SEARCH · PubMed Health

Results for “Sarcoma, Ewing”

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.

At least 271 records · Page 15Linked to original sources

PubMed1999

Molecular characterization of the genomic breakpoint junction in a t(11;22) translocation in Ewing sarcoma.

Polymerase chain reaction (PCR)-based nucleotide sequence analysis was performed in 12 cases of Ewing sarcoma on the cDNA and/or genomic DNA breakpoint regions of a t(11;22)(q24;q12), which joins the EWS gene located on chromosome 22 with the FLI1 gene located on chromosome 11, in order to understand the molecular mechanism of this translocation. Reverse transcriptase-PCR on total tumor cell RNA from the examined cases showed five types of EWS-FLI1 chimeric product, resulting from various junctions between EWS exon 7 or 10 with FLI1 exon 5, 6, or 8. Sequencing of the genomic fusion junctions of EWS-FLI1 in seven cases showing three types of the chimeric cDNA products revealed that most of the breakpoint junctions shared common nucleotide(s) from both genes, and that the breakpoints in EWS introns 7 and 10 clustered within 100 bp and 300 bp, respectively. All the junctions were found to be flanked by various oligomers, among which a consensus sequence, 5'-AGAAAARDRR-3', was found near the breakpoints of both genes in four cases, suggesting that these oligomers may have a functional significance in the genesis of t(11;22). In addition to these oligomers, sequences highly homologous to Alu repeats and/or eukaryotic topoisomerase II cleavage sites were located near, or flanked, or even encompassed, the breakpoints in most of the cases examined. Thus, these sequences may also mediate DNA double-strand breakage and rejoining to generate the t(11;22). Genomic sequence analysis of both EWS-FLI1 and FLI1-EWS chimeric genes in three of the seven cases demonstrated a deletion and duplication of both EWS and FLI1 sequences in two cases and no gain or loss in one case. The present findings suggest that multiple mechanisms may be operative for the break and rejoining of the fragments of chromosomes 11 and 22 in the genesis of t(11;22), and that some of these translocations are asymmetric at the molecular level.

Adolescent↗

PubMed2006

Targeted therapies in Ewing's sarcoma.

Ewing's sarcoma, the second most common malignant bone tumor, is an extremely aggressive neoplasm, mainly occurring in children and adolescents. Ewing's sarcoma shows a low survival rate despite the adoption of multimodal treatments, including local control of the disease by surgery and/or radiotherapy and multidrug adjuvant chemotherapy. No new effective drugs have been recently described and proposed for sarcomas and, therefore, innovative treatment modalities are very welcome and needed. In this respect, two new entry sites for therapeutic intervention may derive from tailored therapies against the insulin-like growth factor receptor I (IGF-IR) or CD99, a cell surface transmembrane protein highly expressed in Ewing's sarcoma. Neutralizing IGF-IR functions was shown to significantly affect Ewing's sarcoma malignancy. However, it is only recently that new clinically applicable drugs targeting IGF-IR are available and represent a concrete opportunity. Engagement of CD99 induces massive apoptosis of Ewing's sarcoma cells through caspase-independent mechanisms and reduces their malignant potential. Since the apoptotic functions of this molecule are of potential clinical interest, the effects of a tailored therapy triggering CD99 were analyzed against Ewing's sarcoma local tumors and distal (lung and bone) metastases in athymic mice. The effects of targeted therapies against CD99 or IGF-IR were evaluated in combination with conventional chemotherapeutic agents to assess best drug-drug interactions and treatment schedule. Toxic effects of these tailored therapies were also considered to offer the necessary rationale for the application of possible forthcoming clinical trials.

12E7 Antigen↗

PubMed2005

Current treatment for Ewing's sarcoma.

Ewing's sarcoma is the second most common primary bone tumor seen in children and adolescents, and was described by James Ewing in 1921 as a diffuse endothelioma of bone. It is one of the differential diagnoses of pediatric small round blue cell tumors. This is not a single condition, but a group of morphologically and clinically closely related disorders with similar molecular biology -- expression of tumor-specific chimeric oncoproteins through balanced chromosomal translocations involving the EWS gene -- often referred to as the Ewing family of tumors. This includes Ewing's sarcoma of bone, extra-osseous Ewing's sarcoma, Askin tumor and peripheral neuroectodermal tumor. These are aggressive neoplasms with almost 25% of patients having clinically evident metastases at presentation. Ewing's sarcoma has therefore been considered as a systemic disease necessitating local as well as systemic treatment. An aggressive multidisciplinary approach has resulted in significant improvement in prognosis for patients with these tumors. Despite aggressive treatment, 20-40% of patients with localized disease and almost 80% of patients with metastatic disease at presentation succumb to the illness. Advances in understanding the molecular biology of these tumors will hopefully result in the development of novel treatment approaches. The aim of this article is to review the existing treatment methods and to highlight the more recent approaches to the treatment of this condition.

