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Sample records for chemo-resistant ewing sarcoma

  1. Ewing sarcoma

    MedlinePLUS

    Ewing sarcoma is a malignant (cancerous) bone tumor that affects children. ... Ewing sarcoma can occur anytime during childhood and young adulthood. But it usually develops during puberty, when bones are ...

  2. Stages of Ewing Sarcoma

    MedlinePLUS

    ... of recurrent Ewing sarcoma. High-dose chemotherapy with stem cell rescue High-dose chemotherapy with stem cell rescue is a way of giving high doses ... replacing blood -forming cells destroyed by cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  3. Extraskeletal Ewing's sarcoma.

    PubMed

    El-Essawy, Manar T

    2009-06-01

    We report 2 rare cases of extraskeletal Ewing's sarcoma, one is arising primarily from the posterior mediastinum in a middle-aged man (patient 1), and the other one is arising from the left kidney in a young male patient (patient 2). The CT in the first case showed a large mass of heterogeneous texture, with areas of cystic changes in the right side of the posterior mediastinum, no underlying bony changes or intra-spinal extension, and this mass was diagnosed as lymphoma. The second case showed almost complete replacement of the left kidney by a mass with extension through the renal vein and inferior vena cava, and it was diagnosed as renal cell carcinoma. The histological analysis of these lesions revealed extraskeletal Ewing's sarcoma. PMID:19526172

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

    ClinicalTrials.gov

    2013-06-20

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

  5. Collecting and Storing Biological Samples From Patients With Ewing Sarcoma

    ClinicalTrials.gov

    2015-11-12

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

  6. Genetics Home Reference: Ewing sarcoma

    MedlinePLUS

    ... bone cancer is called osteosarcoma). What are the genetic changes related to Ewing sarcoma? The most common ... Center . Where can I find general information about genetic conditions? The Handbook provides basic information about genetics ...

  7. Treatment Option Overview (Ewing Sarcoma)

    MedlinePLUS

    ... of recurrent Ewing sarcoma. High-dose chemotherapy with stem cell rescue High-dose chemotherapy with stem cell rescue is a way of giving high doses ... replacing blood -forming cells destroyed by cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  8. General Information about Ewing Sarcoma

    MedlinePLUS

    ... of recurrent Ewing sarcoma. High-dose chemotherapy with stem cell rescue High-dose chemotherapy with stem cell rescue is a way of giving high doses ... replacing blood -forming cells destroyed by cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  9. Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

    ClinicalTrials.gov

    2015-12-01

    Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  10. Ewing's sarcoma of the mandible.

    PubMed

    Rao, B H Sripathi; Rai, Gunachander; Hassan, Shahid; Nadaf, Afreen

    2011-07-01

    Ewing's sarcoma is a malignant tumor of bones that primarily affects children and young adults. The true origin of this small round cell lesion still remains controversial. It was originally described by James Ewing in 1921 as arising from undifferentiated osseous mesenchymal cells; however, recent studies suggest that Ewing's tumor might be neuroectodermally derived from various degrees of differentiation of the primitive neural tissues. This paper reports a rare case of ES of the mandible in an 11-year-old girl, which had been previously misdiagnosed and treated as a dental abscess. In the clinical examination, a hard immobile expansive mass of 2 cm diameter was observed on the left side of the mandible. Radiographic examination revealed a diffuse radiolucent lesion with ill-defined borders and wide vestibular bone plate destruction. Microscopically, the tumor was composed by monotonous small round cells that exhibited immunoreactivity for CD99, vimentin and desmin. Surgical resection of mandible followed by mandibular reconstruction was adopted. The patient was subjected to multiagent chemotherapy with Vincristine [VC], Dactinomycin [AC], Cyclophosphamide [CP] and Doxorubicin [AD]). PMID:22639511

  11. Ewing's sarcoma of the mandible

    PubMed Central

    Rao, B. H. Sripathi; Rai, Gunachander; Hassan, Shahid; Nadaf, Afreen

    2011-01-01

    Ewing's sarcoma is a malignant tumor of bones that primarily affects children and young adults. The true origin of this small round cell lesion still remains controversial. It was originally described by James Ewing in 1921 as arising from undifferentiated osseous mesenchymal cells; however, recent studies suggest that Ewing's tumor might be neuroectodermally derived from various degrees of differentiation of the primitive neural tissues. This paper reports a rare case of ES of the mandible in an 11-year-old girl, which had been previously misdiagnosed and treated as a dental abscess. In the clinical examination, a hard immobile expansive mass of 2 cm diameter was observed on the left side of the mandible. Radiographic examination revealed a diffuse radiolucent lesion with ill-defined borders and wide vestibular bone plate destruction. Microscopically, the tumor was composed by monotonous small round cells that exhibited immunoreactivity for CD99, vimentin and desmin. Surgical resection of mandible followed by mandibular reconstruction was adopted. The patient was subjected to multiagent chemotherapy with Vincristine [VC], Dactinomycin [AC], Cyclophosphamide [CP] and Doxorubicin [AD]). PMID:22639511

  12. Multiple primary Ewings sarcomas in cerebral cranium of a child: a case report and review of the literature

    PubMed Central

    Wang, Dawei; Guo, Zongze

    2015-01-01

    Ewings sarcoma is the second most common pediatric bone tumor. Primary Ewings sarcoma occurring in the cerebral cranium is exceptionally rare, with only one reported case of multiple tumor lesions in adolescence to date. We report a case of a 5-year-old male patient with multiple primary Ewings sarcomas associated with the cranial bones, the first pediatric case report to date. We also review 71 cases Ewings sarcoma involving intracranial extension. The purpose of this article is to provide data concerning the clinical and therapeutic course of multiple primary Ewings sarcomas in associated with cerebral cranium. PMID:26261672

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

    SciTech Connect

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

    1985-02-01

    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.

  14. Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma

    PubMed Central

    Attia, Steven; Okuno, Scott H.; Robinson, Steven I.; Webber, Nicholas P.; Indelicato, Daniel J.; Jones, Robin L.; Bagaria, Sanjay P.; Jones, Robin L.; Sherman, Courtney; Kozak, Kevin R.; Cortese, Cherise M.; McFarland, Thomas; Trent, Jonathan C.; Maki, Robert G.

    2015-01-01

    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. PMID:26266019

  15. Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma.

    PubMed

    Attia, Steven; Okuno, Scott H; Robinson, Steven I; Webber, Nicholas P; Indelicato, Daniel J; Jones, Robin L; Bagaria, Sanjay P; Jones, Robin L; Sherman, Courtney; Kozak, Kevin R; Cortese, Cherise M; McFarland, Thomas; Trent, Jonathan C; Maki, Robert G

    2015-05-01

    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. PMID:26266019

  16. Tumor-Targeting Salmonella typhimurium A1-R Arrests a Chemo-Resistant Patient Soft-Tissue Sarcoma in Nude Mice

    PubMed Central

    Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Zhang, Nan; Maawy, Ali; Murakami, Takashi; Mii, Sumiyuki; Uehara, Fuminari; Yamamoto, Mako; Miwa, Shinji; Yano, Shuya; Momiyama, Masashi; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

    2015-01-01

    A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) Salmonella typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). S. typhimurium A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). S. typhimurium A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting S. typhimurium A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma. PMID:26237416

  17. An Unusual Location of Extraosseous Ewing's Sarcoma

    PubMed Central

    Geens, Lisanne; Robays, Johan Van; Geert, Verswijvel; der Speeten, Kurt Van

    2013-01-01

    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. PMID:23898272

  18. Anti-Epileptic Drug Targets Ewing Sarcoma

    PubMed Central

    Kayarthodi, Shubhalaxmi; Fujimura, Yasuo; Fang, Jinbo; Morsalin, Sharif; Rao, Veena N.; Reddy, E. Shyam P.

    2014-01-01

    Ewing Sarcoma (ES) is a rare form of bone cancer that most commonly affects children and adolescents. Chromosomal translocations are fundamental to the development of Ewing Sarcoma, linked to the changes in gene expression affecting transcription factors. Histone acetyl transferases (HATs) and histone deacetylases (HDACs) regulate transcription by modifying acetylation of both histones and transcription factors. Despite the use of multimodal therapeutic approaches current therapies are associated with significant short and long-term side effects. Hence, new therapeutic approaches are needed. In this study, we show that ERG/EWS-ERG, inhibits transcriptional activation properties of RXR?. These results suggest that ERG/EWS-ERG/EWS-Fli-1 may target transcriptional co-activators and transcriptional repressors and thereby regulate RXR? transcriptional activity. To understand the molecular mechanism of action, how the fusion protein targets nuclear receptor function, and to provide a clue for the cancer health disparity seen in Ewing Sarcoma, we hypothesized that the aberrant fusion protein, EWS-ERG/EWS-Fli-1 regulates HDACs-mediated repressor complex and inhibits the binding of transcriptional activator complex causing transcriptional repression of RXR? activity. Since it is known that HDACs regulate nuclear receptors, we proposed that HDAC inhibitor, valproic acid (VPA), an anti-epileptic drug, may reverse the inhibitory properties of EWS-ERG/EWS-Fli-1 oncoprotein on RXR? transcriptional activity and might therefore be used as therapeutic agent in ES. We demonstrate that VPA reverses the inhibitory effect of EWSERG/EWS-Fli-1 on RXR? transcriptional activity and also inhibits the cell growth. Furthermore, VPA induces apoptosis and restored the expression of RXR? target genes RAR?, CRABPII and p21 activity and repressed the expression of aberrant fusion proteins, EWS-ERG and EWS-Fli-1 in Ewing Sarcoma cells. Thus, therapeutic regulation of transcriptional repressor properties of EWS-ERG/EWS-Fli-1 with an anti-epileptic drug with a promising new potential might have a profound impact on prevention, management and treatment of Ewing Sarcoma. Therapeutic use of VPA in minority patients may help reduce the health disparity. PMID:25664332

  19. Ewing Sarcoma of the Posterior Fossa in an Adolescent Girl

    PubMed Central

    Stark, Andreas M.; Leuschner, Ivo; Mehdorn, H. Maximilian; Claviez, Alexander

    2014-01-01

    Medulloblastoma, astrocytoma, and ependymoma represent the most common infratentorial tumors in childhood, while Ewing sarcomas in that localization are extremely rare. A large left infratentorial space-occupying lesion was diagnosed in a 12-year-old girl with signs of increased intracranial pressure. Following total tumor resection, histological and molecular examination revealed Ewing sarcoma with rearranged EWSR-1 gene. The patient achieved complete remission following adjuvant chemotherapy and radiotherapy according to Euro-EWING 2008 treatment protocol. Intracranial Ewing sarcoma, although rare, should be an important differential diagnosis of intracranial tumors in childhood which requires aggressive multimodal treatment. PMID:25614743

  20. Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

    ClinicalTrials.gov

    2016-02-19

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

  1. CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas.

    PubMed

    Yoshida, Akihiko; Goto, Keisuke; Kodaira, Makoto; Kobayashi, Eisuke; Kawamoto, Hiroshi; Mori, Taisuke; Yoshimoto, Seiichi; Endo, Otone; Kodama, Narihito; Kushima, Ryoji; Hiraoka, Nobuyoshi; Motoi, Toru; Kawai, Akira

    2016-03-01

    The CIC gene rearrangement exists in a subset of small round cell sarcomas. As the nosologic relationship of these sarcomas to Ewing sarcomas remains undetermined, we examined 20 CIC-rearranged sarcomas to compare their clinicopathologic features with those of Ewing sarcomas. The CIC-rearranged sarcomas were from a group of 14 men and 6 women with a median age of 24.5 years. The primary tumor sites included the limbs, trunk wall, internal trunk, lung, cerebrum, and pharynx. A comparison of the demographic and clinical characteristics of the 20 patients with CIC-rearranged sarcomas with those of the 53 near-consecutive patients with EWSR1-rarranged Ewing sarcomas showed that there were no differences with respect to their ages and sexes. Although none of the CIC-rearranged sarcomas arose in the bone, 40% of the Ewing sarcomas primarily affected the skeleton. The overall survival of patients with Ewing sarcomas was significantly better than that for patients with CIC-rearranged sarcomas. A histologic comparison of the CIC-rearranged sarcomas with 20 EWSR1-rearranged Ewing sarcomas showed significantly higher degrees of lobulation, nuclear pleomorphism, the prominence of the nucleoli, spindle cell elements, and myxoid changes in the CIC-rearranged sarcomas. Distinguishing immunohistochemical features included heterogenous CD99 reactivity, nuclear WT1 expression, and calretinin expression in the CIC-rearranged sarcomas and NKX2.2 expression in the Ewing sarcomas. CIC-rearranged sarcomas are distinct from Ewing sarcomas clinically, morphologically, and immunohistochemically, and they should be considered a separate entity rather than being grouped within the same family of tumors. PMID:26685084

  2. Ewing's sarcoma of the vertebral column

    SciTech Connect

    Pilepich, M.V.; Vietti, T.J.; Nesbit, M.E.; Tefft, M.; Kissane, J.; Burgert, O.; Pritchard, D.; Gehan, E.A.

    1981-01-01

    Twenty-two patients with vertebral primaries were registered in the Intergroup Ewing's Sarcoma Study between 1973 and 1977. The radiation doses to the primary tumors ranged between 3800 and 6200 rad. All patients received intensive combination chemotherapy. After a followup ranging between 14 and 62 months, 14 patients remained disease-free. All patients with primary tumor of the cervical and dorsal spine remained disease-free. Of eight patients with lesions in the distal spine, (sacrococcygeal region) six developed recurrence, in three a local recurrence was observed despite doses of 6000 rad or higher. Doses of 5000 rad or less (in addition to combination chemotherapy as used in the Intergroup Ewing's Study) appear adequate in controlling the primary tumors of the proximal segments of the spinal column.

  3. Ewings sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors

    PubMed Central

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

    2014-01-01

    Ewings 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 Ewings sarcomaassociated 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 Ewings sarcomalike 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-ETSdependent 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 ?-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewings sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewings sarcoma and provide clues to the histogenesis of Ewings sarcoma in bone. PMID:24911143

  4. Ewing's Sarcoma of Ilium, Presenting as Right Lower Quadrant Pain

    PubMed Central

    Alshaya, Osama Saleh; Abbasher, Munzir Izzeldin; Wani, Mubashir Maqbool

    2015-01-01

    Ewing's sarcoma is a highly malignant tumor of bone and is more common in children in the age group of 10 to 20 years. Sometimes the classic clinical and radiological presentation of Ewing's sarcoma may not be the norm and patient may have an atypical presentation leading to diagnostic confusion. This situation is especially true for Ewing's sarcoma involving iliac bone. We report a case of Ewing's sarcoma involving the right ilium in a patient presenting with right lower quadrant pain and nonspecific radiological changes. To the best of our knowledge, this scenario has not been reported in literature. We recommend early magnetic resonance imaging and computed tomography to diagnose the disease early when there is slightest suspicion of the disease. PMID:26697251

  5. Primary paraesophageal Ewings sarcoma: an uncommon case report and literature review

    PubMed Central

    Tarazona, Noelia; Navarro, Lara; Cejalvo, Juan Miguel; Gambardella, Valentina; Prez-Fidalgo, J Alejandro; Sempere, Alejo; Navarro, Samuel; Cervantes, Andrs

    2015-01-01

    Ewings sarcoma is a rare and highly aggressive cancer most frequently arising in people under 20 years of age. We report an uncommon case of primary paraesophageal Ewings sarcoma in a 25-year-old male harboring the infrequent EWSR1/ERG fusion transcript with multiple splice variants coexisting in the same tumor. The patient was totally refractory to chemotherapy and died 17 months after diagnosis. We underscore the need for better understanding of the molecular pathogenesis of the disease and improved systemic therapy options. PMID:25999740

  6. Atypical Presentation of Ewings Sarcoma with a Single Left Orbital Metastasis

    PubMed Central

    Puglia, Marta; Acquaviva, Alessandra; Ponsiglione, Andrea; Barbuto, Luigi; Di Paolo, Nilde; De Rosa, Dario; Sicuranza, Simonetta; Maurea, Simone; Imbriaco, Massimo

    2015-01-01

    Summary Background We present an uncommon case of Ewings sarcoma in a 16-year-old boy. Case Report This case can be considered unique because of the atypical presentation, normal laboratory tests and absence of the typical symptoms such as pain, masses or swelling, fatigue or weight loss, breathing problems linked to lung metastases or pathologic fractures. The only event that brought the patient to our attention was the sudden onset of left proptosis. Conclusions The final histopathology together with CT and PET-CT findings led to the diagnosis of a multi-metastatic Ewings sarcoma involving the orbit, skeleton, bone marrow and lymph nodes. PMID:26568777

  7. BCOR-CCNB3 (Ewing-like) sarcoma: a clinicopathologic analysis of 10 cases, in comparison with conventional Ewing sarcoma.

    PubMed

    Puls, Florian; Niblett, Angela; Marland, Gillian; Gaston, Czar Louie L; Douis, Hassan; Mangham, D Chas; Sumathi, Vaiyapuri P; Kindblom, Lars-Gunnar

    2014-10-01

    BCOR-CCNB3 fusion transcripts resulting from an X-chromosomal paracentric inversion were recently identified in a series of unclassifiable soft tissue and bone sarcomas with Ewing sarcoma-like morphology. The morphologic and clinical features of these sarcomas are, as yet, not well characterized. Here we describe the clinicopathologic features of 10 cases of BCOR-CCNB3 sarcoma and compare their clinical course with typical Ewing sarcoma. Nine of 10 patients were male, and all were 11 to 18 years of age. Seven tumors were located in the bone and 3 in the deep soft tissues. The histomorphologic spectrum was quite wide, with 7 tumors predominately showing small primitive cell morphology with angulated nuclei simulating so-called atypical Ewing sarcoma and 3 predominately showing spindle cell morphology. Recurrent and metastatic lesions showed increased cellularity and marked pleomorphism. Immunohistochemistry showed expression of CCNB3 (100%), bcl2 (90%), CD99 (60%), and CD117 (60%). Reverse transcription polymerase chain reaction for BCOR-CCNB3 fusion transcripts was positive in all 9 cases, which yielded sufficient extracted RNA. Five- and 10-year survival rates were 75% and 56%, respectively. BCOR-CCNB3 sarcomas located in axial skeleton and soft tissues showed a significantly shorter survival. The Ewing sarcoma overall survival was not statistically different, although there was a trend for longer survival of patients with BCOR-CCNB3 sarcomas in the extremities. In conclusion, this study provides a detailed description of the histologic spectrum, immunohistochemical features, and clinical characteristic of BCOR-CCNB3 sarcoma justifying distinction from Ewing sarcoma with its typical EWS/FUS-ETS translocations. Ideally immunohistochemistry is used in combination with reverse transcription polymerase chain reaction for definitive diagnosis. PMID:24805859

  8. Immunostimulation by OX40 Ligand Transgenic Ewing Sarcoma Cells.

    PubMed

    Reuter, Dajana; Staege, Martin S; Kühnöl, Caspar D; Föll, Jürgen

    2015-01-01

    Interleukin-2 (IL-2) transgenic Ewing sarcoma cells can induce tumor specific T and NK cell responses and reduce tumor growth in vivo and in vitro. Nevertheless, the efficiency of this stimulation is not high enough to inhibit tumor growth completely. In addition to recognition of the cognate antigen, optimal T-cell stimulation requires signals from so-called co-stimulatory molecules. Several members of the tumor necrosis factor superfamily have been identified as co-stimulatory molecules that can augment antitumor immune responses. OX40 (CD134) and OX40 ligand (OX40L = CD252; also known as tumor necrosis factor ligand family member 4) is one example of such receptor/ligand pair with co-stimulatory function. In the present investigation, we generated OX40L transgenic Ewing sarcoma cells and tested their immunostimulatory activity in vitro. OX40L transgenic Ewing sarcoma cells showed preserved expression of Ewing sarcoma-associated (anti)gens including lipase member I, cyclin D1 (CCND1), cytochrome P450 family member 26B1 (CYP26B1), and the Ewing sarcoma breakpoint region 1-friend leukemia virus integration 1 (EWSR1-FLI1) oncogene. OX40L-expressing tumor cells showed a trend for enhanced immune stimulation against Ewing sarcoma cells in combination with IL-2 and stimulation of CD137. Our data suggest that inclusion of the OX40/OX40L pathway of co-stimulation might improve immunotherapy strategies for the treatment of Ewing sarcoma. PMID:26579494

  9. Immunostimulation by OX40 Ligand Transgenic Ewing Sarcoma Cells

    PubMed Central

    Reuter, Dajana; Staege, Martin S.; Kühnöl, Caspar D.; Föll, Jürgen

    2015-01-01

    Interleukin-2 (IL-2) transgenic Ewing sarcoma cells can induce tumor specific T and NK cell responses and reduce tumor growth in vivo and in vitro. Nevertheless, the efficiency of this stimulation is not high enough to inhibit tumor growth completely. In addition to recognition of the cognate antigen, optimal T-cell stimulation requires signals from so-called co-stimulatory molecules. Several members of the tumor necrosis factor superfamily have been identified as co-stimulatory molecules that can augment antitumor immune responses. OX40 (CD134) and OX40 ligand (OX40L = CD252; also known as tumor necrosis factor ligand family member 4) is one example of such receptor/ligand pair with co-stimulatory function. In the present investigation, we generated OX40L transgenic Ewing sarcoma cells and tested their immunostimulatory activity in vitro. OX40L transgenic Ewing sarcoma cells showed preserved expression of Ewing sarcoma-associated (anti)gens including lipase member I, cyclin D1 (CCND1), cytochrome P450 family member 26B1 (CYP26B1), and the Ewing sarcoma breakpoint region 1-friend leukemia virus integration 1 (EWSR1-FLI1) oncogene. OX40L-expressing tumor cells showed a trend for enhanced immune stimulation against Ewing sarcoma cells in combination with IL-2 and stimulation of CD137. Our data suggest that inclusion of the OX40/OX40L pathway of co-stimulation might improve immunotherapy strategies for the treatment of Ewing sarcoma. PMID:26579494

  10. Unusual Presentation of a Primary Ewings Sarcoma of the Spine with Paraplegia: A Case Report

    PubMed Central

    Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-01-01

    Ewings 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 Ewings sarcoma in the spine is very rare. Ewings sarcoma occurring in the spine is divided into two types, Ewings sarcoma of sacral spine which are very aggressive with poor prognosis and Ewings 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 Ewings sarcoma and patient was started on combination chemotherapy and radiotherapy. PMID:25954672

  11. Primary Ewings Sarcoma of the temporal bone in an infant

    PubMed Central

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

    2015-01-01

    Introduction : Ewings sarcoma is the second most common primary malignant tumor of bone found in children after Osteosarcoma. It accounts for 49% of primary malignant bone tumors and it affects bones of the skull or face in only 14% 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 Ewings 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. PMID:25922651

  12. [Treatment of Ewing's sarcoma with special reference to radiotherapy].

    PubMed

    Petschen, I; Minguell, J; Amador, R; Tormo, A

    1981-01-01

    The authors study 31 cases of Ewing's sarcoma. The survival after 5 years in only 25% for the initially localized tumors because lung and bone metastases finally develop in spite of any treatment. Polychemotherapy defers the appearance of metastases and increases the number of survivors. Patients being less than 15 years old offer a worst prognosis. The tumor localization, existence of general symptoms and their duration, and the alterations of the blood picture were not related with significant variations in the evolution of the Ewing's sarcoma in the studied cases. Probably the prophylactic irradiation of the lungs delays the appearance of metastases. PMID:7052567

  13. Ewing Sarcoma of the Kidney: A Rare Entity

    PubMed Central

    Almeida, Maria Fernanda Arruda; Patnana, Madhavi; Korivi, Brinda Rao; Kalhor, Neda; Marcal, Leonardo

    2014-01-01

    Ewing sarcoma and primitive peripheral neuroectodermal tumor (PNET) are high-grade malignant tumors typically found in children and adolescents. These tumors belong to the family of small round cell tumors and are of neuroectodermal origin. Primary Ewing sarcoma of the kidney is rare and because of that is an infrequent differential diagnosis in urologic malignancies. Renal PNET mostly presents with nonspecific symptoms such as hematuria and abdominal pain. The imaging findings are uncharacteristic. The diagnosis is based on the histology, immunohistochemistry, and molecular pathologic findings. Once PNET has been diagnosed, multimodal treatment is indicated. Despite all treatment options, the prognosis of those with metastatic disease is poor. PMID:24523977

  14. Ewings Sarcoma Multifocal Metastases to Temporal and Occipital Bone: A Rare Presentation

    PubMed Central

    Wadhwa, Vikram; Bhargava, Eishaan Kamta; Batra, Vasun; Mandal, Shramana

    2015-01-01

    Ewings sarcoma (ES) is a common malignant bone tumour seen to involve long bones, flat pelvic bones and ribs and vertebrae in majority of cases. Here, we present a rare case of aggressive primary ES of pelvic bones with multifocal metastases to temporal bone and occipital bone. The patient presented with facial palsy and an occipital swelling, and was referred for chemotherapy. PMID:26266142

  15. Ewing sarcoma superimposed on a previous osteochondroma in multiple osteochondromatosis.

    PubMed

    Marrero Barrera, Pablo A; Marrero Ortiz, Pablo V

    2014-04-01

    It has been reported that patients with hereditary multiple exostoses (called multiple osteochondromatosis by the World Health Organization) are at increased risk for malignant transformation of osteochondromas to secondary chondrosarcomas. A review of the literature found 14 cases showing transformation of osteochondromas into osteosarcomas; however, Ewing sarcoma has never been reported superimposed on an osteochondroma. This article presents the case of a boy who underwent biopsy of a previously existent osteochondroma for which the pathology report showed cytologic and immunohistochemical properties consistent with Ewing sarcoma. A 13-year-old boy with hereditary multiple exostoses (multiple osteochondromatosis) presented to an orthopedic clinic because of waxing and waning pain superficial to a previous osteochondroma on the lateral aspect of the right leg, below the knee, of 1 month's duration. On examination, inflammation was noted over a bony mass associated with tenderness to palpation of the affected area. There was no evidence of penetrating injury or trauma, and the patient reported no constitutional symptoms, including fever. Radiographs showed marked osteolysis and signs of periosteal reaction. Magnetic resonance imaging showed evidence of cortical bone erosion and extension of the mass into soft tissue. Malignant transformation was suspected, and the patient underwent biopsy. The pathology findings were consistent with Ewing sarcoma. The highly uncommon presentation of this malignancy must serve as a red flag to other physicians who treat patients with hereditary multiple exostoses. Ewing sarcoma tends to be of higher grade and have a worse prognosis than other malignancies that are more commonly seen in these patients. PMID:24762849

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

    PubMed

    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. PMID:26051470

  17. 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

    ClinicalTrials.gov

    2016-03-15

    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

  18. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Cancer.gov

    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

  19. Assessment of minimal residual disease in ewing sarcoma.

    PubMed

    Wagner, Lars M; Smolarek, Teresa A; Sumegi, Janos; Marmer, Daniel

    2012-01-01

    Advances in molecular pathology now allow for identification of rare tumor cells in cancer patients. Identification of this minimal residual disease is particularly relevant for Ewing sarcoma, given the potential for recurrence even after complete remission is achieved. Using RT-PCR to detect specific tumor-associated fusion transcripts, otherwise occult tumor cells are found in blood or bone marrow in 20-30% of Ewing sarcoma patients, and their presence is associated with inferior outcomes. Although RT-PCR has excellent sensitivity and specificity for identifying tumor cells, technical challenges may limit its widespread applicability. The use of flow cytometry to identify tumor-specific antigens is a recently described method that may circumvent these difficulties. In this manuscript, we compare the advantages and drawbacks of these approaches, present data on a third method using fluorescent in situ hybridization, and discuss issues affecting the further development of these strategies. PMID:22550426

  20. [Severe neuropathy after chemo- and radiotherapy of Ewing sarcoma].

    PubMed

    Lilje, C; Sauter, S; Hinkelbein, W; Korinthenberg, R; Niemeyer, C

    1995-01-01

    A 15 year old patient presenting with a lumbar Ewing's Sarcoma was treated according to the EICESS-92 pilot study (EVAIA branch). Local therapy consisted of definitive irradiation given simultaneously to chemotherapy courses 5 to 7. Close to the end of treatment the patient developed progressive peripheral neurologic deficits. Such combined toxic treatment side effects are unique and unforeseen in the study protocol. PMID:7564152

  1. Whole Abdominal-Pelvic Radiotherapy in the Management of Primary Ewing Sarcoma of the Peritoneal Cavity

    PubMed Central

    Garant, Aurelie; Shakir, Shakir; Brossard, Josee; Garde-Granger, Perrine; Freeman, Carolyn

    2016-01-01

    Ewing sarcoma of the abdomen is a rare entity in pediatric oncology and represents a technical challenge both for surgeons and radiation oncologists. We document the case of a young female patient with primary disseminated, intraperitoneal Ewing sarcoma who after an excellent response to chemotherapy received preoperative whole abdominal-pelvic radiotherapy with good tolerance.

  2. Short-term followup after surgical treatment of Ewings sarcoma

    PubMed Central

    Rastogi, Shishir; Kumar, Ashok; Gupta, Himanshu; Khan, Shah Alam; Bakhshi, Sameer

    2010-01-01

    Background: Results of surgical treatment in Indian patients of Ewings sarcoma managed with multimodality treatment with chemotherapy and/or radiotherapy are insufficient. We report a retrospective evaluation of a series of cases of Ewings sarcoma managed with chemotherapy, surgery with or without radiotherapy. Materials and Methods: 54 patients of biopsy-proven Ewings sarcoma of the bone, except craniofacial and vertebral bones were included. The patients having recurrence or having previous treatment were excluded from the study. Local and systemic extent of the sarcoma was defined, staged, and patients were subjected to the chemotherapy, surgery, and in some cases radiotherapy. Patients were evaluated for results of surgery with respect to complications, recurrence, and metastases at 3, 6, 9, 12, 18 and 24 months of follow-up Results: Average age of patients was 15.6 years (range 7-26 years); average delay in treatment was 4.1 months (1-7 months); follow-up ranged from 2 to 5 years (median 3.1 years); 14 patients (25.9%) had pulmonary metastases at their initial presentation. Twenty-one patients (38.9%) underwent resection and intercalary reconstruction with bone grafting, fixed with locking plates. Allograft was also used in 11 of these. Sixteen patients underwent resection and reconstruction with endoprosthesis, while seven patients (13.0%) underwent resection and arthrodesis. An above-knee amputation was required in 7.4% (four patients). Mesh was used for containing the graft longitudinally in five patients (femoral and tibial intercalary reconstructions) and for soft tissue attachment in two patients (hip and shoulder endoprostheses). Two patients had deep wound infection. One patient presented 1 year later with implant failure. The disease-free survival at 2 years from the time of diagnosis was 57.5% (23 out of 40) for patients without preoperative metastases and 42.9% (6 out of 14) for those with preoperative metastases. Overall, the disease-free survival at 2 years was 53.7% (29 out of 54 patients). Overall survival rate at 2 years was 61.1% (33 out of 54 patients). Conclusion: Results of surgical treatment in this study are comparable with the current literature in spite of involvement of long bony segment and large soft tissue component. Intramedullary fibular autograft with morcellized cancellous autograft and allograft contained longitudinally in a mesh appears to be a good alternative with such large bone tumors. PMID:20924478

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

    PubMed

    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. PMID:26363896

  4. Modeling Ewing sarcoma tumors in vitro with 3D scaffolds.

    PubMed

    Fong, Eliza Li Shan; Lamhamedi-Cherradi, Salah-Eddine; Burdett, Emily; Ramamoorthy, Vandhana; Lazar, Alexander J; Kasper, F Kurtis; Farach-Carson, Mary C; Vishwamitra, Deeksha; Demicco, Elizabeth G; Menegaz, Brian A; Amin, Hesham M; Mikos, Antonios G; Ludwig, Joseph A

    2013-04-16

    The pronounced biological influence of the tumor microenvironment on cancer progression and metastasis has gained increased recognition over the past decade, yet most preclinical antineoplastic drug testing is still reliant on conventional 2D cell culture systems. Although monolayer cultures recapitulate some of the phenotypic traits observed clinically, they are limited in their ability to model the full range of microenvironmental cues, such as ones elicited by 3D cell-cell and cell-extracellular matrix interactions. To address these shortcomings, we established an ex vivo 3D Ewing sarcoma model that closely mimics the morphology, growth kinetics, and protein expression profile of human tumors. We observed that Ewing sarcoma cells cultured in porous 3D electrospun poly(?-caprolactone) scaffolds not only were more resistant to traditional cytotoxic drugs than were cells in 2D monolayer culture but also exhibited remarkable differences in the expression pattern of the insulin-like growth factor-1 receptor/mammalian target of rapamycin pathway. This 3D model of the bone microenvironment may have broad applicability for mechanistic studies of bone sarcomas and exhibits the potential to augment preclinical evaluation of antineoplastic drug candidates for these malignancies. PMID:23576741

  5. Whole-Body Radiation Therapy, Systemic Chemotherapy, and High-Dose Chemotherapy Followed By Stem Cell Rescue in Treating Patients With Poor-Risk Ewing Sarcoma

    ClinicalTrials.gov

    2015-01-07

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

  6. Ewing Sarcoma Protein: A Key Player in Human Cancer

    PubMed Central

    2013-01-01

    The Ewing sarcoma protein (EWS) is a well-known player in cancer biology for the specific translocations occurring in sarcomas. The EWS-FLI1 gene fusion is the prototypical translocation that encodes the aberrant, chimeric transcription factor, which is a landmark of Ewing tumors. In all described Ewing sarcoma oncogenes, the EWS RNA binding domains are completely missing; thus RNA binding properties are not retained in the hybrid proteins. However, it is currently unknown whether the absence of EWS function in RNA metabolism plays a role in oncogenic transformation or if EWS plays a role by itself in cancer development besides its contribution to the translocation. In this regard, recent reports have highlighted an essential role for EWS in the regulation of DNA damage response (DDR), a process that counteracts genome stability and is often deregulated in cancer cells. The first part of this review will describe the structural features of EWS and its multiple roles in the regulation of gene expression, which are exerted by coordinating different steps in the synthesis and processing of pre-mRNAs. The second part will examine the role of EWS in the regulation of DDR- and cancer-related genes, with potential implications in cancer therapies. Finally, recent advances on the involvement of EWS in neuromuscular disorders will be discussed. Collectively, the information reviewed herein highlights the broad role of EWS in bridging different cellular processes and underlines the contribution of EWS to genome stability and proper cell-cycle progression in higher eukaryotic cells. PMID:24082883

  7. Ewing's Sarcoma of the Kidney Complicated by a Wunderlich Syndrome

    PubMed Central

    Manescu, Mihai Razvan; Sahyoun, Achraf; Froment, Nicolas; Crisan, Nicolae; Girot, Vincent

    2015-01-01

    The Wunderlich syndrome found after the rupture of primitive renal Ewing's sarcoma is not a situation that we find often in everyday practice. The clinical findings are not specific, which is why the differential diagnosis must be made with a multitude of benign and malignant renal masses until the correct diagnosis can be made by the pathologist. The CT and MRI images are not characteristic. One treatment option is the multidisciplinary approach; however, the prognosis remains poor for patients with metastatic disease. PMID:25922782

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

    SciTech Connect

    Rombi, Barbara; DeLaney, Thomas F.; MacDonald, Shannon M.; Huang, Mary S.; Ebb, David H.; Liebsch, Norbert J.; Raskin, Kevin A.; Yeap, Beow Y.; Marcus, Karen J.; Tarbell, Nancy J.; Yock, Torunn I.

    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. Antagonism Pattern Detection between MicroRNA and Target Expression in Ewings Sarcoma

    PubMed Central

    Martignetti, Loredana; Laud-Duval, Karine; Tirode, Franck; Pierron, Gaelle; Reynaud, Stphanie; Barillot, Emmanuel; Delattre, Olivier; Zinovyev, Andrei

    2012-01-01

    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 Ewings 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 Ewings sarcoma disease. It can be considered as a valid statistical approach to discover new insights in the miRNA regulatory mechanisms. PMID:22848594

  10. Angiogenesis and Vascular Targeting in Ewing Sarcoma: A Review of Preclinical and Clinical Data

    PubMed Central

    DuBois, Steven G.; Marina, Neyssa; Glade-Bender, Julia

    2009-01-01

    Ewing sarcoma is the second most common type of bone cancer in children and young adults. In recent years, the mechanisms by which these tumors develop and maintain their vascular supply have been elucidated. Additional work has demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of Ewing sarcoma mouse xenografts. Early clinical data suggest that these results may also extend to patients with Ewing sarcoma treated with anti-angiogenic or anti-vascular therapies. This review summarizes the available data supporting this approach. PMID:20029966

  11. Unusual form and location for a tumor: multiosseous Ewing sarcoma in the foot.

    PubMed

    Jamshidi, Khodamorad; Shiradi, Mehdi Ramezan

    2015-01-01

    Ewing sarcoma, as the prototype of a small round blue cell tumor of bone, typically affects adolescents and young adults. The most commonly involved sites include the diaphyses of long bones, ribs, and flat bones, such as the pelvis and scapula. We report a case of multifocal Ewing sarcoma involving multiple bones in the foot. Given the multifocal nature of the disease confined to the foot, the initial impression was that of osteomyelitis. We describe the histologic, radiologic, and diagnostic features of the tumor and outline treatment and prognosis. To our knowledge, this is the first report of multifocal Ewing sarcoma involving multiple bones in the foot. PMID:25566563

  12. Extensive primary Ewings' sarcoma in the greater wing of the sphenoid bone.

    PubMed

    Apostolopoulos, Kostas; Ferekidis, Eleftherios

    2003-01-01

    We describe a rare case of an extensive primary cranial Ewing's sarcoma located in the greater wing of the sphenoid bone with extension to the orbit, the endocranium, the parapharyngeal and infratemporal space. The patient presented with diplopia, anosmia and prolapse of the left eye. He was given chemo- and radiotherapy and was free of symptoms on re-examination 1.5 years later. The prognosis of Ewing's sarcoma in the absence of surgery is uncertain, but prompt treatment appears to have a satisfactory therapeutic outcome. In the future, more cases should be studied in order to investigate the biological behaviour of a primary cranial Ewing's sarcoma. PMID:14564101

  13. Sequencing Overview of Ewing Sarcoma: A Journey across Genomic, Epigenomic and Transcriptomic Landscapes

    PubMed Central

    Sand, Laurens G. L.; Szuhai, Karoly; Hogendoorn, Pancras C. W.

