SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Three patients with intracranial Ewing's sarcoma had neuro-ophthalmologic manifestations. In one patient, the primary tumor was in the skull and in two, it involved the long bones. Two patients complained of intermittent headache associated with bilateral, transient visual symptoms suggestive of migraine, which prompted imaging that showed occipital metastases. The third patient had an orbital syndrome.
OBJECTIVE: Within soft-tissue sarcoma, primitive neuroectodermal tumors have been shown to cover a wide spectrum of small round cell sarcomas, including Ewing's sarcomas (ES) and primitive neuroectodermal tumors (PNET). The role of the stem cell factor/kit pathway has been investigated in different human tumors especially in chronic myelocytic leukemia and gastrointestinal stromal tumor and an autocrine loop has been assumed in small cell lung carcinoma, and recently in ES and PNET. Our aim is to investigate the c-kit expression in ES and PNET and also to assessed if c-kit has any role in disease process. METHODS: 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. RESULTS: The patient's 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, localization, metastatic status, treatment modalities and tumor. Although in survival analysis, patients treated with surgery alone lived longer, while >50% of patients treated with c-kit expression lived for a shorter period. CONCLUSION: We suggest that therapy with tyrosine kinase inhibitor for PNET and ES patients may be an alternative in addition to standard therapy modalities, especially in patients non-responsive to standard therapy.
A case of extraskeletal Ewing's sarcoma presenting as a large gluteal mass is reported. This is a rare tumor with a frequently grim prognosis. Although the definitive diagnosis requires histological examination, magnetic resonance imaging is useful for determining the location of the tumor, evaluating its spread, and eliminating skeletal Ewing's sarcoma by establishing the integrity of the neighboring bone marrow. The tumor is seen on T1-weighted images as low signal with heterogeneous postgadolinium enhancement. Signal intensity on T2-weighted images is variable. In the case reported here, combination chemotherapy with external beam radiation therapy was ineffective, and the patient died 12 months after the diagnosis.
Somatic cell hybrids, obtained after fusion of translocation (11;22)-positive Ewing sarcoma cells and Chinese hamster fibroblasts, were assayed for the presence of immunoglobulin C lambda, Philadelphia chromosome breakpoint cluster region, and c-sis oncogene sequences. It was found that c-sis was translocated from chromosome 22 to chromosome 11 in the Ewing sarcoma cells used, indicating that the breakpoint must be proximal to this locus. Moreover, we found that the chromosome 22-linked C lambda and breakpoint cluster region sequences are not translocated. This result confirms an earlier cytogenetic observation that the Ewing sarcoma-associated breakpoint in chromosome 22 is distal to those observed in translocation (8;22)-positive Burkitt lymphoma and in Philadelphia chromosome-positive chronic myeloid leukemia.
The Ewing's sarcoma family of tumors (ESFT) is the second most common pediatric malignancy originating in the bone and is characterized by the t(11; 22) translocation. PAX3, a member of the paired box family of genes, is expressed during embryonal development of neural crest cells and is involved in the t(2; 13) translocation found in alveolar rhabdomyosarcoma. Since ESFTs are believed to be derived from neural crest tissue, we screened a series of Ewing's sarcoma and peripheral neuroectodermal tumor cell lines and tumor specimens for expression of PAX3. We found expression of PAX3 in most, but not all, of the specimens analyzed, including cell lines and patient material.
A case of extraskeletal Ewing's sarcoma was studied ultrastructurally, cytologically, and cytochemically. This tumor was, as in that of osseous origin, composed of densely packed highly undifferentiated blastemic cells and so-called "darker cells." The principal tumor cells were undifferentiated cells, which were characterized by the scant cytoplasm containing a variable amount of glycogen granules, large round or oval nuclei with dispersed chromatin, and rudimentary cytoplasmic junctional complexes. Some of the darker cells seemed to show somewhat histiocytic differentiation from principal blastemic cells, but the others were degenerating. Cytochemically, no tumor cells revealed the presence of peroxidase, lysozymes, and Factor VIII-related antigen. It is likely that both Ewing's sarcomas of osseous and extraosseous origin are defined as undifferentiated sarcoma merely characterized by the presence of glycogen.