Adolescent↗

PubMed1981

Control of a human tumour (Ewing sarcoma) in mice by a single lethal dose of dimethyl-myleran and bone marrow.

A Ewing sarcoma grown in immunosuppressed mice was eradicated with a single lethal dose of dimethylmyleran (DMM) followed by autologous or syngeneic bone marrow. Sarcomas treated 2 weeks after grafting in a phase of rapid proliferation disappeared and large sarcomas treated after 6 or 10 weeks were reduced to necrotic tissue. A human osteosarcoma also regressed distinctly after this therapy while a human colon carcinoma responded poorly. Sub-lethal DMM treatment induced complete remissions in only 62% of the mice. Tumours which display sensitivity in this model may be treated clinically with lethal doses of DMM and autologous marrow transplantations.

Animals↗

PubMed2003

Multimodal therapy for the treatment of nonmetastatic Ewing sarcoma of pelvis.

The purpose of this study was to evaluate the outcome of patients with Ewing sarcoma (ES) of the pelvis, attempting to identify prognostic factors to select patients for more aggressive treatment. Seventy-seven patients with nonmetastatic ES of the pelvis were treated at Rizzoli Institute between 1979 and 1996. Four different protocols of chemotherapy were used successively. Two protocols consisted of VACAc, and two of VACAc plus ifosfamide and etoposide. Local treatment consisted of surgery in 5 patients, radiotherapy in 60, and surgery followed by radiotherapy in 12. Mean follow-up was 11 years (range 5-25 years). Thirty-three patients remained continuously free of disease; 43 relapsed (24 due to metastases and 19 to local recurrence and metastases); 1 died of treatment-related complications. The 5- and 10-year event-free survival rates were 45% and 44%, respectively, and the 5- and 10-year overall survival rates were 48 and 44. These results are significantly worse than the ones achieved in 329 contemporary patients with extrapelvic lesions treated with the same protocols of chemotherapy (5- and 10-year event-free survival = 46% vs. 64% and 44% vs. 69%). Thus, despite associated chemotherapy, the outcome of ES localized in the pelvis remains poor, and new innovative methods for the treatment of this tumor are needed.

Adolescent↗

PubMed2007

Concurrent Ewing sarcoma family of tumors and fibrous dysplasia: possible diagnostic pitfall.

We present 2 patients with synchronous Ewing sarcoma family of tumors (ESFTs) and fibro-osseous lesion in the independent sites, possibly causing misjudgment in staging. Each patient showed another activity apart from the primary ESFT lesion on gallium and/or thallium scintigraphy at initial presentation. Of note is that such lesions showed no obvious radiologic change even though the primary ESFT lesions were mildly shrunken during chemotherapy. The biopsies confirmed fibrous dysplasia (FD) in the first patient and fibro-osseous lesion, possibly FD in the second patient. As far as we know, concurrent ESFT and FD in independent sites have never been described. However, this unusual combination emphasized the possibility of concurrent FD mimicking metastasis in a patient with malignancy and the view that exploratory biopsy should be performed in a critical case to make staging. Further investigation will be required about whether the co-occurrence of ESFD and FD in our patients is coincidence or genetic linkage.

Adolescent↗

PubMed2005

[18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors.