    2015-01-01

    Ewing sarcoma is an aggressive neoplasm occurring predominantly in adolescent Caucasians. At the genome level, a pathognomonic EWSR1-ETS translocation is present. The resulting fusion protein acts as a molecular driver in the tumor development and interferes, amongst others, with endogenous transcription and splicing. The Ewing sarcoma cell shows a poorly differentiated, stem-cell like phenotype. Consequently, the cellular origin of Ewing sarcoma is still a hot discussed topic. To further characterize Ewing sarcoma and to further elucidate the role of EWSR1-ETS fusion protein multiple genome, epigenome and transcriptome level studies were performed. In this review, the data from these studies were combined into a comprehensive overview. Presently, classical morphological predictive markers are used in the clinic and the therapy is dominantly based on systemic chemotherapy in combination with surgical interventions. Using sequencing, novel predictive markers and candidates for immuno- and targeted therapy were identified which were summarized in this review. PMID:26193259

  14. Wunderlich syndrome as the first manifestation of an extraskeletal Ewing sarcoma

    PubMed Central

    Kim, Jong Wook; Chae, Ji Yun; Yoon, Cheol Yong; Oh, Mi Mi; Park, Hong Seok; Moon, Du Geon

    2015-01-01

    We recently encountered an extremely rare case of spontaneous perirenal hemorrhage in a 34-year-old man. He initially had undergone radical nephrectomy owing to suspicion of renal cell carcinoma. The final diagnosis was extraskeletal Ewing sarcoma. PMID:26425232

  15. Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma

    ClinicalTrials.gov

    2016-03-29

    Metastatic Ewing Sarcoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Bone Marrow; Metastatic Malignant Neoplasm in the Lung; Metastatic Peripheral Primitive Neuroectodermal Tumor of Bone; Peripheral Primitive Neuroectodermal Tumor of Soft Tissues

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

    PubMed

    van der Schaft, Daisy W J; Hillen, Femke; Pauwels, Patrick; Kirschmann, Dawn A; Castermans, Karolien; Egbrink, Mirjam G A Oude; Tran, Maxine G B; Sciot, Rafael; Hauben, Esther; Hogendoorn, Pancras C W; Delattre, Olivier; Maxwell, Patrick H; Hendrix, Mary J C; Griffioen, Arjan W

    2005-12-15

    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 sarcoma cells form vessel-like tubes in vitro and express genes associated with vasculogenic mimicry. In tumor models, we show that there is blood flow through the blood lakes, suggesting that these structures in Ewing sarcoma contribute to the circulation. Furthermore, we present evidence that reduced oxygen tension may be instrumental in tube formation by plastic tumor cells. The abundant presence of these vasculogenic structures, in contrast to other tumor types, makes Ewing sarcoma the ideal model system to study these phenomena. The results suggest that optimal tumor treatment may require targeting of these structures in combination with prevention of angiogenesis. PMID:16357161

  17. Conservative Treatment of Ewing's Sarcoma of the Uterus in Young Women

    PubMed Central

    Loverro, Giuseppe; Resta, Leonardo; Di Naro, Edoardo; Caringella, Anna Maria; Mastrolia, Salvatore Andrea; Vicino, Mario; Tartagni, Massimo; Schonauer, Luca Maria

    2015-01-01

    Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiations. ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus published in the literature as far as we know. We describe a case of Ewing sarcoma of the uterus occurring in a 17-year-old woman presenting with a two-month history of pelvic pain. After surgical excision and microscopic, immunohistochemical, and electron microscopy examination, the diagnosis of Ewing sarcoma of the uterus was suggested. This report will discuss the diagnosis and surgical and clinical management of Ewing uterine sarcoma in young women, according to the available literature. In spite of the rarity of ES/PNETs, they should be taken into account in the differential diagnosis of uterine neoplasms in young women. PMID:25960901

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

    SciTech Connect

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

    1985-04-01

    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.

  19. Sequencing Overview of Ewing Sarcoma: A Journey across Genomic, Epigenomic and Transcriptomic Landscapes.

    PubMed

    Sand, Laurens G L; Szuhai, Karoly; Hogendoorn, Pancras C W

    2015-01-01

    Ewing sarcoma is an aggressive neoplasm occurring predominantly in adolescent Caucasians. At the genome level, a pathognomonic EWSR1-ETS translocation is present. The resulting fusion protein acts as a molecular driver in the tumor development and interferes, amongst others, with endogenous transcription and splicing. The Ewing sarcoma cell shows a poorly differentiated, stem-cell like phenotype. Consequently, the cellular origin of Ewing sarcoma is still a hot discussed topic. To further characterize Ewing sarcoma and to further elucidate the role of EWSR1-ETS fusion protein multiple genome, epigenome and transcriptome level studies were performed. In this review, the data from these studies were combined into a comprehensive overview. Presently, classical morphological predictive markers are used in the clinic and the therapy is dominantly based on systemic chemotherapy in combination with surgical interventions. Using sequencing, novel predictive markers and candidates for immuno- and targeted therapy were identified which were summarized in this review. PMID:26193259

  20. 3D Tissue-Engineered Model of Ewing Sarcoma

    PubMed Central

    Lamhamedi-Cherradi, Salah-Eddine; Santoro, Marco; Ramammoorthy, Vandhana; Menegaz, Brian A.; Bartholomeusz, Geoffrey; Iles, Lakesla R.; Amin, Hesham M.; Livingston, Andrew J.; Mikos, Antonios G.; Ludwig, Joseph A.

    2015-01-01

    Despite longstanding reliance upon monolayer culture for studying cancer cells, and numerous advantages from both a practical and experimental standpoint, a growing body of evidence suggests more complex three-dimensional (3D) models are necessary to properly mimic many of the critical hallmarks associated with the oncogenesis, maintenance and spread of Ewing sarcoma (ES), the second most common pediatric bone tumor. And as clinicians increasingly turn to biologically-targeted therapies that exert their effects not only on the tumor cells themselves, but also on the surrounding extracellular matrix, it is especially important that preclinical models evolve in parallel to reliably measure antineoplastic effects and possible mechanisms of de novo and acquired drug resistance. Herein, we highlight a number of innovative methods used to fabricate biomimetic ES tumors, encompassing both the surrounding cellular milieu and extracellular matrix (ECM), and suggest potential applications to advance our understanding of ES biology, preclinical drug testing, and personalized medicine. PMID:25109853

  1. Palliation of recurrent Ewing sarcoma of the pelvis with cryoablation and somatosensory-evoked potentials.

    PubMed

    Lessard, Anne-Marie I; Gilchrist, James; Schaefer, Leah; Dupuy, Damian E

    2009-01-01

    Palliation of recurrent Ewing sarcoma can be difficult to treat due to tumor resistance to chemotherapy and previously received maximum dose radiotherapy. We report the successful use of cryoablation for pain palliation in a patient with recurrent pelvic Ewing sarcoma. Tumor location necessitated use of somatosensory-evoked potentials to prevent nerve damage to the S1 nerve root. Clinical and imaging aspects of the case are discussed. PMID:19125081

  2. Molecular pathogenesis and targeted therapeutics in Ewing sarcoma/primitive neuroectodermal tumours

    PubMed Central

    2012-01-01

    Background Ewing sarcoma/PNET is managed with treatment paradigms involving combinations of chemotherapy, surgery, and sometimes radiation. Although the 5-year survival rate of non-metastatic disease approaches 70%, those cases that are metastatic and those that recur have 5-year survival rates of less than 20%. Molecularly targeted treatments offer the potential to further improve treatment outcomes. Methods A PUBMED search was performed from 1997 to 2011. Published literature that included the topic of the Ewing sarcoma/PNET was also referenced. Results Insulin-like growth factor-1 receptor (IGF-1R) antagonists have demonstrated modest single agent efficacy in phase I/II clinical trials in Ewing sarcoma/PNET, but have a strong preclinical rationale. Based on in vitro and animal data, treatment using antisense RNA and cDNA oligonucleotides directed at silencing the EWS-FLI chimera that occurs in most Ewing sarcoma/PNET may have potential therapeutic importance. However drug delivery and degradation problems may limit this therapeutic approach. Protein-protein interactions can be targeted by inhibition of RNA helicase A, which binds to EWS/FLI as part of the transcriptional complex. Tumour necrosis factor related apoptosis inducing ligand induction using interferon has been used in preclinical models. Interferons may be incorporated into future chemotherapeutic treatment paradigms. Histone deacetylase inhibitors can restore TGF-? receptor II allowing TFF-? signalling, which appears to inhibit growth of Ewing sarcoma/PNET cell lines in vitro. Immunotherapy using allogeneic natural killer cells has activity in Ewing sarcoma/PNET cell lines and xenograft models. Finally, cyclin dependent kinase inhibitors such as flavopiridol may be clinically efficacious in relapsed Ewing sarcoma/PNET. Conclusion Preclinical evidence exists that targeted therapeutics may be efficacious in the ESFT. IGF-1R antagonists have demonstrated efficacy in phase I/II clinical trials, although predicting responses remains a challenge. The future treatment of Ewing sarcoma/PNET is likely to be improved by these scientific advances. PMID:22587874

  3. EWS/FLI1 Target Genes and Therapeutic Opportunities in Ewing Sarcoma.

    PubMed

    Cidre-Aranaz, Florencia; Alonso, Javier

    2015-01-01

    Ewing sarcoma is an aggressive bone malignancy that affect children and young adults. Ewing sarcoma is the second most common primary bone malignancy in pediatric patients. Although significant progress has been made in the treatment of Ewing sarcoma since it was first described in the 1920s, in the last decade survival rates have remained unacceptably invariable, thus pointing to the need for new approaches centered in the molecular basis of the disease. Ewing sarcoma driving mutation, EWS-FLI1, which results from a chromosomal translocation, encodes an aberrant transcription factor. Since its first characterization in 1990s, many molecular targets have been described to be regulated by this chimeric transcription factor. Their contribution to orchestrate Ewing sarcoma phenotype has been reported over the last decades. In this work, we will focus on the description of a selection of EWS/FLI1 targets, their functional role, and their potential clinical relevance. We will also discuss their role in other types of cancer as well as the need for further studies to be performed in order to achieve a broader understanding of their particular contribution to Ewing sarcoma development. PMID:26258070

  4. EWS/FLI1 Target Genes and Therapeutic Opportunities in Ewing Sarcoma

    PubMed Central

    Cidre-Aranaz, Florencia; Alonso, Javier

    2015-01-01

    Ewing sarcoma is an aggressive bone malignancy that affect children and young adults. Ewing sarcoma is the second most common primary bone malignancy in pediatric patients. Although significant progress has been made in the treatment of Ewing sarcoma since it was first described in the 1920s, in the last decade survival rates have remained unacceptably invariable, thus pointing to the need for new approaches centered in the molecular basis of the disease. Ewing sarcoma driving mutation, EWSFLI1, which results from a chromosomal translocation, encodes an aberrant transcription factor. Since its first characterization in 1990s, many molecular targets have been described to be regulated by this chimeric transcription factor. Their contribution to orchestrate Ewing sarcoma phenotype has been reported over the last decades. In this work, we will focus on the description of a selection of EWS/FLI1 targets, their functional role, and their potential clinical relevance. We will also discuss their role in other types of cancer as well as the need for further studies to be performed in order to achieve a broader understanding of their particular contribution to Ewing sarcoma development. PMID:26258070

  5. Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.

    PubMed

    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

    2015-09-20

    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 radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed. PMID:26304893

  6. Evaluation of Polymorphisms in EWSR1 and Risk of Ewing Sarcoma: A Report from the Childhood Cancer Survivor Study

    PubMed Central

    DuBois, Steven G.; Goldsby, Robert; Segal, Mark; Woo, Jonathan; Copren, Kirsten; Kane, John P.; Pullinger, Clive R.; Matthay, Katherine K.; Witte, John; Lessnick, Stephen L.; Robison, Leslie L.; Bhatia, Smita; Strong, Louise C.

    2011-01-01

    Background Ewing sarcoma is a malignant bone tumor characterized by a high frequency of somatic EWSR1 translocations. Ewing sarcoma is less common in people of African or African-American ancestry, suggesting a genetic etiology. Procedure Germline DNA from white patients with Ewing sarcoma (n = 135), white controls with Wilms tumor (n = 200), and African-American controls (n = 285) was genotyped at 21 SNPs in the EWSR1 gene. Intron 7 of EWSR1, the most common site of translocation, was also sequenced in all subjects. Genetic variation between groups was evaluated statistically using exact logistic regression and Fisher exact tests. Results One SNP in EWSR1 (rs2857461) showed a low level of statistical association with the diagnosis of Ewing sarcoma compared to Wilms tumor. The odds ratio for having Ewing sarcoma in people with at least one copy of the minor allele of rs2857461 was 3.57 (95% confidence interval 0.79 21.7; p = 0.07). No other SNPs or variations in intron 7 of EWSR1 were associated with Ewing sarcoma. The median relative difference in minor allele frequencies between white subjects with Ewing sarcoma and African-American controls at the evaluated EWSR1 SNPs was 45%. Conclusions Variations in EWSR1 at known SNPs or across intron 7 are not associated with the diagnosis of Ewing sarcoma. EWSR1 does not appear to be a Ewing sarcoma susceptibility gene. The genetic basis for this disease remains unknown. PMID:21793187

  7. Primary Ewing sarcoma of the kidney: a symptomatic presentation and review of the literature

    PubMed Central

    Hakky, Tariq S.; Gonzalvo, Americo A.; Lockhart, Jorge L.

    2013-01-01

    The objective of this review is to discuss the unique nature of primary renal Ewing sarcoma, including incidence, presentation and management. We also report on a common pattern of presentation, consisting of acute flank pain mimicking a renal stone colic, with or without hydronephrosis, and a renal mass discovered during imaging studies of renal Ewing sarcoma. We present our case of renal Ewing sarcoma along with imaging and pathological analysis. We also performed a retrospective review of all cases of renal Ewing sarcoma using PubMed. A total of 48 cases of renal EWS sarcoma have been reported and analyzed in this review. A mean age of 30.4 years was found along with a 61% male predominance. The mean survival was 26.14 months with a lower median survival in patients with advanced metastatic disease. Primary Ewing sarcoma of the kidney is rare. The diagnosis of primary renal EWS can be difficult and is based on a combination of electron microscopy, immunohistochemistry, chromosomal analysis, fluorescence in situ hybridization (FISH) and light microscopy. PMID:23730330

  8. [Ewing/PNET sarcoma family of tumors: towards a new paradigm?].

    PubMed

    Renard, Caroline; Ranchre-Vince, Dominique

    2015-01-01

    Ewing sarcoma family of tumors are mainly aggressive sarcomas of bone and also arising in soft tissues, which share common features: morphological features of basophilic round cell tumors, immunohistochemical features by expression of membrane CD99 protein, and genetic features with a translocation involving EWS and FLI1 in approximately 90% of cases. The discovery of this translocation has made it possible to unify in a single entity several lesions such as PNET, neuropitheliomas, Askin tumors, Ewing sarcomas Since then, the extensive use of molecular/genetic methods has helped to identify an increasing number of molecular anomalies in unclassified round cell sarcomas, these sarcomas often harboring an atypical morphology and a less frequent CD99 positivity. Besides the rearrangements between the FET family of genes (EWS or FUS) and the wide ETS family of genes (FLI1, ERG, FEV, ETV), new partner genes are gradually identified: cases with EWS-non ETS partners are extremely rare, but there are more important groups which are CIC-DUX4 and BCOR-CCNB3 translocation-positive sarcomas. These findings raise the problem of the nosological borders of the Ewing/PNET entity and its links with new "Ewing-like" groups of tumors, and raise the therapeutic problems. The forward-looking identification of new round cell sarcomas should enable studies of wider series to try to answer these questions. PMID:25534668

  9. An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma.

    PubMed

    Insabato, Luigi; Guadagno, Elia; Natella, Valentina; Somma, Anna; Bihl, Michel; Pizzolorusso, Antonio; Mainenti, Pier Paolo; Apice, Gaetano; Tornillo, Luigi

    2015-09-01

    Very recently a new designation of "Malignant Neuroectodermal Gastrointestinal Tumor" has been proposed for an aggressive form of neuroectodermal tumor with features similar to that of Clear Cell Sarcoma of Soft Tissue, however without a melanocytic differentiation. Also known as "clear cell sarcoma-like tumors of the gastrointestinal tract", these tumors show some features strongly suggesting an origin from a gastrointestinal neuroectodermal precursor cell unable to differentiate along the melanocytic lineage. They occur mainly in young and middle-aged adults, and have a poor prognosis with a high rate of liver and lymphnode metastases. Histologically they are composed of epithelioid or oval-to spindle cells with a sheet-like or nested pattern of growth, strongly positive for neural markers (S-100, SOX10, and vimentin) and negative for the melanocytic ones. EWSR1 gene rearrangements including EWSR1-ATF1 or EWSR1-CREB1 GENE fusions are typically assessed in these tumors. Here we report a case of malignant neuroectodermal gastrointestinal tumor which immunophenotypically unusually expressed FLI-1, occurring in a 29-year-old man with a previous medical history of Ewing sarcoma. We finally suggest that this case might be a further evidence of a link between these two entities. PMID:26163185

  10. A monoclonal antibody specifically reactive with Ewing's sarcoma.

    PubMed Central

    Hara, S.; Ishii, E.; Tanaka, S.; Yokoyama, J.; Katsumata, K.; Fujimoto, J.; Hata, J.

    1989-01-01

    We have developed a mouse monoclonal antibody 5C11 (IgG2a) against cell surface antigen of Ewing's sarcoma (ES). 5C11 specifically reacted with ESs but not with other small round cell tumours in childhood, i.e. neuroblastomas, primitive neuroectodermal tumours (PNETs), rhabdomyosarcomas and malignant lymphomas. 5C11 did not react with any other tumours in children except for hepatoblastomas. No reactivity has been identified in normal tissues with the exception of fetal hepatocytes. Immunoelectron microscopically, 5C11 reactive antigen was located on cell membrane of ES cells. Biochemically, 5C11 immunoprecipitated a cell surface protein having molecular weight of 81,000 Da. 5C11 is the first antibody which can clearly distinguish ES from neurogenic tumours, especially from PNETs which were recently reported to have common features to ESs regarding chromosal abnormality and proto-oncogene expression but show evident differentiation into neurogenic direction. The results strongly indicate the usefulness of 5C11 not only for diagnostic purpose when no specific marker is available but also for studying the histogenesis of ES. In addition, no reactivity in normal tissue implies its potential application as a therapeutic reagent when the management of ES patients is still a great problem in clinical field. Images Figure 1 Figure 2 Figure 4 PMID:2605097

  11. ERBB4 confers metastatic capacity in Ewing sarcoma

    PubMed Central

    Mendoza-Naranjo, Ariadna; El-Naggar, Amal; Wai, Daniel H; Mistry, Priti; Lazic, Nikola; Ayala, Fernanda Rocha Rojas; da Cunha, Isabela Werneck; Rodriguez-Viciana, Pablo; Cheng, Hongwei; Tavares Guerreiro Fregnani, Jose H; Reynolds, Patrick; Arceci, Robert J; Nicholson, Andrew; Triche, Timothy J; Soares, Fernando A; Flanagan, Adrienne M; Wang, Yuzhuo Z; Strauss, Sandra J; Sorensen, Poul H

    2013-01-01

    Metastatic spread is the single-most powerful predictor of poor outcome in Ewing sarcoma (ES). Therefore targeting pathways that drive metastasis has tremendous potential to reduce the burden of disease in ES. We previously showed that activation of the ERBB4 tyrosine kinase suppresses anoikis, or detachment-induced cell death, and induces chemoresistance in ES cell lines in vitro. We now show that ERBB4 is transcriptionally overexpressed in ES cell lines derived from chemoresistant or metastatic ES tumours. ERBB4 activates the PI3K-Akt cascade and focal adhesion kinase (FAK), and both pathways contribute to ERBB4-mediated activation of the Rac1 GTPase in vitro and in vivo. ERBB4 augments tumour invasion and metastasis in vivo, and these effects are blocked by ERBB4 knockdown. ERBB4 expression correlates significantly with reduced disease-free survival, and increased expression is observed in metastatic compared to primary patient-matched ES biopsies. Our findings identify a novel ERBB4-PI3K-Akt-FAK-Rac1 pathway associated with aggressive disease in ES. These results predict that therapeutic targeting of ERBB4, alone or in combination with cytotoxic agents, may suppress the metastatic phenotype in ES. PMID:23681745

  12. Targeting the DNA Repair Pathway in Ewing Sarcoma

    PubMed Central

    Stewart, Elizabeth; Goshorn, Ross; Bradley, Cori; Griffiths, Lyra M.; Benavente, Claudia; Twarog, Nathaniel R.; Miller, Gregory M.; Caufield, William; Freeman, Burgess B.; Bahrami, Armita; Pappo, Alberto; Wu, Jianrong; Loh, Amos; Karlstrm, sa; Calabrese, Chris; Gordon, Brittney; Tsurkan, Lyudmila; Hatfield, M. Jason; Potter, Philip M.; Snyder, Scott; Thiagarajan, Suresh; Shirinifard, Abbas; Sablauer, Andras; Shelat, Anang A.; Dyer, Michael A.

    2015-01-01

    Ewing sarcoma (EWS) is a tumor of the bone and soft-tissue that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive, but patients with metastatic or recurrent disease have a poor outcome. We found that EWS cell lines are defective in DNA break repair and are sensitive to PARP inhibitors (PARPis). PARPi-induced cytotoxicity in EWS cells was 10- to 1,000-fold higher after administration of the DNA-damaging agents irinotecan or temozolomide. We developed an orthotopic EWS mouse model and performed pharmacokinetic and pharmacodynamic studies using 3 different PARPis that are in clinical development for pediatric cancer. Irinotecan administered on a low-dose, protracted schedule previously optimized for pediatric patients was an effective DNA-damaging agent when combined with PARPis; it was also better tolerated than combinations with temozolomide. Combining PARPis with irinotecan and temozolomide gave complete and durable responses in more than 80% of the mice. PMID:25437539

  13. Macrophage Infiltration Predicts a Poor Prognosis for Human Ewing Sarcoma

    PubMed Central

    Fujiwara, Toshifumi; Fukushi, Jun-ichi; Yamamoto, Shunsaku; Matsumoto, Yoshihiro; Setsu, Nokitaka; Oda, Yoshinao; Yamada, Hisakata; Okada, Seiji; Watari, Kosuke; Ono, Mayumi; Kuwano, Michihiko; Kamura, Satoshi; Iida, Keiichiro; Okada, Yuko; Koga, Mihoko; Iwamoto, Yukihide

    2011-01-01

    Ewing sarcomaprimitive neuroectodermal tumor (EWS) is associated with the most unfavorable prognosis of all primary musculoskeletal tumors. The objective of the present study was to investigate whether tumor-associated macrophages (TAMs) affect the development of EWS. TAMs were isolated from mouse xenografts using CD11b magnetic beads and examined for their cytokine expression and osteoclastic differentiation. To evaluate the role of TAMs in xenograft formation, liposome-encapsulated clodronate was used to deplete TAMs in mice. Macrophage infiltration and tumor microvascular density were histologically evaluated in 41 patients with EWS, and association with prognosis was examined using Kaplan-Meier survival analysis. In mouse EWS xenografts, TAMs expressed higher concentrations of cytokines including interleukin-6, keratinocyte-derived chemokine, and monocyte chemotactic protein-1. TAMs were more capable than normal monocytes of differentiating into tartrate-resistant acid phosphatasepositive giant cells. Depleting macrophages using liposome-encapsulated clodronate significantly inhibited development of EWS xenografts. In human EWS samples, higher levels of CD68-positive macrophages were associated with poorer overall survival. In addition, enhanced vascularity, increase in the amount of C-reactive protein, and higher white blood cell counts were also associated with poor prognosis and macrophage infiltration. TAMs seem to enhance the progression of EWS by stimulating both angiogenesis and osteoclastogenesis. Further investigation of the behavior of TAMs may lead to development of biologically targeted therapies for EWS. PMID:21771572

  14. Fine-needle aspiration cytology of extraskeletal Ewing's sarcoma.

    PubMed

    Bakhos, R; Andrey, J; Bhoopalam, N; Jensen, J; Reyes, C V

    1998-02-01

    Extraskeletal Ewing's sarcoma (EES) is a round-cell malignancy that manifests most commonly in the paravertebral and intercostal regions. It occurs predominantly in adolescents and young adults, between the ages of 10 and 30 yr, and follows an aggressive course with a high recurrence rate. Distant metastasis is also common. The tumor is often confused with other round, small-cell neoplasms, including primitive neuroectodermal tumor, neuroblastoma, embryonal rhabdomyosarcoma, and lymphoma. This report pertains to a fine-needle aspiration cytologic diagnosis of EES, supported by clinicopathologic and fine structural correlations in a 56-yr-old man who presented with a rapidly growing, massive, right groin mass. The smears showed a diffuse cellular population of malignant round cells composed of two types: one group of larger cell exhibiting a thin-rim, pale cytoplasm, less hyperchromatic nuclei, nucleoli, and diffusely dispersed chromatinic nuclear details; and the second group of smaller and darker cells with highly hyperchromatic and almost smudged nuclei. These are chief cells and dark cells, respectively. Special studies revealed significant intracytoplasmic glycogen and positive vimentin and HBA-71 immunostaining. Cytogenetic findings of chromosomal 11;22 translocation is also supportive of the diagnosis of EES. PMID:9484643

  15. Oncostatin M is a growth factor for Ewing sarcoma.

    PubMed

    David, Emmanuelle; Tirode, Franck; Baud'huin, Marc; Guihard, Pierre; Laud, Karine; Delattre, Olivier; Heymann, Marie F; Heymann, Dominique; Redini, Franoise; Blanchard, Frdric

    2012-11-01

    Primary bone tumors, osteosarcomas and chondrosarcomas, derive from mesenchymal stem cells committed into osteoblasts and chondrocytes; in Ewing sarcomas (ESs), the oncogenic fusion protein EWS-FLI1 prevents mesenchymal differentiation and induces neuroectodermic features. Oncostatin M (OSM) is a cytokine from the IL-6 family that modulates proliferation and differentiation in numerous cells. The basis for inhibition versus induction of proliferation by this cytokine is obscure, although MYC was described as a potent molecular switch in OSM signaling. We show herein that, in contrast to osteosarcomas and chondrosarcomas, for which OSM was cytostatic, OSM induced proliferation of ES cell lines. Knockdown experiments demonstrated that growth induction by OSM depends on both types I [leukemia inhibitory factor receptor (LIFR)] and II [OSM receptor (OSMR)] receptors, high STAT3 activation, and induction of MYC to a high expression level. Indeed, ES cell lines, mice xenografts, and patient biopsy specimens poorly expressed LIF, precluding LIFR lysosomal degradation and OSMR transcriptional induction, thus leading to a high LIFR/OSMR ratio. Because other neuroectodermic tumors (ie, glioma, medulloblastoma, and neuroblastoma) had a similar expression profile, the main role of EWS-FLI1 could be through maintenance of stemness and neuroectodermic features, characterized by a low LIF, a high LIFR/OSMR ratio, and high MYC expression. Thus, this study on rare bone malignancies gives valuable insights on more common cancer regulatory mechanisms and could provide new therapeutic opportunities. PMID:22982441

  16. Targeting the DNA repair pathway in Ewing sarcoma.

    PubMed

    Stewart, Elizabeth; Goshorn, Ross; Bradley, Cori; Griffiths, Lyra M; Benavente, Claudia; Twarog, Nathaniel R; Miller, Gregory M; Caufield, William; Freeman, Burgess B; Bahrami, Armita; Pappo, Alberto; Wu, Jianrong; Loh, Amos; Karlstrm, sa; Calabrese, Chris; Gordon, Brittney; Tsurkan, Lyudmila; Hatfield, M Jason; Potter, Philip M; Snyder, Scott E; Thiagarajan, Suresh; Shirinifard, Abbas; Sablauer, Andras; Shelat, Anang A; Dyer, Michael A

    2014-11-01

    Ewing sarcoma (EWS) is a tumor of the bone and soft tissue that primarily affects adolescents and young adults. With current therapies, 70% of patients with localized disease survive, but patients with metastatic or recurrent disease have a poor outcome. We found that EWS cell lines are defective in DNA break repair and are sensitive to PARP inhibitors (PARPis). PARPi-induced cytotoxicity in EWS cells was 10- to 1,000-fold higher after administration of the DNA-damaging agents irinotecan or temozolomide. We developed an orthotopic EWS mouse model and performed pharmacokinetic and pharmacodynamic studies using three different PARPis that are in clinical development for pediatric cancer. Irinotecan administered on a low-dose, protracted schedule previously optimized for pediatric patients was an effective DNA-damaging agent when combined with PARPis; it was also better tolerated than combinations with temozolomide. Combining PARPis with irinotecan and temozolomide gave complete and durable responses in more than 80% of the mice. PMID:25437539

  17. Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma.

    PubMed

    Hung, Yin P; Fletcher, Christopher D M; Hornick, Jason L

    2016-04-01

    Ewing sarcoma shows considerable histologic overlap with other round cell tumors. NKX2-2, a homeodomain transcription factor involved in neuroendocrine/glial differentiation and a downstream target of EWSR1-FLI1, has been reported as an immunohistochemical marker for Ewing sarcoma. We assessed the specificity of NKX2-2 for Ewing sarcoma compared with other round cell malignant neoplasms and other soft tissue tumors with EWSR1 translocations. We evaluated whole-tissue sections from 270 cases: 40 Ewing sarcomas (4 with atypical/large cell features), 20 CIC-DUX4 sarcomas, 5 BCOR-CCNB3 sarcomas, 9 unclassified round cell sarcomas, 10 poorly differentiated synovial sarcomas, 10 lymphoblastic lymphomas, 10 alveolar rhabdomyosarcomas, 10 embryonal rhabdomyosarcomas, 10 Merkel cell carcinomas, 10 small cell carcinomas, 20 melanomas, 5 NUT midline carcinomas, 10 Wilms tumors, 10 neuroblastomas, 10 olfactory neuroblastomas, 12 mesenchymal chondrosarcomas, 10 angiomatoid fibrous histiocytomas, 10 clear cell sarcomas, 5 gastrointestinal clear cell sarcoma-like tumors, 5 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas, 10 soft tissue and cutaneous myoepitheliomas, and 19 myoepithelial carcinomas. NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells. NKX2-2 was positive in 37/40 (93%) Ewing sarcomas, including all atypical Ewing sarcomas and cases with known EWSR1-FLI1 or EWSR1-ERG fusion; 85% of Ewing sarcomas showed diffuse (>50%) staining. NKX2-2 was positive in 9 (75%) mesenchymal chondrosarcomas, 8 (80%) olfactory neuroblastomas, 1 CIC-DUX4 sarcoma, 1 poorly differentiated synovial sarcoma, 1 neuroblastoma, 2 unclassified round cell sarcomas, and 3 small cell carcinomas; all other EWSR1-associated tumors were negative for NKX2-2, apart from 1 desmoplastic small round cell tumor, 1 myoepithelioma, and 1 myoepithelial carcinoma. In summary, NKX2-2 is a sensitive but imperfectly specific marker for Ewing sarcoma. Nonetheless, NKX2-2 may be helpful to distinguish Ewing sarcoma from some histologic mimics including CIC-DUX4 and BCOR-CCNB3 sarcomas. Most other EWSR1-associated soft tissue tumors are negative for NKX2-2. PMID:26847175

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

    PubMed Central

    Sanchez-Sanchez, Ana M.; Antolin, Isaac; Puente-Moncada, Noelia; Suarez, Santos; Gomez-Lobo, Marina; Rodriguez, Carmen; Martin, Vanesa

    2015-01-01

    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-1? 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. PMID:26252771

  19. XI-006 induces potent p53-independent apoptosis in Ewing sarcoma

    PubMed Central

    Pishas, Kathleen I.; Adwal, Alaknanda; Neuhaus, Susan J.; Clayer, Mark T.; Farshid, Gelareh; Staudacher, Alexander H.; Callen, David F.

    2015-01-01

    There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of MDM4 is frequently observed in sarcomas, this study examined the therapeutic potential of XI-006 for the treatment of Ewing and osteosarcoma. XI-006 treatment of Ewing and osteosarcoma cell lines (n?=?11) resulted in rapid and potent apoptosis at low micro-molar concentrations specifically in Ewing sarcoma cell lines (48?hr IC50 0.0991.61??M). Unexpectedly, apoptotic response was not dependent on MDM4 mRNA/protein levels or TP53 status. Alkaline/neutral comet and ?H2AX immunofluorescence assays revealed that the cytotoxic effects of XI-006 could not be attributed to the induction of DNA damage. RNA expression analysis revealed that the mechanism of action of XI-006 could be accredited to the inhibition of cell division and cycle regulators such as KIF20A and GPSM2. Finally, potent synergy between XI-006 and olaparib (PARP inhibitor) were observed due to the down-regulation of Mre11. Our findings suggest that XI-006 represents a novel therapeutic intervention for the treatment of Ewing sarcoma. PMID:26095524

  20. Growth-Promoting Role of the miR-106a∼363 Cluster in Ewing Sarcoma

    PubMed Central

    Dylla, Layne; Jedlicka, Paul

    2013-01-01

    MicroRNAs (miRs) have been identified as potent regulators of both normal development and the hallmarks of cancer. Targeting of microRNAs has been shown to have preclinical promise, and select miR-based therapies are now in clinical trials. Ewing Sarcoma is a biologically aggressive pediatric cancer with little change in clinical outcomes despite improved chemotherapeutic regimens. There is a substantial need for new therapies to improve Ewing Sarcoma outcomes and to prevent chemotherapy-related secondary sequelae. Most Ewing Sarcoma tumors are driven by the EWS/Fli-1 fusion oncoprotein, acting as a gain-of-function transcription factor causing dysregulation of a variety of targets, including microRNAs. Our previous studies, and those of others, have identified upregulation of miRs belonging to the related miR-17∼92a, miR-106b∼25, and miR-106a∼363 clusters in Ewing Sarcoma. However, the functional consequences of this have not been characterized, nor has miR blockade been explored as an anti-cancer strategy in Ewing Sarcoma. To simulate a potential therapeutic approach, we examined the effects of blockade of these clusters, and their component miRs. Using colony formation as a read-out, we find that blockade of selected individual cluster component miRs, using specific inhibitors, has little or no effect. Combinatorial inhibition using miR “sponge” methodology, on the other hand, is inhibitory to colony formation, with blockade of whole clusters generally more effective than blockade of miR families. We show that a miR-blocking sponge directed against the poorly characterized miR-106a∼363 cluster is a particularly potent inhibitor of clonogenic growth in a subset of Ewing Sarcoma cell lines. We further identify upregulation of miR-15a as a downstream mechanism contributing to the miR-106a∼363 sponge growth-inhibitory effect. Taken together, our studies provide support for a pro-oncogenic role of the miR-106a∼363 cluster in Ewing Sarcoma, and identify miR-106a∼363 blockade, as well as miR-15a replacement, as possible strategies for inhibition of Ewing Sarcoma growth. PMID:23638178

  1. The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing Sarcoma.

    PubMed

    Parrish, J K; Sechler, M; Winn, R A; Jedlicka, P

    2015-01-01

    Ewing Sarcoma is a biologically aggressive bone and soft tissue malignancy affecting children and young adults. Ewing Sarcoma pathogenesis is driven by EWS/Ets fusion oncoproteins, of which EWS/Fli1 is the most common. We have previously shown that microRNAs (miRs) regulated by EWS/Fli1 contribute to the pro-oncogenic program in Ewing Sarcoma. Here we show that miR-22, an EWS/Fli1-repressed miR, is inhibitory to Ewing Sarcoma clonogenic and anchorage-independent cell growth, even at modest overexpression levels. Our studies further identify the H3K9me1/2 histone demethylase KDM3A (JMJD1A/JHDM2A) as a new miR-22-regulated gene. We show that KDM3A is overexpressed in Ewing Sarcoma, and that its depletion inhibits clonogenic and anchorage-independent growth in multiple patient-derived cell lines, and tumorigenesis in a xenograft model. KDM3A depletion further results in augmentation of the levels of the repressive H3K9me2 histone mark, and downregulation of pro-oncogenic factors in Ewing Sarcoma. Together, our studies identify the histone demethylase KDM3A as a new, miR-regulated, tumor promoter in Ewing Sarcoma. PMID:24362521

  2. EWS/FLI utilizes NKX2-2 to repress mesenchymal features of Ewing sarcoma

    PubMed Central

    Fadul, John; Bell, Russell; Hoffman, Laura M.; Beckerle, Mary C.; Engel, Michael E.; Lessnick, Stephen L.

    2015-01-01

    In Ewing sarcoma, NKX2-2 is a critical activated target of the oncogenic transcription factor EWS/FLI that is required for transformation. However, its biological function in this malignancy is unknown. Here we provide evidence that NKX2-2 mediates the EWS/FLI-controlled block of mesenchymal features. Transcriptome-wide RNA sequencing revealed that NKX2-2 represses cell adhesion and extracellular matrix organization genes. NKX2-2-depleted cells form more focal adhesions and organized actin stress fibers, and spread over a wider area—hallmarks of mesenchymally derived cells. Furthermore, NKX2-2 represses the actin-stabilizing protein zyxin, suggesting that these morphological changes are attributable to zyxin de-repression. In addition, NKX2-2-knockdown cells display marked increases in migration and substrate adhesion. However, only part of the EWS/FLI phenotype is NKX2-2-dependent; consequently, NKX2-2 is insufficient to rescue EWS/FLI repression of mesenchymalization. Strikingly, we found that EWS/FLI-and NKX22-repressed genes are activated by ZEB2, which was previously shown to block Ewing sarcoma epithelialization. Together, these data support an emerging theme wherein Ewing sarcoma cells highly express transcription factors that maintain an undifferentiated state. Importantly, co-opting epithelial and mesenchymal traits by Ewing sarcoma cells may explain how the primary tumor grows rapidly while also “passively” metastasizing, without the need for transitions toward differentiated states, as in carcinomas. PMID:26000096

  3. Pure Erythroid Leukemia Mimicking Ewing Sarcoma/Primitive Neuroectodermal Tumor in an Infant.

    PubMed

    Lapadat, Razvan; Tower, Richard L; Tam, Wayne; Orazi, Attilio; Gheorghe, Gabriela

    2016-05-01

    Pure erythroid leukemia (PEL) is a rare type of acute myeloid leukemia (AML) with a very aggressive clinical course. Presentation as a myeloid/erythroid sarcoma is exceedingly rare. We describe an infantile PEL presenting as a multifocal myeloid sarcoma, clinically and pathologically mimicking Ewing sarcoma/PNET family of tumors. The patient died 8 weeks after the initial presentation due to widespread disease. Our case shows that PEL needs to be considered in the differential diagnosis of small round blue cell tumors in infancy. A meticulous workup including immunohistochemistry, flow cytometry, molecular, and cytogenetic studies was required to reach the diagnosis. PMID:26773805

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

    PubMed Central

    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. PMID:26779435

  5. Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone

    PubMed Central

    Park, Hyewon; Turkalo, Timothy K; Nelson, Kayla; Folmsbee, Stephen Sai; Robb, Caroline; Roper, Brittany; Azuma, Mizuki

    2014-01-01

    Ewing sarcoma is a malignant bone cancer that primarily occurs in children and adolescents. Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene. Previously, we demonstrated that an interaction between EWS/FLI1 and wild-type EWS led to the inhibition of EWS activity and mitotic dysfunction. Although defective mitosis is considered to be a critical step in cancer initiation, it is unknown how interference with EWS contributes to Ewing sarcoma formation. Here, we demonstrate that EWS/FLI1- and EWS-knockdown cells display a high incidence of defects in the midzone, a midline structure located between segregating chromatids during anaphase. Defects in the midzone can lead to the failure of cytokinesis and can result in the induction of aneuploidy. The similarity among the phenotypes of EWS/FLI1- and EWS siRNA-transfected HeLa cells points to the inhibition of EWS as the key mechanism for the induction of midzone defects. Supporting this observation, the ectopic expression of EWS rescues the high incidence of midzone defects observed in Ewing sarcoma A673 cells. We discovered that EWS interacts with Aurora B kinase, and that EWS is also required for recruiting Aurora B to the midzone. A domain analysis revealed that the R565 in the RGG3 domain of EWS is essential for both Aurora B interaction and the recruitment of Aurora B to the midzone. Here, we propose that the impairment of EWS-dependent midzone formation via the recruitment of Aurora B is a potential mechanism of Ewing sarcoma development. PMID:25483190

  6. Differentially Expressed miRNAs in Ewing Sarcoma Compared to Mesenchymal Stem Cells: Low miR-31 Expression with Effects on Proliferation and Invasion

    PubMed Central

    Karnuth, Bianca; Dedy, Nicolas; Spieker, Tilmann; Lawlor, Elizabeth R.; Gattenlhner, Stefan; Ranft, Andreas; Dirksen, Uta; Jrgens, Heribert; Bruninger, Andreas

    2014-01-01

    Ewing sarcoma, the second most common bone tumor in children and young adults, is an aggressive malignancy with a strong potential to metastasize. Ewing sarcoma is characterised by translocations encoding fusion transcription factors with an EWSR1 transactivation domain fused to an ETS family DNA binding domain. microRNAs are post-transcriptional regulators of gene expression and aberrantly expressed microRNAs have been identified as tumor suppressors or oncogenes in most cancer types. To identify potential oncogenic and tumor suppressor microRNAs in Ewing sarcoma, we determined and compared the expression of 377 microRNAs in 40 Ewing sarcoma biopsies, 6 Ewing sarcoma cell lines and mesenchymal stem cells, the putative cellular origin of Ewing sarcoma, from 6 healthy donors. Of the 35 differentially expressed microRNAs identified (fold change >4 and q<0.05), 19 were higher and 16 lower expressed in Ewing sarcoma. In comparisons between Ewing sarcoma samples with EWS-FLI or EWS-ERG translocations, with differing dissemination characteristics and of primary samples and metastases no significantly differential expressed microRNAs were detected using various stringency criteria. For miR-31, the microRNA with lowest expression in comparison to mesenchymal stem cells, functional analyses were performed to determine its potential as a tumor suppressor in Ewing sarcoma. Two of four miR-31 transfected Ewing sarcoma cell lines showed a significantly reduced proliferation (19% and 33% reduction) due to increased apoptosis in one and increased length of G1-phase in the other cell line. All three tested miR-31 transfected Ewing sarcoma cell lines showed significantly reduced invasiveness (56% to 71% reduction). In summary, we identified 35 microRNAs differentially expressed in Ewing sarcoma and demonstrate that miR-31 affects proliferation and invasion of Ewing sarcoma cell lines in ex vivo assays. PMID:24667836

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

    PubMed Central

    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

  8. The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation

    PubMed Central

    Hesketh, Anthony J.; Maloney, Caroline; Behr, Christopher A.; Edelman, Morris C.; Glick, Richard D.; Al-Abed, Yousef; Symons, Marc; Soffer, Samuel Z.; Steinberg, Bettie M.

