 production, M002 resulted in higher CD8:MDSC and CD8:T regulatory cell (Treg ratios, suggesting that M002 creates a more favorable immune tumor microenvironment. These data provide support for clinical trials targeting sarcomas with oncolytic HSV-1. These models provide an exciting opportunity to explore combination therapies for soft tissue sarcomas that rely on an intact immune system to reach full therapeutic potential.

Sarcoma de Kaposi em membros inferiores: relato de caso Kaposi sarcoma in the lower limbs: case report

Directory of Open Access Journals (Sweden)

Jorge Agle Kalil

2010-12-01

Full Text Available O sarcoma de Kaposi é uma neoplasia angioproliferativa maligna que na maioria das vezes se restringe à pele e ao tecido subcutâneo; porém, pode aparecer de forma mais agressiva, atingindo a cavidade oral, o trato gastrointestinal e os pulmões (sarcoma de Kaposi visceral. É classificado com quatro variantes clínco-epidemiológicas: clássica, endêmica, iatrogênica e epidêmica, todas associadas ao herpes vírus humano tipo 8. O objetivo desta publicação foi relatar um caso raro de sarcoma de Kaposi em paciente idosa imunossuprimida, não relacionado à síndrome da imunodeficiência adquirida, que evoluiu de forma desfavorável em um período de cinco meses a partir do aparecimento de lesões bolhosas hemáticas e necróticas que, posteriormente, progrediram com intensa exsudação local, desidratação, insuficiência renal e piora do estado geral, evoluindo então a óbito, tendo como causa mortis a falência de múltiplos órgãos.The Kaposi sarcoma is an angio-proliferative malignant neoplasm that mostly affects the skin and subcutaneous tissue, although it can present in a more aggressive form, involving the oral cavity, lungs and gastrointestinal tract (visceral Kaposi sarcoma. It is classified into 4 clinical-epidemiological types: classic, endemic, iatrogenic and epidemic, all of them associated with the human herpesvirus 8. We report a rare case of Kaposi sarcoma in an elderly immunodepressed female patient, not related to the acquired immunodeficiency syndrome, that evolved fatally in five months, since the appearance of hematic necrotic bullous lesions which progressed with intense local exudation, dehydration, renal insufficiency and worsening of the clinical status, ending in death, caused by multiple organ failure.

Osseous Kaposi sarcoma in an HIV-positive patient

International Nuclear Information System (INIS)

Thanos, Loukas; Mylona, Sofia; Kalioras, Vasilios; Pomoni, Maria; Batakis, Nikolaos

2004-01-01

A case of osseous Kaposi sarcoma in a 35-year-old man is described. The patient (HIV-positive for 8 years) suffered from cutaneous Kaposi sarcoma and presented with right-sided chest pain. He underwent a chest CT scan that revealed three osteolytic lesions involving rib and vertebra with large soft tissue masses, without cutaneous lesions at these sites. CT-guided core needle biopsy led to a histological diagnosis of Kaposi sarcoma. (orig.)

The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

DEFF Research Database (Denmark)

Aggerholm-Pedersen, Ninna; Maretty-Kongstad, Katja; Keller, Johnny

2016-01-01

sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI......OBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic...... with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils...

Delays in the management of retroperitoneal sarcomas

DEFF Research Database (Denmark)

Seinen, Jojanneke; Almquist, Martin; Styring, Emelie

2010-01-01

Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal...... sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care...... delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23¿days (0-17¿months) and median health care delay of 94¿days (1-40¿months) with delays of median 15¿days...

Ewing's sarcoma, a rare but dangerous tumor

Directory of Open Access Journals (Sweden)

Theophilus Maksha Dabkana

2015-01-01

Full Text Available Ewing's sarcoma or Ewing tumor is a rare primary bone tumor that affects mainly children and adolescents. It belongs to a group of cancers known collectively as Ewing sarcoma family tumors or Ewing family tumors. By the time, the patients present and diagnosis is made, the disease is usually advanced. We reviewed the case files of two patients managed in our hospital within one (2013. Fine-needle aspirations for cytology (FNAC and tissue biopsy were used for diagnosis in the two patients we had. The two patients, both males aged 20 years and 38 years presented late and FNAC and tissue biopsy revealed Ewing's sarcoma. They were referred for radio- and chemotherapy. However, due to poor socioeconomic status, they died of their primary disease. Unless diagnosed early, and in the absence of a multidisciplinary approach, Ewing's sarcoma is a fatal disease.

Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

Directory of Open Access Journals (Sweden)

Andrea J O'Hara

2009-04-01

Full Text Available MicroRNAs (miRNA have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS and (ii to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

Snail1 Expression Is Required for Sarcomagenesis

Directory of Open Access Journals (Sweden)

Lorena Alba-Castellón

2014-05-01

Full Text Available Snail1 transcriptional repressor is a major inducer of epithelial-to mesenchymal transition but is very limitedly expressed in adult animals. We have previously demonstrated that Snail1 is required for the maintenance of mesenchymal stem cells (MSCs, preventing their premature differentiation. Now, we show that Snail1 controls the tumorigenic properties of mesenchymal cells. Increased Snail1 expression provides tumorigenic capabilities to fibroblastic cells; on the contrary, Snail1 depletion decreases tumor growth. Genetic depletion of Snail1 in MSCs that are deficient in p53 tumor suppressor downregulates MSC markers and prevents the capability of these cells to originate sarcomas in immunodeficient SCID mice. Notably, an analysis of human sarcomas shows that, contrarily to epithelial tumors, these neoplasms display high Snail1 expression. This is particularly clear for undifferentiated tumors, which are associated with poor outcome. Together, our results indicate a role for Snail1 in the generation of sarcomas.

Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG).

Science.gov (United States)

2018-04-01

Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%-0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.

Sarcoma de Kaposi em paciente transplantada renal em uso de Fk-506 Kaposi's Sarcoma in a renal transplant patient receiving Fk-506

Directory of Open Access Journals (Sweden)

Jorge David Rocha Zanol

2002-12-01

Full Text Available O Sarcoma de Kaposi (SK é neoplasia maligna multicêntrica, cutânea e extracutânea, que tem sido descrita em pacientes transplantados renais que recebem terapia imunossupressora clássica. Este estudo descreve um caso de sarcoma de Kaposi em paciente transplantada renal recebendo FK-506, que surgiu 10 meses após o transplante.Kaposi's sarcoma is a cutaneous and extra cutaneous multicentric malignancy that has been widely described in renal-transplant patients under classic immunosuppressive therapy. This study describes a renal-transplant patient under immunosuppressive therapy with FK-506 who presented Kaposi's sarcoma 10 months after the transplantation.

Clinical activity of pazopanib in metastatic extraosseous Ewing sarcoma

Directory of Open Access Journals (Sweden)

Steven Attia

2015-05-01

Full Text Available We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371. This national multi-institutional study is ongoing.

Multimodality management of primary diaphragmatic synovial sarcoma: First report

Directory of Open Access Journals (Sweden)

Preyas J Vaidya

2016-01-01

Full Text Available Synovial cell sarcoma is an extremely rare tumor of mesenchymal origin. It commonly affects the soft tissues of the extremities but could possibly origin from the head and neck, heart, lung, pleura, mediastinum, esophagus, abdominal wall and the mesentery, and retroperitoneum. Primary synovial sarcoma of pleura, mediastinum, and lung have been reported. Primary synovial sarcoma of the diaphragm has not been reported to the best of our knowledge. We report a case of primary synovial cell sarcoma of the diaphragm presenting as a recurrent pleural effusion and pain in the left hypochondrium managed with multimodality approach.

Sarcomas arising after radiotherapy for peptic ulcer disease

International Nuclear Information System (INIS)

Lieber, M.R.; Winans, C.S.; Griem, M.L.; Moossa, R.; Elner, V.M.; Franklin, W.A.

1985-01-01

Therapeutic gastric irradiation has been used to reduce peptic juice secretion in patients with peptic ulcer disease. Between 1937 and 1968 a total of 2049 patients received such therapy at the University of Chicago. Three of these patients are known to have developed sarcomas in the field of radiation. Two gastric leiomyosarcomas of the stomach were diagnosed 26 and 14 years after treatment and a malignant fibrous histiocytoma of the anterior chest wall was removed six years after gastric irradiation. Of 743 peptic ulcer patients treated without irradiation and constituted as a control group for the study of therapeutic gastric radiation, none is known to have developed sarcoma. As the incidence of sarcoma in these patient groups is known only from the tumor registry of the University of Chicago, other cases of sarcoma may exist in the groups. While an increased incidence of sarcoma has not been proven to occur in patients who received therapeutic gastric irradiation for peptic ulcer disease, the possibility of such a risk should be borne in mind by physicians caring for such patients

Clinical experience with intravenous radiosensitizers in unresectable sarcomas

International Nuclear Information System (INIS)

Kinsella, T.J.; Glatstein, E.

1987-01-01

Traditionally, adult bone and soft tissue sarcomas have been considered to be ''radioresistant.'' Because of this philosophy, patients who present with locally advanced, unresectable sarcomas often are treated in a palliative fashion, usually with low-dose radiotherapy. Over the last 6 years, 29 patients with unresectable primary or metastatic sarcomas were treated using a combination of intravenous chemical radiosensitizers and high-dose irradiation. Twenty-two of 29 patients achieved clinical local control, with six patients having a complete clinical response. The time to tumor response is often several months or longer, which is in contrast to other tumor histologies (carcinomas, lymphomas), where tumor response usually occurs over several weeks. Several large tumors have shown only a minimal tumor response, yet were found to be sterilized in posttreatment biopsy or autopsy examination. Of 15 patients with primary sarcomas without metastases, 11 patients (73%) remain free of local tumor progression from 12 to 83 months. Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear

Adult prostate sarcoma: the M. D. Anderson Cancer Center Experience.

Science.gov (United States)

Sexton, W J; Lance, R E; Reyes, A O; Pisters, P W; Tu, S M; Pisters, L L

2001-08-01

Sarcoma of prostate origin is rare. Historically, long-term survival rates for adult patients with prostate sarcoma are poor. We analyzed the experience of 1 institution with prostate sarcoma during the last 3 decades. The records of 21 patients with prostate sarcoma were reviewed to identify symptoms at presentation, diagnostic procedures, presence and development of metastases, staging evaluation, histological subtype, grade and size of the primary tumor, and treatment sequence, including surgery, and preoperative and postoperative therapies. Several clinicopathological variables were assessed for prognostic importance. Most patients presented with urinary obstruction. The diagnosis of prostate sarcoma was usually established with ultrasound guided biopsy or transurethral resection. Histological subtypes were leiomyosarcoma in 12, rhabdomyosarcoma in 4, malignant fibrous histiocytoma in 1 and unclassified sarcoma in 4 patients. At last followup, 8 patients had no evidence of disease after a median of 81.5 months (range 10 to 197). The remaining 13 patients died of sarcoma (median survival 18 months, range 3 to 94). The 1, 3 and 5-year actuarial survival rates for all 21 patients were 81%, 43% and 38%, respectively. Factors predictive of long-term survival were negative surgical margins (p = 0.0005) and absence of metastatic disease at presentation (p = 0.0004). Tumor size and grade, and the histological subtype of prostate sarcoma had no significant influence on actuarial survival. The long-term disease specific survival rate for adults with prostate sarcoma is poor. Early diagnosis and complete surgical resection offer patients the best chance for cure.

Ewing sarcoma versus osteomyelitis: differential diagnosis with magnetic resonance imaging

International Nuclear Information System (INIS)

Henninger, B.; Glodny, B.; Rudisch, A.; Trieb, T.; Loizides, A.; Judmaier, W.; Schocke, M.F.; Putzer, D.

2013-01-01

To find and evaluate characteristic magnetic resonance imaging (MRI) patterns for the differentiation between Ewing sarcoma and osteomyelitis. We identified 28 consecutive patients referred to our department for MRI (1.5 T) of an unclear bone lesion with clinical symptoms suggestive of Ewing sarcoma or osteomyelitis. MRI scans were re-evaluated by two experienced radiologists, typical MR imaging features were documented and a diagnostic decision between Ewing sarcoma and osteomyelitis was made. Statistical significance of the association between MRI features and the biopsy-based diagnosis was assessed using Fisher's exact test. The most clear-cut pattern for determining the correct diagnosis was the presence of a sharp and defined margin of the bone lesion, which was found in all patients with Ewing sarcoma, but in none of the patients with osteomyelitis (P < 0.0001). Contrast enhancing soft tissue was present in all cases with Ewing sarcoma and absent in 4 patients with osteomyelitis (P = 0.0103). Cortical destruction was found in all patients with Ewing sarcoma, 4 patients with osteomyelitis did not present any cortical reaction (P = 0.0103). Cystic or necrotic areas were identified in 13 patients with Ewing sarcoma and in 1 patient with osteomyelitis (P = 0.004). Interobserver reliability was very good (kappa = 1) in Ewing sarcoma and moderate (kappa = 0.6) in patients with osteomyelitis. A sharp and defined margin, optimally visualized on T1-weighted images in comparison to short tau inversion recovery (STIR) images, is the most significant feature of Ewing sarcoma in differentiating from osteomyelitis. (orig.)

Three-dimensional (3D) culture in sarcoma research and the clinical significance.

Science.gov (United States)

Gao, Songtao; Shen, Jacson; Hornicek, Francis; Duan, Zhenfeng

2017-08-03

Sarcomas are rare malignant tumors that arise from transformed cells of mesenchymal origin. Despite the progress in diagnosis and treatment, sarcomas have a high mortality rate due to local recurrence, metastasis, and the development of drug resistance to chemotherapy. New models for sarcoma research are required to further understand the disease and to develop new therapies. In vitro sarcoma modeling is challenging because of significant genetic heterogeneities, diverse pathological, and overlapping clinical characteristics. Studies on the mechanisms of recurrence, metastasis, and drug resistance in sarcoma have resulted in the generation of novel three-dimensional (3D) culture models for sarcoma research. 3D culture models aim to recapitulate the tumor microenvironment that plays a critical role in the pathogenesis of sarcoma using biomaterial scaffolds of natural biological materials and artificial polymers. An ideal 3D culture model can properly mimic not only the microenvironment, oncogenesis, and maintenance of sarcoma cell growth, but also imitate the interactions between cells and to the extracellular matrix. More recently, 3D cell culture has been used to research the biological behavior and mechanism of chemotherapy and radiotherapy resistance in different sarcoma models. Ultimately, findings using 3D models that more accurately reflect human sarcoma biology are likely to translate into improved clinical outcomes. In this review, we discuss the most recent advances of 3D culture technologies in sarcoma research and emerging clinical applications.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

Science.gov (United States)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

Retroperitoneal lipo sarcoma: report of 6 cases

International Nuclear Information System (INIS)

Santamarina, Mario G.; Baltazar, Alberto D.; Stagno, Diego; Kristal, Marcos; Lopez, Jessica

2003-01-01

Objective: To determine CT and MRI imaging features in patients with a diagnosis of retroperitoneal lipo sarcoma. Material and Methods: Retrospective analysis of 6 cases, studied with CT and/or MRI in patients with retroperitoneal lipo sarcoma during the last 4 years at our institution. We analyzed symptoms, treatment and prognosis with special focus on the CT and MRI findings and their histological correlation. Results: the most frequent histological subtype in our group of patients was the pleomorphic lipo sarcoma (n=3). In the others cases, 2 were well differentiated and one was round-cell type. Retroperitoneal lipo sarcoma, especially the well differentiated, presented certain imaging patterns which allowed to suspect the subtype of tumor. Recurrences occurred in 50% (n=3). Mortality rate was 33.4% (n=2) (follow-up, 16 months). Conclusion: Both CT and MRI are methods which aid in the detection of this rare disorder, as well as in its diagnosis and follow-up. (author)

Postradiation sarcoma of bone: review of 78 Mayo Clinic cases

International Nuclear Information System (INIS)

Weatherby, R.P.; Dahlin, D.C.; Ivins, J.C.

1981-01-01

Postradiation sarcoma of bone is an uncommon but serious sequela of radiation therapy. Seventy-eight Mayo Clinic patients have been treated for sarcomas arising in irradiated bones. They received their initial radiotherapy for a wide variety of nonneoplastic and neoplastic conditions, both benign and malignant. Thirty-five sarcomas arose in bone that was normal at the time of radiotherapy, and 43 arose in irradiated preexisting osseous lesions. The latent period between radiotherapy and diagnosis of sarcoma averaged 14.3 years. Ninety percent of the postradiation sarcomas were either osteosarcomas or fibrosarcomas; chondrosarcoma, malignant (fibrous) histiocytoma, malignant lymphoma, Ewing's tumor, and metastasizing chondroblastoma also occurred. Prompt radical surgery, when feasible, is usually the treatment of choice for the sarcoma. About 30% of patients with sarcomas of the extremities or craniofacial bones survived 5 years without recurrence; there were no disease-free survivors among patients with tumors of the vertebral column, pelvis, or shoulder girdle. The low risk of sarcoma following radiotherapy for the treatment of cancer should not be a contraindication to its use in these patients; however, radiation therapy for benign bone tumors should be reserved for lesions that are not amenable to surgical treatment. An unusual case is also reported herein in which a fibrosarcoma was discovered in the humerus of a patient who had received radiotherapy 55 years previously for a verified osteosarcoma in the same site

Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma.

Science.gov (United States)

Le Boeuf, Fabrice; Selman, Mohammed; Son, Hwan Hee; Bergeron, Anabel; Chen, Andrew; Tsang, Jovian; Butterwick, Derek; Arulanandam, Rozanne; Forbes, Nicole E; Tzelepis, Fanny; Bell, John C; Werier, Joel; Abdelbary, Hesham; Diallo, Jean-Simon

2017-09-15

The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Although few pre-clinical studies using distinct OVs have been performed and demonstrated therapeutic benefit in sarcoma models, a side-by-side comparison of clinically relevant OV platforms has not been performed. Four clinically relevant OV platforms (Reovirus, Vaccinia virus, Herpes-simplex virus and Rhabdovirus) were screened for their ability to infect and kill human and canine sarcoma cell lines in vitro, and human sarcoma specimens ex vivo. In vivo treatment efficacy was tested in a murine model. The rhabdovirus MG1 demonstrated the highest potency in vitro. Ex vivo, MG1 productively infected more than 80% of human sarcoma tissues tested, and treatment in vivo led to a significant increase in long-lasting cures in sarcoma-bearing mice. Importantly, MG1 treatment induced the generation of memory immune response that provided protection against a subsequent tumor challenge. This study opens the door for the use of MG1-based oncolytic immunotherapy strategies as treatment for sarcoma or as a component of a combined therapy. © 2017 UICC.