PURPOSE: Response to neoadjuvant chemotherapy is a significant prognostic factor for the Ewing sarcoma family of tumors (ESFTs). [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that accurately predicts histopathologic response in several malignancies. To determine the prognostic value of FDG PET response for progression-free survival (PFS) in ESFTs, we reviewed the University of Washington Medical Center experience. PATIENTS AND METHODS: Thirty-six patients with ESFTs were evaluated by FDG PET. All patients received neoadjuvant and adjuvant chemotherapy. FDG PET standard uptake values before (SUV1) and after (SUV2) chemotherapy were analyzed and correlated with chemotherapy response, as assessed by histopathology in surgically excised tumors. Thirty-four patients had both SUV1 and SUV2. RESULTS: The mean SUV1, SUV2, and ratio of SUV2 to SUV1 (SUV2:1) were 7.9 (range, 2.3 to 32.8), 2.1 (range, 0 to 4.3), and 0.36 (range, 0.00 to 1.00), respectively. Good FDG PET response was defined as SUV2 less than 2.5 or SUV2:1 < or = 0.5. FDG PET response by SUV2 or SUV2:1 was concordant with histologic response in 68% and 69% of patients, respectively. SUV2 was associated with outcome (4-year PFS 72% for SUV2 < 2.5 v 27% for SUV2 > or = 2.5, P = .01 for all patients; 80% for SUV2 < 2.5 v 33% for SUV2 > or = 2.5, P = .036 for localized at diagnosis patients). SUV2:1 < or = 0.5 was not predictive of PFS. CONCLUSION: FDG PET imaging of ESFTs correlates with histologic response to neoadjuvant chemotherapy. SUV2 less than 2.5 is predictive of PFS independent of initial disease stage.

Adolescent↗

PubMed2001

Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor.

PURPOSE: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT). MATERIALS AND METHODS: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures. RESULTS: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow. CONCLUSIONS: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow-up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone.

Biomarkers, Tumor↗

PubMed2024

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.

Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer driven by the fusion transcription factor EWS::FLI1. We integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis. Subsequent genomic profiling and high-resolution chromatin interaction data from Capture Hi-C indicated that cohesin-STAG2 facilitates communication between EWS::FLI1-bound long GGAA repeats, presumably acting as neoenhancers, and their target promoters. Changes in CTCF-dependent chromatin contacts involving signature genes, unrelated to EWS::FLI1 binding, were also identified. STAG1 is unable to compensate for STAG2 loss and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, likely affecting DNA looping dynamics. These results illuminate how STAG2 loss modifies the chromatin interactome of Ewing sarcoma cells and provide a list of potential biomarkers and therapeutic targets.

Sarcoma, Ewing↗

PubMed1993

Ewing's sarcoma.

Ewing's sarcoma is a highly malignant tumor of uncertain origin. A strong relationship is suggested between Ewing's sarcoma and tumors of neural origin. The radiologic manifestation of Ewing's sarcoma are protean and lesions may be lytic, mixed lytic-sclerotic, or rarely, predominantly sclerotic. The lower extremity long bones are predominantly affected and most lesions are diaphyseal or metadiaphyseal. CT and particularly MR imaging are invaluable in further delineating the extent of disease not readily manifested on plain radiographs. Gallium scintigraphy and gadolinium-enhanced MR images are best for following the response to therapy. Ewing's sarcoma must be distinguished from other round cell tumors including lymphoma, neuroblastoma, and primitive neuroectodermal tumor of bone as well as from osteosarcoma.

Bone Neoplasms↗

PubMed2005

Philadelphia chromosome-positive acute lymphoblastic leukemia secondary to chemoradiotherapy for Ewing sarcoma. Report of two cases and concise review of the literature.

Survivors of childhood solid tumors including Ewing sarcoma (ES) have an increased risk of secondary malignant neoplasms (SMNs) as a consequence of exposure to chemotherapy and/or radiation (see: Bhatia S, Sklar C. Nat Rev Cancer 2002;2:124-132). The most common hematologic SMNs are myelodysplasia (MDS) and acute myelogenous leukemia (AML). Acute lymphoblastic leukemia (ALL) is uncommon in this patient population, and Philadelphia chromosome positive (Ph+) ALL in particular, is rare. We report herein two cases of young adult patients who were both diagnosed with Ph+ ALL 19 years after successful treatment for ES with combined modality therapy. A review of the relevant literature follows the case reports.

Adult↗

PubMed1984

Spinal Ewing sarcoma: misleading appearances.

The plain radiographic and computed tomographic (CT) findings in two unusual cases of spinal Ewing sarcoma are reported. Radiographic features resembling neuroblastoma in one case and aneurysmal bone cyst in the other were present. These findings may be misleading and distinguishing characteristics in each case are discussed.

Aneurysm↗

PubMed1988

The role of magnetic resonance imaging in the evaluation of Ewing sarcoma. A report of 27 cases.