In the human Ewing's sarcoma cell line WE-68, saturation analysis using 3H-labelled neuropeptide Y ([3H]NPY) as the radioligand disclosed a homogeneous population of binding sites with a dissociation constant (Kd) of 4.5 nM and maximal binding capacity (B(max)) of 712 fmol/mg cell protein. Besides the WE-68 cell line, ten other human Ewing's sarcoma cell lines (FM-62, HS-80, HT-78, HT-M1-78, NT-68, RM-82, RS-63, VH-64, WE-M1-68, WE-M2-68) were also found to display NPY receptors with Kd varying from 3.5 nM to 10.7 nM and B(max) = 247-3744 fmol/mg cell protein. NPY, its natural analogues and the Y1-receptor-specific peptide ligand [Leu31,Pro34]NPY inhibited [3H]NPY binding in the potency order: [Leu31,Pro34]NPY greater than or equal to human NPY greater than or equal to peptide YY (PYY) greater than salmon pancreatic polypeptide (PP) greater than human PP greater than porcine NPY13-36 much greater than NPY22-36. In the Ewing's sarcoma cell lines NPY provoked inhibition of forskolin-stimulated cyclic AMP formation by up to 98%. Pertussis toxin alleviated the cyclic-AMP-inhibitory response to NPY. In isolated Ewing's sarcoma plasma membranes pertussis toxin [32P]ADP-ribosylated a 41-kDa protein. The ability of NPY and analogues to inhibit cyclic AMP accumulation paralleled their potencies in displacing radioligand binding. By contrast, a cell line derived from an atypical form of Ewing's sarcoma did not express specific and functional NPY receptors. These results demonstrate that conventional Ewing's sarcoma cells possess Gi-protein-coupled NPY receptors of the Y1 type, which upon interaction with NPY, PYY, and PP mediate inhibition of cyclic AMP generation.
Two types of telomere maintenance mechanisms (TMMs) have been described in human tumors: telomerase activation and alternative lengthening of telomeres (ALT). Although the vast majority of epithelial tumors rely on telomerase activation, many mesenchymal tumors rely on ALT for telomere maintenance, but within this tumor group, the TMMs used by translocation-associated sarcomas have not been systematically studied. We studied telomere lengths and telomerase expression and activity in 30 uncultured tumor samples and in 10 cell lines of Ewing's sarcoma, a prototypical translocation-associated sarcoma, and compared the data to an identical analysis of 60 osteosarcomas, the most common type of sarcoma lacking a specific translocation. Telomerase activity was demonstrated in 21 Ewing's sarcoma tumor samples (70%) and in 9 of 10 Ewing's sarcoma cell lines. Evidence of ALT, indicated by the presence of long and heterogeneous telomeres, was observed only in the cell line without telomerase activity and in none of the 30 Ewing's sarcoma tumor samples. The 9 Ewing's sarcoma patients whose tumors lacked detectable telomerase activity did not differ significantly from the remaining patients in age, stage, EWSR1-FLI1 fusion type, prevalence of TP53 point mutations, or overall survival. The low prevalence of ALT in Ewing's sarcoma contrasted sharply with our data on TMMs in 60 osteosarcomas, which showed ALT in 38 of 60 cases (P<0.0001). The present study, together with emerging published data on other sarcoma types, suggests that a predominance of telomerase activation in the absence of ALT may characterize sarcomas with specific chromosomal translocations (such as Ewing's sarcoma), whereas a high prevalence of ALT appears typical of sarcomas with nonspecific complex karyotypes (such as osteosarcoma).