Postradiation sarcoma of bone: review of 78 Mayo Clinic cases

Energy Technology Data Exchange (ETDEWEB)

Weatherby, R.P.; Dahlin, D.C.; Ivins, J.C.

1981-05-01

Postradiation sarcoma of bone is an uncommon but serious sequela of radiation therapy. Seventy-eight Mayo Clinic patients have been treated for sarcomas arising in irradiated bones. They received their initial radiotherapy for a wide variety of nonneoplastic and neoplastic conditions, both benign and malignant. Thirty-five sarcomas arose in bone that was normal at the time of radiotherapy, and 43 arose in irradiated preexisting osseous lesions. The latent period between radiotherapy and diagnosis of sarcoma averaged 14.3 years. Ninety percent of the postradiation sarcomas were either osteosarcomas or fibrosarcomas; chondrosarcoma, malignant (fibrous) histiocytoma, malignant lymphoma, Ewing's tumor, and metastasizing chondroblastoma also occurred. Prompt radical surgery, when feasible, is usually the treatment of choice for the sarcoma. About 30% of patients with sarcomas of the extremities or craniofacial bones survived 5 years without recurrence; there were no disease-free survivors among patients with tumors of the vertebral column, pelvis, or shoulder girdle. The low risk of sarcoma following radiotherapy for the treatment of cancer should not be a contraindication to its use in these patients; however, radiation therapy for benign bone tumors should be reserved for lesions that are not amenable to surgical treatment. An unusual case is also reported herein in which a fibrosarcoma was discovered in the humerus of a patient who had received radiotherapy 55 years previously for a verified osteosarcoma in the same site.

Vaccine-associated feline sarcoma: current perspectives

Directory of Open Access Journals (Sweden)

Saba CF

2017-01-01

Full Text Available Corey F Saba Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA Abstract: Feline injection site sarcomas (FISS; also known as vaccine-associated sarcomas have been recognized for >20 years. Although uncommon, these tumors are iatrogenic, and vaccination against rabies and feline leukemia virus is perhaps the most common inciting cause. The exact etiopathogenesis is unknown, but it is widely accepted that inflammation induced by vaccines or other injections likely plays a critical role in tumor development. Injection site sarcomas are extremely locally invasive. Multimodal therapy, incorporating combinations of surgery, radiation therapy, and sometimes chemotherapy or immunotherapy, is recommended. However, tumor recurrences are common even with aggressive treatment, and many cats with FISS ultimately succumb to this devastating disease. While vaccination protocols play an important role in the management and control of infectious disease, veterinarians must be diligent in following established vaccination guidelines to minimize individual patient risk of FISS development. Early tumor detection and client education are also vital in the successful treatment of FISS. Keywords: injection site sarcoma, cat, cancer, oncology

Extraskeletal presentation of Ewing's Sarcoma.

Science.gov (United States)

Mangual, Danny; Bisbal-Matos, Luis A; Jiménez-Lee, Ricardo; Vélez, Román; Noy, Miguel

2018-03-01

The case of a 27-year-old Hispanic female who presented with an occipito-parietal tumor after suffering trauma to the area. A physical examination revealed no tenderness to palpation and with evidence of healing ulcerations. The biopsy was consistent with a synovial sarcoma. A wide excision of the mass (15cm x 14cm x 6cm) followed by a pericranial flap was performed. A follow-up CT showed recurrence involving the parietal sagittal sinus. After a second biopsy the mass was determined to be a small-cell sarcoma, consistent with Ewing's sarcoma. Chemotherapy included 8 cycles of doxorubicin, vincristine, and cyclophosphamide, with alternating cycles of etoposide and ifosfamide. A year later, a second wide excision of the mass was performed, followed by bilaminate skin substitute and skin graft placement for reconstruction of the soft-tissue defect. After chemotherapy, a follow-up PET scan showed no signs of re-uptake in any soft tissue or skeletal structures. After 2 years, the patient remains in complete remission.

Clinical and biochemical function of polymorphic NR0B1 GGAA-microsatellites in Ewing sarcoma: a report from the Children's Oncology Group.

Directory of Open Access Journals (Sweden)

Michael J Monument

Full Text Available The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite.Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes.A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed across a wide range of GGAA motifs, with maximal expression observed in constructs containing 20-26 GGAA motifs. Relative to white European and African controls, the NR0B1 GGAA-microsatellite in tumor cells demonstrated a strong bias for haplotypes containing 21-25 GGAA motifs suggesting a relationship between microsatellite function and disease susceptibility. This selection bias was not a product of microsatellite instability in tumor samples, nor was there a correlation between NR0B1 GGAA-microsatellite polymorphisms and survival outcomes.These data suggest that GGAA-microsatellite polymorphisms observed in human populations modulate EWS/FLI-mediated gene expression and may influence disease susceptibility in Ewing sarcoma.

Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

African Journals Online (AJOL)

Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Ewing’s Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue

Directory of Open Access Journals (Sweden)

Antonina Parafioriti

2016-04-01

Full Text Available The molecular mechanism responsible for Ewing’s Sarcoma (ES remains largely unknown. MicroRNAs (miRNAs, a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

Primary extra-skeletal Ewing's sarcoma mimicking a disc protrusion.

Science.gov (United States)

Ruelle, A; Boccardo, M

1987-07-01

One of the rarest cases of primary epidural neoplasm is a soft tissue sarcoma histologically similar to Ewing's sarcoma of the bone. In the literature only eleven cases of such an extra-skeletal Ewing's sarcoma have been described. The authors report an additional case presenting as a disc protrusion in a young male. The authors include some diagnostic, prognostic and nosologic remarks about this condition.

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast

OpenAIRE

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-01-01

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

Science.gov (United States)

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-06-21

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

Extra osseous primary Ewing's sarcoma.

Science.gov (United States)

Ali, Syed Asad; Muhammad, Agha Taj; Soomro, Abdul Ghani; Siddiqui, Akmal Jamal

2010-01-01

The case of 20 years old boy with an extra osseous Ewing's sarcoma is described. He was initially diagnosed as a case of infiltrative malignant tumour of left suprarenal gland on the basis of preoperative workup but postoperative biopsy of surgically excised specimen confirmed Extra-osseous Ewing's Sarcoma (EES) suprarenal gland with no evidence of malignancy on skeletal scintiscan, bone marrow aspirate and histopathology Suprarenal location of primary EES is unknown and probably has not been reported in literature. We report a unique case of EES.

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Science.gov (United States)

Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

2011-01-01

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Directory of Open Access Journals (Sweden)

Ashley A. Kowalewski

2011-01-01

Full Text Available Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22(q24;q12. This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

Granulocytic Sarcoma of the Stomach Presenting as Dysphagia during Pregnancy

Directory of Open Access Journals (Sweden)

Anuradha Sekaran

2011-01-01

Full Text Available Granulocytic sarcoma also known as extramedullary myeloid sarcoma or chloroma is an uncommon manifestation of leukemia and presents as a deposit of leukemic cells outside the bone marrow. We report a case of a twenty-five-year-old pregnant woman who presented with progressive dysphagia and recurrent postprandial vomiting. Upper GI endoscopy had shown large flat laterally spread nodular lesions in the cardia and proximal body of stomach. Biopsies from the gastric lesion showed granulocytic sarcoma of the stomach. Concurrent peripheral and bone marrow picture was suggestive of acute myeloid leukemia (AML–M4. There is limited reported literature on granulocytic sarcoma of the stomach. Concurrent gastric granulocytic sarcoma involving cardia and AML in pregnancy has not been reported till date.

Rare Cause of Stricture Esophagus—Sarcoma: A Case Report and Review of the literature

Directory of Open Access Journals (Sweden)

S. Patricia

2011-01-01

Full Text Available Adenocarcinoma and squamous cell carcinoma account for the vast majority of oesophageal malignancies. Other malignancies known to occur in the oesophagus include melanoma, sarcoma, and lymphoma. Among the sarcomas, carcinosarcoma is the commonest with both carcinomatous and sarcomatous elements followed by leiomyosarcoma of mesenchymal origin. Other sarcomas reported in the literature are liposarcoma, synovial sarcoma, myxofibrosarcoma, Ewing's sarcoma, granulocytic sarcoma, histiocytic sarcoma, schwannoma rhabdomyosarcoma, and epithelioid sarcoma. We report a case of malignant spindle cell tumour of oesophagus. Sarcomas of esophagus present as a polypoid exophytic soft tissue mass. Our patient presented with a stricture which is a rare presentation. Locally aggressive treatment with surgery is beneficial, and local palliative treatment including radiotherapy is worthwhile.

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

Science.gov (United States)

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

Science.gov (United States)

2018-02-27

Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

Osteogenic sarcoma

International Nuclear Information System (INIS)

Morales A, Nilson; Lozano B, Mauricio; Mejia P, Fernando

1990-01-01

Osteogenic sarcoma is one of the two main bone neoplasms in our population. It is very important for the radiologist to be familiar with its clinical and radio graphical features. This article is a literature review of its most important aspects, with some comments on our observations at the National Cancer Institute

GTI: a novel algorithm for identifying outlier gene expression profiles from integrated microarray datasets.

Directory of Open Access Journals (Sweden)

John Patrick Mpindi

Full Text Available BACKGROUND: Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type ('outlier genes', a hallmark of potential oncogenes. METHODOLOGY: A new statistical method (the gene tissue index, GTI was developed by modifying and adapting algorithms originally developed for statistical problems in economics. We compared the potential of the GTI to detect outlier genes in meta-datasets with four previously defined statistical methods, COPA, the OS statistic, the t-test and ORT, using simulated data. We demonstrated that the GTI performed equally well to existing methods in a single study simulation. Next, we evaluated the performance of the GTI in the analysis of combined Affymetrix gene expression data from several published studies covering 392 normal samples of tissue from the central nervous system, 74 astrocytomas, and 353 glioblastomas. According to the results, the GTI was better able than most of the previous methods to identify known oncogenic outlier genes. In addition, the GTI identified 29 novel outlier genes in glioblastomas, including TYMS and CDKN2A. The over-expression of these genes was validated in vivo by immunohistochemical staining data from clinical glioblastoma samples. Immunohistochemical data were available for 65% (19 of 29 of these genes, and 17 of these 19 genes (90% showed a typical outlier staining pattern. Furthermore, raltitrexed, a specific inhibitor of TYMS used in the therapy of tumour types other than glioblastoma, also effectively blocked cell proliferation in glioblastoma cell lines, thus highlighting this outlier gene candidate as a potential therapeutic target. CONCLUSIONS/SIGNIFICANCE: Taken together, these results support the GTI as a novel approach to identify potential oncogene outliers and drug targets. The algorithm is

Sarcoma as a second malignancy after treatment for breast cancer

International Nuclear Information System (INIS)

Yap, Johnny; Chuba, Paul J.; Thomas, Ron; Aref, Amr; Lucas, David; Severson, Richard K.; Hamre, Merlin

2002-01-01

Background: Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer. Methods: Cases with primary invasive breast cancer (n=274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973-1997). The database was then queried to determine the cases developing subsequent sarcomas (n=263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method. Results: The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE=0.2) cumulative incidence at 15 years post diagnosis, respectively (p=0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE=0.2) and 0.1 per 1,000 for cases not receiving radiation (SE<0.1). Overall survival was poor for cases of sarcoma after breast cancer (27-35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer. Conclusions: Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is

LONG-TERM TREATMENT RESULTS OF BONE SARCOMA PATIENTS WITH CONSIDERATION OF SERUM METALLOPROTEINASE LEVELS

Directory of Open Access Journals (Sweden)

I. V. Babkina

2015-01-01

Full Text Available Background: Bone sarcomas are extremely malignant prone to rapid hematogenic metastasing. Evaluation of biological marker expression by the tumor is important not only for the search of new potential chemotherapy targets, but for the assessment of the disease prognosis.Aim: A comparative evaluation of matrix metalloproteinases (MMP-2, -7, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in the serum of patients with primary bone tumors and in healthy people to identify their potential association with the histological characteristics of the tumor and the disease prognosis.Materials and methods: A comparative study of serum MMP-2, -7, -9, and TIMP-1 levels was performed in 54 patients with primary bone tumors (malignant, 45 patients, including central osteosarcoma in 21, periosteal osteosarcoma in 4, Ewing's sarcoma in 11, primary chondrosarcoma in 6, undifferentiated pleomorphic sarcoma in 3, and borderline giant cell tumors in 9 and in 26 healthy individuals with the use of the immunoenzyme technique (Biosource, USA, for TIMP-1 and R&D, USA, for MMP-2, -7, and -9. Results: The TIMP-1 levels in the serum of patients with central and periosteal osteosarcomas were significantly higher than in the serum of healthy controls (р = 0.038 and p = 0.007, respectively. The MMP-9 levels in patients with bone malignancies were significantly lower than that in the normal controls (p < 0.05. There was a positive correlation between serum TIMP-1 and MMP-9 levels in patients with central, periosteal and Ewing's sarcomas (r = 0.37, p = 0.024. No significant differences in the 5-year survival rates related to serum TIMP-1, MMP-2, -7, -9 levels were found in patients with bone sarcomas. However, in those with osteosarcoma and serum MMP-2 > 160 ng/ml, the overall 5-year survival rate was 1.6-fold higher than in those with lower MMP-2 levels, and in those with ММP-9 levels < 377 ng/ml, the 5-year survival rate was 1.4-fold higher than in patients with �

Multiple skeletal muscle metastases revealing a cardiac intimal sarcoma

Energy Technology Data Exchange (ETDEWEB)

Crombe, Amandine [Institut Bergonie, Department of Radiology, Bordeaux (France); Lintingre, Pierre-Francois; Dallaudiere, Benjamin [Clinique du Sport de Bordeaux-Merignac, Department of Musculoskeletal Radiology, Merignac (France); Le Loarer, Francois [Institut Bergonie, Department of Pathology, Bordeaux (France); Lachatre, Denis [Dupuytren University Hospital, Department of Radiology, Limoges (France)

2018-01-15

We report the case of a 59-year-old female with progressive bilateral painful swelling of the thighs. MRI revealed multiple intramuscular necrotic masses with similar morphologic patterns. Whole-body CT and 18-FDG PET-CT scans demonstrated additional hypermetabolic muscular masses and a lobulated lesion within the left atrial cavity. As biopsy of a muscular mass was compatible with a poorly differentiated sarcoma with MDM2 oncogene amplification, two diagnoses were discussed: a dedifferentiated liposarcoma with muscle and heart metastases or a primary cardiac sarcoma, mainly a cardiac intimal sarcoma, with muscular metastases, which was finally confirmed by array-comparative genomic hybridization (aCGH) in a sarcoma reference center. This case emphasizes the potential for intimal sarcoma to disseminate in skeletal muscle prior to any other organ and the need for a genomic approach in addition to classical radiopathologic analyses to distinguish primary from secondary locations facing simultaneous tumors of the heart and skeletal muscles with MDM2 amplification. (orig.)

Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

International Nuclear Information System (INIS)

Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik

2008-01-01

Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses

Mediastinal nonleukemic granulocytic sarcoma with cardiac infiltration Sarcoma granulocítico mediastinal não associado à leucemia com infiltração cardíaca

Directory of Open Access Journals (Sweden)

Gabrielle G. Lima

2008-08-01

Full Text Available We report on a case of mediastinal granulocytic sarcoma with cardiac infiltration in a young man with no evidence of leukemia involving the bone marrow or peripheral blood. Diagnosis was accomplished by immuno-histochemistry with expressions of myeloperoxidase and CD99 antigens. The patient achieved clinical remission, but evolved with febrile neutropenia during chemotherapy and died. Although subclinical cardiac infiltrations are commonly found at autopsy in patients with acute non-lymphoblastic leukemia, only one case of involvement of the heart with granulocytic sarcoma in the absence of bone marrow disease has been published in the literature. A diagnosis of granulocytic sarcoma should not be excluded when the biopsy of the bone marrow does not show any evidence of leukemic infiltration.Relata-se o caso de um adulto jovem com sarcoma granulocítico (SG mediastinal com infiltração cardíaca sem evidência de leucemia envolvendo medula óssea ou sangue periférico. O diagnóstico foi revelado pela imuno-histoquímica com positividade para mieloperoxidase e CD99. O paciente apresentou remissão clínica, porém evoluiu com neutropenia febril durante a quimioterapia e foi a óbito. Embora infiltrados cardíacos subclínicos sejam comumente detectados na autópsia em pacientes com leucemia aguda nãolinfoblástica, somente um caso de SG com envolvimento cardíaco na ausência de doença na medula óssea foi descrito na literatura. Um diagnóstico de SG não deve ser excluída quando a biópsia da medula óssea não mostrar nenhuma evidência de infiltração leucêmica.

Clinic-radiology findings at limp-sparing surgery of alveolar sarcoma

International Nuclear Information System (INIS)

Tzekov, A.; Penchev, V.; Niagolova, S.; Kovachev, V.