The experience with magnetic resonance imaging (MRI) in 27 patients with Ewing sarcoma is reported and compared with computed tomography (CT) and plain films. Plain radiography proved to be the best imaging method to asses probable histological diagnosis in all cases (n = 6). For the evaluation of chemotherapeutic response (n = 4), CT and MRI gave the same information about the variation in size of the tumor. In this small series, the high signal in T2 weighted images was not altered significantly by therapy. In preoperative evaluation (n = 14), MRI gave better information than CT of soft tissue involvement and extension within the bone marrow in two cases each. The ability of MRI to accurately define extension through the epiphyseal plate in two cases permitted limb salvage which otherwise would not have been possible. In the long-term follow-up (n = 12), three patients without recurrence one year after therapy showed a low signal in the surgical area in T2 weighted images. Nine patients had a high signal in T2 weighted images: four were reactive lesions, two had obvious recurrence, and one was a hematoma. In the two remaining cases plain films and CT were normal, in the presence of both active tumor and reactive lesions. It was not possible with MRI to differentiate active tumor from reactive change, even after Gd-DTPA infusion.

Adolescent↗

PubMed2003

Detection of a novel reciprocal t(16;22)(q11.2;q12) in a Ewing sarcoma.

Several structural and numerical chromosomal abnormalities have been identified as primary and secondary chromosomal aberrations in Ewing sarcoma (ES). The majority of these are t(11;22) and trisomies, especially of chromosome 8. Specific chromosomal abnormalities often correlate with particular morphologic or phenotypic subtypes of tumor and play an important role in prognosis. The objective of this report is the cytogenetic evaluation of a case of ES using G-banding, fluorescence in situ hybridization, and spectral karyotyping techniques. Multiple chromosomal aberrations were identified including a novel reciprocal t(16;22)(q11.2;q12).

Adult↗

PubMed1996

In vitro proliferative advantage of bone marrow cells with tetrasomy 8 in Ewing sarcoma.

We describe a case of a 14.5-year-old boy with a clinically aggressive pelvic Ewing sarcoma. The tumor cells showed the presence of a typical t(11;22)(q24;q12) aberration and gains of chromosomes 8, 10, 14, and 21. To determine the size of the trisomy and tetrasomy 8 clones an interphase analysis by fluorescence in situ hybridization with a centromere-specific chromosome 8 probe was performed. Significant quantitative differences between metaphase and interphase data were obtained. It was shown that culturing of bone marrow cells leads to enrichment of tetrasomy 8 population that may be explained by the proliferative advantage of the tetrasomy 8 cells.

Adolescent↗

PubMed1979

[Contribution to combined therapy of the Ewing-sarcoma (author's transl)].

The techniques and results from the treatment of 15 own cases with Ewing-sarcoma having undergone different therapeutic schemes are reviewed with the help of universal literature. These tumors are shown to need individual treatment which has to be adapted to the present data in each case.

Adolescent↗

PubMedDate not supplied

Ewing sarcoma of the skull with an unusual pattern of reactive sclerosis: MR characteristics.

A case of primary Ewing sarcoma involving the occipital bone with an unusual radiographic feature--markedly thickened bone--is described. Magnetic resonance imaging was more helpful than CT in determining the lesion extent due to lack of bone artifact and since it showed the precise relationship of the neoplasm to the tentorium on direct coronal imaging.

Adolescent↗

PubMed1982

The radiographic follow-up of patients with Ewing sarcoma: a demonstration of a general method.

An analysis of the patterns of detectable tumor recurrence using the concepts of hazard rate, predictive value, and cumulative probability was undertaken to assess the appearance of metastases in Ewing sarcoma. This study comprises 107 patients who were seen between 1964 and 1977. The distribution of the sites of metastases indicates that repeated examinations of both lungs and bones are necessary for the effective surveillance of both truncal and extremity primary lesions. The hazard rates for metastases suggest that these serial examinations should be concentrated early in the follow-up period for truncal primaries and more uniformly distributed for extremity primaries. The method used is general and is applicable to any disease for which the surveillance for recurrence or a complication is of major concern. The results of the analysis may be used in the selection and scheduling of follow-up examinations for patients with Ewing sarcoma, and in advising the patient of the prognosis for continued remission.

Bone Neoplasms↗