WorldWideScience

Sample records for sarcoma ewings

  1. 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- ...

  2. 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.

  3. 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)

  4. 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 ...

  5. 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 ...

  6. 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 ...

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Therapy of Ewing's sarcoma

    International Nuclear Information System (INIS)

    Dunst, J.; Sauer, R.

    1993-01-01

    Therapy of Ewing's sarcoma requires a qualified clinical, radiological, and pathohistological diagnosis and, in particular, an optimal therapy by an experienced team of oncological specialists. Important prognostic factors are the presence of hematogenous metastases at diagnosis, the initial tumor volume, the response to chemotherapy, and adequate local therapy. Presently, cure rates of more than 60% can be achieved for localized Ewing's sarcoma by combination of local therapy and chemotherapy. The four-drug combination VACA (vincristin, actinomycin D, cyclophosphamide, adriamycin) can be considered as cytostatic gold standard. More aggressive regimens (VAIA, EVAIA, autologous bone marrow transplant) may be beneficial in subgroups and are under investigation. Concerning local therapy adequate radiotherapy plays a major role and achieves the same survival rates as radical surgery, comparable patient selection provided. Several factors have impact on radiotherapeutic results, especially total dose (45 Gy large volume, 55 Gy to the primary tumor), target volume (safety margin at least 2 cm according to the pretreatment volume, at least 5 cm in proximal and distal extension of long bones), timing of radiotherapy (as early as possible) and quality of treatment. Radiotherapy as sole local treatment is indicated in inoperable lesions (spine, sacrum, skull) and in small, good-responding tumors. High-risk patients should receive combined radiotherapeutic-surgical treatment, preferably as pre-operative irradiation. The value of hyperfractionation is not yet proven despite theoretical advantages. (orig.) [de

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.)

  3. Ewing's Sarcoma and Second Malignancies

    Directory of Open Access Journals (Sweden)

    Joshua D. Schiffman

    2011-01-01

    Full Text Available Ewing's sarcoma (ES is a rare tumor that is most common in children and young adults. Late effects of ES therapy include second cancers, a tragic outcome for survivors of such a young age. This paper will explore the frequencies and types of malignancies that occur after ES. Additionally, it will review how second malignancies have changed with the shift in treatment from high-dose radiation to chemotherapy regimens including alkylators and epipodophyllotoxins. The risk of additional cancers in ES survivors will also be compared to survivors of other childhood cancers. Finally, the possible genetic contribution to ES and second malignancies will be discussed.

  4. 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.

  5. 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

  6. 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.

  7. Ewing Sarcoma: An Eponym Window to History

    Directory of Open Access Journals (Sweden)

    Timothy P. Cripe

    2011-01-01

    Full Text Available Ewing sarcoma was named after James R. Ewing, an eminent American pathologist at Cornell who described the first cases in 1921. Although he is best remembered for this singular achievement, Ewing's contributions to the study of cancer were far more profound and influential. He essentially launched oncology as a discipline with the publication of his seminal textbook and founded the major American cancer societies that exist today. His vision of comprehensive cancer centers still drives our research infrastructure. Since his initial report, these organizations have helped us achieve numerous milestones in understanding and treating patients with Ewing sarcoma.

  8. 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.

  9. 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...

  10. 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.

  11. Targeted Therapy of Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Vivek Subbiah

    2011-01-01

    Full Text Available Refractory and/or recurrent Ewing's sarcoma (EWS remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22 translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Diagnosis and treatment of Ewing's sarcoma

    International Nuclear Information System (INIS)

    Iwamoto, Yukihide

    2007-01-01

    Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, primitive neuroectodermal tumors and Askin's tumors. Therefore, these lesions have become regarded as a single entity, dubbed the Ewing's family of tumors. Reverse transcription polymerase chain reaction (RT-PCR) to detect EWS-ETS gene arrangements is widely used to confirm the diagnosis of Ewing's family of tumors. Experimental results suggest that inhibition of the signaling pathway downstream of the EWS-ETS gene may lead to the development of molecularly targeted therapy in the future. (author)

  17. Ewing's sarcoma presenting as a solitary cyst

    International Nuclear Information System (INIS)

    Hammoud, S.; Frassica, F.J.; McCarthy, E.F.

    2006-01-01

    This case describes a 10-year-old girl who developed a Ewing's sarcoma in her proximal fibula. The radiologic features mimicked those of a unicameral bone cyst. The presence of pain and the atypical location led to a prompt biopsy and the correct diagnosis. The mechanism of this unusual radiographic presentation is discussed. (orig.)

  18. Extraosseous Ewing's sarcoma: review of a case

    International Nuclear Information System (INIS)

    Quevedo Moreno, P.; Hernandez Moreno, L.; Perez Diaz, M.; Lafuente Martinez, J.L.; Arozamena Laso, M.

    1994-01-01

    Extraosseous Ewing's sarcoma (EES) is an uncommon lesion included in the group of soft tissue tumors. We present a case in a 19-year-old woman in which the diagnosis was not initially suspected because of the absence of clinical and radiological evidence. (Author)

  19. 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

  20. 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

  1. 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.

  2. 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

  3. EXTRA-OSSEOUS EWING SARCOMA

    NARCIS (Netherlands)

    van den Berg, Hendrik; Heinen, Richard C.; van der Pal, Heleen J.; Merks, Johannes H. M.

    2009-01-01

    Background: Clinical data and data on outcome of extra-osseous Ewing tumors are scarce. Procedure: After a search for Ewing tumors in the database of a single institution over a period of 20 years, 16 out of 192 cases were found to have extra-osseous primary tumors. Results: Ages at initial

  4. 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)

  5. Evaluation of therapeutic results in Ewing's sarcoma

    International Nuclear Information System (INIS)

    Johnson, R.E.; Pomeroy, T.C.

    1975-01-01

    The philosophy pervading the treatment approach to Ewing's sarcoma was to have therapy encompass all foci of disease, including sites of occult or potential involvement in addition to obvious clinical manifestations. The experience with integrated methods of treatment in 66 consecutive patients at the National Cancer Institute is reviewed. A median survival of 18 months (44 percent 2 year survival rate) for patients with recognizable metastases on admission bears impressive witness to the value of adjuvant therapy in Ewing's sarcoma. Even more encouraging, an uncorrected 5 year survival rate of 53 percent (42 percent continuously free of disease) for patients given ''pyrophylactic'', adjuvant therapy indicates the potential for permanent control of disease in a significant fraction of cases with clinically localized primary tumors. (U.S.)

  6. 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

  7. An Unusual Location of Extraosseous Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Lisanne Geens

    2013-05-01

    Full Text Available Ewing's sarcoma (ES is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen.

  8. Ewing's sarcoma of the tarsal bone

    International Nuclear Information System (INIS)

    Kwon, Jung Hyeok; Kim, Yong Sun; Kim, Tae Hun; Park, In Kyu; Kim, Yong Joo; Kang, Duk Sik; Sohn, Kyung Rak

    1985-01-01

    The Ewing's sarcoma comprises approximately less than 10 percent of malignant bone tumors and 5 percent of all bone tumors, occurs in almost all bones of the body, and presents a widely divergent roentgenographic manifestations. The tarsal bones are involved only 2 percent in the Ewing's sarcoma. Two cases experienced by authors and ten cases published in literatures of Ewing's sarcoma of the tarsal bone were analyzed retrospectively. The result were as follows: 1. Of the tarsal bones, the calcaneus was 7 cases, the talus 4 cases, cuneiform 1 case. 2. Female was affected more commonly than male, the ratio being 4 to 1 in the tarsal bones. 3. About sixty percent of total cases in the tarsal bones had evidence of diffuse sclerotic pattern. All the cases of the talus had evidence of diffuse sclerotic pattern. 4. The diseases to be considered in differential diagnosis are as follows: avascular necrosis, tuberculous osteomyelitis, osteosarcoma, and pyogenic osteomyelitis. 5. The diffuse sclerosis radiographically showed a close relation with dead bone resulting from avascular necrosis due to tumor infiltration histologically. Periosteal reactive new bone and osteoid deposition on the dead bone were also correlated with diffuse sclerosis. 6. Because it is difficult to differentiate sclerotic lesions in the tarsal bones by radiographic methods alone, all such lesions should be subject to biopsy as early as possible

  9. Ewing's sarcoma of the tarsal bone

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jung Hyeok; Kim, Yong Sun; Kim, Tae Hun; Park, In Kyu; Kim, Yong Joo; Kang, Duk Sik; Sohn, Kyung Rak [College of Medicine, Kyungpook National University, Daegu (Korea, Republic of)

    1985-06-15

    The Ewing's sarcoma comprises approximately less than 10 percent of malignant bone tumors and 5 percent of all bone tumors, occurs in almost all bones of the body, and presents a widely divergent roentgenographic manifestations. The tarsal bones are involved only 2 percent in the Ewing's sarcoma. Two cases experienced by authors and ten cases published in literatures of Ewing's sarcoma of the tarsal bone were analyzed retrospectively. The result were as follows: 1. Of the tarsal bones, the calcaneus was 7 cases, the talus 4 cases, cuneiform 1 case. 2. Female was affected more commonly than male, the ratio being 4 to 1 in the tarsal bones. 3. About sixty percent of total cases in the tarsal bones had evidence of diffuse sclerotic pattern. All the cases of the talus had evidence of diffuse sclerotic pattern. 4. The diseases to be considered in differential diagnosis are as follows: avascular necrosis, tuberculous osteomyelitis, osteosarcoma, and pyogenic osteomyelitis. 5. The diffuse sclerosis radiographically showed a close relation with dead bone resulting from avascular necrosis due to tumor infiltration histologically. Periosteal reactive new bone and osteoid deposition on the dead bone were also correlated with diffuse sclerosis. 6. Because it is difficult to differentiate sclerotic lesions in the tarsal bones by radiographic methods alone, all such lesions should be subject to biopsy as early as possible.

  10. [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.

  11. 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.

  12. 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

  13. 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

  14. 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)

  15. 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

  16. 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...

  17. 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.

  18. 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

  19. Ewing sarcoma of the foot. Radiological findings

    International Nuclear Information System (INIS)

    Albisinni, U.; Capanna, R.; Nigrisoli, M.

    1987-01-01

    Ewing's Sarcoma (ES) is the most frequent malignant bone tumor of the foot. The radiological picture is characterized, in 14 patients, by a pure osteolytic lesion (9 cases) or by a mixed one (5 cases); the interruption of the cortical bone and swelling of the soft tissues were always present; the periostal reaction was occasional. The radiological aspects cannot be considered typical of the ES and it is suggested that biopsies should always be performed in the presence of structural alteration of the bone

  20. 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.

  1. 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

  2. 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.)

  3. Radiotherapy in complex management of Ewing sarcoma

    International Nuclear Information System (INIS)

    Ruseva, Tz.; Marinova, L.; Hristozova, I.; Sokolov, T.

    1996-01-01

    Over the period 1981-1995, 32 patients with non-metastatic Ewing sarcoma, aged 2 to 22 years, underwent treatment and follow-up study. A locally advanced tumor is found in 85% of patients. Complex radio- and chemotherapy is carried out in all patients, and additional radical surgery - in eight. 60 Co-radiotherapy with gradual radiation field reduction is applied, applying a local dose of 60 - 64 Gy in the tumor area. Chemotherapy is performed according to the VACA protocol. Local tumor control is achieved in all patients with primary tumor located in long bones, and only in 1 of 5 patients with pelvic localization. The overall survival established is as follows: 1 year survival - 100 %, 2 years - 50 %, 3 years - 40 % and 5 years - 34 %. Local recurrence is recorded in 2 cases (6.2%). The distant metastases observed involve the lungs (13), bones (4), lung and bones (2) and soft tissues (3). The Ewing sarcoma is sensible to chemo- and radiotherapy, but the conventional methods do not improve survival. Based on the analysis of the clinical results, emphasis is laid on the necessity of complex treatment with a special reference to alternative therapeutic approaches. 13 refs., 4 figs., 2 tabs

  4. 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...

  5. 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.

  6. 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)

  7. 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...

  8. Extra-skeletal Ewing's sarcoma of the nasal fossa.

    Science.gov (United States)

    Lane, S; Ironside, J W

    1990-07-01

    Extraskeletal Ewing's sarcoma is rarely found arising in the head and neck region. An unusual case arising in the nasal fossa in a young child is reported and the differential diagnosis, pathology and treatment discussed.

  9. 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.

  10. 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.)

  11. 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.

  12. 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.

  13. 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

  14. Sacral Ewing's Sarcoma and Challenges in it's Diagnosis on MRI

    Directory of Open Access Journals (Sweden)

    Albert D'Souza

    2009-01-01

    Full Text Available A 15-yr old boy presented with low backache for 4 months associated with weakness of left lower limb. MRI of lumbosacral spine showed a sacral lesion with intraspinal and presacral soft tissue extension with neural compression. A diagnosis of tuberculosis was considered in the view of high prevalence in this part of the world, however biopsy revealed Ewing's sarcoma. Ewing's tumor of sacrum is rare, but should be suspected in low backache in children. Differential diagnosis for a sacral lesion includes tuberculosis, pyogenic osteomyelitis, lymphoma, chordoma, osteosarcoma and Ewing's sarcoma. MRI is sensitive in detecting these lesions but is nonspecific requiring histopathological examination for confirmation.

  15. 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...

  16. 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.

  17. Primary Disseminated Multifocal Ewing Sarcoma: Results of the Euro-EWING 99 Trial

    NARCIS (Netherlands)

    Ladenstein, Ruth; Pötschger, Ulrike; Le Deley, Marie Cécile; Whelan, Jeremy; Paulussen, Michael; Oberlin, Odile; van den Berg, Henk; Dirksen, Uta; Hjorth, Lars; Michon, Jean; Lewis, Ian; Craft, Alan; Jürgens, Heribert

    2010-01-01

    Purpose To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept. Patients and Methods From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to

  18. 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 ...

  19. 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

  20. 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.

  1. 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.

  2. 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.)

  3. 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.

  4. [Ewing sarcoma located in the mandible: A case report].

    Science.gov (United States)

    Hernandez, M; Droz, D; Mansuy, L; Simon, E; Chastagner, P

    2015-06-01

    Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. Clinical presentation is usually dominated by local pain and a palpable mass. These symptoms justify imaging investigations: the first one, when an osseous lesion is suspected, is usually a conventional radiograph in two planes. Ewing sarcoma appears as a poorly defined osteolytic lesion that may frequently be associated with cortical erosion or laminar periosteal response ("onion skin"). However, this aspect is not pathognomonic and the definitive diagnosis is made by biopsy. Absence of pain or an unusual localization can lead to misdiagnosis. We report the case of a 7-year-old boy with Ewing sarcoma located in the mandible with a clinical picture including progressive mandibular swelling but no pain. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. 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

  6. 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.)

  7. Primary Adult Renal Ewing's Sarcoma: A Rare Entity

    Science.gov (United States)

    Mukkunda, Ravindra; Venkitaraman, Ramachandran; Thway, Khin; Min, Toon; Fisher, Cyril; Horwich, Alan; Judson, Ian

    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 patients with primary renal Ewing's sarcoma were identified. All four patients with nonmetastatic disease had radical nephrectomy and received adjuvant chemotherapy +/− radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease-free survival in patients with nonmetastatic disease after combined modality treatment was 30.3 months. Conclusion. Primary adult renal Ewing's sarcoma is an aggressive tumor with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival. PMID:19478963

  8. Primary Adult Renal Ewing's Sarcoma: A Rare Entity

    Directory of Open Access Journals (Sweden)

    Ravindra Mukkunda

    2009-01-01

    Full Text Available 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 patients with primary renal Ewing's sarcoma were identified. All four patients with nonmetastatic disease had radical nephrectomy and received adjuvant chemotherapy +/− radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease-free survival in patients with nonmetastatic disease after combined modality treatment was 30.3 months. Conclusion. Primary adult renal Ewing's sarcoma is an aggressive tumor with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival.

  9. 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

  10. 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.

  11. 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...

  12. An Unusual Cause of Urinary Incontinence: Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Serhan Kupeli

    2015-03-01

    Full Text Available Urinary incontinence in children can be originated mostly from urinary tract infections, but constipation, neurologic disorders, obstruction and tumors can also be considered among other causes. Pelvic tumors may present with back pain, bladder or bowel dysfunction. Ewing's sarcoma is among the small round-cell tumors of the childhood and potentially can arise from any part of the body. Here, we report an 11-year-old male presented with urinary incontinence and diagnosed as Ewing's sarcoma after 6 weeks' delay. Clinicians should suspect from pelvic tumors in the presence of urinary incontinence especially associated with low back pain. [Cukurova Med J 2015; 40(Suppl 1: 94-96

  13. 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....

  14. [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.

  15. Ewing's Sarcoma of the Peritoneum: a Rare Location for Extraskeletal Ewing's Sarcoma.

    Science.gov (United States)

    Saglam, Muzaffer; Ozdemir, Yavuz; Yigit, Taner; Kucukodaci, Zafer; Sonmez, Guner

    2016-11-01

    A 38-year-old male presented to the emergency department with abdominal pain and bulge. He had a history of irritable bowel syndrome for 1 year with complaint of dyspepsia. Physical examination revealed a distended abdomen with a huge palpable mass located in the paraumblical region. Laboratory findings revealed a high white blood cell count with neutrophil predominance. Contrast-enhanced computed tomography (CT) showed a 23-cm, oval-shaped, grossly necrotic, low-attenuation mass with peripherally located dominant vessels. Magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) suggested a highly malignant tumor with prominent diffusion restriction especially at the periphery of the mass. On surgery, macroscopic examination showed a macrolobulated, hypervascular, reddish brown mass attached to the parietal peritoneum with a stalk. Ewing's sarcoma (ES) was diagnosed on histopathological examination with small round cells.

  16. Sarcoma de Ewing en paciente masculino Ewing's sarcoma in a male patient

    Directory of Open Access Journals (Sweden)

    Eddy Millán Escalona

    2010-09-01

    Full Text Available El sarcoma de Ewing es un tumor óseo maligno de células redondas pequeñas. Es el segundo tumor óseo maligno más frecuente en la infancia, y se puede presentar en cualquier momento durante la niñez y comienzos de la edad adulta. El tumor puede originarse en cualquier parte del cuerpo, generalmente en los huesos largos de las extremidades, la pelvis o el tórax, al igual que en el cráneo o en los huesos planos del tronco. Se trata de un paciente masculino, mestizo, de 38 años de edad, que acude a consulta externa en el hospital de Nickerie, Suriname, por presentar aumento de volumen en la región lateral derecha del abdomen. Refiere que ha presentado pérdida de peso, decaimiento marcado y anorexia. Estos síntomas se iniciaron 3 meses antes, y se han incrementado paulatina y progresivamente. Tiene también dificultad para deambular y dolor en la pierna derecha.The Ewing's sarcoma is a malignant bone tumor of round cells. The second malignant bone tumor more frequent in childhood and may to appear in any moment during this life stage and at onset of adulthood. Tumor may to originate in any place of body, generally in limbs long bones, pelvis or thorax as well as in skull or in trunk flat bones. This case is a black male patient aged 38 seen in external consultation in the hospital of Nickerie, Surinam presenting with a volume increase in the right lateral region of abdomen. He refers a weight loss, a marked weakness and anorexia. These symptoms appeared three months before increasing in a gradual and progressively way. He has difficulty to walk and pain in the right leg.

  17. 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.

  18. 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

  19. 18F-FLT Positron Emission Tomography and Diffusion-Weighted Magnetic Resonance Imaging in Planning Surgery and Radiation Therapy and Measuring Response in Patients With Newly Diagnosed Ewing Sarcoma

    Science.gov (United States)

    2017-11-16

    Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

  20. Recurrence of Ewing Sarcomas of the Chest Wall

    NARCIS (Netherlands)

    Meys, Karlijn M. E.; Heinen, Richard C.; van den Berg, Henk; Aronson, Daniel C.

    2008-01-01

    Background. Ewing sarcomas (ES) of the chest wall are rare. Local recurrences occur in approximately 20% of these patients; however literature on this topic is scarce. Our aim was to analyze the influence of the extent of surgical resection on outcome, and to find positive prognostic factors for

  1. Ewing's sarcoma presenting as a solitary cyst

    Energy Technology Data Exchange (ETDEWEB)

    Hammoud, S. [Johns Hopkins University, School of Medicine, Baltimore, MD (United States); Johns Hopkins Outpatient Center, School of Medicine, Department of Orthopaedic Surgery, Baltimore, MD (United States); Frassica, F.J. [Johns Hopkins Outpatient Center, School of Medicine, Department of Orthopaedic Surgery, Baltimore, MD (United States); McCarthy, E.F. [Johns Hopkins Outpatient Center, School of Medicine, Department of Orthopaedic Surgery, Baltimore, MD (United States); Department of Pathology, Division of Surgical Pathology, Baltimore, MD (United States)

    2006-07-15

    This case describes a 10-year-old girl who developed a Ewing's sarcoma in her proximal fibula. The radiologic features mimicked those of a unicameral bone cyst. The presence of pain and the atypical location led to a prompt biopsy and the correct diagnosis. The mechanism of this unusual radiographic presentation is discussed. (orig.)

  2. 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.

  3. Primary Ewing's Sarcoma of the temporal bone in an infant.

    Science.gov (United States)

    Goudarzipour, Kourosh; Shamsian, Shahin; Alavi, Samin; Nourbakhsh, Kazem; Aghakhani, Roxana; Eydian, Zahra; Arzanian, Mohammad Taghi

    2015-04-01

    Introduction : Ewing's sarcoma is the second most common primary malignant tumor of bone found in children after Osteosarcoma. It accounts for 4-9% of primary malignant bone tumors and it affects bones of the skull or face in only 1-4% of cases. Hence it rarely affects the head and neck. Subject and Method : In this case report, we describe a case of primary Ewing's sarcoma occurring in the temporal bone. The tumor was surgically excised, and the patient underwent chemotherapy for ten months. Results : Neither recurrence nor distant metastasis was noted in these 10 months after surgery but about 18 months after surgery our patient was expired. Conclusion : Although the prognosis of Ewing's sarcoma is generally poor because of early metastasis to the lungs and to other bones, a review of the article suggested that Ewing's sarcoma occurring in the skull can often be successfully managed by intensive therapy with radical excision and chemotherapy. This result was supported by the case reported here.

  4. 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

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Smita Srivastava

    2016-01-01

    Full Text Available Extraskeletal Ewing's sarcoma (EES is a rare soft tissue tumor that is morphologically indistinguishable from skeletal ES. We report a case of a 25-year-old female with recurrent EES/primitive neuroectodermal tumor of right breast with imaging findings on mammogram, ultrasound, magnetic resonance imaging breast, and positron emission tomography–computed tomography.

  8. Survival of patients with Ewing's sarcoma in Yazd-Iran.

    Science.gov (United States)

    Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

    2014-01-01

    The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

  9. 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

  10. Computed Tomography and Magnetic Resonance Features of Renal Ewing Sarcoma

    International Nuclear Information System (INIS)

    Ekram, T.; Elsayes, K.M.; Cohan, R.H.; Francis, I.R.

    2008-01-01

    Ewing sarcoma (ES) is a rare malignant tumor that primarily involves long and flat bones but can develop in almost any bone or soft tissue. ES accounts for 2.3-3.5% of tumors in patients under the age of 19, and is rarely found in the adult population. Sarcomas, in general, account for less than 1% of tumors in adults. Several reports of renal ES have been described in the pediatric population, but only a few cases have been described in the adult population. To the best of our knowledge, fewer than 10 cases of renal Ewing sarcoma in adults have been described in the English literature. None of these cases described the computed tomography (CT) and magnetic resonance imaging (MRI) features. We report a case of a 46-year-old woman, including CT and MRI characteristics

  11. 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...

  12. FOXM1 is an oncogenic mediator in Ewing Sarcoma.

    Directory of Open Access Journals (Sweden)

    Laura Christensen

    Full Text Available Ewing Family Tumors (Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor are common bone and soft tissue malignancies of childhood, adolescence and young adulthood. Chromosomal translocation in these tumors produces fusion oncogenes of the EWS/ETS class, with EWS/FLI1 being by far the most common. EWS/ETS chimera are the only well established driver mutations in these tumors and they function as aberrant transcription factors. Understanding the downstream genes whose expression is modified has been a central approach to the study of these tumors. FOXM1 is a proliferation associated transcription factor which has increasingly been found to play a role in the pathogenesis of a wide range of human cancers. Here we demonstrate that FOXM1 is expressed in Ewing primary tumors and cell lines. Reduction in FOXM1 expression in Ewing cell lines results in diminished potential for anchorage independent growth. FOXM1 expression is enhanced by EWS/FLI1, though, unlike other tumor systems, it is not driven by expression of the EWS/FLI1 target GLI1. Thiostrepton is a compound known to inhibit FOXM1 by direct binding. We show that Thiostrepton diminishes FOXM1 expression in Ewing cell lines and this reduction reduces cell viability through an apoptotic mechanism. FOXM1 is involved in Ewing tumor pathogenesis and may prove to be a useful therapeutic target in Ewing tumors.

  13. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  14. Periosteal Ewing's Sarcoma: Report of Two New Cases and Review of the Literature

    OpenAIRE

    Kollender, Yehuda; Shabat, Shay; Nirkin, Alexander; Issakov, Josephine; Flusser, Gideon; Merimsky, Ofer; Meller, Isaac

    1999-01-01

    Background. The origin of Ewing's sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better prognosis when confined between periosteum and bone. Is it the same for periosteal Ewing's sarcoma? Methods. We describe two new cases and comprehensively review the literature consisting of 18 documented cases since the condition was first described in 1986 (S.M. Bator.Cancer 58:1781– 4). Results. Periosteal Ewing's sarcoma differ...

  15. Primary Pulmonary Ewing's Sarcoma: Rare Cause of Superior Vena Cava Syndrome in Children.

    Science.gov (United States)

    Mehra, Shibani; Atwal, Swapndeep Singh; Garga, Umesh Chandra

    2014-08-01

    Ewing's sarcoma is a common malignant bone tumour presenting in children and young adults. Rarely extra- skeletal soft tissues and visceral organs can also be the site of origin of Ewing's sarcoma. Primary pulmonary Ewing's sarcoma is an extremely rare malignancy which occurs in the paediatric population. We report an unusual case of primary pulmonary Ewing's sarcoma in a nine year old girl who presented with features of superior vena cava syndrome in the emergency department. The diagnosis was confirmed pathologically both by light microscopy and immunohistochemistry. The patient was put on chemotherapy and surgery was planned but the patient expired within three days of starting chemotherapy.

  16. Rare extraskeletal Ewing's sarcoma mimicking as adenocarcinoma of the sigmoid.

    Science.gov (United States)

    Mertens, Michelle; Haenen, Filip W N; Siozopoulou, Vasiliki; Van Cleemput, Marc

    2017-06-01

    Extraskeletal Ewing's sarcoma (EES) is a rare finding in comparison with Ewing's sarcoma of bone and usually manifests in young patients. However, even in older patients, one must consider the diagnosis. In this case, we describe a 52-year-old woman diagnosed with EES, mimicking as adenocarcinoma of the sigmoid. The tumor was not visualized by a multi-slice spiral computed tomography of the abdomen and pelvis with intravenous contrast, and eventually the diagnosis was made by positive immunohistochemical staining for CD99 and by molecular testing for EWSR1 translocation. This combination of the patient's age and the localization of the tumor mimicking an adenocarcinoma of the sigmoid has never been described before.

  17. Hyperfractionated radiotherapy with simultaneous chemotherapy in Ewing's sarcoma

    International Nuclear Information System (INIS)

    Dunst, J.; Sauer, R.; Burgers, J.M.V.; Hawlicek, R.; Trott, K.R.; Juergens, H.

    1988-01-01

    In 1981, the German Society of Pediatric Oncology initiated a multi-institutional study for the treatment of Ewing's sarcoma. The protocol (Cooperative Ewing's Sarcoma Study, CESS 81) consisted of four courses of a four-drug-regimen (VACA), each course taking nine weeks. Local therapy (radical surgery or resection plus irradiation or radiotherapy alone) was performed after the second course. The results of CESS 81 can be summarized as follows: VACA-chemotherapy is effective in controlling systemic disease. Initial tumor mass and response to initial chemotherapy are of major prognostic value for local control and survival. Permanent local control is a problem, especially in irradiated patients. The high local failure rate in irradiated patients in CESS 81 could be attributable to the following reasons: Late start of local therapy (after 18 weeks of chemotherapy), uneven distribution of prognostic parameters: Large tumors were more often irradiated than operated, protocol deviations in irradiated patients. (orig.)

  18. Combinatorial drug screening identifies Ewing sarcoma-specific sensitivities

    OpenAIRE

    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 p...

  19. BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

    Directory of Open Access Journals (Sweden)

    Françoise eREDINI

    2015-12-01

    Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  20. [Clinical, pathological and imaging features of primary pelvic Ewing's sarcoma].

    Science.gov (United States)

    Liu, J; Chen, Y; Ling, X L; Gong, Y; Ding, J P; Zhang, Z K; Wang, Y J

    2016-07-19

    To explore the clinical, pathological and imaging features of Ewing's sarcoma in pelvis and to improve knowledge and diagnosis of the disease. A retrospective analysis of the clinical, pathological and imaging data of pathologically confirmed 13 cases of Ewing's sarcoma in pelvis was carried out between May 2008 and March 2016 in the Affiliated Hospital of Hangzhou Normal University, the Third Hospital of Hebei Medical University and the Second Hospital of Hebei Medical University. The median age 13 cases of pelvic primary Ewing's sarcoma was 17 years old.The X-ray and CT imagings showed osteolytic and mixed bone destruction, CT showed mixed type in 10 cases, 8 cases of bone tumors as a flocculent, 10 cases of bone expansion failure, 10 cases of periosteal reaction, the layered 5 cases, radial in 5 cases.Thirteen cases showed soft tissue mass, soft tissue mass was equal or slightly lower density.Four cases showed heterogeneous contrast enhancement.The lesions showed low signal in T1WI and mixed high signal in T2WI of magnetic resonance imaging(MRI). The boundary of the lesions were obscure, and 5 cases had patchy necrosis area, and 9 cases had incomplete false capsule, surrounding soft tissue was violated.Four cases showed heterogeneous contrast enhancement after MRI enhancement scan. The age of onset of Ewing's sarcoma of the pelvis is more concentrated in about 15 years.The imaging feaures are mixed bone destruction and more bone is swelling and permeability damage, soft tissue mass is larger, bone tumor is cloudy or acicular, periosteal reaction in a layered and radial, most cases show that the false envelope is not complete.Combined with clinical and imaging examination, the diagnosis of the disease can be made.

  1. Extra-skeletal Ewing's sarcoma resembling acute abdomen. Case report.

    Science.gov (United States)

    Valdivia Gómez, Gilberto Guzmán; Soto Guerrero, María Teresa; Cedillo de la Cruz, María Isabel

    2010-01-01

    Extraosseous Ewing's sarcoma is a rare tumor of neuroectodermal origin. It presents mainly in the soft tissue of the extremities and thorax. Histologically, it is similar to Ewing's sarcoma of the bone. We present the case of a male who arrived at the emergency room with acute abdomen, leucocytosis and imaging techniques (abdominal ultrasound and computed tomography) suggestive of complicated diverticular disease. He was treated with emergency surgery. Intraoperative findings were an unsuspected tumor (20 x 15 x 15 cm). Treatment consisted of extirpation of the tumor, separating it from the adjacent viscera and followed by chemotherapy based on epirubicin, cyclophosphamide and vincristine for six cycles. Because the control abdominal CT demonstrated tumor activity in the retroperitoneum adjacent to the ascending colon and cecum, further resection was decided upon. In a review of the literature, no previous reports of extraosseous Ewing's sarcoma were found presenting as acute abdomen. Due to the rarity of this tumor, only case reports or series have been found in the literature without randomized or comparative studies. Surgery was the cornerstone of treatment, without reports of preoperative chemotherapy. If the patient's condition permits, percutaneous needle biopsy is mandatory to obtain optimum treatment as well as to improve prognosis.

  2. (q24: q12) translocation is common in Ewing's sarcoma/peripheral ...

    Indian Academy of Sciences (India)

    The Ewing's sarcoma family can present diagnostic difficulties. In the past the basis of diagnosis has been a exclusion. Identification of a specific translocation especially t(11; 22) (EWS-FLI 1 fusion gene), which is seen in nearly 85% of Ewing's sarcoma cases can help in precise diagnosis. We have carried out a study on ...

  3. Extraosseous Ewing's sarcoma, a case report on a rare diagnosis in ...

    African Journals Online (AJOL)

    Extraosseous or extraskeletal Ewing's sarcoma is a very rare mesenchymal soft tissue malignancy. We report on a case of abdominal swelling in an 80-year-old woman caused by a large intra-abdominal EES. This case report illustrates that Ewing's sarcoma can occur in adults and elderly, and highlights the importance of ...

  4. 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.

  5. Diagnosis of Ewing's sarcoma in the thoracic spine - problems in differential diagnosis

    International Nuclear Information System (INIS)

    Schaub, T.; Dittrich, H.M.; Gutjahr, P.; Antoniadis, A.; Wolff, P.

    1986-01-01

    Spinal Ewing's sarcomas are rare and cause problems in differential diagnosis. The radiologic, nuclear medicine and CT findings in two children with histologically proven Ewing's sarcoma are presented and problems in differential diagnosis discussed. Biopsy should be done early. (orig.) [de

  6. 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.

  7. Recurrence of Ewing sarcoma: Is detection by imaging follow-up protocol associated with survival advantage?

    NARCIS (Netherlands)

    Heinemann, Melina; Ranft, Andreas; Langer, Thorsten; Jürgens, Herbert; Kreyer, Justus; Vieth, Volker; Schäfers, Michael; Weckesser, Matthias; Simon, Thorsten; Hassenpflug, Wolf; Corbacioglu, Selim; Bielack, Stefan; Mayer-Steinacker, Regina; Kühne, Thomas; van den Berg, Henk; Gelderblom, Hans; Bauer, Sebastian; Stegger, Lars; Dirksen, Uta

    2018-01-01

    The Cooperative Ewing Sarcoma Study and the Late Effects Surveillance System of the Society for Paediatric Oncology and Haematology recommend a structured follow-up imaging protocol (FUIP) for patients with Ewing sarcoma (EwS) with decreasing frequency of imaging over the first 5 years. The present

  8. Primary ewing sarcoma of the anterior mandible localized to the midline

    NARCIS (Netherlands)

    Ko, E.; Brouns, E.R.E.A.; Korones, D.N.; Pochal, W.F.; Philipone, E.M.; Zegarelli, D.J.; Yoon, A.J.

    2013-01-01

    Ewing sarcoma is a malignant, small, round blue-cell tumor of the bone that is usually located in the long bones and the pelvis. Fewer than 3% of all Ewing sarcomas originate in the head and neck region and these are mostly located in the posterior mandible. We report the case of a 17-year-old girl

  9. Bone scintigraphy in Ewing's sarcoma during and after treatment - prognostic information from the primary tumor site

    International Nuclear Information System (INIS)

    Piers, D.A.; Veenhoven, R.H.; Kamps, W.A.; Woldring, M.G.

    1988-01-01

    A bone scan can be negative in Ewing's sarcoma. The bone scan during and after treatment can give prognostic information on the primary tumor site: A persisting hot spot strongly suggests the presence of local malignancy, while a hot spot becomming negative points to local cure of Ewing's sarcoma. (orig.)

  10. Periosteal Ewing's Sarcoma: Report of Two New Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yehuda Kollender

    1999-01-01

    Full Text Available Background. The origin of Ewing's sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better prognosis when confined between periosteum and bone. Is it the same for periosteal Ewing's sarcoma?

  11. 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.

  12. 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

  13. Impact of treatment protocol on outcome of localized Ewing's sarcoma.

    Science.gov (United States)

    Nasaka, Srividya; Gundeti, Sadashivudu; Ganta, Ranga Raman; Arigela, Ravi Sankar; Linga, Vijay Gandhi; Maddali, Lakshmi Srinivas

    2016-01-01

    The outcome of localized Ewing's sarcoma has improved with multi-disciplinary approach. Survivals of Ewing's sarcoma from the Asian countries differed between centers. We retrospectively analyzed the records of newly diagnosed localized Ewing's sarcoma patients from 2002 to 2012. The patients were analyzed in three groups; Group 1(2002-2004) who received non-ifosfomide based regimens, Group 2(2005-2008) who received VDC/IE for 12 cycles, and Group 3(2009-2012), who received VDC/IE for 17 cycles. The groups were compared for their baseline characteristics, treatment protocol and outcome. Seventy three patients were included in the study. The median age of presentation was 15 years, with slight male predominance. Axial primary was seen in 62%. The median RFS of the three groups was 26.4, 31.4 and 36.8 months respectively ( P = 0.0018). The median OS was 27.9, 35 and 43 months respectively ( P = 0.0007). At a median follow-up of 35 months, the 3 year RFS and OS for the three treatment groups were 17%, 31%, 60% and 35%, 45% and 70% respectively. Larger tumor size, axial primary, high LDH were associated with poorer survival. Radiotherapy was associated with inferior local control and survival. We found that the survival of our ESFT patients improved over time with intensified multiagent chemotherapy and with lesser time to local therapy. But the results were still inferior to those reported in literature. We had majority of patients presenting in axial site and radiotherapy as the predominant mode of local control. The outcome may further improve with surgery as local control procedure.

  14. Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report.

    Science.gov (United States)

    Hernando-Cubero, Jorge; Sanz-Moncasi, Pilar; Hernández-García, Alba; Pajares-Bernard, Isabel; Martínez-Trufero, Javier

    2016-10-01

    The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant tumors. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin ® ) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In cases of inadequate response, there are a number of second-line regimens available. However, further treatment options are required for those patients with disease unresponsive to standard treatment. Trabectedin is a novel treatment option for patients with ESFT. The present study reports the case of a Caucasian 69-year-old female patient who presented with a soft tissue mass on the chest wall that had developed 7 months earlier. A computed tomography scan revealed a 9×8×7-cm mass on the anterior chest wall above the pectoral muscle. Histopathological evaluations and molecular analysis indicated that it was consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was treated with an alternating VAC/IE regimen; however, an inadequate response was observed. The patient received second-line treatment with a gemcitabine and dacarbazine combination regimen, but the disease progressed. Subsequently, treatment with trabectedin (1.5 mg/m 2 as a 24-h continuous infusion every 3 weeks) was initiated. Trabectedin treatment resulted in long-lasting (18 months) progression-free survival. It is vital that novel drugs continue to being developed for patients with ESFT following progression subsequent to standard chemotherapy. The current report presents a case of a patient with metastatic, pre-treated Ewing's sarcoma achieving disease stabilization with trabectedin. Based on these results and the observed tolerability profile, trabectedin represents an alternative treatment for patients with ESFT. Further studies are required in order to determine the efficacy of trabectedin as monotherapy or in combination with other drugs. It is also important to

  15. Ewing's sarcoma of the cervix, a diagnostic dilemma: a case report and review of the literature.

    Science.gov (United States)

    Mashriqi, Nazia; Gujjarlapudi, Jaya Kranthi; Sidhu, Jagmohan; Zur, Michael; Yalamanchili, Madhuri

    2015-11-09

    Ewing's sarcoma belongs to a spectrum of neoplastic diseases known as Ewing's family of tumors. This family of tumors is usually seen in osseous sites. Ewing's sarcoma of the cervix is extremely rare, with only 18 cases reported in the English literature. The immunohistochemical profile of Ewing's sarcoma overlaps with other malignancies like small cell carcinoma. The rarity and complex pathologic picture of Ewing's sarcoma of the cervix creates the potential for misdiagnosis. Hence, we believe this case needs to be reported to add to the available literature. A 49-year-old white Caucasian woman presented with vaginal bleeding. A pelvic examination revealed a cystic lesion arising from her cervix. Examination of a biopsy specimen revealed a poorly differentiated neoplasm, with sheets of small hyperchromatic cells, staining weakly for neuroendocrine markers. She was diagnosed with small cell carcinoma and started on concurrent chemotherapy and radiation. However, additional positive immunostaining for CD99 was strongly suggestive of Ewing's sarcoma. Fluorescence in situ hybridization revealed ESWR1 gene rearrangement, confirming Ewing's sarcoma. Our patient underwent surgery, which confirmed stage IIB Ewing's sarcoma. She received adjuvant chemotherapy but died from progressive metastatic disease after four cycles. With early diagnosis and appropriate treatment, Ewing's sarcoma of the cervix can be a potentially curable disease. However, owing to overlapping clinical and histopathological features, the diagnosis poses a challenge to oncologists and pathologists. This article guides pathologists to consider Ewing's sarcoma in the differential diagnosis of small cell carcinoma with weak staining for neuroendocrine markers. This literature review will benefit oncologists encountering this rare entity.