    2015-01-01

    Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma. PMID:26709919

  9. Incidence and management of secondary malignancies in patients with retinoblastoma and Ewing's sarcoma

    SciTech Connect

    Smith, L.M.; Donaldson, S.S. )

    1991-05-01

    Childhood cancer survivors at highest risk of developing a secondary malignancy are those with hereditary retinoblastoma. The majority of such secondary cancers will be sarcomas, most commonly of bone. One-third of these occur outside a typical radiation field, commonly in an extremity. Bone sarcoma is also the most commonly reported secondary cancer to develop among survivors of Ewing's sarcoma. In this group, radiation doses greater than 60 Gy as well as alkylating agent chemotherapy have been identified as contributors to the increased risk. The prognosis for patients with a secondary sarcoma has been poor, with few cures reported to date. However, an aggressive, combined modality approach, including radical resection, postoperative radiation, and adjuvant chemotherapy, may improve the survival rate.

  10. Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma

    PubMed Central

    Crompton, Brian; Cowley, Glenn; Vazquez, Francisca; Weir, Barbara A.; Tsherniak, Aviad; Parasuraman, Sudha; Kim, Sunkyu; Alexe, Gabriela; Stegmaier, Kimberly

    2015-01-01

    Ewing sarcoma is an aggressive bone and soft tissue tumor in children and adolescents, with treatment remaining a clinical challenge. This disease is mediated by somatic chromosomal translocations of the EWS gene and a gene encoding an ETS transcription factor, most commonly, FLI1. While direct targeting of aberrant transcription factors remains a pharmacological challenge, identification of dependencies incurred by EWS/FLI1 expression would offer a new therapeutic avenue. We used a combination of super-enhancer profiling, near-whole genome shRNA-based and small-molecule screening to identify cyclin D1 and CDK4 as Ewing sarcoma-selective dependencies. We revealed that super-enhancers mark Ewing sarcoma specific expression signatures and EWS/FLI1 target genes in human Ewing sarcoma cell lines. Particularly, a super-enhancer regulates cyclin D1 and promotes its expression in Ewing sarcoma. We demonstrated that Ewing sarcoma cells require CDK4 and cyclin D1 for survival and anchorage-independent growth. Additionally, pharmacologic inhibition of CDK4 with selective CDK4/6 inhibitors led to cytostasis and cell death of Ewing sarcoma cell lines in vitro and growth delay in an in vivo Ewing sarcoma xenograft model. These results demonstrated a dependency in Ewing sarcoma on CDK4 and cyclin D1 and support exploration of CDK4/6 inhibitors as a therapeutic approach for patients with this disease. PMID:26337082

  11. Extraosseous Ewing sarcoma in the mesentery: the first report of cases in children.

    PubMed

    Shibuya, Soichi; Takamizawa, Shigeru; Hatata, Tomoko; Komori, Kazutoshi; Ogiso, Yoshifumi; Yoshizawa, Katsumi; Yoshizawa, Kazuki

    2015-10-01

    Extraosseous ewing sarcoma (EES) is a rare soft-tissue tumor usually found in the extremities or paraspinal region. We describe the case of a 4-year-old boy with a large cystic mass in the mesentery diagnosed as mesenteric lymphangioma preoperatively and as EES after partial resection and histopathological examination. EES in the mesentery is extremely rare, with only 2 reports described in the English literature. This represents the first report of EES in a child. PMID:26280743

  12. Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma.

    PubMed

    Postel-Vinay, Sophie; Vron, Amlie S; Tirode, Franck; Pierron, Gaelle; Reynaud, Stphanie; Kovar, Heinrich; Oberlin, Odile; Lapouble, Eve; Ballet, Stelly; Lucchesi, Carlo; Kontny, Udo; Gonzlez-Neira, Anna; Picci, Piero; Alonso, Javier; Patino-Garcia, Ana; de Paillerets, Brigitte Bressac; Laud, Karine; Dina, Christian; Froguel, Philippe; Clavel-Chapelon, Franoise; Doz, Francois; Michon, Jean; Chanock, Stephen J; Thomas, Gilles; Cox, David G; Delattre, Olivier

    2012-03-01

    Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2. PMID:22327514

  13. EWS and RE1-Silencing Transcription Factor Inhibit Neuronal Phenotype Development and Oncogenic Transformation in Ewing Sarcoma

    PubMed Central

    Sankar, Savita; Gomez, Nicholas C.; Bell, Russell; Patel, Mukund; Davis, Ian J.; Lessnick, Stephen L.

    2013-01-01

    The gene encoding EWS (EWSR1) is involved in various chromosomal translocations that cause the production of oncoproteins responsible for multiple cancers including Ewing sarcoma, myxoid liposarcoma, soft tissue clear cell sarcoma, and desmoplastic small round cell sarcoma. It is well known that EWS fuses to FLI to create EWS/FLI, which is the abnormal transcription factor that drives tumor development in Ewing sarcoma. However, the role of wild-type EWS in Ewing sarcoma pathogenesis remains unclear. In the current study, we identified EWS-regulated genes and cellular processes through RNA interference combined with RNA sequencing and functional annotation analyses. Interestingly, we found that EWS and EWS/FLI co-regulate a significant cluster of genes, indicating an interplay between the 2 proteins in regulating cellular functions. We found that among the EWSdown-regulated genes are a subset of neuronal genes that contain binding sites for the RE1-silencing transcription factor (REST or neuron-restrictive silencer factor [NRSF]), neuron-restrictive silencer element (NRSE), suggesting a cooperative interaction between REST and EWS in gene regulation. Co-immunoprecipitation analysis demonstrated that EWS interacts directly with REST. Genome-wide binding analysis showed that EWS binds chromatin at or near NRSE. Furthermore, functional studies revealed that both EWS and REST inhibit neuronal phenotype development and oncogenic transformation in Ewing sarcoma cells. Our data implicate an important role of EWS in the development of Ewing sarcoma phenotype and highlight a potential value in modulating EWS function in the treatment of Ewing sarcoma and other EWS translocationbased cancers. PMID:24069508

  14. Ewing's sarcoma as second malignancy following a short latency in unilateral retinoblastoma.

    PubMed

    Tahasildar, Naveen; Goni, Vijay; Bhagwat, Kishan; Tripathy, Sujit Kumar; Panda, Bijnya Birajita

    2011-09-01

    Second malignancies, mostly in the form of bone sarcomas, are known to occur in hereditary retinoblastomas, which usually present with bilateral disease. Only 2 cases of Ewing's sarcoma have been reported in the literature following sporadic unilateral retinoblastoma. A 5-year-old boy presented to our hospital with Ewing's sarcoma of the right humerus (proven by biopsy and immunohistochemistry) following successful treatment of retinoblastoma of the left eye with enucleation and chemotherapy 2 years previously. He was treated with 2 cycles of chemotherapy followed by radiation therapy. At 15 months follow-up, the tumor had reduced in size and the child had a good functional outcome. The cumulative risk of second malignancies in retinoblastoma survivors is 32%. Ninety-eight percent of second malignancies occur in patients with bilateral retinoblastoma. Germ line mutations have been considered in sporadic tumors occurring bilaterally and multifocal unilateral sporadic tumors. Bone and soft tissue sarcomas are the most common second malignancies. Radiation therapy increases the risk of developing a second malignancy in the irradiated field. Unilateral retinoblastomas, which comprise the majority of retinoblastomas, are not immune from the development of second malignancies. Close follow-up of all retinoblastomas--even in the early period--can improve the outcome by facilitating the early detection and aggressive treatment of second malignancies. PMID:21826516

  15. High ALDH Activity Identifies Chemotherapy-Resistant Ewing's Sarcoma Stem Cells That Retain Sensitivity to EWS-FLI1 Inhibition

    PubMed Central

    Gul, Naheed; Katuri, Varalakshmi; O'Neill, Alison; Kong, Yali; Brown, Milton L.; Toretsky, Jeffrey A.; Loeb, David M.

    2010-01-01

    Background Cancer stem cells are a chemotherapy-resistant population capable of self-renewal and of regenerating the bulk tumor, thereby causing relapse and patient death. Ewing's sarcoma, the second most common form of bone tumor in adolescents and young adults, follows a clinical pattern consistent with the Cancer Stem Cell model remission is easily achieved, even for patients with metastatic disease, but relapse remains frequent and is usually fatal. Methodology/Principal Findings We have isolated a subpopulation of Ewing's sarcoma cells, from both human cell lines and human xenografts grown in immune deficient mice, which express high aldehyde dehydrogenase (ALDHhigh) activity and are enriched for clonogenicity, sphere-formation, and tumor initiation. The ALDHhigh cells are resistant to chemotherapy in vitro, but this can be overcome by the ATP binding cassette transport protein inhibitor, verapamil. Importantly, these cells are not resistant to YK-4-279, a small molecule inhibitor of EWS-FLI1 that is selectively toxic to Ewing's sarcoma cells both in vitro and in vivo. Conclusions/Significance Ewing's sarcoma contains an ALDHhigh stem-like population of chemotherapy-resistant cells that retain sensitivity to EWS-FLI1 inhibition. Inhibiting the EWS-FLI1 oncoprotein may prove to be an effective means of improving patient outcomes by targeting Ewing's sarcoma stem cells that survive standard chemotherapy. PMID:21085683

  16. A novel oncogenic mechanism in Ewing sarcoma involving IGF pathway targeting by EWS/Fli1-regulated microRNAs

    PubMed Central

    McKinsey, EL; Parrish, JK; Irwin, AE; Niemeyer, BF; Kern, HB; Birks, DK; Jedlicka, P

    2015-01-01

    MicroRNAs (miRs) are a novel class of cellular bioactive molecules with critical functions in the regulation of gene expression in normal biology and disease. MiRs are frequently misexpressed in cancer, with potent biological consequences. However, relatively little is known about miRs in pediatric cancers, including sarcomas. Moreover, the mechanisms behind aberrant miR expression in cancer are poorly understood. Ewing sarcoma is an aggressive pediatric malignancy driven by EWS/Ets fusion oncoproteins, which are gain-of-function transcriptional regulators. We employed stable silencing of EWS/Fli1, the most common of the oncogenic fusions, and global miR profiling to identify EWS/Fli1-regulated miRs with oncogenesis-modifying roles in Ewing sarcoma. In this report, we characterize a group of miRs (100, 125b, 22, 221/222, 27a and 29a) strongly repressed by EWS/Fli1. Strikingly, all of these miRs have predicted targets in the insulin-like growth factor (IGF) signaling pathway, a pivotal driver of Ewing sarcoma oncogenesis. We demonstrate that miRs in this group negatively regulate the expression of multiple pro-oncogenic components of the IGF pathway, namely IGF-1, IGF-1 receptor, mammalian/mechanistic target of rapamycin and ribosomal protein S6 kinase A1. Consistent with tumor-suppressive functions, these miRs manifest growth inhibitory properties in Ewing sarcoma cells. Our studies thus uncover a novel oncogenic mechanism in Ewing sarcoma, involving post-transcriptional derepression of IGF signaling by the EWS/Fli1 fusion oncoprotein via miRs. This novel pathway may be amenable to innovative therapeutic targeting in Ewing sarcoma and other malignancies with activated IGF signaling. PMID:21643012

  17. Antagonizing Bcl-2 Family Members Sensitizes Neuroblastoma and Ewings Sarcoma to an Inhibitor of Glutamine Metabolism

    PubMed Central

    Olsen, Rachelle R.; Mary-Sinclair, Michelle N.; Yin, Zhirong; Freeman, Kevin W.

    2015-01-01

    Neuroblastomas (NBL) and Ewings 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. PMID:25615615

  18. Functional genomic screening reveals splicing of the EWS-FLI1 fusion transcript as a vulnerability in Ewing sarcoma

    PubMed Central

    Grohar, Patrick J.; Kim, Suntae; Rangel Rivera, Guillermo O.; Sen, Nirmalya; Haddock, Sara; Harlow, Matt L.; Maloney, Nichole K.; Zhu, Jack; O’Neill, Maura; Jones, Tamara L.; Huppi, Konrad; Grandin, Magdalena; Gehlhaus, Kristen; Klumpp-Thomas, Carleen A.; Buehler, Eugen; Helman, Lee J.; Martin, Scott E.; Caplen, Natasha J.

    2016-01-01

    Summary Ewing sarcoma cells depend on the EWS-FLI1 fusion transcription factor for cell survival. Using an assay of EWS-FLI1 activity and genome-wide RNAi screening, we have identified proteins required for the processing of the EWS-FLI1 pre-mRNA. We show Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1 require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1. We also demonstrate the sensitivity of EWS-FLI1 fusion transcripts to the loss-of-function of the U2 snRNP component, SF3B1. Disrupted splicing of the EWS-FLI1 transcript alters EWS-FLI1 protein expression and EWS-FLI1 driven expression. Our results show that the processing of the EWS-FLI1 fusion RNA is a potentially targetable vulnerability in Ewing sarcoma cells. PMID:26776507

  19. Functional Genomic Screening Reveals Splicing of the EWS-FLI1 Fusion Transcript as a Vulnerability in Ewing Sarcoma.

    PubMed

    Grohar, Patrick J; Kim, Suntae; Rangel Rivera, Guillermo O; Sen, Nirmalya; Haddock, Sara; Harlow, Matt L; Maloney, Nichole K; Zhu, Jack; O'Neill, Maura; Jones, Tamara L; Huppi, Konrad; Grandin, Magdalena; Gehlhaus, Kristen; Klumpp-Thomas, Carleen A; Buehler, Eugen; Helman, Lee J; Martin, Scott E; Caplen, Natasha J

    2016-01-26

    Ewing sarcoma cells depend on the EWS-FLI1 fusion transcription factor for cell survival. Using an assay of EWS-FLI1 activity and genome-wide RNAi screening, we have identified proteins required for the processing of the EWS-FLI1 pre-mRNA. We show that Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1 require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1. We also demonstrate the sensitivity of EWS-FLI1 fusion transcripts to the loss of function of the U2 snRNP component, SF3B1. Disrupted splicing of the EWS-FLI1 transcript alters EWS-FLI1 protein expression and EWS-FLI1-driven expression. Our results show that the processing of the EWS-FLI1 fusion RNA is a potentially targetable vulnerability in Ewing sarcoma cells. PMID:26776507

  20. EWS-FLI1 inhibits TNF{alpha}-induced NF{kappa}B-dependent transcription in Ewing sarcoma cells

    SciTech Connect

    Lagirand-Cantaloube, Julie; Laud, Karine; Institut Curie, Genetique et biologie des cancers, Paris ; Lilienbaum, Alain; Tirode, Franck; Institut Curie, Genetique et biologie des cancers, Paris ; Delattre, Olivier; Institut Curie, Genetique et biologie des cancers, Paris ; Auclair, Christian; Kryszke, Marie-Helene

    2010-09-03

    Research highlights: {yields} EWS-FLI1 interferes with TNF-induced activation of NF{kappa}B in Ewing sarcoma cells. {yields} EWS-FLI1 knockdown in Ewing sarcoma cells increases TNF-induced NF{kappa}B binding to DNA. {yields} EWS-FLI1 reduces TNF-stimulated NF{kappa}B-dependent transcriptional activation. {yields} Constitutive NF{kappa}B activity is not affected by EWS-FLI1. {yields} EWS-FLI1 physically interacts with NF{kappa}B 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 (NF{kappa}B) is a tightly regulated transcription factor controlling cell survival, proliferation and differentiation, as well as tumorigenesis. NF{kappa}B activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NF{kappa}B 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 NF{kappa}B basal activity, but impairs TNF-induced NF{kappa}B-driven transcription, at least in part through inhibition of NF{kappa}B binding to DNA. We detected an in vivo physical interaction between the fusion protein and NF{kappa}B 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 NF{kappa}B.

  1. The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent STAG2 Mutation

    PubMed Central

    Brohl, Andrew S.; Solomon, David A.; Chang, Wendy; Wang, Jianjun; Song, Young; Sindiri, Sivasish; Patidar, Rajesh; Hurd, Laura; Chen, Li; Shern, Jack F.; Liao, Hongling; Wen, Xinyu; Gerard, Julia; Kim, Jung-Sik; Lopez Guerrero, Jose Antonio; Machado, Isidro; Wai, Daniel H.; Picci, Piero; Triche, Timothy; Horvai, Andrew E.; Miettinen, Markku; Wei, Jun S.; Catchpool, Daniel; Llombart-Bosch, Antonio; Waldman, Todd; Khan, Javed

    2014-01-01

    The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared to population data (OR 7.1, p = 0.006). Using whole transcriptome sequencing, we find that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and that these tumors do not have a characteristic Ewing sarcoma gene expression signature. We identify samples harboring novel fusion genes including FUS-NCATc2 and CIC-FOXO4 that may represent distinct small round blue cell tumor variants. In an independent EFT tissue microarray cohort, we show that STAG2 loss as detected by immunohistochemistry may be associated with more advanced disease (p = 0.15) and a modest decrease in overall survival (p = 0.10). These results significantly advance our understanding of the genomic and molecular underpinnings of Ewing sarcoma and provide a foundation towards further efforts to improve diagnosis, prognosis, and precision therapeutics testing. PMID:25010205

  2. Primary Ewing's sarcoma of the orbit with intracranial extension abutting the temporal lobe: a rare case report.

    PubMed

    Naqvi, Syed Hassan Abbas; Hameed, Saad; Naqvi, Syed Hassan Shiraz; Musani, Muhammad Anis

    2014-10-01

    Ewing's sarcoma is a small, blue, round-cell tumor of mesenchymal origin which typically presents itself during the first and the second decades of life. Typically, it is noticed in the long bones of the limbs, pelvis, or ribs. There have been few reports worldwide with none in Pakistan of this rare phenomenon. We report here the case of a 16-year-old female diagnosed with Ewing's sarcoma with intracranial extension abutting the temporal lobe resulting in proptosis and partial loss of vision in the left eye. The purpose of this case is to discuss the clinicoradiological presentation, microscopic description, and management of the patient. PMID:24696360

  3. A Radiological Review of Ewing's Sarcoma of Mandible: A Case Report with One Year Follow-up

    PubMed Central

    Thomas, Valsa; Kattoor, Jayasree; Kusumakumari, P

    2013-01-01

    ABSTRACT Ewing's sarcoma (ES) is an uncommon round cell tumor with an aggressive course affecting mainly children and young adults. Only 1% of cases is reported with jaw involvement and have mandibular predilection. Radiographic finding in ES reflect many destructive nature of the lesion, like osteolysis, cortical erosion, periostitis and soft tissue mass. A case of ES of the mandible is reported with special consideration to the radiological appearance. How to cite this article: Krishna KBB, Thomas V, Kattoor J, Kusumakumari P. A Radiological Review of Ewing's Sarcoma of Mandible: A Case Report with One Year Follow-up. Int J Clin Pediatr Dent 2013;6(2):109-114. PMID:25206203

  4. Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe.

    PubMed

    Bölling, T; Braun-Munzinger, G; Burdach, S; Calaminus, G; Craft, A; Delattre, O; Deley, M-C L; Dirksen, U; Dockhorn-Dworniczak, B; Dunst, J; Engel, S; Faldum, A; Fröhlich, B; Gadner, H; Göbel, U; Gosheger, G; Hardes, J; Hawkins, D S; Hjorth, L; Hoffmann, C; Kovar, H; Kruseova, J; Ladenstein, R; Leuschner, I; Lewis, I J; Oberlin, O; Paulussen, M; Potratz, J; Ranft, A; Rössig, C; Rübe, C; Sauer, R; Schober, O; Schuck, A; Timmermann, B; Tirode, F; van den Berg, H; van Valen, F; Vieth, V; Willich, N; Winkelmann, W; Whelan, J; Womer, R B

    2015-05-01

    Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival. PMID:25985445

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

    PubMed Central

    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. 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. PMID:24391423

  6. [Secondary TFE3-associated renal cell carcinoma in a child treated for Ewing sarcoma].

    PubMed

    Fedhila Ben Ayed, F; Rhayem, S; Doghri, R; Ben Hassine, L; Khemiri, M; Mrad, K; Bellagha, I; Barsaoui, S

    2016-02-01

    Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents. PMID:26702489

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

    SciTech Connect

    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.

  8. Intensive combined modality therapy including low-dose TBI in high-risk Ewing's sarcoma patients

    SciTech Connect

    Kinsella, T.J.; Glaubiger, D.; Diesseroth, A.; Makuch, R.; Waller, B.; Pizzo, P.; Glatstein, E.

    1983-12-01

    Twenty-four high-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiaiton (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patterns of granulocyte recovery following consolidative therapy (including TBI and ABMI) were recognized. The time to platelet recovery was different for the groups with early and late granulocyte recovery. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. It is concluded that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

  9. Stereotactic body radiotherapy for metastatic and recurrent ewing sarcoma and osteosarcoma.

    PubMed

    Brown, Lindsay C; Lester, Rachael A; Grams, Michael P; Haddock, Michael G; Olivier, Kenneth R; Arndt, Carola A S; Rose, Peter S; Laack, Nadia N

    2014-01-01

    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. PMID:25548538

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

    PubMed

    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. PMID:23657987

  11. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations

    PubMed Central

    Tirode, Franck; Surdez, Didier; Ma, Xiaotu; Parker, Matthew; Le Deley, Marie Ccile; Bahrami, Armita; Zhang, Zhaojie; Lapouble, Eve; Grossette-Lalami, Sandrine; Rusch, Michael; Reynaud, Stphanie; Rio-Frio, Thomas; Hedlund, Erin; Wu, Gang; Chen, Xiang; Pierron, Gaelle; Oberlin, Odile; Zaidi, Sakina; Lemmon, Gordon; Gupta, Pankaj; Vadodaria, Bhavin; Easton, John; Gut, Marta; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Shurtleff, Sheila; Laurence, Valrie; Michon, Jean; Marec-Brard, Perrine; Gut, Ivo; Downing, James; Dyer, Michael; Zhang, Jinghui; Delattre, Olivier

    2014-01-01

    Ewing sarcoma is a primary bone tumor initiated by EWSR1ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2 immuno-negative cells in relapsed tumors as compared with matched diagnostic samples. PMID:25223734

  12. EWS-FLI1 inhibits TNFalpha-induced NFkappaB-dependent transcription in Ewing sarcoma cells.

    PubMed

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

    2010-09-01

    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 (NFkappaB) is a tightly regulated transcription factor controlling cell survival, proliferation and differentiation, as well as tumorigenesis. NFkappaB activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NFkappaB 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 NFkappaB basal activity, but impairs TNF-induced NFkappaB-driven transcription, at least in part through inhibition of NFkappaB binding to DNA. We detected an in vivo physical interaction between the fusion protein and NFkappaB 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 NFkappaB. PMID:20691659

  13. The clinical use of biomarkers as prognostic factors in Ewing sarcoma

    PubMed Central

    2012-01-01

    Ewing Sarcoma is the second most common primary bone sarcoma with 900 new diagnoses per year in Europe (EU27). It has a poor survival rate in the face of metastatic disease, with no more than 10% survival of the 35% who develop recurrence. Despite the remaining majority having localised disease, approximately 30% still relapse and die despite salvage therapies. Prognostic factors may identify patients at higher risk that might require differential therapeutic interventions. Aside from phenotypic features, quantitative biomarkers based on biological measurements may help identify tumours that are more aggressive. We audited the research which has been done to identify prognostic biomarkers for Ewing sarcoma in the past 15 years. We identified 86 articles were identified using defined search criteria. A total of 11,625 patients were reported, although this number reflects reanalysis of several cohorts. For phenotypic markers, independent reports suggest that tumour size > 8 cm and the presence of metastasis appeared strong predictors of negative outcome. Good histological response (necrosis > 90%) after treatment appeared a significant predictor for a positive outcome. However, data proposing biological biomarkers for practical clinical use remain un-validated with only one secondary report published. Our recommendation is that we can stratify patients according to their stage and using the phenotypic features of metastases, tumour size and histological response. For biological biomarkers, we suggest a number of validating studies including markers for 9p21 locus, heat shock proteins, telomerase related markers, interleukins, tumour necrosis factors, VEGF pathway, lymphocyte count, and a number of other markers including Ki-67. PMID:22587879

  14. Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti-CD99 antibody

    PubMed Central

    O'Neill, Allison F.; Dearling, Jason L.J.; Wang, Yuchuan; Tupper, Tanya; Sun, Yanping; Aster, Jon C.; Calicchio, Monica L.; Perez-Atayde, Antonio R.; Packard, Alan; Kung, Andrew L.

    2014-01-01

    Purpose Ewing sarcoma is a tumor of the bone and soft tissue characterized by diffuse cell membrane expression of CD99 (MIC2). Single-site, surgically resectable disease is associated with an excellent 5-year event-free survival; conversely, patients with distant metastases have a poor prognosis. Non-invasive imaging is the standard approach to identifying sites of metastatic disease. We sought to develop a CD99-targeted imaging agent for staging Ewing sarcoma and other CD99-expressing tumors. Experimental Design We identified a CD99 antibody with highly specific binding in vitro and labeled this antibody with 64Cu. Mice with either subcutaneous Ewing sarcoma xenograft tumors or micrometastases were imaged with the 64Cu-labeled anti-CD99 antibody and these results were compared to conventional MRI and FDG-PET imaging. Results 64Cu-labeled anti-CD99 antibody demonstrated high avidity for the CD99 positive subcutaneous tumors, with a high tumor-to-background ratio, greater than that demonstrated with FDG-PET. Micrometastases, measuring 1-2 mm on MRI, were not detected with FDG-PET but readily visualized with the 64Cu-labeled anti-CD99 antibody. Probe biodistribution studies demonstrated high specificity of the probe for CD99 positive tumors. Conclusions 64Cu-labeled anti-CD99 antibody can detect subcutaneous Ewing sarcoma tumors and metastatic sites with high sensitivity, outperforming FDG-PET in preclinical studies. This targeted radiotracer may have important implications for the diagnosis, surveillance, and treatment of Ewing sarcoma. Similarly, it may impact the management of other CD99 positive tumors. PMID:24218512

  15. Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells.

    PubMed

    Alhaddad, Anna; Adam, Marie-Pierre; Botsoa, Jacques; Dantelle, Graldine; Perruchas, Sandrine; Gacoin, Thierry; Mansuy, Christelle; Lavielle, Solange; Malvy, Claude; Treussart, Franois; Bertrand, Jean-Rmi

    2011-11-01

    The ability of diamond nanoparticles (nanodiamonds, NDs) to deliver small interfering RNA (siRNA) into Ewing sarcoma cells is investigated with a view to the possibility of in-vivo anticancer nucleic-acid drug delivery. siRNA is adsorbed onto NDs that are coated with cationic polymer. Cell uptake of NDs is demonstrated by taking advantage of the NDs' intrinsic fluorescence from embedded color-center defects. Cell toxicity of these coated NDs is shown to be low. Consistent with the internalization efficacy, a specific inhibition of EWS/Fli-1 gene expression is shown at the mRNA and protein level by the ND-vectorized siRNA in a serum-containing medium. PMID:21913326

  16. The many faces of Ewing sarcoma: difficult to diagnose pediatric cases.

    PubMed

    Fouda, Asharf; Mansour, Ahmed; Al-Tonbary, Youssef

    2009-01-01

    Ewing sarcoma (ES) is the second most frequent primary malignant bone cancer, following osteosarcoma. ES is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. We describe four children aged 3, 3.5, 9, and 9.5 years, who presented with two femur masses simultaneously (patient 1), a huge mediastinal mass (patient 2), an abdomino-mediastinal mass with dysphagia (patient 3), and a huge abdomino-pelvic mass (patient 4). Our patients were of younger age and had abnormal presentations that made initial diagnosis difficult, but also are representative of the different problems encountered in pediatric practice. Biopsy initially revealed round cell tumor and by immunohistochemistry, CD99 was positive, which confirmed the diagnosis of ES. Our patients were difficult to diagnosis.The patients were misdiagnosed initially, so there was a delay in diagnosis. Definitive diagnosis required use of various radiological imaging methods and immunohistochemistry. PMID:20139055

  17. Local control of Ewing's sarcoma of bone with radiotherapy and combination chemotherapy

    SciTech Connect

    Tepper, J.; Glaubiger, D.; Lichter, A.; Wackenhut, J.; Glatstein, E.

    1980-11-01

    Between 1964 and 1977, 94 patients with Ewing's sarcoma of bone were treated at the National Cancer Institute. They received 5000 rad to the whole bone and progressively more aggressive chemotherapy protocols. The patients were divided according to site of primary lesion into central, proximal and distal lesions, with 19%, 33% and 57%, respectively, alive and well. The local control rate is high (93%), with good functional results in the distal lesions, and no changes are needed in radiation therapy dose or volume. Control is not as satisfactory for central and proximal lesions and efforts need to be made to increase control at these sites. We are at present attempting to define more accurately the extent of soft tissue disease, increasing the dose to 6000 rad for central lesions, and using a more aggressive chemotherapy program, in the hope of increasing the local control in these more aggressive tumors.

  18. Unilateral pulmonary metastases from Ewing's sarcoma shown in a technetium-99m-methylene-diphosphonate bone scan.

    PubMed

    Gholamrezanezhad, Ali; Moinian, Davoud; Mirpour, Sahar; Hajimohammadi, Hadi

    2006-01-01

    A 32-year-old man with a history of painful swelling of the right ankle underwent bone scintigraphy, which showed increased uptake in the right ankle and also unexpected diffuse uptake throughout the right hemithorax. A single photon emission tomography scan performed after the intravenous injection of 740 MBq of technetium-99m methylene-diphosphonate ((99m)Tc-MDP) showed abnormal uptake throughout the right lung. Computed tomography (CT) revealed a large mass in the right lower lobe. CT-guided biopsy of this mass led to a diagnosis of metastatic Ewing's sarcoma. Although lung uptake on bone scans has been noted in various occasions (such as: pulmonary alveolar microlithiasis, Pneumocystis carinii pneumonia, and various tumoral lesions), increased uptake of (99m)Tc-MDP in lung metastases of Ewing's sarcoma has not been reported according to our knowledge until now. We report such a case. PMID:17160160

  19. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma

    PubMed Central

    Rheinbay, Esther; Boulay, Gaylor; Suv, Mario L.; Rossetti, Nikki E.; Boonseng, Wannaporn E.; Oksuz, Ozgur; Cook, Edward B.; Formey, Aurlie; Patel, Anoop; Gymrek, Melissa; Thapar, Vishal; Deshpande, Vikram; Ting, David T.; Hornicek, Francis J.; Nielsen, G. Petur; Stamenkovic, Ivan; Aryee, Martin J.

    2015-01-01

    Summary The aberrant transcription factor EWS-FLI1 drives Ewing sarcoma yet its molecular function is incompletely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements, which lack evolutionary conservation and regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild type ETS transcription factors. These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators, while activating oncogenes and new potential therapeutic targets, such as the kinase VRK1. Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation. PMID:25453903

  20. Reversible LSD1 inhibition interferes with global EWS/ETS transcriptional activity and impedes Ewing sarcoma tumor growth

    PubMed Central

    Sankar, Savita; Theisen, Emily R.; Bearss, Jared; Mulvihill, Timothy; Hoffman, Laura M.; Sorna, Venkataswamy; Beckerle, Mary C.; Sharma, Sunil; Lessnick, Stephen L.

    2014-01-01

    Purpose Ewing sarcoma is a pediatric bone tumor which absolutely relies on the transcriptional activity of the EWS/ETS family of fusion oncoproteins. While the most common fusion, EWS/FLI, utilizes lysine-specific demethylase 1 (LSD1) to repress critical tumor suppressors, small molecule blockade of LSD1 has not yet been thoroughly explored as a therapeutic approach for Ewing sarcoma. We therefore evaluated the translational potential of potent and specific LSD1 inhibition with HCI2509 on the transcriptional program of both EWS/FLI and EWS/ERG as well as the downstream oncogenic phenotypes driven by EWS/ETS fusions in both in vitro and in vivo models of Ewing sarcoma. Experimental Design RNA-seq was used to compare the transcriptional profiles of EWS/FLI, EWS/ERG, and treatment with HCI-2509 in both EWS/FLI and EWS/ERG containing cell lines. We then evaluated morphological phenotypes of treated cells with immunofluorescence. The induction of apoptosis was evaluated using caspase 3/7 activation and TUNEL staining. Colony forming assays were used to test oncogenic transformation and xenograft studies with patient-derived cell lines were used to evaluate the effects of HCI-2509 on tumorigenesis. Results HCI2509 caused a dramatic reversal of both the up- and down-regulated transcriptional profiles of EWS/FLI and EWS/ERG accompanied by the induction of apoptosis, and disruption of morphological and oncogenic phenotypes modulated by EWS/FLI. Importantly, HCI2509 displayed single-agent efficacy in multiple xenograft models. Conclusions These data support epigenetic modulation with HCI2509 as a therapeutic strategy for Ewing sarcoma, and highlight a critical dual role for LSD1 in the oncogenic transcriptional activity of EWS/ETS proteins. PMID:24963049

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

    SciTech Connect

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

    1984-07-01

    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/sub 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/sup -4/-10/sup -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.

  2. Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite.

    PubMed

    Grnewald, Thomas G P; Bernard, Virginie; Gilardi-Hebenstreit, Pascale; Raynal, Virginie; Surdez, Didier; Aynaud, Marie-Ming; Mirabeau, Olivier; Cidre-Aranaz, Florencia; Tirode, Franck; Zaidi, Sakina; Perot, Galle; Jonker, Anneliene H; Lucchesi, Carlo; Le Deley, Marie-Ccile; Oberlin, Odile; Marec-Brard, Perrine; Vron, Amlie S; Reynaud, Stephanie; Lapouble, Eve; Boeva, Valentina; Rio Frio, Thomas; Alonso, Javier; Bhatia, Smita; Pierron, Galle; Cancel-Tassin, Geraldine; Cussenot, Olivier; Cox, David G; Morton, Lindsay M; Machiela, Mitchell J; Chanock, Stephen J; Charnay, Patrick; Delattre, Olivier

    2015-09-01

    Deciphering the ways in which somatic mutations and germline susceptibility variants cooperate to promote cancer is challenging. Ewing sarcoma is characterized by fusions between EWSR1 and members of the ETS gene family, usually EWSR1-FLI1, leading to the generation of oncogenic transcription factors that bind DNA at GGAA motifs. A recent genome-wide association study identified susceptibility variants near EGR2. Here we found that EGR2 knockdown inhibited proliferation, clonogenicity and spheroidal growth in vitro and induced regression of Ewing sarcoma xenografts. Targeted germline deep sequencing of the EGR2 locus in affected subjects and controls identified 291 Ewing-associated SNPs. At rs79965208, the A risk allele connected adjacent GGAA repeats by converting an interspaced GGAT motif into a GGAA motif, thereby increasing the number of consecutive GGAA motifs and thus the EWSR1-FLI1-dependent enhancer activity of this sequence, with epigenetic characteristics of an active regulatory element. EWSR1-FLI1 preferentially bound to the A risk allele, which increased global and allele-specific EGR2 expression. Collectively, our findings establish cooperation between a dominant oncogene and a susceptibility variant that regulates a major driver of Ewing sarcomagenesis. PMID:26214589

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

    SciTech Connect

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

    2011-09-01

    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. Biology and treatment of metastasis of sarcoma to the brain.

    PubMed

    Ahmad, Omar; Chan, Michael; Savage, Paul; Watabe, Kounosuke; Lo, Hui-Wen; Qasem, Shadi

    2016-01-01

    Sarcomas are rare tumors with devastating clinical consequences, often affecting children as well as adults. Brain metastasis in sarcoma is frequently preceded by lung metastasis. Common offenders include Ewing sarcoma, osteosarcoma and leiomyosarcoma. Although our understanding of sarcoma metastasis remains limited, several cellular factors and signaling pathways appear to play regulatory roles and/or exhibit prognostic values in sarcoma metastasis. In addition, MicroRNAs have been shown to have either positive or negative impact on sarcoma biology and metastasis. Sarcoma is considered one of the classic radio- and chemo-resistant brain metastasis, hence the use of multiple modalities in order to improve the therapeutic ratio and overcome the inherent resistance. Treatment modalities include surgical resection, chemotherapy, gamma knife radiosurgery and/or fractionated whole-brain radiotherapy. The efficacy of chemotherapy is limited by the ability of the drug(s) to cross the blood-brain barrier (BBB), and the chemosensitivity of the tumor to the chemotherapeutic agent. In this review, we discuss the pathology, biology and therapy for sarcoma brain metastasis. PMID:26709659

  5. EWS/FLI and its Downstream Target NR0B1 Interact Directly to Modulate Transcription and Oncogenesis in Ewing's Sarcoma

    PubMed Central

    Kinsey, Michelle; Smith, Richard; Iyer, Anita K.; McCabe, Edward R.B.; Lessnick, Stephen L.