2007-01-01

Soft-tissue sarcomas are a rare and heterogeneous group of tumors. Alveolar soft part sarcoma is a rare sarcoma of an unclear cause. It is representing 0.2-1 percent of soft tissue sarcomas. Unique biologic behaviors of soft-tissue sarcomas features include formation of a reactive zone, intra-compartmental growth, and, rarely, the presence of skip metastases. Although the soft-tissue sarcomas have a unique morphology, biological behavior, and prognosis, they share biological characteristics and are treated in a similar fashion. The concept of limb-sparing surgery, or limb salvage, has gradually evolved over the past 25 years. Prior to this the basic principles of surgical oncology for the extremities consisted solely of determining the correct level at which to perform an amputation. The three stages of a limb-sparing procedure are as follows: tumor resection skeletal reconstruction and soft-tissue coverage and muscle transfers to restore function. Imaging diagnostic is a key step in the limp-sparing surgery of a soft tissue sarcomas at relation of: preoperatively - the diagnosis of lesion, the decision for biopsy, about location of the lesion and what is the safest anatomic route to that location, possibly lung and bone metastases; postoperative - checking the position of the prosthesis, inflammatory, mechanic and oncology complications. (authors)

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005)

NARCIS (Netherlands)

Ferrari, A.; de Salvo, G. L.; Brennan, B.; van Noesel, M. M.; de Paoli, A.; Casanova, M.; Francotte, N.; Kelsey, A.; Alaggio, R.; Oberlin, O.; Carli, M.; Ben-Arush, M.; Bergeron, C.; Merks, J. H. M.; Jenney, M.; Stevens, M. C.; Bisogno, G.; Orbach, D.

2015-01-01

To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a

Radiation-induced spindle cell sarcoma: A rare case report

Directory of Open Access Journals (Sweden)

Khan Mubeen

2009-01-01

Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

Molecular profiling of sarcomas: new vistas for precision medicine.

Science.gov (United States)

Al-Zaid, Tariq; Wang, Wei-Lien; Somaiah, Neeta; Lazar, Alexander J

2017-08-01

Sarcoma is a large and heterogeneous group of malignant mesenchymal neoplasms with significant histological overlap. Accurate diagnosis can be challenging yet important for selecting the appropriate treatment approach and prognosis. The currently torrid pace of new genomic discoveries aids our classification and diagnosis of sarcomas, understanding of pathogenesis, development of new medications, and identification of alterations that predict prognosis and response to therapy. Unfortunately, demonstrating effective targets for precision oncology has been elusive in most sarcoma types. The list of potential targets greatly outnumbers the list of available inhibitors at the present time. This review will discuss the role of molecular profiling in sarcomas in general with emphasis on selected entities with particular clinical relevance.

Ewing's Sarcoma of Bone Tumor Cells Produce MCSF that Stimulates Monocyte Proliferation in a Novel Mouse Model of Ewing's Sarcoma of Bone

OpenAIRE

Margulies, BS; DeBoyace, SD; Damron, TA; Allen, MJ

2015-01-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, cr...

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

Energy Technology Data Exchange (ETDEWEB)

Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Bosch, Walter [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Roberge, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Haas, Rick L.M. [Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Catton, Charles N. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Olsen, Jeffrey R. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Deville, Curtiland [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Chen, Yen-Lin [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Finkelstein, Steven E. [Translational Research Consortium, 21st Century Oncology, Scottsdale, Arizona (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Dian [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

2015-08-01

Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

International Nuclear Information System (INIS)

Baldini, Elizabeth H.; Abrams, Ross A.; Bosch, Walter; Roberge, David; Haas, Rick L.M.; Catton, Charles N.; Indelicato, Daniel J.; Olsen, Jeffrey R.; Deville, Curtiland; Chen, Yen-Lin; Finkelstein, Steven E.; DeLaney, Thomas F.; Wang, Dian

2015-01-01

Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed

Inhibition of survivin influences the biological activities of canine histiocytic sarcoma cell lines.

Directory of Open Access Journals (Sweden)

Hiroki Yamazaki

Full Text Available Canine histiocytic sarcoma (CHS is an aggressive malignant neoplasm that originates from histiocytic lineage cells, including dendritic cells and macrophages, and is characterized by progressive local infiltration and a very high metastatic potential. Survivin is as an apoptotic inhibitory factor that has major functions in cell proliferation, including inhibition of apoptosis and regulation of cell division, and is expressed in most types of human and canine malignant neoplasms, including melanoma and osteosarcoma. To investigate whether survivin was expressed at high levels in CHS and whether its expression was correlated with the aggressive biological behavior of CHS, we assessed relation between survivin expression and CHS progression, as well as the effects of survivin inhibition on the biological activities of CHS cells. We comparatively analyzed the expression of 6 selected anti-apoptotic genes, including survivin, in specimens from 30 dogs with histiocytic sarcoma and performed annexin V staining to evaluate apoptosis, methylthiazole tetrazolium assays to assess cell viability and chemosensitivity, and latex bead assays to measure changes in phagocytic activities in 4 CHS cell lines and normal canine fibroblasts transfected with survivin siRNA. Survivin gene expression levels in 30 specimens were significantly higher than those of the other 6 genes. After transfection with survivin siRNA, apoptosis, cell growth inhibition, enhanced chemosensitivity, and weakened phagocytic activities were observed in all CHS cell lines. In contrast, normal canine fibroblasts were not significantly affected by survivin knockdown. These results suggested that survivin expression may mediate the aggressive biological activities of CHS and that survivin may be an effective therapeutic target for the treatment of CHS.

Cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia.

Science.gov (United States)

Hurley, M Yadira; Ghahramani, Grant K; Frisch, Stephanie; Armbrecht, Eric S; Lind, Anne C; Nguyen, Tudung T; Hassan, Anjum; Kreisel, Friederike H; Frater, John L

2013-05-01

We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.

Granulocytic sarcoma.

Science.gov (United States)

Hutchison, R E; Kurec, A S; Davey, F R

1990-12-01

Granulocytic sarcoma is a variant presentation of acute myeloblastic leukemia, occurring in extramedullary locations. It is uncommon, but it may occur at any site and at any age, which necessitates its inclusion in the differential diagnosis of all undifferentiated tumors. Histology, touch-imprint cytology, cytochemistry, immunocytochemistry, electron microscopy, and molecular studies all contribute to the diagnosis.

Advanced oral HIV-associated Kaposi sarcoma with facial ...

African Journals Online (AJOL)

Rapidly progressive facial lymphoedoema that develops concurrently with or immediately after rapid enlargement of oral Kaposi sarcoma in human immunodeficiency virus (HIV) -seropositive persons forebodes death. Previously, we reported on three patients with HIV-associated Kaposi sarcoma who had not been ...

Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

Science.gov (United States)

Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

2011-01-01

Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

Synovial Sarcoma of the Buccal Mucosa: A Rare Case Report

Directory of Open Access Journals (Sweden)

Kumar T. S. Mahesh

2013-01-01

Full Text Available Synovial sarcoma (SS is a rare malignant neoplasm that arises most commonly in joint capsules and articular tendons, but its relationship to the synovium is not always obvious. Synovial sarcoma is a malignant soft tissue tumor representing 5.6% to 10% of all soft tissue sarcomas. They are termed SS because of their histologic resemblance to the synovium, but they rarely involve a synovial structure and are thought to arise from pluripotential mesenchymal cells. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the para-articular regions of the extremities, with approximately 9% occurring in the head and neck region. Synovial sarcoma has been reported rarely in the oral cavity. We report a very rare case of Synovial sarcoma of the buccal mucosa in a 24-year-old male patient.

Normalization of tumor microenvironment by neem leaf glycoprotein potentiates effector T cell functions and therapeutically intervenes in the growth of mouse sarcoma.

Directory of Open Access Journals (Sweden)

Subhasis Barik

Full Text Available We have observed restriction of the murine sarcoma growth by therapeutic intervention of neem leaf glycoprotein (NLGP. In order to evaluate the mechanism of tumor growth restriction, here, we have analyzed tumor microenvironment (TME from sarcoma bearing mice with NLGP therapy (NLGP-TME, in comparison to PBS-TME. Analysis of cytokine milieu within TME revealed IL-10, TGFβ, IL-6 rich type 2 characters was switched to type 1 microenvironment with dominance of IFNγ secretion within NLGP-TME. Proportion of CD8(+ T cells was increased within NLGP-TME and these T cells were protected from TME-induced anergy by NLGP, as indicated by higher expression of pNFAT and inhibit related downstream signaling. Moreover, low expression of FasR(+ cells within CD8(+ T cell population denotes prevention from activation induced cell death. Using CFSE as a probe, better migration of T cells was noted within TME from NLGP treated mice than PBS cohort. CD8(+ T cells isolated from NLGP-TME exhibited greater cytotoxicity to sarcoma cells in vitro and these cells show higher expression of cytotoxicity related molecules, perforin and granzyme B. Adoptive transfer of NLGP-TME exposed T cells, but not PBS-TME exposed cells in mice, is able to significantly inhibit the growth of sarcoma in vivo. Such tumor growth inhibition by NLGP-TME exposed T cells was not observed when mice were depleted for CD8(+ T cells. Accumulated evidences strongly suggest NLGP mediated normalization of TME allows T cells to perform optimally to inhibit the tumor growth.

Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

Science.gov (United States)

Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

2014-01-01

Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

Blue Cell Tumour at Unusual Site: Retropritoneal Ewings Sarcoma

OpenAIRE

Javalgi, Anita P; Karigoudar, Mahesh H; Palur, Katyayani

2016-01-01

Ewing’s sarcoma is a highly malignant tumour of osseous or non-osseous origin, tremed as extra-skeletal Ewings sarcoma if arising from soft tissue. It is rare occurrence tumor most commonly occurring in paravertebral area, chest wall, head & neck and retroperitoneum. Reporting an interesting case of retroperitoneal Ewing’s sarcoma in 39 years old female. Patient had complains of abdominal discomfort & vague pain since 2 months, following weakness in lower limb and loss of weight. On detail hi...

Management of HIV associated Kaposi's Sarcoma in Malawi ...

African Journals Online (AJOL)

Kaposi's sarcoma is a common malignancy in Malawi and is often managed with single agent vincristine. This article outlines feasible combination chemotherapy for Kaposi's sarcoma in Malawi which should be made more widely available. Malawi Medical Journal Vol. 20 (4) 2008: pp. 129-132.

Fibromyxoid sarcoma of the pancreas

Directory of Open Access Journals (Sweden)

Čolović Radoje

2008-01-01

Full Text Available Introduction Fibromyxoid sarcoma is a rare mesenchymal neoplasm, usually appearing in the soft tissue of the extremities, less frequently in the groin, trunk, neck, and upper extremities. Within the abdomen, the tumour is usually localised within the retroperitoneum. Case OutlineWe present a 56-year-old woman in whom, during the routinely performed investigation for atacks of choking with lots of bronchial secretion, and arterial hypertension, an ultrasonographer found a tumour within the head of the pancreas 6×6 cm in diameter. At operation, a dark pink, lobulated soft tumour, surrounded by a tiny capsule, clearly different from the completely normal pancreatic tissue of the posterior side of the head of the pancreas, was easily and ideally excised.The postoperative recovery was stormy. She developed postoperative pancreatitis, temporary biliary and duodenal fistula, which all settled by conservative treatment. The histology of the 80 g weighing tumour showed a circumscribed fibromyxoid sarcoma of low malignancy. Immunohistochemistry showed diffuse vimentin and CD34 strong positivity, as well as focal anti-SMA and anti-EMA immunopositivity. Six months after surgery, she died with signs of cerebrovascular insult, asthmatic status, and recurrent suppurative abdominal fistula, probably related to the previous pancreatitis. Ultrasonography showed a possible liver secondary. The exact cause of death was not confirmed as the autopsy was refused by the family. Conclusion Primary sarcomas of the pancreas are very rare, but should be considered in differential diagnosis of pancreatic neoplasms. To the best of our knowledge, there has been no previously described fibromyxoid sarcoma of the pancreas. .

Primary Occipital Ewing's Sarcoma with Subsequent Spinal Seeding.

Science.gov (United States)

Alqahtani, Ali; Amer, Roaa; Bakhsh, Eman

2017-01-01

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Imaging of the most frequent superficial soft-tissue sarcomas

International Nuclear Information System (INIS)

Morel, Melanie; Taieb, Sophie; Ceugnart, Luc; Penel, Nicolas; Mortier, Laurent; Vanseymortier, Luc; Robin, Y.M.; Gosset, Pierre; Cotten, Anne

2011-01-01

Superficial soft-tissue sarcomas are malignant mesenchymal tumors located within the cutaneous and/or subcutaneous layers. Most superficial soft-tissue sarcomas are low-grade tumors; yet, the risk of local recurrence is high, and initial wide surgery is the main prognostic factor. Some of these superficial sarcomas may grow, following an infiltrative pattern, and their real extent may be underestimated clinically. Imaging techniques are useful to determine precisely the real margins of the tumor, especially in cases of clinically doubtful or recurrent or large superficial lesions. Imaging tools enable one to determine the relationship with the superficial fascia separating the subcutaneous layer from the underlying muscle. In our institution ultrasonographic examination is followed by magnetic resonance (MR) imaging when the size of the lesion exceeds 3-5 cm. Imaging assessment is performed prior to biopsy, enabling optimal surgical management. Imaging features of the main superficial sarcomas are detailed in the following article, according to their major locations: those arising in the epidermis and/or dermis, which are most often diagnosed by dermatologists, and the subcutaneous sarcomas. (orig.)

Imaging of the most frequent superficial soft-tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Morel, Melanie; Taieb, Sophie; Ceugnart, Luc [Centre Oscar Lambret, Department of Radiology, Lille (France); Penel, Nicolas [Centre Oscar Lambret, Department of Oncology, Lille (France); Mortier, Laurent [Centre Hospitalier Universitaire de Lille, Department of Dermatology, Hopital Claude Huriez, Lille (France); Vanseymortier, Luc [Centre Oscar Lambret, Department of Surgery, Lille (France); Robin, Y.M. [Centre Oscar Lambret, Departement of Pathology, Lille (France); Gosset, Pierre [Groupement Hospitalier de l' Institut Catholique-Faculte Libre de Medecine de Lille, Department of Pathology, Hopital Saint-Philibert, Lomme (France); Cotten, Anne [Centre Hospitalier Universitaire de Lille, Department of Musculoskeletal Radiology, Centre Hopital Roger Salengro, Lille (France)

2011-03-15

Superficial soft-tissue sarcomas are malignant mesenchymal tumors located within the cutaneous and/or subcutaneous layers. Most superficial soft-tissue sarcomas are low-grade tumors; yet, the risk of local recurrence is high, and initial wide surgery is the main prognostic factor. Some of these superficial sarcomas may grow, following an infiltrative pattern, and their real extent may be underestimated clinically. Imaging techniques are useful to determine precisely the real margins of the tumor, especially in cases of clinically doubtful or recurrent or large superficial lesions. Imaging tools enable one to determine the relationship with the superficial fascia separating the subcutaneous layer from the underlying muscle. In our institution ultrasonographic examination is followed by magnetic resonance (MR) imaging when the size of the lesion exceeds 3-5 cm. Imaging assessment is performed prior to biopsy, enabling optimal surgical management. Imaging features of the main superficial sarcomas are detailed in the following article, according to their major locations: those arising in the epidermis and/or dermis, which are most often diagnosed by dermatologists, and the subcutaneous sarcomas. (orig.)

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

Science.gov (United States)

Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

2015-07-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical and MRI features of prostate sarcoma: comparison with prostate adenocarcinoma

International Nuclear Information System (INIS)

Ding Jianping; Wang Xiaoying; Wang Zhenzhong; Zhou Liangping; Jiang Xuexiang

2004-01-01

Objective: To summarize the clinical and imaging features of prostate sarcoma, and to compare the features with those of prostate adenocarcinoma (PCa). Method: Six cases of prostate sarcoma proved pathologically were enrolled in this study. The clinical material and imaging features were compared with those of the PCa. Results: (1) Pathological result: Among the 6 prostate sarcomas, 3 were rhabdomyosarcoma, 1 was leiomyosarcoma, and 2 were sarcoma originated from interstitial tissue that could not be classified. (2) Clinical result: The 6 patients of sarcoma were younger (median age 36.5, 15-71 years) than the patients of PCa (median age 72, 50-78 years) (P -3 ng/L] was normal and lower than that of the PCa patients [median 27.80, (1.55-352.00) x 10 -3 ng/ L] (P 3 ) was larger than that of PCa (median 41.57, 17.16-179.44 cm 3 ) (P 2 -weighted images, with grossly normal structure of the prostate. Excapsular extension was more common in the sarcomas than in the PCa (83.3% vs 66.7%). Conclusion: The clinical and imaging features of prostate sarcoma are different from those of prostate adenocarcinoma

Soft Tissue Sarcomas In Children And Adolescents

International Nuclear Information System (INIS)

Bajciova, V.

2008-01-01

Soft tissue sarcomas are rare tumors, they may occur at any age. It is heterogenous group of different histology types, different biology and different clinical behavior. Different treatment strategy is used for children and adults. Adolescents with sarcomas could be managed by both pediatric and medical oncologists. Decision regarding location of treatment should be based on the best patient interest. (author)

Double Feature: Carcinoma and Sarcoma Present in a Single Breast Tumor

Directory of Open Access Journals (Sweden)

Catherine M. Stefaniuk

2012-01-01

Full Text Available Introduction. Primary breast sarcomas (PBSs are rare nonepithelial breast tumors compromised of mesenchymal mammary tissue. Although its rare nature has made the best mode of PBS treatment difficult to determine, it seems better to treat it more like a sarcoma creating clear negative margins verses breast carcinoma utilizing lumpectomy, partial mastectomy, and total mastectomy. Case. A 47-year-old obese Caucasian postmenopausal female G2P2 presents with a breast lump demonstrating a histological sample with a biphasic pattern consistent with both ductal carcinoma containing typical malignant epithelial cells and sarcomatous differentiation of carcinosarcoma. Conclusion. Carcinosarcoma is a rare breast malignancy. Sarcomas of the breast tend to be negative for estrogen receptor and lack known risk factors. Current recommended treatment is to treat breast sarcomas like other soft tissue sarcomas by performing wide local excision instead of partial mastectomy. Antiestrogens and other chemotherapeutic agents typically used in breast epithelial malignancies are not recommended since these sarcomas tend to be negative with these receptors.