  16. 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.

  17. 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.

  18. Potential approaches to the treatment of Ewing's sarcoma.

    Science.gov (United States)

    Yu, Hongjiu; Ge, Yonggui; Guo, Lianying; Huang, Lin

    2017-01-17

    Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise. There has also been increasing interest in the immune responses of ES patients. Immunotherapies using T cells, NK cells, cancer vaccines and monoclonal antibodies have been considered for ES, especially for recurrent patients. Because understanding the pathogenesis of ES is extremely important for the development of novel treatments, this review focuses on the mechanisms and functions of targeted therapies and immunotherapies in ES. It is anticipated that integrating the knowledge obtained from basic research and translational and clinical studies will lead to the development of novel therapeutic strategies for the treatment of ES.

  19. 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

  20. Primary Vaginal Extraosseous Ewing Sarcoma/Primitive Neuroectodermal Tumor with Cranial Metastasis

    Directory of Open Access Journals (Sweden)

    Chi-Man Yip

    2009-06-01

    Full Text Available Extraosseous Ewing sarcoma is now regarded as a member of the Ewing sarcoma/primitive neuroectodermal tumor (PNET family. It typically involves the soft tissues of the chest wall, pelvis, paravertebral region, abdominal wall, retroperitoneal region and extremities of children, adolescents and young adults, but it seldom occurs in the female genital tract. We report an extremely rare case of retrospective diagnosis of vaginal extraosseous Ewing sarcoma/PNET which metastasized to the right frontoparietal scalp, skull, and dura. Surgical resection, followed by adjuvant radiotherapy and chemotherapy resulted in a favourable clinical outcome. Both the vaginal and head tumors had similar light microscopic features supporting the diagnosis.

  1. Retrotracheal Extraskeletal Ewing's Sarcoma: Case Report and Discussion on Airway Management.

    Science.gov (United States)

    Van Der Meer, Graeme; Linkhorn, Hannah; Gruber, Maayan; Mahadevan, Murali; Barber, Colin

    2017-03-01

    Extraskeletal Ewing's sarcoma is a rare tumor, and the management of airway compromise in case of cervical Ewing's sarcoma has not been established. This report describes the case of a patient with retrotracheal Ewing's sarcoma and discusses a successful approach to airway management. A 12-year-old male presented with a 2-week history of sore throat and sleep-disordered breathing and 48 hours of stridor. Imaging confirmed a retrotracheal soft tissue mass with airway compromise. A planned and controlled approach to his airway management resulted in a secure airway prior to definitive treatment.

  2. Primary soft tissue Ewing's sarcoma of the maxillary sinus in elderly patients: presentation, management and prognosis.

    Science.gov (United States)

    Dutta, M; Ghatak, S; Biswas, G; Sen, A

    2014-06-01

    Nonosseous or soft tissue Ewing's sarcoma is a rare form of Ewing's sarcoma/primitive neuroectodermal tumour that seldom affects the head and neck region. Involvement of the nose and paranasal sinuses is extremely uncommon, with only eight of such patients being reported to date, mostly affecting adolescents and young adults. To our knowledge, this study is the first comprehensive report of primary soft tissue Ewing's sarcoma involving the paranasal sinuses in an elderly patient who successfully completed treatment. We herein discuss the pathogenesis, management and factors affecting the prognosis of this rare group of tumours involving the nose and paranasal sinuses, in relation to the available literature.

  3. 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.

  4. Unusual Presentation of a Primary Ewing's Sarcoma of the Spine with Paraplegia: A Case Report.

    Science.gov (United States)

    Kannan, Karthik Kailash; Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-03-01

    Ewing's sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing's sarcoma in the spine is very rare. Ewing's sarcoma occurring in the spine is divided into two types, Ewing's sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing's sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing's sarcoma and patient was started on combination chemotherapy and radiotherapy.

  5. [Extra skeletal Ewing's sarcoma. Report of two cases. Ultrastructural study of one case (author's transl)].

    Science.gov (United States)

    Krulik, M; Brechot, J M; de Saint-Maur, P; Lecomte, D; Mougeot-Martin, M; Audebert, A A; Zylberait, D; Debray, J

    The authors report two cases of extra skeletal Ewing's sarcoma. The first case concerns a 26 years old woman presenting a tumor at the level of the sacrum area, locally recurrent, metastazing to the lungs and the lumbar column, despite of radiotherapy and chemotherapy and leading to death after a course of 18 months. The second one is that of a 30 years old man bearing a tumor of the shoulder area probably already metastazed to bones, rapidly recurrent and metastazing to the lungs and cause of death after 9 months in spite of intensive therapy. About these 2 observations a review of the literature of the cases of extra skeletal Ewing's sarcoma is done. Whatever nosologic discussion it seems that Ewing's sarcoma may present essentially as a tumor of soft tissues. An ultrastructural study has been performed in the second case. The findings are similar to those reported in Ewing's sarcoma.

  6. A Novel Role for Keratin 17 in Coordinating Oncogenic Transformation and Cellular Adhesion in Ewing Sarcoma

    Science.gov (United States)

    Sankar, Savita; Tanner, Jason M.; Bell, Russell; Chaturvedi, Aashi; Randall, R. Lor; Beckerle, Mary C.

    2013-01-01

    Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant transcription factor fusion oncogene. Glioma-associated oncogene homolog 1 (GLI1) is a critical target gene activated by EWS/FLI, but the mechanism by which GLI1 contributes to the transformed phenotype of Ewing sarcoma was unknown. In this work, we identify keratin 17 (KRT17) as a direct downstream target gene upregulated by GLI1. We demonstrate that KRT17 regulates cellular adhesion by activating AKT/PKB (protein kinase B) signaling. In addition, KRT17 is necessary for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1-mediated transformation function but via a mechanism independent of AKT signaling. Taken together, our data reveal previously unknown molecular functions for a cytoplasmic intermediate filament protein, KRT17, in coordinating EWS/FLI- and GLI1-mediated oncogenic transformation and cellular adhesion in Ewing sarcoma. PMID:24043308

  7. Radiographic features of Ewing's sarcoma of the bones of the hands and feet

    Energy Technology Data Exchange (ETDEWEB)

    Baraga, J.J.; Amrami, K.K.; Swee, R.G. [Mayo Clinic, Rochester, MN (United States). Dept. of Radiology; Wold, L. [Mayo Clinic, Rochester, MN (United States).. Dept. of Laboratory Medicine and Pathology; Unni, K.K. [Mayo Clinic, Rochester, MN (United States). Dept. of Surgical Pathology

    2001-03-01

    The radiographic features of Ewing's sarcoma of the bones of the hands and feet are reviewed utilizing cases obtained from the Mayo Clinic patient files and the consultation files of Drs. D.C. Dahlin and K.K. Unni. This series consists of a total of 43 cases of pathologically proven Ewing's sarcoma involving the small bones of the hands and feet. The classic radiographic features of Ewing's sarcoma in the long bones, including lytic, permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass, are also seen in the bones of the hands and feet, with similar frequency. These classic features are most commonly present in lesions affecting the short tubular bones. Lesions affecting the tarsal bones more often demonstrate atypical radiographic features. These atypical radiographic appearances may play a role in the reported delay in diagnosis of Ewing's sarcoma within the tarsal bones. (orig.)

  8. Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review.

    Science.gov (United States)

    García-Castellano, José M; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H

    2012-01-01

    Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into "good" and "poor" responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

  9. Primary Ewing's sarcoma of the skull: radical resection and immediate cranioplasty after chemotherapy. A technical note.

    Science.gov (United States)

    Castle, Maria; Rivero, Mónica; Marquez, Javier

    2013-02-01

    The current standard treatment of Ewing's sarcoma is chemotherapy followed by surgery, making an immediate cranial reconstruction in a one-step surgical procedure possible. We describe the technique used to repair a cranial defect after the resection of a primary Ewing's sarcoma of the skull in a one-step surgical procedure. Bone repair with a custom-made cranioplasty immediately after resection of a primary Ewing's sarcoma of the skull avoids deformities and late complications associated with reconstructive surgery after radiotherapy and not interfere with radiotherapy and neither with follow-up. A one-step surgical procedure after chemotherapy for primary Ewing's sarcoma of the skull could be safer, less aggressive and more radical; avoiding deformities and late complications.

  10. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    International Nuclear Information System (INIS)

    Trigg, M.E.; Makuch, R.; Glaubiger, D.

    1985-01-01

    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

  11. Radiographic features of Ewing's sarcoma of the bones of the hands and feet

    International Nuclear Information System (INIS)

    Baraga, J.J.; Amrami, K.K.; Swee, R.G.; Wold, L.; Unni, K.K.

    2001-01-01

    The radiographic features of Ewing's sarcoma of the bones of the hands and feet are reviewed utilizing cases obtained from the Mayo Clinic patient files and the consultation files of Drs. D.C. Dahlin and K.K. Unni. This series consists of a total of 43 cases of pathologically proven Ewing's sarcoma involving the small bones of the hands and feet. The classic radiographic features of Ewing's sarcoma in the long bones, including lytic, permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass, are also seen in the bones of the hands and feet, with similar frequency. These classic features are most commonly present in lesions affecting the short tubular bones. Lesions affecting the tarsal bones more often demonstrate atypical radiographic features. These atypical radiographic appearances may play a role in the reported delay in diagnosis of Ewing's sarcoma within the tarsal bones. (orig.)

  12. Primary Ewing's Sarcoma of the Temporal Bone: A Rare Case Report and Literature Review.

    Science.gov (United States)

    Gupta, Divya; Gulati, Achal; Purnima

    2017-09-01

    Ewing's sarcoma is a malignant, round cell tumor arising from the bones and primarily affecting children and adolescent, accounting for 3 % of all childhood malignancies. Although the long bones and the trunk are typically affected, rare cases of it involving isolated bones throughout the body have been reported. Involvement of the skull bones is rare, constituting 1-6 % of the total Ewing's sarcoma cases but those affecting the cranial bones are rarer still, constituting only 1 %. We describe an 8 months old infant having Ewing sarcoma, of the petrous and mastoid parts of temporal bone along with the occipital bone, whose clinical presentation mimicked mastoiditis with facial nerve palsy. We discuss the clinical and therapeutic course of an extensive primary Ewing sarcoma of the temporal bone, which was treated without performing surgery and review this entity's literature in detail.

  13. Ten-Year Follow-Up of a Patient with Metastatic Ewing's Sarcoma of the Pelvis

    Directory of Open Access Journals (Sweden)

    Robert U. Ashford

    2002-01-01

    Full Text Available Patient: We report a 32-year-old women with a pelvic Ewing's sarcoma, who developed skeletal metastases within 20 months of diagnosis but following treatment remains disease-free at 10 years.

  14. 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.

  15. Primary Ewing's sarcoma of the vertebral column

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Sundaram, Murali [Department of Radiology, Mayo Clinic, Ch2-290 200 First Street, SW, Rochester, 55905, MN (United States); Unni, K.Krishnan [Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, 55905, Rochester, MN (United States); Dekutoski, Mark B. [Department of Orthopedic Surgery, Mayo Clinic, 200 First Street, SW, 55905, Rochester, MN (United States)

    2004-09-01

    To determine the demographics, imaging findings, clinical symptoms, and prognosis of primary vertebral Ewing's sarcoma (PVES). A retrospective review of medical records and radiological studies of patients diagnosed with PVES from 1936 through 2001 in our institution and Department of Pathology consultation files was undertaken. Metastatic and soft tissue Ewing's sarcoma cases were excluded. From a total of 1,277 cases of Ewing's sarcoma, 125 (9.8%) had a primary vertebral origin. There were 48 females and 76 males. Patient ages ranged from 4 to 54 (mean 19.3, standard deviation 10.7, median 16) years. Vertebral column distribution was four cervical (3.2%), 13 thoracic (10.5%), 31 lumbar (25%), and 67 sacrum (53.2%). More than one vertebral segment was involved in ten cases (8%). Satisfactory imaging studies were available in 51 patients: 49 radiographs, 27 computerized tomography (CT), and 23 magnetic resonance imaging (MRI) studies. The majority of tumors were lytic (93%). Three cases were mixed lytic and sclerotic (6%) and one sclerotic. In the nonsacral spine, the majority of lesions (12/20) involved the posterior elements with extension into the vertebral body. Five cases were centered in the vertebral body with extension into the posterior elements. Two cases were limited to the posterior elements, and one case solely involved the vertebral body. Ala was the most frequently affected site in the sacrum (18/26). Spinal canal invasion was frequent (91%). Detailed clinical information was available in 53 patients. Duration of symptoms ranged from 1 to 30 (mean 7) months. Local pain was the first symptom and seen in all cases. Neurological deficits were present in 21 (40%) cases. All patients received radiation in various dosages; 70% additionally received chemotherapy. Twenty-five patients had surgery, and two patients received bone marrow transplantation. Forty-five patients had follow-up; the five-year disease-free survival probability is 0

  16. [Extra-skeletal Ewing's sarcoma. A case report with detailed review of the literature].

    Science.gov (United States)

    Auge, B; Pusel, J

    1990-01-01

    Extra-skeletal Ewing's Sarcoma (EES): a clinico-pathological entity described in 1975 by L. Angervall and F.M. Enzinger. This article reports a new case in which the primary was localized in the right forearm and metastasized to the left lung fourteen years later. A detailed review of the literature emphasized similarities and differences between osseous and extra-osseous Ewing's Sarcoma.

  17. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma

    OpenAIRE

    Redini, Fran?oise; Heymann, Dominique

    2015-01-01

    Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due t...

  18. Local control of Ewing's sarcoma: an analysis of 67 patients

    International Nuclear Information System (INIS)

    Brown, A.P.; Fixsen, J.A.; Plowman, P.N.

    1987-01-01

    Local control of Ewing's sarcoma was analysed in a series of 67 patients treated by surgery and/or radiotherapy as well as combination chemotherapy. Radiotherapy was employed with or without surgery in 60 patients and produced an overall local control rate of 55%; complete excision of the primary lesion seemed to be beneficial. There was a marked variation in control rates depending on the site of the primary lesion: limb 85%, rib 53%, pelvis 31% and other sites 33%.Primary tumours greater than 10 cm in diameter were significantly less likely to be controlled. Using daily fractions of approximately 180 cGy, total doses in excess of 6000 cGy seem more likely to produce serious late morbidity amd may not increase the local control rate. No cases of second malignancy arising in irradiated tissue have been observed to date, but one patient developed acute lymphoblastic leukaemia. (author)

  19. Extra-skeletal Ewing's sarcoma of the submandibular gland.

    Science.gov (United States)

    Agir, Hakan; Brasch, Helen D; Tan, Swee T

    2007-01-01

    Extra-skeletal Ewing's sarcoma (EES) is an uncommon malignancy, especially in the head and neck region that may arise in various extra-osseous tissues. We report a 22-year-old male with an EES of the submandibular gland, which to the best of our knowledge, has not been described previously. The patient who underwent combined treatment with surgical resection and chemo-irradiation was disease free for 22 months but succumbed to multi-organ metastases 14 months later. This case highlights the combined diagnostic role of immunohistochemical, cytogenetic and radiological evaluation of EES. EES is an aggressive cancer that requires multidisciplinary management with wide surgical excision and adjunctive chemo-irradiation for the best outcome.

  20. Endoscopic Treatment of Ewing Sarcoma of the Sinonasal Tract.

    Science.gov (United States)

    Lepera, Davide; Volpi, Luca; Facco, Carla; Turri-Zanoni, Mario; Battaglia, Paolo; Bernasconi, Barbara; Piski, Zalán; Freguia, Stefania; Castelnuovo, Paolo; Bignami, Maurizio

    2016-06-01

    The extra-skeletal form is an unusual type of Ewing sarcoma (ES) arising from soft tissue and in the literature there are reports of less than 50 patients describing the tumor in the paranasal sinuses and skull base. The histological diagnosis is crucial to plan the correct treatment and the molecular confirmation is mandatory in equivocal patients. A multimodality treatment with chemotherapy, surgery and radiotherapy improved the outcomes of these diseases during the last decades and a free-margin resection with the endoscopic transnasal technique is one of the most recent ways to manage these pathologies in selected patients, reducing the morbidities of the external approaches and preserving the quality of life of the patient.Here, the authors present the first patient of primary sinonasal ES free from disease after 5 years of follow-up and treated with an endoscopic endonasal approach and a second patient of sinonasal metastases of ES treated with and endoscopic transnasal approach.

  1. Intravenous lignocaine infusion for intractable pain in Ewing's sarcoma

    Directory of Open Access Journals (Sweden)

    Nivedita Page

    2018-01-01

    Full Text Available A 23-year-old female presented to our palliative care center with Ewing's sarcoma of the humerus with lung metastases. Pain in her arm was unrelieved by nonsteroidal anti-inflammatory drugs, neuropathic medication as well as morphine. She could not tolerate any further increase in opioid dose but was so distraught due to the pain that she wanted to die. An intravenous lignocaine infusion in a dose of 2 mg/kg was given over an hour for three successive days. This successfully relieved her pain after which she was settled with her original medication. We feel that in palliative care settings, where intractable pain and tolerance to morphine are so common, intravenous lignocaine infusions could provide a safe and effective tool for pain relief.

  2. 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)

  3. 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.

  4. Extra-skeletal Ewing's sarcoma in adults: presentation of two cases.

    Science.gov (United States)

    Lipski, Samuel M; Cermak, Katia; Shumelinsky, Felix; Gil, Thierry; Gebhart, Michael J

    2010-12-01

    Extraosseous Ewing's sarcoma represents about 5% of the Ewing family of tumours. Two cases in adult patients are presented, emphasizing the complexity of a multi-modality treatment approach of this tumour. Clinical presentation, chemotherapeutical, surgical and radiotherapeutical approaches are discussed. A thorough literature search was done to correlate our therapeutic attitude with current knowledge of this very rare disease.

  5. Tumor cell plasticity in Ewing sarcoma, an alternative circulatory system stimulated by hypoxia

    NARCIS (Netherlands)

    Schaft, van der D.W.J.; Hillen, F.; Pauwels, P.; Kirschmann, D.A.; Castermans, Karolien; Oude Egbrink, M.G.A.; Tran, M.G.; Sciot, R.; Hauben, E.; Hogendoorn, P.C.W.; Delattre, O.; Maxwell, P.H.; Hendrix, M.J.C.; Griffioen, A.W.

    2005-01-01

    A striking feature of Ewing sarcoma is the presence of blood lakes lined by tumor cells. The significance of these structures, if any, is unknown. Here, we report that the extent of blood lakes correlates with poor clinical outcomes, whereas variables of angiogenesis do not. We also show that Ewing

  6. The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES)

    NARCIS (Netherlands)

    Haeusler, Julia; Ranft, Andreas; Boelling, Tobias; Gosheger, Georg; Braun-Munzinger, Gabriele; Vieth, Volker; Burdach, Stefan; van den Berg, Henk; Juergens, Heribert; Dirksen, Uta

    2010-01-01

    The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES) was investigated. We analyzed 120 patients registered into the European Ewing Tumor Working Initiative of National Groups (EURO-E.W.I.N.G. 99) trial at the trial center of Muenster from 1998 to

  7. Post-relapse survival in patients with Ewing sarcoma.

    Science.gov (United States)

    Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

    2015-06-01

    Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

  8. Ewing sarcoma of the rib with normal blood flow and blood pool imagings on a 3-phase bone scan.

    Science.gov (United States)

    Alfeeli, Mahmoud A; Naddaf, Sleiman Y; Syed, Ghulam M S

    2005-09-01

    Ewing sarcoma is the second most common pediatric malignant bone tumor. It usually presents as a hot spot on a 3-phase bone scan as a result of increased vascularity of the tumor and new bone formation. However, aggressive Ewing sarcoma can also appear as a cold lesion. We present the features of a Ewing sarcoma of the rib on a 3-phase bone scan in a child who was being investigated for rib fracture after trauma.

  9. Role of radiation therapy in the management of nonmetastatic Ewing's sarcoma of bone. Report of the intergroup Ewing's sarcoma study

    International Nuclear Information System (INIS)

    Perez, C.A.; Tefft, M.; Nesbit, M.; Burgert, E.O. Jr.; Vietti, T.; Kissane, J.; Pritchard, D.J.; Gehan, E.A.

    1981-01-01

    The role of radiation therapy in local tumor control and decreased incidence of pulmonary metastasis is reported in 271 patients who were entered into the Intergroup Ewing's Sarcoma Study with more than one year follow-up and on whom all radiotherapy records were reviewed. The majority of the patients were irradiated to the primary tumor with doses of 4500 to 6500 rad in five to six weeks in combination with systemic administration of three drugs (vincristine, actinomycin-D and cyclophosphamide) or four drugs (vincristine, actinomycin-D, cyclophosphamide and adriamycin). One of the groups of patients was treated with three drugs and bilateral pulmonary irradiation (1500 rad, uncorrected dose, in two weeks). Preliminary analysis shows an overall local primary tumor control of 89%. Patients with lesions in the pelvis had a local failure rate of 17% (9 of 52) and in the humerus 23% (7 of 31). Factors affecting local recurrences are analyzed in detail. Distant metastases have been noted in 40% of all patients; the highest proportion was noted in the pelvis (49%). There was a significant difference in the appearance of pulmonary metastases in the patients who were treated with four drugs (9.7%) and in the group who received three drugs and pulmonary irradiation (23.5%) when compared with the patients treated with three drugs only (37%). Intensive chemotherapy and radiotherapy significantly improve local tumor control and survival of patients with localized Ewing's sarcoma. However, the high incidence of metastasis suggests the need for more effective systemic chemotherapy to further improve treatment results. It is very important to determine the optimal dose of irradiation and minimal volume to be treated in order to achieve optimal survival and primary tumor control with the least sequela

  10. Radiation therapy in the multimodal management of Ewing's sarcoma of bone: report of the Intergroup Ewing's Sarcoma Study

    International Nuclear Information System (INIS)

    Perez, C.A.; Tefft, M.; Nesbit, M.E. Jr.; Burgert, E.O. Jr.; Vietti, T.J.; Kissane, J.; Pritchard, D.J.; Gehan, E.A.

    1981-01-01

    This paper is a progress report on the role of radiation therapy (RT) in local tumor control and the decreased incidence of pulmonary metastasis in 251 patients entered in the Intergroup Ewing's Sarcoma Study. All were followed for more that 1 year, and their RT records were reviewed. Doses to the primary tumor in the range of 4,500--6,500 rad were administered over approximately 5 to 6 weeks in combination with 4 drugs, i.e., vincristine (VCR), dactinomycin (DAC), cyclophosphamide (CY), and adriamycin, or only the first 3. One group of patients received the 3 drugs and bilateral pulmonary irradiation (approximately 1,500 rad in 2 wk). Preliminary analysis showed a local primary tumor control of approximately 90%. Patients with lesions in the pelvis and humerus had local failure rates of 13% (7 of 54) and 21.4% (6 of 28), respectively. The treatment groups differed significantly in the incidence of pulmonary metastasis. Patients treated with the 4 drugs (regimen 1) had a 14% incidence, whereas 42% of those treated with only 3 drugs (regimen 2) developed pulmonary metastases. Of all patients treated with 3 drugs and pulmonary irradiation (regimen 3), 18% showed lung metastases. The study indicated that intensive chemotherapy and RT significantly improved the local control and survival of patients with localized Ewing's sarcoma. However, the high incidence of metastasis indicated the need for more effective systemic chemotherapy for further improvement of treatment results. More studies are needed so we can define the volume to be treated and the optimal dose of irradiation to determine a therapeutic strategy that will yield optimal survival and tumor control with the fewest sequelae

  11. IGF-1R/MDM2 relationship confers enhanced sensitivity to RITA in Ewing sarcoma cells.

    Science.gov (United States)

    Di Conza, Giusy; Buttarelli, Marianna; Monti, Olimpia; Pellegrino, Marsha; Mancini, Francesca; Pontecorvi, Alfredo; Scotlandi, Katia; Moretti, Fabiola

    2012-06-01

    Ewing sarcoma is one of the most frequent bone cancers in adolescence. Although multidisciplinary therapy has improved the survival rate for localized tumors, a critical step is the development of new drugs to improve the long-term outcome of recurrent and metastatic disease and to reduce side effects of conventional therapy. Here, we show that the small molecule reactivation of p53 and induction of tumor cell apoptosis (RITA, NSC652287) is highly effective in reducing growth and tumorigenic potential of Ewing sarcoma cell lines. These effects occur both in the presence of wt-p53 as well as of mutant or truncated forms of p53, or in its absence, suggesting the presence of additional targets in this tumor histotype. Further experiments provided evidence that RITA modulates an important oncogenic mark of these cell lines, insulin-like growth factor receptor 1 (IGF-1R). Particularly, RITA causes downregulation of IGF-1R protein levels. MDM2 degradative activity is involved in this phenomenon. Indeed, inhibition of MDM2 function by genetic or pharmacologic approaches reduces RITA sensitivity of Ewing sarcoma cell lines. Overall, these data suggest that in the cell context of Ewing sarcoma, RITA may adopt additional mechanism of action besides targeting p53, expanding its field of application. Noteworthy, these results envisage the promising utilization of RITA or its derivative as a potential treatment for Ewing sarcomas. ©2012 AACR

  12. Ewing sarcoma of the left big toe with trans-articular skip lesion

    Directory of Open Access Journals (Sweden)

    Ahmad F. Kamal

    2009-06-01

    Full Text Available We report the case of the patient who had Ewing Sarcoma in whom radiological and hystopathological appearances revealed a tumor mass in the left big toe along with trans-artikular skip lesion on the left diaphysis of tibia. In Cipto Mangunkusomo Hospital since 1995 until 2004 we have found 20 Ewing sarcoma cases, but only one skip lesion Ewing sarcoma was found. The diagnosis of transarticular skip lesion in association of Ewing sarcoma was confirmed in clinicopathological conferrence. The initial evaluation of all patients included the recording of the medical history, physical examination, and hematological studies. Radiographs of the chest and the site of the primary tumor were made routinely. Systemic staging was performed with use of total-body bone scan. Ray amputation of left big toe and open biopsy from mass of mid-shaft of tibia had been done to confirm the diagnosis. The patient underwent induction chemotherapy and above knee amputation. Ten months after diagnosis, he died because of advanced-distant metastasis. (Med J Indones 2008; 18: 139-44Key words: Ewing sarcoma, trans-articular skip lesion

  13. 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.

  14. Ewing's sarcoma: analysis of single nucleotide polymorphism in the EWS gene.

    Science.gov (United States)

    Silva, Deborah S B S; Sawitzki, Fernanda R; De Toni, Elisa C; Graebin, Pietra; Picanco, Juliane B; Abujamra, Ana Lucia; de Farias, Caroline B; Roesler, Rafael; Brunetto, Algemir L; Alho, Clarice S

    2012-11-10

    We aimed to investigate single nucleotide polymorphisms (SNPs) in the EWS gene breaking region in order to analyze Ewing's sarcoma susceptibility. The SNPs were investigated in a healthy subject population and in Ewing's sarcoma patients from Southern Brazil. Genotyping was performed by TaqMan® assay for allelic discrimination using Real-Time PCR. The analysis of incidence of SNPs or different SNP-arrangements revealed a higher presence of homozygote TT-rs4820804 in Ewing's sarcoma patients (p=0.02; Chi Square Test). About 300 bp from the rs4820804 SNP lies a palindromic hexamer (5'-GCTAGC-3') and three nucleotides (GTC), which were previously identified to be in close vicinity of the breakpoint junction in both EWS and FLI1 genes. This DNA segment surrounding the rs4820804 SNP is likely to indicate a breakpoint region. If the T-rs4820804 allele predisposes a DNA fragment to breakage, homozygotes (TT-rs4820804) would have double the chance of having a chromosome break, increasing the chances for a translocation to occur. In conclusion, the TT-rs4820804 EWS genotype can be associated with Ewing's sarcoma and the SNP rs4820804 can be a candidate marker to understand Ewing's sarcoma susceptibility. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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)

  17. 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.

  18. Prognostic significance of serum lactate dehydrogenase levels in Ewing's sarcoma: A meta-analysis.

    Science.gov (United States)

    Li, Suoyuan; Yang, Qing; Wang, Hongsheng; Wang, Zhuoying; Zuo, Dongqing; Cai, Zhengdong; Hua, Yingqi

    2016-12-01

    A number of studies have investigated the role of serum lactate dehydrogenase (LDH) levels in patients with Ewing's sarcoma, although these have yielded inconsistent and inconclusive results. Therefore, the present study aimed to systematically review the published studies and conduct a meta-analysis to assess its prognostic value more precisely. Cohort studies assessing the prognostic role of LDH levels in patients with Ewing's sarcoma were included. A pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) or 5-year disease-free survival (DFS) was used to assess the prognostic role of the levels of serum LDH. Nine studies published between 1980 and 2014, with a total of 1,412 patients with Ewing's sarcoma, were included. Six studies, with a total of 644 patients, used OS as the primary endpoint and four studies, with 795 patients, used 5-year DFS. Overall, the pooled HR evaluating high LDH levels was 2.90 (95% CI: 2.09-4.04) for OS and 2.40 (95% CI: 1.93-2.98) for 5-year DFS. This meta-analysis demonstrates that high levels of serum LDH are associated with lower OS and 5-year DFS rates in patients with Ewing's sarcoma. Therefore, serum LDH levels are an effective biomarker of Ewing's sarcoma prognosis.

  19. Clinicopathologic characteristics and outcome of childhood and adolescent Ewing's sarcoma in center of Iran.

    Science.gov (United States)

    Akhavan, A; Binesh, F; Hashemi, A; Shamshiri, H

    2014-01-01

    Ewing's sarcoma family is a group of small round cells tumors. The aim of this study is to evaluate clinicopathologic characteristics and outcome of Ewing's sarcoma in children and adolescents in Yazd, Iran. All patients under 19 years with documented pathology of Ewing's sarcoma family tumor who referred to Shahid Ramazanzadeh Radiotherapy center between 2002 to 2010 were enrolled in this retrospective study. Overall survival and disease free survival and prognostic factors were evaluated. Among approximately 80,000 patients who referred to Shahid Sadoughi pathology department, over an 8-year period, the total number of patients with Ewing sarcoma was 32, of which, 18 cases were under the age 19 . The mean age was 13.72 years. Five patients (27.8%) had metastatic disease at the time of diagnosis. Complete response had been achieved in 8 (44.4%) of the patients. Local recurrence occurred in 4 (22.2%) of the patients. During the follow up 13 (72.2%) of the patients showed metastases. The mean overall survival was 34.79 months (95% CI: 22.27-47.32) .One, two, four and five year survival was 72%, 39%, 25% and 17% respectively. Complete remission occurred in 10 patients (63.6%). A trend of better overall survival was found in these patients (p=0. 55). When the brain and bone metastases occurred, the overall survival decreased significantly (p=0. 003 ). The overall survival rate of Ewing's sarcoma is very low in comparison with other parts of the world.

  20. Needle aspiration biopsy in the diagnosis of lytic bone lesions in histiocytosis X, Ewing's sarcoma and neuroblastoma

    International Nuclear Information System (INIS)

    Thommesen, P.; Frederiksen, P.; Loewhagen, T.; Willems, J.S.

    1978-01-01

    Cytologic smears obtained by needle aspiration biopsy of lytic bone lesions in 15 patients with histiocytosis X, Ewing's sarcoma and neuroblastoma were reviewed. After conventional staining, histiocytosis X could be diagnosed and differentiated from small cell tumours such as Ewing's sarcoma and neuroblastoma. The need for sampling material for cytochemical and ultrastructural analysis of these small cell tumours by needle aspiration is emphasized. (Auth.)

  1. Long-term follow-up of 15 patients with non-metastatic Ewing's sarcoma and a skip lesion

    NARCIS (Netherlands)

    Jiya, T.U.; Wuisman, P.I.J.M.

    2005-01-01

    Background: Skip lesions in Ewing's sarcoma of the bone seem to be rare; to our knowledge only 7 cases have been published in the English medical literature. Methods: We retrospectively reviewed imaging and histological data relating to 235 patients with non-metastatic Ewing's sarcoma of the bone

  2. 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.)

  3. Ewing sarcoma in adults treated with modern radiotherapy techniques

    International Nuclear Information System (INIS)

    Casey, Dana L.; Meyers, Paul A.; Alektiar, Kaled M.; Magnan, Heather; Healey, John H.; Boland, Patrick J.; Wolden, Suzanne L.

    2014-01-01

    Background and purpose: To evaluate local control and survival outcomes in adults with Ewing sarcoma (ES) treated with radiotherapy (RT). Material and methods: Retrospective review of all 109 patients age ⩾18 treated for ES with RT to the primary site at Memorial Sloan Kettering Cancer Center between 1990 and 2011. RT was used as the definitive local control modality in 44% of patients, preoperatively for 6%, and postoperatively for 50%. Results: Median age at diagnosis was 27 years (range, 18–67). The 5-year local failure (LF) was 18%. Differences in LF were not identified when evaluated by modality of local control (RT versus combined surgery and RT), RT dose, fractionation, and RT technique. However, margin status at time of resection significantly predicted LF. The 5-year event-free survival and overall survival rates were 44% and 66% for patients with localized disease, compared with 16% and 26% for metastatic disease (p = 0.0005 and 0.0002). Tumor size, histopathologic response to chemotherapy, and treatment on or according to a protocol were also significantly associated with survival. Conclusions: This series of adults treated with modern chemotherapy and RT had prognostic factors and outcomes similar to adolescents with ES. All adults with ES should be treated with an aggressive, multidisciplinary approach

  4. IDH Mutation Analysis in Ewing Sarcoma Family Tumors

    Directory of Open Access Journals (Sweden)

    Ki Yong Na

    2015-05-01

    Full Text Available Background: Isocitrate dehydrogenase (IDH catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG with production of reduced nicotinamide adenine dinucleotide (NADH. Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis. Methods: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs, using a pentose nucleic acid clamping method and direct sequencing. Results: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. Conclusions: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

  5. Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum

    Science.gov (United States)

    Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

    2016-01-01

    Abstract Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor. PMID:26886614

  6. Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Stomach

    Directory of Open Access Journals (Sweden)

    Safi Khuri

    2016-11-01

    Full Text Available Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET is a tumor of small round cells arising in skeletal tissues. These tumors rarely arise in the stomach. We present a 31-year-old healthy female patient who was admitted to our surgical ward due to upper gastrointestinal hemorrhage. Upper endoscopy revealed a large ulcerated bleeding mass originating from the lesser curvature. Biopsy revealed tumor cell immunoreactivity positive for CD99, vimentin, and Ki67 (an index of proliferation. These findings were compatible with gastric ES/PNET. The fluorescence in situ hybridization analysis result for the EWSR1 gene rearrangement (11: 22 translocation was positive. The patient refused neoadjuvant treatment and thus underwent an operation during which a mass at the lesser curvature of the stomach was found. The mass was adhering to the pancreatic tail and to the mesentery of the transverse and descending colon. Total gastrectomy, distal pancreatectomy, splenectomy, and left adrenalectomy were done. The patient refused adjuvant treatment. She is free of disease 3 years after surgery.

  7. Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells.

    Directory of Open Access Journals (Sweden)

    Ana M Sanchez-Sanchez

    Full Text Available Melatonin kills or inhibits the proliferation of different cancer cell types, and this is associated with an increase or a decrease in reactive oxygen species, respectively. Intracellular oxidants originate mainly from oxidative metabolism, and cancer cells frequently show alterations in this metabolic pathway, such as the Warburg effect (aerobic glycolysis. Thus, we hypothesized that melatonin could also regulate differentially oxidative metabolism in cells where it is cytotoxic (Ewing sarcoma cells and in cells where it inhibits proliferation (chondrosarcoma cells. Ewing sarcoma cells but not chondrosarcoma cells showed a metabolic profile consistent with aerobic glycolysis, i.e. increased glucose uptake, LDH activity, lactate production and HIF-1α activation. Melatonin reversed Ewing sarcoma metabolic profile and this effect was associated with its cytotoxicity. The differential regulation of metabolism by melatonin could explain why the hormone is harmless for a wide spectrum of normal and only a few tumoral cells, while it kills specific tumor cell types.

  8. Effective radiation therapy on two cases of primary Ewing's sarcoma of the rib

    International Nuclear Information System (INIS)

    Monzen, Yoshio; Nakanishi, Kazue; Ajimu, Akira; Ishida, Yutaka; Fujimoto, Toshifumi; Hayashi, Kuniaki; Hombo, Zenichiro; Amamoto, Yuhei.

    1987-01-01

    Two cases of primary Ewing's sarcoma of the rib are reported, in which radiation therapy was quite effective. Case 1 was an 18-year-old female who had had an operation and radiation therapy for Ewing's sarcoma of the left 7th rib. She was referred to our hospital after a recurrent tumor was found. Radiation therapy (tumor dose 46.2 Gy) and chemotherapy were given. The tumor disappeared and there has been no relapse for 1 year and 3 months after the treatment. Case 2 was a 2-year-old-infant. Radiation therapy (tumor dose 74 Gy) was given for primary Ewing's sarcoma of the left 6th rib. The tumor became small and was successfully removed at operation. There has been no relapse or distant metastasis for 8 months following the operation. We emphasize the importance of multidisciplinary treatment in case 1 and the usefulness of preoperative radiotherapy in case 2. (author)

  9. 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

  10. Microarray-based DNA methylation study of Ewing's sarcoma of the bone.

    Science.gov (United States)

    Park, Hye-Rim; Jung, Woon-Won; Kim, Hyun-Sook; Park, Yong-Koo

    2014-10-01

    Alterations in DNA methylation patterns are a hallmark of malignancy. However, the majority of epigenetic studies of Ewing's sarcoma have focused on the analysis of only a few candidate genes. Comprehensive studies are thus lacking and are required. The aim of the present study was to identify novel methylation markers in Ewing's sarcoma using microarray analysis. The current study reports the microarray-based DNA methylation study of 1,505 CpG sites of 807 cancer-related genes from 69 Ewing's sarcoma samples. The Illumina GoldenGate Methylation Cancer Panel I microarray was used, and with the appropriate controls (n=14), a total of 92 hypermethylated genes were identified in the Ewing's sarcoma samples. The majority of the hypermethylated genes were associated with cell adhesion, cell regulation, development and signal transduction. The overall methylation mean values were compared between patients who survived and those that did not. The overall methylation mean was significantly higher in the patients who did not survive (0.25±0.03) than in those who did (0.22±0.05) (P=0.0322). However, the overall methylation mean was not found to significantly correlate with age, gender or tumor location. GDF10 , OSM , APC and HOXA11 were the most significant differentially-methylated genes, however, their methylation levels were not found to significantly correlate with the survival rate. The DNA methylation profile of Ewing's sarcoma was characterized and 92 genes that were significantly hypermethylated were detected. A trend towards a more aggressive behavior was identified in the methylated group. The results of this study indicated that methylation may be significant in the development of Ewing's sarcoma.