    2009-01-01

    Most Ewing's sarcomas harbor chromosomal translocations that encode fusions between EWS and ETS family members. The most common fusion, EWS/FLI, consists of an EWSR1-derived strong transcriptional activation domain fused, in frame, to the DNA binding domain-containing portion of FLI1. EWS/FLI functions as an aberrant transcription factor to regulate genes that mediate the oncogenic phenotype of Ewing's sarcoma. One of these regulated genes, NR0B1, encodes a co-repressor protein, and likely plays a transcriptional role in tumorigenesis. However, the genes that NR0B1 regulates and the transcription factors it interacts with in Ewing's sarcoma are largely unknown. We used transcriptional profiling and chromatin immunoprecipitation to identify genes that are regulated by NR0B1, and compared these data to similar data for EWS/FLI. While the transcriptional profile overlapped as expected, we also found that the genome-wide localization of NR0B1and EWS/FLI overlapped as well, suggesting that they regulate some genes coordinately. Further analysis revealed that NR0B1 and EWS/FLI physically interact. This protein-protein interaction is likely to be relevant for Ewing's sarcoma development because mutations in NR0B1 that disrupt the interaction have transcriptional consequences and also abrogate oncogenic transformation. Taken together, these data suggest that EWS/FLI and NR0B1 physically interact, coordinately modulate gene expression, and mediate the transformed phenotype of Ewing's sarcoma. PMID:19920188

  6. [Retroperitoneal extraskeletal Ewing'? sarcoma difficult to differentiate from adrenocortical carcinoma : a case report].

    PubMed

    Sato, Masahiko; Miyazato, Minoru; Yamada, Shigeyuki; Shimada, Shuichi; Kaiho, Yasuhiro; Ishidoya, Shigeto; Arai, Yoichi

    2011-06-01

    A 15-year-old man complained of left upper abdominal distention. Ultrasonography, computed tomography, and magnetic resonance imaging (MRI) revealed a large multilocular tumor measuring 151014 cm in the left retroperitoneal space. MRI showed the high intensity tumor on the T1 and T2 weighted images and enhanced septum above the left kidney. Positron emission tomography revealed high uptake(SUV max 7.9) in the marginal region. Because the left adrenal gland could not be identified on images, we diagnosed the tumor as adrenocortical carcinoma, preoperatively. In February 2010, tumor excision combined with left nephrectomy and adrenalectomy was performed via transperitoneal approach. Left adrenal gland was identified separately from the tumor, but a small tumor was observed in the gland. The pathological specimen showed sheet-like monotonous proliferation of small round cells which had glycogen. Immunostaining technique showed highly positive CD-99 and neuron specific enolase (NSE). Fluorescence in situ hybridization (FISH) showed translocation of EWS gene. Similar pathological findings were observed in the left adrenal tumor. We diagnosed the tumor as retroperitoneal extraskeletal Ewing' s sarcoma with metastasis to the left adrenal gland. Considering it a high risk, we started adjuvant VAIA(vincristine, dactinomycin, ifosfamide, and doxorubicin) chemotherapy soon after the operation. However, there was left retroperitoneal recurrence 9 months after the operation. We changed the chemotherapy regimen to gemcitabine and docetaxel and are continuing chemotherapy. PMID:21795832

  7. Endoplasmic reticulum targeting in Ewing's sarcoma by the alkylphospholipid analog edelfosine

    PubMed Central

    Bonilla, Ximena; Dakir, EL-Habib; Mollinedo, Faustino; Gajate, Consuelo

    2015-01-01

    Ewing's sarcoma (ES) is the second most common bone cancer in children and young people. Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) is the prototype of a family of synthetic antitumor compounds, collectively known as alkylphospholipid analogs (APLs). We have found that APLs ranked edelfosine>perifosine>erucylphosphocholine>miltefosine for their capacity to promote apoptosis in ES cells. Edelfosine accumulated in the endoplasmic reticulum (ER) and triggered an ER stress response that eventually led to caspase-dependent apoptosis in ES cells. This apoptotic response involved mitochondrial-mediated processes, with cytochrome c release, caspase-9 activation and generation of reactive oxygen species. Edelfosine-induced apoptosis was also dependent on sustained c-Jun NH2-terminal kinase activation. Oral administration of edelfosine showed a potent in vivo antitumor activity in an ES xenograft animal model. Histochemical staining gave evidence for ER stress response and apoptosis in the ES tumors isolated from edelfosine-treated mice. Edelfosine showed a preferential action on ES tumor cells as compared to non-transformed osteoblasts, and appeared to be well suited for combination therapy regimens. These results demonstrate in vitro and in vivo antitumor activity of edelfosine against ES cells that is mediated by caspase activation and ER stress, and provide the proof of concept for a putative edelfosine- and ER stress-mediated approach forES treatment. PMID:25999349

  8. Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer

    PubMed Central

    Bilke, Sven; Schwentner, Raphaela; Yang, Fan; Kauer, Maximilian; Jug, Gunhild; Walker, Robert L.; Davis, Sean; Zhu, Yuelin J.; Pineda, Marbin; Meltzer, Paul S.; Kovar, Heinrich

    2013-01-01

    Deregulated E2F transcription factor activity occurs in the vast majority of human tumors and has been solidly implicated in disturbances of cell cycle control, proliferation, and apoptosis. Aberrant E2F regulatory activity is often caused by impairment of control through pRB function, but little is known about the interplay of other oncoproteins with E2F. Here we show that ETS transcription factor fusions resulting from disease driving rearrangements in Ewing sarcoma (ES) and prostate cancer (PC) are one such class of oncoproteins. We performed an integrative study of genome-wide DNA-binding and transcription data in EWSR1/FLI1 expressing ES and TMPRSS2/ERG containing PC cells. Supported by promoter activity and mutation analyses, we demonstrate that a large fraction of E2F3 target genes are synergistically coregulated by these aberrant ETS proteins. We propose that the oncogenic effect of ETS fusion oncoproteins is in part mediated by the disruptive effect of the E2F–ETS interaction on cell cycle control. Additionally, a detailed analysis of the regulatory targets of the characteristic EWSR1/FLI1 fusion in ES identifies two functionally distinct gene sets. While synergistic regulation in concert with E2F in the promoter of target genes has a generally activating effect, EWSR1/FLI1 binding independent of E2F3 is predominantly associated with repressed differentiation genes. Thus, EWSR1/FLI1 appears to promote oncogenesis by simultaneously promoting cell proliferation and perturbing differentiation. PMID:23940108

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

    SciTech Connect

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

    1991-10-01

    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.

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

    PubMed Central

    Cope, Judith U.; Reaman, Gregory H.; Tonning, Joseph M.

    2015-01-01

    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. PMID:26064078

  11. Zoledronic acid as a new adjuvant therapeutic strategy for Ewing's sarcoma patients.

    PubMed

    Odri, Guillaume A; Dumoucel, Sophie; Picarda, Galle; Battaglia, Sverine; Lamoureux, Franois; Corradini, Nadge; Rousseau, Julie; Tirode, Franck; Laud, Karine; Delattre, Olivier; Gouin, Franois; Heymann, Dominique; Redini, Franoise

    2010-10-01

    Ewing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 ?g/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G(2)M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy. PMID:20841471

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

    SciTech Connect

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G.; Eggleton, Paul; MRC Immunochemistry Unit, University of Oxford, Oxford OX1 3QU ; Lorson, Christian L.; Young, Philip J.

    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.

  13. Intercohort Gene Expression Co-analysis Reveals Chemokine Receptors as Prognostic Indicators in Ewing's Sarcoma

    PubMed Central

    Bennani-Baiti, Idriss M.; Cooper, Aaron; Lawlor, Elizabeth R.; Kauer, Maximilian; Ban, Jozef; Aryee, Dave N.T.; Kovar, Heinrich

    2010-01-01

    Purpose We report a novel analytical method, named intercohort co-analysis or Ican, which aids in the discovery of genes with predictive value for the progression or outcome of diseases from small-size cohorts. We tested this premise in Ewing's sarcoma (ES), a highly metastatic cancer of bone and soft tissues that lacks validated molecular metastasis and prognostic indicators. Experimental Design To uncover genes significantly expressed in ES patient subsets, we first determined a non-arbitrary gene expression significance cutoff based on expression levels in validated expressing and non-expressing tissues. We next searched for genes that were consistently significantly expressed in several ES cohort and cell line datasets. Significantly expressed genes were independently validated by quantitative RT-PCR in an additional ES cohort. Results Analysis of ES cohorts revealed marked intercohort gene expression variability. After filtering out the intercohort variability, CXCR4 and CXCR7 were found to be consistently associated with specific ES subsets. Pairwise analyses showed CXCR4 to correlate with ES metastases, and CXCR4 and CXCR7 to patient survival, but not with several other clinicopathological variables. Conclusion Ican is a powerful novel method to identifying genes consistently associated with particular disease states in cancers for which large cohorts are not available, currently the case of most cancers. We report for the first time that high CXCR4 expression preferentially associates with metastatic ES and that of CXCR7 with poor patient survival. PMID:20525755

  14. The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin

    PubMed Central

    Carcaboso, Angel M.; Herrero-Martn, David; Garca-Macas, Mara del Carmen; Sevillano, Vicky; Alonso, Diego; Pascual-Pasto, Guillem; San-Segundo, Laura; Vila-Ubach, Monica; Rodrigues, Telmo; Fraile, Susana; Teodosio, Cristina; Mayo-Iscar, Agustn; Aracil, Miguel; Galmarini, Carlos Mara; Tirado, Oscar M.; Mora, Jaume; de lava, Enrique

    2015-01-01

    Recent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh disrupts the DDR machinery. Thus, given the impact and apparent specificity of both agents with regard to the DNA damage/DDR system and EWSR1-FLI1 activity in ES, we decided to explore the activity of combining PARPinh and Trabectedin in in vitro and in vivo experiments. The combination of Olaparib and Trabectedin was found to be highly synergistic, inhibiting cell proliferation, inducing apoptosis, and the accumulation of G2/M. The drug combination also enhanced ?H2AX intranuclear accumulation as a result of DNA damage induction, DNA fragmentation and global DDR deregulation, while EWSR1-FLI1 target expression remained unaffected. The effect of the drug combination was corroborated in a mouse xenograft model of ES and, more importantly, in two ES patient-derived xenograft (PDX) models in which the tumors showed complete regression. In conclusion, the combination of the two agents leads to a biologically significant deregulation of the DDR machinery that elicits relevant antitumor activity in preclinical models and might represent a promising therapeutic tool that should be further explored for translation to the clinical setting. PMID:26056084

  15. Systems biology of Ewing sarcoma: a network model of EWS-FLI1 effect on proliferation and apoptosis

    PubMed Central

    Stoll, Gautier; Surdez, Didier; Tirode, Franck; Laud, Karine; Barillot, Emmanuel; Zinovyev, Andrei; Delattre, Olivier

    2013-01-01

    Ewing sarcoma is the second most frequent pediatric bone tumor. In most of the patients, a chromosomal translocation leads to the expression of the EWS-FLI1 chimeric transcription factor that is the major oncogene in this pathology. Relative genetic simplicity of Ewing sarcoma makes it particularly attractive for studying cancer in a systemic manner. Silencing EWS-FLI1 induces cell cycle alteration and ultimately leads to apoptosis, but the exact molecular mechanisms underlying this phenotype are unclear. In this study, a network linking EWS-FLI1 to cell cycle and apoptosis phenotypes was constructed through an original method of network reconstruction. Transcriptome time-series after EWS-FLI1 silencing were used to identify core modulated genes by an original scoring method based on fitting expression profile dynamics curves. Literature data mining was then used to connect these modulated genes into a network. The validity of a subpart of this network was assessed by siRNA/RT-QPCR experiments on four additional Ewing cell lines and confirmed most of the links. Based on the network and the transcriptome data, CUL1 was identified as a new potential target of EWS-FLI1. Altogether, using an original methodology of data integration, we provide the first version of EWS-FLI1 network model of cell cycle and apoptosis regulation. PMID:23935076

  16. Systems biology of Ewing sarcoma: a network model of EWS-FLI1 effect on proliferation and apoptosis.

    PubMed

    Stoll, Gautier; Surdez, Didier; Tirode, Franck; Laud, Karine; Barillot, Emmanuel; Zinovyev, Andrei; Delattre, Olivier

    2013-10-01

    Ewing sarcoma is the second most frequent pediatric bone tumor. In most of the patients, a chromosomal translocation leads to the expression of the EWS-FLI1 chimeric transcription factor that is the major oncogene in this pathology. Relative genetic simplicity of Ewing sarcoma makes it particularly attractive for studying cancer in a systemic manner. Silencing EWS-FLI1 induces cell cycle alteration and ultimately leads to apoptosis, but the exact molecular mechanisms underlying this phenotype are unclear. In this study, a network linking EWS-FLI1 to cell cycle and apoptosis phenotypes was constructed through an original method of network reconstruction. Transcriptome time-series after EWS-FLI1 silencing were used to identify core modulated genes by an original scoring method based on fitting expression profile dynamics curves. Literature data mining was then used to connect these modulated genes into a network. The validity of a subpart of this network was assessed by siRNA/RT-QPCR experiments on four additional Ewing cell lines and confirmed most of the links. Based on the network and the transcriptome data, CUL1 was identified as a new potential target of EWS-FLI1. Altogether, using an original methodology of data integration, we provide the first version of EWS-FLI1 network model of cell cycle and apoptosis regulation. PMID:23935076

  17. Ewing's sarcoma of the ulna treated with sub-total resection and reconstruction using a non-vascularized, autogenous fibular graft and hernia mesh: A case report

    PubMed Central

    WANG, CONG; LIN, NONG

    2015-01-01

    Ewing's sarcoma of the bone is the second most frequently occurring malignant bone tumor in children and adolescents. Ewing's sarcoma in the ulna are extremely rare. Thus, the surgical options for reconstruction of the elbow are limited and technically challenging. In the current study, a 29-year-old male with Ewing's sarcoma of the ulna was treated with a sub-total resection and reconstruction using a non-vascularized, autogenous fibular graft and hernia mesh. At the 2-year follow-up, the patient had returned to his previous occupation with no evidence of local recurrence or distant metastasis. The functional recovery was satisfactory, and the patient could perform active movement of the elbow from 0 to 135, forearm pronation to 30, supination to 85 and had full hand function. The grip power of the left hand was 36 kg, which was 86% of the contralateral side (42 kg). PMID:26622797

  18. Quantification of the Heterogeneity of Prognostic Cellular Biomarkers in Ewing Sarcoma Using Automated Image and Random Survival Forest Analysis

    PubMed Central

    Yu, Haiyue; Branford White, Harriet; Schfer, 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 material could be achieved. Such an automated and integrated methodology has potential application in the identification of prognostic classifiers based on tumour cell heterogeneity. PMID:25243408

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

    PubMed

    Bhnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schfer, 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 material could be achieved. Such an automated and integrated methodology has potential application in the identification of prognostic classifiers based on tumour cell heterogeneity. PMID:25243408

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

    PubMed Central

    Picarda, Galle; Matous, Etienne; Amiaud, Jrme; Charrier, Cline; Lamoureux, Franois; Heymann, Marie-Franoise; Tirode, Franck; Pitard, Bruno; Trichet, Valrie; Heymann, Dominique; Redini, Franoise

    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.

  1. Ewings sarcoma of patella: A rare entity treated with a novel technique of extensor mechanism reconstruction using tendoachilles auto graft

    PubMed Central

    Valsalan, Rejith Mannambeth; Zacharia, Balaji

    2015-01-01

    We report a case of Ewings sarcoma (ES) involving the patella in a young female. ES of patella is a rare entity. The patient was presented with anterior knee pain and swelling arising from the patella. She was treated with neoadjuvant chemotherapy followed by wide excision of the patella and reconstruction of the extensor mechanism using split tendoachilles auto graft. The patella is an uncommon site for primary or metastatic tumors of the bone. ES, though rare, should be included in the differential diagnosis of swellings arising from the patella. Auto graft from the tendoachilles is a good alternative for reconstructing the extensor mechanism of the knee. PMID:26495252

  2. Primary Ewing's sarcoma of the squamous part of temporal bone in a young girl treated with adjuvant volumetric arc therapy.

    PubMed

    Nandi, Moujhuri; Bhattacharya, Jibak; Goswami, Suchanda; Goswami, Chanchal

    2015-01-01

    Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumors usually arise in the long bones of children and young adults. Primary ES of the cranium is unusual. Treatment involves multi-modality therapy incorporating surgery, radiotherapy and chemotherapy; outcomes are similar to those arising from long bones. We report a case of Primary ES of the squamous part of temporal bone with intracranial extension in a 9-year-old girl who was treated with surgery, chemotherapy followed by adjuvant radiotherapy by volumetric arc therapy. Post 1-year of treatment the girl is performing well in her classes. PMID:26881573

  3. Circulating miR-125b as a biomarker of Ewing's sarcoma in Chinese children.

    PubMed

    Nie, C L; Ren, W H; Ma, Y; Xi, J S; Han, B

    2015-01-01

    Previous studies indicated that microRNA-125b (miR-125b) has an important role in the progression of Ewing's sarcoma (ES). The purpose of the current study was to examine expression changes of miR-125b in the serum of ES patients and evaluate if the expression level of miR-125b could serve as a new biomarker for ES. This study was performed on patients who underwent surgical resection at our hospital between 2005 and 2013 after an initial diagnosis of ES. We measured serum miR-125b levels in 63 patients with ES and 126 healthy control patients using a real-time quantitative reverse transcriptase-PCR (qRT-PCR) method. Expression levels of serum miR-125b were distinctly decreased in ES patients when compared with healthy controls (P < 0.001). ES cases that had a poor response to chemotherapy presented a significant down-regulation of miR-125b (P = 0.001). The ROC curve showed that the serum miR-125b could serve as a valuable biomarker for differentiating ES patients from healthy controls with an AUC of 0.879 (95%CI = 0.817-0.924; P < 0.001). At a cut-off value of 2.203 for miR-125b, the sensitivity was 72.8% and the specificity was 87.2% in discriminating ES from the controls. Our results indicate that serum miR- 125b may serve as a useful noninvasive biomarker for ES. PMID:26782555

  4. Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma

    PubMed Central

    Santoro, Marco; Lamhamedi-Cherradi, Salah-Eddine; Menegaz, Brian A.; Ludwig, Joseph A.; Mikos, Antonios G.

    2015-01-01

    Three-dimensional tumor models accurately describe different aspects of the tumor microenvironment and are readily available for mechanistic studies of tumor biology and for drug screening. Nevertheless, these systems often overlook biomechanical stimulation, another fundamental driver of tumor progression. To address this issue, we cultured Ewing sarcoma (ES) cells on electrospun poly(?-caprolactone) 3D scaffolds within a flow perfusion bioreactor. Flow-derived shear stress provided a physiologically relevant mechanical stimulation that significantly promoted insulin-like growth factor-1 (IGF1) production and elicited a superadditive release in the presence of exogenous IGF1. This finding is particularly relevant, given the central role of the IGF1/IGF-1 receptor (IGF-1R) pathway in ES tumorigenesis and as a promising clinical target. Additionally, flow perfusion enhanced in a rate-dependent manner the sensitivity of ES cells to IGF-1R inhibitor dalotuzumab (MK-0646) and showed shear stress-dependent resistance to the IGF-1R blockade. This study demonstrates shear stress-dependent ES cell sensitivity to dalotuzumab, highlighting the importance of biomechanical stimulation on ES-acquired drug resistance to IGF-1R inhibition. Furthermore, flow perfusion increased nutrient supply throughout the scaffold, enriching ES culture over static conditions. Our use of a tissue-engineered model, rather than human tumors or xenografts, enabled precise control of the forces experienced by ES cells, and therefore provided at least one explanation for the remarkable antineoplastic effects observed by some ES tumor patients from IGF-1R targeted therapies, in contrast to the lackluster effect observed in cells grown in conventional monolayer culture. PMID:26240353

  5. Role of Radiotherapy in the Multimodal Treatment of Ewing Sarcoma Family Tumors

    PubMed Central

    Choi, Yunseon; Lim, Do Hoon; Lee, Soo Hyun; Lyu, Chuhl Joo; Im, Jung Ho; Lee, Yun-Han; Suh, Chang-Ok

    2015-01-01

    Purpose The aim of this study was to evaluate the role of radiotherapy (RT) in the management of Ewing sarcoma family tumors (ESFT). Materials and Methods Retrospective analysiswas performed on 91 patientswith localized ESFT treated from 1988 to 2012. Primary tumor size was ? 8 cm in 33 patients. Surgery, RT, and combined surgery with RT were applied in 37, 15, and 33 patients, respectively. Results Median follow-up was 43.8 months. Forty-three patients (47.3%) showed recurrence or progressive disease. Twelve patients (13.2%) showed local failure after initial treatment. Thirty-nine patients (42.9%) experienced distant metastases. The 5-year overall survival (OS), progression-free survival, and local control (LC) were 60.5%, 58.2%, and 85.1%, respectively. According to treatment, 5-year LCwas 64.8% with RT and 90.2% with combined surgery and RT (p=0.052). Prognostic factors for OS were tumor size (? 8 cm, p < 0.001) and surgical resection (p < 0.001). In large tumors (? 8 cm), combined surgery and RT produced better LC compared to RT (p=0.033). However, in smaller tumors (< 8 cm), RT without surgery resulted in a similar LC rate as RT with surgery (p=0.374). Conclusion RT used for patients with unfavorable risk factors resulted in worse outcome than for patientswho received surgery. Smallertumors could be controlled locallywith chemotherapy and RT. For large tumors, combined surgery and RT is needed. Proper selection of local treatment modality, RT, surgery, or both is crucial in the management of ESFT. PMID:25687849

  6. Ewing Sarcoma of the Bone in Children under 6 Years of Age

    PubMed Central

    De Ioris, Maria Antonietta; Prete, Arcangelo; Cozza, Raffaele; Podda, Marta; Manzitti, Carla; Pession, Andrea; Schiavello, Elisabetta; Contoli, Benedetta; Balter, Rita; Fagioli, Franca; Bisogno, Gianni; Amoroso, Loredana

    2013-01-01

    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 KaplanMeier 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, 5883%) and 72% (95% CI 5783%) for patients with localized disease and 38% (95% CI 1760%) and 21% (95% CI 545%) 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 20002008 were 89% (95% CI 7196%) and 86% (95% CI 6694%), 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. PMID:23382839

  7. gamma-Glutamyl transpeptidase expression in Ewing's sarcoma cells: up-regulation by interferons.

    PubMed Central

    Bouman, Lena; Sancau, Josiane; Rouillard, Dany; Bauvois, Brigitte

    2002-01-01

    The genetic hallmark of Ewing's sarcoma family of tumours (ET) is the presence of the translocation t(11;22)(q24;q12), which creates the ET fusion gene, leading to cellular transformation. Five human gamma-glutamyl transpeptidase (gamma-GT) genes are located near the chromosomal translocation in ET. gamma-GT is a major enzyme involved in glutathione homoeostasis. Five human cell lines representative of primary or metastatic tumours were investigated to study whether gamma-GT alterations could occur at the chromosomal breaks and rearrangements in ET. As shown by enzymic assays and FACS analyses, all ET cell lines consistently expressed a functional gamma-GT which however did not discriminate steps of ET progression. As shown previously [Sancau, Hiscott, Delattre and Wietzerbin (2000) Oncogene 19, 3372-3383], ET cells respond to the antiproliferative effects of interferons (IFNs) type I (alpha and beta) and to a much less degree to IFN type II (gamma). IFN-alpha and -beta arrested cells in the S-phase of the cell cycle. We found an enhancement of gamma-GT mRNA species with IFN-alpha and -beta by reverse transcriptase-PCR analyses. This is reflected by up-regulation of gamma-GT protein, which coincides with the increase in gamma-GT-specific enzymic activity. Similarly, IFNs up-regulate the levels of gamma-GT in another IFN-responsive B cell line. Whether this up-regulation of gamma-GT by IFNs is of physiological relevance to cell behaviour remains to be studied. PMID:12049636

  8. Characterization and Drug Resistance Patterns of Ewing's Sarcoma Family Tumor Cell Lines

    PubMed Central

    May, William A.; Grigoryan, Rita S.; Keshelava, Nino; Cabral, Daniel J.; Christensen, Laura L.; Jenabi, Jasmine; Ji, Lingyun; Triche, Timothy J.; Lawlor, Elizabeth R.; Reynolds, C. Patrick

    2013-01-01

    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. PMID:24312454

  9. Gene expression profiling of peripheral blood cells: new insights into Ewing sarcoma biology and clinical applications.

    PubMed

    Przybyl, Joanna; Kozak, Katarzyna; Kosela, Hanna; Falkowski, Slawomir; Switaj, Tomasz; Lugowska, Iwona; Szumera-Cieckiewicz, Anna; Ptaszynski, Konrad; Grygalewicz, Beata; Chechlinska, Magdalena; Pienkowska-Grela, Barbara; Debiec-Rychter, Maria; Siedlecki, Janusz A; Rutkowski, Piotr

    2014-08-01

    Ewing sarcoma (ES) is a group of highly aggressive small round cell tumors of bone or soft tissue with high metastatic potential and low cure rate. ES tumors are associated with a rapid osteolysis and necrosis. The currently accepted clinical prognostic parameters do not accurately predict survival of high-risk patients. Moreover, neither the subtype of EWS-FLI1/ERG in the tumor, nor the detection of fusion transcripts in the peripheral blood (PB) samples, has prognostic value in ES patients. We evaluated the prevalence of circulating tumor cells (CTCs) in 34 adult ES patients. Since CTCs were confirmed in only small subset of patients, we further explored the expression profiles of PB leukocytes using a panel of genes associated with immune system status and increased tumor invasiveness. Moreover, we analyzed the alterations of the routine blood tests in the examined cohort of patients and correlated our findings with the clinical outcome. A uniform decrease in ZAP70 expression in PB cells among all ES patients, as compared to healthy individuals, was observed. Monocytosis and the abnormal expression of CDH2 and CDT2 genes in the PB cells significantly correlated with poor prognosis in ES patients. Our study supports the previously proposed hypothesis of systemic nature of ES. Based on the PB cell expression profiles, we propose a mechanism by which immune system may be involved in intensification of osteoclastogenesis and disease progression in ES patients. Moreover, we demonstrate the prognostic value of molecular PB testing at the time of routine histopathological diagnosis. PMID:25008066

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

    SciTech Connect

    La, Trang H.; Meyers, Paul A.; Wexler, Leonard H.; Alektiar, Kaled M.; Healey, John H.; Laquaglia, Michael P.; Boland, Patrick J.; Wolden, Suzanne L. . E-mail: woldens@mskcc.org

    2006-02-01

    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.

  11. Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone.

    PubMed

    Hatano, Mihoko; Matsumoto, Yoshihiro; Fukushi, Jun-Ichi; Matsunobu, Tomoya; Endo, Makoto; Okada, Seiji; Iura, Kunio; Kamura, Satoshi; Fujiwara, Toshifumi; Iida, Keiichiro; Fujiwara, Yuko; Nabeshima, Akira; Yokoyama, Nobuhiko; Fukushima, Suguru; Oda, Yoshinao; Iwamoto, Yukihide

    2015-08-01

    Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (P < 0.05, logistic regression) and poorer overall survival (P < 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES. PMID:26092671

  12. The association between let-7, RAS and HIF-1α in Ewing Sarcoma tumor growth

    PubMed Central

    Yaniv, Isaac; Ash, Shifra; Cohen, Ian J.; Kodman, Yona; Haklai, Ronit; Elad-Sfadia, Galit; Kloog, Yoel; Chepurko, Elena; Feinmesser, Meora; Issakov, Josephine; Sher, Osnat; Luria, Drorit; Kollender, Yehuda; Weizman, Avraham; Avigad, Smadar

    2015-01-01

    Ewing Sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. microRNAs (miRNAs) are involved in cancer as tumor suppressors or oncogenes. We studied the involvement of miRNAs located on chromosomes 11q and 22q that participate in the most common translocation in ES. Of these, we focused on 3 that belong to the let-7 family. We studied the expression levels of let-7a, and let-7b and detected a significant correlation between low expression of let-7b and increased risk of relapse. let-7 is known to be a negative regulator of the RAS oncogene. Indeed, we detected an inverse association between the expression of let-7 and RAS protein levels and its downstream target p-ERK, following transfection of let-7 mimics and inhibitors. Furthermore, we identified let-7 as a negative regulator of HIF-1α and EWS-FLI-1. Moreover, we were able to show that HIF-1α directly binds to the EWS-FLI-1 promoter. Salirasib treatment in-vitro resulted in the reduction of cell viability, migration ability, and in the decrease of cells in S-phase. A significant reduction in tumor burden and in the expression levels of both HIF-1α and EWS-FLI-1 proteins were observed in mice after treatment. Our results support the hypothesis that let-7 is a tumor suppressor that negatively regulates RAS, also in ES, and that HIF-1α may contribute to the aggressive metastatic behavior of ES. Moreover, the reduction in the tumor burden in a mouse model of ES following Salirasib treatment, suggests therapeutic potential for this RAS inhibitor in ES. PMID:26393682

  13. Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells.

    PubMed

    Uren, A; Merchant, M S; Sun, C J; Vitolo, M I; Sun, Y; Tsokos, M; Illei, P B; Ladanyi, M; Passaniti, A; Mackall, C; Toretsky, J A

    2003-04-17

    The Ewing's sarcoma family of tumors (ESFT) contain a translocation, t(11;22), which results in the novel oncogenic fusion protein EWS/FLI1. Platelet-derived growth factors (PDGF) and their receptors (PDGFR) are involved in the induction and proliferation of numerous solid tumors and are the potential candidates for novel targeted antitumor therapy. Since a relation was reported between PDGF-C and EWS/FLI1, we sought to characterize the PDGF signaling pathway in ESFT. Eight out of nine ESFT cell lines were found to express significant levels of beta-PDGFR. Interestingly, none of the tested cell lines expressed alpha-PDGFR, which is the receptor isotype required for PDGF-C binding. By immunohistochemical staining 47 of 52 (90.4%) archival tumor samples from patients with ESFT were positive for beta-PDGFR. ESFT cell lines were treated with PDGF-AA or PDGF-BB ligands to evaluate downstream signaling. Autophosphorylation of beta-PDGFR and tyrosine phosphorylation of PLC-gamma, PI3Kp85 and Shc were detected only in PDGF-BB-stimulated cells that express beta-PDGFR. Receptor function was further evaluated using chemotaxis assays that showed TC-32 cell migration towards PDGF-BB. A specific PDGFR kinase inhibitor AG1295 blocked beta-PDGFR activation, downstream signaling, growth in cell culture and chemotaxis of TC-32 cells. AG1295 also delayed tumor formation and prolonged survival in an ESFT animal model. We conclude that ESFT express beta-PDGFR and that this is a functional and potentially crucial signaling pathway. Therefore, beta-PDGFRs may provide a novel therapeutic target in ESFT that can be utilized to design better treatment modalities. PMID:12700668

  14. The association between let-7, RAS and HIF-1? in Ewing Sarcoma tumor growth.

    PubMed

    Hameiri-Grossman, Michal; Porat-Klein, Adi; Yaniv, Isaac; Ash, Shifra; Cohen, Ian J; Kodman, Yona; Haklai, Ronit; Elad-Sfadia, Galit; Kloog, Yoel; Chepurko, Elena; Feinmesser, Meora; Issakov, Josephine; Sher, Osnat; Luria, Drorit; Kollender, Yehuda; Weizman, Avraham; Avigad, Smadar

    2015-10-20

    Ewing Sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. microRNAs (miRNAs) are involved in cancer as tumor suppressors or oncogenes. We studied the involvement of miRNAs located on chromosomes 11q and 22q that participate in the most common translocation in ES. Of these, we focused on 3 that belong to the let-7 family.We studied the expression levels of let-7a, and let-7b and detected a significant correlation between low expression of let-7b and increased risk of relapse. let-7 is known to be a negative regulator of the RAS oncogene. Indeed, we detected an inverse association between the expression of let-7 and RAS protein levels and its downstream target p-ERK, following transfection of let-7 mimics and inhibitors. Furthermore, we identified let-7 as a negative regulator of HIF-1? and EWS-FLI-1. Moreover, we were able to show that HIF-1? directly binds to the EWS-FLI-1 promoter. Salirasib treatment in-vitro resulted in the reduction of cell viability, migration ability, and in the decrease of cells in S-phase. A significant reduction in tumor burden and in the expression levels of both HIF-1? and EWS-FLI-1 proteins were observed in mice after treatment.Our results support the hypothesis that let-7 is a tumor suppressor that negatively regulates RAS, also in ES, and that HIF-1? may contribute to the aggressive metastatic behavior of ES. Moreover, the reduction in the tumor burden in a mouse model of ES following Salirasib treatment, suggests therapeutic potential for this RAS inhibitor in ES. PMID:26393682

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

    SciTech Connect

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

    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.

  16. Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma.

    PubMed

    Santoro, Marco; Lamhamedi-Cherradi, Salah-Eddine; Menegaz, Brian A; Ludwig, Joseph A; Mikos, Antonios G

    2015-08-18

    Three-dimensional tumor models accurately describe different aspects of the tumor microenvironment and are readily available for mechanistic studies of tumor biology and for drug screening. Nevertheless, these systems often overlook biomechanical stimulation, another fundamental driver of tumor progression. To address this issue, we cultured Ewing sarcoma (ES) cells on electrospun poly(?-caprolactone) 3D scaffolds within a flow perfusion bioreactor. Flow-derived shear stress provided a physiologically relevant mechanical stimulation that significantly promoted insulin-like growth factor-1 (IGF1) production and elicited a superadditive release in the presence of exogenous IGF1. This finding is particularly relevant, given the central role of the IGF1/IGF-1 receptor (IGF-1R) pathway in ES tumorigenesis and as a promising clinical target. Additionally, flow perfusion enhanced in a rate-dependent manner the sensitivity of ES cells to IGF-1R inhibitor dalotuzumab (MK-0646) and showed shear stress-dependent resistance to the IGF-1R blockade. This study demonstrates shear stress-dependent ES cell sensitivity to dalotuzumab, highlighting the importance of biomechanical stimulation on ES-acquired drug resistance to IGF-1R inhibition. Furthermore, flow perfusion increased nutrient supply throughout the scaffold, enriching ES culture over static conditions. Our use of a tissue-engineered model, rather than human tumors or xenografts, enabled precise control of the forces experienced by ES cells, and therefore provided at least one explanation for the remarkable antineoplastic effects observed by some ES tumor patients from IGF-1R targeted therapies, in contrast to the lackluster effect observed in cells grown in conventional monolayer culture. PMID:26240353

  17. Synthesis and StructureActivity Relationship Studies of Small Molecule Disruptors of EWS-FLI1 Interactions in Ewings Sarcoma

    PubMed Central

    2015-01-01

    EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewings sarcoma family tumors (ESFT). Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized a focused library of analogues. The functional inhibition of the analogues was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired cell screening approach measuring effects on growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines devoid of the oncoprotein. Our data revealed that substitution of electron donating groups at the para-position on the phenyl ring was the most favorable for inhibition of EWS-FLI1 by analogs of 2. Compound 9u (with a dimethylamino substitution) was the most active inhibitor with GI50 = 0.26 0.1 ?M. Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase reporter activity was established (R2 = 0.84). Finally, we designed and synthesized a biotinylated analogue and determined the binding affinity for recombinant EWS-FLI1 (Kd = 4.8 2.6 ?M). PMID:25432018

  18. Microdeletions in 9p21.3 induce false negative results in CDKN2A FISH analysis of Ewing sarcoma.

    PubMed

    Savola, S; Nardi, F; Scotlandi, K; Picci, P; Knuutila, S

    2007-01-01

    Deletion of the CDKN2A locus at 9p21.3 has been reported to be a poor prognostic sign in the Ewing sarcoma family of tumours. In clinical applications CDKN2A deletion is primarily detected using fluorescent in situ hybridisation (FISH) with a commercial probe, size approximately 190 kb. Due to limitations in resolution, FISH analysis may fail to detect microdeletions smaller than 190 kb. In the present study, we performed 44K array comparative genomic hybridisation (CGH) on eleven Ewing sarcoma cell lines and 26 tissue samples in order to define the sizes of 9p21.3 deletions. Microarray CGH analysis revealed 9p21.3 deletions encompassing the CDKN2A locus in eight cell lines (73%) and in six tumours (23%). In four cases (two cell lines and two tissue samples) the deletion was less than 190 kb in size. In one cell line sample, we detected a microdeletion of approximately 58 kb in 9p21.3 harbouring the CDKN2A locus. We confirmed this result using 244K microarray CGH and TaqMan quantitative RT-PCR analysis and further performed FISH analysis on this cell line sample. Here, we show that CDKN2A FISH analysis can give false negative results in cases with small microdeletions. Our results suggest that new and more accurate FISH methods should be developed for detection of deletions in the CDKN2A locus. PMID:18160777

  19. Molecular localization of the t(11; 22)(q24; q12) translocation of Ewing sarcoma by chromosomal in situ suppression hybridization

    SciTech Connect

    Selleri, L.; Hermanson, G.G.; Eubanks, J.H.; Lewis, K.A.; Evans, G.A. )

    1991-02-01

    Chromosome translocations are associated with a variety of human leukemias, lymphomas, and solid tumors. To localize molecular markers flanking the t(11;22)(q24;q12) breakpoint that occurs in virtually all cases of Ewing sarcoma and peripheral neuroepithelioma, high-resolution chromosomal in situ suppression hybridization was carried out using a panel of cosmid clones localized and ordered on chromosome 11q. The location of the Ewing sarcoma translocation breakpoint was determined relative to the nearest two cosmid markers on 11q, clones 23.2 and 5.8, through the analysis of metaphase chromosome hybridization. By in situ hybridization to interphase nuclei, the approximate physical separation of these two markers was determined. In both Ewing sarcoma and peripheral neuroepithelioma, cosmid clone 5.8 is translocated from chromosome 11q24 to the derivative chromosome 22 and a portion of chromosome 22q12 carrying the leukemia inhibitory factor gene is translocated to the derivative chromosome 11. The physical distance between the flanking cosmid markers on chromosome 11 was determined to be in the range of 1,000 kilobases, and genomic analysis using pulsed-field gel electrophoresis showed no abnormalities over a region of 650 kilobases in the vicinity of the leukemia inhibitory factor gene on chromosome 22. This approach localizes the Ewing sarcoma breakpoint to a small region on chromosome 11q24 and provides a rapid and precise technique for the molecular characterization of chromosomal aberrations.

  20. Long-term Survivors of Childhood Ewing Sarcoma: Report From the Childhood Cancer Survivor Study

    PubMed Central

    Goodman, Pamela; Leisenring, Wendy; Ness, Kirsten K.; Meyers, Paul A.; Wolden, Suzanne L.; Smith, Stephanie M.; Stovall, Marilyn; Hammond, Sue; Robison, Leslie L.; Oeffinger, Kevin C.