Sarcoma pleomórfico primário do pulmão Primary pleomorphic sarcoma of the lung

Directory of Open Access Journals (Sweden)

Marcus da Matta Abreu

2008-07-01

Full Text Available A classificação recente da Organização Mundial da Saúde (OMS para os tumores pulmonares unificou o heterogéneo grupo do carcinoma de não pequenas células (CPNPC, que engloba os sarcomas e os tumores com componentes sarcomatosos, sob a denominação “carcinoma com elementos pleomórficos, sarcomatóides ou sarcomatosos”. Este grupo inclui diferentes entidades, como o carcinoma pleomórfico (CP, o carcinoma de células fusiformes (CCF, carcinoma de células gigantes (CCG, os carcinossarcomas (CS e o blastoma pulmonar (BP. De uma forma geral, estes tumores são raros e representam 0,1% a 0,4% de todas as neoplasias pulmonares. Ocorrem mais comummente em homens fumadores, com alta carga tabágica, e acomete-os em torno dos 60 anos e comummente tem evolução clínica muito agressiva. Os autores relatam o caso de um doente portador de sarcoma pleomórfico primário pulmonar e revêem a literatura sobre o assunto.The World Health Organization (WHO classification of lung cancers ranks the heterogeneous nonsmall cell lung cancer (N-SCLC group, encompassing sarcoma or sarcoma-containing tumours under one heading: “carcinomas with pleomorphic, sarcomatoid or sarcomatous elements”. This group contains entities such as pleomorphic carcinoma (PC, spindle cell carcinoma (SCC, giant cell carcinoma (GCC, carcinosarcoma (CS and pulmonary blastoma (PB. These tumors are rare overall, making up approx. 0.1-0.4% of all lung malignancies. They are more commonly found in males who are heavy smokers, diagnosed at the age of 60 on average and follow an aggressive clinical course. The authors describe the case of a male patient with primary pleomorphic lung sarcoma and also include a review of the literature.

The Value of Surgery for Retroperitoneal Sarcoma

Directory of Open Access Journals (Sweden)

Sepideh Gholami

2009-01-01

Full Text Available Introduction. Retroperitoneal sarcomas are uncommon large malignant tumors. Methods. Forty-one consecutive patients with localized retroperitoneal sarcoma were retrospectively studied. Results. Median age was 58 years (range 20–91 years. Median tumor size was 17.5 cm (range 4–41 cm. Only 2 tumors were <5 cm. Most were liposarcoma (44% and high-grade (59%. 59% were stage 3 and the rest was stage 1. Median followup was 10 months (range 1–106 months. Thirty-eight patients had an initial complete resection; 15 (37% developed recurrent sarcoma and 12 (80% had a second complete resection. Patients with an initial complete resection had a 5-year survival of 46%. For all patients, tumor grade affected overall survival (=.006. Complete surgical resection improved overall survival for high-grade tumors (=.03. Conclusions. Tumor grade/stage and complete surgical resection for high-grade tumors are important prognostic variables. Radiation therapy or chemotherapy had no significant impact on overall or recurrence-free survival. Complete surgical resection is the treatment of choice for patients with initial and locally recurrent retroperitoneal sarcoma.

EWS/FLI1 regulates EYA3 in Ewing's sarcoma via modulation of microRNA-708, resulting in increased cell survival and chemoresistance

Science.gov (United States)

Robin, Tyler P; Smith, Anna; McKinsey, Erin; Reaves, Lisa; Jedlicka, Paul; Ford, Heide L.

2012-01-01

Ewing's sarcoma is an aggressive pediatric cancer of the bone and soft tissue, in which patients whose tumors have a poor histological response to initial chemotherapy have a poor overall prognosis. Therefore, it is important to identify molecules involved in resistance to chemotherapy. Herein, we demonstrate that the DNA-repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing's sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell of origin of Ewing's sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor. We further demonstrate that EWS/FLI1 mediates upregulation of EYA3 via repression of miR-708, a microRNA that targets the EYA3 3′UTR, rather than by binding the EYA3 promoter directly. Importantly, we demonstrate that high levels of EYA3 significantly correlate with low levels of miR-708 in Ewing's sarcoma samples, suggesting that this miR-mediated mechanism of EYA3 regulation holds true in human cancers. Because EYA proteins are important for cell survival during development, we examine, and demonstrate, that loss of EYA3 decreases survival of Ewing's sarcoma cells. Most importantly, knockdown of EYA3 in Ewing's sarcoma cells leads to sensitization to DNA-damaging chemotherapeutics used in the treatment of Ewing's sarcoma, and as expected, after chemotherapeutic treatment, EYA3 knockdown cells repair DNA damage less effectively than their control counterparts. These studies identify EYA3 as a novel mediator of chemoresistance in Ewing's sarcoma and define the molecular mechanisms of both EYA3 overexpression and of EYA3-mediated chemoresistance. PMID:22723308

Kaposi's Sarcoma Of The Lung: A Case Report.

African Journals Online (AJOL)

user

2004-12-02

Dec 2, 2004 ... E-mail: eussiri@yahoo.com. Pulmonary Kaposi's sarcoma is a rare condition. Its diagnosis may be tricky due to its similarities in clinical and radiological features with pulmonary opportunistic infections as well as other lung lesions. Treatment for Kaposi's sarcoma include radiotherapy, chemotherapy and/or.

Mechanisms of Ewing sarcoma metastasis : biochemistry and biophysics

NARCIS (Netherlands)

Beletkaia, Elena

2015-01-01

Ewing sarcoma (ES) is a special type of bone cancer, first described by Dr. James Ewing in his paper ‘Diffusive endothelioma of bone’. Today Ewing sarcoma represents the second most common bone cancer among adolescents and young adults. Contrary to the positive achievement in treatment of localized

Differential display technique of RNA from tumorigenic and non-tumorigenic variants of hamster cells transformed with avian sarcoma virus

International Nuclear Information System (INIS)

Leksa, V.; Altaner, C.

1997-01-01

Differential display technique was applied to study expression of RNA in tumorigenic and non-tumorigenic cell variants of avian sarcoma virus transformed hamster cells. Methodical conditions were worked out, which allowed identifying a cDNA fragment of an unknown gene expressed in non-tumorigenic cell variant only. Its role in tumor suppression remains to be determined. (author)

The role of imaging in the evaluation of extraskeletal Ewing's sarcoma

African Journals Online (AJOL)

Primary bone tumours account for 5% of all adolescent and child cancers. When Ewing's sarcoma arises in soft tissue rather than bone, it is referred to as extraskeletal Ewing's sarcoma (ESS). Computed tomography (CT) scanning and magnetic resonance imaging (MRI) features of Ewing's sarcoma are non-specific, and a ...

Leukosis/Sarcoma Group

Science.gov (United States)

The leukosis/sarcoma (L/S) group of diseases designates a variety of transmissible benign and malignant neoplasms of chickens caused by members that belong to the family Retroviridae. Because the expansion of the literature on this disease, it is no longer feasible to cite all relevant publications ...

Synovial sarcoma mechanisms

DEFF Research Database (Denmark)

Svejstrup, Jesper Q

2013-01-01

Human synovial sarcoma is caused by a chromosome translocation, which fuses DNA encoding SSX to that encoding the SS18 protein. Kadoch and Crabtree now show that the resulting cellular transformation stems from disruption of the normal architecture and function of the human SWI/SNF (BAF) complex....

Recurrent PAX3-MAML3 Fusion in Biphenotypic Sinonasal Sarcoma

Science.gov (United States)

Wang, Xiaoke; Bledsoe, Krista L.; Graham, Rondell P.; Asmann, Yan W.; Viswanatha, David S.; Lewis, Jean E.; Lewis, Jason T.; Chou, Margaret M.; Yaszemski, Michael J.; Jen, Jin; Westendorf, Jennifer J.; Oliveira, André M.

2014-01-01

Biphenotypic sinonasal sarcoma (SNS) is a newly described tumor of the nasal and paranasal areas. Herein, we report the novel recurring chromosomal translocation t(2;4)(q35;q31.1) in SNS. The translocation results in the formation of the fusion protein PAX3-MAML3, which is a potent transcriptional activator of PAX3 response elements. The SNS phenotype is characterized by aberrant expression of genes involved in neuroectodermal and myogenic differentiation, which closely simulates the developmental roles of PAX3. PMID:24859338

Oxidative stress and antioxidant status in primary bone and soft tissue sarcoma

International Nuclear Information System (INIS)

Nathan, Fatima M; Singh, Vivek A; Dhanoa, Amreeta; Palanisamy, Uma D

2011-01-01

Oxidative stress is characterised by an increased level of reactive oxygen species (ROS) that disrupts the intracellular reduction-oxidation (redox) balance and has been implicated in various diseases including cancer. Malignant tumors of connective tissue or sarcomas account for approximately 1% of all cancer diagnoses in adults and around 15% of paediatric malignancies per annum. There exists no information on the alterations of oxidant/antioxidant status of sarcoma patients in literature. This study was aimed to determine the levels of oxidative stress and antioxidant defence in patients with primary bone and soft tissue sarcoma and to investigate if there exists any significant differences in these levels between both the sarcomas. The study cohort consisted of 94 subjects; 20 soft tissue sarcoma, 27 primary bone sarcoma and 47 healthy controls. Malondialdehyde (MDA) and protein carbonyls were determined to assess their oxidative stress levels while antioxidant status was evaluated using catalase (CAT), superoxide dismutase (SOD), thiols and trolox equivalent antioxidant capacity (TEAC). Sarcoma patients showed significant increase in plasma and urinary MDA and serum protein carbonyl levels (p < 0.05) while significant decreases were noted in TEAC, thiols, CAT and SOD levels (p < 0.05). No significant difference in oxidative damage was noted between both the sarcomas (p > 0.05). In conclusion, an increase in oxidative stress and decrease in antioxidant status is observed in both primary bone and soft tissue sarcomas with a similar extent of damage. This study offers the basis for further work on whether the manipulation of redox balance in patients with sarcoma represents a useful approach in the design of future therapies for bone disease

RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

Science.gov (United States)

Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

2010-08-18

Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

Primary Ewing’s sarcoma of the spine: case report Sarcoma de Ewing primário da coluna vertebral: relato de caso

Directory of Open Access Journals (Sweden)

Leandro I. Dini

2006-09-01

Full Text Available Primary malignant sarcomas of the spine are extremely rare. Because of biological heterogeneity, these tumors have variable sensitivity to radiation and chemotherapy. Adequate local control through complete tumor removal is an important therapeutic goal. However, aggressive resection of tumors in the spinal column must be coupled with restoration of spinal column stability and minimization of neural deficits. The balance of these factors makes treatment of primary sarcomas of the spine challenging, and dictates an individual approach to treatment. We report on a 18 years old man with primary Ewing's sarcoma of the nonsacral spine. The clinical picture and imaging characteristics were analyzed as well as the management modalities and outcome.Sarcomas malignos primários da coluna são extremamente raros. Devido sua heterogeneidade biológica, estes tumores apresentam sensibilidade variada à radioterapia e à quimioterapia.O controle local adequado através da ressecção tumoral completa é um objetivo terapêutico importante. Contudo, a ressecção completa dos tumores da coluna vertebral deve ser realizada com a restauração da estabilidade espinhal e minimização do déficit neurológico. O equilíbrio entre estes fatores torna o tratamento dos sarcomas da coluna desafiador, exigindo-se uma abordagem individualizada para o tratamento de cada paciente. Relatamos um caso de sarcoma de Ewing da coluna não-sacral em um homem de 18 anos. O quadro clínico e características de imagem foram analisados, bem como a modalidades de manejo e o prognóstico.

Radioimmunoimaging of osteogenic sarcoma xenografts in nude mice using monoclonal antibodies to osteogenic sarcoma

International Nuclear Information System (INIS)

Sakahara, H.; Endo, K.; Nakashima, T.

1985-01-01

The authors have developed several monoclonal antibodies against human osteogenic sarcoma, one of which; OST7 (IgGl) selectively localized in osteogenic sarcoma xenografts in nude mice. In the present study, F(ab')/sub 2/ fragment was compared with whole IgG and those labeled with In-111 as well as I-131 were used as a radiotracer for the scintigraphic imaging of tumors. IgC and F(ab')/sub 2/ were labeled with I-131 using chloramine-T method and injected into nude mice bearing human osteogenic sarcoma. Scintigrams at day 2 clearly delineated the site of tumors with almost no radioactivity in other organs with F(ab')/sub 2/, which yielded much better images than whole IgG. Tumor-to-blood ratio of 6.09-27.87 was obtained at day 2 using F(ab')/sub 2/, whereas it was 0.76-1.12 at day 2 and 2.05-3.27 at day 7 with IgG. I-131 labeled nonspecific F(ab')/sub 2/ or IgG resulted in no or very low tumor uptake with tumor-to-blood ratio of 0.94-1.18 at day 2 for F(ab')/sub 2/ and 0.67-0.76 at day 7 for IgG, respectively. In-111 labeled F(ab')/sub 2/ fragment of OST7, which was prepared using DTPA as a bifunctional chelate, also showed a high tumor accumulation with tumor-to-blood ratio of 11.67-17.54 at day 2, but higher background activity in the liver and kidney was observed than I-131 labeled one. These results indicate that F(ab')/sub 2/ fragment of OST7 labeled with either I-131 or In-111, has a great potential for the radioimmunoimaging of osteogenic sarcoma

A Unique Case of Classic Kaposi's sarcoma restricted to the toes.

Science.gov (United States)

Renteria, Anne S; Marshall, Vickie A; Sun, Yanyu; Chockalingam, Porselvi; Cooper, Jay S; Huang, Yiwu; Whitby, Denise

2013-01-01

Kaposi's sarcoma associated-herpesvirus causes all forms of Kaposi's sarcoma, and six major subtypes have been described based on the amino acid sequences of the open reading frame K1. A 71-year-old man from China, HIV negative, presented with nodules on the dorsal aspect of his toes. Biopsy confirmed the diagnosis of Kaposi's sarcoma and virology studies of his blood and saliva confirmed the presence of Kaposi's sarcoma associated-herpesvirus infection. Viral genotyping was consistent with subtype C3. Intervention has been deferred as our patient has remained clinically asymptomatic and without evident growth of his lesions over a 2-year follow up. We herein report the first known case of Kaposi's sarcoma restricted to the toes caused by the viral subtype C3 in an HIV-negative patient from Harbin, China.

Podoplanin (D2-40): A New Immunohistochemical Marker for Reactive Follicular Dendritic Cells and Follicular Dendritic Cell Sarcomas

Science.gov (United States)

Xie, Qingmei; Chen, Lugen; Fu, Kai; Harter, Josephine; Young, Ken H; Sunkara, Jaya; Novak, Deborah; Villanueva-Siles, Esperanza; Ratech, Howard

2008-01-01

The diagnosis of follicular dendritic cell (FDC) sarcoma can be challenging because of its morphologic overlaps with many other spindle cell neoplasms and, therefore, new phenotypic markers will be helpful in its differential diagnosis. Podoplanin is a mucin-type transmembrane glycoprotein that has recently been detected in reactive FDCs. In this study, we investigated the expression patterns of podoplanin using a new mouse monoclonal antibody D2-40, and compared them with CD21, a well-established FDC marker, in a comprehensive panel of cases. The panel included 4 FDC sarcomas, 38 spindle cell neoplasms of other types, 25 reactive lymphoid hyperplasia, and 117 lymphoid and 5 myeloid malignant hematopoietic neoplasms. Our study revealed that D2-40 strongly stained 3 of 4 FDC sarcomas. In contrast, D2-40 stained only 2/38 other spindle cell neoplasms tested. Furthermore, we observed that D2-40 highlighted more FDC meshworks than CD21 in Castleman's disease, follicular lymphoma, nodular lymphocyte predominance Hodgkin lymphoma, and residual reactive germinal centers in a variety of lymphoma types. D2-40 and CD21 stained an equal number of cases of reactive lymphoid hyperplasia, progressively transformed germinal centers and angioimmunoblastic T-cell lymphoma. No expression of podoplanin was detected in normal or neoplastic lymphoid and myeloid cells. We conclude that podoplanin (D2-40) is a sensitive and specific FDC marker, which is superior or equal to CD21 in evaluating both reactive and neoplastic FDCs. In addition, our results suggest that podoplanin (D2-40) can be used to support the diagnosis of FDC sarcoma. PMID:18784810

Aggressive Ewing's sarcoma appearing as a cold lesion on bone scan

International Nuclear Information System (INIS)

Chatti, K.; Guezguez, M.; Maha Ben Fredj, M.; Sfar, R.; Essabbah, H.; Mtaoumi, M.; Chatti, K.