  11. Sarcoma de Ewing: aspectos clínicos e radiográficos de 226 casos Ewing's sarcoma: clinical and radiographic aspects of 226 cases

    Directory of Open Access Journals (Sweden)

    Julian Catalan

    2005-09-01

    Full Text Available OBJETIVO: Avaliar os aspectos radiográficos e clínicos presentes em pacientes com o diagnóstico de sarcoma de Ewing confirmado por histopatologia. MATERIAIS E MÉTODOS: Foram analisados, neste trabalho, os dados clínicos e radiográficos (quando disponíveis de 226 pacientes com o diagnóstico de sarcoma de Ewing ósseo. RESULTADOS: Dos casos avaliados, 61,5% (139 eram do sexo masculino e 83,7% (189 eram brancos. A mediana de idade dos pacientes foi de 14 anos e a topografia mais freqüente das lesões foi o osso ilíaco, em 13,7% (31 dos casos. O aspecto radiográfico mais comum foi o de lesão lítica com reação periosteal (padrões variados, em 32,7% (74 dos casos. CONCLUSÃO: O sarcoma de Ewing ósseo é uma neoplasia bastante agressiva, ocorrendo mais comumente em indivíduos na segunda década de vida e cujo aspecto radiográfico mais comum é o de lesão lítica com reação periosteal típica de lesão agressiva.OBJECTIVE: To review the clinical and radiographic findings in patients with histologically confirmed Ewing's sarcoma. MATERIALS AND METHODS: Clinical and radiological (whenever available data of 226 patients with Ewing's sarcoma of the bone were analyzed. RESULTS: Of the evaluated cases, 61.5% (139 were male and 83.7% (189 were white. The average age was 14 years old and the most common site of the lesions was the iliac bone, seen in 13.7% (31 of the cases. The most common radiological findings were lytic lesion with periosteal reaction, seen in 32.7% (74 of the patients. CONCLUSION: Ewing's sarcoma of bone is an aggressive neoplasm, occurring mainly in the second decade of life, which main radiological findings are lytic lesions with periosteal reaction, typical characteristic of aggressive lesions.

  12. Gene Expression Music Algorithm-Based Characterization of the Ewing Sarcoma Stem Cell Signature

    Directory of Open Access Journals (Sweden)

    Martin Sebastian Staege

    2016-01-01

    Full Text Available Gene Expression Music Algorithm (GEMusicA is a method for the transformation of DNA microarray data into melodies that can be used for the characterization of differentially expressed genes. Using this method we compared gene expression profiles from endothelial cells (EC, hematopoietic stem cells, neuronal stem cells, embryonic stem cells (ESC, and mesenchymal stem cells (MSC and defined a set of genes that can discriminate between the different stem cell types. We analyzed the behavior of public microarray data sets from Ewing sarcoma (“Ewing family tumors,” EFT cell lines and biopsies in GEMusicA after prefiltering DNA microarray data for the probe sets from the stem cell signature. Our results demonstrate that individual Ewing sarcoma cell lines have a high similarity to ESC or EC. Ewing sarcoma cell lines with inhibited Ewing sarcoma breakpoint region 1-Friend leukemia virus integration 1 (EWSR1-FLI1 oncogene retained the similarity to ESC and EC. However, correlation coefficients between GEMusicA-processed expression data between EFT and ESC decreased whereas correlation coefficients between EFT and EC as well as between EFT and MSC increased after knockdown of EWSR1-FLI1. Our data support the concept of EFT being derived from cells with features of embryonic and endothelial cells.

  13. Camptothecin-Based Regimens for Treatment of Ewing Sarcoma: sPast Studies and Future Directions

    Directory of Open Access Journals (Sweden)

    Lars Wagner

    2011-01-01

    Full Text Available New therapies are needed to improve survival for patients with Ewing sarcoma. Over the past decade, camptothecin agents such as topotecan and irinotecan have demonstrated activity against Ewing sarcoma, especially in combination with alkylating agents. Previous studies have shown camptothecin-based combinations to be tolerable outpatient strategies that are attractive for salvage therapy. This paper highlights important issues related to drug dosing, schedule of administration, pharmacokinetics, toxicity, and activity of commonly used camptothecin-based regimens. Also discussed are strategies for incorporating these regimens into therapy for newly diagnosed patients, including several potential possibilities for combination with targeted agents.

  14. Sarcoma de Ewing epidural lombar primário: Relato de caso

    Directory of Open Access Journals (Sweden)

    Kadri Paulo Abdo do Seixo

    2002-01-01

    Full Text Available Relatamos o caso de uma jovem de 15 anos, com quadro de paraparesia de inicio agudo, secundário a processo expansivo epidural na coluna lombar, cujo diagnóstico histopatológico foi consistente com sarcoma de Ewing, sem envolvimento ósseo. Revisando a literatura encontramos apenas outros 17 casos de sarcoma de Ewing extra-esquelético de localização primária no espaço epidural raqueano.

  15. Acute lymphoblastic leukemia with multiple cytogenetic abnormalities secondary to treatment of Ewing's sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Al-Homaidhi, A.M. [Department of Medicine, Princess Margaret Hospital and The University of Toronto, 610 University Ave, Rm. 4-429, Toronto, Ont. M5G 2M9 (Canada); Patterson, B. [Department of Pathology, Princess Margaret Hospital and The University of Toronto, 610 University Ave, Rm. 4-429, Toronto, Ont. M5G 2M9 (Canada); Rubin, S. [Moncton Hospital, Moncton, New Brunswick (Canada); Lipton, J.H. [Department of Medicine, Princess Margaret Hospital and The University of Toronto, 610 University Ave, Rm. 4-429, Toronto, Ont. M5G 2M9 (Canada)

    1999-06-01

    We report the case of a 22-year-old man with Ewing's sarcoma who attained a complete remission (CR) after combination radiotherapy and chemotherapy. Secondary acute lymphoblastic leukemia with multiple cytogenetic abnormalities involving chromosome 5 and 7 developed 16 years later. The patient underwent induction chemotherapy and entered a CR. Peripheral blood stem cell transplantation from a matched sibling was performed successfully and he is in complete remission of both ALL and Ewing's sarcoma. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. Acute lymphoblastic leukemia with multiple cytogenetic abnormalities secondary to treatment of Ewing's sarcoma

    International Nuclear Information System (INIS)

    Al-Homaidhi, A.M.; Patterson, B.; Rubin, S.; Lipton, J.H.

    1999-01-01

    We report the case of a 22-year-old man with Ewing's sarcoma who attained a complete remission (CR) after combination radiotherapy and chemotherapy. Secondary acute lymphoblastic leukemia with multiple cytogenetic abnormalities involving chromosome 5 and 7 developed 16 years later. The patient underwent induction chemotherapy and entered a CR. Peripheral blood stem cell transplantation from a matched sibling was performed successfully and he is in complete remission of both ALL and Ewing's sarcoma. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. Ewing's sarcoma recurrence vs radiation necrosis in dynamic contrast-enhanced MR imaging: a case report

    International Nuclear Information System (INIS)

    El Khadrawy, A.M.; Hoffer, F.A.; Reddick, W.E.

    1999-01-01

    Purpose. We report a case of Ewing's sarcoma in the right distal femur in a 6-year-old male to demonstrate how dynamic contrast-enhanced magnetic resonance imaging (DEMRI) findings predicted histopathology. Materials and methods. DEMRI was performed at presentation and during and after completion of chemotherapy and radiation therapy. Histopathologic studies were done at presentation, at 77 weeks (20 weeks after a pathological fracture), and from the en bloc resection at 104 weeks. Results. DEMRI predicted the early tumor response, absence of tumor recurrence, presence of necrosis and lack of fracture healing, confirmed by histopathology. Conclusion. DEMRI is a clinically useful tool in managing Ewing's sarcoma. (orig.)

  18. Metastatic Ewing's Sarcoma: Revisiting the “Evidence on the Fence”

    Science.gov (United States)

    Khanna, Nehal; Pandey, Avinash; Bajpai, Jyoti

    2017-01-01

    Metastatic Ewing's sarcoma is a challenging disease for oncology care providers with wide spectrum of disease at presentation, widely varying approach to the treatment and varied outcomes. The paucity of randomized evidence is a barrier in developing a consensus. This perspective provides the evidence ”for and against” the benefit of aggressive approach including local and systemic therapy in patients presenting with metastatic Ewing's sarcoma and provide general recommendations so as to help select patients who will benefit with definitive intent treatment and also, avoid aggressive approach in patients with dismal outcome. PMID:28900327

  19. Renal artery stenosis after radiotherapy for Ewing's sarcoma

    International Nuclear Information System (INIS)

    Tacconi, S.; Bieri, S.

    2008-01-01

    Background: the fact that therapeutic irradiation can induce significant stenosis in the arteries of the head, neck, and chest, as welt as in the aorta and the iliac arteries, is familiar in daily practice and well documented in the literature. By contrast, radiation-induced renal artery stenosis seems to be a less widely known complication. Patients and methods: the sudden onset of medically refractory arterial hypertension and coma in a 27-year-old man is reported, who had been treated at age 20 with chemotherapy and radiotherapy for Ewing's sarcoma in the lumbar region. This treatment had been performed at the hospital of Sion, Switzerland in 2001. Also, the relevant literature from 1965 to 2007 is reviewed to underscore various aspects of this problem and to demonstrate the clinical relevance of renal artery stenosis as a potential long-term sequela of radiotherapy. Conclusion: radiation-induced renal artery stenosis has only rarely been described in the literature, but arterial hypertension due to radiation-induced renal artery stenosis is a serious long-term sequela that can appear at a latency of up to 20 years after treatment. The paucity of reports presumably reflects the lesser frequency of radiotherapy for retroperitoneal tumors as compared to head-and-neck cancers, as well as lower awareness of the problem due to diagnostic bias in the era before CT and MRI were in routine use: at that time, carotid artery stenosis was easy to diagnose by ultrasonography, while radiation-induced renal artery stenosis, whose real incidence may well be higher, probably often went undetected. Thus, when a patient with a history of abdominal or retroperitoneal radiotherapy unexpectedly develops intractable hypertension, radiation-induced renal artery stenosis must be included in the differential diagnosis. (orig.)

  20. Modeling initiation of Ewing sarcoma in human neural crest cells.

    Directory of Open Access Journals (Sweden)

    Cornelia von Levetzow

    2011-04-01

    Full Text Available Ewing sarcoma family tumors (ESFT are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC and/or neural crest (NCSC stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC. Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

  1. Congenital Ewing's Sarcoma in a neonate in Uyo - a case report ...

    African Journals Online (AJOL)

    Congenital Ewing's sarcoma is a very rare occurrence indeed with only one case involving the humerus and none involving the ulna that has been noted in the literature to our knowledge. It is one of those tumours that not only do they rarely occur in the neonatal period, but is also very uncommon in black people.

  2. Solitary extra-skeletal sinonasal metastasis from a primary skeletal Ewing's sarcoma.

    Science.gov (United States)

    Hayes, S M; Jani, T N; Rahman, S M; Jogai, S; Harries, P G; Salib, R J

    2011-08-01

    Ewing's sarcoma is a rare, malignant tumour predominantly affecting young adolescent males. We describe a unique case of an isolated extra-skeletal metastasis from a skeletal Ewing's sarcoma primary, arising in the right sinonasal cavity of a young man who presented with severe epistaxis and periorbital cellulitis. Histologically, the lesion comprised closely packed, slightly diffuse, atypical cells with round, hyperchromatic nuclei, scant cytoplasm and occasional mitotic figures, arranged in a sheet-like pattern. Immunohistochemical analysis showed positive staining only for cluster of differentiation 99 glycoprotein. Fluorescent in situ hybridisation identified the Ewing's sarcoma gene, confirming the diagnosis. Complete surgical resection was achieved via a minimally invasive endoscopic transnasal approach; post-operative radiotherapy. Ten months post-operatively, there were no endoscopic or radiological signs of disease. Metastatic Ewing's sarcoma within the head and neck is incredibly rare and can pose significant diagnostic and therapeutic challenges. An awareness of different clinical presentations and distinct histopathological features is important to enable early diagnosis. This case illustrates one potential management strategy, and reinforces the evolving role of endoscopic transnasal approaches in managing sinonasal cavity and anterior skull base tumours.

  3. Severe gonadotoxic insult manifests early in young girls treated for Ewing sarcoma

    DEFF Research Database (Denmark)

    Mörse, Helena; Elfving, Maria; Turkiewicz, Aleksandra

    2016-01-01

    We prospectively investigated anti-Müllerian hormone (AMH) as a measure of ovarian insult in young females during and after treatment for Wilms tumor (WT), osteosarcoma (OS), and Ewing sarcoma (ES).Twenty-one female childhood cancer patients, with a mean age of 7.9 years (range 0.6-17), entered...

  4. Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

    Directory of Open Access Journals (Sweden)

    David Olmos

    2011-01-01

    Full Text Available Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response.

  5. Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

    Science.gov (United States)

    Olmos, David; Martins, Ana Sofia; Jones, Robin L.; Alam, Salma; Scurr, Michelle; Judson, Ian R.

    2011-01-01

    Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response. PMID:21647361

  6. Ewing's sarcoma arising from the adrenal gland in a young male: a case report.

    Science.gov (United States)

    Zahir, Muhammad Nauman; Ansari, Tayyaba Zehra; Moatter, Tariq; Memon, Wasim; Pervez, Shahid

    2013-12-13

    Ewing's sarcoma uncommonly arises from extraosseous soft tissue or parenchymal organs. Primary adrenal Ewing's Sarcoma, although very rare, is extremely aggressive and commonly fatal. A 17 year old Pakistani male was referred to the outpatient oncology clinic at our center with a three month history of concomitant pain, swelling and dragging sensation in the right hypochondrium. Abdominal examination revealed a large, firm mass in the right hypochondrium extending into the right lumbar region and epigastrium. His genital exam was unremarkable and there were no stigmata of hepatic or adrenal disease.Computed tomography scans revealed a large peripherally enhancing mass in the hepatorenal area, biopsy of which showed a neoplastic lesion composed of small round blue cells which exhibited abundance of glycogen and stained diffusely positive for CD99 (MIC2 antigen). Fluorescence in situ hybridization demonstrated gene rearrangement at chromosome 22q12 which confirmed the diagnosis of Ewing's sarcoma. Staging scans revealed pulmonary metastasis and hence he was commenced on systemic chemotherapy. This case report highlights the importance of keeping Ewing's sarcoma in mind when a young patient presents with a large non-functional adrenal mass.

  7. Maturation toward neuronal tissue in a Ewing sarcoma of bone after chemotherapy

    NARCIS (Netherlands)

    Salet, Maria Carolina Wilhelmina; Vogels, Rob; Brons, Paul P. T.; Schreuder, Bart; Flucke, Uta

    2016-01-01

    Background: Ewing sarcoma is the second most common bone tumor, occurring mainly in children and young adults. It shows a typical primitive, small round cell morphology and a characteristic fusion oncogene involving EWSR1 and members of the ETS family in most of the cases. Neuronal maturation after

  8. Very Late Local Relapse of Ewing's Sarcoma of the Head and Neck treated with Aggressive Multimodal Therapy

    Directory of Open Access Journals (Sweden)

    J. Thariat

    2008-01-01

    Full Text Available Ewing's sarcoma's relapse rarely occurs more than two years after the initial diagnosis. We report the case of a 26-year-old man with a history of Ewing's sarcoma of the left maxillary sinus at the age of 10 who presented with a very late local relapse, 16 years after the first occurrence of disease. Ultimate control was achieved after multimodal therapy including surgery, high-dose chemotherapy, and radiotherapy. This report indicates that local relapses of Ewing's sarcoma can be treated with curative intent in selected cases.

  9. Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

    Science.gov (United States)

    Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

    2013-11-01

    Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

  10. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

    Science.gov (United States)

    Redini, Françoise; Heymann, Dominique

    2015-01-01

    Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  11. 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.

  12. 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.

  13. Distinguishing Osteomyelitis From Ewing Sarcoma on Radiography and MRI

    Science.gov (United States)

    McCarville, M. Beth; Chen, Jim Y.; Coleman, Jamie L.; Li, Yimei; Li, Xingyu; Adderson, Elisabeth E.; Neel, Mike D.; Gold, Robert E.; Kaufman, Robert A.

    2017-01-01

    OBJECTIVE The purpose of this study was to determine whether clinical and imaging features can distinguish osteomyelitis from Ewing sarcoma (EWS) and to assess the accuracy of percutaneous biopsy versus open biopsy in the diagnosis of these diseases. MATERIALS AND METHODS Three radiologists reviewed the radiographs and MRI examinations of 32 subjects with osteomyelitis and 31 subjects with EWS to determine the presence of 36 imaging parameters. Information on demographic characteristics, history, physical examination findings, laboratory findings, biopsy type, and biopsy results were recorded. Individual imaging and clinical parameters and combinations of these parameters were tested for correlation with findings from histologic analysis. The diagnostic accuracy of biopsy was also determined. RESULTS On radiography, the presence of joint or metaphyseal involvement, a wide transition zone, a Codman triangle, a periosteal reaction, or a soft-tissue mass, when tested individually, was more likely to be noted in subjects with EWS (p ≤ 0.05) than in subjects with osteomyelitis. On MRI, permeative cortical involvement and soft-tissue mass were more likely in subjects with EWS (p ≤ 0.02), whereas a serpiginous tract was more likely to be seen in subjects with osteomyelitis (p = 0.04). African Americans were more likely to have osteomyelitis than EWS (p = 0). According to the results of multiple regression analysis, only ethnicity and soft-tissue mass remained statistically significant (p ≤ 0.01). The findings from 100% of open biopsies (18/18) and 58% of percutaneous biopsies (7/12) resulted in the diagnosis of osteomyelitis, whereas the findings from 88% of open biopsies (22/25) and 50% of percutaneous biopsies (3/6) resulted in a diagnosis of EWS. CONCLUSION Several imaging features are significantly associated with either EWS or osteomyelitis, but many features are associated with both diseases. Other than ethnicity, no clinical feature improved diagnostic

  14. 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

  15. Cutaneous and subcutaneous Ewing's sarcoma: an indolent disease

    International Nuclear Information System (INIS)

    Chow, Edward; Merchant, Thomas E.; Pappo, Alberto; Jenkins, Jesse J.; Shah, Amit B.; Kun, Larry E.

    2000-01-01

    Purpose: The occurrence of extraosseous Ewing's sarcoma (ES) in deep soft tissues has been well described, but cases in which this tumor occurs in a primary cutaneous or subcutaneous site have rarely been reported. The superficial variant may be less aggressive than are the more common bony and deep soft tissue counterparts with an apparently favorable outcome. A retrospective review of patients with cutaneous or subcutaneous ES was conducted to analyze outcome and patterns of failure. Methods and Materials: Between July 1985 and March 1997, 14 patients with cutaneous or subcutaneous ES were treated at St. Jude Children's Research Hospital. The median age at presentation was 16 years (range 7-21 years). Anatomic locations included trunk and pelvis (7), upper or lower extremity (4), and head and neck (3). The median size of the lesion was 3 cm (range, 1-12 cm). Thirteen had definitive surgical resections, and one had biopsy of the mass at the time of referral. They were enrolled on institutional (12) or cooperative group (2) protocols. All patients received chemotherapy, composed of vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and dactinomycin. Patients on institutional protocols received radiation (36 Gy) to the operative bed (150-180 cGy/fraction/day). Postoperative radiotherapy was omitted for 2 patients who had complete resection on the cooperative group study. Results: No patients had metastatic disease at presentation. Thirteen patients had wide local excision of the primary tumors prior to enrollment on chemotherapy; surgical margins were negative (10), microscopically positive (2), and indeterminate (1). Eleven patients received radiotherapy to the tumor bed; 2 with clear surgical margins were treated without irradiation. The patient who had biopsy only received induction chemotherapy followed by definitive surgical resection and postoperative radiotherapy. The median follow-up was 77 months (range 17-111 months). None of the patients

  16. High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123 for Extraskeletal Ewing's Sarcoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Tomoya Sakabe

    2011-01-01

    Full Text Available Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123 contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment.

  17. Does surgery or radiation provide the best overall survival in Ewing's sarcoma? A review of the National Cancer Data Base.

    Science.gov (United States)

    Miller, Benjamin J; Gao, Yubo; Duchman, Kyle R

    2017-09-01

    There is continuing debate regarding the ideal modality for local control of the primary tumor for patients with Ewing's sarcoma. The primary aim of this study is to investigate the impact of the method of local control on overall survival in patients with Ewing's sarcoma. The National Cancer Data Base was used to identify patients Ewing's sarcoma of bone. A Kaplan-Meier survival analysis was performed at 2, 5, and 10 years. Factors with a level of significance of P 8 cm, and male sex while controlling for tumor site. Surgery alone was consistently the method of local control that resulted in the highest overall survival. Surgery alone resulted in the best overall survival for patients with Ewing's sarcoma of bone. The results of this investigation provide support to the approach of surgical resection with negative margins when possible. © 2017 Wiley Periodicals, Inc.

  18. Expression of neural cell adhesion molecules and neurofilament protein isoforms in Ewing's sarcoma of bone and soft tissue sarcomas of other than rhabdomyosarcoma

    NARCIS (Netherlands)

    Molenaar, W.M.; Muntinghe, F.L.H.

    1999-01-01

    In a previous study, it was shown that rhabdomyosarcomas widely express "neural" markers, such as neural cell adhesion molecules (N-CAM) and neurofilament protein isoforms, In the current study, a series of Ewing's sarcomas of bone and soft tissue sarcomas other than rhabdomyosarcoma was probed for

  19. Long-term results following multidisciplinary treatment of localized Ewing's sarcoma in children and adolescents

    International Nuclear Information System (INIS)

    Ullmann, C.; Sauer, R.; Grabenbauer, G.G.; Dunst, J.

    2008-01-01

    Purpose: To identify results and prognostic factors on long-term survival and local control following treatment of localized Ewing's sarcoma. Patients and Methods: Between 1979 and 2004, a total of 60 children and young adults with Ewing's sarcoma were treated. Patients with distant metastases at presentation (n = 6) and recurrent cases (n = 2) were excluded from this analysis. Patients were exclusively treated within ongoing national and international protocols CESS-81, CESS-86, EICESS-92, EURO-EWING-99. All patients received local irradiation with a total dose of 45-60 Gy; in addition, 41 (79%) of the patients had local surgical procedures, 27 (52%) of them with clear margins. Results: Overall survival rates at 5 and 10 years were 56% and 45%, respectively. Patients ≤ 14 years at diagnosis had overall survival rates of 66% and 61% at 5 and 10 years compared to older patients with corresponding survival rates of 47% and 31%, respectively (p = 0.05). Patients with tumors of lower volume (≤ 100 ml) had significantly better survival rates at 5 and 10 years: 82% and 60% versus 42% und 39% (p = 0.03). Seven of 52 (14%) patients experienced local failure; no significant impact was noted for any of the following factors: treatment protocol, radiation dose, surgery. Conclusion: Radiotherapy with and without surgery of Ewing's sarcoma is a highly effective local treatment option. It seems preferable to mutilating surgery. (orig.)

  20. 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

  1. 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

  2. Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

    Directory of Open Access Journals (Sweden)

    Kelly M. Bailey

    2016-08-01

    Full Text Available Metastatic Ewing sarcoma has a very poor prognosis and therefore new investigations into the biologic drivers of metastatic progression are key to finding new therapeutic approaches. The tumor microenvironment is highly dynamic, leading to exposure of different regions of a growing solid tumor to changes in oxygen and nutrient availability. Tumor cells must adapt to such stress in order to survive and propagate. In the current study, we investigate how Ewing sarcoma cells respond to the stress of growth factor deprivation and hypoxia. Our findings reveal that serum deprivation leads to a reversible change in Ewing cell cytoskeletal phenotypes. Using an array of migration and invasion techniques, including gelatin matrix degradation invadopodia assays, we show that exposure of Ewing sarcoma cells to serum deprivation and hypoxia triggers enhanced migration, invadopodia formation, matrix degradation and invasion. Further, these functional changes are accompanied by and dependent on activation of Src kinase. Activation of Src, and the associated invasive cell phenotype, were blocked by exposing hypoxia and serum-deprived cells to the Src inhibitor dasatinib. These results indicate that Ewing sarcoma cells demonstrate significant plasticity in response to rapidly changing micro-environmental stresses that can result from rapid tumor growth and from necrosis-causing therapies. In response to these stresses, Ewing cells transition to a more migratory and invasive state and our data show that Src is an important mediator of this stress response. Our data support exploration of clinically available Src inhibitors as adjuvant agents for metastasis prevention in Ewing sarcoma.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Etoposide and carbo-or cisplatin combination therapy in refractory or relapsed Ewing sarcoma: a large retrospective study

    NARCIS (Netherlands)

    van Maldegem, Annemiek M.; Benson, Charlotte; Rutkowski, Piotr; Blay, Jean-Yves; van den Berg, Henk; Placzke, Joanna; Rasper, Meybrit; Judson, Ian; Juergens, Heribert; Dirksen, Uta; Gelderblom, Hans

    2015-01-01

    Patients with Ewing sarcoma (EWS) who develop refractory or relapsed disease have limited treatment options. In some sarcoma centres in Europe the combination of etoposide with carbo- or cisplatin is being used for these patients, however, there are no published data available yet. Here we

  9. Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval Involvement in a Pregnant Woman.

    Science.gov (United States)

    Ding, Yinghui; Huang, Zhenlin; Ding, Yafei; Jia, Zhankui; Gu, Chaohui; Xue, Rui; Yang, Jinjian

    2016-01-01

    In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible. © 2016 S. Karger AG, Basel.

  10. Roentgenographic-pathologic correlation of diffuse sclerosis in Ewing sarcoma of bone

    International Nuclear Information System (INIS)

    Shirley, S.K.; Kissane, J.M.; Siegal, G.P.; Askin, F.B.; Foulkes, M.A.; University of Texas Cancer Center, Houston

    1984-01-01

    Roentgenographic review of the first 210 cases of Ewing sarcoma (ES) in the Intergroup Ewing Sarcoma Study revealed that 37.6% of cases has evidence of diffusely increased intraosseous density or diffuse sclerosis (DS). In these cases the sclerosis was usually mixed with various patterns of lysis and/or combined with a periosteal reaction. A radiograph blinded histologic review of selected biopsies showed an 83% incidence of dead bone compared to 23% in those without DS. Ten percent of the cases with DS had appositional new bone formation on dead bone whereas none of the cases without DS showed such reactions. Pathologic explanation of the roentgenographically identified diffuse sclerosis in ES has not been previously well documented in the medical literature. (orig.)

  11. Extraosseous Ewing's sarcoma / primitive neuroectodermal tumor of the sacral nerve plexus

    International Nuclear Information System (INIS)

    Narula, MK; Gupta, Nishant; Anand, Rama; Kapoor, Sudhir

    2009-01-01

    We report an unusual case of Ewing's sarcoma / primitive neuroectodermal tumor (PNET) of the sacral nerve plexus in a 9-year-old boy who presented with a soft tissue swelling and severe piercing pain in the lower back region. MRI of the lumbosacral spine showed a lobulated soft tissue mass with clubbed finger-like projections along the path of the sacral nerves, which had caused widening of the spinal canal and the sacral foramina (S2–S4 level). There was presacral extension and posterior scalloping of the sacral vertebrae. Histopathology of the lesion confirmed Ewing's sarcoma / PNET of the sacral spinal nerve plexus. The patient responded favorably to chemotherapy and radiotherapy, showing clinical and radiological improvement

  12. Ewing's sarcoma of the cranial vault: a case report.

    Science.gov (United States)

    Feki, Jihene; Guermazi, Zeineb; Kammoun, Brahim; Khanfir, Afef; Toumi, Nabil; Boudawara, Tahiya; Boudawara, Zaher; Daoud, Jamel; Frikha, Mounir

    2017-12-01

    Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

  13. Second malignancies after treatment for Ewing's sarcoma: a report of the CESS-studies

    International Nuclear Information System (INIS)

    Dunst, Juergen; Ahrens, Susanne; Paulussen, Michael; Ruebe, Christian; Winkelmann, Wilfried; Zoubek, Andreas; Harms, Dieter; Juergens, Herbert

    1998-01-01

    Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (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 in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. Results: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but

  14. Extraskeletal ewing's sarcoma family of tumors in adults. Prognostic factors and clinical outcome

    International Nuclear Information System (INIS)

    Tural, D.; Molinas Mandel, N.; Dervisoglu, S.

    2012-01-01

    The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma. (author)

  15. Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI

    International Nuclear Information System (INIS)

    Taets ven Amerongen, A.H.M.; Kaiser, M.C.; Waal, F.C. de

    1987-01-01

    A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted an MRI appearance allowing us to exclude tumor outgrowth into the brain. (orig.)

  16. Diagnostic value of MRI signs in differentiating Ewing sarcoma from osteomyelitis.

    Science.gov (United States)

    Kasalak, Ömer; Overbosch, Jelle; Adams, Hugo Ja; Dammann, Amelie; Dierckx, Rudi Ajo; Jutte, Paul C; Kwee, Thomas C

    2018-01-01

    Background The value of magnetic resonance imaging (MRI) signs in differentiating Ewing sarcoma from osteomyelitis has not be thoroughly investigated. Purpose To investigate the value of various MRI signs in differentiating Ewing sarcoma from osteomyelitis. Material and Methods Forty-one patients who underwent MRI because of a bone lesion of unknown nature with a differential diagnosis that included both Ewing sarcoma and osteomyelitis were included. Two observers assessed several MRI signs, including the transition zone of the bone lesion, the presence of a soft-tissue mass, intramedullary and extramedullary fat globules, and the penumbra sign. Results Diagnostic accuracies for discriminating Ewing sarcoma from osteomyelitis were 82.4% and 79.4% for the presence of a soft-tissue mass, and 64.7% and 58.8% for a sharp transition zone of the bone lesion, for readers 1 and 2 respectively. Inter-observer agreement with regard to the presence of a soft-tissue mass and the transition zone of the bone lesion were moderate (κ = 0.470) and fair (κ = 0.307), respectively. Areas under the receiver operating characteristic curve of the diameter of the soft-tissue mass (if present) were 0.829 and 0.833, for readers 1 and 2 respectively. Mean inter-observer difference in soft-tissue mass diameter measurement ± limits of agreement was 35.0 ± 75.0 mm. Diagnostic accuracies of all other MRI signs were all value in this setting.

  17. A decade in banking Ewing sarcoma: a report from the children’s oncology group

    Directory of Open Access Journals (Sweden)

    Scott C. Borinstein

    2013-03-01

    Full Text Available Outcomes for patients with metastatic and recurrent Ewing sarcoma remain poor and a better understanding of the biology of this malignancy is critical to the development of prognostic biomarkers and novel therapies. Therefore, the Children’s Oncology Group (COG has created tissue banking protocols designed to collect high quality clinically annotated tumor specimens that can be distributed to researchers to perform basic science and correlative investigation. Data from the COG Ewing sarcoma tissue banking protocols AEWS02B1 and its successor study AEWS07B1 were reviewed in this study. 635 patients were enrolled on AEWS02B1 and 396 patients have had tissue submitted to AEWS07B1. The average age of participation was 13.2 years. 86% were less than 19 years old and only 6% were greater than 21 years of age at diagnosis. When compared to SEER data, approximately 18% of all cases and only 8% of all patients >20 years old diagnosed with Ewing sarcoma annually in the United States have had tumor banked. The majority of participants submitted formalin fixed paraffin embedded primary tumor and blood samples. In total, fresh frozen tissue was submitted for only 29% of cases. Only 7 metastatic tumor samples have been collected. Although the COG has been successful in collecting tumor samples from patients newly diagnosed with Ewing sarcoma, fresh frozen tumor specimens from primary and metastatic disease are critically needed, especially from young adult patients, in order to conduct high quality basic science and translational research investigation with a goal of developing better treatments.

  18. Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Taets ven Amerongen, A.H.M.; Kaiser, M.C.; Waal, F.C. de

    1987-03-01

    A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted an MRI appearance allowing us to exclude tumor outgrowth into the brain.

  19. Intradural extramedullary Ewing's sarcoma: A case report and review of the literature.

    Science.gov (United States)

    Paterakis, Konstantinos; Brotis, Alexandros; Tasiou, Anastasia; Kotoula, Vasiliki; Kapsalaki, Eftychia; Vlychou, Marianna

    Extra-skeletal Ewing's sarcomas are very rare lesions to the spine surgeon, with the intradural, extramedullary lesions being even rarer. Herein we present a patient with an intradural, extramedullary form of Ewing's sarcoma and review the relevant literature. The medical records, operative reports, radiographical studies and histological examinations of a single patient are retrospectively reviewed. A 31-year old male presented with back-pain, right-leg progressive paraparesis, and inability to walk. Both motor and sensory disturbances were revealed on the right leg at the clinical examination. Lumbar MRI showed two lesions. The first one was an intradural, extramedullary lesion at the L2-L3 level, while the second was smaller, located at the bottom of the dural sac. The patient underwent gross total resection of the L2-L3 lesion after a bilateral laminectomy. Histological examination was compatible with Ewing's sarcoma, and was verified by molecular analysis. No other extra-skeletal or skeletal lesion was found. A chemotherapy scheme was tailored to the patients' histological diagnosis. The patient presented with local recurrence and bone metastasis 2 years after his initial diagnosis. A second operation was performed and the follow up of the patient showed no disease progression 18 months after revision surgery. The spine surgeon should be aware of the existence of such rare entities, in order to timely fulfill the staging process and institute the proper therapy. The management of patients with extra-skeletal Ewing's sarcomas involves professionals as members of a multidisciplinary team, all of which should co-operate for the patient's optimal outcome. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  20. A Decade in Banking Ewing Sarcoma: A Report from the Children’s Oncology Group

    Science.gov (United States)

    Borinstein, Scott C.; Beeler, Natalie; Block, John J.; Gorlick, Richard; Grohar, Patrick; Jedlicka, Paul; Krailo, Mark; Morris, Carol; Phillips, Sharon; Siegal, Gene P.; Lawlor, Elizabeth R.; Lessnick, Stephen L.

    2013-01-01

    Outcomes for patients with metastatic and recurrent Ewing sarcoma remain poor and a better understanding of the biology of this malignancy is critical to the development of prognostic biomarkers and novel therapies. Therefore, the Children’s Oncology Group (COG) has created tissue banking protocols designed to collect high quality, clinically annotated, tumor specimens that can be distributed to researchers to perform basic science and correlative investigation. Data from the COG Ewing sarcoma tissue banking protocols AEWS02B1 and its successor study AEWS07B1 were reviewed in this study. Six-hundred and thirty five patients were enrolled on AEWS02B1 and 396 patients have had tissue submitted to AEWS07B1. The average age of participation was 13.2 years. About 86% were less than 19 years old and only 6% were greater than 21 years of age at diagnosis. When compared to SEER data, approximately 18% of all cases and only 8% of all patients >20 years old diagnosed with Ewing sarcoma annually in the United States have had tumor banked. The majority of participants submitted formalin fixed, paraffin embedded, primary tumor and blood samples. In total, fresh frozen tissue was submitted for only 29% of cases. Only seven metastatic tumor samples have been collected. Although the COG has been successful in collecting tumor samples from patients newly diagnosed with Ewing sarcoma, fresh frozen tumor specimens from primary and metastatic disease are critically needed, especially from young adult patients, in order to conduct high quality basic science and translational research investigation with a goal of developing better treatments. PMID:23519678

  1. Extraskeletal Ewing's sarcoma family of tumors in adults: prognostic factors and clinical outcome.

    Science.gov (United States)

    Tural, Deniz; Molinas Mandel, Nil; Dervisoglu, Sergulen; Oner Dincbas, Fazilet; Koca, Sedat; Colpan Oksuz, Didem; Kantarci, Fatih; Turna, Hande; Selcukbiricik, Fatih; Hiz, Murat

    2012-05-01

    The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥ 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8 ≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma.

  2. Unusual presentation of a lymphoma that simulated an Ewing sarcoma: clinical, radiological and pathological differential diagnostic

    International Nuclear Information System (INIS)

    Fox, Javier; Lopez, Jorge; Suarez, Amaranto; Terselich, Greti and others

    2003-01-01

    In this paper, the case of a 12-year old girl with a clinical manifestation simulating Ewing's Sarcoma is presented. Supplementary studies with light microscopy, immuno phenotypic, and cytogenetic evaluation confirm pre-B lymphoblastic lymphoma, with t(1;19)(q23:p13) translocation. The characteristics d of this neoplasia, and the importance of complementary immuno phenotypic, and cytogenetic studies, to perform an accurate diagnosis are discussed

  3. Does radiotherapy after surgery affect outcomes in Ewing's sarcoma of the pelvis?

    Directory of Open Access Journals (Sweden)

    Ajay Puri

    2018-01-01

    Full Text Available Background: The impact of postoperative radiotherapy (PORT on outcomes has been a matter of debate after adequate resection in Ewing's sarcoma of the pelvis. We evaluated our cases after surgical excision in pelvic Ewing's sarcoma and assessed local control and overall survival (OS with respect to PORT and chemotherapy-induced percentage necrosis. Materials and Methods: Forty four surgically operated patients (June 2002–November 2014 of localized Ewing's sarcoma were retrospectively reviewed. There were 31 males and 13 females. Age ranged from 2 to 53 years. All patients received institutional chemotherapy protocol. No patient received preoperative radiotherapy. Specimen was analyzed for margins and chemotherapy-induced percentage necrosis. PORT was offered to patients on case-by-case basis. Presence of a large preoperative soft-tissue component, margin evaluation, and percentage necrosis were factors considered. At time of the last followup, 29 patients were alive, 11 died, and 4 were lost to followup. Survivors had a minimum followup of 2 years (range: 31–118 months, mean = 69 months. Results: One of twenty (5% patients with PORT had a local recurrence as against 2 of 24 (8% without PORT. OS of all patients was 76% at 5 years. Twelve patients with 90% necrosis had OS of 83% (P = 0.040. OS of patients with PORT was 74%, without PORT was 78% (P = 0.629. Conclusions: The decision to offer PORT after surgical excision in pelvic Ewing's sarcoma is multifactorial; the absence of PORT in selected cases is not detrimental to local control. Poor responders to chemotherapy had poorer survival while PORT did not impact on outcomes.

  4. Does Radiotherapy after Surgery Affect Outcomes in Ewing's Sarcoma of the Pelvis?

    Science.gov (United States)

    Puri, Ajay; Gulia, Ashish; Crasto, Saniya; Vora, Tushar; Khanna, Nehal; Laskar, Siddharth

    2018-01-01

    The impact of postoperative radiotherapy (PORT) on outcomes has been a matter of debate after adequate resection in Ewing's sarcoma of the pelvis. We evaluated our cases after surgical excision in pelvic Ewing's sarcoma and assessed local control and overall survival (OS) with respect to PORT and chemotherapy-induced percentage necrosis. Forty four surgically operated patients (June 2002-November 2014) of localized Ewing's sarcoma were retrospectively reviewed. There were 31 males and 13 females. Age ranged from 2 to 53 years. All patients received institutional chemotherapy protocol. No patient received preoperative radiotherapy. Specimen was analyzed for margins and chemotherapy-induced percentage necrosis. PORT was offered to patients on case-by-case basis. Presence of a large preoperative soft-tissue component, margin evaluation, and percentage necrosis were factors considered. At time of the last followup, 29 patients were alive, 11 died, and 4 were lost to followup. Survivors had a minimum followup of 2 years (range: 31-118 months, mean = 69 months). One of twenty (5%) patients with PORT had a local recurrence as against 2 of 24 (8%) without PORT. OS of all patients was 76% at 5 years. Twelve patients with 90% necrosis had OS of 83% ( P = 0.040). OS of patients with PORT was 74%, without PORT was 78% ( P = 0.629). The decision to offer PORT after surgical excision in pelvic Ewing's sarcoma is multifactorial; the absence of PORT in selected cases is not detrimental to local control. Poor responders to chemotherapy had poorer survival while PORT did not impact on outcomes.