    2010-01-01

    Background The survival of Ewing sarcoma (ES) patients has improved since the 1970s but is associated with considerable future health risks. Methods The study population consisted of long-term (≥5-year) survivors of childhood ES diagnosed before age 21 from 1970 to 1986. Cause-specific mortality was evaluated in eligible survivors (n = 568), and subsequent malignant neoplasms, chronic health conditions, infertility, and health status were evaluated in the subset participating in the Childhood Cancer Survivor Study (n = 403). Outcomes were compared with the US population and sibling control subjects (n = 3899). Logistic, Poisson, or Cox proportional hazards models, with adjustments for sex, age, race/ethnicity, and potential intrafamily correlation, were used. Statistical tests were two-sided. Results Cumulative mortality of ES survivors was 25.0% (95% confidence interval [CI] = 21.1 to 28.9) 25 years after diagnosis. The all-cause standardized mortality ratio was 13.3 (95% CI = 11.2 to 15.8) overall, 23.1 (95% CI = 17.6 to 29.7) for women, and 10.0 (95% CI = 7.9 to 12.5) for men. The nonrecurrence-progression non-external cause standardized mortality ratio (subsequent non-ES malignant neoplasms and cardiac and pulmonary causes potentially attributable to ES treatment) was 8.7 (95% CI = 6.2 to 12.0). Twenty-five years after ES diagnosis, cumulative incidence of subsequent malignant neoplasms, excluding nonmelanoma skin cancers, was 9.0% (95% CI = 5.8 to 12.2). Compared with siblings, survivors had an increased risk of severe, life-threatening, or disabling chronic health conditions (relative risk = 6.0, 95% CI = 4.1 to 9.0). Survivors had lower fertility rates (women: P = .005; men: P < .001) and higher rates of moderate to extreme adverse health status (P < .001). Conclusion Long-term survivors of childhood ES exhibit excess mortality and morbidity. PMID:20656964

  1. Prognostic and therapeutic relevance of the IGF pathway in Ewing's sarcoma patients.

    PubMed

    van de Luijtgaarden, A C M; Versleijen-Jonkers, Y M H; Roeffen, M H S; Schreuder, H W B; Flucke, U E; van der Graaf, W T A

    2013-12-01

    The optimal target and timing of drugs interfering with the insulin-like growth factor (IGF) signaling system in Ewing's sarcoma (ES) remain undetermined. We examined the expression of IGF signaling proteins in ES samples taken before and after chemotherapy, and speculate about the optimal way of treating ES patients in the future. Tumor material (36 initial biopsies and 24 resection specimens after neoadjuvant chemotherapy) and follow-up data of 41 patients treated for ES at the Radboud University Nijmegen Medical Centre were analyzed. Immunohistochemical staining was done for IGF1, IGF2, IGFBP3, IGF-1R, phosphorylated AKT (pAKT), phosphorylated mTOR (pmTOR), and phosphorylated ERK (pERK), and staining intensity was scored semiquantitatively. Change of protein expression during treatment, correlations of effector cascade signaling, and influence on progression-free (PFS) and overall survival (OS) were tested. All potential targets were widely expressed at both time points. After chemotherapy, pmTOR expression decreased significantly (p = 0.021) while IGFBP3 increased (p = 0.005). Correlations exist between IGF-1R and pERK (ρ = 0.286, p = 0.031), IGF-1R and pAKT (ρ = 0.269, p = 0.045), pAKT and pERK (ρ = 0.460, p = 0.000), and pERK and pmTOR (ρ = 0.273, p = 0.038). In therapy-naive samples, combined expression of pAKT, pmTOR, and pERK predicted worse PFS (median, 11 vs. 32 months; p = 0.039) and OS (median, 18 vs. 83 months; p = 0.023). We identify an unfavorable prognostic group of ES patients with widely activated IGF-effector cascades, demonstrate cooperation between the different downstream pathways, and show how expression of IGF-related proteins may change after exposure to chemotherapy. These findings should be taken into account when designing future trials with IGF-targeting agents. We suggest the prospective exploration of chemotherapy and multi-target tyrosine kinase inhibitors in the first-line setting. PMID:23292309

  2. Trial of Dasatinib in Advanced Sarcomas

    ClinicalTrials.gov

    2014-12-17

    Rhabdomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Chondrosarcoma; Sarcoma, Ewing's; Sarcoma, Alveolar Soft Part; Chordoma; Epithelioid Sarcoma; Giant Cell Tumor of Bone; Hemangiopericytoma; Gastrointestinal Stromal Tumor (GIST)

  3. A peculiar case of large primary cutaneous Ewings sarcoma of the foot: Case report and review of the literature

    PubMed Central

    Grassetti, Luca; Torresetti, Matteo; Brancorsini, Donatella; Rubini, Corrado; Lazzeri, Davide; Di Benedetto, Giovanni

    2015-01-01

    Introduction Primary cutaneous extraskeletal Ewings sarcomas (ESs) are extremely rare tumors, limited to the skin and generally appear as a single small lesion, circumscribed mid-to-deep dermis or involving subcutis. Due to their rarity and morphological similarity to other cutaneous tumors, ESs are subject to being clinically and pathologically subdiagnosed. Presentation of case A 37-year-old man presented a large rapidly growing mass of the first toe measuring 9.5נ8cm with no radiological evidence of bone involvement. The patient underwent wide surgical tumor resection; histological, immunohistochemical and molecular evaluation confirmed the diagnosis of ESs. Postoperative examinations revealed no metastasis and after 11 months follow-up no recurrences were detected. Discussion Current literature reports only a few isolated cases or small series. ESs are generally described as small masses with a favorable clinical behavior. Despite lower extremity is a relatively frequent site, only rare and small ESs of the foot have been reported. To our knowledge the present case is the largest ES of the foot. Despite its large size, the patient did not report any metastases confirming the hypothesis of treating superficial ES with surgery alone, thus avoiding adjuvant radiotherapy and/or chemotherapy and their related side-effects. Conclusion ESs still remain exceedingly rare tumors and they could not be taken in consideration into differential diagnosis. This case represents a peculiar example of large ES in an uncommon site as the foot successfully treated with surgery alone, and may serve as an alert for those physicians who approach such rapidly growing superficial lesions. PMID:26318136

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

    SciTech Connect

    Yang, Liu; Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108 ; Hu, Hsien-Ming; Zielinska-Kwiatkowska, Anna; Chansky, Howard A.; Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108

    2010-11-05

    Research highlights: {yields} Inducible and reversible siRNA knockdown of an oncogenic fusion protein such as EWS-Fli1 is feasible and more advantageous than other siRNA methods. {yields} The tumor suppressor gene FOXO1 is a new EWS-Fli1 target. {yields} While trans-activators are known for the FOXO1 gene, there has been no report on negative regulators of FOXO1 transcription. {yields} 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.

  5. Pathobiologic Markers of the Ewing Sarcoma Family of Tumors: State of the Art and Prediction of Behaviour

    PubMed Central

    Pinto, Alfredo; Dickman, Paul; Parham, David

    2011-01-01

    Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT. In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development. PMID:20981347

  6. Ewing's sarcoma of the pelvis: an unusual, but not to be missed, cause of an irritable hip.

    PubMed

    Ray, Partha; Girach, Julekha; Sanghrajka, Anish Pradip

    2016-01-01

    A 15-year-old girl presented with a 2-month history of non-specific right hip pain associated with pain in the back, right flank and foot. Her symptoms deteriorated, interfering with weight-bearing. Following admission, she was found to be febrile with a flexion deformity of her right-hip, and tenderness over the iliac crest and posterior pelvis. A markedly elevated C reactive protein and erythrocyte sedimentation rate, with an ultrasound-proven scan effusion within the right hip were all suggestive of septic arthritis. However, full blood count demonstrated a significant anaemia, which together with the tenderness around the pelvis was not in keeping with this diagnosis. Surgical washout was therefore delayed to obtain a MRI scan of the pelvis. The scan revealed a 5×5×3 cm necrotic soft tissue mass within the gluteal muscles, arising from the right ilium, which biopsy confirmed to be a Ewing's sarcoma. PMID:26795741

  7. Ewing-like sarcoma with CIC-DUX4 gene fusion in a patient with neurofibromatosis type 1. A hitherto unreported association.

    PubMed

    Tardo, Juan C; Machado, Isidro; Navarro, Lara; Idrovo, Franklin; Sanz-Ortega, Julin; Pelln, Antonio; Llombart-Bosch, Antonio

    2015-11-01

    Sarcoma with CIC-DUX4 gene fusion is emerging as the most prevalent subset of Ewing-like undifferentiated small round cell sarcomas with around 50 cases published. We report hereby the case of a 40-year-old male who presented a CIC-DUX4 sarcoma in deep soft tissues in his thigh. He had been diagnosed with neurofibromatosis type 1 at age 19 and over the years underwent resection of multiple neural neoplasms, including two malignant peripheral nerve sheath tumors with classical spindle-cell histopathology. The CIC-DUX4 sarcoma was treated with surgical resection, radiation and chemotherapy, but lung and brain metastases developed and the patient died from the disease 14 months after diagnosis. This is the first case of sarcoma with CIC-DUX4 gene fusion reported in a patient with NF1. Whether this association is coincidental or CIC-DUX4 sarcomas could be related to NF1 remains to be clarified. Study of alternative molecular alterations in EWSR1-negative undifferentiated small round cell sarcomas is clinically relevant, since CIC-DUX4 sarcomas seem to be a very aggressive subset with poor response to the presently used therapeutic regimens. PMID:26386605

  8. Evaluation of PAX8 Expression and Its Potential Diagnostic and Prognostic Value in Renal and Extra-Renal Ewing Sarcomas/PNETs.

    PubMed

    Markow, Michael; Bui, Marilyn M; Lin, Hui-Yi; Lloyd, Mark; Sexton, Wade J; Dhillon, Jasreman

    2016-01-01

    PAX8 is a transcription factor involved in the regulation of organogenesis of the thyroid gland, kidney, and Mllerian system. It is commonly expressed in epithelial tumors of thyroid and parathyroid glands, kidney, thymus, and female genital tract. PAX8 is increasingly used in the establishment of tissue of origin in carcinomas and has recently been identified in a subset of small blue round cell tumors including Ewing sarcomas/PNETs. However, it is unclear if this association in ES/PNETs is due to renal origin or is PNET specific. In this study we investigated the PAX8 staining pattern of primary renal and extra-renal ES/PNETs to explore its potential diagnostic and prognostic role. A tissue microarray (TMA) of 22 cases of extra-renal Ewing/PNETs and two separate cases of primary renal PNET whole slide sections were immunohistochemically stained with rabbit polyclonal PAX8 antibody. PAX8 was positive in 2 of 2 primary renal PNETs and in 14 (64%) cases of the extra renal PNETs. The association between PAX8 immunoreactivity and Ewing/PNET was identified in both primary renal and extra-renal Ewing/PNETs for the first time. Further studies are warranted to verify these findings and to shed light in the tumorigenesis of Ewing/PNET. However, PAX8 is not useful in establishing a diagnosis of Ewing/PNET due to its presence in different tumors like carcinomas, lymphomas and sarcomas. PAX8 does not seem to have prognostic value. PMID:26350056

  9. Clinical and Biochemical Function of Polymorphic NR0B1 GGAA-Microsatellites in Ewing Sarcoma: A Report from the Children's Oncology Group

    PubMed Central

    Monument, Michael J.; Johnson, Kirsten M.; McIlvaine, Elizabeth; Abegglen, Lisa; Watkins, W. Scott; Jorde, Lynn B.; Womer, Richard B.; Beeler, Natalie; Monovich, Laura; Lawlor, Elizabeth R.; Bridge, Julia A.; Schiffman, Joshua D.; Krailo, Mark D.; Randall, R. Lor; Lessnick, Stephen L.

    2014-01-01

    Background 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. Objectives 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. Results 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 2026 GGAA motifs. Relative to white European and African controls, the NR0B1 GGAA-microsatellite in tumor cells demonstrated a strong bias for haplotypes containing 2125 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. Conclusions 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. PMID:25093581

  10. A Unique Case of Primary Ewing's Sarcoma of the Cervical Spine in a 53-Year-Old Male: A Case Report and Review of the Literature

    PubMed Central

    Holland, Marshall T.; Flouty, Oliver E.; Close, Liesl N.; Reddy, Chandan G.; Howard, Matthew A.

    2015-01-01

    Extraskeletal Ewing's sarcoma (EES) is a rare presentation, representing only 15% of all primary Ewing's sarcoma cases. Even more uncommon is EES presenting as a primary focus in the spinal canal. These rapidly growing tumors often present with focal neurological symptoms of myelopathy or radiculopathy. There are no classic characteristic imaging findings and thus the physician must keep a high index of clinical suspicion. Diagnosis can only be definitively made by histopathological studies. In this report, we discuss a primary cervical spine EES in a 53-year-old man who presented with a two-month history of left upper extremity pain and acute onset of weakness. Imaging revealed a cervical spinal canal mass. After undergoing cervical decompression, histopathological examination confirmed a diagnosis of Ewing's sarcoma. A literature search revealed fewer than 25 reported cases of primary cervical spine EES published in the past 15 years and only one report demonstrating this pathology in a patient older than 30 years of age (age = 38). Given the low incidence of this pathology presenting in this age group and the lack of treatment guidelines, each patient's plan should be considered on a case-by-case basis until further studies are performed to determine optimal evidence based treatment. PMID:25802527

  11. Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.

    PubMed

    Ozdemirli, M; Fanburg-Smith, J C; Hartmann, D P; Shad, A T; Lage, J M; Magrath, I T; Azumi, N; Harris, N L; Cossman, J; Jaffe, E S

    1998-07-01

    Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy. PMID:9669342

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

    SciTech Connect

    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

    2015-06-01

    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 radiation therapy for patients who have poor histologic response after R0 resection.

  13. Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)

    ClinicalTrials.gov

    2014-04-01

    Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  14. Twenty Years On – What Do We Really Know About Ewing Sarcoma And What Is The Path Forward?

    PubMed Central

    Lawlor, Elizabeth R.; Sorensen, Poul H.

    2015-01-01

    Ewing sarcoma (ES) is a highly aggressive bone and soft tissue tumor with peak incidence in adolescents and young adults. Despite advances in local control and systemic chemotherapy, metastatic relapse after an initial clinical remission remains a significant clinical problem. In addition, metastasis at the time of presentation or at relapse continues to be the leading cause of death for patients diagnosed with ES. Since the discovery over 20 years ago of the pathognomonic EWS-FLI1 fusion gene, much has been learned about the molecular and cellular biology of ES pathogenesis. In addition, more recent exploitation of advances in stem cell and developmental biology has provided key insights into the cellular origins of ES and the role of epigenetic deregulation in tumor initiation and maintenance. Nevertheless, the mechanisms that drive tumor relapse and metastasis remain largely unknown. These gaps in our knowledge continue to hamper the development of novel therapeutic strategies that will improve outcomes for patients with relapsed and metastatic disease. In this chapter we will review the current status of ES biology research, highlighting areas of investigation that we propose have the greatest potential to yield findings that will translate into clinically significant advances. PMID:26349414

  15. Biomarkers in Ewing Sarcoma: The Promise and Challenge of Personalized Medicine. A Report from the Childrens Oncology Group

    PubMed Central

    Shukla, Neerav; Schiffman, Joshua D.; Reed, Damon; Davis, Ian J.; Womer, Richard B.; Lessnick, Stephen L.; Lawlor, Elizabeth R.

    2013-01-01

    A goal of the COG Ewing Sarcoma (ES) Biology Committee is enabling identification of reliable biomarkers that can predict treatment response and outcome through the use of prospectively collected tissues and correlative studies in concert with COG therapeutic studies. In this report, we aim to provide a concise review of the most well-characterized prognostic biomarkers in ES, and to provide recommendations concerning design and implementation of future biomarker studies. Of particular interest and potentially high clinical relevance are studies of cell-cycle proteins, sub-clinical disease, and copy number alterations. We discuss findings of particular interest from recent biomarker studies and examine factors important to the success of identifying and validating clinically relevant biomarkers in ES. A number of promising biomarkers have demonstrated prognostic significance in numerous retrospective studies and now need to be validated prospectively in larger cohorts of equivalently treated patients. The eventual goal of refining the discovery and use of clinically relevant biomarkers is the development of patient specific ES therapeutic modalities. PMID:23761859

  16. High neuropeptide Y release associates with Ewing sarcoma bone dissemination - in vivo model of site-specific metastases.

    PubMed

    Hong, Sung-Hyeok; Tilan, Jason U; Galli, Susana; Izycka-Swieszewska, Ewa; Polk, Taylor; Horton, Meredith; Mahajan, Akanksha; Christian, David; Jenkins, Shari; Acree, Rachel; Connors, Katherine; Ledo, Phuong; Lu, Congyi; Lee, Yi-Chien; Rodriguez, Olga; Toretsky, Jeffrey A; Albanese, Chris; Kitlinska, Joanna

    2015-03-30

    Ewing sarcoma (ES) develops in bones or soft tissues of children and adolescents. The presence of bone metastases is one of the most adverse prognostic factors, yet the mechanisms governing their formation remain unclear. As a transcriptional target of EWS-FLI1, the fusion protein driving ES transformation, neuropeptide Y (NPY) is highly expressed and released from ES tumors. Hypoxia up-regulates NPY and activates its pro-metastatic functions. To test the impact of NPY on ES metastatic pattern, ES cell lines, SK-ES1 and TC71, with high and low peptide release, respectively, were used in an orthotopic xenograft model. ES cells were injected into gastrocnemius muscles of SCID/beige mice, the primary tumors excised, and mice monitored for the presence of metastases. SK-ES1 xenografts resulted in thoracic extra-osseous metastases (67%) and dissemination to bone (50%) and brain (25%), while TC71 tumors metastasized to the lungs (70%). Bone dissemination in SK-ES1 xenografts associated with increased NPY expression in bone metastases and its accumulation in bone invasion areas. The genetic silencing of NPY in SK-ES1 cells reduced bone degradation. Our study supports the role for NPY in ES bone invasion and provides new models for identifying pathways driving ES metastases to specific niches and testing anti-metastatic therapeutics. PMID:25714031

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

    PubMed Central

    Patel, Nikul; Black, Jennifer; Chen, Xi; Marcondes, A. Mario; Grady, William M.; Lawlor, Elizabeth R.; Borinstein, Scott C.

    2012-01-01

    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. PMID:23024594

  18. Tumor suppressive microRNA-138 inhibits metastatic potential via the targeting of focal adhesion kinase in Ewing's sarcoma cells.

    PubMed

    Tanaka, Kazuhiro; Kawano, Masanori; Itonaga, Ichiro; Iwasaki, Tatsuya; Miyazaki, Masashi; Ikeda, Shinichi; Tsumura, Hiroshi

    2016-03-01

    Short non-coding RNAs, called microRNAs (miRNAs), regulate cell biology by affecting the expression of target genes. However, we know little about the miRNAs regulating the growth and progression of Ewing's sarcoma (ES). To identify possible oncogenic factors in ES, we used a microarray-based approach to profile the changes in the expression of miRNAs and the downstream mRNAs in five ES cell lines. One miRNA, miR?138, was significantly downregulated, whereas the expression of focal adhesion kinase (FAK) was significantly upregulated in all tested ES cells. When miR?138 was transfected into ES cell lines, the expression of FAK in these cells was greatly suppressed and inhibited the proliferation and mobility of ES cells. Overexpression of miR?138 invitro resulted in further inhibition of the cell cycle at the G1 phase and in the induction of anoikis, in a dose- and time-dependent manner. Moreover, miR?138 overexpression in ES cells significantly suppressed the number of distant metastases invivo. The data in the present study demonstrates for the first time a novel mechanism that regulates the expression of FAK via miR?138 in ES cells. PMID:26782922

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

    PubMed Central

    Yamamoto, Yoshinari; Yamazaki, Kazuto; Ishida, Yasuo

    2015-01-01

    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. PMID:25948942

  20. The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma

    PubMed Central

    Fleuren, Emmy D.G.; Hillebrandt-Roeffen, Melissa H.S.; Flucke, Uta E.; te Loo, D. Maroeska W.M.; Boerman, Otto C.; van der Graaf, Winette T.A.; Versleijen-Jonkers, Yvonne M.H.

    2014-01-01

    New targets for Ewing sarcoma (ES) patients are urgently needed. Therefore, we investigated the expression and genetic aberrations of the oncogenic receptor tyrosine kinase (RTK) AXL in ES and determined the efficacy of AXL targeting on cell viability and migration. First, AXL and Gas6 (ligand) mRNA expression was determined by RT-PCR on 29 ES samples. Low, medium and high AXL mRNA expression was observed in 31% (n = 9), 48% (n = 14) and 21% (n = 6) of samples. Gas6 was abundantly present in all specimens. We next tested AXL protein expression immunohistochemically in 36 tumors (primary, post-chemotherapy, metastasized and relapsed samples) from 25 ES patients. Low, medium and high AXL protein expression was observed in 17% (n = 6), 19% (n = 7) and 36% (n = 13) of samples. In primary tumors (n = 15), high AXL expression correlated significantly with a worse overall survival compared to patients with lower expression (61 vs. 194 months, p = 0.026). No genetic aberrations were detected in the AXL RTK domain (n = 29). The AXL-inhibitor BGB324 affected viability (IC50 0.79–2.13 μmol/L) and migratory potential of all tested ES cell lines in vitro (n = 5–6). BGB324 chemosensitized chemotherapy-resistant ES-4 cells to vincristine and doxorubicin. These data suggest that AXL is a potential novel, druggable therapeutic target in ES. PMID:25528764

  1. Primary Ewing's sarcoma of the sinonasal tract, eroding the ethmoid and sphenoid sinus with intracranial extension: A rare case report

    PubMed Central

    NEGRU, MARIA EMANUELA; SPONGHINI, ANDREA PIETRO; RONDONOTTI, DAVID; PLATINI, FRANCESCA; GIAVARRA, MARCO; FORTI, LAURA; LOMBARDI, MARIANGELA; MASINI, LAURA; BOLDORINI, RENZO; GALETTO, ALESSANDRA

    2015-01-01

    Ewing's sarcoma (ES) is an aggressive tumour that may present with skeletal and extraskeletal forms. The extraskeletal form is rarely encountered in the head and neck region and is extremely rare in the sinonasal tract. This is the case report of a ES of the ethmoid sinus with intracranial and orbital extension in a 33-year-old male patient who presented with anosmia, epistaxis, reduction of visual acuity in the left eye and headache. On otorhinolaryngological clinical examination and biopsy via flexible endoscope, the lesion was misdiagnosed as ethmoid sinus carcinoma. The subsequent magnetic resonance imaging (MRI) of the brain revealed a large mass (6×7 cm) eroding the ethmoid and sphenoid sinuses, extending beyond the orbits and occupying the anterior cranial fossa with a maximum extension of ~5 cm. The patient underwent surgical resection and the microscopic examination of the specimen established the diagnosis of ES (immunohistochemically positive for CD99, neuron-specific enolase, CD56, synaptophysin, pancytokeratin, low-molecular weight cytokeratins and vimentin. The periodic acid Schiff stain exhibited strong intracytoplasmic block positivity and fluorescence in situ hybridization revealed a t(22;11) translocation. First-line chemotherapy was administered for 3 cycles; however, on restaging MRI, local disease progression was diagnosed. The patient received radiotherapy and second-line chemotherapy for 6 cycles. At 15 months after the diagnosis, the patient remains recurrence-free and maintains a good functional status and quality of life. PMID:26171185

  2. High neuropeptide Y release associates with Ewing sarcoma bone dissemination - in vivo model of site-specific metastases

    PubMed Central

    Hong, Sung-Hyeok; Tilan, Jason U.; Galli, Susana; Izycka-Swieszewska, Ewa; Polk, Taylor; Horton, Meredith; Mahajan, Akanksha; Christian, David; Jenkins, Shari; Acree, Rachel; Connors, Katherine; Ledo, Phuong; Lu, Congyi; Lee, Yi-Chien; Rodriguez, Olga; Toretsky, Jeffrey A.; Albanese, Chris; Kitlinska, Joanna

    2015-01-01

    Ewing sarcoma (ES) develops in bones or soft tissues of children and adolescents. The presence of bone metastases is one of the most adverse prognostic factors, yet the mechanisms governing their formation remain unclear. As a transcriptional target of EWS-FLI1, the fusion protein driving ES transformation, neuropeptide Y (NPY) is highly expressed and released from ES tumors. Hypoxia up-regulates NPY and activates its pro-metastatic functions. To test the impact of NPY on ES metastatic pattern, ES cell lines, SK-ES1 and TC71, with high and low peptide release, respectively, were used in an orthotopic xenograft model. ES cells were injected into gastrocnemius muscles of SCID/beige mice, the primary tumors excised, and mice monitored for the presence of metastases. SK-ES1 xenografts resulted in thoracic extra-osseous metastases (67%) and dissemination to bone (50%) and brain (25%), while TC71 tumors metastasized to the lungs (70%). Bone dissemination in SK-ES1 xenografts associated with increased NPY expression in bone metastases and its accumulation in bone invasion areas. The genetic silencing of NPY in SK-ES1 cells reduced bone degradation. Our study supports the role for NPY in ES bone invasion and provides new models for identifying pathways driving ES metastases to specific niches and testing anti-metastatic therapeutics. PMID:25714031

  3. Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution

    PubMed Central

    Huh, Jimi; Park, Seong Joon; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon; Tirumani, Sree Harsha; Ramaiya, Nikhil H.

    2015-01-01

    Objective To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. Materials and Methods We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for ? 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Results Among the 70 patients (mean age, 35.8 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9%). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Conclusion Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites. PMID:26175577

  4. Overexpression of miR-199b-5p inhibits Ewing's sarcoma cell lines by targeting CCNL1

    PubMed Central

    LI, WEIHUA; LI, YUXIA; GUO, JIANKUO; PAN, HUAGANG; ZHANG, YONGLE; WANG, XIAO

    2015-01-01

    MicroRNAs (miRNAs) are known to regulate the expression of a variety of genes, which are important in the development of several types of tumor, including Ewing's sarcoma (ES), at the post-transcriptional level. Although previous studies have identified that the expression of miRNA-199b-5p was downregulated in various types of tumor, the expression levels of miR-199b-5p in ES cells remain to be elucidated. The mechanism underlying ES via the miRNA pathway remains to be elucidated. The present study demonstrated that miR-199b-5p was an important regulator in ES cells and its expression was downregulated in ES originated A673/TC252 cells. The ES cell lines, A673 and TC252, were transfected with an miR-199b-5p mimic to overexpress the levels of this miRNA. This forced expression of miR-199b-5p suppressed the cell proliferation and invasion, arrested cell cycle progression, and promoted cell apoptosis. Furthermore, CCNL1 was identified by bioinformatic software as a potential target gene of miR-199b-5p. Following this, the present study identified CCNL1 as a direct target of miR-199b-5p in ES cells. Taken together, the present study established a functional link between ES, miR-199b-5p and CCNL1, and suggested that miR-199b-5p acts as a tumor suppressor and may be of diagnostic and therapeutic importance for human ES. PMID:26043836

  5. Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs

    PubMed Central

    Svoboda, Laurie K; Harris, Ashley; Bailey, Natashay J; Schwentner, Raphaela; Tomazou, Eleni; von Levetzow, Cornelia; Magnuson, Brian; Ljungman, Mats; Kovar, Heinrich; Lawlor, Elizabeth R

    2014-01-01

    The polycomb proteins BMI-1 and EZH2 are highly overexpressed by Ewing sarcoma (ES), a tumor of stem cell origin that is driven by EWS-ETS fusion oncogenes, most commonly EWS-FLI1. In the current study we analyzed expression of transcription programs that are controlled by polycomb proteins during embryonic development to determine if they are abnormal in ES. Our results show that polycomb target gene expression in ES deviates from normal tissues and stem cells and that, as expected, most targets are relatively repressed. However, we also discovered a paradoxical up regulation of numerous polycomb targets and these were highly enriched for homeobox (HOX) genes. Comparison of HOX profiles between malignant and non-malignant tissues revealed a distinctive HOX profile in ES, which was characterized by overexpression of posterior HOXD genes. In addition, ectopic expression of EWS-FLI1 during stem cell differentiation led to aberrant up regulation of posterior HOXD genes. Mechanistically, this up regulation was associated with altered epigenetic regulation. Specifically, ES and EWS-FLI1+ stem cells displayed a relative loss of polycomb-dependent H3K27me3 and gain of trithorax-dependent H3K4me3 at the promoters of posterior HOXD genes and also at the HOXD11.12 polycomb response element. In addition, a striking correlation was evident between HOXD13 and other genes whose regulation is coordinately regulated during embryonic development by distal enhancer elements. Together, these studies demonstrate that epigenetic regulation of polycomb target genes, in particular HOXD genes, is altered in ES and that these changes are mediated downstream of EWS-FLI1. PMID:25625846

  6. WEE1 accumulation and deregulation of S-phase proteins mediate MLN4924 potent inhibitory effect on Ewing sarcoma cells.

    PubMed

    Mackintosh, C; Garca-Domnguez, D J; Ordez, J L; Ginel-Picardo, A; Smith, P G; Sacristn, M P; de lava, E

    2013-03-14

    Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor of children and young adults in which finding effective new targeted therapies is imperative. Here, we report an in-depth preclinical study of the investigational cullin-RING ubiquitin ligase (CRL) inhibitor MLN4924 in ES, as we have recently demonstrated the implication of a CRL component in the ES pathogenesis. First, our results support a high sensitivity of ES cells to MLN4924 growth inhibition both in vitro (14 ES cell lines tested, median IC50=81?nM) and in tumor xenografts (tumor regression achieved with 60?mg/kg BID, subcutaneously, n=9). Second, we report a dual mechanism of action of MLN4924 in ES cells: while a wide range of MLN4924 concentrations (?30-300?nM) trigger a G2 arrest that can only be rescued by WEE1 kinase inhibition or depletion, saturating doses of the drug (>300?nM) cause a delay in S-phase progression concomitant with unbalanced CDK2-Cyclin E and CDK2-Cyclin A relative levels (accumulation of the first and depletion of the latter). The aberrant presence of CDC6 in the nucleus at late S-phase cell cycle stage confirmed the loss of CDK2-Cyclin A-specific functions. Remarkably, other mechanisms explored (P27 accumulation and DNA damage signaling pathways) were found unable to explain MLN4924 effects, strengthening the specificity of our findings and suggesting the absence of functionality of some CRL substrates accumulated in response to MLN4924. This study renders a rationale for clinical trials and contributes molecular mechanisms for a better understanding of this promising antitumoral agent. PMID:22641220

  7. 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma.

    PubMed

    Mackintosh, C; Ordez, J L; Garca-Domnguez, D J; Sevillano, V; Llombart-Bosch, A; Szuhai, K; Scotlandi, K; Alberghini, M; Sciot, R; Sinnaeve, F; Hogendoorn, P C W; Picci, P; Knuutila, S; Dirksen, U; Debiec-Rychter, M; Schaefer, K-L; de lava, E

    2012-03-01

    Despite extensive characterization of the role of the EWS-ETS fusions, little is known about secondary genetic alterations and their clinical contribution to Ewing sarcoma (ES). It has been demonstrated that the molecular structure of EWS-ETS lacks prognostic value. Moreover, CDKN2A deletion and TP53 mutation, despite carrying a poor prognosis, are infrequent. In this scenario identifying secondary genetic alterations with a significant prevalence could contribute to understand the molecular mechanisms underlying the most aggressive forms of ES.We screened a 67 ES tumor set for copy number alterations by array comparative genomic hybridization. 1q gain (1qG), detected in 31% of tumor samples, was found markedly associated with relapse and poor overall and disease-free survival and demonstrated a prognostic value independent of classical clinical parameters. Reanalysis of an expression dataset belonging to an independent tumor set (n=37) not only validated this finding but also led us to identify a transcriptomic profile of severe cell cycle deregulation in 1qG ES tumors. Consistently, a higher proliferation rate was detected in this tumor subset by Ki-67 immunohistochemistry. CDT2, a 1q-located candidate gene encoding a protein involved in ubiquitin ligase activity and significantly overexpressed in 1qG ES tumors, was validated in vitro and in vivo proving its major contribution to this molecular and clinical phenotype. This integrative genomic study of 105 ES tumors in overall renders the potential value of 1qG and CDT2 overexpression as prognostic biomarkers and also affords a rationale for the application of already available new therapeutic compounds selectively targeting the protein-ubiquitin machinery. PMID:21822310

  8. Potential of herpesvirus saimiri-based vectors to reprogram a somatic Ewing's sarcoma family tumor cell line.

    PubMed

    Brown, Hannah F; Unger, Christian; Whitehouse, Adrian

    2013-06-01

    Herpesvirus saimiri (HVS) infects a range of human cell types with high efficiency. Upon infection, the viral genome can persist as high-copy-number, circular, nonintegrated episomes that segregate to progeny cells upon division. This allows HVS-based vectors to stably transduce a dividing cell population and provide sustained transgene expression in vitro and in vivo. Moreover, the HVS episome is able to persist and provide prolonged transgene expression during in vitro differentiation of mouse and human hemopoietic progenitor cells. Together, these properties are advantageous for induced pluripotent stem cell (iPSC) technology, whereby stem cell-like cells are generated from adult somatic cells by exogenous expression of specific reprogramming factors. Here we assess the potential of HVS-based vectors for the generation of induced pluripotent cancer stem-like cells (iPCs). We demonstrate that HVS-based exogenous delivery of Oct4, Nanog, and Lin28 can reprogram the Ewing's sarcoma family tumor cell line A673 to produce stem cell-like colonies that can grow under feeder-free stem cell culture conditions. Further analysis of the HVS-derived putative iPCs showed some degree of reprogramming into a stem cell-like state. Specifically, the putative iPCs had a number of embryonic stem cell characteristics, staining positive for alkaline phosphatase and SSEA4, in addition to expressing elevated levels of pluripotent marker genes involved in proliferation and self-renewal. However, differentiation trials suggest that although the HVS-derived putative iPCs are capable of differentiation toward the ectodermal lineage, they do not exhibit pluripotency. Therefore, they are hereby termed induced multipotent cancer cells. PMID:23596304

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

    PubMed Central

    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. PMID:26571493

  10. Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.

    PubMed

    Svoboda, Laurie K; Harris, Ashley; Bailey, Natashay J; Schwentner, Raphaela; Tomazou, Eleni; von Levetzow, Cornelia; Magnuson, Brian; Ljungman, Mats; Kovar, Heinrich; Lawlor, Elizabeth R

    2014-12-01

    The polycomb proteins BMI-1 and EZH2 are highly overexpressed by Ewing sarcoma (ES), a tumor of stem cell origin that is driven by EWS-ETS fusion oncogenes, most commonly EWS-FLI1. In the current study we analyzed expression of transcription programs that are controlled by polycomb proteins during embryonic development to determine if they are abnormal in ES. Our results show that polycomb target gene expression in ES deviates from normal tissues and stem cells and that, as expected, most targets are relatively repressed. However, we also discovered a paradoxical up regulation of numerous polycomb targets and these were highly enriched for homeobox (HOX) genes. Comparison of HOX profiles between malignant and non-malignant tissues revealed a distinctive HOX profile in ES, which was characterized by overexpression of posterior HOXD genes. In addition, ectopic expression of EWS-FLI1 during stem cell differentiation led to aberrant up regulation of posterior HOXD genes. Mechanistically, this up regulation was associated with altered epigenetic regulation. Specifically, ES and EWS-FLI1+ stem cells displayed a relative loss of polycomb-dependent H3K27me3 and gain of trithorax-dependent H3K4me3 at the promoters of posterior HOXD genes and also at the HOXD11.12 polycomb response element. In addition, a striking correlation was evident between HOXD13 and other genes whose regulation is coordinately regulated during embryonic development by distal enhancer elements. Together, these studies demonstrate that epigenetic regulation of polycomb target genes, in particular HOXD genes, is altered in ES and that these changes are mediated downstream of EWS-FLI1. PMID:25625846

  11. Combining poly(ADP-ribose) polymerase 1 (PARP-1) inhibition and radiation in Ewing sarcoma results in lethal DNA damage

    PubMed Central

    Lee, Hae-June; Yoon, Changhwan; Schmidt, Benjamin; Park, Do Joong; Zhang, Alexia Y.; Erkizan, Hayriye V.; Toretsky, Jeffrey A.; Kirsch, David G.; Yoon, Sam S.

    2013-01-01

    Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to an ETS transcription factor, most commonly FLI1. The EWS-FLI1 fusion acts in a positive feedback loop to maintain expression of poly(ADP-ribose) polymerase 1 (PARP-1), which is involved in repair of DNA damage. Here, we examine the effects of PARP-1 inhibition and radiation therapy (RT) on ES. In proliferation assays, the ES cell lines RD-ES and SK-N-MC were much more sensitive than non-ES cell lines to the PARP-1 inhibitor olaparib (Ola) (IC50 0.51 uM vs >5 uM) and to radiation (IC50 24 Gy vs >6 Gy). PARP-1 inhibition with shRNA or Ola sensitized ES cells but not non-ES cells to RT in both proliferation and colony formation assays. Using the Comet assay, radiation of ES cells with Ola, compared to without Ola, resulted in more DNA damage at 1 hr (mean tail moment 3654 vs. 2628) and sustained DNA damage at 24 hr (2429 vs. 68). This DNA damage led to a 2.94.0 fold increase in apoptosis and a 1.62.4 fold increase in cell death. The effect of PARP-1 inhibition and RT on ES cells was lost when EWS-FLI1 was silenced by shRNA. A small dose of RT (4 Gy), when combined with PARP-1 inhibition, stopped growth of SK-N-MC flank tumors xenografts. In conclusion, PARP-1 inhibition in ES amplifies the level and duration of DNA damage caused by RT leading to synergistic increases in apoptosis and cell death in a EWS-FLI1 dependent manner. PMID:23966622

  12. Cytodiagnosis of metastatic Ewing's sarcoma of orbital mass and its confirmation by demonstration of EWS/friend leukemia integration 1 fusion gene

    PubMed Central

    Kar, Asaranti; Das, Upasana; Parija, Nimain C; Rout, Niranjan

    2014-01-01

    Ewing's sarcoma (EWS) is an undifferentiated sarcoma of bone. Its morphologic appearance resembles many other malignant small round cell tumors. Due to the morphologic overlap, there is diagnostic difficulty and for accurate diagnosis, requires special studies such as immunohistochemistry, electron microscopy, cytogenetics, and molecular genetic analysis. We report a case of metastatic EWS from orbital mass in a 14-year-old female child diagnosed by cytology after clinicopathologic evaluation. She presented with low back ache of 1 year followed by proptosis of the right eye and swelling of the right side chest wall. Cytosmear and Tru-cut biopsy was taken from the orbital mass showed features of EWS. It was confirmed later by further studies including demonstration of EWS/friend leukemia integration-1 fusion gene by molecular genetic analysis. PMID:25190984

  13. Long-range restriction map of human chromosome 22q11-22q12 between the lambda immunoglobulin locus and the Ewing sarcoma breakpoint

    SciTech Connect

    McDermid, H.E. ); Budarf, M.L.; Emanuel, B.S. Children's Hospital of Philadelphia, PA )

    1993-11-01

    A long-range restriction map of the region between the immunoglobulin lambda locus and the Ewing sarcoma breakpoint has been constructed using the rare-cutting enzymes NotI, NruI, AscI, and BsiWI. The map spans approximately 11,000 kb and represents about one-fifth of the long arm of chromosome 22. Thirty-nine markers, including seven NotI junction clones as well as numerous genes and anonymous sequences, were mapped to the region with a somatic cell hybrid panel. These probes were then used to produce the map. The seven NotI junction clones each identified a possible CpG island. The breakpoints of the RAJ5 hybrid and the Ewing sarcoma t(11;22) were also localized in the resulting map. This physical map will be useful in studying chromosomal rearrangements in the region, as well as providing the details to examine the fidelity of the YAC and cosmid contigs currently under construction. Comparisons of this physical map to genetic and radiation hybrid maps are discussed. 52 refs., 7 figs., 3 tabs.