2009-01-01

Ewing's sarcoma classically presents as a hot spot on bone scan as a result of increased vascularity of the tumor and new bone formation. Purpose We report and analyze an uncommon pattern of a 'cold' lesion in Ewing's sarcoma on bone scan and its pathophysiologic significance. Case report A 15-year-old boy complaining of thigh pain. CT scan evoked Ewing's sarcoma or osteitis. MRI evoked chronic osteitis. Scintigraphy showed a fairly intense and heterogeneous uptake on the femoral lesion and no abnormal uptake elsewhere. Biopsy showed none pathologic pattern. Three months later, a second biopsy concluded to Ewing's sarcoma. Bone scan showed a larger lesion with peripheral intense uptake centered by enlarged 'cold' area in the left femoral diaphysis and no evident bone metastasis. The patient underwent chemotherapy and surgery. Three months later, bone scan showed extensive skeletal metastasis. Conclusion Ewing's sarcoma appears usually as an intense lesion on bone scan. Nevertheless, decreased radiopharmaceutical uptake or 'cold' lesion may be seen in aggressive Ewing's sarcoma with lytic tumor, growth of which is very rapid and bony reaction is minimal. (authors)

Post-radiation soft tissue sarcoma

International Nuclear Information System (INIS)

Tomita, Yasuhiko; Kuratsu, Shigeyuki; Myoui, Akira; Ohsawa, Masahiko; Aozasa, Katsuyuki; Uchida, Atsumasa; Ono, Keiro

1993-01-01

Seven patients received radiation for malignancies, and two received for benign tumors. The latency period from radiation to symptom ranged from two years to 36 years (mean 17.2 years). Post-radiation soft tissue sarcomas (PRS) comprised six cases of malignant fibrous histiocytomas, two leiomyosarcomas, and one angiosarcoma. The five-year survival of PRS was 16.7% showing a worse prognosis than spontaneously occurring soft tissue sarcomas. Seven PRS occurred superficially, and two were deeply located. Four cases occurring in the superficial tissues had histories of radiation-induced dermatitis. The radiation-induced dermatitis was suggested to be a risk factor for development of PRS. (author)

A case of synovial sarcoma in the submandibular region

International Nuclear Information System (INIS)

Sakata, Chie; Kinoshita, Toshibumi; Kaminou, Toshio; Adachi, Akira; Kinoshita, Fumiko; Ogawa, Toshihide

2005-01-01

Synovial sarcomas are a less common cervical tumor in young patients. We report a 23-year-old man with synovial sarcoma in the submandibular region. T2-weighted MR images demonstrated a mixed-intensity tumor attached to the submandibular gland. T1-weighted MR images revealed a focal area with mildly increased signal intensity, indicating intratumoral hemorrhage. MR images were also useful for visualization of tumor extension. Synovial sarcoma should be considered in the differential diagnosis of well-defined in homogeneous tumors adjacent to the submandibular gland in young adults. (author)

Primary Cystic Pleuropulmonary Synovial Sarcoma Presenting as Recurrent Pneumothorax

Directory of Open Access Journals (Sweden)

Eric D. Johnson

2017-07-01

Full Text Available Primary pleuropulmonary synovial sarcomas are quite rare, representing 0.1–0.5% of all pulmonary malignancies. We report an entirely cystic monophasic synovial sarcoma in a 25-year-old male who presented with recurrent pneumothorax and no evidence of a mass lesion on imaging. The purpose of this case report is to increase awareness of neoplasms clinically presenting as a pneumothorax with no imagining evidence of a mass-forming lesion and emphasize the significance of fluorescent in situ hybridization testing in nontypical synovial sarcoma cases.

AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6

International Nuclear Information System (INIS)

Miles, S.A.; Rezai, A.R.; Salazar-Gonzalez, J.F.; Meyden, M.V.; Stevens, R.H.; Mitsuyasu, R.T.; Martinez-Maza, O.; Logan, D.M.; Taga, Tetsuya; Hirano, Toshio; Kishimoto, Tadamitsu

1990-01-01

Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1β, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, the authors examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. The authors found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [ 3 H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at >10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells

Role of defective Oct-2 and OCA-B expression in immunoglobulin production and Kaposi's sarcoma-associated herpesvirus lytic reactivation in primary effusion lymphoma.

Science.gov (United States)

Di Bartolo, Daniel L; Hyjek, Elizabeth; Keller, Shannon; Guasparri, Ilaria; Deng, Hongyu; Sun, Ren; Chadburn, Amy; Knowles, Daniel M; Cesarman, Ethel

2009-05-01

Primary effusion lymphoma (PEL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by the presence of Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8). Despite having a genotype and gene expression signature of highly differentiated B cells, PEL does not usually express surface or cytoplasmic immunoglobulin (Ig). We show the lack of Oct-2 and OCA-B transcription factors to be responsible, at least in part, for this defect in Ig production. Like Ig genes, ORF50, the key regulator of the switch from latency to lytic reactivation, contains an octamer motif within its promoter. We therefore examined the impact of Oct-2 and OCA-B on ORF50 activation. The binding of Oct-1 to the ORF50 promoter has been shown to significantly enhance ORF50 transactivation. We found that Oct-2, on the other hand, inhibited ORF50 expression and consequently lytic reactivation by competing with Oct-1 for the octamer motif in the ORF50 promoter. Our data suggest that Oct-2 downregulation in infected cells would be favorable to KSHV in allowing for efficient viral reactivation.

Dermatomyositis with Kaposi’s Sarcoma in a Patient without Human Immunodeficiency Virus-1 Infection

Directory of Open Access Journals (Sweden)

Dana Liang

1991-01-01

Full Text Available The first case of dermatomyositis complicating cutaneous and visceral Kaposi’s sarcoma is presented in a 75-year-old man without human immunodeficiency virus infection. Dermatomyositis preceded a definitive diagnosis of Kaposi’s sarcoma by six months, although in retrospect unrecognized lesions may have presented simultaneously. He was treated with prednisone and azathioprine, thus raising the possibility of the role of immunosuppression in promoting progression of the sarcoma. It is suggested that although the association between dermatomyositis and Kaposi’s sarcoma occurs rarely, dermatomyositis should be considered a paraneoplastic syndrome of Kaposi’s sarcoma. Further, the finding of cutaneous lesions of Kaposi’s sarcoma could predict gastrointestinal involvement when dermatomyositis and Kaposi’s sarcoma occur in the same patient.

Clear cell sarcoma of the abdominal wall with peritoneal sarcomatosis: CT features

International Nuclear Information System (INIS)

Sabate, J.M.; Fernandez, A.; Torrubia, S.; Villanueva, A.; Monill, J.M.

1999-01-01

Clear cell sarcoma, also called malignant melanoma of soft parts, is an uncommon neoplasm that involves tendons or aponeuroses of the lower extremity. The CT features of a clear cell sarcoma arising from the abdominal wall with later peritoneal dissemination are described. Peritoneal sarcomatosis from soft tissue sarcomas is a very rare condition previously unreported in the radiologic literature. Metastases to peritoneal surfaces must therefore be considered a possible site for systemic dissemination of soft tissue sarcomas. (orig.)

Neurotensin receptors in human neoplasms: high incidence in Ewing's sarcomas.

Science.gov (United States)

Reubi, J C; Waser, B; Schaer, J C; Laissue, J A

1999-07-19

Receptors for regulatory peptides, such as somatostatin or vasoactive intestinal peptide (VIP), expressed at high density by neoplastic cells, can be instrumental for tumor diagnosis and therapy. Little is known about the expression of neurotensin receptors in human tumors. In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand. Neurotensin receptors were identified and localized in tumor cells of 11/17 Ewing's sarcomas, 21/40 meningiomas, 10/23 astrocytomas, 5/13 medulloblastomas, 7/24 medullary thyroid cancers and 2/8 small cell lung cancers. They were rarely found in non-small cell lung cancers and breast carcinomas; they were absent in prostate, ovarian, renal cell and hepatocellular carcinomas, neuroendocrine gut tumors, pituitary adenomas, schwannomas, neuroblastomas and lymphomas. When present, the receptors bound with nanomolar affinity neurotensin and acetyl-neurotensin-(8-13), with lower affinity neuromedin N, diethylenetriamine penta-acetic acidneurotensin-(8-13) and SR 48692, but not neurotensin-(1-11). They were all of the NT1 type, without high affinity for levocabastine. Further, in 2 receptor-positive Ewing's sarcomas, neurotensin mRNA was detected by in situ hybridization techniques. Since neurotensin is known to stimulate cell proliferation, the presence of neurotensin receptors in human neoplasia may be of biological relevance, possibly as an integrative part of an autocrine feedback mechanism of tumor growth stimulation.

3 cases of radiation-induced sarcoma

International Nuclear Information System (INIS)

Shiba, Keiichiro; Fukuma, Hisatoshi; Beppu, Yasuo; Hirota, Teruyuki; Shinohara, Norio.

1982-01-01

Criteria for the diagnosis of radiation-induced sarcoma have been previously described. All cases must have a history of irradiation and the second neoplasm must have arisen in the area of the radiation field. A latent period of several years must have elapsed after irradiation before clinical evidence of a second malignant neoplasm. Most important thing is that, all suspected cases must have been proved histologically. We have experienced 3 cases of radiation-induced sarcoma, they were 42-years-old man who developed an osteosarcoma of the lumbar spine at the field of postoperative irradiation for seminoma 7 years previously, 69-years-old woman who developed a malignant fibrous histiocytoma of the buttock at the field of radical radiation for uterine carcinoma 7 years previously and 59-years-old woman who developed an extraskeletal osteosarcoma of the abdominal wall at the field of postoperative irradiation for uterine sarcoma 7 years previously. The last case is very rare and only 8 cases of radiation-induced extraskeletal osteosarcoma have been reported. Since there has been a definite trend in the treatment of cancer toward employing radiation for more favorable cases, in addition to technical improvements in the administration of radiotherapy and more modern equipment, survival data may have been altered considerably in many malignant tumors. Accordingly, more radiation-induced tumors may be encountered in the future. The clinical presentation and histopathology of these radiation-induced sarcomas are presented with a review of the literature. (author)

Synovial Sarcoma-A Rare Tumor of the Larynx

Directory of Open Access Journals (Sweden)

Ghodrat Mohammadi

2016-05-01

Full Text Available Introduction: Malignant mesenchymal tumors of the larynx are rare. One type of malignant mesenchymal tumor is synovial sarcoma with unknown histogenesis, which occurs predominantly in the lower extremities of young adults. The head and neck region is a relatively rare location. There are few cases of malignant mesenchymal tumors with laryngeal localization in literature.  Case Report: In this report, a new case in a 23-year-old man, which was referred with increasing hoarseness for eight months, and dysphagia, odynophagia, and dyspnea since nearly one year ago, is reported. Indirect laryngoscopy revealed a laryngeal submucosal mass. The patient was operated and the histopathological diagnosis of synovial sarcoma was confirmed by IHC (Immunohistochemisry.  Conclusion:  Synovial sarcoma occurs predominantly in the lower extremities of young adults. Because very few cases of laryngeal synovial sarcoma are reported, every new case will bring some new information about diagnosis and therapy. It is of utmost importance to get to know new aspects and therapeutical modalities of this rare tumor.

An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

Science.gov (United States)

Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

2011-10-01

Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study.

Science.gov (United States)

Olmos, David; Postel-Vinay, Sophie; Molife, L Rhoda; Okuno, Scott H; Schuetze, Scott M; Paccagnella, M Luisa; Batzel, Gretchen N; Yin, Donghua; Pritchard-Jones, Kathryn; Judson, Ian; Worden, Francis P; Gualberto, Antonio; Scurr, Michelle; de Bono, Johann S; Haluska, Paul

2010-02-01

Figitumumab is a fully human IgG2 monoclonal antibody targeting the insulin-like growth-factor-1 receptor (IGF-1R). Preclinical data suggest a dependence on insulin-like growth-factor signalling for sarcoma subtypes, including Ewing's sarcoma, and early reports show antitumour activity of IGF-1R-targeting drugs in these diseases. Between January, 2006, and August, 2008, patients with refractory, advanced sarcomas received figitumumab (20 mg/kg) in two single-stage expansion cohorts within a solid-tumour phase 1 trial. The first cohort (n=15) included patients with multiple sarcoma subtypes, age 18 years or older, and the second cohort (n=14) consisted of patients with refractory Ewing's sarcoma, age 9 years or older. The primary endpoint was to assess the safety and tolerability of figitumumab. Secondary endpoints included pharmacokinetic profiling and preliminary antitumour activity (best response by Response Evaluation Criteria in Solid Tumours [RECIST]) in evaluable patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov, number NCT00474760. 29 patients, 16 of whom had Ewing's sarcoma, were enrolled and received a total of 177 cycles of treatment (median 2, mean 6.1, range 1-24). Grade 3 deep venous thrombosis, grade 3 back pain, and grade 3 vomiting were each noted once in individual patients; one patient had grade 3 increases in aspartate aminotransferase and gammaglutamyltransferase concentrations. This patient also had grade 4 increases in alanine aminotransferase concentrations. The only other grade 4 adverse event was raised concentrations of uric acid, noted in one patient. Pharmacokinetics were comparable between patients with sarcoma and those with other solid tumours. 28 patients were assessed for response; two patients, both with Ewing's sarcoma, had objective responses (one complete response and one partial response) and eight patients had disease stabilisation (six with Ewing's sarcoma, one with

Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

OpenAIRE

Bhagyalakshmi Atla; B Satya Vara Prasad; K Satya Sri; Geeta Vandana

2011-01-01

Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the li...

Congenital extraskeletal Ewing′s sarcoma of chest wall - A rare case report

Directory of Open Access Journals (Sweden)

Bhagyalakshmi Atla

2011-01-01

Full Text Available Congenital extraskeletal Ewing′s sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing′s sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing′s sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing′s sarcoma in neonates are reported in the literature.

A review of soft-tissue sarcomas: translation of biological advances into treatment measures

Directory of Open Access Journals (Sweden)

Hoang NT

2018-05-01

Full Text Available Ngoc T Hoang,* Luis A Acevedo,* Michael J Mann, Bhairavi Tolani Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA *These authors contributed equally to this work Abstract: Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease. Keywords: sarcoma, molecular pathways, immunotherapy, genomics

Bilateral parietal extradural metastatic ewing's sarcoma simulating acute epidural hematoma

International Nuclear Information System (INIS)

Aslam, E.; Imran, M.; Faridi, N.M.

2006-01-01

Sarcomas usually metastasize to lugs. The following case report describes an unusual metastasis of Ewing's sarcoma to extradural parietal region bilaterally. The primary was found at lower end of ulna. (author)

Indian data on bone and soft tissue sarcomas: A summary of published study results

Directory of Open Access Journals (Sweden)

Anant Ramaswamy

2016-01-01

Full Text Available Bone sarcomas are rare tumors, approximating 0.2% of all cancers, with osteosarcoma (OGS, chondrosarcoma, and Ewing sarcoma being the most common cancers in this subset. The formation of disease management groups/clinics focused on sarcomas has resulted in better understanding and management of these uncommon tumors. Multiple large-scale retrospective data from Tata Memorial Hospital (TMH and All India Institute of Medical Sciences have reported outcomes comparable to Western data in the field of OGS and Ewing sarcoma, with interesting prognostic factors identified for further evaluation. Soft tissue sarcomas are a rare heterogeneous group of tumors, more than 50 different tumor entities. The common subtypes identified in India include Ewing sarcoma and synovial sarcoma. Valuable work regarding brachytherapy has been done by radiation oncologists from the TMH, especially in pediatric patients.

Improved survival using specialized multidisciplinary board in sarcoma patients.

Science.gov (United States)

Blay, J-Y; Soibinet, P; Penel, N; Bompas, E; Duffaud, F; Stoeckle, E; Mir, O; Adam, J; Chevreau, C; Bonvalot, S; Rios, M; Kerbrat, P; Cupissol, D; Anract, P; Gouin, F; Kurtz, J-E; Lebbe, C; Isambert, N; Bertucci, F; Toumonde, M; Thyss, A; Piperno-Neumann, S; Dubray-Longeras, P; Meeus, P; Ducimetière, F; Giraud, A; Coindre, J-M; Ray-Coquard, I; Italiano, A; Le Cesne, A

2017-11-01

Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dose-response relationships for radium-induced bone sarcomas

International Nuclear Information System (INIS)

Rowland, R.E.; Stehney, A.F.; Lucas, H.F. Jr.

1981-01-01

The incidence of bone sarcomas among 3055 female radium-dial workers who entered the dial industry before 1950 was used to determine dose-response relationships for the induction of bone sarcomas by radium. Two subpopulations were analyzed: all measured cases who survived at last five years after the start of employment and all cases who survived at least two years after first measurement. The first constituted a group based on year of entry; it contained 1468 women who experienced 42 bone sarcomas; the expected number was 0.4. The second comprised a group based on first measurement; it contained 1257 women who experienced 13 bone sarcomas; the expected number was 0.2. The dose-response function, I = (C + αD + #betta#D 2 )e/sup -#betta#D/, and simplifications of this general form, were fit to each data set. Two functions, I = (C + αD + #betta#D 2 )e/sup -#betta#D/ and I = (C + #betta#D 2 )e/sup -#betta#D/, fit the data for year of entry (p greater than or equal to 0.05); both these functions and I = (C + αD) fit the data for first measurement. The function I = (C + #betta#D 2 )e/sup -#betta#D/ was used to predict the number of bone sarcomas in all other pre-1950 radium cases (medical, laboratory, and other exposure); fewer were actually observed than the fit of this function to the female dial workers predicted

Analysis of gene expression profiles of soft tissue sarcoma using a combination of knowledge-based filtering with integration of multiple statistics.

Directory of Open Access Journals (Sweden)

Anna Takahashi

Full Text Available The diagnosis and treatment of soft tissue sarcomas (STS have been difficult. Of the diverse histological subtypes, undifferentiated pleomorphic sarcoma (UPS is particularly difficult to diagnose accurately, and its classification per se is still controversial. Recent advances in genomic technologies provide an excellent way to address such problems. However, it is often difficult, if not impossible, to identify definitive disease-associated genes using genome-wide analysis alone, primarily because of multiple testing problems. In the present study, we analyzed microarray data from 88 STS patients using a combination method that used knowledge-based filtering and a simulation based on the integration of multiple statistics to reduce multiple testing problems. We identified 25 genes, including hypoxia-related genes (e.g., MIF, SCD1, P4HA1, ENO1, and STAT1 and cell cycle- and DNA repair-related genes (e.g., TACC3, PRDX1, PRKDC, and H2AFY. These genes showed significant differential expression among histological subtypes, including UPS, and showed associations with overall survival. STAT1 showed a strong association with overall survival in UPS patients (logrank p = 1.84 × 10(-6 and adjusted p value 2.99 × 10(-3 after the permutation test. According to the literature, the 25 genes selected are useful not only as markers of differential diagnosis but also as prognostic/predictive markers and/or therapeutic targets for STS. Our combination method can identify genes that are potential prognostic/predictive factors and/or therapeutic targets in STS and possibly in other cancers. These disease-associated genes deserve further preclinical and clinical validation.

Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators Detecção imuno-histoquímica do antígeno nuclear latente-1 do herpesvirus tipo 8 para diferenciar o sarcoma de Kaposi epidêmico cutâneo de seus simuladores histológicos

Directory of Open Access Journals (Sweden)

Patricia Fonseca Pereira

2013-04-01

Full Text Available Kaposi's sarcoma is the most common neoplasia diagnosed in AIDS patients and the expression of the human herpesvirus-8 (HHV-8 latent nuclear antigen-1 has been useful for its histological diagnosis. The aim of this study is to confirm that immunohistochemistry is a valuable tool for differentiating KS from its simulators in skin biopsies of HIV patients. Immunohistochemical and histological analyses were performed in 49 Kaposi's sarcoma skin biopsies and 60 of its histological simulators. Positivity was present in the 49 Kaposi's sarcoma skin biopsies and no staining was observed in the 60 simulators analyzed, resulting in sensibility and specificity of 100%. HHV-8 immunohistochemical detection is an effective tool for diagnosing Kaposi's sarcoma, especially in early lesions in which neoplastic features are not evident. It also contributes to its histological differential diagnosis.O sarcoma de Kaposi é a neoplasia mais diagnosticada em pacientes com SIDA e a expressão do antígeno nuclear latente-1 do herpesvírus humano tipo-8 (HHV-8 tem se mostrado útil no seu diagnóstico histológico. O objetivo deste estudo é confirmar que o método imuno-histoquímico é uma ferramenta útil para diferenciar o sarcoma de Kaposi cutâneo de seus simuladores histológicos em pacientes HIV positivos. Análise histológica e imuno-histoquímica foram realizadas em 49 casos de sarcoma de Kaposi cutâneo e 60 casos de seus simuladores histológicos. Positividade à imuno-histoquímica para o antígeno nuclear latente 1 do HHV-8 foi observada nos 49 casos de sarcoma de Kaposi e nenhuma reação foi detectada nos 60 simuladores analisados, resultando em 100% de sensibilidade e especificidade. A detecção do HHV-8 por imuno-histoquímica é uma ferramenta útil para o diagnóstico de sarcoma de Kaposi, especialmente na lesão inicial cujo caráter neoplásico não é evidente, e contribui para seu diagnóstico diferencial histológico.

Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

Science.gov (United States)

Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Hornick, Jason L; Woda, Bruce; Yu, Hongbo

2016-08-01

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma

OpenAIRE

Hettmer, Simone; Schinzel, Anna C; Tchessalova, Daria; Schneider, Michaela; Parker, Christina L; Bronson, Roderick T; Richards, Nigel GJ; Hahn, William C; Wagers, Amy J

2015-01-01

eLife digest Sarcoma is a type of cancer that forms in the connective tissues of the body, such as bone, cartilage, muscle and fat. Usually, treatment involves surgical removal of the tumor and/or radiation to kill the tumor cells. However, if sarcomas spread to other parts of the body, the treatment options are limited. Genetic studies have revealed several genetic changes that contribute to the formation of sarcomas. Many sarcomas have a mutation in a gene that encodes a protein called Ras....

Erythroblastic Sarcoma Presenting as Bilateral Ovarian Masses in an Infant with Pure Erythroid Leukemia

Science.gov (United States)

Wang, Huan-You; Huang, Lily Jun-shen; Garcia, Rolando; Li, Shiyong; Galliani, Carlos A.

2010-01-01

Pure erythroid leukemia is a rare subtype of acute erythroid leukemia that is characterized by a predominant erythroid population, and erythroblastic sarcoma has not yet been described in the English literature. Here we report a first case of erythroblastic sarcoma which presented as bilateral ovarian masses in a three and half month old baby girl with pure erythroid leukemia. Bone marrow aspirate and biopsy showed the marrow was completely replaced by large-sized blasts consistent with erythroblasts. Immunophenotypically, both the tumor cells from the ovarian mass and bone marrow blasts were positive for CD117, glycophorin A, and hemoglobin A, demonstrating erythroid differentiation. Reverse transcriptase polymerase chain reaction showed the tumor cells from ovarian mass expressed hemoglobin F and α1 spectrin, confirming their erythroid lineage. Conventional karyotype of the bone marrow aspirates revealed del(6) (q23q25) and trisomy 7 in all 21 cells examined. Fluorescence in situ hybridization of the ovarian mass demonstrated loss of C-MYB at 6q23 locus in 41% of the cells, and deletion of chromosome 7 and 7q in 37% and 66% of cells, respectively. Taken together, we showed, for the first time, that pure erythroid leukemia presented as a myeloid sarcoma in the form of ovarian masses. PMID:21237494

Effectiveness of Vascular Markers (Immunohistochemical Stains) in Soft Tissue Sarcomas.

Science.gov (United States)

Naeem, Namra; Mushtaq, Sajid; Akhter, Noreen; Hussain, Mudassar; Hassan, Usman

2018-05-01

To ascertain the effectiveness of IHC markers of vascular origin like CD31, CD34, FLI1 and ERG in vascular soft tissue sarcomas including angiosarcomas, Kaposi sarcomas, epithelioid hemangioendothelioma and a non-vascular soft tissue sarcoma (Epithelioid sarcoma). Descriptive study. Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2011 to 2017. Diagnosed cases of angiosarcomas (n=48), epithelioid hemangioendothelioma (n=9), Kaposi sarcoma (n=9) and epithelioid sarcoma (n=20) were selected. Immunohistochemical staining as performed on formalin fixed paraffin embedded sections. The sections were stained for the following markers: CD34 (VENTANA clone Q Bend 10), CD31 (Leica clone 1 A 10), FLI1 (CELL MARQUE clone MRQ-1) and ERG (CELL MARQUE clone EP111). A complete panel of CD34, CD31 and ERG was applied on 8/48 cases of angiosarcomas with triple positivity in 6 cases. Eight cases showed positivity for only CD31 and ERG and 2 cases showed positivity for only ERG. A complete panel of CD34, CD31 and ERG was applied on 3/9 cases of epithelioid hemangioendothelioma with positivity for all markers in 2 cases. Combined positivity for ERG and CD34 was seen in 2 cases and on 4 cases only CD31 immunohistochemical was solely applied with 100% positivity. FLI1 was not applied on any case. Among 9 cases of Kaposi sarcoma, ERG, CD34 and CD31 in combination were applied on only 1 case with triple positivity. Remaining cases show positivity for either CD34, CD31 or FLI1. Majority of cases of epithelioid sarcomas were diagnosed on the basis of cytokeratin and CD34 positivity with loss of INI1. The other vascular markers showed negativity in all cases. Among these four markers, ERG immunohistochemical stain is highly effective for endothelial differentiation due to its specific nuclear staining pattern in normal blood vessel endothelial cells (internal control) as well as neoplastic cells of vascular tumors and lack of background staining.

Ewing Sarcoma: Current Management and Future Approaches Through Collaboration

NARCIS (Netherlands)

Gaspar, Nathalie; Hawkins, Douglas S.; Dirksen, Uta; Lewis, Ian J.; Ferrari, Stefano; Le Deley, Marie-Cecile; Kovar, Heinrich; Grimer, Robert; Whelan, Jeremy; Claude, Line; Delattre, Olivier; Paulussen, Michael; Picci, Piero; Sundby Hall, Kirsten; van den Berg, Hendrik; Ladenstein, Ruth; Michon, Jean; Hjorth, Lars; Judson, Ian; Luksch, Roberto; Bernstein, Mark L.; Marec-Bérard, Perrine; Brennan, Bernadette; Craft, Alan W.; Womer, Richard B.; Juergens, Heribert; Oberlin, Odile

2015-01-01

Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or

Long-term risk of sarcoma following radiation treatment for breast cancer

International Nuclear Information System (INIS)

Taghian, A.; de Vathaire, F.; Terrier, P.; Le, M.; Auquier, A.; Mouriesse, H.; Grimaud, E.; Sarrazin, D.; Tubiana, M.

1991-01-01

Between 1954 and 1983, 7620 patients were treated for breast carcinoma at Institut Gustave Roussy (France). Of these patients, 6919 were followed for at least 1 year. Out of these, 11 presented with sarcomas thought to be induced by irradiation, 2 of which were Steward-Treves Syndrome, and 9 of which were sarcomas within the irradiated fields. All histological slides were reviewed and a comparison with those of breast cancer was done. The sites of these sarcomas were: parietal wall, 1 case; second costal cartilage, 1 case; infraclavicular region, 1 case; supraclavicular region, 2 cases; internal third of the clavicle, 2 cases; axillary region 2 cases; and the internal side of the upper arm (Stewart-Treves syndrome), 2 cases. The median age of these 11 patients at the diagnosis of sarcomas was 65.8 (49-83). The mean latent period was 9.5 years (4-24). Three patients underwent radical mastectomy and nine modified radical mastectomy. Only one patient received chemotherapy. The radiation doses received at the site of the sarcoma were 45 Gy/18 fr. for 10 cases and 90-100 Gy for 1 case (due to overlapping between two fields). The histology was as follows: malignant fibrous histiocytoma, 5 cases; fibrosarcoma, 3 cases; lymphangiosarcoma, 2 cases; and osteochondrosarcoma, 1 case. The median survival following diagnosis of sarcoma was 2.4 years (4 months-9 years). Two patients are still alive: one with recurrence of her breast cancer, the other in complete remission, with 7 and 3 years follow-up, respectively. All other patients died from their sarcomas. The cumulative incidence of sarcoma following irradiation of breast cancer was 0.2% (0.09-0.47) at 10 years. The standardized incidence ratio (SIR) of sarcoma (observed n number-sign of cases (Obs)/expected n number-sign of cases (Exp) computed from the Danish Cancer Registry for the same period) was 1.81 (CI 0.91-3.23)

Sarcomas in north west England: I. Histopathological peer review.

Science.gov (United States)

Harris, M; Hartley, A L; Blair, V; Birch, J M; Banerjee, S S; Freemont, A J; McClure, J; McWilliam, L J

1991-08-01

A total of 468 cases of bone, soft tissue and visceral sarcomas (and certain other tumours) diagnosed during the years 1982-84 in North West England were entered in a study of histopathological peer review, incidence and survival. This paper describes the effects of peer review. Material was reviewed by a panel of five pathologists for 413 of the 450 cases originally registered as sarcomas with the Regional Cancer Registry. The diagnosis of sarcomas was confirmed in 76% cases and and there was agreement on sub-type for 53% cases. Measures of agreement were lowest for the two sub-types most commonly diagnosed i.e. malignant fibrous histiocytoma and leiomyosarcoma. Degree of agreement between individual pathologists and final panel diagnosis was also very variable but never less than 65%. It is concluded that second opinion is essential in cases of presumed sarcomas for studies of incidence and aetiology and to ensure that appropriate treatment is selected.

Extraskeletal Ewing's Sarcoma: insight into a ten years follow-up.

Science.gov (United States)

Zitelli, A; Manfredelli, S; Brunotti, G; Marcantonio, M; Pontone, S; Angelici, A

2013-01-01

Extraskeletal Ewing's sarcoma is a rare malignant soft tissue tumor, classified within the Ewing's Sarcoma Family Tumors. While the classical Ewing's Sarcoma affects mainly the bone during youth, the Extraskeletal histotype differs for age incidence, primary location and prognosis. Peak incidence and typical location are during adolescence and in the extremities respectively. We report a 30 year old woman case with a positive outcome after ten years from first diagnosis of Extraskeletal Ewing's sarcoma. Treatment was achieved through surgical resection plus adjuvant chemoradiotherapy derived from EW93 and IRS III trials. Conclusion. Our report represents an unusual case due to age of presentation, neoplasm location and long survival reached. In last decades several trials results demonstrated that long survival could be achieved by combined surgery and adjuvant multi-drug treatment.

Combined use of expression and CGH arrays pinpoints novel candidate genes in Ewing sarcoma family of tumors

International Nuclear Information System (INIS)

Savola, Suvi; Knuutila, Sakari; Klami, Arto; Tripathi, Abhishek; Niini, Tarja; Serra, Massimo; Picci, Piero; Kaski, Samuel; Zambelli, Diana; Scotlandi, Katia

2009-01-01

Ewing sarcoma family of tumors (ESFT), characterized by t(11;22)(q24;q12), is one of the most common tumors of bone in children and young adults. In addition to EWS/FLI1 gene fusion, copy number changes are known to be significant for the underlying neoplastic development of ESFT and for patient outcome. Our genome-wide high-resolution analysis aspired to pinpoint genomic regions of highest interest and possible target genes in these areas. Array comparative genomic hybridization (CGH) and expression arrays were used to screen for copy number alterations and expression changes in ESFT patient samples. A total of 31 ESFT samples were analyzed by aCGH and in 16 patients DNA and RNA level data, created by expression arrays, was integrated. Time of the follow-up of these patients was 5–192 months. Clinical outcome was statistically evaluated by Kaplan-Meier/Logrank methods and RT-PCR was applied on 42 patient samples to study the gene of the highest interest. Copy number changes were detected in 87% of the cases. The most recurrent copy number changes were gains at 1q, 2, 8, and 12, and losses at 9p and 16q. Cumulative event free survival (ESFT) and overall survival (OS) were significantly better (P < 0.05) for primary tumors with three or less copy number changes than for tumors with higher number of copy number aberrations. In three samples copy number imbalances were detected in chromosomes 11 and 22 affecting the FLI1 and EWSR1 loci, suggesting that an unbalanced t(11;22) and subsequent duplication of the derivative chromosome harboring fusion gene is a common event in ESFT. Further, amplifications on chromosomes 20 and 22 seen in one patient sample suggest a novel translocation type between EWSR1 and an unidentified fusion partner at 20q. In total 20 novel ESFT associated putative oncogenes and tumor suppressor genes were found in the integration analysis of array CGH and expression data. Quantitative RT-PCR to study the expression levels of the most interesting

Metastatic Ewing's sarcoma to the right ventricle

OpenAIRE

Datrice, Nicole; Milliken, Jeffrey; Kirsh, M.; Abolhoda, Amir; Saremi, Farhood; Sender, Leonard

2011-01-01

Ewing's sarcoma is a round cell neoplasm derived from neural crest cells that is part of the primitive neuroectodermal tumor (PNET) family. It is a rare, aggressive malignancy that affects young people, most commonly in the second decade of life. The treatment of localized disease has improved greatly over the past four decades, but the prognosis for metastatic disease remains poor. Cardiac metastases of Ewing's sarcoma are exceedingly rare, with only a few reported cases. This...

Collecting and Storing Tissue, Blood, and Bone Marrow Samples From Patients With Rhabdomyosarcoma or Other Soft Tissue Sarcoma

Science.gov (United States)

2017-12-11

Adult Rhabdomyosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Chordoma; Desmoid Tumor; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Previously Untreated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

[Soft tissue sarcomas: the role of histology and molecular pathology for differential diagnosis].

Science.gov (United States)

Poremba, C

2006-01-01

Soft tissue sarcomas include a wide spectrum of different entities. The so-called small round blue cell tumors and spindle cell tumors are difficult to classify based solely on conventional histology. To identify different subtypes of tumors special histochemical and immunohistochemical techniques are necessary. Analysis of protein expression by immunohistochemistry provides a helpful tool to investigate the histogenesis of tumors. A basic spectrum of antibodies should be included to study these tumors: Desmin and myogenin (or MyoD1) for skeletal differentiation; S-100, NSE, CD56, and synaptophysin for neural/neuroendocrine differentiation; CD3, CD20, and CD79 alpha for malignant lymphomas; CD34, sm-actin, and beta-catenin for spindle cell tumors; additional antigens, e. g. Ki-67 and p 53, for estimation of proliferation and tumor suppressor gene malfunctions. Nevertheless, the molecular analysis of soft tissue sarcomas is necessary for demonstration of specific translocations or gene defects to specify and proof a diagnosis. For this purpose, RT-PCR for RNA expression analysis of gene fusion transcripts and multi-color FISH for analysis of chromosomal rearrangements are used. Further investigations, using DNA microrrays may help to subclassify such tumors, with respect to prognosis or prediction of therapeutic response.

Structure-Function Based Molecular Relationships in Ewing's Sarcoma

Science.gov (United States)

2015-01-01

Ewing's Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing's sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer. PMID:25688366

Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature

International Nuclear Information System (INIS)

Lee, Hae-June; Yoon, Changhwan; Park, Do Joong; Kim, Yeo-Jung; Schmidt, Benjamin; Lee, Yoon-Jin; Tap, William D.; Eisinger-Mathason, T.S. Karin; Choy, Edwin; Kirsch, David G.; Simon, M. Celeste

2015-01-01

Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm 3 within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm 3 for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature

Primary retroperitoneal soft tissue sarcoma: Imaging appearances, pitfalls and diagnostic algorithm.

Science.gov (United States)

Messiou, C; Moskovic, E; Vanel, D; Morosi, C; Benchimol, R; Strauss, D; Miah, A; Douis, H; van Houdt, W; Bonvalot, S

2017-07-01

Although retroperitoneal sarcomas are rare tumours, they can be encountered by a wide variety of clinicians as they can be incidental findings on imaging or present with non specific symptoms and signs. Surgical resection can offer hope of cure and patient outcomes are improved when patients are managed in high-volume specialist centers. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in inexperienced centers. Therefore it is critical that a diagnosis of retroperitoneal sarcoma should be considered in the differential diagnosis of a retroperitoneal mass with prompt referral to a soft tissue sarcoma unit. In particular, the most common retroperitoneal sarcoma subtypes, liposarcoma and leiomyosarcoma, have characteristic imaging appearances which are discussed. This review therefore aims to set the context and guide clinicians through a diagnostic pathway for retroperitoneal masses in adults which arise extrinsic to the solid abdominal viscera. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Primary Synovial Sarcoma of External Auditory Canal: A Case Report.

Science.gov (United States)

Devi, Aarani; Jayakumar, Krishnannair L L

2017-07-20

Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression.

Synovial sarcoma mimicking benign peripheral nerve sheath tumor

Energy Technology Data Exchange (ETDEWEB)

Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

2017-11-15

To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

Sarcomas: etiología y síntomas

Directory of Open Access Journals (Sweden)

Roberto Gabriel Albín Cano

2012-05-01

Full Text Available Debido a la amplia diversidad de sarcomas, casi son inexistentes los textos que incluyen todas las variedades de este tipo de cáncer. Generalmente, su descripción y revisión se incluyen en las del sistema de órganos afectados específicamente, y la literatura que los aborda está muy fragmentada en las diferentes especialidades médicas. Se realiza una revisión bibliográfica sobre la etiología y síntomas de la mayor parte de los diferentes tipos de sarcomas. Es objetivo de esta revisión, lograr unir la información más actual disponible acerca de la etiología y síntomas de los sarcomas. Se han identificado diferentes factores de riesgo y factores etiológicos, tanto genéticos, infecciosos, como ambientales. Los grandes descubrimientos en relación con los mecanismos genéticos involucrados en los diferentes tipos de sarcoma, han abierto un camino de inestimable valor para introducir nuevos tratamientos, que incluyen ensayos con anticuerpos monoclonales y nuevos fármacos de terapia génica.