  5. Limb saving surgery for Ewing's sarcoma of the distal tibia: a case report.

    Science.gov (United States)

    Mizoshiri, Naoki; Shirai, Toshiharu; Terauchi, Ryu; Tsuchida, Shinji; Mori, Yuki; Katsuyama, Yusei; Hayashi, Daichi; Oka, Yoshinobu; Kubo, Toshikazu

    2018-05-02

    Ewing's sarcoma is a primary malignant tumor of bone occurring mostly in childhood. Few effective reconstruction techniques are available after wide resection of Ewing's sarcoma at the distal end of the tibia. Reconstruction after wide resection is especially difficult in children, as it is necessary to consider the growth and activity of the lower limbs. A 12-year-old Japanese boy had presented with right lower leg pain at age 8 years. Imaging examination showed a bone tumor accompanied by a large extra-skeletal mass in the distal part of his tibia. The tumor was histologically diagnosed as Ewing's sarcoma. The patient received chemotherapy, followed by wide resection. Reconstruction consisted of a bone transport method involving external fixation of Taylor Spatial Frame. To prevent infection after surgery, the external fixation pin was coated with iodine. One year after surgery, the patient showed poor consolidation of bone, so iliac bone transplantation was performed on the extended bones and docking site of the distal tibia. After 20 months, tibia formation was good. Three years after surgery, there was no evidence of tumor recurrence or metastases; bone fusion was good, and he was able to run. The bone transport method is an effective surgical method of reconstruction after wide resection of a bone tumor at the distal end of the tibia, if a pin can be inserted into the distal bone fragment. Coating external fixation pins with iodine may prevent postoperative infection.

  6. Ewing sarcoma of the adrenal gland: a case report and review of the literature.

    Science.gov (United States)

    Eddaoualline, Hanane; Mazouz, Khadija; Rafiq, Bouchra; El Mghari Tabib, Ghizlane; El Ansari, Nawal; Belbaraka, Rhizlane; El Omrani, Abdelhamid; Khouchani, Mouna

    2018-03-16

    Ewing sarcoma/primitive neuroectodermal tumor is a family of highly malignant proliferation of neuroectodermal origin, most often skeletal, adrenal localization is extremely rare. Only few cases have been reported in the literature. Classical management includes radical surgery with adjuvant chemotherapy or radiotherapy or both. This case report is the only one where recurrence was surgically removed, and it confirms the importance of adjuvant treatment, and the efficacy of neoadjuvant chemotherapy. We report the case of a 23-year-old Moroccan woman presenting with flank pain. An abdominal computed tomography scan showed a large and enhancing left suprarenal mass. After radical nephrectomy, histologic examination revealed a small round cell proliferation. The diagnosis of Ewing sarcoma was confirmed by molecular analysis; time to final diagnosis was 5 months due to financial and coordination issues. Computed tomography (on an asymptomatic patient) revealed a locoregional recurrence, our patient received 12 cycles of the vincristine, doxorubicin and cyclophosphamide/ifosfamide and etoposide protocol used in an alternating schedule, with partial radiologic response (62%) and pathologic complete response, then underwent adjuvant radiotherapy of 45 Gy. The young women is still in remission after 36 months of follow-up. Our patient had an early recurrence due to absence of adjuvant treatment, but did respond well to neoadjuvant chemotherapy with a pathologic complete response. Management of adrenal Ewing sarcoma could be extrapolated from skeletal one with good outcomes even in locoregional recurrence.

  7. 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.

  8. sarcome d'ewing

    African Journals Online (AJOL)

    7 mai 2012 ... Le sarcome d'Ewing est une tumeur osseuse rare corres- pondant à la ... Introduction : petrous Ewing sarcoma is exceptional. We report a ..... (15) Iriz A, Albayrak L, Eryilmaz A. Extraskeletal primary Ewing's sarcoma of the.

  9. [Treatment of pelvic Ewing's sarcoma in children and the effect on the skeletal growth and development].

    Science.gov (United States)

    Fu, Jun; Guo, Zheng; Wang, Zhen; Li, Xiang-dong; Li, Jing; Chen, Guo-jing; Wu, Zhi-gang

    2012-12-01

    To explore the effect of neo-adjuvant chemotherapy and computer-assisted surgery on children and adolescents with primary pelvic Ewing's sarcoma, and assess the therapeutic effect on the pelvic skeletal growth and development. This is a retrospective analysis of 10 children with primary pelvic Ewing's sarcoma treated between Jan 2001 and Oct 2010 at the Department of Oncologic Orthopaedics at Xijing Hospital. There were 3 girls and 7 boys in the age of 7 to 16 years (average 12.7 years). All patients were pathologically diagnosed as Ewing's sarcoma. There were two cases in the sacroiliac joint, one in the ilium, one in the pubic bone, and 6 cases in peri-acetabular area including 5 below the triradiate cartilage and one above the triradiate cartilage, without cartilage invasion. All patients underwent neo-adjuvant chemotherapy, resection and reconstruction surgery and postoperative chemotherapy. CDP, ADM and IFO regimen chemotherapy were given as the main treatment. Five cases were treated by traditional resection and reconstruction, and after 2008, five cases were treated by computer-assisted surgery. During the reconstruction, the hip rotation center was put at a depressed location. All of the 10 cases underwent postoperative radiotherapy in a dose of 45-55 Gy. All patients were followed-up for 12-72 months (mean: 37.8 months). One child had tumor recurrence and lung metastasis and 9 patients had no evidence of disease (NED). After neo-adjuvant chemotherapy, the oncologic statuses (RECIST) were: 1 CR, 8 PR and 1 SD. The functional recoveries after surgery (Enneking's) were: 4 cases excellent, 4 good, 1 fair and 1 poor. Five cases who underwent computer-assisted surgery achieved a good reconstruction without local recurrence. There were no effects on skeletal growth in 8 cases. An unbalanced hip rotational center occurred in one case, and a compemsatory scoliosis was found in another case. There were no serious complications in all patients. The comprehensive

  10. Radiation induced expression of survivin in Ewing sarcoma cell-lines

    International Nuclear Information System (INIS)

    Sheikh-Mounessi, F.; Willich, N.; Greve, B.

    2009-01-01

    Full text: Introduction: Survivin belongs to the Inhibitor of Apoptosis Protein Family (IAP), is a protein of 16.5 kD and active as a homodimer. It is overexpressed in nearly all human tumors and has a vital function in cell division and apoptotic processes. Beside its role as a relevant prognostic and predictive factor it was described to be a molecular target to improve effectiveness of radiotherapy. We investigated the radiation induced survivin expression in Ewing sarcoma cell-lines. Methods: Ewing sarcoma cells were either irradiated with 10 Gy X-ray and harvested at different time points (0, 2, 4, 6, 10 and 24 h) or irradiated with different doses (0, 2, 5 and 10 Gy) and harvested 24 h later. Protein and mRNA expression was analysed by Westernblot or Real-Time PCR. Results: Directly after irradiation with 10 Gy X-ray survivin mRNA expression was increased in relation to the reference GAPDH. Protein expression was increased in a time dependent manner and reached a maximum after 24h. Three of four investigated cell-lines showed a significant dose dependent increase of survivin protein concentration 24h after irradiation. The same three cell-lines showed a LD50 of >30 Gy. The line with the lowest dose dependent survivin induction was investigated to be most radiosensitive (LD50 = 24 Gy). Discussion: Ewing sarcoma is a childhood tumor with relatively poor prognosis. This tumor often shows significant therapeutic resistance to chemo- and/or radiotherapy. It would be of high interest to find new therapeutic approaches for its treatment. We found a remarkable overexpression of survivin in untreated Ewing sarcoma and a time and dose dependent increase of survivin protein concentration after irradiation with X-ray. The cell-line with the lowest survivin induction showed the highest radiosensitivity. In conclusion, our results show that survivin is an inducible radioresistance factor in Ewing sarcoma. This may open new therapeutic options to treat this aggressive

  11. Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

    Science.gov (United States)

    Worch, Jennifer; Ranft, Andreas; DuBois, Steven G; Paulussen, Michael; Juergens, Heribert; Dirksen, Uta

    2018-06-01

    The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations. © 2018 Wiley Periodicals, Inc.

  12. Recombinant methioninase effectively targets a Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model.

    Science.gov (United States)

    Murakami, Takashi; Li, Shukuan; Han, Qinghong; Tan, Yuying; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Hwang, Ho Kyoung; Miyake, Kentaro; Singh, Arun S; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; Hiroshima, Yukihiko; Lwin, Thinzar M; DeLong, Jonathan C; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2017-05-30

    Methionine dependence is due to the overuse of methionine for aberrant transmethylation reactions in cancer. Methionine dependence may be the only general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino-γ-mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant methioninase, or rMETase, has been tested in mouse models of human cancer cell lines. Ewing's sarcoma is recalcitrant disease even though development of multimodal therapy has improved patients'outcome. Here we report efficacy of rMETase against Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model. Eight Ewing's sarcoma PDOX mice were randomized into untreated control group (n = 4) and rMETase treatment group (n = 4). rMETase (100 units) was injected intraperitoneally (i.p.) every 24 hours for 14 consecutive days. All mice were sacrificed on day-15, 24 hours after the last rMETase administration. rMETase effectively reduced tumor growth compared to untreated control. The methionine level both of plasma and supernatants derived from sonicated tumors was lower in the rMETase group. Body weight did not significantly differ at any time points between the 2 groups. The present study is the first demonstrating rMETase efficacy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as Ewing's sarcoma.

  13. Survival outcomes of pediatric osteosarcoma and Ewing's sarcoma: a comparison of surgery type within the SEER database, 1988-2007.

    Science.gov (United States)

    Schrager, Justin; Patzer, Rachel E; Mink, Pamela J; Ward, Kevin C; Goodman, Michael

    2011-01-01

    Survival following diagnosis of pediatric Ewing's sarcoma or osteosarcoma is increasing in the United States, but whether survival differs between patients who receive limb salvage surgery compared to amputation has not been evaluated in nationally representative, population-based data. Multivariable-adjusted survival was calculated using Cox regression models among surgically treated pediatric (age Ewing's sarcoma patients with bone cancer of the limbs or joints reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program during 1988-2007. Over half (66.3%) of the 890 osteosarcoma patients underwent limb salvage surgery. Five-year overall survival among patients who received limb salvage was 72.7% for osteosarcoma patients and 71.8% for Ewing's sarcoma patients. Among patients who received amputation, 5-year survival was 60.1% for osteosarcoma and 63.1% for Ewing's sarcoma patients. After multivariable adjustment, the mortality was 35% greater for amputation vs limb salvage (HR=1.35, 95% CI: 1.05-1.75). Among 165 Ewing's sarcoma patients, 73.9% underwent limb salvage (vs amputation), and the adjusted mortality was higher for patients receiving amputation, although results were not statistically significant (HR=1.61, 95% CI: 0.80-3.21). Limb salvage surgery (vs amputation) is associated with longer survival among pediatric patients with bone cancer of the limbs or joints. Patient and physician characteristics and the effectiveness of neoadjuvant therapy may play a role in surgery choice, but we were unable to control for these factors.

  14. Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

    Directory of Open Access Journals (Sweden)

    Li YJ

    2017-09-01

    Full Text Available Yong-Jiang Li, Xi Yang, Wen-Biao Zhang, Cheng Yi, Feng Wang, Ping Li Department of Oncology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR, platelet–lymphocyte ratio (PLR, Glasgow Prognostic Score (GPS, C-reactive protein to albumin ratio (CRP/Alb ratio, lymphocyte–monocyte ratio (LMR, and neutrophil–platelet score (NPS, were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC analysis was generated to determine optimal cutoff values; areas under the curves (AUCs were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005, GPS (HR 2.27, P=0.006, NLR (HR 2.07, P=0.013, and PLR (HR 1.85, P=0.032 were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and

  15. EWING'S SARCOMA: EPIDEMIOLOGY AND PROGNOSIS FOR PATIENTS TREATED AT THE PEDIATRIC ONCOLOGY INSTITUTE, IOP-GRAACC-UNIFESP.

    Science.gov (United States)

    Bellan, Davi Gabriel; Filho, Reynaldo Jesus-Garcia; Garcia, Jairo Greco; de Toledo Petrilli, Marcelo; Maia Viola, Dan Carai; Schoedl, Murillo Ferri; Petrilli, Antonio Sérgio

    2012-01-01

    To outline the epidemiological profile and prognosis for Ewing's sarcoma in the Brazilian population. The medical records of 64 patients with intraosseous Ewing's sarcoma who were treated at the Pediatric Oncology Institute, IOP-GRAACC-Unifesp, between 1995 and 2010, were retrospectively evaluated. The statistical analysis on the data obtained did not correlate factors such as sex, trauma, pathological fracture and time taken for case diagnosis with the treatment outcome. Factors such as initial metastasis, lung metastasis, tumor site, age, recurrence and type of surgery showed results corroborating what has been established in the literature. The prognosis in cases of Ewing's sarcoma was mainly influenced by the presence of metastases at the time of diagnosis.

  16. 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.

  17. 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.

  18. Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: Two Unusual Presentations of a Rare Tumor

    Directory of Open Access Journals (Sweden)

    E. C. Castro

    2012-01-01

    Full Text Available Only few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present here two cases of renal ES/PNET with an uncanny presentation. The first case was discovered after the patient presented clinically with irradiating flank pain, mimicking the pain related with kidney stones. The second case had clinical presentation of pulmonary thromboembolism after the patient was involved in an automobilist accident. The tumors were mainly composed of small blue cells which by immunohistochemical were positive for neural markers, and FISH revealed the translocation 22q12 for the EWSR1 gene. The diagnosis of renal primitive neuroectodermal tumor/EWING tumor is very rare and usually involves several different diagnostic techniques. The differential diagnosis is usually broad with frequent overlapping features between the entities. The cases presented in this paper illustrated the difficulties with which routine anatomical pathologist is faced when dealing with rare renal poorly differentiated neoplasm in adults.

  19. Progress in the treatment of Ewing sarcoma: are the rumors of the demise of cytotoxic chemotherapy premature?

    Science.gov (United States)

    Rosen, G

    2015-05-01

    In this issue, Bollling et. al. review the development of treatment of Ewing sarcoma as it evolved over the past 30 years of clinical trials in Europe, largely under the leadership of Heribert Jurgens to whom this review is dedicated. The 44 authors were teachers, colleagues, students and co-investigators of Jurgens. The authors attribute the ability to make progress in the treatment of Ewing sarcoma through the establishment of larger and still larger cooperative studies in order to demonstrate statistically significant advances in the treatment of this rare disease. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Risk analysis factors for local recurrence in Ewing's sarcoma: when should adjuvant radiotherapy be administered?

    Science.gov (United States)

    Albergo, J I; Gaston, C L L; Parry, M C; Laitinen, M K; Jeys, L M; Tillman, R M; Abudu, A T; Grimer, R J

    2018-02-01

    The aim of this study was to analyse a group of patients with non-metastatic Ewing's sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. A retrospective review of all patients with a Ewing's sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (sd 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Local recurrence significantly affects the overall survival in patients with a Ewing's sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247-55. ©2018 The British Editorial Society of Bone & Joint Surgery.

  1. Primary spinal epidural extraosseous Ewing's sarcoma: Report of five cases and literature review

    International Nuclear Information System (INIS)

    Mukhopadhyay, P.; Gairola, M.; Julka, P.K.; Rath, G.K.; Sharma, M.C.; Thulkar, S.

    2001-01-01

    Ewing's sarcoma is the most common malignant bone tumour occurring in children and adolescents and exists in two different clinico pathological entities: osseous Ewing's sarcoma (OES) and extraosseous Ewing's sarcoma (EES). Five cases of primary epidural EES are described, which presented with non-specific symptoms leading to a long diagnostic delay. The median age at diagnosis was 22 years (range 13-36 years). The median diagnostic delay was 3 months. All patients had one or more neurological deficits. All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46-50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles. The mean follow-up period is 21.2 months (range 11-32 months). Four of the five patients achieved a complete remission and are disease free at the time of writing this report. Two patients have a residual neurological deficit - both having presented with long history of neurological deficit. Primary spinal epidural EES should be suspected whenever young patients present with back pain and/or radicular pain, have abnormal neurology and an extradural mass is demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy) and combination chemotherapy (VAC alternating with ICE) achieved local and systemic control in these patients. A greater number of patients and longer follow up are required to evolve a generally accepted treatment policy for this aggressive but potentially curable malignancy. Copyright (2001) Blackwell Science Pty Ltd

  2. A case of extraskeletal Ewing sarcoma originating from the visceral pleura

    OpenAIRE

    Karatziou, C; Pitta, X; Stergiouda, T; Karadimou, V; Termentzis, G

    2011-01-01

    Extra skeletal Ewing Sarcoma (EES) is a rare entity which predominantly occurs in adolescents and young adults. It usually arises from the soft tissues of the trunk or the extremities. We present a case of EES arising from the left visceral pleura in a 21 year old female patient who presented to the emergency room of our institution with fever, productive cough and sternal pain radiating to the back for the last 3 days. Chest radiograph was firstly performed, followed by chest CT examination....

  3. Ewing's sarcoma of the humerus mimicking fibrous dysplasia on imaging and biological behavior

    International Nuclear Information System (INIS)

    Sundaram, Murali; Inwards, Carrie Y.; Shives, Thomas E.; Anderson, Peter M.

    2005-01-01

    We present the case of a 12-year-old girl who presented with a pathological fracture through a benign-appearing osteolytic lesion that was presumed to represent fibrous dysplasia. The fracture healed, and over the next 2.5 years there was further refracturing and healing with progressive osteolysis. A biopsy was performed and revealed Ewing's sarcoma. The disease was locally controlled by neoadjuvant chemotherapy and radiation therapy. The patient is disease free with excellent function 6 years following the discovery of the lesion. We illustrate and discuss the sequence of events. (orig.)

  4. Coverage of Megaprosthesis with Human Acellular Dermal Matrix after Ewing's Sarcoma Resection: A Case Report

    Directory of Open Access Journals (Sweden)

    Robert M. Whitfield

    2011-01-01

    Full Text Available A 23-year-old female with Ewing's Sarcoma underwent tibial resection and skeletal reconstruction using proximal tibial allograft prosthetic reconstruction with distal femur endoprosthetic reconstruction and rotating hinge. Human acellular dermal matrix, (Alloderm, LifeCell, Branchburg, NJ, USA, was used to wrap the skeletal reconstruction. Soft tissue reconstruction was completed with a rotational gastrocnemius muscle flap and skin graft. Despite prolonged immobilization, the patient quickly regained full range of motion of her skeletal reconstruction. Synthetic mesh, tapes and tubes are used to perform capsule reconstruction of megaprosthesis. This paper describes the role of human acellular dermal matrix in capsule reconstruction around a megaprosthesis.

  5. Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

    Science.gov (United States)

    Jin, Shu-Guang; Jiang, Xiao-Ping; Zhong, Lin

    2016-10-01

    Ewing's sarcoma (EWS) and peripheral primitive neuroectodermal tumor (pPNET) are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment. Copyright © 2014. Published by Elsevier B.V.

  6. Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Shu-Guang Jin

    2016-10-01

    Full Text Available Ewing's sarcoma (EWS and peripheral primitive neuroectodermal tumor (pPNET are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment.

  7. Peripheral soft tissue ewing's sarcoma: a rare case report

    Directory of Open Access Journals (Sweden)

    Farzana Shegufta

    2013-07-01

    Full Text Available A 22 years male patient presented with gradual left forearm swelling for 6 months. X ray forearm revealed large soft tissue swelling with tiny calcification and mild scalloping at inner aspect of ulna and ultrasonogram (USG revealed soft tissue mass having calcification and necrotic areas within and spectral Doppler showed arterial type of blood flow with no augmentation. Later computerized tomography (CT scan showed soft tissue mass with necrotic area and calcification with no bony involvement. Magnetic resonance imaging (MRI with contrast revealed a large heterogeneously enhancing lobulated mixed intensity lesion in antero-medial compartment of the left forearm involving flexor group of muscles causing displacement of fat plane. MRI and subsequent histopathology of the lesion revealed it as a rare soft tissue Ewing’s sarcoma / primitive neuroectodermal tumor (PNET in extremity. Ibrahim Med. Coll. J. 2013; 7(2: 43-46

  8. Proton Radiotherapy for Pediatric Ewing's Sarcoma: Initial Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Rombi, Barbara [ATreP (Provincial Agency for Proton Therapy), Trento (Italy); DeLaney, Thomas F.; MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Huang, Mary S.; Ebb, David H. [Department of Pediatric Hematology and Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Liebsch, Norbert J. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Raskin, Kevin A. [Department of Orthopaedic Surgery, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Marcus, Karen J. [Division of Radiation Oncology, Children' s Hospital Boston, MA (United States); Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States)

    2012-03-01

    Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.

  9. Detection and characterization of side population in Ewing's sarcoma SK-ES-1 cells in vitro

    International Nuclear Information System (INIS)

    Yang, Min; Zhang, Rui; Yan, Ming; Ye, Zhengxu; Liang, Wei; Luo, Zhuojing

    2010-01-01

    Dye exclusion is a valuable technique to isolate cancer stem cells (CSCs) based on an ability of stem cell to efflux fluorescent DNA-binding dye, especially for tumors without unique surface markers. It has been proven that side population (SP) cells that exclude Hoechst 33342 dye are enriched with stem-like cells in several cancer cell lines. In this study, we isolated and characterized SP cells from human Ewing's sarcoma cell line SK-ES-1 in vitro. SP cells were detected in SK-ES-1 and comprised 1.2% of total cell population. Only SP cells had the capacity to regenerate both SP and non-SP cells. The proliferation rates were similar between SP and non-SP cells. However, the clonogenicity and invasiveness of SP cells were significantly higher than that of non-SP cells. Further characterization of this SP phenotype presented other properties. SP cells exhibited increased multi-drug resistance and the ATP binding cassette protein (ABC) transporters were up-regulated in SP population. These findings suggest that SP cells derived from Ewing's sarcoma play the critical role in tumor metastasis and recurrence and might be an ideal target for clinical therapy.

  10. A case of extraskeletal Ewing sarcoma originating from the visceral pleura.

    Science.gov (United States)

    Karatziou, C; Pitta, X; Stergiouda, T; Karadimou, V; Termentzis, G

    2011-10-01

    Extra skeletal Ewing Sarcoma (EES) is a rare entity which predominantly occurs in adolescents and young adults. It usually arises from the soft tissues of the trunk or the extremities. We present a case of EES arising from the left visceral pleura in a 21 year old female patient who presented to the emergency room of our institution with fever, productive cough and sternal pain radiating to the back for the last 3 days. Chest radiograph was firstly performed, followed by chest CT examination. Finally open lung biopsy revealed a small round cell malignancy. The mass was resected and the histological examination revealed Extra skeletal Ewing Sarcoma (EES) of the visceral pleura without involvement of the adjacent lung. Secondary multiple nodules at the lateral wall of the pleura were also noticed and so postoperative multiagent chemotherapy was performed. EES should be considered in the differential diagnosis of any patient, especially adolescents or young adults, with a soft tissue mass of the trunk or the extremities.

  11. Diagnostic difficulties in extraosseous Ewing's sarcoma: A proposal for diagnostic criteria

    International Nuclear Information System (INIS)

    Christie, D.R.H.; Bilous, A.M.; Carr, P.J.A.

    1997-01-01

    Five cases diagnosed as extraosseous Ewing's sarcoma (EES) during a 15 year period, and the relevant literature, were reviewed. The diagnosis in these cases was difficult to confirm, mainly because the distinction between the osseous form of Ewing's sarcoma (OES) and either periosteal reactions or direct tumour invasion into adjacent bone by EES was often unclear. The literature suggests that other authors have also encountered difficulties. The authors believe that many cases reported as EES are likely to have been OES. This distinction has some importance, as the two conditions are usually treated in differing ways. The following criteria are proposed for the diagnosis of primary EES: (i) no evidence of bony involvement on magnetic resonance imaging; (ii) no evidence of increased uptake in bone or periosteum adjacent to the tumour on static isotope bone scan images; (iii) a small round cell tumour with no differentiating features on light microscopy, immunochemistry or electron microscopy; and (iv) demonstration of cytoplasmic glycogen. 19 refs., 2 tabs., 6 figs

  12. Stereotactic Body Radiotherapy for Metastatic and Recurrent Ewing Sarcoma and Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Lindsay C. Brown

    2014-01-01

    Full Text Available Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES, in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma. Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012. Results. We identified 14 patients with a total of 27 lesions from osteosarcoma (n=19 or ES (n=8. The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions. The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions. Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation. Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.

  13. Primary Ewing's sarcoma of the sinonasal tract in adults: A challenging disease.

    Science.gov (United States)

    Lombardi, Davide; Mattavelli, Davide; Redaelli De Zinis, Luca O; Accorona, Remo; Morassi, Maria L; Facchetti, Fabio; Ferrari, Vittorio; Farina, Davide; Bertulli, Rossella; Nicolai, Piero

    2017-03-01

    Sinonasal localization of Ewing's sarcoma in adults is an exceedingly rare event. The clinical records of 5 patients with primary sinonasal Ewing's sarcoma treated from 1992 to 2012 were retrospectively analyzed. All pathologic slides were reviewed by 2 experienced pathologists. All patients underwent multimodality treatments. Median age was 36 years (range, 25-52 years). At referral, 2 patients had the original diagnosis changed by review of the histologic slides. Tumors were classified as T4aN0M0 (4 patients) and T2N0M0 (1 patient). Median follow-up was 110 months (range, 70-139 months). Only 1 patient, who started treatment elsewhere based on an incorrect histologic diagnosis, experienced multiple recurrences and eventually died of widespread metastasis. Correct pathologic diagnosis can have a crucial impact on treatment planning and outcome. Multimodality therapy is the key for long-term successful results. Because of the rarity of the tumor, referral to highly experienced care centers is strongly recommended. © 2016 Wiley Periodicals, Inc. Head Neck 39: E45-E50, 2017. © 2016 Wiley Periodicals, Inc.

  14. 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.

  15. Unusual progress of disease in a case of Ewing sarcoma in a man aged 19 by now

    International Nuclear Information System (INIS)

    Keim, H.; Wachter, P.

    1980-01-01

    We report on a case of Ewing sarcoma which was exclusively irradiated because no consent could be obtained from the patient for cytostatic treatment. There were two remarkable observations: Lung metastases (vanished) during the time of irradiation, and the survival time of the patient so far is ten years. (orig.) [de

  16. Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.

    Science.gov (United States)

    Rao, Donald D; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

    2016-08-01

    The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.

  17. Prognostic factors for survival in patients with Ewing's sarcoma using the surveillance, epidemiology, and end results (SEER) program database.

    Science.gov (United States)

    Duchman, Kyle R; Gao, Yubo; Miller, Benjamin J

    2015-04-01

    The current study aims to determine cause-specific survival in patients with Ewing's sarcoma while reporting clinical risk factors for survival. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients with osseous Ewing's sarcoma from 1991 to 2010. Patient, tumor, and socioeconomic variables were analyzed to determine prognostic factors for survival. There were 1163 patients with Ewing's sarcoma identified in the SEER Program database. The 10-year cause-specific survival for patients with non-metastatic disease at diagnosis was 66.8% and 28.1% for patients with metastatic disease. Black patients demonstrated reduced survival at 10 years with an increased frequency of metastatic disease at diagnosis as compared to patients of other race, while Hispanic patients more frequently presented with tumor size>10cm. Univariate analysis revealed that metastatic disease at presentation, tumor size>10cm, axial tumor location, patient age≥20 years, black race, and male sex were associated with decreased cause-specific survival at 10 years. Metastatic disease at presentation, axial tumor location, tumor size>10cm, and age≥20 years remained significant in the multivariate analysis. Patients with Ewing's sarcoma have decreased cause-specific survival at 10 years when metastatic at presentation, axial tumor location, tumor size>10cm, and patient age≥20 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    NARCIS (Netherlands)

    Kasalak, Omer; Glaudemans, Andor W. J. M.; Overbosch, Jelle; Jutte, Paul C.; Kwee, Thomas C.

    OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND

  19. 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.

  20. Management Head and Neck Ewing's Sarcoma Family of tumors: Experience of the National Cancer Institute, Cairo University

    International Nuclear Information System (INIS)

    Abdel Rahman, M.; El-Baradie, T.; Bahaa, Sh.; Shalan, M.; El-Baradie, M.

    2010-01-01

    Ewing's sarcoma accounts for 4-6% of primary malignant bone tumors and it affects the head and neck in only 1-4% of cases. The purpose of this study was to review the NCI experience with Ewing's sarcoma of the head and neck in children. Patients and Methods: A retrospective analysis of patient files with head and neck Ewing's sarcoma treated at the National Cancer Institute, Cairo University, Egypt, during the period from 1997 to 2008 was done. Files were reviewed and data for patients, tumor and treatment profile were extracted. Results: Twenty patients out of 280 with Ewing's sarcoma were identified during an 11 -year period. Patients had a median age of 11.5 years (range 5 months - 22 years) with a male to female ratio of 1:1. The most common tumor site was in the mandible (9/20, 45%) followed by a neck mass (4/20, 20%) and a clavicular mass (3/20, 15%). Six patients (30%) were metastatic at presentation. Most of the patients (19/20, 95%) received chemotherapy. Local therapy was in the form of radical radiotherapy for 8 patients (40%), 2 patients (10%) had surgery alone, while five patients (25%) had surgical resection and postoperative radiotherapy. Overall survival ranged from 1 to 128 months, with a median of 36 months. At the end of the study, 9 patients (45%) were alive in CR, 6 (30%) were lost to FU in disease progression, while 5 patients died from disease progression. Conclusion: Ewing's sarcoma of the head and neck is a disease of a rare incidence with debate about the optimum local therapy. Small non-metastatic tumors with good response to chemotherapy have abetter outcome.

  1. 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.

  2. 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.

  3. Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes

    International Nuclear Information System (INIS)

    Sole, Claudio V.; Calvo, Felipe A.; Polo, Alfredo; Cambeiro, Mauricio; Gonzalez, Carmen; Desco, Manuel; Martinez-Monge, Rafael

    2015-01-01

    Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates

  4. The irony of highly-effective bacterial therapy of a patient-derived orthotopic xenograft (PDOX) model of Ewing's sarcoma, which was blocked by Ewing himself 80 years ago.

    Science.gov (United States)

    Murakami, Takashi; Kiyuna, Tasuku; Kawaguchi, Kei; Igarashi, Kentaro; Singh, Arun S; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Miyake, Kentaro; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; DeLong, Jonathan C; Lwin, Thinzar M; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2017-06-03

    William B. Coley developed bacterial therapy of cancer more than 100 years ago and had clinical success. James Ewing, a very famous cancer pathologist for whom the Ewing sarcoma is named, was Coley's boss at Memorial Hospital in New York and terminated Coley's bacterial therapy of cancer. A tumor from a patient with soft-tissue Ewing's sarcoma, who failed doxorubicin (DOX) therapy, was previously implanted in nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the Ewing's sarcoma PDOX was treated with tumor-targeting S. typhimurium A1-R expressing green fluorescent (GFP), alone and in combination with DOX. S. typhimurium A1-R-GFP was detected in the tumors after intratumor (i.t.) or intravenous (i.v.) injection. The combination of S. typhimurium A1-R and DOX significantly reduced tumor weight (37.8 ± 15.6 mg) compared to the untreated control (73.8 ± 10.1 mg, P Ewing's sarcoma had in the patient. S. typhimurium A1-R converted the Ewing's sarcoma from DOX resistant to sensitive. One can only wonder how bacterial therapy and immunotherapy of cancer would have developed over the past 80 years if Ewing did not stop Coley.

  5. Histone deacetylase inhibitors enhance expression of NKG2D ligands in Ewing sarcoma and sensitize for natural killer cell-mediated cytolysis

    NARCIS (Netherlands)

    Berghuis, D.; Schilham, M.W.; Vos, H.I.; Santos, S.J.; Kloess, S.; Buddingh, E.P.; Egeler, R.M.; Hogendoorn, P.C.; Lankester, A.C.

    2012-01-01

    BACKGROUND: Ewing sarcoma patients have a poor prognosis despite multimodal therapy. Integration of combination immunotherapeutic strategies into first-/second-line regimens represents promising treatment options, particularly for patients with intrinsic or acquired resistance to conventional

  6. Pelvic Ewing sarcomas. Three-dimensional conformal vs. intensity-modulated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mounessi, F.S.; Lehrich, P.; Haverkamp, U.; Eich, H.T. [Muenster Univ. (Germany). Dept. of Radiation Oncology; Willich, N. [Muenster Univ. (Germany). Dept. of Radiation Oncology; Universitaetsklinikum Muenster (Germany). RiSK - Registry for the Evaluation of Late Side Effects after Radiotherapy in Childhood and Adolescence; Boelling, T. [Center for Radiation Oncology, Osnabrueck (Germany)

    2013-04-15

    The goal of the present work was to assess the potential advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3D-CRT) planning in pelvic Ewing's sarcoma. A total of 8 patients with Ewing sarcoma of the pelvis undergoing radiotherapy were analyzed. Plans for 3D-CRT and IMRT were calculated for each patient. Dose coverage of the planning target volume (PTV), conformity and homogeneity indices, as well as further parameters were evaluated. Results The average dose coverage values for PTV were comparable in 3D-CRT and IMRT plans. Both techniques had a PTV coverage of V{sub 95} > 98 % in all patients. Whereas the IMRT plans achieved a higher conformity index compared to the 3D-CRT plans (conformity index 0.79 {+-} 0.12 vs. 0.54 {+-} 0.19, p = 0.012), the dose distribution across the target volumes was less homogeneous with IMRT planning than with 3D-CRT planning. This difference was statistically significant (homogeneity index 0.11 {+-} 0.03 vs. 0.07 {+-} 0.0, p = 0.035). For the bowel, D{sub mean} and D{sub 1%}, as well as V{sub 2} to V{sub 60} were reduced in IMRT plans. For the bladder and the rectum, there was no significant difference in D{sub mean}. However, the percentages of volumes receiving at least doses of 30, 40, 45, and 50 Gy (V{sub 30} to V{sub 50}) were lower for the rectum in IMRT plans. The volume of normal tissue receiving at least 2 Gy (V{sub 2}) was significantly higher in IMRT plans compared with 3D-CRT, whereas at high dose levels (V{sub 30}) it was significantly lower. Compared to 3D-CRT, IMRT showed significantly better results regarding dose conformity (p = 0.012) and bowel sparing at dose levels above 30 Gy (p = 0.012). Thus, dose escalation in the radiotherapy of pelvic Ewing's sarcoma can be more easily achieved using IMRT. (orig.)

  7. 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.

  8. Preclinical Testing of an Oncolytic Parvovirus in Ewing Sarcoma: Protoparvovirus H-1 Induces Apoptosis and Lytic Infection In Vitro but Fails to Improve Survival In Vivo.

    Science.gov (United States)

    Lacroix, Jeannine; Kis, Zoltán; Josupeit, Rafael; Schlund, Franziska; Stroh-Dege, Alexandra; Frank-Stöhr, Monika; Leuchs, Barbara; Schlehofer, Jörg R; Rommelaere, Jean; Dinsart, Christiane

    2018-06-03

    About 70% of all Ewing sarcoma (EWS) patients are diagnosed under the age of 20 years. Over the last decades little progress has been made towards finding effective treatment approaches for primarily metastasized or refractory Ewing sarcoma in young patients. Here, in the context of the search for novel therapeutic options, the potential of oncolytic protoparvovirus H-1 (H-1PV) to treat Ewing sarcoma was evaluated, its safety having been proven previously tested in adult cancer patients and its oncolytic efficacy demonstrated on osteosarcoma cell cultures. The effects of viral infection were tested in vitro on four human Ewing sarcoma cell lines. Notably evaluated were effects of the virus on the cell cycle and its replication efficiency. Within 24 h after infection, the synthesis of viral proteins was induced. Efficient H-1PV replication was confirmed in all four Ewing sarcoma cell lines. The cytotoxicity of the virus was determined on the basis of cytopathic effects, cell viability, and cell lysis. These in vitro experiments revealed efficient killing of Ewing sarcoma cells by H-1PV at a multiplicity of infection between 0.1 and 5 plaque forming units (PFU)/cell. In two of the four tested cell lines, significant induction of apoptosis by H-1PV was observed. H-1PV thus meets all the in vitro criteria for a virus to be oncolytic towards Ewing sarcoma. In the first xenograft experiments, however, although an antiproliferative effect of intratumoral H-1PV injection was observed, no significant improvement of animal survival was noted. Future projects aiming to validate parvovirotherapy for the treatment of pediatric Ewing sarcoma should focus on combinatorial treatments and will require the use of patient-derived xenografts and immunocompetent syngeneic animal models.

  9. Preclinical Testing of an Oncolytic Parvovirus in Ewing Sarcoma: Protoparvovirus H-1 Induces Apoptosis and Lytic Infection In Vitro but Fails to Improve Survival In Vivo

    Directory of Open Access Journals (Sweden)

    Jeannine Lacroix

    2018-06-01

    Full Text Available About 70% of all Ewing sarcoma (EWS patients are diagnosed under the age of 20 years. Over the last decades little progress has been made towards finding effective treatment approaches for primarily metastasized or refractory Ewing sarcoma in young patients. Here, in the context of the search for novel therapeutic options, the potential of oncolytic protoparvovirus H-1 (H-1PV to treat Ewing sarcoma was evaluated, its safety having been proven previously tested in adult cancer patients and its oncolytic efficacy demonstrated on osteosarcoma cell cultures. The effects of viral infection were tested in vitro on four human Ewing sarcoma cell lines. Notably evaluated were effects of the virus on the cell cycle and its replication efficiency. Within 24 h after infection, the synthesis of viral proteins was induced. Efficient H-1PV replication was confirmed in all four Ewing sarcoma cell lines. The cytotoxicity of the virus was determined on the basis of cytopathic effects, cell viability, and cell lysis. These in vitro experiments revealed efficient killing of Ewing sarcoma cells by H-1PV at a multiplicity of infection between 0.1 and 5 plaque forming units (PFU/cell. In two of the four tested cell lines, significant induction of apoptosis by H-1PV was observed. H-1PV thus meets all the in vitro criteria for a virus to be oncolytic towards Ewing sarcoma. In the first xenograft experiments, however, although an antiproliferative effect of intratumoral H-1PV injection was observed, no significant improvement of animal survival was noted. Future projects aiming to validate parvovirotherapy for the treatment of pediatric Ewing sarcoma should focus on combinatorial treatments and will require the use of patient-derived xenografts and immunocompetent syngeneic animal models.

  10. 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

  11. 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

  12. CT differential diagnosis of primary pelvic osteosarcoma, chondrosarcoma and Ewing's sarcoma

    International Nuclear Information System (INIS)

    Heller, M.; Heyer, D.; Spielmann, R.P.; Buecheler, E.