  14. Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing's sarcoma A673-xenograft growth and normalize tumor vascular architecture.

    PubMed

    Ackermann, Maximilian; Morse, Brent A; Delventhal, Vera; Carvajal, Irvith M; Konerding, Moritz A

    2012-12-01

    Increasing experimental evidence suggests that IGF-1 may modulate tumor angiogenesis via activation of the expression of VEGF in Ewing sarcomas and rhabdomyosarcomas. This study investigates the effects of the PEGylated Adnectins CT-322, a VEGFR2-inhibitor and AT580Peg40, an IGF-1R inhibitor, as monotherapy and in combination in a murine A673 xenograft tumor model. The combination of Adnectins CT-322 and AT580Peg40 revealed a 83% reduction in tumor growth, a nearly 5 times lower vessel density, less necrotic areas and less appearance of intussusceptive angiogenesis. Monotherapy with IGF-1R or CT-322 revealed equally a significant inhibition of tumor and vessel growth. Combinatory inhibition of IGF-1R and VEGFR2 shows a downregulation of IGF-binding protein 2 and a compensatory upregulation of VEGF levels. Immunohistological analysis showed remodeling vascular effects of CT-322-treatment or combination therapy. The vascular architecture in Adnectin-treated tumors was characterized by a strong normalization of vasculature. 3D-evaluation in microvascular corrosion casts showed significantly higher intervascular and interbranching distances in Adnectin-treated tumors. CT-322-treatment and combinatory inhibition reveal a significant reduction of intussusceptive angiogenesis. These pronounced effects on tumor vasculature suggest potential therapeutic benefit of combinatorial IGF1- and VEGF-pathways inhibition in Ewing's sarcoma. PMID:22914877

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

    PubMed Central

    Alhaddad, Anna; Durieu, Catherine; Dantelle, Graldine; Le Cam, Eric; Malvy, Claude; Treussart, Franois; Bertrand, Jean-Rmi

    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

  16. Is the EWS/FLI-1 fusion transcript specific for Ewing sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types.

    PubMed Central

    Thorner, P.; Squire, J.; Chilton-MacNeil, S.; Marrano, P.; Bayani, J.; Malkin, D.; Greenberg, M.; Lorenzana, A.; Zielenska, M.

    1996-01-01

    The presence of t(11;22)(q24;q12) is often considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor. We report four cases, all of which possessed this translocation as detected by reverse transcriptase polymerase chain reaction and confirmed by sequencing with or without fluorescent in situ hybridization, but none of which were Ewing sarcoma or peripheral primitive neuroectodermal tumor by histological criteria. Two were polyphenotypic tumors and two were mixed embryonal and alveolar rhabdomyosarcomas. Only one case was positive for MIC2 by immunohistochemistry and only in a rare cell. Two cases (one polyphenotypic tumor and one rhabdomyosarcoma) had double minute chromosomes with > 100 copies of the MDM2 gene. The presence of the t(11;22)(q24;ql2) translocation should probably not be considered diagnostic of Ewing sarcoma and peripheral primitive neuroectodermal tumor in the absence of supporting histological evidence. The presence of this translocation in Ewing sarcoma and peripheral primitive neuroectodermal tumor has been taken as evidence that these two tumors are related. Extending this relationship to include some polyphenotypic tumors and some rhabdomyosarcomas may not be justified unless additional evidence is gathered. Pathologists and oncologists will need to decide whether treatment regimens for tumors are better based on phenotype rather than genotype when these two profiles are seemingly in conflict. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8644855

  17. Full-term newborn after repeated ovarian tissue transplants in a patient treated for Ewing sarcoma by sterilizing pelvic irradiation and chemotherapy.

    PubMed

    Rodriguez-Wallberg, Kenny A; Karlstrm, Per-Olof; Rezapour, Masoumeh; Castellanos, Enrique; Hreinsson, Julius; Rasmussen, Carsten; Sheikhi, Mona; Ouvrier, Bettina; Bozky, Bla; Olofsson, Jan I; Lundqvist, Monalill; Hovatta, Outi

    2015-03-01

    We report the first successful transplantation of cryopreserved ovarian cortical tissue into heavily irradiated tissues in a patient who had received sterilizing pelvic radiotherapy (54 Gy) and 40 weeks of intensive high-dose chemotherapy for the treatment of Ewing's sarcoma 14 years earlier. Repeated transplantation procedures were required to obtain fully functional follicular development. Enlargement of the transplants over time and increase of the size of the uterus were demonstrated on sequential ultrasonographic examinations. Eggs of good quality that could be fertilized in vitro were obtained only after a substantial incremental increase of the amount of ovarian tissue transplanted. Single embryo replacement resulted in a normal pregnancy and the birth of a healthy child by cesarean section at full-term. No neonatal or maternal postoperative complications occurred. Women facing high-dose pelvic radiotherapy should not be systematically excluded from fertility preservation options, as is currently the trend. PMID:25545009

  18. Stages of Ewing Sarcoma

    MedlinePLUS

    ... them from spreading. Monoclonal antibodies are given by infusion . They may be used alone or to carry ... and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) ...

  19. Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline isolated from Uncaria tomentosa bark on human Ewing's sarcoma and breast cancer cell lines.

    PubMed

    Garca Gimnez, Dolores; Garca Prado, Elena; Senz Rodrguez, Teresa; Fernndez Arche, Angeles; De la Puerta, Roco

    2010-02-01

    Preparations from Uncaria tomentosa, a South American Rubiaceae, have been used in the Peruvian traditional medicine for the treatment of infective, inflammatory and tumoral processes. In this study, the pentacyclic oxindole alkaloid mitraphylline was isolated from the dried inner bark of this plant species, and its structure elucidated by analysis of NMR spectroscopic data. Mitraphylline was differentially identified from its stereoisomeric pair isomitraphylline by (15)N-NMR. Its antiproliferative and cytotoxic effects have been tested on human Ewing's sarcoma MHH-ES-1 and breast cancer MT-3 cell lines, using cyclophosphamide and vincristine as reference controls. A Coulter counter was used to determine viable cell numbers, followed by the application of the tetrazolium compound MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] an inner salt. A colorimetric method was employed to evaluate cell viability in this cytotoxic assay. Micromolar concentrations of mitraphylline (5 microM to 40 microM) inhibited the growth of both cell lines in a dose-dependent manner. The IC (50) +/- SE values were 17.15 +/- 0.82 microM for MHH-ES-1 and 11.80 +/- 1.03 microM for MT-3 for 30 hours, smaller than those obtained for the reference compounds. This action suggests that the pentacyclic oxindole alkaloid mitraphylline might be a new promising agent in the treatment of both human sarcoma and breast cancer. PMID:19724995

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

    PubMed Central

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

    2016-01-01

    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. PMID:26942051

  1. Targeted therapy for sarcomas

    PubMed Central

    Forscher, Charles; Mita, Monica; Figlin, Robert

    2014-01-01

    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 Ewings sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewings 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. PMID:24669185

  2. Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

    ClinicalTrials.gov

    2014-08-26

    Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

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

    PubMed Central

    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 ?5 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 ?5 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

  4. Spontaneous conception in a young woman who had ovarian cortical tissue cryopreserved before chemotherapy and radiotherapy for a Ewing's sarcoma of the pelvis: case report.

    PubMed

    Bath, L E; Tydeman, G; Critchley, H O D; Anderson, R A; Baird, D T; Wallace, W H B

    2004-11-01

    We report the case of a 14 year old girl who presented with a non-metastatic Ewing's sarcoma involving her superior pubic ramus. She received 14 courses of alkylating agent-based chemotherapy and direct radiation to her hemi-pelvis (55 Gy) and is alive and disease-free 8 years later. Multiple biopsies of ovarian cortical tissue were cryopreserved, with her written consent, before treatment began. Ovarian failure was confirmed on completion of treatment with cessation of menses and persistently elevated serum gonadotrophin and low estradiol levels on repeated measurement over 2 years. HRT was initiated. Irregular vaginal bleeding occurred due to radiation vaginitis. Reimplantation of ovarian cortical tissue was considered at 19 years as fertility was desired, but the decision deferred. A spontaneous conception occurred 1 year later and a healthy boy (birthweight 2.9 kg, 3rd-10th centile) was delivered at term by elective Caesarean section. This is the first case of a spontaneous conception occurring in a young woman with documented ovarian failure in whom ovarian cortical tissue had been cryopreserved. Clinicians should be aware of the possibility of spontaneous conception despite confirmed ovarian failure in young women successfully treated for cancer. PMID:15310731

  5. Genotoxic stress inhibits Ewing sarcoma cell growth by modulating alternative pre-mRNA processing of the RNA helicase DHX9

    PubMed Central

    Volpe, Elisabetta; Miana, Beln; Caporossi, Daniela; Paronetto, Maria Paola

    2015-01-01

    Alternative splicing plays a key role in the DNA damage response and in cancer. Ewing Sarcomas (ES) are aggressive tumors caused by different chromosomal translocations that yield in-frame fusion proteins driving transformation. RNA profiling reveals genes differentially regulated by UV light irradiation in two ES cell lines exhibiting different sensitivity to genotoxic stress. In particular, irradiation induces a new isoform of the RNA helicase DHX9 in the more sensitive SK-N-MC cells, which is targeted to nonsense-mediated decay (NMD), causing its downregulation. DHX9 protein forms a complex with RNA polymerase II (RNAPII) and EWS-FLI1 to enhance transcription. Silencing of DHX9 in ES cells sensitizes them to UV treatment and impairs recruitment of EWS-FLI1 to target genes, whereas DHX9 overexpression protects ES cells from genotoxic stress. Mechanistically, we found that UV light irradiation leads to enhanced phosphorylation and decreased processivity of RNAPII in SK-N-MC cells, which in turn causes inclusion of DHX9 exon 6A. A similar effect on DHX9 splicing was also elicited by treatment with the chemotherapeutic drug etoposide, indicating a more general mechanism of regulation in response to DNA damage. Our data identify a new NMD-linked splicing event in DHX9 with impact on EWS-FLI1 oncogenic activity and ES cell viability. PMID:26450900

  6. Synergistic induction of apoptosis by a polo-like kinase 1 inhibitor and microtubule-interfering drugs in Ewing sarcoma cells.

    PubMed

    Wei, Lilly Magdalena; Hugle, Manuela; Romero, Sarah; Fulda, Simone

    2016-01-15

    Since polo-like kinase 1 (PLK1) is highly expressed in Ewing sarcoma (ES), we evaluated the therapeutic potential of the PLK1 inhibitor BI 6727. Here, we identify a synergistic induction of apoptosis by BI 6727 and several microtubule-interfering drugs in ES cells, including vincristine (VCR), vinblastine (VBL), vinorelbine (VNR) and eribulin. Synergistic drug interaction is confirmed by calculation of combination index (CI). Also, BI 6727 and VCR act in concert to reduce long-term clonogenic survival. Mechanistically, BI 6727/VCR co-treatment cooperates to trigger mitotic arrest, phosphorylation of BCL-2 and BCL-XL and downregulation of MCL-1. This inactivation of anti-apoptotic BCL-2 family proteins in turn promotes activation of BAX and BAK, activation of caspase-9 and -3 and caspase-dependent apoptosis. Overexpression of BCL-2 or simultaneous knockdown of BAX and BAK significantly rescue BI 6727/VCR-induced apoptosis, indicating that engagement of the mitochondrial pathway is critical for BI 6727/VCR-mediated apoptosis. The clinical relevance of PLK1 inhibitor-based combination therapies is underscored by the fact that BI 6727 is currently evaluated in phase I clinical trials in childhood cancer. In conclusion, PLK1 inhibitors such as BI 6727 may provide a new strategy to chemosensitize ES. PMID:26260582

  7. Genotoxic stress inhibits Ewing sarcoma cell growth by modulating alternative pre-mRNA processing of the RNA helicase DHX9.

    PubMed

    Fidaleo, Marco; Svetoni, Francesca; Volpe, Elisabetta; Miana, Beln; Caporossi, Daniela; Paronetto, Maria Paola

    2015-10-13

    Alternative splicing plays a key role in the DNA damage response and in cancer. Ewing Sarcomas (ES) are aggressive tumors caused by different chromosomal translocations that yield in-frame fusion proteins driving transformation. RNA profiling reveals genes differentially regulated by UV light irradiation in two ES cell lines exhibiting different sensitivity to genotoxic stress. In particular, irradiation induces a new isoform of the RNA helicase DHX9 in the more sensitive SK-N-MC cells, which is targeted to nonsense-mediated decay (NMD), causing its downregulation. DHX9 protein forms a complex with RNA polymerase II (RNAPII) and EWS-FLI1 to enhance transcription. Silencing of DHX9 in ES cells sensitizes them to UV treatment and impairs recruitment of EWS-FLI1 to target genes, whereas DHX9 overexpression protects ES cells from genotoxic stress. Mechanistically, we found that UV light irradiation leads to enhanced phosphorylation and decreased processivity of RNAPII in SK-N-MC cells, which in turn causes inclusion of DHX9 exon 6A. A similar effect on DHX9 splicing was also elicited by treatment with the chemotherapeutic drug etoposide, indicating a more general mechanism of regulation in response to DNA damage. Our data identify a new NMD-linked splicing event in DHX9 with impact on EWS-FLI1 oncogenic activity and ES cell viability. PMID:26450900

  8. The role of surgical margins in treatment of Ewing's sarcoma family tumors: Experience of a single institution with 512 patients treated with adjuvant and neoadjuvant chemotherapy

    SciTech Connect

    Bacci, Gaetano . E-mail: gaetano.bacci@ior.it; Longhi, Alessandra; Briccoli, Antonio; Bertoni, Franco; Versari, Michela; Picci, Piero

    2006-07-01

    Purpose: To evaluate the importance of surgical margins for local and systemic control of Ewing's sarcoma family tumors (ESFT). Methods and Materials: Between 1979 and 1999, 512 patients with ESFTs entered 4 different adjuvant and neoadjuvant studies performed at a single institution. Of these patients, 335 were treated with surgery alone (196) or surgery followed by radiotherapy at doses of 44.8 Gy (139). We compared their outcome with that of the 177 patients who were locally treated by radiotherapy at 60 Gy. Results: Local control (88.8% vs. 80.2%, p < 0.009) and 5-year disease-free survival (63.8% vs. 47.6%, p < 0.0007) were significantly better in patients treated with surgery and, among them, in those with adequate surgical margins (96.6% vs. 71,7%, p < 0.0008, and 69.6% vs. 46.3%, p < 0.0002). Nonetheless, better results were observed only in extremity tumors. Conclusions: Surgery is better than radiotherapy in cases of extremity ESFT with achievable adequate surgical margins, and in cases of inadequate surgical margins, adjuvant reduced-dose radiotherapy is ineffective. Therefore, when inadequate margins are expected, patients are better treated with full-dose radiotherapy from the start.

  9. Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS-ERG and common pitfalls in detecting EWSR1-ERG fusions by FISH.

    PubMed

    Chen, Sonja; Deniz, Kemal; Sung, Yun-Shao; Zhang, Lei; Dry, Sarah; Antonescu, Cristina R

    2016-04-01

    The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1-ERG being identified in 5-10% of cases, while only a handful of reports document a FUS-ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS-ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS-positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG-rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1-ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3-color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break-apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT-PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG-rearranged SBRCTs. © 2015 Wiley Periodicals, Inc. PMID:26690869

  10. Formation and Rupture of the Internal Carotid Artery Aneurysm after Multiple Courses of Intensity-Modulated Radiation Therapy for Management of the Skull Base Ewing Sarcoma/PNET: Case Report

    PubMed Central

    Tamura, Manabu; Kogo, Kasei; Masuo, Osamu; Oura, Yoshinori; Matsumoto, Hiroyuki; Fujita, Koji; Nakao, Naoyuki; Uematsu, Yuji; Itakura, Toru; Chernov, Mikhail; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi

    2013-01-01

    Background?Aneurysm formation after stereotactic irradiation of skull base tumors is rare. The formation and rupture of an internal carotid artery (ICA) aneurysm in a patient with skull base Ewing sarcoma/primitive neuroectodermal tumor (PNET), who underwent surgery followed by multiple courses of intensity-modulated radiation therapy (IMRT) and chemotherapy, is described. Case Description?A 25-year-old man presented with a sinonasal tumor with intraorbital and intracranial growth. At that time cerebral angiography did not reveal any vascular abnormalities. The lesion was resected subtotally. Histopathologic diagnosis was Ewing sarcoma/PNET. The patient underwent multiple courses of chemotherapy and three courses of IMRT at 3, 28, and 42 months after initial surgery. The total biologically effective dose delivered to the right ICA was 220.2 Gy. Seven months after the third IMRT, the patient experienced profound nasal bleeding that resulted in hypovolemic shock. Angiography revealed a ruptured right C4C5 aneurysm and irregular stenotic changes of the ICA. Lifesaving endovascular trapping of the right ICA was done. The patient recovered well after surgery but died due to tumor recurrence 6 months later. Conclusion?Excessive irradiation of the ICA may occasionally result in aneurysm formation, which should be borne in mind during stereotactic irradiation of malignant skull base tumors. PMID:24303346

  11. Formation and Rupture of the Internal Carotid Artery Aneurysm after Multiple Courses of Intensity-Modulated Radiation Therapy for Management of the Skull Base Ewing Sarcoma/PNET: Case Report.

    PubMed

    Tamura, Manabu; Kogo, Kasei; Masuo, Osamu; Oura, Yoshinori; Matsumoto, Hiroyuki; Fujita, Koji; Nakao, Naoyuki; Uematsu, Yuji; Itakura, Toru; Chernov, Mikhail; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi

    2013-12-01

    Background?Aneurysm formation after stereotactic irradiation of skull base tumors is rare. The formation and rupture of an internal carotid artery (ICA) aneurysm in a patient with skull base Ewing sarcoma/primitive neuroectodermal tumor (PNET), who underwent surgery followed by multiple courses of intensity-modulated radiation therapy (IMRT) and chemotherapy, is described. Case Description?A 25-year-old man presented with a sinonasal tumor with intraorbital and intracranial growth. At that time cerebral angiography did not reveal any vascular abnormalities. The lesion was resected subtotally. Histopathologic diagnosis was Ewing sarcoma/PNET. The patient underwent multiple courses of chemotherapy and three courses of IMRT at 3, 28, and 42 months after initial surgery. The total biologically effective dose delivered to the right ICA was 220.2 Gy. Seven months after the third IMRT, the patient experienced profound nasal bleeding that resulted in hypovolemic shock. Angiography revealed a ruptured right C4-C5 aneurysm and irregular stenotic changes of the ICA. Lifesaving endovascular trapping of the right ICA was done. The patient recovered well after surgery but died due to tumor recurrence 6 months later. Conclusion?Excessive irradiation of the ICA may occasionally result in aneurysm formation, which should be borne in mind during stereotactic irradiation of malignant skull base tumors. PMID:24303346

  12. Pericytes in sarcomas of bone.

    PubMed

    Chang, Le; Nguyen, Vi; Nguyen, Alan; Scott, Michelle A; James, Aaron W

    2015-07-01

    Pericytes are mesenchymal cells that closely enwrap small blood vessels, lying in intimate association with the endothelium. Pericytes have recently gained attention as an important mediator of vascular biology and angiogenesis in cancer. Although better studied in carcinoma, pericytes have known interaction with sarcomas of bone, including Ewing's sarcoma, osteosarcoma, and chondrosarcoma. Best studied is Ewing's sarcoma (ES), which displays a prominent perivascular growth pattern. Signaling pathways of known importance in intratumoral pericytes in ES include Notch, PDGF/PDGFR-β, and VEGF signaling. In summary, pericytes serve important functions in the tumor microenvironment. Improved understanding of pericyte biology may hold significant implications for the development of new therapies in sarcoma. PMID:26076804

  13. Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2015-05-22

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

  14. Genetics Home Reference: Ewing sarcoma

    MedlinePLUS

    ... binds) to DNA and regulates an activity called transcription, which is the first step in the production ... development of some cell types by regulating the transcription of certain genes. The EWS protein, produced from ...

  15. Treatment Options for Ewing Sarcoma

    MedlinePLUS

    ... them from spreading. Monoclonal antibodies are given by infusion . They may be used alone or to carry ... and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) ...

  16. High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant.

    PubMed

    Farnie, Gillian; Sotgia, Federica; Lisanti, Michael P

    2015-10-13

    Chemo-resistance is a clinical barrier to more effective anti-cancer therapy. In this context, cancer stem-like cells (CSCs) are thought to be chemo-resistant, resulting in tumor recurrence and distant metastasis. Our hypothesis is that chemo-resistance in CSCs is driven, in part, by enhanced mitochondrial function. Here, we used breast cell lines and metastatic breast cancer patient samples to begin to dissect the role of mitochondrial metabolism in conferring the CSC phenotype. More specifically, we employed fluorescent staining with MitoTracker (MT) to metabolically fractionate these cell lines into mito-high and mito-low sub-populations, by flow-cytometry. Interestingly, cells with high mitochondrial mass (mito-high) were specifically enriched in a number of known CSC markers, such as aldehyde dehydrogenase (ALDH) activity, and they were ESA+/CD24-/low and formed mammospheres with higher efficiency. Large cell size is another independent characteristic of the stem cell phenotype; here, we observed a >2-fold increase in mitochondrial mass in large cells (>12-?m), relative to the smaller cell population (4-8-?m). Moreover, the mito-high cell population showed a 2.4-fold enrichment in tumor-initiating cell activity, based on limiting dilution assays in murine xenografts. Importantly, primary human breast CSCs isolated from patients with metastatic breast cancer or a patient derived xenograft (PDX) also showed the co-enrichment of ALDH activity and mitochondrial mass. Most significantly, our investigations demonstrated that mito-high cells were resistant to paclitaxel, resulting in little or no DNA damage, as measured using the comet assay. In summary, increased mitochondrial mass in a sub-population of breast cancer cells confers a stem-like phenotype and chemo-resistance. As such, our current findings have important clinical implications for over-coming drug resistance, by therapeutically targeting the mito-high CSC population. PMID:26421710

  17. High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant

    PubMed Central

    Farnie, Gillian; Sotgia, Federica; Lisanti, Michael P.

    2015-01-01

    Chemo-resistance is a clinical barrier to more effective anti-cancer therapy. In this context, cancer stem-like cells (CSCs) are thought to be chemo-resistant, resulting in tumor recurrence and distant metastasis. Our hypothesis is that chemo-resistance in CSCs is driven, in part, by enhanced mitochondrial function. Here, we used breast cell lines and metastatic breast cancer patient samples to begin to dissect the role of mitochondrial metabolism in conferring the CSC phenotype. More specifically, we employed fluorescent staining with MitoTracker (MT) to metabolically fractionate these cell lines into mito-high and mito-low sub-populations, by flow-cytometry. Interestingly, cells with high mitochondrial mass (mito-high) were specifically enriched in a number of known CSC markers, such as aldehyde dehydrogenase (ALDH) activity, and they were ESA+/CD24-/low and formed mammospheres with higher efficiency. Large cell size is another independent characteristic of the stem cell phenotype; here, we observed a >2-fold increase in mitochondrial mass in large cells (>12-μm), relative to the smaller cell population (4–8-μm). Moreover, the mito-high cell population showed a 2.4-fold enrichment in tumor-initiating cell activity, based on limiting dilution assays in murine xenografts. Importantly, primary human breast CSCs isolated from patients with metastatic breast cancer or a patient derived xenograft (PDX) also showed the co-enrichment of ALDH activity and mitochondrial mass. Most significantly, our investigations demonstrated that mito-high cells were resistant to paclitaxel, resulting in little or no DNA damage, as measured using the comet assay. In summary, increased mitochondrial mass in a sub-population of breast cancer cells confers a stem-like phenotype and chemo-resistance. As such, our current findings have important clinical implications for over-coming drug resistance, by therapeutically targeting the mito-high CSC population. PMID:26421710

  18. Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

    ClinicalTrials.gov

    2015-03-19

    Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Gliosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma

  19. Molecular pathology in sarcomas.

    PubMed

    de Alava, E

    2007-03-01

    Bone and soft tissue sarcomas are an infrequent group of tumours. Their prevalence is 4 in 100,000 people/year, making the disease quite rare. Some of these tumours, such as synovial sarcoma, Ewing tumour and osteosarcoma, are more usual in adolescents or in young adults; there are, though, some neoplasias such as leiomyosarcoma or liposarcoma that are more frequent in patients over 55 years. There are more than a hundred different types of sarcomas from the histological point of view. This is the main limitation at the time of finding major clinic essays on patients with specific types of sarcomas. From the molecular point of view, these neoplasias are grouped into two main types: (a) sarcomas showing specific genetic alterations and relatively simple karyotypes, and translocations which originate gene fusions (e.g., EWS-FLI1 in Ewing tumour); or specific genetic mutations (e.g., c-kit in the gastrointestinal stromal tumour), and (b) sarcomas showing unspecific gene alterations and very complex karyotypes, and very numerous gains and losses. This review describes diverse types of molecular alterations as well, their utility in the clinical domain, as well as implications for the pathologist in translational research in sarcomas. PMID:17403624

  20. The Epidemiology of Sarcoma

    PubMed Central

    2012-01-01

    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 Kaposis 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 <0.001). A recent meta-analysis reported that children with a history of hernias have a greater risk of developing Ewings sarcoma (adjusted OR 3.2, 95% CI 1.9, 5.7). Bone development during pubertal growth spurts has been associated with osteosarcoma development. Occupational factors such as job type, industry, and exposures to chemicals such as herbicides and chlorophenols have been suggested as risk factors for sarcomas. A case-control study found a significant increase in soft tissue sarcoma risk among gardeners (adjusted OR 4.1, 95% CI 1.00, 14.00), but not among those strictly involved in farming. A European-based study reported an increased risk in bone tumors among blacksmiths, toolmakers, or machine-tool operators (adjusted OR 2.14, 95% CI 1.08, 4.26). Maternal and paternal characteristics such as occupation, age, smoking status, and health conditions experienced during pregnancy also have been suggested as sarcoma risk factors and would be important to assess in future studies. The limited studies we identified demonstrate significant relationships with sarcoma risk, but many of these results now require further validation on larger populations. Furthermore, little is known about the biologic mechanisms behind each epidemiologic association assessed in the literature. Future molecular epidemiology studies may increase our understanding of the genetic versus environmental contributions to tumorigenesis in this often deadly cancer in children and adults. PMID:23036164

  1. Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-?B-dependent pathway downregulating MGMT expression.

    PubMed

    Lan, Fengming; Yang, Yang; Han, Jing; Wu, Qiaoli; Yu, Huiming; Yue, Xiao

    2016-02-01

    The survival benefits of patients with glioblastoma (GBM) remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ). We elucidated the mechanisms of sulforaphane (SFN) reverse TMZ resistance in TMZ-inducing cell lines by inhibiting nuclear factor-?B (NF-?B) transcriptional activity. TMZ-resistant cell lines (U87-R and U373-R) were generated by stepwise (6months) exposure of parental cells to TMZ. Luciferase reporter assay, biochemical assays and subcutaneous tumor establishment were used to characterize the antitumor effect of SFN. MGMT expression and 50% inhibiting concentration(IC50) values of TMZ in GBM cell lines were assessed. Next, we established that U87-R and U373-R cells presenting high IC50 of TMZ, activated NF-?B transcription and significantly increased MGMT expression compared with untreated cells. Furthermore, we revealed that SFN could significantly suppress proliferation of TMZ-resistant GBM cells. In addition, SFN effectively inhibited activity of NF-?B signaling pathway and then reduced MGMT expression to reverse the chemo-resistance to TMZ in T98G, U87-R and U373-R cell lines. Sequential combination with TMZ synergistically inhibited survival capability and increased the induction of apoptosis in TMZ-resistant GBM cells. Finally, a nude mouse model was established with U373-R cell subcutaneous tumor-bearing mice, and results showed that SFN could remarkably suppress cell growth and enhance cell death in chemo-resistant xenografts in the nude mouse model. Collectively, the present study suggests that the clinical efficacy of TMZ-based chemotherapy in TMZ-resistant GBM may be improved by combination withSFN. PMID:26648123

  2. Targeted therapies for bone sarcomas

    PubMed Central

    Heymann, Dominique; Rdini, Franoise

    2013-01-01

    Bone sarcomas include a very large number of tumour subtypes, which originate form bone and more particularly from mesenchymal stem cell lineage. Osteosarcoma, Ewing's sarcoma and chondrosarcoma, the three main bone sarcoma entities develop in a favourable microenvironment composed by bone cells, blood vessels, immune cells, based on the seed and soil theory'. Current therapy associates surgery and chemotherapy, however, bone sarcomas remain diseases with high morbidity and mortality especially in children and adolescents. In the past decade, various new therapeutic approaches emerged and target the tumour niche or/and directly the tumour cells by acting on signalling/metabolic pathways involved in cell proliferation, apoptosis or drug resistance. The present review gives a brief overview from basic to clinical assessment of the main targeted therapies of bone sarcoma cells. PMID:24422100

  3. APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

    PubMed Central

    2009-01-01

    Background 5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets. Methods Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified. Results APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set. Stratified analysis revealed that protein expression of APRIL in the tumour stroma is associated with survival in adjuvant 5FU treated patients only (n = 103, p < 0.001), and is independently predictive of lack of clinical benefit from adjuvant 5FU [HR 6.25 (95%CI 1.48-26.32), p = 0.013]. Conclusions A combined investigative model, analysing the transcriptional response in clinical tumour specimens and cancers cell lines, has identified APRIL, a novel chemo-resistance biomarker with independent predictive impact in 5FU-treated CRC patients, that may represent a target for novel therapeutics. PMID:20003335

  4. Mir-34a Mimics Are Potential Therapeutic Agents for p53-Mutated and Chemo-Resistant Brain Tumour Cells

    PubMed Central

    Fan, Yuen Ngan; Meley, Daniel; Pizer, Barry; Se, Violaine

    2014-01-01

    Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma) and adult (glioblastoma) brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs) have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1). Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells. PMID:25250818

  5. Epidemiology and therapies for metastatic sarcoma

    PubMed Central

    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

  6. Kaposi's Sarcoma

    MedlinePLUS

    ... Rights Job Postings Sections of the JAOCD JAOCD Archive Published Members Online Dermatology Journals Edit This Favorite Name: Category: Share: Yes No, Keep Private Kaposi’s Sarcoma Share | Kaposi’s sarcoma (KS) is a ...

  7. The importance of Src signaling in sarcoma

    PubMed Central

    CHEN, QUANCHI; ZHOU, ZIFEI; SHAN, LIANCHENG; ZENG, HUI; HUA, YINGQI; CAI, ZHENGDONG

    2015-01-01

    Src is a tyrosine kinase that is of significance in tumor biology. The present review focuses on Src, its molecular structure, and role in cancer, in addition to its expression and function in sarcoma. In addition, the feasibility of Src as a potential drug target for the treatment of sarcoma is also discussed. Previous studies have suggested that Src has essential functions in cell proliferation, apoptosis, invasion, metastasis and the tumor microenvironment. Thus, it may be a potential target for cancer therapy. Src has been found to enhance proliferation, reduce apoptosis and promote metastasis in certain subtypes of sarcoma, including osteosarcoma, chondrosarcoma and Ewing's sarcoma. Furthermore, a number of novel effective therapeutic agents, such as SI-83, which target Src have been investigated in vitro and in vivo. Bosutinib and dasatinib, which inhibit Src, have been approved by the U.S. Food and Drug Administration for the treatment of chronic myelogenous leukemia. In addition, vandetanib is approved for the treatment of medullary thyroid cancer. Furthermore, the Src inhibitor, saracatinib, is currently in clinical trials for the treatment of a variety of solid tumors, including breast and lung cancers. Thus, Src is considered to be an important factor in sarcoma progression and may present a novel clinical therapeutic target. This review demonstrates the importance and clinical relevance of Src in sarcoma, and discusses a number of small molecular inhibitors of src kinase, such as dasatinib and sarcatinib, which are currently in clinical trials for the treatment of sarcoma patients. PMID:26170970

  8. Round cell sarcomas - biologically important refinements in subclassification.

    PubMed

    Mario-Enrquez, Adrin; Fletcher, Christopher D M

    2014-08-01

    Round cell sarcomas are a heterogeneous group of tumors that often affect children and young adults and, if untreated, often pursue a very aggressive clinical course. Specific subtypes of round cell sarcoma, like Ewing sarcoma or rhabdomyosarcoma, respond to well-defined therapeutic regimens so that proper classification is crucial for appropriate patient management. A subset of round cell sarcomas, however, lack specific clinical, morphologic, and immunophenotypic features and cannot be unequivocally classified based on such features. Systematic application of cytogenetics and molecular genetic techniques has allowed for the identification of an increasing number of genetically defined subgroups within this category of undifferentiated tumors. Although the clinical relevance of these molecular categories is yet to be proven, the systematic identification of lesions that share reproducible biologic, and often morphologic and immunophenotypic features, has great impact in terms of biologic understanding and coherent classification schemes, and will help to guide the potential development of rational new therapies. In this review we discuss the main categories of undifferentiated round cell sarcoma, in relation to Ewing sarcoma and its molecular variants, with particular emphasis on the genetic and biologic features of recently described entities including desmoplastic small round cell tumor and CIC-DUX4 as well as BCOR-CCNB3-associated round cell sarcomas. This article is part of a Directed Issue entitled: Rare Cancers. PMID:24801613

  9. Celecoxib enhanced the cytotoxic effect of cisplatin in chemo-resistant gastric cancer xenograft mouse models through a cyclooxygenase-2-dependent manner.

    PubMed

    Xu, Hong-Bin; Shen, Fu-Ming; Lv, Qian-Zhou

    2016-04-01

    Our previous study suggested that co-administration of celecoxib increased chemo-sensitivity of multidrug-resistant human gastric cancer SGC-7901/DDP cells to cisplatin (DDP) in vitro. The present study was designed to investigate whether celecoxib had the similar activities in vivo. SGC-7901/DDP and SGC-7901 xenograft mouse models were established. At the end of the experiment, cisplatin treatment alone significantly inhibited tumor growth in SGC-7901 xenograft, as compared with that in SGC-7901/DDP xenograft, suggesting that it maintained cisplatin sensitivity. When cisplatin and celecoxib were co-administrated, their antitumor activities were augmented in SGC-7901/DDP xenograft. The levels of Ki67 and PCNA after combination therapy were significantly decreased in SGC-7901/DDP xenograft, as compared with those of cisplatin treatment alone. Moreover, examining the apoptotic index by TUNEL assay showed similar results. Further studies demonstrated the inhibitory effect of celecoxib on cyclooxygenase-2 and P-glycoprotein expression was the possible reason to increase sensitivity of SGC-7901/DDP cells to cisplatin in vivo. However, the ratio of thromboxane B2 and prostaglandin F1α was elevated after celecoxib treatment in mice. This has been proposed to increase the risk of thrombogenesis. Further studies are required to evaluate the efficacy and safety of celecoxib for reducing chemo-resistance in gastric cancer. PMID:26879869

  10. [Molecular biology of sarcoma and therapeutic choices].

    PubMed

    Dufresne, Armelle; Cassier, Philippe; Heudel, Pierre; Pissaloux, Daniel; Wang, Qing; Blay, Jean-Yves; Ray-Coquard, Isabelle

    2015-01-01

    Soft tissue sarcomas (STS) are a set of very heterogeneous tumors with numerous histological categories. The development of the molecular biology allowed identifying recurring molecular anomalies in certain subgroups of sarcomas, being able to represent diagnostic, prognosis and therapeutic tools. The molecular classification of STS includes until today 5 main groups of abnormalities: sarcomas with "simple genomic profile" showing reciprocal (1) chromosomal translocations, (2) activating mutation, (3) inhibitive mutation or (4) simple amplification; (5) sarcomas with "complex genomic profile" can include several tens of molecular abnormalities. The development of new-targeted therapies is based on the identification of a target, specific of a tumors subgroup and involved in carcinogenesis mechanisms and/or tumoral growth. Then, the aim of clinical research is to establish the proof of the concept through clinical trials, demonstrating the benefit brought to the patient and ending in the marketing of the drug. This proof of the concept was clearly established for imatinib, sunitinib and regorafenib in gastrointestinal stromal tumors, for imatinib in dermatofibrosarcoma protuberans and pigmented vilo-nodular synovitis, for denosumab in giant cell tumors of the bone, ending in the authorization to use these new therapies in these indications. It is in progress and promising for anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory tumors, for mTOR inhibitor in PEComas... The role of molecular abnormalities identified in the mechanisms of tumoral progress for sarcomas and their potential therapeutic impact will be detailed. PMID:25609490

  11. Novel peptide binds EWS-FLI1 and reduces the oncogenic potential in Ewing tumors

    PubMed Central

    Erkizan, Hayriye V; Scher, Lauren J; Gamble, S Ellen; Barber-Rotenberg, Julie S; Sajwan, Kamal P; Üren, Aykut

    2011-01-01

    Ewing tumor is driven by the oncogenic EWS-FLI1 fusion protein that functions as an aberrant transcription factor. The identification of EWS-FLI1 protein partners is essential to enhance its vulnerability as a therapeutic target. We utilized phage display library screening against recombinant EWS-FLI1 protein. We identified 27 unique Ewing Sarcoma binding peptides. The cytotoxicity evaluation of these peptides with in EWS-FLI1 containing cell lines yielded one potent peptide called ESAP1 (TMRGKKKRTRAN). ESAP1 binds EWS-FLI1 with 0.202 micromolar affinity as measured in surface plasmon resonance. The minimal interaction region of ESAP1 is characterized and found that the lysine residues are critical for cellular cytotoxicity. ESAP1 reduces the transcriptional activity of EWS-FLI1 as well as disrupts cell cycle kinetics in Ewing tumor cells. These findings provide both a novel experimental probe and a potential therapeutic scaffold for Ewing tumor. PMID:21926473

  12. Sensitization of Chemo-Resistant Human Chronic Myeloid Leukemia Stem-Like Cells to Hsp90 Inhibitor by SIRT1 Inhibition

    PubMed Central

    Kim, Hak-Bong; Lee, Su-Hoon; Um, Jee-Hyun; Kim, Mi-Ju; Hyun, Suh-Kyung; Gong, Eun-Ji; Oh, Won Keun; Kang, Chi-Dug; Kim, Sun-Hee

    2015-01-01

    Development of effective therapeutic strategies to eliminate cancer stem-like cells (CSCs), which play a major role in drug resistance and disease recurrence, is critical to improve cancer treatment outcomes. The current investigation was undertaken to examine the effectiveness of the combination treatment of Hsp90 inhibitor and SIRT1 inhibitor in inhibiting the growth of chemo-resistant stem-like cells isolated from human chronic myeloid leukemia K562 cells. Inhibition of SIRT1 by use of SIRT1 siRNA or SIRT1 inhibitors (amurensin G and EX527) effectively potentiated sensitivity of Hsp90 inhibitors (17-AAG and AUY922) in CD44high K562 stem-like cells expressing high levels of CSC-related molecules including Oct4, CD34, ?-catenin, c-Myc, mutant p53 (mut p53), BCRP and P-glycoprotein (P-gp) as well as CD44. SIRT1 depletion caused significant down-regulation of heat shock factor 1 (HSF1)/heat shock proteins (Hsps) as well as these CSC-related molecules, which led to the sensitization of CD44high K562 cells to Hsp90 inhibitor by SIRT1 inhibitor. Moreover, 17-AAG-mediated activation of HSF1/Hsps and P-gp-mediated efflux, major causes of Hsp90 inhibitor resistance, was suppressed by SIRT1 inhibitor in K562-CD44high cells. Our data suggest that combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be an effective therapeutic approach to target CSCs that are resistant to current therapies. PMID:26157347

  13. Combination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX-2 signaling pathways

    SciTech Connect

    Hwang, Jin-Taek; Ha, Joohun; Park, Ock Jin . E-mail: ojpark@hannam.ac.kr

    2005-07-01

    5-Fluorouracil (5-FU) is one of the widely used chemotherapeutic drugs targeting various cancers, but its chemo-resistance remains as a major obstacle in clinical settings. In the present study, HT-29 colon cancer cells were markedly sensitized to apoptosis by both 5-FU and genistein compared to the 5-FU treatment alone. There is an emerging evidence that genistein, soy-derived phytoestrogen, may have potential as a chemotherapeutic agent capable of inducing apoptosis or suppressing tumor promoting proteins such as cyclooxygenase-2 (COX-2). However, the precise mechanism of cellular cytotoxicity of genistein is not known. The present study focused on the correlation of AMPK and COX-2 in combined cytotoxicity of 5-FU and genistein, since AMPK is known as a primary cellular homeostasis regulator and a possible target molecule of cancer treatment, and COX-2 as cell proliferation and anti-apoptotic molecule. Our results demonstrated that the combination of 5-FU and genistein abolished the up-regulated state of COX-2 and prostaglandin secretion caused by 5-FU treatment in HT-29 colon cancer cells. These appear to be followed by the specific activation of AMPK and the up-regulation of p53, p21, and Bax by genistein. Under same conditions, the induction of Glut-1 by 5-FU was diminished by the combination treatment with 5-FU and genistein. Furthermore, the reactive oxygen species (ROS) was found as an upstream signal for AMPK activation by genistein. These results suggested that the combination of 5-FU and genistein exert a novel chemotherapeutic effect in colon cancers, and AMPK may be a novel regulatory molecule of COX-2 expression, further implying its involvement in cytotoxicity caused by genistein.