The stem cell factor/c-kit tyrosine kinase receptor pathway has been shown to be important for tumor growth and progression in several cancers, including mast cell diseases, gastrointestinal stromal tumor, acute myeloid leukemia, small cell lung carcinoma, and Ewing sarcoma. Studies using the oral agent STI-571 (Gleevec, Novartis), an inhibitor of the tyrosine kinases bcr-abl, c-kit, and PDGFR, have shown significant responses in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. With the aim of identifying additional groups of tumors that may use the stem cell factor/c-kit pathway and secondarily may be responsive to STI-571 treatment, this study surveyed 151 primary tumors from patients treated at St. Jude Children's Research Hospital for immunohistochemical expression of c-kit. Formalin-fixed, paraffin-embedded sections were stained with rabbit polyclonal anti-human c-kit (CD117, Dako) using standard avidin-biotin-peroxidase complex technique, antigen retrieval, and an automated stainer. Strong, diffuse staining for c-kit was seen in a proportion of synovial sarcomas, osteosarcomas, and Ewing sarcomas. Strong, diffuse staining was less common in neuroblastomas, Wilms' tumors, and rhabdomyosarcomas and was negative in alveolar soft part sarcomas and desmoplastic small round cell tumors. Tumors with strong, diffuse staining for c-kit in a pattern similar to gastrointestinal stromal tumor may represent suitable targets for new therapeutic agents.
Ewing's sarcoma is a distinctive clinical and pathologic entity that may be intraosseous or of soft-tissue origin. In the facial bones, the incidence of the sarcoma is estimated at 2.5% of all Ewing's sarcoma of bone. The soft tissue of the head and neck account for 11% of extraskeletal sites of the neoplasm. Combined modality treatment has modified its high-grade malignancy.
The histogenesis of Ewing's sarcoma remains unknown. Recent studies have suggested a relationship to an unusual form of childhood neural tumor, often termed peripheral neuroepithelioma or primitive neuroectodermal tumor. Five Ewing's sarcoma tumor cell lines were studied for evidence of a neural phenotype. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. Treatment with retinoic acid, an agent known to induce marked neural differentiation in neuroblastoma, had no demonstrable effect. Treatment with either cyclic AMP or TPA, in contrast, induced pronounced morphologic evidence of neural differentiation. Cells developed elongate processes with varicosities by phase-contrast microscopy; filaments, microtubules, and uraniffin-positive dense core granules were present by electron microscopy. Three neural markers (NSE, NFTP, and cholinesterase) were absent or barely detectable in untreated cells, but became abundant after treatment. These results provide convincing evidence for a neural histogenesis of Ewing's sarcoma. They also suggest a close relationship between Ewing's sarcoma and peripheral neural tumors, including the chest wall tumor described by Askin, but only a distant relationship to neuroblastoma.
The outcome of patients with Ewing Sarcoma Family of Tumors (ESFT) in our country is poor in comparison with American and European. We performed a review of the relevant data regarding the current status in the treatment of ESFT. The results of the major American and European cooperative groups were discussed, including the treatment strategies used and the prognostic factors identified for both localized and metastatic ESFT. We also discussed a new trial for the establishment of the standard treatment of ESFT in our country.
Thirty-two children were treated for metastatic Ewing sarcoma by high-dose chemotherapy followed by autologous bone marrow transplantation. Fourteen patients entered phase II studies of high-dose alkylating agents. The response rate observed was 61%. High-dose chemotherapy was used as consolidation in complete remission of 18 patients. Disease free survival appears to be better than that observed under conventional altered chemotherapy. However, with only 4/18 long term survivors, these results remain unsatisfactory, taking into account the recent encouraging results of semi-continuous conventional chemotherapy.
One of the rarest case of primary epidural neoplasm is a soft tissue sarcoma histologically similar to Ewing's sarcoma of the bone. In literature have been described only eleven cases of such extraskeletal Ewing's sarcoma. The authors report an additional case presenting as a disc protrusion in a young male. The Authors include some diagnostic, prognostic and nosologic remarks of this affection.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.