    1990-01-01

    The value of CT for the differential diagnosis of primary malignant tumours in the pelvis was investigated in the case of three types of tumour: Osteosarcomas, chondrosarcomas and Ewing's sarcomas. A total of 78 CT examinations in 29 patients was used. The results show that CT, using suitable techniques (high resolution etc.) constitutes a valuable diagnostic method for differentiating these bone tumours. This applies not only for the localisation of the tumour and for defining its extent, but also for showing the morphology of intra- and extra-osseous soft tissue components and their patterns of calcification. It is possible to recognise patterns of growth and of tissue destruction that are typical of individual tumours. (orig.) [de

  13. Antagonism pattern detection between microRNA and target expression in Ewing's sarcoma.

    Directory of Open Access Journals (Sweden)

    Loredana Martignetti

    Full Text Available MicroRNAs (miRNAs have emerged as fundamental regulators that silence gene expression at the post-transcriptional and translational levels. The identification of their targets is a major challenge to elucidate the regulated biological processes. The overall effect of miRNA is reflected on target mRNA expression, suggesting the design of new investigative methods based on high-throughput experimental data such as miRNA and transcriptome profiles. We propose a novel statistical measure of non-linear dependence between miRNA and mRNA expression, in order to infer miRNA-target interactions. This approach, which we name antagonism pattern detection, is based on the statistical recognition of a triangular-shaped pattern in miRNA-target expression profiles. This pattern is observed in miRNA-target expression measurements since their simultaneously elevated expression is statistically under-represented in the case of miRNA silencing effect. The proposed method enables miRNA target prediction to strongly rely on cellular context and physiological conditions reflected by expression data. The procedure has been assessed on synthetic datasets and tested on a set of real positive controls. Then it has been applied to analyze expression data from Ewing's sarcoma patients. The antagonism relationship is evaluated as a good indicator of real miRNA-target biological interaction. The predicted targets are consistently enriched for miRNA binding site motifs in their 3'UTR. Moreover, we reveal sets of predicted targets for each miRNA sharing important biological function. The procedure allows us to infer crucial miRNA regulators and their potential targets in Ewing's sarcoma disease. It can be considered as a valid statistical approach to discover new insights in the miRNA regulatory mechanisms.

  14. 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

  15. Multimodality Treatment in Ewing's Sarcoma Family Tumors of the Maxilla and Maxillary Sinus: Review of the Literature

    Science.gov (United States)

    Mamot, Christoph; Krasniqi, Fatime; Metternich, Frank

    2016-01-01

    The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series. We hereby present a review of the literature published on ESFTs reported in the maxilla and maxillary sinus region from 1968 to 2016. PMID:27413360

  16. 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.

  17. In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Kinsella, T.J.; Mitchell, J.B.; McPherson, S.; Miser, J.; Triche, T.; Glatstein, E.

    1984-01-01

    Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have studied in the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's lines showed a larger D 0 and anti-n compared to the bone marrow CFU. No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma lines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10 -4 -10 -5 ) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined

  18. Evidence-based guideline recommendations on treatment strategies for localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy.

    Science.gov (United States)

    Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

    2016-06-01

    (1) To provide recommendations regarding the choice of surgery, radiation therapy (RT), or the combination of surgery plus RT in patients with localized Ewing's sarcoma of bone following neoadjuvant chemotherapy. (2) To determine the appropriate surgical planning imaging (pre-chemotherapy magnetic resonance imaging [MRI] or post-chemotherapy MRI) to identify optimal resection margins in patients with localized Ewing's sarcoma who undergo surgery following neoadjuvant chemotherapy. MEDLINE, EMBASE, the Cochrane Library (1999 to February 2015), main guideline websites, and relevant annual meeting abstracts (2012 to January 2015) were searched. Internal and external reviews were conducted. 1. Recommendation (1) - In patients with localized Ewing's sarcoma of bone following neoadjuvant chemotherapy: (a) Surgery alone or RT alone are two reasonable treatment options; the combination of surgery plus RT is not recommended as an initial treatment option. (b) The local treatment for an individual patient should be decided by a multidisciplinary tumour board together with the patient after consideration of the following: (1) patient characteristics (e.g., age, tumour location, tumour size, response to neoadjuvant chemotherapy, and existing comorbidities), (2) the potential benefit weighed against the potential complications from surgery and/or toxicities associated with RT, and (3) patient preferences. 2. Recommendation (2) - In patients with localized Ewing's sarcoma who will undergo surgery: (a) Both pre-chemotherapy and post-chemotherapy MRI scans should be taken into consideration for surgical planning. In certain anatomic locations with good chemotherapy response, the post-chemotherapy MRI may be the appropriate imaging modality to plan surgical resection margins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Preoperative evaluation and monitoring chemotherapy in patients with high-grade osteogenic and Ewing's sarcoma: review of current imaging modalities

    International Nuclear Information System (INIS)

    Woude, H.-J. van der; Bloem, J.L.; Hogendoorn, P.C.W.

    1998-01-01

    Diagnostic imaging is pivotal in the initial detection, characterization, staging and post-treatment follow-up of patients with high-grade osteogenic and Ewing's sarcoma. In the present review article, conventional and new imaging modalities are discussed with regard to the monitoring of the effect of neoadjuvant chemotherapy in such patients. Presurgical monitoring of response to chemotherapy may have an impact on modification of neoadjuvant treatment protocols, on patient selection for the performance and timing of limb-salvage surgery and on planning of radiation therapy (in non-operated Ewing's sarcomas) and selection of postoperative chemotherapy regimens. Dynamic contrast-enhanced MR imaging, as part of a routine MR protocol, assists in the detection of the most viable parts of the tumour and serves as an initial standard for follow-up of the metabolic activity of the tumour during and after chemotherapy, both in small intraosseous tumours and in tumours with an associated soft tissue mass. In combination with selected morphological features, dynamic imaging parameters are therefore advocated for monitoring the effect of neoadjuvant chemotherapy in patients with osteogenic and Ewing's sarcoma. (orig.)

  20. 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.

  1. 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.

  2. Local control and functional results after twice-daily radiotherapy for Ewing's sarcoma of the extremities

    International Nuclear Information System (INIS)

    Bolek, Timothy W.; Marcus, Robert B.; Mendenhall, Nancy Price; Scarborough, Mark T.; Graham-Pole, John

    1996-01-01

    Purpose: Radiotherapy (RT) has been the predominant local treatment for Ewing's sarcoma of bone at the University of Florida. Twice-daily hyperfractionated RT was initiated in 1982 to improve local control and functional outcome. This retrospective review compares the results of once-daily vs. twice-daily RT in patients with primary Ewing's sarcoma of an extremity, with emphasis on functional outcome. Methods and Materials: Between June 1971 and January 1990, 37 patients were treated at the University of Florida for nonmetastatic Ewing's sarcoma of bone with a primary lesion in an extremity. Three patients underwent amputation. Of 34 patients treated with RT, 31 had RT alone and 3 had a combination of RT and local excision. Before 1982, 14 patients received once-daily RT; since 1982, 17 patients have received twice-daily RT. Doses of once-daily RT varied from 47 to 61 Gy at 1.8-2 Gy per fraction. Doses of twice-daily RT varied, depending on the response of the soft-tissue component of the tumor to chemotherapy, and ranged from 50.4 to 60 Gy at 1.2 Gy per fraction. Some patients in the twice-daily RT group also received total body irradiation 1-3 months after local RT as part of a conditioning regimen before marrow-ablative therapy with stem cell rescue. They received either 8 Gy in two once-daily fractions or 12 Gy in six twice-daily fractions. The six patients who received surgery were excluded from local control analysis. Local control rates were calculated using the Kaplan-Meier (actuarial) method. Fifteen patients had a formal functional evaluation. Results: In the 31 patients treated with RT alone, the actuarial local control rate at 5 years was 81% for patients treated twice daily and 77% for those treated once daily (p = NS). No posttreatment pathologic fractures occurred in patients treated twice daily, whereas five fractures occurred in those treated once daily (p = 0.01). On functional evaluation, less loss in range of motion (15 deg. vs. 28 deg. of loss

  3. Chest Wall Ewing Sarcoma Family of Tumors: Long-Term Outcomes

    International Nuclear Information System (INIS)

    Indelicato, Daniel J.; Keole, Sameer R.; Lagmay, Joanne P.; Morris, Christopher G.; Gibbs, C. Parker; Scarborough, Mark T.; Islam, Saleem; Marcus, Robert B.

    2011-01-01

    Purpose: To review the 40-year University of Florida experience treating Ewing sarcoma family of tumors of the chest wall. Methods and Materials: Thirty-nine patients were treated from 1966 to 2006. Of the patients, 22 were treated with radiotherapy (RT) alone, and 17 patients were treated with surgery with or without RT. Of 9 patients with metastatic disease, 8 were treated with RT alone. The risk profiles of each group were otherwise similar. The median age was 16.6 years, and the most frequent primary site was the rib (n = 17). The median potential follow-up was 19.2 years. Results: The 5-year actuarial overall survival (OS), cause-specific survival (CSS), and local control (LC) rates were 34%, 34%, and 72%, respectively. For the nonmetastatic subset (n = 30), the 5-year OS, CSS, and LC rates were 44%, 44%, and 79%, respectively. LC was not statistically significantly different between patients treated with RT alone (61%) vs. surgery + RT (75%). None of the 4 patients treated with surgery alone experienced local failure. No patient or treatment variable was significantly associated with local failure. Of the patients, 26% experienced Common Toxicity Criteria (CTC) Grade 3+ toxicity, including 2 pulmonary deaths. Modern intensive systemic therapy helped increase the 5-year CSS from 7% to 49% in patients treated after 1984 (p = 0.03). Conclusions: This is the largest single-institution series describing the treatment of chest wall Ewing tumors. Despite improvements in survival, obtaining local control is challenging and often accompanied by morbidity. Effort should be focused on identifying tumors amenable to combined-modality local therapy and to improving RT techniques.

  4. Radiation therapy in Ewing's sarcoma: an update of the CESS 86 trial

    International Nuclear Information System (INIS)

    Dunst, Juergen; Juergens, Herbert; Sauer, Rolf; Pape, Hildegard; Paulussen, Michael; Winkelmann, Winfried; Ruebe, Christian

    1995-01-01

    Purpose: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors 3 ), or vincristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-risk tumors (central tumors and extremity tumors ≥ 100 cm 3 ). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for conventional fractionation). For quality assurance in radiotherapy, a central treatment planning program was part of the protocol. Results: Forty-four patients (25%) received definitive radiotherapy; 39 (22%) had surgery, and 93 (53%) had resection plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiotherapy, 26% after radical surgery, and 34% after combined local treatment. The better local control after radical surgery (100%) and resection plus radiotherapy (95%) as compared to definitive radiotherapy (86%) was not associated with an improvement in relapse-free or overall survival because of a higher frequency of distant metastases after surgery (26% vs. 29% vs. 16%). In irradiated patients, hyperfractionated split-course irradiation and conventional fractionation yielded the same

  5. 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

  6. Contribution of magnetic resonance imaging in the diagnosis of talus skip metastases of Ewing's sarcoma of the calcaneus in a child: a case report

    Directory of Open Access Journals (Sweden)

    Fikry Tarik

    2011-09-01

    Full Text Available Abstract Introduction Ewing's sarcoma of the calcaneus is rare. About thirty cases with calcaneus involvement have been reported in the literature. Talus skip metastases have rarely been described in the available literature Case presentation We report a case of a 14-year-old Moroccan boy, who presented with Ewing's sarcoma of his right calcaneus, diagnosed by swelling of the calcaneus evolving over a year. Radiography, computed tomography and magnetic resonance imaging showed an important tumoral process of the calcaneus and talus skip metastases. The diagnosis was confirmed with histology after a biopsy. In spite of amputation and postoperative chemotherapy, our patient died six months later due to secondary respiratory distress after lung metastasis. Conclusion Imaging, especially magnetic resonance, is important in the diagnosis of Ewing sarcoma and skeletal skip metastases. Treatment of Ewing's sarcoma consists of chemotherapy, radiation therapy and surgical resection depending on the stage and extent of the disease. With the exception of lesions in the calcaneus, the prognosis for disease-free survival of Ewing's sarcoma of the foot is excellent.

  7. Correlation of non-mass-like abnormal MR signal intensity with pathological findings surrounding pediatric osteosarcoma and Ewing's sarcoma

    International Nuclear Information System (INIS)

    Masrouha, Karim Z.; Haidar, Rachid; Saghieh, Said; Musallam, Khaled M.; Samra, Alexis Bou; Tawil, Ayman; Chakhachiro, Zaher; Abdallah, Abeer; Khoury, Nabil J.; Saab, Raya; Muwakkit, Samar; Abboud, Miguel R.

    2012-01-01

    The aim of this work was to determine the role of MRI in interpreting abnormal signals within bones and soft tissues adjacent to tumor bulk of osteosarcoma and Ewing's sarcoma in a pediatric population by correlating MR findings with histopathology. Thirty patients met the inclusion criteria, which included (1) osteosarcoma or Ewing's sarcoma, (2) MR studies no more than 2 months prior to surgery, (3) presence of abnormal MR signal surrounding the tumor bulk, (4) pathological material from resected tumor. The patients received standard neoadjuvant chemotherapy. Using grid maps on gross pathology specimens, the abnormal MR areas around the tumor were matched with the corresponding grid sections. Histopathology slides of these sections were then analyzed to determine the nature of the regions of interest. The MR/pathological correlation was evaluated using Mann-Whitney U test and Fisher's exact test. Twenty-seven patients had osteosarcoma and three patients had Ewing's sarcoma. Of the studied areas, 17.4% were positive for tumor (viable or necrotic). There was no statistically significant correlation between areas positive for tumor and age, gender, signal extent and intensity on MRI, or tissue type. There was, however, a statistically significant correlation between presence of tumor and the appearance of abnormal soft tissue signals. A feathery appearance correlated with tumor-negative areas whereas a bulky appearance correlated with tumor-positive regions. MR imaging is helpful in identifying the nature of abnormal signal areas surrounding bone sarcomas that are more likely to be tumor-free, particularly when the signal in the soft tissues surrounding the tumor is feathery and edema-like in appearance. (orig.)

  8. Medication Exposures and Subsequent Development of Ewing Sarcoma: A Review of FDA Adverse Event Reports

    Directory of Open Access Journals (Sweden)

    Judith U. Cope

    2015-01-01

    Full Text Available Background. Ewing sarcoma family of tumors (ESFT are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT. Methods. This is a retrospective, descriptive study. A query of the FDA Adverse Event Reporting System (FAERS was conducted for all reports of ESFT, January 1, 1998, through December 31, 2013. Report narratives were individually reviewed for patient characteristics, underlying conditions and drug exposures. Results. Over 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drugs and biologics including immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies. Conclusions. This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While this study was not designed to demonstrate any clear causative association between ESFT and prior use of a single product or drug class, many drugs were used to treat immune-related disease and growth or hormonal disturbances. Further studies may be warranted to better understand possible immune or neuroendocrine abnormalities or exposure to specific classes of drugs that may predispose to the later development of ESFT.

  9. IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells.

    Directory of Open Access Journals (Sweden)

    Luisa Cironi

    Full Text Available BACKGROUND: The EWS-FLI-1 fusion protein is associated with 85-90% of Ewing's sarcoma family tumors (ESFT, the remaining 10-15% of cases expressing chimeric genes encoding EWS or FUS fused to one of several ets transcription factor family members, including ERG-1, FEV, ETV1 and ETV6. ESFT are dependent on insulin-like growth factor-1 (IGF-1 for growth and survival and recent evidence suggests that mesenchymal progenitor/stem cells constitute a candidate ESFT origin. METHODOLOGY/PRINCIPAL FINDINGS: To address the functional relatedness between ESFT-associated fusion proteins, we compared mouse progenitor cell (MPC permissiveness for EWS-FLI-1, EWS-ERG and FUS-ERG expression and assessed the corresponding expression profile changes. Whereas all MPC isolates tested could stably express EWS-FLI-1, only some sustained stable EWS-ERG expression and none could express FUS-ERG for more than 3-5 days. Only 14% and 4% of the total number of genes that were respectively induced and repressed in MPCs by the three fusion proteins were shared. However, all three fusion proteins, but neither FLI-1 nor ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression. CONCLUSION/SIGNIFICANCE: Whereas expression of different ESFT-associated fusion proteins may require distinct cellular microenvironments and induce transcriptome changes of limited similarity, IGF1 induction may provide one common mechanism for their implication in ESFT pathogenesis.

  10. Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.

    Science.gov (United States)

    Park, Jeong-Yeol; Lee, Sun; Kang, Hyoung Jin; Kim, Hy-Sook; Park, Sang-Yoon

    2007-08-01

    Primary Ewing's sarcoma-primitive neuroectodermal tumor (ES-PNET) of the uterus is an extremely rare malignancy. A 30-year-old Korean woman presented with abnormal uterine bleeding with uterine enlargement. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen and pelvis showed a huge uterine mass measuring 18 x 20 x 21 cm, metastasis to both pelvic and para-aortic lymph nodes, and omental infiltration. The pathology report of the uterine mass described a uniformly hypercellular tumor, which was arranged in diffuse solid sheets of uniform, small, rounded, and sometimes spindle-shaped cells, with scanty cytoplasm. Immunohistochemically, the mass tested positive for vimentin, CD99, and chromogranin. The patient received several courses of combination chemotherapy and radiotherapy but died from tumor progression 16 months after the initial diagnosis. This is a rare case of primary uterine ES-PNET in a woman of reproductive age. A review of the literature indicates that primary uterine ES-PNET requires early diagnosis and multimodality treatment including surgery, chemotherapy, and radiotherapy. The behavior of this tumor is potentially aggressive.

  11. Ewing's sarcoma. Radiographic pattern of healing and bony complications in patients with long-term survival

    International Nuclear Information System (INIS)

    Ehara, S.; Kattapuram, S.V.; Egglin, T.K.

    1991-01-01

    The radiographic appearance of Ewing's sarcoma was studied retrospectively in 22 patients who survived 5 years or longer after diagnosis and treatment. Expected changes from treatment, including regression of the extraosseous soft tissue mass, periostitis, and reconstitution of the cortex, occurred in all patients. Local recurrence occurred in one patient 10 years after complete remission whereas secondary osteosarcoma occurred more than 5 years after complete remission in two other cases. Both recurrent and secondary tumors presented as new lytic foci at the site of the original primary lesion. Lytic changes from radiation (radiation osteitis) may develop more than 2 years after treatment and in this sample; such findings were widely distributed in the radiation port. The authors conclude that bone remodeling and postradiation changes occur slowly over 2 years after treatment, and that any localized lysis at the primary site is suspicious for recurrence or secondary neoplasm. Knowledge of the expected changes and patterns of local recurrence and secondary neoplasms helps one to detect any significant change in its early phase

  12. Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum: A Case Report and Literature Review.

    Science.gov (United States)

    Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

    2016-02-01

    Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor.

  13. Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis.

    Science.gov (United States)

    Karski, Erin E; Matthay, Katherine K; Neuhaus, John M; Goldsby, Robert E; Dubois, Steven G

    2013-02-01

    The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Identification of a tripartite import signal in the Ewing Sarcoma protein (EWS)

    International Nuclear Information System (INIS)

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G.; Eggleton, Paul; Lorson, Christian L.; Young, Philip J.

    2009-01-01

    The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.

  15. Identification of a tripartite import signal in the Ewing Sarcoma protein (EWS)

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G. [Clinical Neurobiology, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom); Eggleton, Paul [Inflammation and Musculoskeletal Disease, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom); MRC Immunochemistry Unit, University of Oxford, Oxford OX1 3QU (United Kingdom); Lorson, Christian L. [Department of Veterinary Pathobiology, Bond Life Sciences Center, 1201 Rollins Road, University of Missouri, Columbia, MO 65211 (United States); Young, Philip J., E-mail: philip.young@pms.ac.uk [Clinical Neurobiology, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom)

    2009-12-25

    The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.

  16. Antagonizing Bcl-2 family members sensitizes neuroblastoma and Ewing's sarcoma to an inhibitor of glutamine metabolism.

    Directory of Open Access Journals (Sweden)

    Rachelle R Olsen

    Full Text Available Neuroblastomas (NBL and Ewing's sarcomas (EWS together cause 18% of all pediatric cancer deaths. Though there is growing interest in targeting the dysregulated metabolism of cancer as a therapeutic strategy, this approach has not been fully examined in NBL and EWS. In this study, we first tested a panel of metabolic inhibitors and identified the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON as the most potent chemotherapeutic across all NBL and EWS cell lines tested. Myc, a master regulator of metabolism, is commonly overexpressed in both of these pediatric malignancies and recent studies have established that Myc causes cancer cells to become "addicted" to glutamine. We found DON strongly inhibited tumor growth of multiple tumor lines in mouse xenograft models. In vitro, inhibition of caspases partially reversed the effects of DON in high Myc expressing cell lines, but not in low Myc expressing lines. We further showed that induction of apoptosis by DON in Myc-overexpressing cancers is via the pro-apoptotic factor Bax. To relieve inhibition of Bax, we tested DON in combination with the Bcl-2 family antagonist navitoclax (ABT-263. In vitro, this combination caused an increase in DON activity across the entire panel of cell lines tested, with synergistic effects in two of the N-Myc amplified neuroblastoma cell lines. Our study supports targeting glutamine metabolism to treat Myc overexpressing cancers, such as NBL and EWS, particularly in combination with Bcl-2 family antagonists.

  17. Rare adrenal gland incidentaloma: an unusual Ewing's sarcoma family of tumor presentation and literature review.

    Science.gov (United States)

    Guo, Hui; Chen, Shuaiqi; Liu, Shukun; Wang, Kaixuan; Liu, Erpeng; Li, Faping; Hou, Yuchuan

    2017-04-04

    Members of the Ewing's sarcoma family of tumor (ESFT) are malignant neoplasms and rarely observed in the adrenal gland. We report an extremely exceptional case of ESFT rising from the adrenal gland in a 57-year-old Chinese man. The patient was hospitalized with abdominal swelling for 2 months. Computed tomography (CT) scan revealed a nearly-circular mass measuring about 8.1 × 10.6 cm in the right adrenal region. The patient underwent right adrenal resection. Histopathologic examination found the tumor was composed of small round blue cells forming typical Homer-Wright rosettes in focal area. The immunohistochemical analysis confirmed the case to be ESFT, which was positive for membranous CD99 and nuclear FLI-1. The patient was scheduled for four courses of large doses of chemotherapy and died for cancer metastasis one year later after surgery. Histopathological evidence of Homer-Wright rosettes and immunohistochemical markers positivity, such as CD99 and FLI-1, are valuable factors for ESFT diagnosis, although cytogenetic analysis is considered as the gold standard. Complete surgery is the treatment of choice for ESFT and adjuvant radiotherapy and combination chemotherapy can significantly improve the survival rate of postoperative patients.

  18. Localizing potentially active post-transcriptional regulations in the Ewing's sarcoma gene regulatory network

    Directory of Open Access Journals (Sweden)

    Delyon Bernard

    2010-11-01

    Full Text Available Abstract Background A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. Results We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted of post-processing the outputs of an open-source tool named BioQuali - an automatic constraint-based analysis mimicking biologist's local reasoning on a large scale. The post-processing relied on differences in the behavior of the transcriptional and post-translational levels in the network. As a case study, we analyzed a network representation of the genes and proteins controlled by an oncogene in the context of Ewing's sarcoma. The analysis allowed us to pinpoint active interactions specific to this cancer. We also identified the parts of the network which were incomplete and should be submitted for further investigation. Conclusions The proposed approach is effective for the qualitative analysis of cancer networks. It allows the integrative use of experimental data of various types in order to identify the specific information that should be considered a priority in the initial - and possibly very large - experimental dataset. Iteratively, new dataset can be introduced into the analysis to improve the network representation and make it more specific.

  19. Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

    Science.gov (United States)

    Thorpe, Steven W.; Weiss, Kurt R.; Goodman, Mark A.; Heyl, Alma E.; McGough, Richard L.

    2012-01-01

    In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease. PMID:22550427

  20. Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment

    Directory of Open Access Journals (Sweden)

    van Maldegem Annemiek M

    2012-01-01

    Full Text Available Abstract Background High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years. Results We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures. Conclusion Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into

  1. Development of a preclinical orthotopic xenograft model of ewing sarcoma and other human malignant bone disease using advanced in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Britta Vormoor

    Full Text Available Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG and Rag2(-/-/γc(-/- mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000-5000 injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised "malignant" bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

  2. 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.

  3. Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma.

    Science.gov (United States)

    Ghisoli, Maurizio; Barve, Minal; Mennel, Robert; Lenarsky, Carl; Horvath, Staci; Wallraven, Gladice; Pappen, Beena O; Whiting, Sam; Rao, Donald; Senzer, Neil; Nemunaitis, John

    2016-08-01

    Ewing's sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG (Vigil) vaccine, in which 12 advanced stage Ewing's patients were safely treated and went on to achieve a predicted immune response (IFNγ ELISPOT). We describe follow-up through year 3 of a prospective, nonrandomized study comparing an expanded group of Vigil-treated advanced disease Ewing's sarcoma patients (n = 16) with a contemporaneous group of Ewing's sarcoma patients (n = 14) not treated with Vigil. Long-term follow-up results show a survival benefit without evidence of significant toxicity (no ≥ grade 3) to Vigil when administered once monthly by intradermal injection (1 × 10e(6) cells/injection to 1 × 10e(7) cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil-treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2-month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing's sarcoma.

  4. 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

  5. Tumor Vessel Development and Expansion in Ewing's Sarcoma: A Review of the Vasculogenesis Process and Clinical Trials with Vascular-Targeting Agents

    Science.gov (United States)

    Stewart, Keri S.; Kleinerman, Eugenie S.

    2011-01-01

    Ewing's sarcoma accounts for a disproportionately high portion of the overall pediatric mortality rate compared to its rare incidence in the pediatric population. Little progress has been made since the introduction of traditional chemotherapies, and understanding the biology of the tumor is critical for developing new therapies. Ewing's sarcomas rely on a functional vascular supply, which is formed by a combination of angiogenesis and vasculogenesis. Recent insights into the molecular regulation of bone marrow (BM) cell participation in vascular development have identified VEGF, SDF-1α, and DLL4 as critical players in the vasculogenesis process. Clinical trials using vascular targeting agents, specifically targeting VEGF or DLL4, are underway. PMID:21785569

  6. Application of infrared spectroscopy in the identification of Ewing sarcoma: A preliminary report

    Science.gov (United States)

    Chaber, Radosław; Łach, Kornelia; Szmuc, Kamil; Michalak, Elżbieta; Raciborska, Anna; Mazur, Damian; Machaczka, Maciej; Cebulski, Józef

    2017-06-01

    Fourier transform infrared (FTIR) spectroscopy is a highly sensitive, non-invasive analytical technique that can provide information about molecular changes in a biological sample. FTIR spectrum is a sum of the frequencies of many biomolecules which reveals a biochemical fingerprint for mineral identification, and can be analyzed for information about the mineral structure of malignant cells. This gives us the potential to differentiate tumor cells from normal cells in the early stage of relapse, before the tumor cells would be detectable in light microscopy. Ewing sarcoma (ES) is the second most common malignant bone tumor found in children and adolescents. ES affects annually almost 3 persons/1,000,000 mostly children and young adults under 20 years of age annually. ES originates from primitive, low-differentiated neuroectodermal cells. The current standard of therapy for ES is the surgical resection of the primary tumor and metastasis in combination with the chemo- and radiotherapy. The aim of this study was to compare the spectra of ES bone samples and the spectra of normal bone tissues, analyzed before and after induction chemotherapy, by means of FTIR spectroscopy. Six patients with ES affecting bones aged 5.5-16.5 years (median age 11.2 years), who were treated between 2011 and 2015, were included to the study. In all analyzed patients, the diagnosis of ES and the assessment of response to the chemotherapy were performed according to the Euro-EWING-2008 protocol. The Fourier transform infrared spectroscope (FT-IR; Vertex 70v from Bruker) was used in this study. Tissue specimens were applied to the attenuated total reflection (ATR) in the infrared (IR) radiation from the mid-infrared range using a single-reflection snap ATR crystal diamond. In the FTIR spectra we observed a shift in the wave number of the phosphate ion (from 3 to 26 [cm-1]) associated with the presence of tumor tissue. After chemotherapy, a change of the FTIR spectrum was associated with the

  7. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Directory of Open Access Journals (Sweden)

    Claudia Bühnemann

    Full Text Available Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases. Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%. The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36 was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality

  8. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Science.gov (United States)

    Bühnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schäfer, Karl L; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C W; Athanasou, Nicholas A; Noble, J Alison; Hassan, A Bassim

    2014-01-01

    Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour

  9. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    International Nuclear Information System (INIS)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C.; Jutte, Paul C.

    2018-01-01

    To determine and compare the value of 18 F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

  10. Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL

    Science.gov (United States)

    Picarda, Gaëlle; Matous, Etienne; Amiaud, Jérôme; Charrier, Céline; Lamoureux, François; Heymann, Marie-Françoise; Tirode, Franck; Pitard, Bruno; Trichet, Valérie; Heymann, Dominique; Redini, Françoise

    2013-01-01

    Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development. Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71 ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor development was observed in the hOPG group as compared to control groups. Marked bone lesions were revealed by micro-computed tomography analyses in control groups whereas a normal bone micro-architecture was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition. In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the relevance of blocking RANKL by OPG as a promising therapy in ES. PMID:26909278

  11. Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

    Science.gov (United States)

    Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

    2014-06-01

    To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

  12. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    Energy Technology Data Exchange (ETDEWEB)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C. [University of Groningen, Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (Netherlands); Jutte, Paul C. [University of Groningen, Department of Orthopedics, University Medical Center Groningen (Netherlands)

    2018-03-15

    To determine and compare the value of {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

  13. CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling

    OpenAIRE

    Manara, Maria Cristina; Terracciano, Mario; Mancarella, Caterina; Sciandra, Marika; Guerzoni, Clara; Pasello, Michela; Grilli, Andrea; Zini, Nicoletta; Picci, Piero; Colombo, Mario P.; Morrione, Andrea; Scotlandi, Katia

    2016-01-01

    CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD9...

  14. Localization of genetic elements of intact and derivative chromosome 11 and 22 territories in nuclei of Ewing sarcoma cells

    Czech Academy of Sciences Publication Activity Database

    Taslerová, R.; Kozubek, Stanislav; Bártová, Eva; Jirsová, Pavla; Kodet, R.; Kozubek, M.

    2006-01-01

    Roč. 155, č. 3 (2006), s. 493-504 ISSN 1047-8477 R&D Projects: GA AV ČR(CZ) 1QS500040508; GA ČR(CZ) GA202/04/0907; GA MZd(CZ) 1A8241; GA AV ČR(CZ) IAA5004306; GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50040507 Keywords : chromatin structure * chromosome territory * Ewing sarcoma Subject RIV: BO - Biophysics Impact factor: 3.496, year: 2006

  15. Mechanisms of transcriptional repression by EWS-FLl1 in Ewing Sarcoma

    International Nuclear Information System (INIS)

    Niedan, S.

    2012-01-01

    The EWS-FLI1 chimeric oncoprotein characterizing Ewing Sarcoma (ES) is a prototypic aberrant ETS transcription factor with activating and repressive gene regulatory functions. Mechanisms of transcriptional regulation, especially transcriptional repression by EWS-FLI1, are poorly understood. We report that EWS-FLI1 repressed promoters are enriched in forkhead box recognition motifs, and identify FOXO1 as a EWS-FLI1 suppressed master regulator responsible for a significant subset of EWS-FLI1 repressed genes. In addition to transcriptional FOXO1 regulation by direct promoter binding of EWS-FLI1, its subcellular localization and activity is regulated by CDK2 and AKT mediated phosphorylation downstream of EWS-FLI1. Functional restoration of nuclear FOXO1 expression in ES cells impaired proliferation and significantly reduced clonogenicity. Gene-expression profiling revealed a significant overlap between EWS-FLI1 repressed and FOXO1-activated genes. Treatment of ES cell lines with Methylseleninic acid (MSA) evoked reactivation of endogenous FOXO1 in the presence of EWS-FLI1 in a dose- and time-dependent manner and induced massive cell death which was found to be partially FOXO1-dependent. In an orthotopic xenograft mouse model, MSA increased FOXO1 expression in the tumor paralleled by a significant decrease in ES tumor growth. Together, these data suggest that a repressive sub-signature of EWS-FLI1 repressed genes precipitates suppression of FOXO1. FOXO1 re-activation by small molecules may therefore constitute a novel therapeutic strategy in the treatment of ES. (author) [de

  16. Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

    International Nuclear Information System (INIS)

    Casey, Dana L.; Alektiar, Kaled M.; Gerber, Naamit K.; Wolden, Suzanne L.

    2014-01-01

    Purpose: To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. Methods and Materials: Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. Results: The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. Conclusion: WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI

  17. V-ATPase is a candidate therapeutic target for Ewing sarcoma.

    Science.gov (United States)

    Avnet, Sofia; Di Pompo, Gemma; Lemma, Silvia; Salerno, Manuela; Perut, Francesca; Bonuccelli, Gloria; Granchi, Donatella; Zini, Nicoletta; Baldini, Nicola

    2013-08-01

    Suppression of oxidative phosphorylation combined with enhanced aerobic glycolysis and the resulting increased generation of protons are common features of several types of cancer. An efficient mechanism to escape cell death resulting from intracellular acidification is proton pump activation. In Ewing sarcoma (ES), although the tumor-associated chimeric gene EWS-FLI1 is known to induce the accumulation of hypoxia-induced transcription factor HIF-1α, derangements in metabolic pathways have been neglected so far as candidate pathogenetic mechanisms. In this paper, we observed that ES cells simultaneously activate mitochondrial respiration and high levels of glycolysis. Moreover, although the most effective detoxification mechanism of proton intracellular storage is lysosomal compartmentalization, ES cells show a poorly represented lysosomal compartment, but a high sensitivity to the anti-lysosomal agent bafilomycin A1, targeting the V-ATPase proton pump. We therefore investigated the role of V-ATPase in the acidification activity of ES cells. ES cells with the highest GAPDH and V-ATPase expression also showed the highest acidification rate. Moreover, the localization of V-ATPase was both on the vacuolar and the plasma membrane of all ES cell lines. The acidic extracellular pH that we reproduced in vitro promoted high invasion ability and clonogenic efficiency. Finally, targeting V-ATPase with siRNA and omeprazole treatments, we obtained a significant selective reduction of tumor cell number. In summary, glycolytic activity and activation of V-ATPase are crucial mechanisms of survival of ES cells and can be considered as promising selective targets for the treatment of this tumor. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Radiation therapy for Ewing's sarcoma: Results from Memorial Sloan-Kettering in the modern era

    International Nuclear Information System (INIS)

    La, Trang H.; Meyers, Paul A.; Wexler, Leonard H.; Alektiar, Kaled M.; Healey, John H.; Laquaglia, Michael P.; Boland, Patrick J.; Wolden, Suzanne L.

    2006-01-01

    Purpose: To evaluate the outcomes of patients with Ewing's sarcoma family of tumors (ESFT) treated with modern radiotherapy techniques with MRI along with optimal chemotherapy. Methods and Materials: The records of all 60 patients with ESFT who received radiation to the primary site between 1990 and 2004 were reviewed. All patients received chemotherapy, including vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. Radiation was used as the sole modality for local control in 31 patients and was given either before (n = 3) or after surgical resection (n = 26) in the remainder. All patients had MRI and CT scan-based treatment planning, and 43% received intensity-modulated radiation therapy. Radiation doses ranged from 30 Gy to 60 Gy (median, 51 Gy), and 35% received hyperfractionated radiotherapy. Results: Median age was 16 years (range, 2-40 years). Because of selection bias for radiotherapy, the majority of primary tumors were centrally located (72%): spine (n = 18), pelvis (n = 15), extremities (n 12), chest wall (n = 5), head and neck (n = 5), and other (n = 5). Thirty-eight percent of patients presented with metastatic disease, and 52% of primary tumors were ≥8 cm. Actuarial 3-year local control was 77%. The presence of metastases at diagnosis was an adverse prognostic factor for local control (84% vs. 61%, p = 0.036). No other predictive factors for local failure were identified. In patients without metastatic disease, 3-year disease-free and overall survival rates were 70% and 86%, respectively, whereas in patients with metastases they were both 21%. Follow-up of surviving patients was 6-178 months (median, 41 months). Conclusion: In this unfavorable cohort of ESFT patients, radiation therapy was an effective modality for local control, especially for patients without metastases. The presence of metastases at diagnosis is a predictive factor not only for death but also for local failure

  19. Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Dana L.; Alektiar, Kaled M.; Gerber, Naamit K.; Wolden, Suzanne L., E-mail: woldens@mskcc.org

    2014-08-01

    Purpose: To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. Methods and Materials: Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. Results: The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. Conclusion: WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI.

  20. Characterization and drug resistance patterns of Ewing's sarcoma family tumor cell lines.

    Directory of Open Access Journals (Sweden)

    William A May

    Full Text Available Despite intensive treatment with chemotherapy, radiotherapy and surgery, over 70% of patients with metastatic Ewing's Sarcoma Family of Tumors (EFT will die of their disease. We hypothesize that properly characterized laboratory models reflecting the drug resistance of clinical tumors will facilitate the application of new therapeutic agents to EFT. To determine resistance patterns, we studied newly established EFT cell lines derived from different points in therapy: two established at diagnosis (CHLA-9, CHLA-32, two after chemotherapy and progressive disease (CHLA-10, CHLA-25, and two at relapse after myeloablative therapy and autologous bone marrow transplantation (post-ABMT (CHLA-258, COG-E-352. The new lines were compared to widely studied EFT lines TC-71, TC-32, SK-N-MC, and A-673. These lines were extensively characterized with regard to identity (short tandem repeat (STR analysis, p53, p16/14 status, and EWS/ETS breakpoint and target gene expression profile. The DIMSCAN cytotoxicity assay was used to assess in vitro drug sensitivity to standard chemotherapy agents. No association was found between drug resistance and the expression of EWS/ETS regulated genes in the EFT cell lines. No consistent association was observed between drug sensitivity and p53 functionality or between drug sensitivity and p16/14 functionality across the cell lines. Exposure to chemotherapy prior to cell line initiation correlated with drug resistance of EFT cell lines in 5/8 tested agents at clinically achievable concentrations (CAC or the lower tested concentration (LTC: (cyclophosphamide (as 4-HC and doxorubicin at CAC, etoposide, irinotecan (as SN-38 and melphalan at LTC; P<0.1 for one agent, and P<0.05 for four agents. This panel of well-characterized drug-sensitive and drug-resistant cell lines will facilitate in vitro preclinical testing of new agents for EFT.

  1. Ewing sarcoma of the bone in children under 6 years of age.

    Directory of Open Access Journals (Sweden)

    Maria Antonietta De Ioris

    Full Text Available BACKGROUND: Ewing Sarcoma Family Tumours (ESFT are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the bone in Italy. METHODS: The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP from 1990 to 2008 were reviewed. The Kaplan-Meier method was used for estimating overall and progression-free survival (OS, PFS curves; multivariate analyses were performed using Cox proportional hazards regression model. RESULTS: This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23% patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58-83% and 72% (95% CI 57-83% for patients with localized disease and 38% (95% CI 17-60% and 21% (95% CI 5-45% for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P<0.01, while patients treated in the last decade had better survival (P = 0.002. In fact, the 5-year OS and PFS for patients diagnosed in the period 2000-2008 were 89% (95% CI 71-96% and 86% (95% CI 66-94%, respectively. CONCLUSION: The axial localization is the most common site of ESFT in pre-scholar children. Patients treated in the most recent period have an excellent outcome.