  14. MicroRNA 192 regulates chemo-resistance of lung adenocarcinoma for gemcitabine and cisplatin combined therapy by targeting Bcl-2

    PubMed Central

    Cao, Jun; He, Yang; Liu, Hong-Qiang; Wang, Sai-Bo; Zhao, Bao-Cheng; Cheng, Ying-Sheng

    2015-01-01

    Lung cancer is the most leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) accounting for over 80% of all lung cancer cases. Patients with NSCLC are mostly treated with platinum-based chemotherapy. Chemoresistance is a leading cause of chemo-therapy failure in NSCLC treatment. Recent studies have shown that dysregulation of microRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. In this paper, we try to test whether miR-192 regulates chemo-resistance in human carcinoma A549 mice model by targeting Bcl-2. Mice model of human lung adenocarcinoma was built up, and was used for gemcitabine and cisplatin combined chemotherapy. MTT assay, real-time RT-PCR, western blotting assay were used to investigate miR-192 expression levels, cell viability ratio and Bcl-2 protein expression levels. MiR-192 expression level in A549 cells is significantly higher than in normal human bronchial epithelial cells. MiR-192 inhibitor treated tumor exhibits sensitivity to cisplatin and gemcitabine therapy. Bcl-2 mRNA and protein expression levels up-regulated in miR-192 inhibitor treated tumor. Bcl-2 is a key regulator for miR-192 related chemotherapy resistance. In this study, we demonstrate that miR-192 regulates chemoresistance for gemcitabine and cisplatin combined chemotherapy in human adenocarcinoma lung cancer A549 cells, and Bcl-2 is the target of miR-192. PMID:26550150

  15. Kaposi's sarcoma.

    PubMed

    Cho, J; Chachoua, A

    1992-08-01

    In the era before the acquired immunodeficiency syndrome, Kaposi's sarcoma was a rare cutaneous event. Most reported cases usually originated from one of two geographic regions, an induced immunosuppressed state, or sporadically with various neoplasms that have been known to cause immunosuppression. Since the first cases described with acquired immunodeficiency syndrome in 1981 from New York and San Francisco, this uncommon disorder has had an increased incidence that crosses geographic boundaries. This article describes the current understanding of the pathogenesis of Kaposi's sarcoma and treatments used to ameliorate this disorder. PMID:1380838

  16. Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival.

    PubMed

    Shor, Audrey C; Keschman, Elizabeth A; Lee, Francis Y; Muro-Cacho, Carlos; Letson, G Douglas; Trent, Jonathan C; Pledger, W Jack; Jove, Richard

    2007-03-15

    Sarcomas are rare malignant mesenchymal tumors for which there are limited treatment options. One potential molecular target for sarcoma treatment is the Src tyrosine kinase. Dasatinib (BMS-354825), a small-molecule inhibitor of Src kinase activity, is a promising cancer therapeutic agent with p.o. bioavailability. Dasatinib exhibits antitumor effects in cultured human cell lines derived from epithelial tumors, including prostate and lung carcinomas. However, the action of dasatinib in mesenchymally derived tumors has yet to be shown. Based on our previous findings of Src activation in human sarcomas, we evaluated the effects of dasatinib in 12 cultured human sarcoma cell lines derived from bone and soft tissue sarcomas. Dasatinib inhibited Src kinase activity at nanomolar concentrations in these sarcoma cell lines. Downstream components of Src signaling, including focal adhesion kinase and Crk-associated substrate (p130(CAS)), were also inhibited at similar concentrations. This inhibition of Src signaling was accompanied by blockade of cell migration and invasion. Moreover, apoptosis was induced in the osteosarcoma and Ewing's subset of bone sarcomas at nanomolar concentrations of dasatinib. Inhibition of Src protein expression by small interfering RNA also induced apoptosis, indicating that these bone sarcoma cell lines are dependent on Src activity for survival. These results show that dasatinib inhibits migration and invasion of diverse sarcoma cell types and selectively blocks the survival of bone sarcoma cells. Therefore, dasatinib may provide therapeutic benefit by preventing the growth and metastasis of sarcomas in patients. PMID:17363602

  17. Two cases with fatal outcome following total lung irradiation for metastatic bone sarcoma

    PubMed Central

    Lia, K.; Bruland, .S.; Randem, H.L.; Aksnes, L.H.; Poulsen, J.P.; Taksdal, I.; Sundby Hall, K.

    2013-01-01

    We report a single institution experience with total lung irradiation in 53 metastatic bone sarcoma patients in the context of two young female patients who died from treatment-induced pulmonary toxicity. A radiation dose of 19.5Gy in 1.5Gy daily fractions was given as two opposing fields with a conventional technique. Both patients succumbed within 3 months following radiotherapy. One patient had osteosarcoma whereas the other advanced Ewing's sarcoma; both with widespread metastases to the lungs at primary diagnosis. In retrospect, most likely high dose methotrexate lung toxicity observed in the osteosarcoma patient, and the GI-toxicity following pelvic radiotherapy in Ewing's case, both observed during the initial phase of their multimodal treatment, might indicate an increased individual radiosensitivity. In view of this, a review of our experience in 53 bone sarcoma patients (19 with Ewing's sarcoma and 34 with osteosarcoma) treated at our institution was conducted. We have not previously experienced significant toxicity following total lung irradiation. Among these, 42% (8/19) with Ewing's sarcoma and 9% (3/34) with osteosarcoma are long-term survivors and without clinically significant lung toxicity.

  18. Kaposi sarcoma

    MedlinePLUS

    ... Kaposi sarcoma is caused by an interaction between HIV, a weakened immune system, and the human herpesvirus-8 (HHV-8). Kaposi ... condition is treated depends on: How much the immune system is ... therapy against HIV, since there is no specific therapy for HHV- ...

  19. Postradiation sarcoma of bone: review of 78 Mayo Clinic cases

    SciTech Connect

    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.

  20. Novel therapeutic approaches in pediatric and young adult sarcomas.

    PubMed

    Anderson, Peter M; Pearson, Margaret

    2006-07-01

    Novel therapy as part of sarcoma treatment schemas can enhance quality of life and is important in improving outcomes of high-risk sarcomas. Additional chemotherapy and biotherapy options to reduce tumor burden and prevent metastases include intra-arterial chemotherapy in osteosarcoma; intrapleural chemotherapy, aerosol 9-nitrocamptothecin, or protracted irinotecan and temozolomide in Ewing's sarcoma; continuous hyperthermic peritoneal perfusion for malignancy involving the peritoneum, such as desmoplastic small round cell tumor; and ifosfamide with muramyl tripeptide phosphatidyl ethanolamine liposomes in osteosarcoma. These treatments bring improved control of symptoms, including reduction in nausea, mucositis, cardiotoxicity, and central nervous system toxicity. Portable infusion devices have facilitated introduction of outpatient doxorubicin, ifosfamide, and methotrexate regimens and home-infusion irinotecan. Physical approaches to eliminate sarcoma tumors and metastases are critical for durable responses. Novel local control measures include embolization before surgery, radiosensitization, anti-vascular endothelial growth factor therapy during chemo-radiotherapy, proton therapy, samarium, thermal ablation (radiofrequency ablation), and cryoablation. PMID:17254532

  1. EXTREMITY SARCOMA SURGERY IN YOUNGER CHILDREN: TEN YEARS OF PATIENTS TEN YEARS AND UNDER

    PubMed Central

    Israelsen, Ryan B; Ilium, Benjamin E; Crabtree, Susie; Randall, R Lor; Jones, Kevin B

    2011-01-01

    Sarcoma surgeons face unique challenges in younger patients with significant skeletal growth remaining. The heightened concerns regarding radiation in the very young and the drastic changes expected in the lengths and cross-sectional areas of bones affect the decision-making for both soft-tissue and bone sarcomas in this population. Nonetheless, there is sparse literature focused on sarcoma surgery in this age group. The records of one tertiary regional sarcoma treatment program were reviewed to identify all patients ten years old or younger at the time of local control surgery for limb or limb-girdle sarcomas. Demographic information, diagnosis, surgery performed, complications, and general outcomes were gleaned from the medical records. 43 patients were identified, including 15 with osteosarcomas, 11 Ewings sarcoma family tumors, five rhabdomyosarcomas, and two synovial sarcomas, among others. Location of tumors varied widely, but demonstrated a predilection for the upper extremity more than is typical in adolescents with the same tumor types. Survival was favorable overall, with only five patients dying from disease. Most patients continued to function well at latest follow-up, but 16 experienced additional surgical interventions following the index procedure. Sarcoma surgery in the younger growing child presents challenges for the surgeon, patient, and parents, but is usually successful in the long-term. PMID:22096434

  2. Pediatric Sarcoma in Central America: Outcomes, Challenges and Plans for Improvement

    PubMed Central

    Friedrich, Paola; Ortiz, Roberta; Strait, Kelly; Fuentes, Soad; Gamboa, Yssica; Aramb, Ingrid; Ah-Chu-Sanchez, Mara; London, Wendy; Rodrguez-Galindo, Carlos; Antilln-Klussmann, Federico; Bez, Fulgencio

    2012-01-01

    Background Children with cancer in middle-income countries have inferior outcomes to those in high-income countries. The magnitude and drivers for this survival gap are not well understood. We sought to describe patterns of clinical presentation, magnitude of treatment abandonment, and survival in children with sarcoma in Central America. Methods Retrospective review of hospital-based registries from national pediatric oncology referral centers. Patients with newly diagnosed osteosarcoma, Ewing sarcoma (Ewing), rhabdomyosarcoma (RMS), and soft tissue sarcomas (STS) between 1/1/00-12/31/09 were included. Survival analysis was performed using standard definitions of overall and event-free survival (OS and EFS) and with abandonment included as an event (AOS and AEFS). Results A total of 785 new cases of pediatric sarcoma were reported (264 osteosarcoma, 175 Ewing, 240 RMS, and 106 STS). Metastatic disease at presentation was high (osteosarcoma 38%, Ewing 39%, RMS 29% and STS 21%). Treatment abandonment rate was high, particularly among patients with extremity bone sarcomas (osteosarcoma 30%, Ewing 15%, RMS 25% and STS 15%). Of 559 patients experiencing a first event, 59% had either relapse or progressive disease. The 4-year OS was 40% (SE3%) and EFS was 30% (SE2%), but further decreased to 31% (SE2%) and 24% (SE2%), when abandonment was taken into account. Conclusion High rate of metastases and treatment abandonment, and difficulty with upfront treatment effectiveness are important contributors to poor survival of children with pediatric sarcomas in Central America. Initiatives for early diagnosis, psychosocial support, quality improvement, and multidisciplinary care are warranted to improve outcomes. PMID:22972687

  3. T1-201 chloride scintigraphy for bone tumors and soft part sarcomas

    SciTech Connect

    Terui, S.; Oyamada, H.; Nishikawa, K.; Beppu, Y.; Fukuma, H.

    1984-01-01

    The author investigated T1-201 chloride as a tumor scanning agent of both tumors and soft part sarcomas. Six bone tumors (2 with Ewing sarcoma, 3 with osteosarcoma and 1 with giant cell tumor) and 3 soft part sarcoma (1 with liposarcoma and 2 with malignant fibrous histiocytoma (MFH)) were examined. All but one MFH were untreated primary cases. The diagnosis was determined from biopsy specimen. One patient with Ewing sarcoma had bone metastases. All cases were subsequently received chemotherpeutic agents. Surgery or local irradiation were also used in treatment. T1-201 scintigraphy were performed with intravenous administration of 2 mCi of T1-201 chloride before initiation of therapy. In addition, follow-up examinations were done in 4 patients (2 with Ewing sarcoma and 2 with osteosarcoma) to study the effect of chemotherapy on T1-201 uptake by the tumor. Tc-99m bone scans were available for comparison in 6 tumor. Ga-67 citrate scans were also examined for the 3 soft part sarcomas. The untreated tumors even in the metastatic lesions of Ewing sarcoma were distinctly visualized with T1-201 in all cases. The distribution of T1-201 in the tumors was sometimes different from that of Tc-99m and similar to that of Ga-67. Of 3 out of the 4 follow-up patients, the post-therapy scan showed reduction in T1-201 uptake more markedly than Tc-99m uptake during effective chemotherapy. The other one patient had not responded to the treatment so that the scan showed no changes in T1-201 uptake. These findings indicate that the tumor imaging with T1-201 is useful in the diagnosis of these malignant tumors and may be of value in assessing the response of bone tumors to chemotherapy.

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

    PubMed Central

    Pasello, Michela; Manara, Maria Cristina; Michelacci, Francesca; Fanelli, Maril; Hattinger, Claudia Maria; Nicoletti, Giordano; Landuzzi, Lorena; Lollini, Pier Luigi; Caccuri, Annamaria; Picci, Piero; Scotlandi, Katia; Serra, Massimo

    2011-01-01

    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-ylthio)hexanol (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. PMID:21673434

  5. Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors

    PubMed Central

    Tranc?u, IO; Huic?, R; Surcel, M; Munteanu, A; Ursaciuc, C

    2015-01-01

    Objectives: EWS/FLI-1 fusion mainly appears in Ewings 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. Methodology: 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. Results: 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. Conclusions: 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. PMID:25914746

  6. The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study.

    PubMed

    Ito, Junko; Asano, Naofumi; Kawai, Akira; Yoshida, Akihiko

    2016-01-01

    Synovial sarcoma is a malignant mesenchymal neoplasm of uncertain histogenesis, characterized by a specific SS18-SSX fusion. The diagnosis of synovial sarcoma can be challenging based on morphology and conventional immunohistochemistry alone, and identification of the fusion gene by molecular genetics may be necessary for diagnosis. Several recent studies have demonstrated the diagnostic utility of the reduced expression of SMARCB1 in synovial sarcomas as measured using immunohistochemistry. Therefore, we undertook a validation study using synovial sarcomas and other spindle or round cell tumors that could enter differential diagnosis of monophasic or poorly differentiated synovial sarcomas. Among 36 synovial sarcomas that were successfully evaluated, the expression of SMARCB1 was diffusely reduced in 33 cases (92%) at variable degrees. In contrast, the expression of SMARCB1 was not reduced in any of the 93 evaluable non-synovial sarcoma tumors (5 thymomas, 5 sarcomatoid mesotheliomas, 10 schwannomas, 9 mesenchymal chondrosarcomas, 20 solitary fibrous tumors, 19 Ewing sarcomas, and 25 malignant peripheral nerve sheath tumors). A few schwannomas and malignant peripheral nerve sheath tumors showed mosaic or complete loss of SMARCB1 expression. Reduced expression of SMARCB1 immunoreactivity was therefore found to be highly sensitive and specific for synovial sarcoma, and can be useful for rapidly and accurately confirming the diagnosis of synovial sarcoma. This reduction in SMARCB1 expression likely reflects the BAF47 ejection mechanism of the SS18-SSX fusion product and can therefore be viewed as an indirect visualization of this fusion product. PMID:26520417

  7. Prognostic value of IGF-1R expression in bone and soft tissue sarcomas: a meta-analysis

    PubMed Central

    Liang, Junbo; Li, Binghao; Yuan, Li; Ye, Zhaoming

    2015-01-01

    Accumulated evidence has indicated a correlation between IGF-1R and bone and soft tissue sarcoma (BSTS) progression. However, research on the prognostic role of IGF-1R in sarcomas has revealed very different or even totally opposite results. This meta-analysis aimed to unveil the controversial role IGF-1R plays in predicting the outcome of BSTS patients. We systematically reviewed the evidence for the effect of IGF-1R expression in multiple types of BSTSs, including osteosarcoma, Ewings sarcoma, synovial sarcoma, liposarcoma, and rhabdomyosarcoma, to elucidate this issue. The prognostic value of IGF-1R expression in BSTS patients was evaluated regarding overall survival, measured by pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Seven studies including 627 patients were enrolled in this meta-analysis. Our results demonstrated that IGF-1R expression was associated with poor outcome in terms of overall survival in BSTS patients (pooled HR =2.15, 95% CI: 1.064.38; P=0.03). In subtypes of BSTSs, elevated IGF-1R expression was revealed to be significantly correlated with worse prognosis in osteosarcoma (pooled HR =2.20, 95% CI: 1.590.03; P<0.001), while no statistical significance was discovered in Ewings sarcoma (pooled HR =1.01, 95% CI: 0.452.27; P=0.99). Expression of IGF-1R could be a negative prognostic biomarker for patients suffering from BSTSs. PMID:26251617

  8. [Treatments of Soft Tissue Sarcomas by Orthopaedic Surgeons in Japan].

    PubMed

    Tanaka, Kazuhiro

    2016-01-01

    In Japan, the treatment of soft tissue sarcomas(STS)has been performed mainly by orthopaedic surgeons. The standard therapy for all cases of STS is surgical resection of the tumor. The prognosis of patients with unresectable tumors or distant metastases is poor despite treatment with intensive chemotherapy. Adjuvant chemotherapy is indicated for patients with resectable tumors. Round-cell STS, including extraskeletal Ewing sarcoma and rhabdomyosarcoma, have high sensitivity to chemotherapy. The standard treatment for round-cell STS is multimodal therapy with surgery and chemotherapy, with or without radiotherapy. On the other hand, non-round cell STS, including leiomyosarcoma, synovial sarcoma, and liposarcoma, have low sensitivity to chemotherapy. Thus, the standard treatment for non-round cell STS is essentially, surgery. Large and high-grade non-round cell STS are also treated using adjuvant chemotherapy along with surgery. In this review, the standard therapies for STS and the future perspective in Japan are discussed. PMID:26809525

  9. Vulvar sarcomas: Short guideline for histopathological recognition and clinical management. Part 2.

    PubMed

    Chokoeva, A A; Tchernev, G; Cardoso, J C; Patterson, J W; Dechev, I; Valkanov, S; Zanardelli, M; Lotti, T; Wollina, U

    2015-06-01

    Malignant tumors of the female reproductive system are a serious health and social problem, as they are the second most common cause of death among women, after breast cancer. Vulvar tumors represent only 4% of all gynecological neoplasms, and they are fourth in frequency after tumors of the cervix, uterus, and ovary. Ninety-eight percent of all vulvar tumors are benign and only 2% are malignant. Sarcomas of the vulva comprise approximately 1-3% of all vulvar cancers. They are characterized by rapid growth, high metastatic potential, frequent recurrences, aggressive behavior, and high mortality rate. In Part 1 of this paper, we presented the most common forms of sarcoma of the vulva: leiomyosarcoma, epithelioid sarcoma, malignant rhabdoid tumor, and rhabdomyosarcoma. The second part of this review will focus mainly on the rarest variants of vulvar sarcoma: low-grade fibromyxoid sarcoma, synovial sarcoma, monophasic synovial sarcoma, carcinosarcoma, Ewing sarcoma, myeloid sarcoma, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, angiomatoid fibrous histiocytoma, liposarcoma, malignant peripheral nerve sheath tumor, and malignant mesothelioma. PMID:25816393

  10. Adult soft tissue sarcoma

    MedlinePLUS

    Soft tissue sarcoma is cancer that forms in the soft tissue of the body. Soft tissue connects, supports, or surrounds other body parts. In adults, soft tissue sarcoma is rare. There are many different types of ...

  11. Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas

    ClinicalTrials.gov

    2016-03-21

    Childhood Solid Neoplasm; Metastatic Melanoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Childhood Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  12. Plasma melatonin in ewes after ovariectomy.

    PubMed

    Arendt, J; Laud, C A; Symons, A M; Pryde, S J

    1983-05-01

    Six ewes were ovariectomized in late November and kept in natural light with 5 intact controls. LH levels were monitored approximately weekly. On Days 16 and 58 after ovariectomy plasma melatonin was determined at 3-h intervals for 24 h in all the ewes. Plasma melatonin concentrations were greater in the ovariectomized ewes than in the controls especially at 16 days when total 24 h secretion was almost 3 times that in the control ewes. These data indicate that, in the ewe, the gonads exert an inhibitory influence on melatonin secretion. PMID:6842454

  13. Topotecan and Cyclophosphamide in Adults with Relapsed Sarcoma

    PubMed Central

    Blanchette, P.; Hogg, D.; Ferguson, P.; Wunder, J. S.; Swallow, C.; Gladdy, R.; Chung, P.; O'Sullivan, B.; Blackstein, M. E.; Catton, C.; Gupta, A. A.

    2012-01-01

    Background. The combination of topotecan and cyclophosphamide (TC) has activity in pediatric patients with recurrent sarcoma, especially Ewing's sarcoma (EWS). We sought to determine the toxicity of and response to TC in adults with recurrent sarcoma. Patients and Methods. Adults treated with TC from 2005 to 2010 were reviewed who received T = topotecan at 0.75?mg/m2/day (days 15) and C = cyclophosphamide at 250?mg/m2/day (days 15) every 21 days. Results. Fifteen patients, median age 31 years (range 17.556) had nonpleomorphic rhabdomyosarcoma (RMS, n = 6), EWS, n = 5, synovial sarcoma (SS, n = 2) leiomyosarcoma (LMS, n = 1), and desmoplastic small round cell tumour (DSRCT, n = 1). Median time to progression was 2.5 months (range 1.613.0). Partial responses were seen in 2/6 RMS and 1/2 SS. Stable disease was seen in 2/5 EWS, 1/2 SS and 1 DSRCT. The most common reason for stopping treatment was progressive disease 12/15, (80%). Hematologic toxicity was common; 7 (47%) patients required blood product transfusion, 5 (33%) patients had fever/neutropenia. At median follow-up time of 7.7 months, all but 1 patient had died of disease. Conclusion: TC combination is tolerable but has only modest activity in adults with recurrent sarcoma. Other regimens deserve exploration for this high-risk group of patients PMID:22851904

  14. Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

    SciTech Connect

    Serizawa, Itsuko; Kagei, Kenji; Kamada, Tadashi; Imai, Reiko; Sugahara, Shinji; Okada, Tohru; Tsuji, Hiroshi; Ito, Hisao; Tsujii, Hirohiko

    2009-11-15

    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{sup 3} and 1,194 cm{sup 3} (median 525 cm{sup 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. ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone

    PubMed Central

    Greco, Nicholas; Schott, Trevor; Mu, Xiaodong; Rothenberg, Adam; Voigt, Clifford; McGough, Richard L.; Goodman, Mark; Huard, Johnny; Weiss, Kurt R.

    2014-01-01

    Osteosarcoma (OS), chondrosarcoma (CSA), and Ewings sarcoma (ES) are the most common primary malignancies of bone, and are rare diseases. As with all sarcomas, the prognosis of these diseases ultimately depends on the presence of metastatic disease. Survival is therefore closely linked with the biology and metastatic potential of a particular bone tumors cells. Here we describe a significant correlation of aldehyde dehydrogenase (ALDH) activity and the presence/absence of distant metastases in ten consecutive cases of human bone sarcomas. Additionally, cultured human CSA cells, which are historically chemo- and radio-resistant, may be sensitive to the ALDH inhibitor, disulfiram. While it is premature to draw broad conclusions from such a small series, the importance of ALDH activity and inhibition in the metastatic potential of primary bone sarcomas should be investigated further. PMID:25328803

  16. Chemotherapy for Soft Tissue Sarcomas

    MedlinePLUS

    ... Next Topic Targeted therapy for soft tissue sarcoma Chemotherapy for soft tissue sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  17. Synovial sarcomas. True carcinosarcomas?

    PubMed

    Leader, M; Patel, J; Collins, M; Kristin, H

    1987-06-15

    The histogenesis of synovial sarcomas remains controversial. An origin from epithelium, synovium, or synovial-related cells and neural tissue has been advanced. Using a combination of a cytokeratin (epithelial marker) antibody and a vimentin (mesenchymal marker) antibody, this study suggests that a synovial sarcoma might be regarded as a carcinosarcoma. It also highlights the diagnostic utility of those antibodies in the diagnosis of synovial sarcomas. PMID:2436745

  18. Metformin as an Adjuvant Drug against Pediatric Sarcomas: Hypoxia Limits Therapeutic Effects of the Drug

    PubMed Central

    Garofalo, Cecilia; Capristo, Mariantonietta; Manara, Maria Cristina; Mancarella, Caterina; Landuzzi, Lorena; Belfiore, Antonino; Lollini, Pier-Luigi; Picci, Piero; Scotlandi, Katia

    2013-01-01

    Metformin, a well-known insulin-sensitizer commonly used for type 2 diabetes therapy, has recently emerged as potentially very attractive drug also in oncology. It is cheap, it is relatively safe and many reports have indicated effects in cancer prevention and therapy. These desirable features are particularly interesting for pediatric sarcomas, a group of rare tumors that have been shown to be dependent on IGF and insulin system for pathogenesis and progression. Metformin exerts anti-mitogenic activity in several cancer histotypes through several molecular mechanisms. In this paper, we analyzed its effects against osteosarcoma, Ewing sarcoma and rhabdomyosarcoma, the three most common pediatric sarcomas. Despite in vitro metformin gave remarkable antiproliferative and chemosensitizing effects both in sensitive and chemoresistant cells, its efficacy was not confirmed against Ewing sarcoma xenografts neither as single agent nor in combination with vincristine. This discrepancy between in vitro and in vivo effects may be due to hypoxia, a common feature of solid tumors. We provide evidences that in hypoxia conditions metformin was not able to activate AMPK and inhibit mTOR signaling, which likely prevents the inhibitory effects of metformin on tumor growth. Thus, although metformin may be considered a useful complement of conventional chemotherapy in normoxia, its therapeutic value in highly hypoxic tumors may be more limited. The impact of hypoxia should be considered when novel therapies are planned for pediatric sarcomas. PMID:24391834

  19. The soft tissue sarcomas

    SciTech Connect

    Eilber, F.R.; Morton, D.L.; Sondak, V.K.; Economou, J.S.

    1987-01-01

    New advances in multimodality therapy of sarcomas in all anatomic sites are thoroughly described. Multimodality therapy with limb-salvage surgery for extremity tumors, sarcomas of the head and neck, trunk, intraabdominal, visceral, and genitourinary tract and cardiopulmonary system are presented. Separate sections are devoted to the management of pediatric sarcomas, pulmonary metastasis and to the pathology and radiobiology, chemotherapy, and immunotherapy of sarcomas. The text also stresses the philosophy of achieving adequate local control without radical amputation by combined surgery and chemo/radiotherapy.

  20. Primary cardiac synovial sarcoma.

    PubMed

    Khan, Imran; Gul, Saira; Tufail, Zafar; Khan, Kamran; Sharma, Praman; Waheed, Abdul

    2015-07-01

    Approximately 10% of soft tissue sarcomas are synovial sarcomas, and 90% of these occur in the extremities. Among the primary tumors in the heart, 25% are malignant. Primary synovial sarcoma of the heart is an extremely rare entity. A myriad of investigations such as histopathology, immunohistochemistry, electron microscopy, and molecular genetic techniques are required for confirmation of the diagnosis. The tumor is nearly always lethal, but surgical resection with chemotherapy may prolong the life of the patient. We describe the case of a young patient with a primary synovial sarcoma arising from the right ventricle. PMID:24585318

  1. Prostate Cancer Heterogeneous High-Metastatic Multi-Organ-Colonizing Chemo-Resistant Variants Selected by Serial Metastatic Passage in Nude Mice Are Highly Enriched for Multinucleate Giant Cells

    PubMed Central

    Zhang, Lei; Wu, Chengyu; Hoffman, Robert M.

    2015-01-01

    In order to further understand the role of tumor heterogeneity in metastasis and chemo-resistance, high metastatic PC-3 human prostate cancer variants were selected by injecting parental PC-3 cells, expressing green fluorescent protein (GFP) in the footpad of nude mice, which then metastasize to inguinal lymph nodes. The PC-3-GFP cells which metastasized to the inguinal lymph nodes were collected and were re-injected to the footpad. After 6 such cycles, the PC-3-GFP cells collected from inguinal lymph nodes (PC-3-GFP-LN) were again injected to the footpad. PC-3-GFP-LN showed 100% metastasis to major lymph nodes (popliteal, inguinal, axillary, and cervical), and 100% metastasis to bone and lung. The percent of giant cell variants was enriched in PC-3-GFP-LN-6 compared to parental cells and increased with each cycle of selection, which in turn had increased metastasis. PC-3-GFP-LN-6 cells were resistant to 5-fluorouracil, doxorubicin and cisplatinum, compared to parental PC-3. However, PC-3-GFP-LN-6 was sensitive to the traditional Chinese medicine (TCM) herbal mixture LQ, similar to the parental cells. These results suggest that PC-3 tumors are heterogenous and that subpopulations of highly metastatic, drug-resistant cells can be step-wise selected using a mouse model of tumor progression. PMID:26536025

  2. Epidemiological Evaluation of Head and Neck Sarcomas in Iran (the Study of 105 Cases Over 13 Years)

    PubMed Central

    Alishahi, Batoul; Kargahi, Neda; Homayouni, Solmaz

    2015-01-01

    Background: 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. Objectives: The aim of this study is to evaluate the epidemiological characteristics of head and neck sarcomas of patients in Isfahan, Iran. Patients and Methods: 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. Results: 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. Conclusions: 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. PMID:26478791

  3. Sarcoma Foundation of America

    MedlinePLUS

    ... 253-8690 info@curesarcoma.org Follow @CureSarcoma on Twitter 10h Please check out the new issue of ... to the extent permitted by law. Facebook Google+ Twitter LinkedIn YouTube © 2016 Sarcoma Foundation of America | All ...

  4. Expression of MDR1/P glycoprotein in human sarcomas.

    PubMed Central

    Vergier, B.; Cany, L.; Bonnet, F.; Robert, J.; de Mascarel, A.; Coindre, J. M.

    1993-01-01

    Conflicting reports of MDR1 gene expression in human tumours are observed according to whether studies are performed at the mRNA or P-glycoprotein level. We have investigated this expression in 22 clinically drug-resistant sarcomas at the mRNA level by Northern blot (NB), Dot blot (DB), in situ hybridisation (ISH), and at the protein level by immunohistochemistry (IHC) using three monoclonal antibodies (MoAbs): C219, JSB1, MRK16. Increased MDR1 mRNA expression was detected by NB, DB, and ISH in 1/22 sarcoma (an Ewing's sarcoma). ISH was perfectly correlated with DB hybridisation and confirmed the expression of tumoral cells alone. Specific staining of 100% of tumoral cells was obtained with the three MoAbs in the same sarcoma. Expression in tumoral cells of 12 other sarcomas was detected with MRK16, and positive staining of stromal cells with both C219 (1/22) and MRK16 (8/22) was observed. This study confirms that MDR1 overexpression occurs in human sarcomas but is not the principal mechanism of drug-resistance. Furthermore, positivity with one antibody does not necessarily imply the presence of P glycoprotein (P-gp) and a disparity may exist between the levels of P-gp and its mRNA in the same sample. So care must be taken in interpreting results and more sensitive techniques such as the polymerase chain reaction (PCR) could prove useful. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7903154

  5. Sarcomas in hereditary retinoblastoma

    PubMed Central

    2012-01-01

    Children diagnosed with the hereditary form of retinoblastoma (Rb), a rare eye cancer caused by a germline mutation in the RB1 tumor suppressor gene, have excellent survival, but face an increased risk of bone and soft tissue sarcomas. This predisposition to sarcomas has been attributed to genetic susceptibility due to inactivation of the RB1 gene as well as past radiotherapy for Rb. The majority of bone and soft tissue sarcomas among hereditary Rb survivors occur in the head, within the radiation field, but they also occur outside the radiation field. Sarcomas account for almost half of the second primary cancers in hereditary Rb survivors, but they are very rare following non-hereditary Rb. Sarcomas among hereditary Rb survivors arise at ages similar to the pattern of occurrence in the general population. There has been a trend over the past two decades to replace radiotherapy with chemotherapy and other focal therapies (laser or cryosurgery), and most recently, chemosurgery in order to reduce the incidence of sarcomas and other second cancers in Rb survivors. Given the excellent survival of most Rb patients treated in the past, it is important for survivors, their families and health care providers to be aware of the heightened risk for sarcomas in hereditary patients. PMID:23036192

  6. Sarcomas in hereditary retinoblastoma.

    PubMed

    Kleinerman, Ruth A; Schonfeld, Sara J; Tucker, Margaret A

    2012-01-01

    Children diagnosed with the hereditary form of retinoblastoma (Rb), a rare eye cancer caused by a germline mutation in the RB1 tumor suppressor gene, have excellent survival, but face an increased risk of bone and soft tissue sarcomas. This predisposition to sarcomas has been attributed to genetic susceptibility due to inactivation of the RB1 gene as well as past radiotherapy for Rb. The majority of bone and soft tissue sarcomas among hereditary Rb survivors occur in the head, within the radiation field, but they also occur outside the radiation field. Sarcomas account for almost half of the second primary cancers in hereditary Rb survivors, but they are very rare following non-hereditary Rb. Sarcomas among hereditary Rb survivors arise at ages similar to the pattern of occurrence in the general population. There has been a trend over the past two decades to replace radiotherapy with chemotherapy and other focal therapies (laser or cryosurgery), and most recently, chemosurgery in order to reduce the incidence of sarcomas and other second cancers in Rb survivors. Given the excellent survival of most Rb patients treated in the past, it is important for survivors, their families and health care providers to be aware of the heightened risk for sarcomas in hereditary patients. PMID:23036192

  7. Primary pericardial synovial sarcoma

    PubMed Central

    Takeshita, Shinji; Tanaka, Yoko; Morooka, Hiroaki; Higure, Ryota; Shiono, Motomi

    2015-01-01

    A 57-year-old man was admitted to our hospital with cardiomegaly on a chest roentgenogram. A mediastinal tumor was observed during a chest computed tomographic scan and the patient was diagnosed with pericardial synovial sarcoma as a result of a tumor biopsy. Surgery, radiotherapy and chemotherapy were carried out, and although the tumor temporarily decreased in size, it subsequently increased and the patient died approximately 3 years following the initial medical examination. Most synovial sarcomas commonly occur in the vicinity of the joints of the extremities. Therefore, we herein report a rare case of synovial sarcoma which occurred in the pericardium. PMID:26623128

  8. Pulmonary Artery Sarcoma

    PubMed Central

    Shomaf, Maha; Obeidat, Nathir; Al-Fares, Fatin; Najjar, Saleh

    2014-01-01

    Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation.

  9. Pulmonary Artery Sarcoma

    PubMed Central

    Shomaf, Maha; Obeidat, Nathir; Najjar, Saleh

    2014-01-01

    Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation. PMID:26425600

  10. [Sarcoma gene signatures].

    PubMed

    Chibon, F; Coindre, J-M

    2011-02-01

    This review reports the main gene signature specific for the diagnosis, prognosis or prediction of drug response in sarcomas. Almost half of sarcomas show a simple genetic lesion which is specific for the diagnosis: recurrent translocations in 10 to 15% of sarcomas, specific activating and inactivating mutations in GIST and rhabdoid tumor respectively, and MDM2 amplification in well-differentiated and dedifferentiated liposarcomas as well as in intimal sarcoma. A recent study reported a gene expression signature which is much better than histological grading for predicting metastasis outcome. This signature is composed of 67 genes all belonging to pathways involved in chromosome integrity suggesting an important role of these mechanisms in the development of metastases. On the other hand, and except for GIST with KIT and PDGFRA mutations, there is no validated predictive gene signature so far. PMID:21287318

  11. What Is Uterine Sarcoma?

    MedlinePLUS

    ... supporting tissues of the uterus (womb). About the uterus The uterus is a hollow organ, about the ... a baby out during childbirth. Cancers of the uterus and endometrium Sarcomas are cancers that start from ...

  12. Bronchopulmonary Kaposi's sarcoma

    PubMed Central

    Bashar, Nada; Innes, Nicholas; Orrell, Julian

    2015-01-01

    Kaposi's sarcoma (KS) is a highly vascular tumour, which was first described by the Hungarian dermatologist Moritz Kaposi Kohn before the discovery of the human immunodeficiency virus (HIV). Historically, KS has been linked to immunosuppression or to elderly male patients, especially in relation to diffuse cutaneous KS. We describe a case of Bronchopulmonary Kaposi's sarcoma in a patient with AIDS who was successfully treated with HAART and Liposomal Doxorubicin chemotherapy. PMID:26236600

  13. Unusual Clinical Presentation of Gastrointestinal Clear Cell Sarcoma

    PubMed Central

    Raskin, Grigory A.; Pozharisski, Kazimir M.; Iyevleva, Aglaya G.; Rikov, Ivan V.; Orlova, Rashida V.; Imyanitov, Evgeny N.

    2015-01-01

    Background Use of molecular assays is gradually becoming a mandatory part of the clinical management of soft tissue tumors, however the choice and the interpretation of these tests may present a challenge. Summary This report demonstrates an unusual presentation of sarcoma, which was initially diagnosed as a tumor of unknown primary site. Given the presence of vimentin, Fli-1, CD99 and S100 markers, lack of immunostaining for melan A, HMB45, MITF, synaptophysin, CD56, myf4, CKAE1/3 and WT-1, as well as the presence of EWSR1 translocation determined by a break-apart FISH assay, Ewing's sarcoma (ES) diagnosis seemed to be well justified. However, polymerase chain reaction testing for ES-specific rearrangements (EWSR1/FLI1, EWSR1/ERG, EWSR1/ETV1, EWSR1/ETV4, EWS/FEV) failed to confirm the ES origin of the neoplastic tissue. We further considered clinical, morphological, immunohistochemical and molecular diagnostic features of other types of EWSR1-rearranged sarcomas and performed molecular testing for gastrointestinal clear cell sarcoma. The polymerase chain reaction assay revealed EWSR1ex7/ATF1ex5 fusion, thus confirming the latter diagnosis. Subsequent high-precision computed tomography of the abdominal cavity revealed a 5-cm tumor of the small bowel, which was subjected to surgical resection. Key Message This report exemplifies that the use of anonymous cytogenetic assays, such as break-apart FISH EWSR1 testing, may not be sufficient even in case of a perfect match with relevant morphological and immunohistochemical tumor features. Practical Implications Explicit identification of the translocation gene partners is indeed important for proper sarcoma diagnosis management. PMID:26675070

  14. Can Kaposi Sarcoma Be Prevented?

    MedlinePLUS

    ... Sarcoma + - Text Size Download Printable Version [PDF] » Causes, Risk Factors, and Prevention TOPICS Document Topics GO » SEE A ... top » Guide Topics What Is Kaposi Sarcoma? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating ...