A case of clear cell sarcoma

DEFF Research Database (Denmark)

Juel, Jacob; Ibrahim, Rami Mossad

2017-01-01

INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour of the soft tissue often misdiagnosed, as it shares characteristics with malignant melanoma (MM). Previously, CCS has been characterised, as malignant melanoma of the soft tissue, contemporary immunohistochemical techniques, however, have made...... this designation obsolete. The true incidence remains unknown, but CCS is believed to represent less than one percent of all sarcomas. PRESENTATION OF CASE: A 22-year-old patient presented with a mass sized 2.6×2.7×2.7cm of the left gluteal region, pain, and malaise. Initially, the symptoms were interpreted...

Cellular immunotherapy for soft tissue sarcomas

Science.gov (United States)

Finkelstein, Steven Eric; Fishman, Mayer; Conley, Anthony P.; Gabrilovich, Dmitry; Antonia, Scott; Chiappori, Alberto

2015-01-01

SUMMARY Soft tissue sarcomas are rare neoplasms, with approximately 9,000 new cases in the United States every year. Unfortunately, there is little progress in the treatment of metastatic soft tissue sarcomas in the past two decades beyond the standard approaches of surgery, chemotherapy, and radiation. Immunotherapy is a modality complementary to conventional therapy,. It is appealing because functional anti-tumor activity could affect both local-regional and systemic disease and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies being developed, including several tumor vaccine, antigen vaccine, and dendritic cell vaccine strategies. PMID:22401634

Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity.

Science.gov (United States)

Ambrosio, Maria Raffaella; De Falco, Giulia; Rocca, Bruno Jim; Barone, Aurora; Amato, Teresa; Bellan, Cristiana; Lazzi, Stefano; Leoncini, Lorenzo

2015-10-01

The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.

Vaccine-associated sarcomas in cats: a unique cancer model.

Science.gov (United States)

McNiel, E A

2001-01-01

Epidemiologic evidence supports a relationship between vaccination of cats for rabies and feline leukemia virus with the development of soft tissue sarcomas at the site of administration. These tumors are locally invasive and histologically aggressive. As with high-grade soft tissue sarcoma in humans, combination treatment with radiation therapy and surgery provides for optimum tumor control. Feline vaccine-associated sarcoma has become a difficult issue for the veterinary profession for legal, ethical, and clinical reasons. Although most research efforts have focused on therapeutic intervention, this tumor has great potential to provide an informative model for carcinogenesis and genetic susceptibility applicable to cancer in all species, including humans.

Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy.

Science.gov (United States)

Della Badia, Carl; Karini, Homa

2010-01-01

Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

MicroRNAs in the Tumor Biology of Soft Tissue Sarcomas

NARCIS (Netherlands)

C.M.M. Gits (Caroline)

2013-01-01

markdownabstract__Abstract__ Soft tissue sarcomas represent a rare, heterogeneous group of mesenchymal tumors. In sarcomas, histological classification, prediction of clinical behaviour and prognosis, and targeted treatment is often a challenge. A better understanding of the biology of soft

Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice

Data.gov (United States)

U.S. Environmental Protection Agency — Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice. This...

Current Molecular Targeted Therapies for Bone and Soft Tissue Sarcomas

Directory of Open Access Journals (Sweden)

Kenji Nakano

2018-03-01

Full Text Available Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib’s approval as a treatment for gastrointestinal stromal tumors (GISTs has been a great achievement. Following imatinib, other tyrosine kinase inhibitors (TKIs have been approved for GISTs such as sunitinib and regorafenib, and pazopanib was approved for non-GIST soft tissue sarcomas. Olaratumab, the monoclonal antibody that targets platelet-derived growth factor receptor (PDGFR-α, was shown to extend the overall survival of soft tissue sarcoma patients and was approved in 2016 in the U.S. as a breakthrough therapy. For bone tumors, new drugs are limited to denosumab, a receptor activator of nuclear factor κB ligand (RANKL inhibitor, for treating giant cell tumors of bone. In this review, we explain and summarize the current molecular targeting therapies approved and in development for bone and soft tissue sarcomas.

Intraduodenal sarcoma recurrence of retroperitoneal origin: an unusual cause for a duodenal obstruction

Directory of Open Access Journals (Sweden)

Bao Jean J

2012-04-01

Full Text Available Abstract Soft tissue sarcomas are uncommon tumors, and intraduodenal soft tissue sarcoma manifestation is even more rare. Only three cases of intraduodenal sarcomas have been reported in the literature thus far. Here, we report a case of an intraduodenal recurrence of a retroperitoneal sarcoma causing bowel obstruction. This unusual recurrence pattern likely relates to the patient’s previous resection and radiation treatment, and highlights the benefits, limitations and follow-up strategies after multimodality treatment.

Undifferentiated granulocytic sarcoma: a case with epidural onset preceding acute promyelocytic leukemia.

Science.gov (United States)

Tosi, A; De Paoli, A; Fava, S; Luoni, M; Sironi, M; Tocci, A; Assi, A; Cassi, E

1995-01-01

This study reports a case of granulocytic sarcoma that developed in the epidural zone 25 days before clinical evidence of an acute promyelocytic leukemia. The case presented the diagnostic difficulties that are common to all aleukemic granulocytic sarcomas. Moreover, it highlights the very rare association between granulocytic sarcoma and acute promyelocytic leukemia, which is far from being explained.

Primary Occipital Ewing’s Sarcoma with Subsequent Spinal Seeding

Directory of Open Access Journals (Sweden)

Ali Alqahtani

2017-01-01

Full Text Available Ewing’s sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing’s sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI showed cerebrospinal fluid (CSF seeding from the L5 to the S4 vertebrae. Primary cranial Ewing’s sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing’s sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing’s sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Giant primary synovial sarcoma of the anterior mediastinum: A case ...

African Journals Online (AJOL)

2015-06-11

Jun 11, 2015 ... We present a case of primary monophasic synovial sarcoma of the anterior ... Here, we report a case of ... fatigue and anorexia, but no weight loss. ..... Primary intrathoracic synovial sarcoma: A clinicopathologic study of. 40 t (X ...

Transarticular spread of Ewing sarcoma mimicking septic arthritis

Energy Technology Data Exchange (ETDEWEB)

Jordanov, Martin I.; Block, John J. [Vanderbilt University Medical Center, Department of Radiology and Radiological Sciences, Nashville, TN (United States); Gonzalez, Adriana L. [Vanderbilt University Medical Center, Department of Pathology, Nashville, TN (United States); Green, Neil E. [Vanderbilt Children' s Hospital, Department of Pediatric Orthopaedics, Nashville, TN (United States)

2009-04-15

Transarticular spread of tumor is rare; it has only been reported in the sacroiliac joint, intervertebral disk spaces, and facet joints. The anatomic and kinetic characteristics of the sacroiliac joint, as well as the changes the joint undergoes during a lifetime, make it particularly vulnerable to transarticular tumor invasion. Although extremely rare, Ewing sarcoma can extend through the sacroiliac joint and be virtually indistinguishable radiologically from septic arthritis. Furthermore, the clinical presentation of a child with Ewing sarcoma can be similar to that of a child with osteomyelitis. Laboratory values are quite nonspecific and are not always helpful in differentiating between the entities. Therefore, the possibility of sacroiliac joint transarticular Ewing sarcoma should be considered in a child presenting with hip pain, despite clinical, radiological and laboratory findings suggesting an infectious process. (orig.)

Transarticular spread of Ewing sarcoma mimicking septic arthritis

International Nuclear Information System (INIS)

Jordanov, Martin I.; Block, John J.; Gonzalez, Adriana L.; Green, Neil E.

2009-01-01

Transarticular spread of tumor is rare; it has only been reported in the sacroiliac joint, intervertebral disk spaces, and facet joints. The anatomic and kinetic characteristics of the sacroiliac joint, as well as the changes the joint undergoes during a lifetime, make it particularly vulnerable to transarticular tumor invasion. Although extremely rare, Ewing sarcoma can extend through the sacroiliac joint and be virtually indistinguishable radiologically from septic arthritis. Furthermore, the clinical presentation of a child with Ewing sarcoma can be similar to that of a child with osteomyelitis. Laboratory values are quite nonspecific and are not always helpful in differentiating between the entities. Therefore, the possibility of sacroiliac joint transarticular Ewing sarcoma should be considered in a child presenting with hip pain, despite clinical, radiological and laboratory findings suggesting an infectious process. (orig.)

Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

Energy Technology Data Exchange (ETDEWEB)

Alpert, Justin S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Boland, Patrick [Memorial Sloan Kettering Cancer Center, Division of Orthopaedic Surgery, Department of Surgery, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Hameed, Meera [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Panicek, David M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States)

2018-01-15

Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear ''tail'' of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging ''tail'' should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma. (orig.)

Complex treatment of localized bone marrow sarcoma in children

International Nuclear Information System (INIS)

Kolygin, B.A.; Punanov, Yu.A.; Malinin, A.P.; Safonova, S.A.

1997-01-01

The retrospective analysis included the results of the treatment of 67 children suffering from localized sarcomas of bone (Ewing's sarcoma, lymphosarcoma). The advantage was demonstrated in patients, received combination of chemotherapy and radiotherapy on the involved bone. The resection of the primary tumor in combination with radio-chemotherapy improves the 10-year survival

management of epidemic kaposi's sarcoma: a recent concern in ...

African Journals Online (AJOL)

DENTISTRY. By: Dr. Jeff Luande, M.D.. Tanzania Tumor Centre. INTRODUCTION: Kaposi's Sarcoma in its classic endemic form has never been a concern in dental practice. Since early this decade the medical practice has witnessed an ever increasing new form of the same sarcoma in its more aggressive form called the ...

Establishment of a Ewing's sarcoma mouse model: JAK/STAT signalling in Ewing's sarcoma

International Nuclear Information System (INIS)

Sax, B.

2011-01-01

The Ewing's sarcoma family of tumours (ESFT) comprises paediatric cancers of bone and soft tissue which presumably originate from mesenchymal progenitor cells(MPC). One hallmark of ESFT is the presence of a chromosomal translocation. In 90% of the cases chromosome 11 fuses with chromosome 22. This translocation generates the EWS/FLI-1 fusion which acts as an aberrant transcription factor deregulating many genes involved in tumour development. Surgery and/or radiotherapy combined with chemotherapy are the usual forms of treatment for ESFT. But since there is only little progress in the field of chemotherapy the need for an animal model for pre-clinical drug testing is evident. Thus, the main focus of this thesis was to establish a mouse model that develops sarcomas resembling the phenotype of ESFT. We used a conditional EWS/FLI-1 mouse model, which upon Cre activity (controlled by a tissue specific promotor) expressed EWS/FLI-1 in the targeted cells. Since ESFT arises in bone and surrounding soft tissue we decided to direct expression of EWS/FLI-1 to the mesenchymal lineage by using different Cre lines. Only when using the Prx1Cre, double transgenic mice tolerated EWS/FLI-1 expression. We observed developmental abnormalities with severe skeletal deformations. Bone formation was impaired due to the absence of mature chondrocytes and osteoblasts and hence a lack of calcified bone. The lack of mature bone cells in EWS/FLI-1 expressing Prx1Cre mice supports in vitro data showing that EWS/FLI-1 impedes differentiation of murine mesenchymal progenitor cells. Currently, the project is extended to analysis of an inducible Prx1Cre system which circumvents the early lethality of Prx1Cre EF mice. This should provide the basis for tumour formation in these mice and hence the development of an appropriate mouse model for pre-clinical research. In the second project of my PhD thesis, the role of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK

Kaposi's sarcoma involving the thyroid in a patient with AIDS

International Nuclear Information System (INIS)

Krauth, P.H.; Katz, J.F.

1987-01-01

A 30-year-old man with acquired immune deficiency syndrome (AIDS) and Kaposi's sarcoma had a palpable thyroid mass and cervical lymphadenopathy. Nuclear medicine and ultrasound scans revealed multiple thyroid nodules. Results of biopsy showed Kaposi's sarcoma metastatic to the thyroid

EWS/FLI-l peptide-pulsed dendritic cells induces the antitumor immunity in a murine Ewing's sarcoma cell model.

Science.gov (United States)

Peng, Wei; Huang, Xunwu; Yang, Dazhi

2014-08-01

An increasing number of T-cell epitopes derived from various tumor-associated antigens have been reported, and they proved to play significant roles for tumor rejection both in vivo and in vitro. Over 85% of Ewing's sarcoma family of tumors (ESFTs) express tumor-specific chimeric protein EWS/FLI-1, making it an attractive target for therapeutic cytotoxic T-lymphocyte responses. Here, we identified a novel peptide epitope derived from the EWS/FLI-1 protein and demonstrated that effectors induced by the peptide could specifically secrete IFN-γ and lyse the tumor cell line of EWS/FLI-1-positive and HLA-matched cells. In addition, mice treated with dendritic cells pulsed with the EWS/FLI-1 epitope were able to reject a lethal tumor inoculation of the Ewing's sarcoma A673 cells. Therefore, these data provide evidence for the use of the EWS/FLI-l peptide epitope in T cell-based immunotherapeutic concepts against Ewing's sarcoma cell in vitro and in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A.

Science.gov (United States)

Fu, Jiaxin; Jiang, Han; Wu, Chenxuan; Jiang, Yi; Xiao, Lianping; Tian, Yonggang

2016-07-01

Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti‑cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase‑A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab‑resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA‑induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re‑sensitized cetuximab‑resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer‑cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.

Extremity perfusion for sarcoma

NARCIS (Netherlands)

Hoekstra, Harald Joan

2008-01-01

For more than 50 years, the technique of extremity perfusion has been explored in the limb salvage treatment of local, recurrent, and multifocal sarcomas. The "discovery" of tumor necrosis factor-or. in combination with melphalan was a real breakthrough in the treatment of primarily irresectable

Human herpesvirus 8 (HHV-8 and the etiopathogenesis of Kaposi's sarcoma Herpesvírus humano tipo 8 (HHV-8 e a etiopatogênese do sarcoma de Kaposi

Directory of Open Access Journals (Sweden)

Jair Carneiro Leão

2002-08-01

Full Text Available OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.OBJETIVO: O objetivo do presente artigo foi revisar a literatura recente em rela

Primary renal undifferentiated sarcoma as an infiltrative mass in a 12 year old boy

International Nuclear Information System (INIS)

Kim, Yong Hee; Kim, Myung Joon; Lee, Mi Jung; Kim, Se Hwa

2015-01-01

Undifferentiated sarcomas are rare tumors not classified into any sarcoma subtype. Due to their rarity, imaging findings of undifferentiated sarcomas are poorly characterized. The purpose of this report was to present imaging findings of a pathologically confirmed undifferentiated sarcoma originated from the left kidney of a 12-year-old boy. The mass was infiltrative involving the renal pelvis. It mimicked massive hilar lymphadenopathy with a preserved renal contour visible by both ultrasonography and CT. Renal vein thrombosis was also observed. Although undifferentiated sarcomas are rare, they should be considered in differential diagnosis of infiltrative renal masses with renal pelvis invasion in children

Primary renal undifferentiated sarcoma as an infiltrative mass in a 12 year old boy

Energy Technology Data Exchange (ETDEWEB)

Kim, Yong Hee; Kim, Myung Joon; Lee, Mi Jung [Dept. of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Se Hwa [Dept. of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2015-09-15

Undifferentiated sarcomas are rare tumors not classified into any sarcoma subtype. Due to their rarity, imaging findings of undifferentiated sarcomas are poorly characterized. The purpose of this report was to present imaging findings of a pathologically confirmed undifferentiated sarcoma originated from the left kidney of a 12-year-old boy. The mass was infiltrative involving the renal pelvis. It mimicked massive hilar lymphadenopathy with a preserved renal contour visible by both ultrasonography and CT. Renal vein thrombosis was also observed. Although undifferentiated sarcomas are rare, they should be considered in differential diagnosis of infiltrative renal masses with renal pelvis invasion in children.

Ewing's sarcoma: a neuroectodermal tumor of the chest wall

International Nuclear Information System (INIS)

Alcaraz, M. J.; Lorente, M. L.; Martin, A. M.; Gonzalez, I.

2000-01-01

Ewing's sarcoma is the second most common malignant bone tumor in children and young adults. It is most prevalent between the ages of 10 and 15 years. There are present two cases of Ewing's sarcoma of the chest wall. The clinical, radiological and pathological features are described and the therapeutic options are discussed. (Author)

Definitive Brachytherapy for Kaposi's Sarcoma

International Nuclear Information System (INIS)

Williams, A.; Ezzell, G.; Zalupski, M.; Fontanesi, J.

1996-01-01

Purpose: To assess the efficacy and possible complications in patients diagnosed with Kaposi's sarcoma and treated with definitive brachytherapy. Methods and Materials: Between January, 1995 and December, 1995, four patients with Kaposi's sarcoma (KS) were treated with brachytherapy. Three patients, all with positive HIV status were treated using Iridium 192 (Ir-192) sources via a high-dose rate remote afterloader. One patient with endemic KS was treated using the application of catheters loaded with Californium 252. Eight sites were treated and included scalp, feet, nose, penis, hand, neck, and back. Dose rate for Ir-192 was 330cGy/fx to a total dose of 990cGy. The Californium was delivered as 100nGy/b.i.d. to a total dose of 900nGy. Follow-up as ranged from 2-6 months. Results: All four patients remain alive. Seven of eight sites have had complete clinical response and each patient has reported durable pain relief that has not subsided through last follow-up of 1/96. Two of eight sites, both treated with surface mold technique with Californium 252 developed moist desquamation. The remaining six sites did not demonstrate significant toxicity. Conclusion: Brachytherapy can offer Kaposi's sarcoma patients results that are equivalent to external beam radiation therapy, with minimal complications, a shorter treatment time and potential cost effectiveness

Discussing sarcoma risks during informed consent for nonhysterectomy management of fibroids: an unmet need.