  2. Let-7a is a direct EWS-FLI-1 target implicated in Ewing's sarcoma development.

    Directory of Open Access Journals (Sweden)

    Claudio De Vito

    Full Text Available Ewing's sarcoma family tumors (ESFT are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

  3. Novel Secondary Somatic Mutations in Ewing's Sarcoma and Desmoplastic Small Round Cell Tumors

    Science.gov (United States)

    Janku, Filip; Ludwig, Joseph A.; Naing, Aung; Benjamin, Robert S.; Brown, Robert E.; Anderson, Pete; Kurzrock, Razelle

    2014-01-01

    Background Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. Methodology Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics. Principal Findings Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression. Conclusions We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy. PMID:25119929

  4. Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005-2012

    Energy Technology Data Exchange (ETDEWEB)

    Johnsen, Boel [Haukeland University Hospital, Centre for Nuclear Medicine and PET, Department of Radiology, P.O. Box 1400, Bergen (Norway); Fasmer, Kristine Eldevik [Haukeland University Hospital, Department of Oncology, Medical Physics Section, Bergen (Norway); Boye, Kjetil [Norwegian Radium Hospital, Oslo University Hospital, Department of Oncology, Oslo (Norway); Rosendahl, Karen; Aukland, Stein Magnus [Haukeland University Hospital, Department of Radiology, Paediatric Section, Bergen (Norway); University of Bergen, Department of Clinical Medicine, Bergen (Norway); Trovik, Clement [University of Bergen, Department of Clinical Medicine, Bergen (Norway); Haukeland University Hospital, Department of Surgery, Orthopaedic Section, Bergen (Norway); Biermann, Martin [Haukeland University Hospital, Centre for Nuclear Medicine and PET, Department of Radiology, P.O. Box 1400, Bergen (Norway); University of Bergen, Department of Clinical Medicine, Bergen (Norway)

    2017-01-15

    Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation. To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether {sup 18}F-fluorodeoxyglucose positron emission tomography - computed tomography ({sup 18}F-FDG PET-CT) is a major contributor of radiation. Twenty Ewing sarcoma patients diagnosed in Norway in 2005-2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient. The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6-70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2-28) and nuclear medicine for 18 mSv (range: 2-47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%). There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT. (orig.)

  5. Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005-2012

    International Nuclear Information System (INIS)

    Johnsen, Boel; Fasmer, Kristine Eldevik; Boye, Kjetil; Rosendahl, Karen; Aukland, Stein Magnus; Trovik, Clement; Biermann, Martin

    2017-01-01

    Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation. To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether 18 F-fluorodeoxyglucose positron emission tomography - computed tomography ( 18 F-FDG PET-CT) is a major contributor of radiation. Twenty Ewing sarcoma patients diagnosed in Norway in 2005-2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient. The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6-70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2-28) and nuclear medicine for 18 mSv (range: 2-47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%). There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT. (orig.)

  6. Murine bone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors.

    Science.gov (United States)

    Duan, Xiaoping; Guan, Hui; Cao, Ying; Kleinerman, Eugenie S

    2009-01-01

    This study evaluated the therapeutic efficacy of interleukin 12 (IL-12) gene therapy in Ewing sarcoma and whether murine mesenchymal stem cells (MSCs) could serve as vehicles for IL-12 gene delivery. MSCs were isolated from murine bone marrow cells. Cells were phenotyped using flow cytometry. Cultured MSCs differentiated into osteocytes and adipocytes using the appropriate media. Freshly isolated MSCs were transfected with adenoviral vectors containing either the beta-galactosidase (Ad:beta-gal) or the IL-12 (Ad:IL-12) gene. Expression of IL-12 was confirmed using reverse transcription polymerase chain reaction. Mice with TC71 Ewing sarcoma tumors were then treated intravenously with MSCs transfected with Ad:beta-gal or Ad:IL-12. Tumors were measured and analyzed by immunohistochemical analysis for expression of IL-12 protein. Expression of both p35 and p40 IL-12 subunits was demonstrated in MSCs transfected in vitro with Ad:IL-12. IL-12 expression was seen in tumors from mice treated with MSCs transfected with Ad:IL-12. Tumor growth was also significantly inhibited compared with that in mice treated with MSCs transfected with Ad:beta-gal. MSCs can be transfected with the IL-12 gene. These transfected cells localize to tumors after intravenous injection and induce local IL-12 protein production and the regression of established tumors. Copyright (c) 2008 American Cancer Society.

  7. The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas

    NARCIS (Netherlands)

    Fleuren, Emmy D. G.; Versleijen-Jonkers, Yvonne M. H.; Heskamp, Sandra; Roeffen, Melissa H. S.; Bouwman, Wilbert H.; Molkenboer-Kuenen, Janneke D. M.; van Laarhoven, Hanneke W. M.; Oyen, Wim J. G.; Boerman, Otto C.; van der Graaf, Winette T. A.

    2013-01-01

    To investigate whether F(ab')2-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')2-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8)

  8. Extraosseal Ewing sarcoma as a rare cause of the blueberry muffin baby syndrome: A case report and the review of the literature

    Czech Academy of Sciences Publication Activity Database

    Křenová, Z.; Křen, L.; Blatný, J.; Falk, Martin; Kazakov, D.; Grossmann, P.; Shimada, H.; Štěrba, J.

    2011-01-01

    Roč. 33, č. 7 (2011), s. 733-735 ISSN 0193-1091 Grant - others:GA MŠk(CZ) LM2010004 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : blueberry muffin baby syndrome * Ewing sarcoma * fluorescence in situ hybridization (FISH) Subject RIV: BO - Biophysics Impact factor: 1.197, year: 2011

  9. Quality of Survivorship in a Rare Disease: Clinicofunctional Outcome and Physical Activity in an Observational Cohort Study of 618 Long-Term Survivors of Ewing Sarcoma

    NARCIS (Netherlands)

    Ranft, Andreas; Seidel, Corinna; Hoffmann, Christiane; Paulussen, Michael; Warby, Ann-Christin; van den Berg, Henk; Ladenstein, Ruth; Rossig, Claudia; Dirksen, Uta; Rosenbaum, Dieter; Juergens, Herbert

    2017-01-01

    PurposeSignificantly improved survival rates in patients with Ewing sarcoma have raised interest in accessing the quality of long-term survivorship. In this study, subjective and objective measurement tools, preclassified as physical or mental scores, were used to assess clinicofunctional outcome

  10. Picropodophyllin inhibits the growth of Ewing's sarcoma cells through the insulin‑like growth factor‑1 receptor/Akt signaling pathway.

    Science.gov (United States)

    Wu, Yong-Tao; Wang, Bao-Jun; Miao, Sheng-Wu; Gao, Jian-Jun

    2015-11-01

    Ewing's sarcoma (ES) is the second most common type of pediatric bone tumor, and is associated with a poor prognosis. Picropodophyllin (PPP), a novel selective inhibitor of insulin‑like growth factor‑1 receptor (IGF‑1R), is able to strongly inhibit various types of cancers. However, the effect of IGF‑1R on ES remains unclear. Following treatment with various concentrations of PPP for various times, cell viability was determined using an MTT assay. In addition, cell proliferation and apoptosis was investigated separately by bromodeoxyuridine staining and flow cytometry, respectively. The PPP‑associated signaling pathway was also investigated. The results of the present study suggested that PPP inhibited cell proliferation and viability of A673 and SK‑ES‑1 human Ewing's sarcoma cells in a dose- and time‑dependent manner. In addition, cell apoptosis rates were increased following treatment with PPP. Further investigation of the underlying mechanism revealed that PPP inhibited Akt phosphorylation. Fumonisin B1, an Akt‑specific activator, reversed the inhibitory effects of PPP on cell growth. Furthermore, the results suggested that PPP decreased the expression levels of IGF‑1R, a common activator of Akt signaling. PPP inhibited the growth of human Ewing's sarcoma cells by targeting the IGF‑1R/Akt signaling pathway. Therefore, PPP may prove useful in the development of an effective strategy for the treatment of Ewing's sarcoma.

  11. 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.

  12. Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients.

    Science.gov (United States)

    Palmerini, E; Jones, R L; Setola, E; Picci, P; Marchesi, E; Luksch, R; Grignani, G; Cesari, M; Longhi, A; Abate, M E; Paioli, A; Szucs, Z; D'ambrosio, L; Scotlandi, K; Fagioli, F; Asaftei, S; Ferrari, S

    2018-03-13

    Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. Patients receiving TEM 100 mg/m 2 /day oral, and IRI 40 mg/m 2 /day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed. The median age of the 51 patients was 21 years (range 3-65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35-63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45-83] for ECOG 0, 34% [95% CI 14-54] for ECOG ≥1; p = .006) and LDH (6-mos PFS 62% [95% CI 44-79] for normal LDH, 22% [95% CI 3-42] for high LDH; p = .02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39-70), with RECIST response (p = .001) and ECOG (p = .0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%. This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.

  13. Sarcoma de Ewing: epidemiologia e prognóstico dos pacientes tratados no Instituto de Oncologia Pediátrica, IOP-GRAACC-UNIFESP Ewing's sarcoma: epidemiology and prognosis for patients treated at the Pediatric Oncology Institute, IOP-GRAACC-UNIFESP

    Directory of Open Access Journals (Sweden)

    Davi Gabriel Bellan

    2012-01-01

    Full Text Available OBJETIVO: Traçar o perfil epidemiológico e o prognóstico do sarcoma de Ewing na população brasileira. Material e MÉTODO: Foram avaliados, retrospectivamente, os prontuários de 64 pacientes tratados, com sarcoma de Ewing intraósseo, no Instituto de Oncologia Pediátrica, IOP-GRAACC-Unifesp, no período de 1995 a 2010. RESULTADOS: A análise estatística dos dados obtidos não correlacionou fatores como sexo, trauma, fratura patológica e tempo ao diagnóstico com o desfecho do tratamento. Fatores como metástase inicial, metástase pulmonar, local do tumor, idade, recidiva e tipo de cirurgia indicam resultados que corroboram a literatura consagrada. CONCLUSÃO: O prognóstico no sarcoma de Ewing foi influenciado principalmente pela presença de metástase ao diagnóstico.OBJECTIVE: To outline the epidemiological profile and prognosis for Ewing's sarcoma in the Brazilian population. Material and METHODS: The medical records of 64 patients with intraosseous Ewing's sarcoma who were treated at the Pediatric Oncology Institute, IOP-GRAACC-Unifesp, between 1995 and 2010, were retrospectively evaluated. RESULTS: The statistical analysis on the data obtained did not correlate factors such as sex, trauma, pathological fracture and time taken for case diagnosis with the treatment outcome. Factors such as initial metastasis, lung metastasis, tumor site, age, recurrence and type of surgery showed results corroborating what has been established in the literature. CONCLUSION: The prognosis in cases of Ewing's sarcoma was mainly influenced by the presence of metastases at the time of diagnosis.

  14. Ewing's sarcoma, fibrogenic tumors, giant cell tumor, hemangioma of bone. Radiology and pathology; Ewing-Sarkom, fibrogene Tumoren, Riesenzelltumor, Haemangiom des Skeletts. Radiologie und Pathologie

    Energy Technology Data Exchange (ETDEWEB)

    Freyschmidt, J. [Beratungsstelle und Referenzzentrum fuer Osteoradiologie, Bremen (Germany); Ostertag, H. [Klinikum Region Hannover GmbH, Pathologisches Institut, Hannover (Germany)

    2016-06-15

    Radiological imaging only reflects the anatomy and its pathological abnormalities. Therefore, the radiologist should be able to recognize the basic features of the pathological anatomy of bone tumors. This can only be learned working closely with a pathologist who is experienced in this field. On the other hand, the pathologist needs from the radiologist their diagnostic assessment with information on size, location, aggressiveness and the existence of a bone tumor's matrix, of the whole lesion, because he usually only receives a small part for examination in the form of a biopsy. In this article, the features and fundamentals (standards) of radiological-pathological cooperation as the mainstay for a precise diagnosis in bone tumors are outlined. The radiological appearance and the histopathological features behind it are presented for Ewing's sarcoma, fibrogenic tumors, giant cell tumor, and hemangioma of the bone. (orig.) [German] Radiologische Bilder spiegeln nichts anderes als die Anatomie und ihre pathologischen Abweichungen wider. Deshalb sollte der Radiologe die Grundzuege der pathologischen Anatomie auch von Knochentumoren kennen. Das kann er nur durch eine enge Zusammenarbeit mit einem auf diesem Gebiet erfahrenen Pathologen erlernen. Andererseits braucht der Pathologe vom Radiologen dessen diagnostische Einschaetzung mit Informationen ueber die Groesse, Lage, Aggressivitaet und das Vorhandensein einer Matrix eines Knochentumors und zwar von der gesamten Laesion, denn er bekommt inform einer Biopsie i. d. R. nur einen mehr oder weniger kleinen Teil zur Untersuchung. In diesem Beitrag werden die Grundzuege und Standards der radiologisch-pathologischen Zusammenarbeit aufgezeigt, auf denen eine praezise Diagnosestellung beruht. Radiologisches Erscheinungsbild und die dahintersteckenden - und erklaerenden - histopathologischen Merkmale werden fuer das Ewing-Sarkom, fuer fibrogene Tumoren, den Riesenzelltumor und das Haemangiom des Knochens

  15. Limberg fasciocutaneous transposition flap for the coverage of an exposed hip implant in a patient affected by ewing sarcoma

    Directory of Open Access Journals (Sweden)

    Mario Faenza

    Full Text Available Introduction: Hemipelvectomy with immediate reconstruction with prosthetic devices for the surgical treatment of malignant tumors is an invasive procedure with many possible complications such as wound breakdown, seroma, hematoma and infection.The treatment of an exposed hip implant in these cluster of patient is extremely challenging and the literature shows how negative pressure wound therapy and myocutaneous, both pedicled and free, flaps are workhorses in these situations. Case report: In this paper we report a successful coverage of exposed prosthetic hip implant with a local fasciocutaneous flap in a patient in which any other kind of reconstruction was not feasible. Discussion: Fasciocutaneous flaps can be considered as an easily performed and minimally invasive surgical procedure, particularly reliable even in patients in poor general conditions, with preservation of future flap options. Keywords: Ewing sarcoma, Hemipelvectomy, Hip implant, Wound healing, Fasciocutaneous flap, Exposed implant

  16. [Primitive neuroectodermal tumor/Ewing's sarcoma of the penis in children: a case report and review of the literature].

    Science.gov (United States)

    Zhang, Da-Wei; Jin, Mei; Zhou, Chun-Ju; Song, Hong-Cheng; Ma, Xiao-Li

    2012-12-01

    To investigate the clinical manifestations, pathological characteristics and treatment of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) of the penis in children. We analyzed the clinical data of a case of PNET/EWS and reviewed relevant literature. The patient was a 5-year-old boy, admitted for penis swelling with pain for 11 months. Biopsy showed a small round cell tumor, CD99 positive by immunohistochemical staining, with EWS translocation by fluorescence in situ hybridization on molecular biological examination. The tumor was confirmed to be PNET/EWS of the penis, and disappeared after 45 weeks of chemotherapy and local radiotherapy. PNET/EWS of the penis is an extremely rare disease, with no specific clinical symptoms except penis enlargement with pain. Immunohistochemistry and molecular biological examination contribute to its diagnosis.

  17. FOXO1 is a direct target of EWS-Fli1 oncogenic fusion protein in Ewing's sarcoma cells

    International Nuclear Information System (INIS)

    Yang, Liu; Hu, Hsien-Ming; Zielinska-Kwiatkowska, Anna; Chansky, Howard A.

    2010-01-01

    Research highlights: → Inducible and reversible siRNA knockdown of an oncogenic fusion protein such as EWS-Fli1 is feasible and more advantageous than other siRNA methods. → The tumor suppressor gene FOXO1 is a new EWS-Fli1 target. → While trans-activators are known for the FOXO1 gene, there has been no report on negative regulators of FOXO1 transcription. → This study provides first evidence that the EWS-Fli1 oncogenic fusion protein can function as a transcriptional repressor of the FOXO1 gene. -- Abstract: Ewing's family tumors are characterized by a specific t(11;22) chromosomal translocation that results in the formation of EWS-Fli1 oncogenic fusion protein. To investigate the effects of EWS-Fli1 on gene expression, we carried out DNA microarray analysis after specific knockdown of EWS-Fli1 through transfection of synthetic siRNAs. EWS-Fli1 knockdown increased expression of genes such as DKK1 and p57 that are known to be repressed by EWS-Fli1 fusion protein. Among other potential EWS-Fli1 targets identified by our microarray analysis, we have focused on the FOXO1 gene since it encodes a potential tumor suppressor and has not been previously reported in Ewing's cells. To better understand how EWS-Fli1 affects FOXO1 expression, we have established a doxycycline-inducible siRNA system to achieve stable and reversible knockdown of EWS-Fli1 in Ewing's sarcoma cells. Here we show that FOXO1 expression in Ewing's cells has an inverse relationship with EWS-Fli1 protein level, and FOXO1 promoter activity is increased after doxycycline-induced EWS-Fli1 knockdown. In addition, we have found that direct binding of EWS-Fli1 to FOXO1 promoter is attenuated after doxycycline-induced siRNA knockdown of the fusion protein. Together, these results suggest that suppression of FOXO1 function by EWS-Fli1 fusion protein may contribute to cellular transformation in Ewing's family tumors.

  18. A systematic review of optimal treatment strategies for localized Ewing's sarcoma of bone after neo-adjuvant chemotherapy.

    Science.gov (United States)

    Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; Di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

    2016-03-01

    To perform a systematic review to investigate the optimal treatment strategy among the options of surgery alone, radiotherapy (RT) alone, and the combination of RT plus surgery in the management of localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy. MEDLINE and EMBASE (1999 to February 2015), the Cochrane Library, and relevant conferences were searched. Two systematic reviews and eight full texts met the pre-planned study selection criteria. When RT was compared with surgery, a meta-analysis combining two papers showed that surgery resulted in a higher event-free survival (EFS) than RT in any location (HR = 1.50, 95% CI 1.12-2.00; p = 0.007). However another paper did not find a statistically significant difference in patients with pelvic disease, and no papers identified a significant difference in overall survival. When surgery plus RT was compared with surgery alone, a meta-analysis did not demonstrate a statistically significant difference for EFS between the two groups (HR = 1.21, 95% CI 0.90-1.63). Both surgical morbidities and radiation toxicities were reported. The existing evidence is based on very low aggregate quality as assessed by the GRADE approach. In patients with localized Ewing's sarcoma, either surgery alone (if complete surgical excision with clear margin can be achieved) or RT alone may be a reasonable treatment option. The optimal local treatment for an individual patient should be decided through consideration of patient characteristics, the potential benefit and harm of the treatment options, and patient preference. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  19. Ewing's sarcoma: only patients with 100% of necrosis after chemotherapy should be classified as having a good response.

    Science.gov (United States)

    Albergo, J I; Gaston, C L; Laitinen, M; Darbyshire, A; Jeys, L M; Sumathi, V; Parry, M; Peake, D; Carter, S R; Tillman, R; Abudu, A T; Grimer, R J

    2016-08-01

    The purpose of this study was to review a large cohort of patients and further assess the correlation between the histological response to chemotherapy in patients with Ewing's sarcoma with the overall (OS) and event-free survival (EFS). All patients treated for Ewing's sarcoma between 1980 and 2012 were reviewed. Of these, 293 patients without metastases at the time of diagnosis and treated with chemotherapy and surgery were included. Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. The mean age at diagnosis was 16 years (1 to 62) and the mean follow-up was 9.1 years (six months to 32.6 years). The OS and EFS for the series were 75% and 65% at five years. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years, respectively) (p < 0.001). There were no significant differences in survival between patients treated between 1980 and 1989 compared with those treated between 1990 and 1999, and those treated between 2000 and 2012 (p = 0.55). Only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumour in the surgical specimen. Cite this article: Bone Joint J 2016;98-B:1138-44. ©2016 The British Editorial Society of Bone & Joint Surgery.

  20. Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

    Science.gov (United States)

    van den Berg, Henk; Paulussen, Michael; Le Teuff, Gwénaël; Judson, Ian; Gelderblom, Hans; Dirksen, Uta; Brennan, Bernadette; Whelan, Jeremy; Ladenstein, Ruth Lydia; Marec-Berard, Perrine; Kruseova, Jarmila; Hjorth, Lars; Kühne, Thomas; Brichard, Benedicte; Wheatley, Keith; Craft, Alan; Juergens, Heribert; Gaspar, Nathalie; Le Deley, Marie-Cécile

    2015-11-01

    Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and

  1. A multi-disciplinary study investigating radiotherapy in Ewing's sarcoma - a final report of POG 8346

    International Nuclear Information System (INIS)

    Donaldson, S.; Torrey, M.; Link, M.; Glicksman, A.; Laurie, F.; Manning, J.; Neff, J.; Thompson, E.; Shuster, J.

    1997-01-01

    Purpose: To determine if involved field radiation (IF) is equivalent to standard whole bone radiation (SF) in local tumor control; to establish patterns of failure following treatment; and to determine response, event free (EFS) and overall survival rates from multi-disciplinary therapy in Ewing's Sarcoma (ES). Materials and Methods: Between 1983 and 1988, 184 children with ES were enrolled onto POG 8346. 178 (97%) met eligibility criteria; 6 had non-ES pathology. Induction treatment of Cyclophosphamide/Adriamycin (C/A) x 12 weeks was followed by local treatment either surgery or radiation therapy (XRT) and C/A, Dactinomycin and Vincristine for 50 weeks. Resection was advised for patients with small primary tumors if accomplished without functional loss. 40 patients were randomized to receive SF, whole bone XRT to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or IF to 55.8 Gy while 84 were assigned to IF XRT. Results: Of 179 eligible patients, 141 (79%) had localized disease and 37 (21%) had metastases. Their 5 yr. EFS was 51% (SE = 5%) and 23% (SE = 7%) respectively. The response rate (RR) to induction chemotherapy was 88% (28% complete, 60% partial), but after XRT the RR increased to 98%. 37 of the localized patients underwent resection of whom 16 (43%) required post-operative XRT with 5 yr. EFS of 80% (SE = 7%). 104 of the localized patients received XRT and had a 5 year EFS of 41% (SE = 5%), with no difference in EFS between those randomized to SF vs. IF. Site of primary tumor correlated with 5 year EFS: Distal extremity - 65% (SE = 8%), Central - 63% (SE = 9%), Proximal extremity - 46% (SE = 8%), and Pelvis - 24% (SE = 10%). Tumor size did not influence EFS. Patterns of failure among the 141 localized patients were: local only - 18 (13%), local and systemic 14 (10%), systemic only 28 (20%). There were 4 (11%) local failures among those resected +/- XRT, but 28 (27%) following XRT alone. By protocol, patients suffering a relapse were required to undergo a biopsy

  2. Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review

    Directory of Open Access Journals (Sweden)

    José M. García-Castellano

    2012-01-01

    Full Text Available Ewing’s sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing’s sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing’s sarcoma into “good” and “poor” responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing’s sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

  3. EXTRA SKELETAL EWINGS SARCOMA OF SMALL INTESTINE ORIGIN: A CASE REPORT

    OpenAIRE

    Satyavani; Sriharsha

    2015-01-01

    This is a case report of Ewing’s sarcoma/PNET arising from small intestine , a rare presentation of Ewing’s sarcoma. The case presented as a mass per abdomen with no other associated symptoms and after excision of the mass along with the adjacent mesentery , the histopathology and immunohistochemistry reported as Ewing’s/PNET with clear margins. Follow up of the case showed no recurrence. This case is reported for its rare occurrence , as only few cases ...

  4. Using Targeted Virotherapy to Treat a Resistant Ewing Sarcoma Model: From the Bedside to the Bench and Back

    Directory of Open Access Journals (Sweden)

    Hesham Abdelbary

    2014-01-01

    Full Text Available Metastatic Ewing sarcoma (EWS is often resistant to current multimodal chemotherapeutic regimens. Oncolytic virus therapy (OV is a novel therapeutic platform whereby viruses can selectively infect as well as replicate in and kill tumor cells, while sparing normal tissues. The purpose of this study is to investigate the efficacy of the biotherapeutic oncolytic agent, vesicular stomatitis virus (VSVΔM51, to kill EWS cells that are resistant to conventional therapy. Our hypothesis is that systemic delivery of VSVΔM51 can demonstrate tumor-specific killing of resistant EWS cells, as well as a significant decrease of tumor burden in EWS bearing mice. Methods. A biopsy sample was obtained from a patient with metastatic EWS and was used to establish a novel EWS cell line. In vitro assays evaluated the oncolytic effect of vesicular stomatitis virus (VSVΔM51 on this cell line. EWS xenograft mice model bearing either lung or subcutaneous tumors was established to evaluate the antitumor specific oncolytic effect of VSVΔM51 after local and systemic delivery. Results. The established EWS cell line shared similar molecular and genetic traits to the patient’s original tumor specimen. VSVΔM51 effectively infected and killed EWS cells in vitro. In vivo, VSVΔM51 selectively infected and killed EWS and led to significant delay in tumor growth. Conclusion. This study has been designed to implement a translational link between the bedside and the bench, where a specific challenging clinical scenario guided this basic science research. This research demonstrated that a sarcoma, which is resistant to current conventional standard therapies, is still susceptible to an alternative therapeutic platform, such as OV. Adding OV to the armamentarium of sarcoma treatment can enhance the future therapeutic approach towards these cancer patients.

  5. Do patients with ewing's sarcoma continue with sports activities after limb salvage surgery of the lower extremity?

    Science.gov (United States)

    Hobusch, Gerhard Martin; Lang, Nikolaus; Schuh, Reinhard; Windhager, Reinhard; Hofstaetter, Jochen Gerhard

    2015-03-01

    Limb salvage surgery has evolved to become the standard method of treating sarcomas of the extremities with acceptable oncologic results. However, little information exists relative to the activity level or ability to participate in sports after tumor reconstructions. The aims of the study were to answer the following questions: (1) Which sports activity levels and what types of sports can be expected in the long term after tumor reconstruction? (2) Which frequency durations are patients with Ewing's sarcoma able to perform in long-term followup after local control? (3) Do surgical complications affect sports activity level? Thirty patients (13 females, 17 males; mean age, 18 ± 8 years; range, 2-36 years at diagnosis; mean followup 16 ± 6 years [minimum, 5 years]) were included. Tumors were located in the pelvis, femur, tibia, and fibula. Surgical procedures included surgical resections alone (n = 8), surgical resection with biological reconstruction (n = 9), or endoprosthetic reconstruction (n = 13). We assessed UCLA sports activity levels, kinds of sports as well as the frequency per week and the duration of each training unit at long term (minimum followup, 5 years). In long-term followup 83% patients (25 of 30) were performing athletic activity regularly. The hours/week of sports depended on type of surgery and were highest after resections in the pelvis and femur (5.8) and were lowest after megaprosthetic reconstruction of the pelvis (1.0). Patients undergoing biologic reconstructions were able to perform high-impact sports. UCLA sports activity levels were high after joint-preserving vascularized fibula for tibia reconstruction (7.4) and after megaprosthetic reconstruction of the lower extremity (6.3-6.4) and were low after tumors located in the fibula (4.2). Complications during followup did not significantly influence sports activity in long-term survivors. Long-term survivors can achieve high levels of sports activity in many instances. Tumor sites are

  6. Arrangement of chromosome 11 and 22 territories, EWSR1 and FLI1 genes, and other genetic elements of these chromosomes in human lymphocytes and Ewing sarcoma cells

    Czech Academy of Sciences Publication Activity Database

    Taslerová, R.; Kozubek, Stanislav; Lukášová, Emilie; Jirsová, Pavla; Bártová, Eva; Kozubek, Michal

    2003-01-01

    Roč. 112, č. 2 (2003), s. 143-155 ISSN 0340-6717 R&D Projects: GA MZd NC5955; GA AV ČR IBS5004010; GA ČR GA301/01/0186 Institutional research plan: CEZ:AV0Z5004920 Keywords : high-resolution cytometry * human leukemic cells * Ewing sarcoma cells Subject RIV: BO - Biophysics Impact factor: 4.022, year: 2003

  7. 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.

  8. 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)

  9. Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy

    Directory of Open Access Journals (Sweden)

    de Groot S

    2017-06-01

    Full Text Available Stefanie de Groot,1 Hans Gelderblom,1 Marta Fiocco,2,3 Judith VMG Bovée,4 Jacobus JM van der Hoeven,1 Hanno Pijl,5 Judith R Kroep1 1Department of Medical Oncology, 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 3Mathematical Department, Leiden University, 4Department of Pathology, 5Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands Background: Activation of the insulin-like growth factor 1 (IGF-1 pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3 can predict event-free survival (EFS and overall survival (OS in Ewing sarcoma patients treated with chemotherapy.Patients and methods: Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t-tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O’Quigley procedure. Survival analyses were performed using Cox regression analysis.Results: High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009–0.602 and HR 0.090, 95% CI 0.011–0.712, respectively in univariate and multivariate analyses (HR 0.063, 95% CI 0.007–0.590 and HR 0.057, 95% CI 0.005–0.585, respectively. OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy (P=0.055 and P=0.023, respectively.Conclusion: High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated

  10. Targeted Morphoproteomic Profiling of Ewing's Sarcoma Treated with Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors: Response/Resistance Signatures

    Science.gov (United States)

    Subbiah, Vivek; Naing, Aung; Brown, Robert E.; Chen, Helen; Doyle, Laurence; LoRusso, Patricia; Benjamin, Robert; Anderson, Pete; Kurzrock, Razelle

    2011-01-01

    Background Insulin-like growth factor 1 receptor (IGF1R) targeted therapies have resulted in responses in a small number of patients with advanced metastatic Ewing's sarcoma. We performed morphoproteomic profiling to better understand response/resistance mechanisms of Ewing's sarcoma to IGF1R inhibitor-based therapy. Methodology/Principal Findings This pilot study assessed two patients with advanced Ewing's sarcoma treated with IGF1R antibody alone followed by combined IGF1R inhibitor plus mammalian target of rapamycin (mTOR) inhibitor treatment once resistance to single-agent IGF1R inhibitor developed. Immunohistochemical probes were applied to detect p-mTOR (Ser2448), p-Akt (Ser473), p-ERK1/2 (Thr202/Tyr204), nestin, and p-STAT3 (Tyr 705) in the original and recurrent tumor. The initial remarkable radiographic responses to IGF1R-antibody therapy was followed by resistance and then response to combined IGF1R plus mTOR inhibitor therapy in both patients, and then resistance to the combination regimen in one patient. In patient 1, upregulation of p-Akt and p-mTOR in the tumor that relapsed after initial response to IGF1R antibody might explain the resistance that developed, and the subsequent response to combined IGF1R plus mTOR inhibitor therapy. In patient 2, upregulation of mTOR was seen in the primary tumor, perhaps explaining the initial response to the IGF1R and mTOR inhibitor combination, while the resistant tumor that emerged showed activation of the ERK pathway as well. Conclusion/Significance Morphoproteomic analysis revealed that the mTOR pathway was activated in these two patients with advanced Ewing's sarcoma who showed response to combined IGF1R and mTOR inhibition, and the ERK pathway in the patient in whom resistance to this combination emerged. Our pilot results suggests that morphoproteomic assessment of signaling pathway activation in Ewing's sarcoma merits further investigation as a guide to understanding response and resistance signatures. PMID

  11. Ewing sarcoma localized on spine: a dose escalation study in child

    International Nuclear Information System (INIS)

    Vogin, G.; Marchesi, V.; Biston, M.C.; Gassa, F.; Amessis, M.; Zefkili, S.; Helfre, S.; De Marzi, L.; Lacroix, F.; Leroy, A.

    2011-01-01

    The authors report the study of dose escalation for the treatment of spinal in two types of Ewing tumours. They used 5 dose levels at the rate of five 1,6 Gy per week. They compare different radiotherapy techniques: three-dimensional conformation radiotherapy, static intensity-modulated conformational radiotherapy, helical tomo-therapy, volume-modulated arc-therapy (VMAT), stereotactic radiotherapy, and proton-therapy (in passive diffusion). It appears that it is possible to safely and efficiently deliver until 70,4 Gy in some Ewing tumours. In child, exclusive radiotherapy might become a local treatment option and would require a clinic trial and comparison with exclusive surgery or post-operative radiotherapy. Short communication

  12. Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

    International Nuclear Information System (INIS)

    Pan, Hubert Y.; Morani, Ajaykumar; Wang, Wei-Lien; Hess, Kenneth R.; Paulino, Arnold C.; Ludwig, Joseph A.; Lin, Patrick P.; Daw, Najat C.; Mahajan, Anita

    2015-01-01

    Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant

  13. Eribulin regresses a doxorubicin-resistant Ewing's sarcoma with a FUS-ERG fusion and CDKN2A-deletion in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

    Science.gov (United States)

    Miyake, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Li, Yunfeng; Singh, Arun S; Dry, Sarah M; Eckardt, Mark A; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2018-01-01

    Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)-resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into three groups when the tumor volume reached 60 mm 3 : G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, Eribulin treated (n = 6, intravenous (i.v.) injection, weekly for 2 weeks). All mice were sacrificed on day 15. Changes in body weight and tumor volume were assessed two times per week. Tumor weight was measured after sacrifice. DOX did not suppress tumor growth compared to the control group (P = 0.589), consistent with the previous results in the patient and PDOX. Eribulin regressed tumor size significantly compared to G1 and G2 (P = 0.006, P = 0.017) respectively. No significant difference was observed in body weight among any group. Our results demonstrate that eribulin is a promising novel therapeutic agent for Ewing's sarcoma. © 2017 Wiley Periodicals, Inc.

  14. Correlation of non-mass-like abnormal MR signal intensity with pathological findings surrounding pediatric osteosarcoma and Ewing's sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Masrouha, Karim Z.; Haidar, Rachid; Saghieh, Said [American University of Beirut Medical Center, Department of Surgery, Beirut (Lebanon); Musallam, Khaled M. [American University of Beirut Medical Center, Internal Medicine Division of Hematology and Oncology, Beirut (Lebanon); Samra, Alexis Bou; Tawil, Ayman; Chakhachiro, Zaher [American University of Beirut Medical Center, Pathology, Beirut (Lebanon); Abdallah, Abeer; Khoury, Nabil J. [American University of Beirut Medical Center, Diagnostic Radiology, Beirut (Lebanon); Saab, Raya; Muwakkit, Samar; Abboud, Miguel R. [American University of Beirut Medical Center, Children' s Cancer Center of Lebanon, Beirut (Lebanon)

    2012-11-15

    The aim of this work was to determine the role of MRI in interpreting abnormal signals within bones and soft tissues adjacent to tumor bulk of osteosarcoma and Ewing's sarcoma in a pediatric population by correlating MR findings with histopathology. Thirty patients met the inclusion criteria, which included (1) osteosarcoma or Ewing's sarcoma, (2) MR studies no more than 2 months prior to surgery, (3) presence of abnormal MR signal surrounding the tumor bulk, (4) pathological material from resected tumor. The patients received standard neoadjuvant chemotherapy. Using grid maps on gross pathology specimens, the abnormal MR areas around the tumor were matched with the corresponding grid sections. Histopathology slides of these sections were then analyzed to determine the nature of the regions of interest. The MR/pathological correlation was evaluated using Mann-Whitney U test and Fisher's exact test. Twenty-seven patients had osteosarcoma and three patients had Ewing's sarcoma. Of the studied areas, 17.4% were positive for tumor (viable or necrotic). There was no statistically significant correlation between areas positive for tumor and age, gender, signal extent and intensity on MRI, or tissue type. There was, however, a statistically significant correlation between presence of tumor and the appearance of abnormal soft tissue signals. A feathery appearance correlated with tumor-negative areas whereas a bulky appearance correlated with tumor-positive regions. MR imaging is helpful in identifying the nature of abnormal signal areas surrounding bone sarcomas that are more likely to be tumor-free, particularly when the signal in the soft tissues surrounding the tumor is feathery and edema-like in appearance. (orig.)

  15. CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling.

    Science.gov (United States)

    Manara, Maria Cristina; Terracciano, Mario; Mancarella, Caterina; Sciandra, Marika; Guerzoni, Clara; Pasello, Michela; Grilli, Andrea; Zini, Nicoletta; Picci, Piero; Colombo, Mario P; Morrione, Andrea; Scotlandi, Katia

    2016-11-29

    CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis. This process, which is not detected in CD99-expressing normal mesenchymal cells, is inhibited by disruption of the IGF-1R signaling, whereas enhanced by IGF-1 stimulation. Induction of IGF-1R/RAS/Rac1 was also observed in the EWS xenografts that respond to anti-CD99 mAb, further supporting the role of the IGF/RAS/Rac1 axis in the hyperstimulation of macropinocytosis and selective death of EWS cells. Thus, we describe a vulnerability of EWS cells, including those resistant to standard chemotherapy, to a treatment with anti-CD99 mAb, which requires IGF-1R/RAS signaling but bypasses the need for their direct targeting. Overall, we propose CD99 targeting as new opportunity to treat EWS patients resistant to canonical apoptosis-inducing agents.

  16. Extra-skeletal Ewing sarcoma of the lumbosacral region in an adult pregnant patient: a case report.

    Science.gov (United States)

    Al Khawaja, Darweesh; Vescovi, Cristina; Dower, Ashraf; Thiruvilangam, Vallapan; Mahasneh, Tamadur

    2017-03-01

    Extra-skeletal Ewing sarcoma in pregnancy is rare. There is thus limited scientific evidence to guide clinicians in its complicated management, particularly within the context of early gestation. We therefore share our successful outcome in a 32-year-old pregnant patient, following a unique management strategy of complete aggressive surgical resection prior to neo-adjuvant therapy. The case involved a 2-month history of right-sided back and gluteal pain, with associated paraesthesia. Lumbosacral magnetic resonance imaging (MRI) revealed an approximate 40×50 mm indeterminate mass in the lower right paraspinal musculature. The mass extended into the first right sacral foramen and the central canal; and also impinged on the S2 exiting nerve. After considering the patients' rapid deterioration, pregnant status and other clinical factors, it was elected to proceed with complete surgical resection prior to any other therapeutic modality. Following surgery, the patient experienced immediate resolution of her pain and by 6 weeks was able to cease the use of all analgesics. At 32-weeks' gestation she underwent an uncomplicated vaginal delivery. At 9 months follow up, she remains disease free and has experienced complete resolution of her back pain and radiculopathy.

  17. Upregulation of NKX2.2, a target of EWSR1/FLI1 fusion transcript, in primary renal Ewing sarcoma

    Directory of Open Access Journals (Sweden)

    Yoshinari Yamamoto

    2015-01-01

    Full Text Available Renal Ewing sarcoma (ES is a rare malignant tumor characterized by fusion of the EWSR1 gene with a member of the ETS family of oncogenes, arising at a specific chromosomal translocation. Diagnosis of ES can be problematic, especially from cytological or small bioptical specimens because the differential diagnoses comprising a diverse group of small round blue cell tumors (SRBCTs. We report a case of primary renal ES in a young male, which had a t(11;22 (q24;q12 chromosome translocation encoding a type2 EWSR1/FLI1 fusion transcript. The tumor cells showed diffuse cytoplasmic immunoreactivity for CD99 and diffuse nuclear immunoreactivity for NKX2.2, an important oncogenic transcriptional target of EWSR1/FLI1, not only in the histological, but also in the cytological specimens. From the results of this case, we speculate that NKX2.2, in combination with CD99, may be a useful immunocytochemical marker to distinguish renal ES from other SRBCTs of kidney.

  18. 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.

  19. 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.

  20. Non-metastatic Ewing's sarcoma family of tumors of bone in adolescents and adults: prognostic factors and clinical outcome-single institution results.

    Science.gov (United States)

    Oksüz, Didem Colpan; Tural, Deniz; Dincbas, Fazilet Öner; Dervisoglu, Sergülen; Turna, Hande; Hiz, Murat; Kantarci, Fatih; Ceylaner, Beyhan; Koca, Sedat; Mandel, Nil Molinas

    2014-01-01

    There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors. From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics. The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis. We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

  1. Superficial EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion: a new variant of Ewing-like tumors with locoregional lymph node metastasis.

    Science.gov (United States)

    Machado, Isidro; Cruz, Julia; Lavernia, Javier; Rubio, Luis; Campos, Jorge; Barrios, María; Grison, Camille; Chene, Virginie; Pierron, Gaelle; Delattre, Olivier; Llombart-Bosch, Antonio

    2013-12-01

    The present study describes a new case of EWSR1-negative undifferentiated sarcoma with CIC/DUX4 gene fusion. This case is similar to tumors described as primitive undifferentiated round cell sarcomas that occur mainly in the trunk and display an aggressive behavior. To our knowledge, this is the first report of such a tumor presenting locoregional lymph node metastasis. In view of previous studies that prove the existence of a particular variant of undifferentiated sarcoma with Ewing-like morphology and CIC/DUX-4 gene fusion, a search for this gene fusion in all undifferentiated round cell sarcomas should be considered if a conclusive diagnosis cannot be reached following other conventional studies. Although additional cases with more extensive follow-up studies are needed, we believe that EWSR1-negative undifferentiated small round cell sarcoma with CIC/DUX4 gene fusion should be added to the list of new sarcoma variants with the possibility of lymph node metastasis.

  2. Front-line window therapy with cisplatin in patients with primary disseminated Ewing sarcoma: A study by the Associazione Italiana di Ematologia ed Oncologia Pediatrica and Italian Sarcoma Group.

    Science.gov (United States)

    Luksch, Roberto; Grignani, Giovanni; D'Angelo, Paolo; Prete, Arcangelo; Puma, Nadia; Podda, Marta; Casanova, Michela; Ferrari, Andrea; Morosi, Carlo; Fagioli, Franca; Aglietta, Massimo; Ferrari, Stefano; Picci, Piero; Massimino, Maura

    2017-12-01

    The aim was to assess the activity of cisplatin (CDDP) in Ewing sarcoma (ES). The study consisted of front-line window therapy with CDDP 120 mg/sqm every 3 weeks for two courses in children and young adults with primary disseminated ES. Response was assessed using the Response Evaluation Criteria in Solid Tumours criteria, and Simon's two-stage design was applied. Twelve consecutive patients were enrolled in stage 1. Only one objective response was observed. Since the target response rate was not achieved, accrual was stopped and CDDP as a single agent in ES was judged unworthy of further assessment. © 2017 Wiley Periodicals, Inc.

  3. Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways.

    Directory of Open Access Journals (Sweden)

    Valerie B Sampson

    Full Text Available Histone deacetylase inhibitors (HDACi have been evaluated in patients with Ewing sarcoma (EWS but demonstrated limited activity. To better understand the potential for HDACi in EWS, we evaluated the combination of the HDACi vorinostat, with DNA damaging agents SN-38 (the active metabolite of irinotecan and topoisomerase 1 inhibitor plus the alkylating agent temozolomide (ST. Drugs were evaluated in sequential and simultaneous combinations in two EWS cell lines. Results demonstrate that cell viability, DNA damage and reactive oxygen species (ROS production are dependent on the sequence of drug administration. Enhanced cytotoxicity is exhibited in vitro in EWS cell lines treated with ST administered before vorinostat, which was modestly higher than concomitant treatment and superior to vorinostat administered before ST. Drug combinations downregulate cyclin D1 to induce G0/G1 arrest and promote apoptosis by cleavage of caspase-3 and PARP. When ST is administered before or concomitantly with vorinostat there is activation of STAT3, MAPK and the p53 pathway. In contrast, when vorinostat is administered before ST, there is DNA repair, increased AKT phosphorylation and reduced H2B acetylation. Inhibition of AKT using the small molecule inhibitor MK-2206 did not restore H2B acetylation. Combining ST with the dual ALK and IGF-1R inhibitor, AZD3463 simultaneously inhibited STAT3 and AKT to enhance the cytotoxic effects of ST and further reduce cell growth suggesting that STAT3 and AKT activation were in part mediated by ALK and IGF-1R signaling. In summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS.

  4. Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

    Energy Technology Data Exchange (ETDEWEB)

    Talleur, Aimee C.; Navid, Fariba [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Spunt, Sheri L. [Department of Pediatrics, Stanford University School of Medicine, Stanford, California (United States); McCarville, M. Beth [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu, John; Mao, Shenghua [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Davidoff, Andrew M. [Department of Surgery, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (United States); Neel, Michael D. [Department of Surgery, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Krasin, Matthew J., E-mail: matthew.krasin@stjude.org [Department of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2016-09-01

    Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

  5. Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

    International Nuclear Information System (INIS)

    Talleur, Aimee C.; Navid, Fariba; Spunt, Sheri L.; McCarville, M. Beth; Wu, John; Mao, Shenghua; Davidoff, Andrew M.; Neel, Michael D.; Krasin, Matthew J.

    2016-01-01

    Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

  6. Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways.

    Science.gov (United States)

    Sampson, Valerie B; Vetter, Nancy S; Kamara, Davida F; Collier, Anderson B; Gresh, Renee C; Kolb, E Anders

    2015-01-01

    Histone deacetylase inhibitors (HDACi) have been evaluated in patients with Ewing sarcoma (EWS) but demonstrated limited activity. To better understand the potential for HDACi in EWS, we evaluated the combination of the HDACi vorinostat, with DNA damaging agents SN-38 (the active metabolite of irinotecan and topoisomerase 1 inhibitor) plus the alkylating agent temozolomide (ST). Drugs were evaluated in sequential and simultaneous combinations in two EWS cell lines. Results demonstrate that cell viability, DNA damage and reactive oxygen species (ROS) production are dependent on the sequence of drug administration. Enhanced cytotoxicity is exhibited in vitro in EWS cell lines treated with ST administered before vorinostat, which was modestly higher than concomitant treatment and superior to vorinostat administered before ST. Drug combinations downregulate cyclin D1 to induce G0/G1 arrest and promote apoptosis by cleavage of caspase-3 and PARP. When ST is administered before or concomitantly with vorinostat there is activation of STAT3, MAPK and the p53 pathway. In contrast, when vorinostat is administered before ST, there is DNA repair, increased AKT phosphorylation and reduced H2B acetylation. Inhibition of AKT using the small molecule inhibitor MK-2206 did not restore H2B acetylation. Combining ST with the dual ALK and IGF-1R inhibitor, AZD3463 simultaneously inhibited STAT3 and AKT to enhance the cytotoxic effects of ST and further reduce cell growth suggesting that STAT3 and AKT activation were in part mediated by ALK and IGF-1R signaling. In summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS.

  7. 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.

  8. Malignant Ewing-Like Neoplasm With an EWSR1-KLF15 Fusion: At the Crossroads of a Myoepithelial Carcinoma and a Ewing-Like Sarcoma. A Case Report With Treatment Options.

    Science.gov (United States)

    Stevens, Todd M; Qarmali, Morad; Morlote, Diana; Mikhail, Fady M; Swensen, Jeffrey; Gatalica, Zoran; Siegal, Gene P; Conry, Robert M

    2018-01-01

    We present a case of a malignant Ewing-like neoplasm of the parotid gland in a 20-year-old woman with an EWSR1-KLF15 gene fusion that presented with pulmonary metastasis. Despite the fact that the tumor was essentially immunohistochemically negative for keratins, p63, and p40, we interpret this neoplasm as an unusual form of a high-grade myoepithelial carcinoma based on its focal plasmacytoid cytology, chondromyxoid matrix, SOX10, S100 protein, and calponin expression, and the knowledge that the EWSR1-KLF15 gene fusion has, to date, only been identified in 2 tumors, both myoepithelial carcinomas of the kidney. We also present a cytogenetic analysis of this unusual tumor. This "Ewing-like myoepithelial carcinoma" initially did not respond to 2 cycles of ifosfamide and etoposide alternated with a cycle of cytoxan, adriamycin, and vincristine, a standard regimen for Ewing sarcoma. Subsequent oral pazopanib therapy did result in a reduction of the patient's pulmonary and nodal disease.

  9. Influence of the internalization pathway on the efficacy of siRNA delivery by cationic fluorescent nanodiamonds in the Ewing sarcoma cell model.

    Directory of Open Access Journals (Sweden)

    Anna Alhaddad

    Full Text Available Small interfering RNAs (siRNAs are powerful tools commonly used for the specific inhibition of gene expression. However, vectorization is required to facilitate cell penetration and to prevent siRNA degradation by nucleases. We have shown that diamond nanocrystals coated with cationic polymer can be used to carry siRNAs into Ewing sarcoma cells, in which they remain traceable over long periods, due to their intrinsic stable fluorescence. We tested two cationic polymers, polyallylamine and polyethylenimine. The release of siRNA, accompanied by Ewing sarcoma EWS-Fli1 oncogene silencing, was observed only with polyethylenimine. We investigated cell penetration and found that the underlying mechanisms accounted for these differences in behavior. Using drugs selectively inhibiting particular pathways and a combination of fluorescence and electronic microscopy, we showed that siRNA gene silencing occurred only if the siRNA:cationic nanodiamond complex followed the macropinocytosis route. These results have potential implications for the design of efficient drug-delivery vectors.

  10. Influence of the Internalization Pathway on the Efficacy of siRNA Delivery by Cationic Fluorescent Nanodiamonds in the Ewing Sarcoma Cell Model

    Science.gov (United States)

    Alhaddad, Anna; Durieu, Catherine; Dantelle, Géraldine; Le Cam, Eric; Malvy, Claude; Treussart, François; Bertrand, Jean-Rémi

    2012-01-01

    Small interfering RNAs (siRNAs) are powerful tools commonly used for the specific inhibition of gene expression. However, vectorization is required to facilitate cell penetration and to prevent siRNA degradation by nucleases. We have shown that diamond nanocrystals coated with cationic polymer can be used to carry siRNAs into Ewing sarcoma cells, in which they remain traceable over long periods, due to their intrinsic stable fluorescence. We tested two cationic polymers, polyallylamine and polyethylenimine. The release of siRNA, accompanied by Ewing sarcoma EWS-Fli1 oncogene silencing, was observed only with polyethylenimine. We investigated cell penetration and found that the underlying mechanisms accounted for these differences in behavior. Using drugs selectively inhibiting particular pathways and a combination of fluorescence and electronic microscopy, we showed that siRNA gene silencing occurred only if the siRNA:cationic nanodiamond complex followed the macropinocytosis route. These results have potential implications for the design of efficient drug-delivery vectors. PMID:23284935

  11. Influence of the internalization pathway on the efficacy of siRNA delivery by cationic fluorescent nanodiamonds in the Ewing sarcoma cell model.

    Science.gov (United States)

    Alhaddad, Anna; Durieu, Catherine; Dantelle, Géraldine; Le Cam, Eric; Malvy, Claude; Treussart, François; Bertrand, Jean-Rémi

    2012-01-01

    Small interfering RNAs (siRNAs) are powerful tools commonly used for the specific inhibition of gene expression. However, vectorization is required to facilitate cell penetration and to prevent siRNA degradation by nucleases. We have shown that diamond nanocrystals coated with cationic polymer can be used to carry siRNAs into Ewing sarcoma cells, in which they remain traceable over long periods, due to their intrinsic stable fluorescence. We tested two cationic polymers, polyallylamine and polyethylenimine. The release of siRNA, accompanied by Ewing sarcoma EWS-Fli1 oncogene silencing, was observed only with polyethylenimine. We investigated cell penetration and found that the underlying mechanisms accounted for these differences in behavior. Using drugs selectively inhibiting particular pathways and a combination of fluorescence and electronic microscopy, we showed that siRNA gene silencing occurred only if the siRNA:cationic nanodiamond complex followed the macropinocytosis route. These results have potential implications for the design of efficient drug-delivery vectors.

  12. Plasma hydrogenated cationic detonation nanodiamonds efficiently deliver to human cells in culture functional siRNA targeting the Ewing sarcoma junction oncogene.

    Science.gov (United States)

    Bertrand, Jean-Rémi; Pioche-Durieu, Catherine; Ayala, Juan; Petit, Tristan; Girard, Hugues A; Malvy, Claude P; Le Cam, Eric; Treussart, François; Arnault, Jean-Charles

    2015-03-01

    The expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, particularly in urine, which is impossible for 35 nm particles. Here, we report that hydrogenated cationic nanodiamonds of primary size 7 nm (ND-H) have also a high affinity for siRNA and are capable of delivering them in cells. With siRNA/ND-H complexes, we measured a high inhibition efficacy of EWS/FLI-1 gene expression in Ewing sarcoma cell line. Electron microscopy investigations showed ND-H in endocytosis compartments, and especially in macropinosomes from which they can escape before siRNA degradation occurred. In addition, the association of EWS/FLI-1 silencing by the siRNA/ND-H complex with a vincristine treatment yielded a potentiation of the toxic effect of this chemotherapeutic drug. Therefore ND-H appears as a promising delivery agent in anti-tumoral gene therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing's sarcoma cell line.

    Science.gov (United States)

    Marx, Christian; Marx-Blümel, Lisa; Lindig, Nora; Thierbach, René; Hoelzer, Doerte; Becker, Sabine; Wittig, Susan; Lehmann, Roland; Slevogt, Hortense; Heinzel, Thorsten; Wang, Zhao-Qi; Beck, James F; Sonnemann, Jürgen

    2018-06-01

    The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting. Tenovin-1 elicited caspase-mediated cell death in p53 wild-type cells, but caspase-independent cell death in p53 null cells. Remarkably, it induced a nonlinear concentration response in the latter: low concentrations of tenovin-1 were much more effective than were higher concentrations. Tenovin-1's effects in p53 null cells involved gene expression changes of Bcl-2 family members, mitochondrial membrane depolarization, nuclear translocation of apoptosis-inducing factor, ROS formation and DNA damage; all these effects followed a bell-shaped pattern. In conclusion, our results provide new insights into tenovin-1's mode of action by demonstrating that it can induce different pathways of cell death.

  14. 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

  15. 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

  16. Longitudinal follow-up of adult survivors of Ewing sarcoma: A report from the Childhood Cancer Survivor Study.

    Science.gov (United States)

    Marina, Neyssa M; Liu, Qi; Donaldson, Sarah S; Sklar, Charles A; Armstrong, Gregory T; Oeffinger, Kevin C; Leisenring, Wendy M; Ginsberg, Jill P; Henderson, Tara O; Neglia, Joseph P; Stovall, Marilyn A; Yasui, Yutaka; Randall, R Lor; Geller, David S; Robison, Leslie L; Ness, Kirsten K

    2017-07-01

    Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown. This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03). Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively. With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551-60. © 2017 American Cancer Society. © 2017 American Cancer Society.

  17. Potential downstream target genes of aberrant ETS transcription factors are differentially affected in Ewing's sarcoma and prostate carcinoma.

    Directory of Open Access Journals (Sweden)

    Maria J Camões

    Full Text Available FLI1 and ERG, the major ETS transcription factors involved in rearrangements in the Ewing's sarcoma family of tumors (ESFT and in prostate carcinomas (PCa, respectively, belong to the same subfamily, having 98% sequence identity in the DNA binding domain. We therefore decided to investigate whether the aberrant transcription factors in both malignancies have some common downstream targets. We crossed a publicly available list of all putative EWSR1-FLI1 target genes in ESFT with our microarray expression data on 24 PCa and 6 non-malignant prostate tissues (NPT and choose four genes among the top-most differentially expressed between PCa with (PCa ERG+ and without (PCa ETS- ETS fusion genes (HIST1H4L, KCNN2, ECRG4 and LDOC1, as well as four well-validated direct targets of the EWSR1-FLI1 chimeric protein in ESFT (NR0B1, CAV1, IGFBP3 and TGFBR2. Using quantitative expression analysis in 16 ESFT and seven alveolar rhabdomyosarcomas (ARMS, we were able to validate the four genes previously described as direct targets of the EWSR1-FLI1 oncoprotein, showing overexpression of CAV1 and NR0B1 and underexpression of IGFBP3 and TGFBR2 in ESFT as compared to ARMS. Although none of these four genes showed significant expression differences between PCa ERG+ and PCa ETS-, CAV1, IGFBP3 and TGFBR2 were less expressed in PCa in an independent series of 56 PCa and 15 NPT, as also observed for ECRG4 and LDOC1, suggesting a role in prostate carcinogenesis in general. On the other hand, we demonstrate for the first time that both HIST1H4L and KCNN2 are significantly overexpressed in PCa ERG+ and that ERG binds to the promoter of these genes. Conversely, KCNN2 was found underexpressed in ESFT relative to ARMS, suggesting that the EWSR1-ETS oncoprotein may have the opposite effect of ERG rearrangements in PCa. We conclude that aberrant ETS transcription factors modulate target genes differently in ESFT and PCa.

  18. Proliferation index: a continuous model to predict prognosis in patients with tumours of the Ewing's sarcoma family.

    Directory of Open Access Journals (Sweden)

    Samantha Brownhill

    Full Text Available The prognostic value of proliferation index (PI and apoptotic index (AI, caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT. Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100 of tumours with a median PI of 14 (range 0-87. Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79 of ESFT; the median AI was 3 (range 0-33. Caspase-8 protein expression was negative (0 in 14% (11/79, low (1 in 33% (26/79, medium (2 in 38% (30/79 and high (3 in 15% (12/79 of tumours, caspase-9 expression was low (1 in 66% (39/59 and high (3 in 34% (20/59, and caspase-10 protein was low (1 in 37% (23/62 and negative (0 in 63% (39/62 of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p = 0.011 and overall survival (OS; p = <0.001 in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p = 0.054, log rank test, although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p = 0.003. Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p = 0.028; patients with a pelvic tumour and a PI≥20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT.

  19. Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

    Directory of Open Access Journals (Sweden)

    Peter Y Yu

    Full Text Available STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5.An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma cell lines at high nanomolar/low micromolar concentrations, as well as specific inhibition of STAT3 phosphorylation without effects on other STAT3 family members. LY5 exhibited excellent oral bioavailability in both mice and healthy dogs, and drug absorption was enhanced in the fasted state with tolerable dosing in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover, concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay were significantly higher than those needed to inhibit STAT3 phosphorylation in vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or prevent pulmonary metastasis in mice.LY5 is a novel small molecule inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and STAT3 knockdown did not induce concordant biologic effects. These data suggest that the anti-cancer effects of LY5 identified in vitro were not mediated through STAT3 inhibition.

  20. Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

    Science.gov (United States)

    Yu, Peter Y; Gardner, Heather L; Roberts, Ryan; Cam, Hakan; Hariharan, Seethalakshmi; Ren, Ling; LeBlanc, Amy K; Xiao, Hui; Lin, Jiayuh; Guttridge, Denis C; Mo, Xiaokui; Bennett, Chad E; Coss, Christopher C; Ling, Yonghua; Phelps, Mitch A; Houghton, Peter; London, Cheryl A

    2017-01-01

    STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5. An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma cell lines at high nanomolar/low micromolar concentrations, as well as specific inhibition of STAT3 phosphorylation without effects on other STAT3 family members. LY5 exhibited excellent oral bioavailability in both mice and healthy dogs, and drug absorption was enhanced in the fasted state with tolerable dosing in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover, concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay were significantly higher than those needed to inhibit STAT3 phosphorylation in vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or prevent pulmonary metastasis in mice. LY5 is a novel small molecule inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and STAT3 knockdown did not induce concordant biologic effects. These data suggest that the anti-cancer effects of LY5 identified in vitro were not mediated through STAT3 inhibition.

  1. Suitability of imaging methods (X-ray, CT, MRI) in the diagnostics of Ewings sarcoma in children - analysis of own material

    International Nuclear Information System (INIS)

    Kuleta-Bosak, E.; Machnik-Broncel, J.; Kluczewska, E.; Madziara, W.; Ciupinska-Kajor, M.; Sojka, D.; Rogala, W.; Juszczyk, J.; Wilk, R.

    2010-01-01

    Background: Ewing sarcoma is a malignant, small round cell bone tumor, presenting predominantly in children and adolescents. Ewing sarcoma may develop in every bone; diaphyses of long bones, ribs and flat bones are the main locations. Local and systemic clinical symptoms are nonspecific - pain, swelling, fever or ill-being. The aim of the study was to assess the role of radiography, computed tomography and magnetic resonance imaging in the analysis of bone lesions in children and young adults with Ewing sarcoma. Material/Methods: Twenty-seven patients, aged between 1 year and 10 months, and 17 years and 2 months, with histologically verified Ewing sarcoma of the bone, referred to the Radiological Department of University Hospital No 6., John Paul II Upper Silesian Centre for Child Health Katowice, in the period from 1996 to 2007, were included in the study.Plain radiography was performed in every child, CT in 20 and MRI in 12 individuals. Tumour location, extension of the tumour, soft tissue mass, and periosteal reaction were taken into consideration in the evaluation of the lesion. In some cases, pathological features of the MRI and CT were compared. The prevalence of some radiological features was compared to the literature data. Results: The most common site of tumor was: ribs (6 children), femoral bone (6 children), pelvis (4 children) and tibia (3 children). In 2 children, a primary tumor was diagnosed in the spine (multifocal in 1 child). X-rays revealed: periosteal reaction in 17 children (63%), soft tissue involvement in 19 children (70%), permeative component in 16 children (59%), and sclerotic component in 5 children (19%). In 10 children (37%), periosteal reaction was not detected. The examination revealed: soft tissue calcifications in 7 cases (26%), a well-delineated focus of destruction within bones in 3 children (11%), cortical thickening in 4 children (15%), cortical destruction in 4 children (15%), saucerisation in 3 children (11%), bone expansion

  2. Ionizing radiation induced production of tumor necrosis factor α in the Ewing's sarcoma cell line RM 82 in vitro and in vivo

    International Nuclear Information System (INIS)

    Ruebe, C.; Schaefer, K.L.; Dockhorn-Dworniczak, B.; Willich, N.

    1997-01-01

    Aim: The expression of cytokines plays an important role in the transmission of the effects of ionizing radiation to tumor cells and normal tissue. Tumor necrosis factor alpha (TNF α), a pleiotropic monokine, is of special interest because of its cytotoxic effect on tumor cells and the induction of hemorrhagic necrosis in tumors. We examined the influence of ionizing radiation on TNF α production in a human Ewing's sarcoma cell line in vitro and in vivo. Methods: The protein and mRNA levels of the Ewing's sarcoma cell line RM 82 were examined in vitro with 'Enhanced Amplified Sensitivity Immunoassay' (EASIA) and semiquantitative RT-PCR before and after treatment with single doses of 2 to 40 Gy, 1 to 72 hours after irradiation. After successful transplantation to nude mice, the time and dose correlation of TNF α mRNA production was examined in vivo. Results: In vitro, RM 82 had a basal protein level of TNF α of 20.1 ± 4.3 pg/ml/10 6 cells. We observed a time- and dose-dependent increase of TNF α expression with a maximum of 125 pg/ml/10 6 (5.9fold) 24 hours after irradiation with 20 Gy. At the mRNA level, the maximal up-regulation occurred 6 to 12 hours after 10 Gy. In vivo, the xenograft tumor maintained the capacity of TNF α expression. Time- and dose-dependency in mRNA production showed a maximum increase 6 hours after treatment with 10 Gy. (orig.) [de

  3. 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

  4. 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.

  5. Effective molecular targeting of CDK4/6 and IGF-1R in a rare FUS-ERG fusion CDKN2A-deletion doxorubicin-resistant Ewing's sarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.

    Science.gov (United States)

    Murakami, Takashi; Singh, Arun S; Kiyuna, Tasuku; Dry, Sarah M; Li, Yunfeng; James, Aaron W; Igarashi, Kentaro; Kawaguchi, Kei; DeLong, Jonathan C; Zhang, Yong; Hiroshima, Yukihiko; Russell, Tara; Eckardt, Mark A; Yanagawa, Jane; Federman, Noah; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2016-07-26

    Ewing's sarcoma is a rare and aggressive malignancy. In the present study, tumor from a patient with a Ewing's sarcoma with cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss and FUS-ERG fusion was implanted in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. The aim of the present study was to determine efficacy of cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors on the Ewing's sarcoma PDOX. The PDOX models were randomized into the following groups when tumor volume reached 50 mm3: G1, untreated control; G2, doxorubicin (DOX) (intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, CDK4/6 inhibitor (palbociclib, PD0332991, per oral (p.o.), daily, for 14 days); G4, IGF-1R inhibitor (linsitinib, OSI-906, p.o., daily, for 14 days). Tumor growth was significantly suppressed both in G3 (palbociclib) and in G4 (linsitinib) compared to G1 (untreated control) at all measured time points. In contrast, DOX did not inhibit tumor growth at any time point, which is consistent with the failure of DOX to control tumor growth in the patient. The results of the present study demonstrate the power of the PDOX model to identify effective targeted molecular therapy of a recalcitrant DOX-resistant Ewing's sarcoma with specific genetic alterations. The results of this study suggest the potential of PDOX models for individually-tailored, effective targeted therapy for recalcitrant cancer.

  6. Extra skeletal Soft Tissue Ewing?s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

    OpenAIRE

    Nagaraj, Prashanth; H, Srinivas C; Rao, Raghavendra; Manohar, Sandesh

    2013-01-01

    Introduction: Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population .lt is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21 ;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have ...

  7. Sarcome d'ewing du rocher | Kaffel | Journal Tunisien d'ORL et de ...

    African Journals Online (AJOL)

    Introduction : Primary cranial Ewing's sarcoma is rare. This tumor was first described in 1921, since then, only a few cases have been reported in the literature. Aim: the aim of this study is to report the clinical and therapeutic aspects of primary cranial Ewing's sarcoma. Method: We report a case of Ewing's sarcoma of the ...

  8. Sarcoma of the Ewing Family in Pregnancy: A Case Report of Intrauterine Fetal Death after Induction of Chemotherapy

    Directory of Open Access Journals (Sweden)

    S. Schur

    2012-11-01

    Full Text Available Ewing’s sarcoma is an ultra-orphan disease (2/1,000,000/year which requires a multimodal therapy approach in high-volume centers. Treatment consists of pre-operative therapy followed by surgery and post-operative combination of chemo-radiotherapy. Experience with diagnosis and therapy of Ewing’s sarcoma in pregnancy is very limited. We herein report the case of an atypical Ewing’s sarcoma detected in the second trimester of gestation. Neoadjuvant chemotherapy was initiated and resulted in substantial tumor shrinkage and intrauterine fetal death. The rare nature of this condition underlines once more the need for a multidisciplinary team to improve the quality of care for this highly special patient collective.

  9. t(4;11 (q21;q23 in acute myeloid leukemia-M0 following treatment [EW92 Protocol] for Ewing's sarcoma Leucemia mielóide aguda-M0 com t(4;11 (q21;q23 após tratamento para sarcoma de Ewing com o protocolo EW92

    Directory of Open Access Journals (Sweden)

    Terezinha J. Marques Salles

    2004-01-01

    Full Text Available We report on a 7-year-old girl with Ewing's Sarcoma (ES who developed a poorly differentiated acute myeloid leukemia (AML-M0 20 months after beginning the EW92 protocol for the treatment of the primary tumor. She received a total dose of 1500 mg of etoposide, a tumor cumulative radiation dose of 35Gy and granulocyte colony-stimulating factor (G-CSF was as predicted in the protocol regimen. At onset of secondary malignancy her laboratorial analysis revealed immature blast cells characterized by CD34+/CD33-/a-MPO+ and a t(4;11(q21;q23 abnormality. This serious complication of ES treatment, which associates etoposide, irradiation and G-CSF schedule, should be weighed against its therapeutic benefits.Nós descrevemos o caso clínico de uma criança do sexo feminino, com 7 anos de idade, portadora de sarcoma de Ewing, que evoluiu com leucemia aguda mielóide pouco diferenciada (LMA-M0 após vinte meses de tratamento utilizando o protocolo EW92. Ela recebeu uma dose total de 1.500 mg de etoposídio, irradiação tumoral na dose total de 35G, e fator de estimulação de colônia granulocítica (G-CSF conforme programação do protocolo terapêutico. Os exames laboratoriais, por ocasião do diagnóstico da segunda malignidade, mostraram células blásticas imaturas caracterizadas pela expressão de CD34+/CD33-/aMPO+ e a translocação t(4;11 (q 21;q23. A exclusão do G-CSF nos esquemas terapêuticos que associam etoposídio e irradiação tumoral se justifica devido a esta séria complicação no tratamento do sarcoma de Ewing.

  10. The PET/T.D.M. with F.D.G. -({sup 18}F) appears more noticeable than the osseous scintigraphy in the Ewing sarcoma with osteo-medullar localizations; La TEP/TDM au FDG-(18F) apparait plus sensible que la scintigraphie osseuse dans le sarcome d'Ewing a localisations osteomedullaires

    Energy Technology Data Exchange (ETDEWEB)

    Girma, A.; Razzouk, M.; Carrier, P.; Darcourt, J. [Unite de medecine nucleaire, CHU l' Archet, Nice, (France); Paycha, F. [unite de medecine nucleaire, CHU Louis-Mourier, Colombes, (France); Deville, A. [unite de pediatrie, CHU l' Archet, Nice, (France); Boyer, C. [unite de radiologie, CHU l' Archet, Nice, (France); Piche, M. [unite d' anatomopathologie, CHU l' Archet, Nice, (France)

    2009-05-15

    The clinical case reported here illustrates the superiority of the PET/T.D.M. with F.D.G.({sup 18}F) on the osseous scintigraphy in the Ewing sarcoma. This difference comes from probably a major inter trabecular medullary injury that arouses only a limited cortical osteoblastic reaction, what explains its appellation of pass-wall tumor by the anatomical pathologists. (N.C.)

  11. Ovarian tissue cryopreserved for fertility preservation from patients with Ewing or other sarcomas appear to have no tumour cell contamination

    DEFF Research Database (Denmark)

    Greve, Tine; Wielenga, Vera Timmermans; Grauslund, Morten

    2013-01-01

    The chemotherapy required to treat patients with sarcoma may as a side-effect induce infertility in girls and young women. If these patients have ovarian cortical tissue cryopreserved prior to chemotherapy, they may, if necessary, have the tissue transplanted and restore their fertility. The aim...

  12. R1507, an Anti-Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing's Sarcoma: Convergence at the IGF/IGFR/Akt Axis

    Science.gov (United States)

    Rodon, Jordi; Sun, Michael; Kuenkele, Klaus-Peter; Parsons, Henrique A.; Trent, Jonathan C.; Kurzrock, Razelle

    2011-01-01

    A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt. PMID:22022506

  13. R1507, an anti-insulin-like growth factor-1 receptor (IGF-1R antibody, and EWS/FLI-1 siRNA in Ewing's sarcoma: convergence at the IGF/IGFR/Akt axis.

    Directory of Open Access Journals (Sweden)

    Helen J Huang

    Full Text Available A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71 was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays. TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.

  14. Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

    Science.gov (United States)

    Dutton, P; Love, S B; Billingham, L; Hassan, A B

    2018-05-01

    Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

  15. 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

  16. Primary Ewing's sarcoma/primitive neuroectodermal tumor of the ileum: case report of a 16-year-old Chinese female and literature review.

    Science.gov (United States)

    Li, Teng; Zhang, Fang; Cao, Yarui; Ning, Shoubin; Bi, Yongmin; Xue, Weicheng; Ren, Li

    2017-05-04

    Ewing's sarcoma (ES) and primitive neuroectodermal tumors (PNET) are closely related tumors. Although soft tissue ES/PNET are common in clinical practice, they are rare in the small intestine. Because of the absence of characteristic clinical symptoms, they are easily misdiagnosed as other benign or malignant diseases. Here, we present the case of a 16-year-old female who complained of anemia and interval hematochezia. Her serum test results showed only a slight elevation of CA-125 and a low level of hemoglobin. Computer tomography and magnetic resonance imaging revealed a cystic and solid mass in the lower abdominal quadrant and pelvic region, which prompted suspicion of a malignant gastrointestinal stromal tumor of the small intestine. After resection, the tumor's histology and immunohistochemistry (positive for CD99, vimentin and synaptophysin) results suggested ES/PNET. Fluorescent in situ hybridization tests proved the breakpoint rearrangement of the EWSR1 gene in chr 22.Ultrastructural analysis revealed neurosecretory and glycogen granules in the tumor cell cytoplasm. Together, these data supported the diagnosis of a rare case of localized ES/PNET in the small intestine without adjuvant chemo- or radiotherapy. To our knowledge, this is the first report from China of a primary small bowel ES/PNET in the English-language literature. In addition, on the basis of findings from previous publications and the current case, the optimal treatment for localized gastrointestinal ES/PNET is discussed.

  17. Primary Ewing's Sarcoma of Frontoparietal Bone with Major Soft Tissue Extension: An Unusual Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anshu Gupta

    2012-01-01

    Full Text Available An 11-year-old girl presented with progressively increasing swelling in scalp of 8-month duration with no neurological deficit. Local examination showed a hard swelling that seemed to be arising from frontal bone. General and systemic examination was normal. MRI revealed a well-defined lytic lesion in left frontoparietal bone with a subgaleal component. The patient was operated upon and excision of tumor with reconstruction of skull was done. Histopathological examination showed a monomorphic small round cell tumor of bone infiltrating into the subcutaneous tissue. Immunohistochemical stain showed diffuse immunopositivity for MIC-2 in tumor cells, thus final diagnosis of Ewing’s sarcoma was made. The patient was kept for follow up for 3 months and had no symptoms.

  18. Diagnostic accuracy of 18F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis

    International Nuclear Information System (INIS)

    Treglia, Giorgio; Salsano, Marco; Stefanelli, Antonella; Mattoli, Maria Vittoria; Giordano, Alessandro; Bonomo, Lorenzo

    2012-01-01

    To systematically review and meta-analyse literature data on the diagnostic performance of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) in patients with Ewing sarcoma family tumours (ESFT). PubMed/MEDLINE, Embase and Scopus databases were searched for articles that evaluated FDG-PET and PET/CT in patients with ESFT from inception to 31 May 2011. Studies that fulfilled the three following criteria were included in the systematic review: FDG-PET or PET/CT performed in patients with ESFT; articles about the diagnostic accuracy of FDG-PET and PET/CT; sample size of at least 10 patients with ESFT were included. Studies in which there were sufficient data to reassess sensitivity and specificity of FDG-PET or PET/CT in ESFT were included in the meta-analysis, excluding duplicate publications. Finally, pooled sensitivity, pooled specificity and area under the receiver operating characteristic (ROC) curve of FDG-PET or PET/CT in ESFT were calculated. We found 13 studies comprising a total of 342 patients with ESFT. The main findings of the studies included are presented. The meta-analysis of five selected studies provided these results about FDG-PET and PET/CT in ESFT: pooled sensitivity: 96% (95% confidence interval [CI] 91-99%); pooled specificity: 92% (95% CI 87-96%); area under the ROC curve: 0.97. With regard to the staging and restaging of patients with ESFT, the sensitivity, specificity and accuracy of FDG-PET and PET/CT are high; the combination of FDG-PET or PET/CT with conventional imaging is a valuable tool for the staging and restaging of ESFT and has a relevant impact on the treatment strategy plan. (orig.)

  19. Diagnostic accuracy of {sup 18}F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Treglia, Giorgio [Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy); Institute of Nuclear Medicine, Positron Emission Tomography Centre, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy); Salsano, Marco; Stefanelli, Antonella; Mattoli, Maria Vittoria; Giordano, Alessandro [Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy); Bonomo, Lorenzo [Institute of Radiology, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy)

    2012-03-15

    To systematically review and meta-analyse literature data on the diagnostic performance of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) in patients with Ewing sarcoma family tumours (ESFT). PubMed/MEDLINE, Embase and Scopus databases were searched for articles that evaluated FDG-PET and PET/CT in patients with ESFT from inception to 31 May 2011. Studies that fulfilled the three following criteria were included in the systematic review: FDG-PET or PET/CT performed in patients with ESFT; articles about the diagnostic accuracy of FDG-PET and PET/CT; sample size of at least 10 patients with ESFT were included. Studies in which there were sufficient data to reassess sensitivity and specificity of FDG-PET or PET/CT in ESFT were included in the meta-analysis, excluding duplicate publications. Finally, pooled sensitivity, pooled specificity and area under the receiver operating characteristic (ROC) curve of FDG-PET or PET/CT in ESFT were calculated. We found 13 studies comprising a total of 342 patients with ESFT. The main findings of the studies included are presented. The meta-analysis of five selected studies provided these results about FDG-PET and PET/CT in ESFT: pooled sensitivity: 96% (95% confidence interval [CI] 91-99%); pooled specificity: 92% (95% CI 87-96%); area under the ROC curve: 0.97. With regard to the staging and restaging of patients with ESFT, the sensitivity, specificity and accuracy of FDG-PET and PET/CT are high; the combination of FDG-PET or PET/CT with conventional imaging is a valuable tool for the staging and restaging of ESFT and has a relevant impact on the treatment strategy plan. (orig.)

  20. Dual-fibular reconstruction of a massive tibial defect after Ewing's sarcoma resection in a pediatric patient with a vascular variation.

    Science.gov (United States)

    Saridis, Alkis G; Megas, Panagiotis D; Georgiou, Christos S; Diamantakis, Georgios M; Tyllianakis, Minos E

    2011-01-01

    In the management of malignancies of the extremities, limb salvage procedures have recently taken on greater significance. For those patients under intense adjuvant chemotherapy and with massive bone loss, free vascularized fibular grafting is currently advocated as a reliable reconstructive option, maybe because of the controversial results of bone transport in similar situations. However, when there is a vascular abnormality of either the recipient or donor extremity, microsurgical procedures are not feasible, further limiting potential reconstructive alternatives. We present the case of a 13-year-old female patient with Ewing's sarcoma of the right tibia. Preoperative angiography showed that vascularity of the affected side depended totally on a single peroneal artery. The patient was treated initially with multiagent chemotherapy, followed by an excision of 23 cm. The defect was bridged by a gradual medial transportation of the ipsilateral fibula with the Ilizarov technique and strengthened by nonvascularized transfer of the contralateral fibula. Total external fixation time was 162 days. After the removal of the Ilizarov frame a walking cast was applied for another month. At 5 years postoperatively there was no recurrence of the malignancy. The patient had full weight-bearing ability on the affected limb, with preservation of the ankle and knee joints motion and without any limb length discrepancy or axial deformity. The functional outcome that was visible was graded excellent. Transverse distraction osteogenesis of the ipsilateral fibula performed well under chemotherapy, showing unproblematic callus formation. Supplemented with nonvascularized transfer of the contralateral fibula, provided a reconstructive option with biological affinity, sufficient biomechanical strength and durability, and with a decreased complication rate. This case report presents a viable option, especially in cases in which vascular abnormalities of either the donor or the recipient

  1. Prognostic value of FDG-PET indices for the assessment of histological response to neoadjuvant chemotherapy and outcome in pediatric patients with Ewing sarcoma and osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Clement Bailly

    Full Text Available The objective of this retrospective work was to evaluate the prognostic value on histological response and survival of quantitative indices derived from FDG-PET performed before and after chemotherapy (CHT, in a homogeneous pediatric Ewing sarcoma (EWS and Osteosarcoma (OST population.Thirty-one patients with EWS and 31 with OST were included. All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had FDG-PET at diagnosis and after CHT, prior to surgery. Several parameters were evaluated: SUVmax, SUVpeak, SUVmean, metabolic tumor volume, total lesion glycolysis, 7 textural features and 3 shape features (SF. The segmentation was performed using an adaptive approach. Results were compared to histopathological regression of the resected tumor and to clinical follow-up for survival evaluation.For EWS, univariate analysis did not highlight any prognostic value on histological response, or survival regardless of all the considered metrics. For OST, only one of the SF, namely elongation, was significantly associated with PFS and OS on both univariate and multivariate analysis (PFS: p = 0.019, HR = 5.583; OS: p = 0.0062, HR = 7.113.Only elongation determined on initial FDG-PET has a potential interest as a prognostic factor of PFS and OS in pediatric OST patients. Unlike recent studies of the literature realized in adult population, all the metrics reveal limited additional prognostic value in pediatric EWS patients. This seems to reinforce the question of whether children experience different subtypes of the same pathologies than older patients, with different outcomes.

  2. Factors affecting survival outcomes of patients with non-metastatic Ewing's sarcoma family tumors in the spine: a retrospective analysis of 63 patients in a single center.