Science.gov (United States)

Seagle, Brandon-Luke L; Alexander, Amy L; Strohl, Anna E; Shahabi, Shohreh

2018-01-01

There is no reliable way to distinguish symptomatic uterine fibroids from sarcoma without a surgical specimen. Many women with a uterine sarcoma are initially managed without hysterectomy under a presumed fibroid diagnosis, without understanding sarcoma risks. Currently many alternatives to hysterectomy, including medical and procedural interventions, for treatment of fibroids are promoted. The sarcoma incidence among women with presumed fibroids is 0.29% (1/340) to 0.05% (1/2000). Nonmetastatic leiomyosarcoma has a 63% 5-year survival rate whereas metastatic leiomyosarcoma has a 14% 5-year survival rate. In uterine sarcoma, we often cannot identify who has sarcoma before making a potentially cure-denying decision by delaying surgery. Therefore, women electing an alternative to hysterectomy for fibroids should undergo an informed consent process that specifically includes discussion of uterine sarcoma incidence and mortality. Alternatives to hysterectomy for presumed fibroids remain preferable treatment options for many women with symptomatic fibroids, so long as underlying sarcoma risks are adequately discussed. The challenge for obstetrician- gynecologists then is how to provide better informed consent and maintain the primacy of patient autonomy over our concern to "First, do no harm." Major threats to patient's autonomy are faced in the sarcoma risk discussion. How we should present sarcoma risk information to avoid being dismissive of sarcoma or frightening women toward hysterectomy is unstudied. Research is needed to determine how to provide sarcoma risk information with less bias during informed consent. Copyright © 2017 Elsevier Inc. All rights reserved.

Extraskeletal ewing sarcoma of cervical epidural region: cases report

Energy Technology Data Exchange (ETDEWEB)

Kim, Ki Jun; Jung, Hyun Seouk; Lee, Jae Hee; Sohn, Kyung Myung; Lee, Sung Yong [Our Lady of Mercy Hospital, Inchon (Korea, Republic of)

2003-01-01

Extraskeletal ewing sarcoma is a rare malignant tumor found in children and young adults. It commonly occurs in deep soft tissue of the trunk, especially in the paravertebral region and extremities. We report two cases of extraskeletal ewing sarcoma occurring as a cervical epidural tumor in elderly patients. The MRI and CT findings showed that paravertebral epidural tumors had invaded the spinal canal through the intervertebral foramen. At T1-weighted MR imaging, the masses were isointense to muscle, and at T2* and T2-weighted images were hyperintense, and heterogeneous contrast enhancement was observed. Extraskeletal ewing sarcoma, though quite rare, should be borne in mind in the differential diagnosis of paraspinal epidural tumors.

Extraskeletal ewing sarcoma of cervical epidural region: cases report

International Nuclear Information System (INIS)

Kim, Ki Jun; Jung, Hyun Seouk; Lee, Jae Hee; Sohn, Kyung Myung; Lee, Sung Yong

2003-01-01

Extraskeletal ewing sarcoma is a rare malignant tumor found in children and young adults. It commonly occurs in deep soft tissue of the trunk, especially in the paravertebral region and extremities. We report two cases of extraskeletal ewing sarcoma occurring as a cervical epidural tumor in elderly patients. The MRI and CT findings showed that paravertebral epidural tumors had invaded the spinal canal through the intervertebral foramen. At T1-weighted MR imaging, the masses were isointense to muscle, and at T2* and T2-weighted images were hyperintense, and heterogeneous contrast enhancement was observed. Extraskeletal ewing sarcoma, though quite rare, should be borne in mind in the differential diagnosis of paraspinal epidural tumors

Deep-seated sarcomas of the penis

Directory of Open Access Journals (Sweden)

Alberto A. Antunes

2005-06-01

Full Text Available Mesenchymal neoplasias represent 5% of tumors affecting the penis. Due to the rarity of such tumors, there is no agreement concerning the best method for staging and managing these patients. Sarcomas of the penis can be classified as deep-seated if they derive from the structures forming the spongy body and the cavernous bodies. Superficial lesions are usually low-grade and show a small tendency towards distant metastasis. In contrast, deep-seated lesions usually show behavior that is more aggressive and have poorer prognosis. The authors report 3 cases of deep-seated primary sarcomas of the penis and review the literature on this rare and aggressive neoplasia.

Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

Energy Technology Data Exchange (ETDEWEB)

Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2008-02-15

Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses.

Primary pericranial Ewing's sarcoma on the temporal bone: A case report.

Science.gov (United States)

Kawano, Hiroto; Nitta, Naoki; Ishida, Mitsuaki; Fukami, Tadateru; Nozaki, Kazuhiko

2016-01-01

Primary Ewing's sarcoma originating in the pericranium is an extremely rare disease entity. A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under the left temporal muscle and attached to the surface of the temporal bone. Head computed tomography revealed a mass with bony spicule formation on the temporal bone, however, it did not show bone destruction or intracranial invasion. F-18 fluorodeoxyglucose positron emission tomography showed no lesions other than the mass on the temporal bone. Magnetic resonance imaging showed that the mass was located between the temporal bone and the pericranium. The mass was completely resected with the underlying temporal bone and the overlying deep layer of temporal muscle, and was diagnosed as primary Ewing's sarcoma. Because the tumor was located in the subpericranium, we created a new classification, "pericranial Ewing's sarcoma," and diagnosed the present tumor as pericranial Ewing's sarcoma. We herein present an extremely rare case of primary pericranial Ewing's sarcoma that developed on the temporal bone.

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma

International Nuclear Information System (INIS)

Marinova, L.; Hristozova, I.; Mihaylova, I.; Perenovska, P.

2015-01-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy ± surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. (authors)

The role of imaging in the evaluation of extraskeletal Ewing’s sarcoma

Directory of Open Access Journals (Sweden)

Pieter Barnardt

2013-03-01

Full Text Available Primary bone tumours account for 5% of all adolescent and child cancers. When Ewing’s sarcoma arises in soft tissue rather than bone, it is referred to as extraskeletal Ewing’s sarcoma (ESS. Computed tomography (CT scanning and magnetic resonance imaging (MRI features of Ewing’s sarcoma are non-specific, and a radiological differential diagnosis should be considered. Ewing’s sarcoma is confirmed by features on histological analysis. In young people who present with soft-tissue tumours, ESS should be considered. In the management of patients with tumours, imaging techniques are useful for biopsy guidance, evaluating the possibility of resection, and tumour response to treatment.

Uterine endometrial stromal sarcoma located in uterine myometrium: MRI appearance

Energy Technology Data Exchange (ETDEWEB)

Ueda, M.; Otsuka, M.; Hatakenaka, M. [Dept. of Radiology, Medical Institute of Bioregulation, Kyushu University, Beppu (Japan); Torii, Y. [Dept. of Radiology, Saga Prefectural Hospital (Japan)

2000-05-01

Two cases of uterine endometrial stromal sarcoma whose main mass was located in uterine myometrium are reported. They mimicked uterine leiomyoma with cystic degeneration or uterine leiomyosarcoma. Endometrial stromal sarcoma should be suggested in the differential diagnosis of mass lesion in uterine myometrium. (orig.)

Tumor - host immune interactions in Ewing sarcoma : implications for therapy

NARCIS (Netherlands)

Berghuis, Dagmar

2012-01-01

In this thesis, we report on various aspects of tumor - host (immune) interactions in Ewing sarcoma patients with the aim to obtain leads for immunotherapeutic or targeted treatment strategies. We demonstrate a key role for interferon gamma (IFNg) in enhancing both Ewing sarcoma immunogenicity and

Monophasic Synovial Sarcoma Presenting as Mitral Valve Obstruction

Science.gov (United States)

Chokesuwattanaskul, Warangkana; Terrell, Jason; Jenkins, Leigh Ann

2010-01-01

We report the case of a 26-year-old man who experienced progressive left-sided chest pain and 2 episodes of near-syncope. Studies revealed a 15-cm mass in the upper left lung, a 10-cm mass in the medial base of the left lung, and a 5-cm left atrial mass that involved the left lung, infiltrated the left pulmonary vein, and prolapsed into the mitral valve, causing intermittent obstruction. The patient underwent surgical excision of the left atrial tumor. Pathologic evaluation confirmed the diagnosis of monophasic synovial sarcoma. To our knowledge, this is only the 3rd report of left atrial invasion and resultant mitral valve obstruction from a synovial sarcoma that infiltrated the pulmonary vein. We believe that this is the 1st documented case of a metastatic left atrial synovial sarcoma in monophasic form. PMID:20844626

Drugs Approved for Kaposi Sarcoma

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

Detection of SYT and EWS gene rearrangements by dual-color break-apart CISH in liquid-based cytology samples of synovial sarcoma and Ewing sarcoma/primitive neuroectodermal tumor.

Science.gov (United States)

Kumagai, Arisa; Motoi, Toru; Tsuji, Kaori; Imamura, Tetsuo; Fukusato, Toshio

2010-08-01

To improve cytologic diagnostic accuracy for translocation-associated sarcomas, we explored dual-color break-apart (dc) chromogenic in situ hybridization (CISH) on liquid-based cytology (LBC) samples of 2 prototypic sarcomas: synovial sarcoma (SS) and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). LBC samples of 10 cases of SS and 9 cases of ES/PNET were subjected to dc-CISH using probes for the specifically rearranged genes in each tumor entity: SYT in SS and EWS in ES/PNET. Rearranged SYT was successfully detected in all SSs but not in any ES/PNETs. In contrast, EWS rearrangement was identified in all ES/PNETs but not in any SSs. These results were validated by dc-fluorescence in situ hybridization and reverse transcription-polymerase chain reaction. dc-CISH on LBC samples is a reliable modality to detect gene rearrangements in sarcomas. This system has a clear advantage over other methods, enabling simultaneous visualization of the genetic abnormality and well-preserved, nonoverlapping cytomorphologic features with clear background under bright-field microscope.

Assessing the reading level of online sarcoma patient education materials.

Science.gov (United States)

Patel, Shaan S; Sheppard, Evan D; Siegel, Herrick J; Ponce, Brent A

2015-01-01

Cancer patients rely on patient education materials (PEMs) to gather information regarding their disease. Patients who are better informed about their illness have better health outcomes. The National Institutes of Health (NIH) recommends that PEMs be written at a sixth- to seventh-grade reading level. The purpose of this study was to evaluate the readability of online PEMs of bone and soft-tissue sarcomas and related conditions. We identified relevant online PEMs from the following websites: American Academy of Orthopaedic Surgeons, academic training centers, sarcoma specialists, Google search hits, Bonetumor.org, Sarcoma Alliance, Sarcoma Foundation of America, and Medscape. We used 10 different readability instruments to evaluate the reading level of each website's PEMs. In assessing 72 websites and 774 articles, we found that none of the websites had a mean readability score at or below 7 (seventh grade). Collectively, all websites had a mean readability score of 11.4, and the range of scores was grade level 8.9 to 15.5. None of the PEMs in this study of bone and soft-tissue sarcomas and related conditions met the NIH recommendation for PEM reading levels. Concerted efforts to improve the reading level of orthopedic oncologic PEMs are necessary.

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

Energy Technology Data Exchange (ETDEWEB)

Nakanishi, Hirofumi; Araki, Nobuhito [Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-Ku, 537-8511, Osaka (Japan); Sawai, Yuka [Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Kudawara, Ikuo [Department of Orthopedic Surgery, Osaka National Hospital, Osaka (Japan); Mano, Masayuki; Ishiguro, Shingo [Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ueda, Takafumi; Yoshikawa, Hideki [Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)

2003-12-01

To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

International Nuclear Information System (INIS)

Nakanishi, Hirofumi; Araki, Nobuhito; Sawai, Yuka; Kudawara, Ikuo; Mano, Masayuki; Ishiguro, Shingo; Ueda, Takafumi; Yoshikawa, Hideki

2003-01-01

To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

Myofibroblastic sarcoma of the base of tongue. Case report and review of the literature

International Nuclear Information System (INIS)

Takacsi-Nagy, Zoltan; Fodor, Janos; Murakoezy, Gyoergyi; Pogany, Peter; Orosz, Zsolt

2009-01-01

Background: Mesenchymal malignancies with myofibroblastic differentiation exhibit a spectrum from low-grade myofibroblastic sarcoma mimicking fibromatosis to pleomorphic high-grade sarcoma. Low-grade myofibroblastic sarcoma shows a wide anatomic distribution with a predilection for the head-and-neck region; however, intermediate- and high-grade myofibroblastic sarcomas in this localization are exceptional. Case Report: A 56-year-old woman with intermediate-grade myofibroblastic sarcoma of the base of tongue is presented. She was treated with surgical excision, but computed tomography proved local residual tumor. Reexcision and chemotherapy were refused by the patient. Irradiation was given to a total dose of 66 Gy. Result: 50 months after completion of radiotherapy, the patient is in good health without any evidence of disease. According to the review of the literature, base of tongue as the primary site of myofibroblastic sarcoma has not been published so far. Conclusion: Similarly to the low-grade form, intermediate- and high-grade myofibroblastic sarcomas may also occur in the head-and-neck region. In case of incomplete excision, radiotherapy may be an effective treatment. (orig.)

Like or Dislike? Impact of Facebook on Ewing Sarcoma Treatment.

Science.gov (United States)

Ruckenstuhl, Paul; Schippinger, Michael; Liebmann, Paul; Leithner, Andreas; Bernhardt, Gerwin

2016-08-25

An increasing number of patients are raising their voices in online forums to exchange health-related information. Facebook is the leading social media platform with more than 1 billion international daily users recorded in the summer of 2015. Facebook has a dynamic audience and is utilized in a number of ways, discussing medical issues being one of them. Ewing sarcoma mainly affects teenagers and young adults. Additionally, many individuals within this age group are regular users of Facebook. However, little is known about the impact of this modern way of communication via Web-based platforms on patients with Ewing sarcoma and their social environment. The aim of this study was to analyze and compare Ewing sarcoma patients' and relatives' behavior on Facebook to draw conclusions regarding the impact of Facebook on Ewing sarcoma treatment. We examined a Facebook group named "Ewing Sarcoma Awareness" that is used to exchange information for both patients and relatives regarding Ewing sarcoma. A self-designed questionnaire was used to compare patients' and relatives' answers. Additionally, we analyzed all processes (posts, likes, threads, links) in the group for 6 consecutive months. A total of 65 members of the Facebook group (26 patients, 39 relatives) out of 2227 international group members participated in our study. More than 70% (46/65) of all participants reported that they use the group Ewing Sarcoma Awareness as a source of information about Ewing sarcoma. Of the participants, 89% (58/65) agreed on our scale from a little to a lot that being in contact with other affected people through the group makes it easier to handle the diagnosis. In this study, 20% (13/65) of all participants reported that the group affected their choice of treatment and 15% (10/65) of participants were influenced in the selection of their specialist. Regarding the recommendation of the Facebook group toward other people, significant differences (P=.003) were found comparing patients

Ewing's Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies.

Science.gov (United States)

Wolpert, Fabian; Grotzer, Michael A; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth; Bode-Lesniewska, Beata

2016-01-01

Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing's sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing's sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing's sarcoma is summarized and possible pathogenic mechanisms are critically discussed.

Patología Molecular de los sarcomas

OpenAIRE

Álava, Enrique de

2005-01-01

Los sarcomas de hueso y tejidos blandos son un grupo poco frecuente de tumores. Su prevalencia es inferior a 1 caso por 10000 habitantes, lo que los convierte en una enfermedad rara. Algunos de estos tumores, como el sarcoma sinovial, el tumor de Ewing o el osteosarcoma, son más habituales en los adolescentes o en los adultos jóvenes, mientras que existen neoplasias como el leiomiosarcoma o el liposarcoma, más frecuentes en pacientes de edad superior a los 55 años. Desde el punto de vista his...

Primary Adult Renal Ewing's Sarcoma: A Rare Entity

OpenAIRE

Ravindra Mukkunda; Ramachandran Venkitaraman; Khin Thway; Toon Min; Cyril Fisher; Alan Horwich; Ian Judson

2009-01-01

Background. Ewing's sarcoma of extraskeletal origin is uncommon and that is of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods. A retrospective review of the clinical features, treatment, and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993–December 2007 is reported. Results. Seven adult patien...

Morphoproteomic profiling of the mammalian target of rapamycin (mTOR) signaling pathway in desmoplastic small round cell tumor (EWS/WT1), Ewing's sarcoma (EWS/FLI1) and Wilms' tumor(WT1).

Science.gov (United States)

Subbiah, Vivek; Brown, Robert E; Jiang, Yunyun; Buryanek, Jamie; Hayes-Jordan, Andrea; Kurzrock, Razelle; Anderson, Pete M

2013-01-01

Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies. This pilot study assessed patients with DSRCT, Wilms' tumor and Ewing's sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls. In DSRCT the PI3K/Akt/mTOR pathway is constitutively activated by p-Akt (Ser 473) expression in the nuclear compartment of the tumor cells and p-mTOR phosphorylated on Ser 2448, suggesting mTORC2 (rictor+mTOR) as the dominant form. Ewing's sarcoma had upregulated p-Akt and p-mTOR, predominantly mTORC2. In Wilm's tumor, the mTOR pathway is also activated with most tumor cells moderately expressing p-mTOR (Ser 2448) in plasmalemmal and cytoplasmic compartments. This coincides with the constitutive activation of one of the downstream effectors of the mTORC1 signaling pathway, namely p-p70S6K (Thr 389). There was constitutive activation of the Ras/Raf/ERK pathway p-ERK 1/2 (Thr202/Tyr204) expression in the Wilms tumor and metastatic Ewing's sarcoma, but not in the DSRCT. MORPHOPROTEOMIC TUMOR ANALYSES REVEALED CONSTITUTIVE ACTIVATION OF THE MTOR PATHWAY AS EVIDENCED BY: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic

Primary Ewing's Sarcoma of the temporal bone in an infant.

Science.gov (United States)