    Science.gov (United States)

    Wan, Wei; Lou, Yan; Hu, Zhiqi; Wang, Ting; Li, Jinsong; Tang, Yu; Wu, Zhipeng; Xu, Leqin; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

    2017-01-01

    Little information has been published in the literature regarding survival outcomes of patients with Ewing's sarcoma family tumors (ESFTs) of the spine. The purpose of this study is to explore factors that may affect the prognosis of patients with non-metastatic spinal ESFTs. A retrospective analysis of survival outcomes was performed in patients with non-metastatic spinal ESFTs. Univariate and multivariate analyses were employed to identify prognostic factors for recurrence and survival. Recurrence-free survival (RFS) and overall survival (OS) were defined as the date of surgery to the date of local relapse and death. Kaplan-Meier methods were applied to estimate RFS and OS. Log-rank test was used to analyze single factors for RFS and OS. Factors with p values ≤0.1 were subjected to multivariate analysis. A total of 63 patients with non-metastatic spinal ESFTs were included in this study. The mean follow-up period was 35.1 months (range 1-155). Postoperative recurrence was detected in 25 patients, and distant metastasis and death occurred in 22 and 36 patients respectively. The result of multivariate analysis suggested that age older than 25 years and neoadjuvant chemotherapy were favorable independent prognostic factors for RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis were favorable independent prognostic factors for OS. Age older than 25 years and neoadjuvant chemotherapy are favorable prognostic factors for both RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis are closely associated with favorable survival.

  3. Process development of a human recombinant diabody expressed in E. coli: engagement of CD99-induced apoptosis for target therapy in Ewing's sarcoma.

    Science.gov (United States)

    Moricoli, Diego; Carbonella, Damiano Cosimo; Dominici, Sabrina; Fiori, Valentina; Balducci, Maria Cristina; Guerzoni, Clara; Manara, Maria Cristina; Pasello, Michela; Laguardia, Maria Elena; Cianfriglia, Maurizio; Scotlandi, Katia; Magnani, Mauro

    2016-05-01

    Ewing's sarcoma (EWS) is the second most common primary bone tumor in pediatric patients characterized by over expression of CD99. Current management consists in extensive chemotherapy in addition to surgical resection and/or radiation. Recent improvements in treatment are still overshadowed by severe side effects such as toxicity and risk of secondary malignancies; therefore, more effective strategies are urgently needed. The goal of this work was to develop a rapid, inexpensive, and "up-scalable" process of a novel human bivalent single-chain fragment variable diabody (C7 dAbd) directed against CD99, as a new therapeutic approach for EWS. We first investigated different Escherichia coli constructs of C7 dAbd in small-scale studies. Starting from 60 % soluble fraction, we obtained a yield of 25 mg C7 dAbd per liter of bacterial culture with the construct containing pelB signal sequence. In contrast, a low recovery of C7 dAbd was achieved starting from periplasmic inclusion bodies. In order to maximize the yield of C7 dAbd, large-scale fermentation was optimized. We obtained from 75 % soluble fraction 35 mg C7 dAbd per L of cell culture grown in a synthetic media containing 3 g/L of vegetable peptone and 1 g/L of yeast extract. Furthermore, we demonstrated the better efficacy of the cell lysis by homogenization versus periplasmic extraction, in reducing endotoxin level of the C7 dAbd. For gram-scale purification, a direct aligned two-step chromatography cascade based on binding selectivity was developed. Finally, we recovered C7 dAbd with low residual process-related impurities, excellent reactivity, and apoptotic ability against EWS cells.

  4. Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewing's sarcoma.

    Science.gov (United States)

    Zöllner, Stefan K; Selvanathan, Saravana P; Graham, Garrett T; Commins, Ryan M T; Hong, Sung Hyeok; Moseley, Eric; Parks, Sydney; Haladyna, Jessica N; Erkizan, Hayriye V; Dirksen, Uta; Hogarty, Michael D; Üren, Aykut; Toretsky, Jeffrey A

    2017-10-03

    Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its antitumor activity. We tested 69 anticancer drugs in combination with YK-4-279 and found that vinca alkaloids exhibited synergy with YK-4-279 in five ES cell lines. The combination of YK-4-279 and vincristine reduced tumor burden and increased survival in mice bearing ES xenografts. We determined that independent drug-induced events converged to cause this synergistic therapeutic effect. YK-4-279 rapidly induced G 2 -M arrest, increased the abundance of cyclin B1, and decreased EWS-FLI1-mediated generation of microtubule-associated proteins, which rendered cells more susceptible to microtubule depolymerization by vincristine. YK-4-279 reduced the expression of the EWS-FLI1 target gene encoding the ubiquitin ligase UBE2C, which, in part, contributed to the increase in cyclin B1. YK-4-279 also increased the abundance of proapoptotic isoforms of MCL1 and BCL2, presumably through inhibition of alternative splicing by EWS-FLI1, thus promoting cell death in response to vincristine. Thus, a combination of vincristine and YK-4-279 might be therapeutically effective in ES patients. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. 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

  6. Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT).

    Science.gov (United States)

    Machado, Isidro; López-Guerrero, Jose Antonio; Scotlandi, Katia; Picci, Piero; Llombart-Bosch, Antonio

    2018-05-01

    Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of PD-L1 and PD-1 and their prognostic significance in clinically localized neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was done considering only clinically localized tumors (n = 217). PD-L1 expression was present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated proliferation index (Ki-67) were associated with higher PD-L1 expression (p = 0.049). Regarding prognosis, no significant association was found between PD-L1 expression and progression-free survival (PFS) or overall survival (OS), whereas lack of PD-1 expression in tumor cells was correlated with both poor PFS (p = 0.02) and poor OS (p = 0.004). Tumor-infiltrating CD8(+) T lymphocytes were observed in 15.4% of ESFT with informative results (347 tumors). No correlation was found between tumor-infiltrating CD8(+) T lymphocytes and ESFT histological subtypes, tumor location, or PD-1 and PD-L1 expression, nor with PFS (p = 0.473) or OS (p = 0.087). PD-L1 expression was not significantly related to prognosis. PD-1 was expressed in 26% of ESFT tumor cells and may have prognostic and therapeutic implications. CD8 expression in tumor-infiltrating lymphocytes was not related to prognosis.

  7. Extraskeletal primary Ewing's scrcoma in the nasal cavity: A case report

    International Nuclear Information System (INIS)

    Jeong, Bo Young; Park, Seok Won; Km, Eo Jin; Choi, Jong Sun; Lee, Eun Ja

    2013-01-01

    Ewing's sarcoma presents a rare tumor of the head and neck, and even rarer in the nasal cavity and/or paranasal sinuses. We report the case of Ewing's sarcoma in the nasal cavity, as presented with nasal obstruction and epistaxis. The CT and MRI examination reveals a mass in the left nasal cavity with extension to contralateral side, ethmoidal sinus, and nasopharynx. We provide an overview of Ewing's sarcoma in the nasal cavity and discuss radiologic findings of this unusual case.

  8. Genetics Home Reference: Ewing sarcoma

    Science.gov (United States)

    ... produced from the FLI1 gene, attaches (binds) to DNA and regulates an activity called transcription , which is the first step in the production ... regulates transcription. The EWS/FLI protein has the DNA-binding function of ... well as the transcription regulation function of the EWS protein. It is ...

  9. Ewing sarcoma localized on spine: a dose escalation study in child; Sarcome d'Ewing localise au rachis: une etude d'escalade de dose chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Vogin, G.; Marchesi, V. [Centre Alexis-Vautrin, Nancy (France); Biston, M.C.; Gassa, F. [Centre Leon-Berard, Lyon (France); Amessis, M.; Zefkili, S.; Helfre, S. [Institut Curie, Paris (France); De Marzi, L.; Lacroix, F.; Leroy, A. [Institut Curie, Orsay (France)

    2011-10-15

    The authors report the study of dose escalation for the treatment of spinal in two types of Ewing tumours. They used 5 dose levels at the rate of five 1,6 Gy per week. They compare different radiotherapy techniques: three-dimensional conformation radiotherapy, static intensity-modulated conformational radiotherapy, helical tomo-therapy, volume-modulated arc-therapy (VMAT), stereotactic radiotherapy, and proton-therapy (in passive diffusion). It appears that it is possible to safely and efficiently deliver until 70,4 Gy in some Ewing tumours. In child, exclusive radiotherapy might become a local treatment option and would require a clinic trial and comparison with exclusive surgery or post-operative radiotherapy. Short communication

  10. EXTRAOSSEOUS EWINGS/PNET-A CASE REPORT BY FNAC

    OpenAIRE

    Bharath; Rakesh

    2013-01-01

    INTRODUCTION: Ewing sarcoma is one of the most common primary tumo r of the bone, but extra-skeletal type is rare. Ewing's sarcoma (ES) and primitive neuroectodermal t umor (PNET) are small round cell tumors showing varying (usuall y minimal) neuroectodermal differentiation [1] .These tumors occur predominately in adolescents and young adults,but rare below four years of age. The cytomorphologic feature s may be confused with other small round cell tu...

  11. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

    1999-01-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

  12. Ewe Pronunciation.

    Science.gov (United States)

    Schneeberg, Nan; Kpotufe, Prosper

    This volume consists of a guide to Ewe pronunciation and an Ewe textbook designed for students who are native speakers of English. Consonants, vowels and tones are introduced in the first section, and exercises that drill the contrasts between the segments are provided. The volume is divided into five units, each unit including a dialogue,…

  13. 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

  14. The combination of temozolomide-irinotecan regresses a doxorubicin-resistant patient-derived orthotopic xenograft (PDOX) nude-mouse model of recurrent Ewing's sarcoma with a FUS-ERG fusion and CDKN2A deletion: Direction for third-line patient therapy.

    Science.gov (United States)

    Miyake, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Miyake, Masuyo; Li, Yunfeng; Nelson, Scott D; Dry, Sarah M; Bouvet, Michael; Elliott, Irmina A; Russell, Tara A; Singh, Arun S; Eckardt, Mark A; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2017-11-28

    The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing's sarcoma PDOX, but not doxorubicin, similar to the patient's resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing's sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm 3 : untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line therapy of the patient.

  15. Reverse chemomodulatory effects of the SIRT1 activators resveratrol and SRT1720 in Ewing's sarcoma cells: resveratrol suppresses and SRT1720 enhances etoposide- and vincristine-induced anticancer activity.

    Science.gov (United States)

    Sonnemann, Jürgen; Kahl, Melanie; Siranjeevi, Priyanka M; Blumrich, Annelie; Blümel, Lisa; Becker, Sabine; Wittig, Susan; Winkler, René; Krämer, Oliver H; Beck, James F

    2016-01-01

    SIRT1-activating compounds (STACs) may have potential in the management of cancer. However, the best-studied STAC, the naturally occurring compound resveratrol, is reported to have contradictory effects in combination chemotherapy regimens: It has been shown both to increase and to decrease the action of anticancer agents. To shed more light on this issue, we comparatively investigated the impact of resveratrol and the synthetic STAC SRT1720 on the responsiveness of Ewing's sarcoma (ES) cells to the chemotherapeutic drugs etoposide and vincristine. Because the effects of STACs can depend on the functionality of the tumor suppressor protein p53, we used three ES cell lines differing in their p53 status, i.e., wild-type p53 WE-68 cells, mutant p53 SK-ES-1 cells and p53 null SK-N-MC cells. Single agent and combination therapy effects were assessed by flow cytometric analyses of propidium iodide uptake and mitochondrial depolarization, by measuring caspase 3/7 activity and by gene expression profiling. When applied as single agents, both STACs were effective in ES cells irrespective of their p53 status. Strikingly, however, when applied in conjunction with cytostatic agents, the STACs displayed reverse effects: SRT1720 largely enhanced etoposide- and vincristine-induced cell death, while resveratrol inhibited it. Combination index analyses validated the antipodal impact of the STACs on the effectiveness of the chemotherapeutics. These findings suggest that the synthetic STAC SRT1720 may be useful to enhance the efficacy of anticancer therapy in ES. But they also suggest that the dietary intake of the natural STAC resveratrol may be detrimental during chemotherapy of ES.

  16. Extraskeletal primary Ewing's scrcoma in the nasal cavity: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Bo Young; Park, Seok Won; Km, Eo Jin; Choi, Jong Sun; Lee, Eun Ja [Dongguk University College of Medicine, Ilsan Hospital, Goyang (Korea, Republic of)

    2013-08-15

    Ewing's sarcoma presents a rare tumor of the head and neck, and even rarer in the nasal cavity and/or paranasal sinuses. We report the case of Ewing's sarcoma in the nasal cavity, as presented with nasal obstruction and epistaxis. The CT and MRI examination reveals a mass in the left nasal cavity with extension to contralateral side, ethmoidal sinus, and nasopharynx. We provide an overview of Ewing's sarcoma in the nasal cavity and discuss radiologic findings of this unusual case.

  17. 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.

  18. 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

  19. 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...

  20. 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

  1. c-Myc Represses Tumor-Suppressive microRNAs, let-7a, miR-16 and miR-29b, and Induces Cyclin D2-Mediated Cell Proliferation in Ewing's Sarcoma Cell Line.

    Directory of Open Access Journals (Sweden)

    Masanori Kawano

    Full Text Available Myc oncogenic transcription factor is known to inhibit tumor suppressive microRNAs (miRNAs, resulting in greater expression of their target protein related to cell cycle, invasion or anti-apoptotic factors in human cancer cells. To explore possible oncogenic factors in Ewing's sarcoma (ES, we conducted microarray-based approach to profile the changes in the expression of miRNAs and its downstream mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs. Three miRNAs, let-7a, miR-16 and miR-29b were significantly down-regulated, whereas c-Myc and cyclin D2 (CCND2 were significantly up-regulated in all tested ES cells compared with hMSCs. To verify that let-7a, miR-16 and miR-29b were the targets of c-Myc in ES cell lines, we transfected siRNA against c-Myc and confirmed the coordinate up-regulation of let-7a, miR-16 and miR-29b through the repression of c-Myc. The ES cells transfected with c-Myc-siRNA and let-7a, miR-16 and miR-29b exhibited the inhibition of the cell cycle progression. The increased expression of let-7a, miR-16 and miR-29b resulted in the reduction of CCND2 protein expression. We also demonstrated that c-Myc-siRNA treatment of ES cells was associated with the decreased expression of CCND2 as a down-stream of three miRNAs. Furthermore, the introduction of let-7a, miR-16 and miR-29b in ES cells could inhibit the c-Myc-mediated up-regulation of CCND2 resulted in the prevention of cell cycle progression. In addition, the transfection of let-7a, miR-16 and miR-29b in ES cells suppressed tumor growth ex vivo treatment. These findings suggests that the up-regulation of c-Myc inhibited the expression of let-7a, miR-16 and miR-29b subsequently induced CCND2 expression in ES cells. The present study might identify a novel oncogenic axis that c-Myc regulates the expression of CCND2 via let-7a, miR-16 and miR-29b, leading to the development new therapeutic targets for ES.

  2. 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 ...

  3. Localisation inhabituelle du sarcome d'Ewing des parties molles ...

    African Journals Online (AJOL)

    Ewing's sarcoma of soft parts is a rare mesenchymal tumor of poor prognosis. Receiving an early diagnosis increases the chance of survival. In the absence of clinical and radiological features, it seems necessary to include it in the differential diagnosis which includes all the primitive tumour of soft parts and to hypothesize ...

  4. 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.

  5. 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)

  6. 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.

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. Primary Ewing’s Sarcoma of the Kidney in a 73-Year-Old Man

    Directory of Open Access Journals (Sweden)

    T. B. Wedde

    2011-01-01

    Full Text Available Objective. Ewing’s sarcoma of the kidney is rare and is usually found in young adults. We present here a single case study of Ewing's sarcoma found in an elderly man. Material and methods. A 73-year-old man underwent routine surgery for hydrocoele of the testis. He developed urinary obstruction symptoms, and radiological examinations revealed a tumour in the right kidney. Results. Microscopical, immunohistochemical, and molecular pathological analysis of the tumour was consistent with Ewing's sarcoma. FISH showed rearrangement of chromosomes 22q12 (EWSR1. The patient subsequently underwent nephrectomy followed by 6 adjuvant chemotherapy cycles. Follow-up after 7 months shows no recurrence. Conclusion. This case report presents not only the rare finding of Ewing's sarcoma in the kidney, but also the occurrence of this tumour entity in an elderly patient. Treatment options for the different types of renal tumours are vastly different and the need for a correct diagnosis is, therefore, vital.

  11. 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: ...

  12. Ewing tumors in infants

    NARCIS (Netherlands)

    van den Berg, Henk; Dirksen, Uta; Ranft, Andreas; Jürgens, Heribert

    2008-01-01

    Malignancies in infancy are extremely rare. Ewing tumors are hardly ever noted in these children. Since it is generally assumed that malignancies in infancy have an extremely poor outcome, we wanted to investigate whether this was also the case in Ewing tumors. We identified in the Munster data

  13. Vascularized fibula grafts for reconstruction of bone defects after resection of bone sarcomas

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hovgaard, Dorrit; Elberg, Jens Jørgen

    2010-01-01

    We evaluated the results of limb-sparing surgery and reconstruction of bone defects with vascularized fibula grafts in 8 consecutive patients (mean age at operation 13.6 years (range 4.1-24.2 years), female/male = 6/2) with bone sarcomas (BS) (osteosarcoma/Ewing's sarcoma/chondrosarcoma= 4....../3/1) operated on form 2000 to 2006. The bone defects reconstructed were proximal femoral diaphysis and epiphysis (n = 2), humeral diaphysis (n = 2), humeral proximal diaphysis and epiphysis (n = 1), femoral diaphysis (n = 1), ulnar diaphysis (n = 1), and tibial diaphysis (n = 1). One patient with Ewing......'s sarcoma had an early hip disarticulation, developed multiple metastases, and died 9 months after the operation. The remaining patients (n = 7) are all alive 50 months (range 26-75 months) after surgery. During the follow-up the following major complications were seen: 1-2 fractures (n = 4), pseudarthrosis...

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. Therapy for Ewing´s Family of Tumours in adults - a case report of 53 years old patient

    International Nuclear Information System (INIS)

    Adamkova Krakorova, D.; Tomasek, J.; Tucek, S.; Janicek, P.; Cerny, J.

    2011-01-01

    Ewing's sarcoma, a highly malignant primary bone tumour, is most frequently observed in children and adolescents, aged 4 - 15 years. 90 % of patients are younger than 20 years. Ewing's sarcomas are rare in patients over the age of 40 years. Prognosis is poor, with 5-year overall survival of 55 % to 70 % in localized and not exceeding 20 % in primarily metastatic disease. Patients with primary bone cancers should be evaluated by a multidisciplinary team with demonstrated expertise in the management of such patients. We introduce you a curiose case report of 53 years old patient. (author)

  19. 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

  20. 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.

  1. Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression.

    Directory of Open Access Journals (Sweden)

    Limin eZhu

    2013-09-01

    Full Text Available The two most common primary bone malignancies, osteosarcoma and Ewing sarcoma, are both aggressive, highly metastatic cancers that most often strike teens, though both can be found in younger children and adults. Despite distinct origins and pathogenesis, both diseases share several mechanisms of progression and metastasis, including neovascularization, invasion, anoikis resistance, chemoresistance and evasion of the immune response. Some of these processes are well-studies in more common carcinoma models, and the observation from adult diseases may be readily applied to pediatric bone sarcomas. Neovascularization, which includes angiogenesis and vasculogenesis, is a clear example of a process that is likely to be similar between carcinomas and sarcomas, since the responding cells are the same in each case. Chemoresistance mechanisms also may be similar between other cancers and the bone sarcomas. Since osteosarcoma and Ewing sarcoma are mesenchymal in origin, the process of epithelial-to-mesenchymal transformation is largely absent in bone sarcomas, necessitating different approaches to study progression and metastasis in these diseases. One process that is less well-studied in bone sarcomas is dormancy, which allows micrometastatic disease to remain viable but not growing in distant sites – typically the lungs – for months or years before renewing growth to become overt metastatic disease. By understanding the basic biology of these processes, novel therapeutic strategies may be developed that could improve survival in children with osteosarcoma or Ewing sarcoma.

  2. Hemithorax irradiation for Ewing tumors of the chest wall

    International Nuclear Information System (INIS)

    Schuck, Andreas; Ahrens, Susanne; Konarzewska, Agnieszka; Paulussen, Michael; Froehlich, Birgit; Koenemann, Stefan; Ruebe, Christian; Ruebe, Claudia E.; Dunst, Juergen; Willich, Normann; Juergens, Heribert

    2002-01-01

    Purpose: In the Cooperative Ewing's Sarcoma Study 86 and the European Intergroup Cooperative Ewing's Sarcoma Study 92, hemithorax irradiation (RT) was performed in patients with Ewing tumors of the chest wall involving the pleura or contaminating the pleural cavity. In a retrospective analysis, the outcomes of these patients were evaluated and compared with those of patients with chest wall tumors who did not receive hemithorax RT. Methods and Materials: Between 1985 and 1996, 138 patients presented with nonmetastatic Ewing tumors of the chest wall. They were treated in a multimodal treatment regimen that included polychemotherapy and local therapy depending on the tumor characteristics. Hemithorax RT was performed at a dose of 15 Gy for patients <14 years old and 20 Gy for patients ≥14 years old. Forty-two patients received hemithorax RT (Group 1) and 86 patients did not (Group 2). The data were insufficient for the other 10 patients. Results: Comparing both groups, the initial pleural effusion, pleural infiltration, and intraoperative contamination of the pleural space were significantly more frequent in Group 1. The event-free survival rate after 7 years was 63% for patients in Group 1 and 46% for patients in Group 2 (not statistically significant). The 7-year local relapse rate (including combined local-systemic relapses) was 12% in Group 1 and 10% in Group 2; the corresponding systemic relapse rates were 22% and 39%. Conclusion: Patients with chest wall tumors who received hemithorax RT were negatively selected; yet the rate of event-free survival was better for patients who received hemithorax RT than for those who did not (although the difference was not statistically significant). This result was due to a reduction of metastases, mainly lung metastases. Local control was equivalent between the two groups. These favorable results have caused us to continue using hemithorax RT to treat high-risk patients with Ewing tumors of the chest wall

  3. 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...

  4. 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 ...

  5. Ewing’s Sarcoma Presenting as Pleural Effusion

    Directory of Open Access Journals (Sweden)

    Nuzhat Husain

    2011-09-01

    Full Text Available  A 20-year-old female presented to the Pulmonary Medicine Department with complaints of fever, left sided chest pain and progressive dyspnoea of four months duration. Radiological examination revealed a mass lesion with massive pleural effusion and rib erosion. Histopathology showed neoplastic cells with scanty cytoplasm, hyperchromatic nuclei and rosette formation suggestive of Ewing sarcoma. The rarity of this tumor and its unusual presentation prompted this report.

  6. Ewe Basic Course. Revised Version.

    Science.gov (United States)

    Warburton, Irene; And Others

    The purpose of this beginning text in Ewe is to provide the student with an introduction to the structure of the Ewe language and "reasonable practice" in speaking. It is intended to be taught with the assistance of a native speaker of Ewe. Linguistic terminology is minimal. Suggested teaching time ranges from two semesters of class meetings of…

  7. Do pathological fractures influence survival and local recurrence rate in bony sarcomas?

    NARCIS (Netherlands)

    Bramer, J. A. M.; Abudu, A. A.; Grimer, R. J.; Carter, S. R.; Tillman, R. M.

    2007-01-01

    The influence of pathological fracture on surgical management, local recurrence and survival was established in patients with high grade, localised, extremity osteosarcoma (n=484), chondrosarcoma (n=130) and Ewing's sarcoma (n=156). Limb salvage was possible in 79% of patients with a fracture

  8. 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.

  9. 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

  10. Diagnosis and treatment of sarcomas and related tumors

    International Nuclear Information System (INIS)

    1978-01-01

    The Cancergram focuses on clinical aspects of sarcomas involving soft tissue and bone, and also includes abstracts on related malignant and benign tumors. Soft tissues are considered as all non-epithelial extra-skeletal tissues of the body, with the exception of the reticuloendothelial system, the neuroglia, and visceral and parenchymal organs. Included, therefore, are sarcomas of the vascular system, fatty tissue, muscle tissues, connective tissues, and synovial tissues. Bone tumors included are osteosarcoma, chondrosarcoma, adamantinoma, chrondroblastoma, Ewing's sarcoma, and other benign and malignant disorders of the bone. This Cancergram excludes disorders of the bone marrow, which are the subjects of separate Cancergrams (see series CT03 for leukemias, and series CT12 for multiple myeloma). The scope includes diagnosis and staging, supportive care, evaluation, and therapy. Selected abstracts concerning epidemiology, etiology and other pre-clinical studies will also be included where they have direct clinical relevance

  11. Nonmetastatic Ewing’s Sarcoma of the Lumbar Spine in an Adult Patient

    Directory of Open Access Journals (Sweden)

    Maurizio Iacoangeli

    2012-01-01

    Full Text Available Although the spine is frequently involved in metastatic Ewing's sarcoma, primary involvement of the spine, beside sacrum, is much less frequent, especially in adult patients. Because of the low incidence of these tumors, there are currently no clinical guidelines outlining their management and a multitude of therapeutic strategies have been employed with varying success. The definitive management of Ewing's sarcoma of the spine, as in other locations, could include the combination of three main modalities: aggressive surgery, radiotherapy, and combined chemotherapy. Whenever possible, en bloc spondylectomy or extralesional resection is preferable, providing a better oncological result with a longer survival and a better preservation of the spine biomechanics. This is the lesson we learned about the case, we present here, of nonmetastatic lumbar localization by Ewing’s sarcoma in as adult patient.

  12. 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 ...

  13. Non-Metastatic Pelvic Ewing's Sarcoma : oncologic outcomes and evaluation of prognostic factors.

    Science.gov (United States)

    Dramis, A; Grimer, R J; Malizos, K; Tillman, R M; Jeys, L; Carter, L R

    2016-08-01

    We are reporting our experience on patients with -pelvic Ewing's Sarcoma treated in our unit. We retrospectively reviewed a series of patients with non-metastatic pelvic Ewing's sarcoma treated between 1977 and 2009. Patients were classified into three groups according to the local treatment received : Group 1. radiotherapy-chemo ; Group 2. surgery-chemo and Group 3. radiotherapy-surgery-chemo. Recurrence free and overall survival rates were calculated using the Kaplan-Meier method. Influence of various factors (age at diagnosis, gender, tumour site and size, chemotherapy response, surgical margins and type of treatment) on survival was assessed with a logistic regression model. A total of 85 patients were treated with a mean follow-up of 65.8 months and mean -tumour volume of 435ml. The 5-year survival for all patients was 40.7% decreased to 36.2% at 10 years. A significant prognostic factor identified was chemotherapy response only. There was a trend for improved survival and local control rates for patients who had chemotherapy and surgery and the results were apparent for all tumours irrespective of size but not statistically significant. Currently, the optimal management of pelvic Ewing's sarcoma is contro-versial but our study shows a trend for improved -survival for patients treated with chemotherapy and surgery.

  14. Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

    International Nuclear Information System (INIS)

    Serizawa, Itsuko; Kagei, Kenji; Kamada, Tadashi; Imai, Reiko; Sugahara, Shinji; Okada, Tohru; Tsuji, Hiroshi; Ito, Hisao; Tsujii, Hirohiko

    2009-01-01

    Purpose: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. Methods and Materials: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologic grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm 3 and 1,194 cm 3 (median 525 cm 3 ). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. Results: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. Conclusions: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.

  15. TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data.

    Science.gov (United States)

    Gamie, Zakareya; Kapriniotis, Konstantinos; Papanikolaou, Dimitra; Haagensen, Emma; Da Conceicao Ribeiro, Ricardo; Dalgarno, Kenneth; Krippner-Heidenreich, Anja; Gerrand, Craig; Tsiridis, Eleftherios; Rankin, Kenneth Samora

    2017-11-28

    Bone sarcomas are rare, highly malignant mesenchymal tumours that affect teenagers and young adults, as well as older patients. Despite intensive, multimodal therapy, patients with bone sarcomas have poor 5-year survival, close to 50%, with lack of improvement over recent decades. TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumour necrosis factor (TNF) ligand superfamily (TNFLSF), has been found to induce apoptosis in cancer cells while sparing nontransformed cells, and may therefore offer a promising new approach to treatment. We cover the existing preclinical and clinical evidence about the use of TRAIL and other death receptor agonists in bone sarcoma treatment. In vitro studies indicate that TRAIL and other death receptor agonists are generally potent against bone sarcoma cell lines. Ewing's sarcoma cell lines present the highest sensitivity, whereas osteosarcoma and chondrosarcoma cell lines are considered less sensitive. In vivo studies also demonstrate satisfactory results, especially in Ewing's sarcoma xenograft models. However, the few clinical trials in the literature show only low or moderate efficacy of TRAIL in treating bone sarcoma. Potential strategies to overcome the in vivo resistance reported include co-administration with other drugs and the potential to deliver TRAIL on the surface of primed mesenchymal or immune cells and the use of targeted single chain antibodies such as scFv-scTRAIL. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. 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...

  17. Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity

    Directory of Open Access Journals (Sweden)

    J. Herzog

    2016-01-01

    Full Text Available Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4. Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.

  18. Epidemiological Evaluation of Head and Neck Sarcomas in Iran (the Study of 105 Cases Over 13 Years).

    Science.gov (United States)

    Alishahi, Batoul; Kargahi, Neda; Homayouni, Solmaz

    2015-08-01

    Head and neck sarcomas are exceedingly rare and they include 4% - 10% of all sarcomas and less than 1% of all neoplasm of head and neck. The aim of this study is to evaluate the epidemiological characteristics of head and neck sarcomas of patients in Isfahan, Iran. In this retrospective study, from the 16000 patients whose files were evaluated, the total number of 105 head and neck sarcomas were collected. They were evaluated with due attention to age, gender of the patients and the most common location of the lesion. From the total number of 105 (0.6%) patients with sarcomas, 56 were men (53.33%) and 49 women (46.66%). The most common head and neck sarcomas among this population were Osteosarcoma (32 cases, 30.47%), Chondrosarcoma (14 cases, 13.33%), and Ewing sarcoma (11 cases, 10.47%).The most common soft tissue sarcoma was Rabdomiosarcoma. Mandible was the most common location for these lesions. In this study, the hard tissue sarcomas were more prevalent than soft tissue ones. Hence, special attention should be paid to the patients when being diagnosed.

  19. Four year experience of sarcoma of soft tissues and bones in a tertiary care hospital and review of literature

    Directory of Open Access Journals (Sweden)

    Ansari Tayyaba Z

    2011-05-01

    Full Text Available Abstract Background Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones. Methods This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted. Results Out of 93 newly diagnosed patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed patients, 5 had soft tissue sarcoma and 9 had bone sarcoma. Mean age was 32.5 years. At presentation, approximately two third patients had localised disease while remaining one third had metastatic disease. The Kaplan Meier estimate of median recurrence free survival was 25 months, 35 months, and 44 months for Osteogenic sarcoma, Ewing's sarcoma and Chondrosarcoma respectively. For Leiomyosarcoma and Synovial sarcoma, it was 20 and 19 months respectively. The grade of the tumour (p = 0.02 and surgical margin status (p = 0.001 were statistically significant for determination of relapse of disease. Conclusion The median recurrence free survival of patients in our study was comparable to the reported literature but with significant lost to follow rate. Further large-scale, multi centre studies are needed to have a more comprehensive understanding of this heterogeneous disease in our population.

  20. 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.

  1. 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.

  2. 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 ...

  3. 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

  4. 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

    with synovial sarcoma. No patients with leiomyosarcoma (n=10) had an objective response. Two (5%) of 40 patients with bone sarcoma had an objective response, including one (5%) of 22 patients with osteosarcoma and one (20%) of five patients with chondrosarcoma. None of the 13 patients with Ewing's sarcoma had an objective response. The most frequent grade 3 or worse adverse events were anaemia (six [14%]), decreased lymphocyte count (five [12%]), prolonged activated partial thromboplastin time (four [10%]), and decreased platelet count (three [7%]) in the bone sarcoma group, and anaemia, decreased lymphocyte count, and prolonged activated partial thromboplastin time in the soft-tissue sarcoma group (three [7%] each). Nine (11%) patients (five [12%] in the bone sarcoma group and four [10%] in the soft-tissue sarcoma group) had treatment-emergent serious adverse events (SAEs), five of whom had immune-related SAEs, including two with adrenal insufficiency, two with pneumonitis, and one with nephritis. The primary endpoint of overall response was not met for either cohort. However, pembrolizumab showed encouraging activity in patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. Enrolment to expanded cohorts of those subtypes is ongoing to confirm and characterise the activity of pembrolizumab. Merck, SARC, Sarcoma Foundation of America, QuadW Foundation, Pittsburgh Cure Sarcoma, and Ewan McGregor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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

  6. 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.

  7. Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

    Science.gov (United States)

    Trancău, I O; Huică, R; Surcel, M; Munteanu, A; Ursaciuc, C

    2015-01-01

    EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

  8. Successful collection of peripheral blood stem cells upon VIDE chemomobilization in sarcoma patients.

    Science.gov (United States)

    Kriegsmann, Katharina; Heilig, Christoph; Cremer, Martin; Novotny, Philipp; Kriegsmann, Mark; Bruckner, Thomas; Müller-Tidow, Carsten; Egerer, Gerlinde; Wuchter, Patrick

    2017-11-01

    In patients with Ewing sarcoma and some distinct subgroups of soft tissue sarcoma (STS), a quantitatively sufficient autologous peripheral blood stem cell (PBSC) collection for stem cell support might facilitate treatment continuation, dose-intensification, and high-dose chemotherapy. Here, we provide a detailed evaluation of PBSC collection upon vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) chemomobilization. Mobilization and collection parameters of 42 sarcoma patients (Ewing sarcoma n = 35, other STS n = 7) were analyzed retrospectively. Data were evaluated with regard to the number of previous VIDE therapy cycles. All patients reached the collection goal of ≥2.0 × 10 6 CD34 + cells/kg body weight (bw) upon VIDE/G-CSF mobilization, in the majority of cases with one single leukapheresis (LP) session (n = 29, 69%). No significant differences were identified with regard to mobilization and collection variables or the number of previous induction VIDE therapy cycles. However, upon 5 cycles of VIDE, we found the highest relative proportion of patients who required two or three LP sessions. Our data demonstrate the feasibility of successful PBSC collection upon VIDE chemomobilization even after up to five cycles of induction therapy, while at the same time the increasing risk of bone marrow exhaustion with every consecutive cycle is outlined. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Disseminated Intracranial Ewing’s Sarcoma in an Adult:A Rare and Difficult Diagnosis

    Directory of Open Access Journals (Sweden)

    Emil Lou

    2012-06-01

    Full Text Available The Ewing sarcoma family of tumors comprises a rare class of cancers of mesenchymal origin. Cases of Ewing’s sarcoma in the central nervous system – specifically, intracranial Ewing’s – are extremely rare. Almost all reported cases have occurred in children. However, this rare presentation can also occur in the adult population. It is important to distinguish these tumors from primitive neuroectodermal tumors at the time of diagnosis. Testing for EWSR1(22q12 gene rearrangement using fluorescence in situ hybridization is a useful tool for making the distinction between these 2 similar but distinct entities. We present here the case of a middle-aged male patient with intracranial Ewing’s sarcoma, and discuss diagnostic challenges and potential new treatment approaches for this rare disease.

  10. STAT3 Regulates Proliferation and Immunogenicity of the Ewing Family of Tumors In Vitro

    Directory of Open Access Journals (Sweden)

    Sam Behjati

    2012-01-01

    Full Text Available The Ewing sarcoma family of tumors (ESFT represents an aggressive spectrum of malignant tumour types with common defining histological and cytogenetic features. To evaluate the functional activation of signal transducer and activator of transcription 3 (STAT3 in ESFT, we evaluated its activation in primary tissue sections and observed the functional consequences of its inhibition in ESFT cell lines. STAT3 was activated (tyrosine 705-phosphorylated in 18 out of 31 primary tumours (58%, either diffusely (35% or focally (23%. STAT3 was constitutively activated in 3 out of 3 ESFT cell lines tested, and its specific chemical inhibition resulted in complete loss of cell viability. STAT3 inhibition in ESFT cell lines was associated with several consistent changes in chemokine profile suggesting a role of STAT3 in ESFT in both cell survival and modification of the cellular immune environment. Together these data support the investigation of STAT3 inhibitors for the Ewing family of tumors.

  11. 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 ...

  12. Concluding Remarks | Ewing | Rwanda Journal

    African Journals Online (AJOL)

    Rwanda Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 2, No 2 (2015) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Concluding Remarks. Helen Ewing. Abstract. No Abstract. Full Text:.

  13. Primitive Neuroectodermal Tumor E wing's Sarcoma Arising from the Cigomatic Arch and the Masticator y Space. A Case Report

    International Nuclear Information System (INIS)

    Arango Bonnet, German; Andres Narvaez, Jorge; Garcia, Sara Eugenia

    2008-01-01

    Peripheral primitive neuroectodermic tumor (PNET) or peripheral neuro epithelioma is a malignant neoplasia consisting of round small blue cells, which derive from the neural crest. Amongst malignant tumors it is one the least differentiated histological types. Ewings sarcoma and PNET are morphologically impossible to differentiate; they are also very similar pathologically in terms of their imagining appearance. Due to these similarities we will consider them as a single entity. These can appear in infants, but are more common in adolescents. Treatment includes hemo therapy,surgery and radiotherapy. We present a case of an 8 year old female patient, diagnosed with Ewing Sarcoma, confirmed by histopathology and immunohistochemistry, we will also present a brief review of the literature.

  14. Prognostic factors for survival among patients with primary bone sarcomas of small bones

    Directory of Open Access Journals (Sweden)

    Wang Z

    2018-05-01

    Full Text Available Zhan Wang,1,* Shu Li,2,* Yong Li,1 Nong Lin,1 Xin Huang,1 Meng Liu,1 Weibo Pan,1 Xiaobo Yan,1 Lingling Sun,1 Hengyuan, Li,1 Binghao Li,1 Hao Qu,1 Yan Wu,1 Peng Lin,1 Zhaoming Ye1 1Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Centre for Orthopaedic Research, Orthopedics Research Institute of Zhejiang University, Hangzhou, China; 2Key Laboratory of Cancer Prevention and Intervention, Key Laboratory of Molecular Biology in Medical Sciences, National Ministry of Education, Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Cancer Institute, Hangzhou, China *These authors contributed equally to this work Background: Primary bone sarcomas of the hands or feet are rare lesions and poorly documented. Moreover, the prognostic determinants of bone sarcomas of the hands or feet have not been reported. Materials and methods: The Surveillance, Epidemiology, and End Results (SEER program database was used to screen patients with bone sarcomas of the hands or feet from 1973 to 2013, with attention paid to chondrosarcoma, Ewing sarcoma, and osteosarcoma. The prognostic values of overall survival (OS and cancer-specific survival (CSS were assessed using Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan–Meier method was used to obtain OS and CSS curves. Results: A total of 457 cases were selected from the SEER database. Chondrosarcoma was the most common form of lesion in hands or feet or both, followed by Ewing sarcoma and osteosarcoma. The 5- and 10-year OS rates of the entire group were 75.7% and 66.1%, respectively. The 5- and 10-year CSS rates were 78.7% and 73.7%, respectively. Multivariate analysis revealed that age under 40 years, localized stage, low grade, surgical treatment, and first primary tumor were associated with improved OS, and decade of diagnosis, stage, grade, and surgery were independent

  15. 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.

  16. Effect of supplementary feeding to ewes and suckling lambs on ewe ...

    African Journals Online (AJOL)

    A trial was conducted to determine the effects on the performance of creep feeding suckling lambs and supplementing ewes that were grazing wheat stubble. Eight experimental units of South African Mutton