  15. Bone mineral density and bone metabolism in children treated for bone sarcomas.

    PubMed

    Ruza, Elena; Sierrasesmaga, Luis; Azcona, Cristina; Patio-Garcia, Ana

    2006-06-01

    In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of life. PMID:16641212

  16. Mutual recognition between ewes and lambs.

    PubMed

    Walser, E S; Alexander, G

    1980-01-01

    Studies to investigate the relative value of sight, hearing and smell in mutual recognition between ewes and lambs are described. The method used was to alter clues that could aid in recognition, rather than interfering with the animal's sensory perception. When lambs were coloured with powdered dyes to change appearance, this produced marked avoidance by the dams of the treated lambs. When lambs were partially coloured, the ewes' greatest reaction was shown to lambs whose heads were coloured. Other experiments compared the role of vision and hearing by observing recognition when the ewes or lambs were hidden behind screening, or muted. The results indicate that while olfaction is important for recognition when the ewe and lamb are close together, visual clues are of major importance in maternal discrimination and auditory clues are important for the lambs as they get older. PMID:7349447

  17. Spinal and Paraspinal Ewing Tumors

    SciTech Connect

    Indelicato, Daniel J.; Keole, Sameer R.; Shahlaee, Amir H.; Morris, Christopher G.; Gibbs, C. Parker; Scarborough, Mark T.; Pincus, David W.; Marcus, Robert B.

    2010-04-15

    Purpose: To perform a review of the 40-year University of Florida experience treating spinal and paraspinal Ewing tumors. Patients and Methods: A total of 27 patients were treated between 1965 and 2007. For local management, 21 patients were treated with radiotherapy (RT) alone and 6 with surgery plus RT. All patients with metastatic disease were treated with RT alone. The risk profiles of each group were otherwise similar. The median age was 17 years, and the most frequent subsite was the sacral spine (n = 9). The median potential follow-up was 16 years. Results: The 5-year actuarial overall survival, cause-specific survival, and local control rate was 62%, 62%, and 90%, respectively. For the nonmetastatic subset (n = 22), the 5-year overall survival, cause-specific survival, and local control rate was 71%, 71%, and 89%, respectively. The local control rate was 84% for patients treated with RT alone vs. 100% for those treated with surgery plus RT. Patients who were >14 years old and those who were treated with intensive therapy demonstrated superior local control. Of 9 patients in our series with Frankel C or greater neurologic deficits at presentation, 7 experienced a full recovery with treatment. Of the 27 patients, 37% experienced Common Toxicity Criteria Grade 3 or greater toxicity, including 2 deaths from sepsis. Conclusion: Aggressive management of spinal and paraspinal Ewing tumors with RT with or without surgery results in high toxicity but excellent local control and neurologic outcomes. Efforts should be focused on identifying disease amenable to combined modality local therapy and improving RT techniques.

  18. BCOR-CCNB3 fusions are frequent in undifferentiated sarcomas of male children.

    PubMed

    Peters, Tricia L; Kumar, Vijetha; Polikepahad, Sumanth; Lin, Frank Y; Sarabia, Stephen F; Liang, Yu; Wang, Wei-Lien; Lazar, Alexander J; Doddapaneni, HarshaVardhan; Chao, Hsu; Muzny, Donna M; Wheeler, David A; Okcu, M Fatih; Plon, Sharon E; Hicks, M John; Lpez-Terrada, Dolores; Parsons, D Williams; Roy, Angshumoy

    2015-04-01

    The BCOR-CCNB3 fusion gene, resulting from a chromosome X paracentric inversion, was recently described in translocation-negative 'Ewing-like' sarcomas arising in bone and soft tissue. Genetic subclassification of undifferentiated unclassified sarcomas may potentially offer markers for reproducible diagnosis and substrates for therapy. Using whole transcriptome paired-end RNA sequencing (RNA-seq) we unexpectedly identified BCOR-CCNB3 fusion transcripts in an undifferentiated spindle-cell sarcoma. RNA-seq results were confirmed through direct RT-PCR of tumor RNA and cloning of the genomic breakpoints from tumor DNA. Five additional undifferentiated sarcomas with BCOR-CCNB3 fusions were identified in a series of 42 pediatric and adult unclassified sarcomas. Genomic breakpoint analysis demonstrated unique breakpoint locations in each case at the DNA level even though the resulting fusion mRNA was identical in all cases. All patients with BCOR-CCNB3 sarcoma were males diagnosed in mid childhood (7-13 years of age). Tumors were equally distributed between axial and extra-axial locations. Five of the six tumors were soft-tissue lesions with either predominant spindle-cell morphology or spindle-cell areas interspersed with ovoid to round cells. CCNB3 immunohistochemistry showed strong nuclear positivity in five tumors before oncologic therapy, but was patchy to negative in post-treatment tumor samples. An RT-PCR assay developed to detect the fusion transcript in archival formalin-fixed tissue was positive in all six cases, with high sensitivity and specificity in both pre- and post-treated samples. This study adds to recent reports on the clinicopathologic spectrum of BCOR-CCNB3 fusion-positive sarcomas, a newly emerging entity within the undifferentiated unclassified sarcoma category and describes a simple RT-PCR assay that in conjunction with CCNB3 immunohistochemistry can be useful in diagnosing these tumors. PMID:25360585

  19. Multicentric myofibroblastic sarcoma.

    PubMed

    Wechalekar, Mihir Dilip; Ayres, Oliver; Farshid, Gelareh; Clayer, Mark; Cleland, Leslie G

    2014-01-01

    We report a case of synchronous, multicentric low-grade myofibroblastic sarcoma presenting in a 62-year-old man. He initially presented with inflammatory symmetric polyarthritis and adhesive capsulitis of his shoulder and hips bilaterally and did not respond to a trial of disease modifying antirheumatic drugs. Over a period of several years he developed progressive restriction of both knees and nodules on his hands, both knees and back. A biopsy of the nodule on his back was inconclusive and subsequent biopsies on his left and then right knee revealed a spindle cell neoplasm with an infiltrative growth pattern, mitotic figures, positive immunostaining for smooth muscle actin and focal myxoid change consistent with myofibroblastic sarcoma. While myofibroblastic sarcoma has been known to metastasise, to our knowledge, a multifocal presentation of this tumour has not been described previously. PMID:25368122

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

    PubMed Central

    Huang, Xin; Park, Haein; Greene, Joseph; Zhou, Sophia X.; Albert, Catherine M.; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V.; Loeb, David M.; Cairo, Mitchell S.; Zhou, Xianzheng

    2015-01-01

    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. PMID:26173023

  1. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

    ClinicalTrials.gov

    2013-02-06

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Stage IV Uterine Sarcoma; Unspecified Adult Solid Tumor, Protocol Specific

  2. Soft tissue sarcomas.

    PubMed

    Spiguel, Andre

    2014-01-01

    Sarcoma is a cancer that arises from cells of mesenchymal origin, such as bone, cartilage, muscle, fat, vascular, or hematopoietic tissue. It is a very rare form of cancer with over 50 histologic subtypes. This chapter discusses selected individual subtypes of sarcomas and characteristics specific to each one. It will broadly go over molecular biology, etiology, risk factors, and the clinical features of this disease. It discusses diagnostic evaluation and the principles of management including imaging, biopsy, staging, treatment, follow-up, and the importance of a multidisciplinary approach. PMID:25070237

  3. To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

    ClinicalTrials.gov

    2016-02-10

    Neuroblastoma;; Rhabdomyosarcoma;; Ewing's Sarcoma;; Ewing's Tumor;; Sarcoma, Ewing's;; Sarcomas, Epitheliod;; Sarcoma, Soft Tissue;; Sarcoma, Spindle Cell;; Melanoma;; Malignant Melanoma;; Clinical Oncology;; Oncology, Medical;; Pediatrics, Osteosarcoma;; Osteogenic Sarcoma;; Osteosarcoma Tumor;; Sarcoma, Osteogenic;; Tumors;; Cancer;; Neoplasia;; Neoplasm;; Histiocytoma;; Fibrosarcoma;; Dermatofibrosarcoma

  4. Altering ewe nutrition in late gestation: I. The impact on pre- and postpartum ewe performance.

    PubMed

    McGovern, F M; Campion, F P; Lott, S; Boland, T M

    2015-10-01

    The present study was conducted to examine the effects of offering a single diet rationed to 80% (80% ME), 100% (100% ME), or 120% (120% ME) of recommended ME requirements from d 119 of gestation to lambing, with concurrent changes in other dietary nutrients. The effects on pre- and postpartum ewe performance, including estimated milk yield and milk fatty acid concentrations, were monitored. Sixty twin-bearing ewes were allocated to 1 of 3 dietary treatments ( = 20 per treatment) and individually fed for the final 4 wk of gestation. Metabolizable energy requirements were individually calculated for each ewe and amended according to treatment. Ewes were rationed daily on the basis of their treatment ME allocation, which led to concurrent alterations in other nutrient intakes. Diets were grass silage based and supplemented with concentrates to meet treatment ME allocation on an individual ewe basis. Ewes offered the 80% ME treatment had a lower liveweight ( = 0.04) and BCS ( = 0.03) at 24 h postpartum when compared with ewes offered the 120% ME diet. Although there was no difference in liveweight at either d 40 ( = 0.18) or 98 postpartum ( = 0.20), the difference in BCS persisted until d 40 postpartum ( = 0.02). Colostrum yield at 1 h postpartum ( = 0.03) and total yield up to 18 h postpartum ( = 0.04) was greater for ewes offered the 120% ME diet than either of the other treatment groups. Similarly, these ewes had a greater estimated milk yield during wk 3 of lactation ( = 0.04) and elevated concentrations of short-chain SFA ( = 0.02) and long-chain SFA ( ? 0.05) from wk 2 through 6 of lactation. In summary, the negative impact of applying a dietary insult to ewes in late gestation is reflected in colostrum and estimated milk yield and fatty acid composition, thus potentially influencing postpartum growth and development of the offspring. PMID:26523579

  5. Leukosis/Sarcoma Group

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Soft Tissue Sarcoma

    MedlinePLUS

    ... risk if you have been exposed to certain chemicals, have had radiation therapy, or have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove the tumor, radiation therapy, chemotherapy, or a combination. NIH: National Cancer Institute

  7. Chemokines and Kaposi's sarcoma.

    PubMed

    Jensen, Kristian K; Lira, Sergio A

    2004-06-01

    Chemokines participate in many biological processes in homeostasis and disease. Recently, they have been implicated in cancer, more specifically in tumor angiogenesis and metastasis. Here we review evidence supporting a role for chemokines in the pathogenesis of Kaposi's sarcoma and discuss a possible role for these molecules in angioproliferation and immune evasion. PMID:15246054

  8. Microenvironmental Targets in Sarcoma

    PubMed Central

    Ehnman, Monika; Larsson, Olle

    2015-01-01

    Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example, in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has led to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject of larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma. PMID:26583076

  9. Leukosis/Sarcoma Group

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The leukosis/sarcoma (L/S) group of diseases designates a variety of transmissible benign and malignant neoplasms of chickens caused by members that belong to the family Retroviridae. Lymphoid leukosis has been the most common form of L/S group of diseases seen in field flocks, although myeloid leuk...

  10. Immunotherapy of Childhood Sarcomas

    PubMed Central

    Roberts, Stephen S.; Chou, Alexander J.; Cheung, Nai-Kong V.

    2015-01-01

    Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing’s family of tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with localized stage are curable with surgery and/or chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New therapies for these patients are urgently needed. Immunotherapy is an established treatment modality for both liquid and solid tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In the past, immunomodulatory agents such as interferon, interleukin-2, and liposomal-muramyl tripeptide phosphatidyl-ethanolamine have been tried, with some activity seen in subsets of patients; additionally, various cancer vaccines have been studied with possible benefit. Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA-4 and PD-1 are being actively explored in pediatric sarcomas. Building on the success of adoptive T cell therapy for EBV-related lymphoma, strategies to redirect T cells using chimeric antigen receptors and bispecific antibodies are rapidly evolving with potential for the treatment of sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and tumor vaccines. The future integration of antibody-based and cell-based therapies into an overall treatment strategy of sarcoma will be discussed. PMID:26301204

  11. R/V Maurice Ewing retires

    NASA Astrophysics Data System (ADS)

    Diebold, John

    2005-07-01

    The R/V Maurice Ewing came into port for the last time on 10 March 2005, tying up at Quonset Point, R.I., astern of the ship slated to be her replacement (Figure 1). M/V Western Legend (Figure 1, left) will, during fall and winter of 2005-2006, be converted as R/V Marcus G. Langseth, and will replace the Maurice Ewing (Figure 1, right) as the primary seismic research vessel within the U.S. academic research vessel fleet.During its distinguished 15-year career, Ewing's operations added fundamentally to the knowledge and understanding of solid Earth dynamics and structure. Ewing began life as the M/V Bernier, and performed seismic offshore exploration for Petro Canada. In an innovative process, which included initialization provided by Columbia University, the U.S. National Science Foundation (NSF) acquired Bernier in 1989, and the ship's title passed to NSF in 1990. Bernier was converted into R/V Ewing for a total expenditure (approximately $12 million) far below the cost of building and outfitting a new seismic research ship.

  12. Radiation Therapy for Soft Tissue Sarcomas

    MedlinePLUS

    ... sarcomas Next Topic Chemotherapy for soft tissue sarcomas Radiation therapy for soft tissue sarcomas Radiation therapy uses ... spread. This is called palliative treatment . Types of radiation therapy External beam radiation therapy: For this treatment, ...

  13. ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor.

    PubMed

    Kohashi, Kenichi; Yamada, Yuichi; Hotokebuchi, Yuka; Yamamoto, Hidetaka; Taguchi, Tomoaki; Iwamoto, Yukihide; Oda, Yoshinao

    2015-02-01

    ERG is immunoexpressed in vascular endothelial tumors, blastic extramedullary myeloid tumors, and tumors with ERG-involved translocation, such as prostate carcinoma or Ewing sarcoma. Recently, ERG immunoexpression was reported in an epithelioid sarcoma, which is a SMARCB1/INI1-deficient tumor, although epithelioid sarcoma is not associated with chromosomal translocations involving ERG and is categorized as a tumor with uncertain differentiation. SALL4 is essential for a proliferation and stabilization of embryonic stem cells. It was reported that SALL4 expression may aid in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. We analyzed the frequency of ERG and SALL4 expressions in 80 SMARCB1/INI1-deficient tumors, including 45 epithelioid sarcomas (conventional-type, 24; proximal-type, 20), 17 malignant rhabdoid tumors, 5 atypical teratoid/rhabdoid tumors, 6 undifferentiated/unclassified sarcomas, 5 myoepithelial tumors, and 4 extraskeletal myxoid chondrosarcomas. We found that ERG expression was present in 18 of the epithelioid sarcomas (41%), including 13 conventional-type (54%) and 5 proximal-type (25%), whereas all 17 of the malignant rhabdoid tumors exhibited negative immunoreactivity. One atypical teratoid/rhabdoid tumor (20%), 1 myoepithelial carcinoma (20%), 1 undifferentiated/unclassified sarcoma (17%), and no extraskeletal myxoid chondrosarcomas (0%) also showed ERG expression. SALL4 expression was recognized in 5 epithelioid sarcomas (11%), 12 malignant rhabdoid tumors (71%), 2 atypical teradoid/rhabdoid tumors (40%), 4 undifferentiated/unclassified sarcomas (67%), 1 myoepithelial tumor (20%), and none of the extraskeletal myxoid chondrosarcomas (0%). Therefore, the evaluation of ERG and SALL4 immunoexpressions may be a useful diagnostic tool to distinguish epithelioid sarcoma, especially proximal type, from malignant rhabdoid tumor. PMID:25479928

  14. Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-11-10

    Sarcoma, Soft Tissue; Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Liposarcoma; Synovial Sarcoma; Myxofibrosarcoma; Angiosarcoma; Fibrosarcoma; Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma

  15. An aza-macrocycle containing maltolic side-arms (maltonis) as potential drug against human pediatric sarcomas

    PubMed Central

    2014-01-01

    Background Identification of new drugs against paediatric sarcomas represents an urgent clinical need that mainly relies on public investments due to the rarity of these diseases. In this paper we evaluated the in vitro and in vivo efficacy of a new maltol derived molecule (maltonis), belonging to the family of molecules named hydroxypyrones. Methods Maltonis was screened for its ability to induce structural alteration of DNA molecules in comparison to another maltolic molecule (malten). In vitro antitumour efficacy was tested using a panel of sarcoma cell lines, representative of Ewing sarcoma, osteosarcoma and rhabdomyosarcoma, the three most common paediatric sarcomas, and in normal human mesenchymal primary cell cultures. In vivo efficacy was tested against TC-71 Ewing sarcoma xenografts. Results Maltonis, a soluble maltol-derived synthetic molecule, was able to alter the DNA structure, inhibit proliferation and induce apoptotic cell death in paediatric sarcoma cells, either sensitive or resistant to some conventional chemotherapeutic drugs, such as doxorubicin and cisplatin. In addition, maltonis was able to induce: i) p21, p15 and Gadd45a mRNA upregulation; ii) Bcl-2, survivin, CDK6 and CDK8 down-regulation; iii) formation of ?-H2AX nuclear foci; iv) cleavage of PARP and Caspase 3. Two independent in vivo experiments demonstrated the tolerability and efficacy of maltonis in the inhibition of tumour growth. Finally maltonis was not extruded by ABCB1, one of the major determinants of chemotherapy failure, nor appeared to be a substrate of the glutathione-related detoxification system. Conclusions Considering that treatment of poorly responsive patients still suffers for the paucity of agents able to revert chemoresistance, maltonis may be considered for the future development of new therapeutic approaches for refractory metastatic patients. PMID:24575739

  16. Radiotherapy in Ewing tumors of the vertebrae: Treatment results and local relapse analysis of the Chess 81/86 and EICESS 92 trials

    SciTech Connect

    Schuck, Andreas . E-mail: schuck@uni-muenster.de; Ahrens, Susanne; Schorlemer, Ines von; Kuhlen, Michaela; Paulussen, Michael; Hunold, Andrea; Gosheger, Georg; Winkelmann, Winfried; Dunst, Juergen; Willich, Normann; Juergens, Heribert

    2005-12-01

    Purpose: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors. Patients and Methods: A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence. Results: A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found. Conclusion: Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field.

  17. Rhodotorula minuta fungemia in a ewe lamb

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An 8-mo-old crossbred ewe, normal upon physical examination, was humanely euthanized for tissue collection. After approximately three weeks in tissue culture, fungi began budding out of cells obtained from the choroid plexus. After an additional three weeks, budding was observed in kidney cell cul...

  18. Purdy Awarded 2006 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Detrick, Robert S.; Purdy, G. Michael

    2007-01-01

    G. Michael Purdy was awarded the Maurice Ewing Medal at the AGU Fall Meeting honors ceremony, which was held on 13 December 2006 in San Francisco, Calif. The medal recognizes significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering technology and instrumentation; or outstanding service to marine science.

  19. Angiography in soft tissue sarcomas.

    PubMed

    Lois, J F; Fischer, H J; Deutsch, L S; Stambuk, E C; Gomes, A S

    1984-01-01

    Angiography was performed in 41 patients with histologically proven soft tissue sarcomas that included tumors derived from a variety of cell types and locations. The leiomyosarcomas and sarcomas of uncertain or mixed origin showed extensive neovascularity. Liposarcomas, synovial cell sarcomas, and fibrous histiocytic sarcomas were moderately vascularized. Sarcomas originating from vascular, fibrous, neural, and osseous tissues had variable degrees of vascularity. In nearly all of the cases studied, angiography revealed tumor size, extent, source, and degree of vascularity and helped to determine the degree of malignancy. While angiography does not provide a histologic diagnosis, it plays an important role in patient management when a conservative therapy plan that uses several modalities is followed. PMID:6099221

  20. Supplementing metabolizable protein to ewes during late gestation: II. Effects on ewe lamb performance and reproductive efficiency.

    PubMed

    Van Emon, M L; Schauer, C S; Eckerman, S R; Maddock Carlin, K R; Vonnahme, K A

    2015-03-01

    The objective of the current study was to determine the effects of maternal MP intake in isocaloric diets during late gestation on female offspring growth from birth to breeding and measure reproductive performance of those offspring in their first breeding season. In yr 1, maternal dietary treatments were applied at d 100 of gestation, were similar in total energy, and contained 60MP1, 60% of MP requirements; 80MP1, 80% of MP requirements; and 100MP1, 100% of the MP requirements on a DM basis during late gestation. In yr 2, maternal dietary treatments were similar in total energy and contained 60MP2, 60% of MP requirements; 100MP2, 100% of the MP requirements; and 140MP2, 140% of MP requirements on a DM basis during late gestation. While there was a quadratic effect ( = 0.003) for ewe lamb birth weight with the ewe lambs from 80MP1 ewes having increased birth weights compared with ewe lambs from 60MP1 and 100MP1 ewes in yr 1, there was no effect ( ? 0.22) of maternal diet on growth of ewe lamb offspring thereafter. A quadratic effect ( = 0.02) was observed for the percentage of ewe lambs bred during the first 17 d of the breeding season, with more ewe lambs born to ewes fed 80MP1 bred compared with ewe lambs born to ewes fed 60MP1 and 100MP1. Ewe lambs giving birth within the first 17 d of lambing season increased ( = 0.001) linearly as MP intake increased in the maternal diet. In yr 2, there was no effect ( ? 0.07) of maternal MP treatment during late gestation on growth of ewe lambs and reproductive performance except ADG from birth to weaning and lamb birth weight. There was a quadratic effect ( = 0.01) for ADG from birth to weaning of ewe lambs from ewes consuming 100MP2 being increased compared with ewe lambs from ewes fed 60MP2 and 140MP2. There was a linear ( = 0.04) reduction in birth weight of lambs born to ewe lambs as the dam's maternal dietary MP intake increased. The data from the current study suggest that feeding 80% or 100% of MP requirements during late gestation may have the greatest positive impacts on female offspring reproductive performance. PMID:26020910

  1. Primary intracranial Ewing’s sarcoma with unusual features

    PubMed Central

    VandenHeuvel, Katherine A; Al-Rohil, Rami N; Stevenson, Michael E; Qian, Jiang; Gross, Naina L; McNall-Knapp, Rene; Li, Shibo; Wartchow, Eric P; Mierau, Gary W; Fung, Kar-Ming

    2015-01-01

    Pediatric primary “small round blue cell” tumors in the CNS represent several entities, some more common than others. Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is rare and must be distinguished from other tumors such as medulloblastoma [1, 2], atypical rhabdoid/teratoid tumor, ependymomal tumors, metastatic sarcomas, hematologic malignancies, and other mimics. Although therapy for ES/pPNET is effective, it brings severe side effects, including cardiac toxicity, making correct recognition important [3]. As small blue cell tumors look similar, diagnosis often depends on special stains, immunohistochemistry, and molecular techniques. While the combination of membranous immunohistochemical reactivity for CD99 with cytoplasmic glycogen provides effective screening, demonstration of characteristic translocations of EWSR1 (chromosome 22) or FUS (chromosome 16) by fluorescent in situ hybridization (FISH) can confirm the diagnosis. We are reporting three primary ES/pPNET of the CNS, two of which occurred in children. While the adult case demonstrates the classic histopathology, the two pediatric cases have histopathology that significantly deviates from the usual. One is suggestive of a primary sarcoma, and the other mimics an ependymoma, but all three cases are confirmed with FISH. These observations suggest that primary ES in the CNS may have histology different from the classic morphology and a high index of suspicion should be maintained in order to make the correct diagnosis. A search of the literature suggests that these tumors are most frequently seen in children and young adults. Imaging often shows a supratentorial enhancing mass that touches the leptomeninges. Survival over three years is good but long term prognosis is unknown [3, 4]. PMID:25755713

  2. Adoptive cell therapy for sarcoma

    PubMed Central

    Mata, Melinda; Gottschalk, Stephen

    2015-01-01

    Current therapy for sarcomas, though effective in treating local disease, is often ineffective for patients with recurrent or metastatic disease. To improve outcomes, novel approaches are needed and cell therapy has the potential to meet this need since it does not rely on the cytotoxic mechanisms of conventional therapies. The recent successes of T-cell therapies for hematological malignancies have led to renewed interest in exploring cell therapies for solid tumors such as sarcomas. In this review, we will discuss current cell therapies for sarcoma with special emphasis on genetic approaches to improve the effector function of adoptively transferred cells. PMID:25572477

  3. Factors influencing the success of transcervical insemination in Merino ewes.

    PubMed

    Windsor, D P

    1995-04-15

    The experiments described examined the effects of a number of factors on the level of uterine insemination achieved in Merino ewes by a transcervical insemination technique (Guelph system for transcervical artificial insemination; GST-AI). Cervical penetration rate is an important limitation to the use of such methods in Merinos. Simulated insemination was performed to estimate the proportion of ewes in which a pipette could be passed through the cervix to the uterus. In Experiment 1, cervical penetration rate (n = 14 to 30) was unaffected by an increase in postpartum interval at AI from 12 to 26 wk. The results of cervical penetration for individual ewes were found to be repeatable (P < 0.05). Experiment 2 (197 ewes) revealed a clear effect of ewe parity on penetration rates in hormonally synchronized ewes during the nonbreeding season (P < 0.05). In Experiment 3, estrus synchronization using progestagen (n = 51) or prostaglandin (n = 50) did not affect penetration rate. The penetration rate was slightly higher in the naturally cycling ewes, but the difference was not significant. Comparison of ewes from Experiments 2 and 3 suggests the possibility of a major effect of stage of the breeding season on the penetration rate (P < 0.05). It is concluded that ewe selection and management techniques may be used to increase the proportion of transcervical insemination attempts resulting in uterine insemination. However, fertility testing will be required to determine whether such improvements translate into correspondingly increased pregnancy rates. PMID:16727688

  4. Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-02-02

    Myxofibrosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Leiomyosarcoma; Recurrent Liposarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Undifferentiated Pleomorphic Sarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma

  5. Postirradiation sarcoma in retinoblastoma. Induction or predisposition

    SciTech Connect

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

    1988-06-01

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

  6. Drugs Approved for Kaposi Sarcoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  7. Synovial sarcoma in childhood

    SciTech Connect

    Israels, S.J.; Chan, H.S.L.; Daneman, A.; Weitzman, S.S.

    1984-04-01

    The clinical and radiologic findings in seven children with synovial sarcoma are described. The five boys and two girls had a mean age at presentation of 4.4 years. All seven had the lesion situated in an extremity. Plain radiographs in four revealed the presence of a soft-tissue mass with no calcification or bone and joint involvement. In two patients studied with computed tomography (CT), the primary lesions had peripheral irregular areas of enhancement with central areas of poor enhancement, reflecting the necrotic, cystic, and hemorrhagic changes found in the centers of these tumors. Although the exact margins of these lesions were difficult to define accurately even with intravenous contrast enhancement, CT is still recommended as the best imaging method for assessing the local extent of the primary tumor and is a useful tool in the planning of appropriate therapy as well as the gauging of the tumor response to ongoing treatment.

  8. Clear cell sarcoma

    PubMed Central

    Ozuguz, Pinar; Kocak, Mukadder; Atasoy, Pinar; Vargel, Ibrahim; Cavusoglu, Tarik

    2014-01-01

    Malignant melanoma (MM) of soft tissue, also called clear cell sarcoma (CCS) of tendons and aponeuroses, derives from the neural crest. CCS is similar morphologically to MM but has no precursor skin lesion, and instead, has a characteristic chromosomal translocation. Prognosis is related to the tumor size. Early recognition and initial radical surgery is the key to a favorable outcome. The tumor has to be differentiated from other benign and malignant lesions of the soft tissues, such as fibrosarcoma. The demonstration of melanin and a positive immunohistochemical reaction for S-100 protein and HMB-45 can assist in the differential diagnosis. We report the case of a 58-year-old woman with CCS arising from the soft tissue of her little finger. PMID:25396137

  9. Treatment of Kaposi's sarcoma.

    PubMed

    Tur, E; Brenner, S

    1996-03-01

    The classic form of Kaposi's sarcoma (KS) is a rare multifocal neoplasm, as described by Kaposi in 1872. One hundred nine years after Kaposi's first description of the disease, the interest in all aspects of this disease escalated because of the emergence of human immunodeficiency virus (HIV), which is frequently accompanied by KS. This prompted zealous research, as reflected by numerous reports. Despite recent important discoveries, we are still far from understanding the pathogenesis of the disease and the mechanism of action of its various treatment modalities. As of today, treatment consists of most of the old modalities, some old ones in an updated improved version, and some new and experimental therapies. Our purpose is to focus on recent or novel data and to mention available treatments and their advantages, disadvantages, and side effects. We will also speculate on future directions. PMID:8607639

  10. Primary parietal myeloid sarcoma

    PubMed Central

    Sivaraju, Laxminadh; Mohan, Dilip; Ghosal, Nandita; Nandeesh, Bevinahalli N.; Hegde, Alangar S.

    2015-01-01

    Intracranial occurrence of myeloid sarcoma without any evidence of systemic hematological disorder is uncommon. We report the case of a 17-year-old girl who presented with features of raised intracranial pressure and paraparesis of short duration. Magnetic resonance imaging showed a 6 cm bilateral middle 1/3rd para sagittal contrast enhancing extra-axial mass with mass effect. The tumor was subtotally excised. Histology and immunohistochemistry proved to be a myelosarcoma. Further evaluation done with peripheral blood smear and bone marrow biopsy ruled out the possibility of leukemia or myeloproliferative disorder. She was referred for chemotherapy and clinically showed improvement after 6 months of follow-up. Authors report a case of intracranial myelosarcoma which closely resembled meningioma both radiologically and in intraoperative morphological appearance. Authors discuss in detail the radiological and histological features of myelosarcoma along with differential diagnoses and treatment options.

  11. Paget's sarcoma of the patella.

    PubMed

    Ansari, Salman; Bonar, Fiona; Stalley, Paul; Brown, Wendy

    2015-07-01

    Paget's sarcoma is a rare complication of Paget's disease and isolated Paget's disease of the patella is extremely rare. We describe a unique case of Paget's sarcoma of the patella in a 69-year-old male farmer who had a remote history of a fracture in the same patella 40years previously. In this case, imaging and pathogenesis of Paget's disease of bone is described and factors implicated in the development of Paget's disease in this patient are evaluated. PMID:25862337

  12. INFLUENCE OF SUPPLEMENT FORM ON EWE PERFORMANCE AND REPRODUCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Providing supplemental protein for ewes grazing dormant rangeland pastures is a common practice. The form of the protein supplement may affect feed intake and animal performance. Thus, an experiment was conducted to determine whether supplement form affected ewe body weight, body condition score, wo...

  13. Oxidative stress and therapeutic opportunities: focus on the Ewing's sarcoma family of tumors.

    PubMed

    Smith, Danielle G; Magwere, Tapiwanashe; Burchill, Susan A

    2011-02-01

    Reactive oxygen species (ROS) are highly reactive by-products of energy production that can have detrimental as well as beneficial effects. Unchecked, high levels of ROS result in an imbalance of cellular redox state and oxidative stress. High levels of ROS have been detected in most cancers, where they promote tumor development and progression. Many anticancer agents work by further increasing cellular levels of ROS, to overcome the antioxidant detoxification capacity of the cancer cell and induce cell death. However, adaptation of the level of cellular antioxidants can lead to drug resistance. The challenge for the design of effective cancer therapeutics exploiting oxidative stress is to tip the cellular redox balance to induce ROS-dependent cell death but without increasing the antioxidant activity of the cancer cell or inducing toxicity in normal cells. PMID:21342042

  14. Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma

    ClinicalTrials.gov

    2014-05-07

    Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Leiomyosarcoma; Adult Malignant Fibrous Histiocytoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  15. Childhood Soft Tissue Sarcoma: Treatment Information

    MedlinePLUS

    ... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

  16. Occupational risk factors for sarcoma subtypes.

    PubMed

    Hoppin, J A; Tolbert, P E; Flanders, W D; Zhang, R H; Daniels, D S; Ragsdale, B D; Brann, E A

    1999-05-01

    Herbicides, chlorophenols, and other occupational exposures are suspected risk factors for soft-tissue sarcoma, but the epidemiologic evidence is inconsistent. Given that soft-tissue sarcomas represent a heterogeneous mix of cancer subtypes and that these subtypes have different disease patterns by race, sex, and age at diagnosis, studying all soft-tissue sarcomas combined may mask subtype-specific associations. Using the Selected Cancers Study, a large population-based case-control study of sarcoma conducted among U.S. men aged 30 to 60 in 1984 to 1988, we explored the occupational risk factors for soft-tissue sarcoma subtypes and skeletal sarcoma. The analysis included 251 living sarcoma cases (48 dermatofibrosarcoma protuberans, 32 malignant fibrohistiocytic sarcoma, 67 leiomyosarcoma, 53 liposarcoma, and 51 skeletal sarcoma) and 1908 living controls. Exact conditional logistic regression models suggested patterns of subtype specificity for occupational exposures. Self-reported herbicide use was associated with malignant fibrohistiocytic sarcoma (OR = 2.9, 95% CI = 1.1-7.3). We found elevated risks for chlorophenol exposure and cutting oil exposure and malignant fibrohistiocytic sarcoma and leiomyosarcoma. We found no occupational risk factor for liposarcoma. Polytomous regression models identified different odds ratios across subtypes for plywood exposure and exposure to wood and saw dust. Although exploratory, this analysis suggests that occupational risk factors for sarcoma are not uniform across subtypes. PMID:10230842

  17. Operative and Conservative Treatment of Uterine Sarcomas

    PubMed Central

    Harter, P.; El-Khalfaoui, K.; Heitz, F.; du Bois, A.

    2014-01-01

    Uterine sarcomas are rare, aggressive mesenchymal tumours with a relatively poor prognosis. The term comprises various histological subtypes, such as leiomyosarcoma, endometrial stromal sarcomas as well as undifferentiated uterine sarcomas, which require different operative and systemic/radiation therapy strategies accordingly. The evidence on operative, adjuvant and palliative treatment currently available is presented here. PMID:24882876

  18. Operative and Conservative Treatment of Uterine Sarcomas.

    PubMed

    Harter, P; El-Khalfaoui, K; Heitz, F; du Bois, A

    2014-03-01

    Uterine sarcomas are rare, aggressive mesenchymal tumours with a relatively poor prognosis. The term comprises various histological subtypes, such as leiomyosarcoma, endometrial stromal sarcomas as well as undifferentiated uterine sarcomas, which require different operative and systemic/radiation therapy strategies accordingly. The evidence on operative, adjuvant and palliative treatment currently available is presented here. PMID:24882876

  19. Trabectedin in soft tissue sarcomas.

    PubMed

    Petek, Bradley J; Loggers, Elizabeth T; Pollack, Seth M; Jones, Robin L

    2015-02-01

    Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas. PMID:25686274

  20. Radiotherapy for Kaposi's sarcoma

    SciTech Connect

    Lo, T.C.; Salzman, F.A.; Smedal, M.I.; Wright, K.A.

    1980-02-15

    Between 1954 and 1976, 60 patients with Kaposi's sarcoma were treated in the Department of Radiotherapy of the Lahey Clinic Foundation at the High Voltage Research Laboratory of Massachusetts Institute of Technology. Only 2 patients were free of clinical disease in the lower extremities at the time of initial presentation, and 40 patients (69%) had cutaneous lesions involving areas extending above the knees. Eight patients (13%) also presented with mucous membrane involvement in addition to skin disease. Twenty-one patients were treated only with megavoltage electrons during the initial course of radiotherapy, and 12 patients were treated with supervoltage photons alone. The remaining 27 patients were treated with a combination of electrons and photons; in 17 patients, the same tumor sites were irradiated with both modalities. Eleven patients received whole-body surface electron irradiation. The choice of treatment modalities was based on the extent and distribution of cutaneous disease and depth of the lesions. The overall response rate was 93% after a single fractionated course of radiotherapy. Twenty-five patients achieved complete regression and 18 were in remission for 2 to 13 years. Response rates were also analyzed with respect to the three subgroups in terms of treatment modalities. A single dose of 800 to 1200 rads or its equivalent was required to control local cutaneous lesions. Widespread visceral metastasis was the most common cause of failure and death; the incidence of second malignancies was increased. Trial of systemic chemotherapy and immunotherapy would seem to be a reasonable therapeutic adjunct.

  1. Testicular myeloid sarcoma: case report

    PubMed Central

    Zago, Luzia Beatriz Ribeiro; Ladeia, Antnio Alexandre Lisba; Etchebehere, Renata Margarida; de Oliveira, Leonardo Rodrigues

    2013-01-01

    Myeloid sarcomas are extramedullary solid tumors composed of immature granulocytic precursor cells. In association with acute myeloid leukemia and other myeloproliferative disorders, they may arise concurrently with compromised bone marrow related to acute myeloid leukemia, as a relapsed presentation, or occur as the first manifestation. The testicles are considered to be an uncommon site for myeloid sarcomas. No therapeutic strategy has been defined as best but may include chemotherapy, radiotherapy and/or hematopoietic stem cell transplantation. This study reports the evolution of a patient with testicular myeloid sarcoma as the first manifestation of acute myeloid leukemia. The patient initially refused medical treatment and died five months after the clinical condition started. PMID:23580888

  2. Ultrasonographic findings in the ovine udder during lactogenesis in healthy ewes or ewes with pregnancy toxaemia.

    PubMed

    Barbagianni, Mariana S; Gouletsou, Pagona G; Valasi, Irene; Petridis, Ioannis G; Giannenas, Ilias; Fthenakis, George C

    2015-08-01

    Objective of the study was to record, by means of ultrasonographic examination, changes occurring during lactogenesis in the udder of healthy ewes and of ewes with pregnancy toxaemia. The work was carried out in 28 ewes, 16 with pregnancy toxaemia (group A) and 12 healthy controls (group B). B-mode and Doppler ultrasonographic examination of the udder of ewes was performed. During the last month of pregnancy, grey-scale intensity values of mammary parenchyma in group A were significantly greater than in group B (P = 0.007), as was also the progressive increase in grey-scale intensity values in both groups (P < 0.001). Blood mammary input was significantly greater in ewes of group B than in ewes of group A (P < 0.05), as was also the progressive increase in blood input in both groups (P < 0.001). Further, differences between the two groups were identified in pulsatility index (P = 0.007) and in mean blood velocity (P = 0.036), but only during the last fortnight of pregnancy. After lambing, grey-scale values decreased sharply compared to those in pregnancy (P < 0.01), whilst blood input, pulsatility index and mean blood velocity continued the same trend as at the last stage of pregnancy, with differences between the two groups still prevalent (P < 0.05). There was a reverse correlation between grey-scale intensity values and milk quantities (P < 0.035) and a correlation between blood input and milk quantities (P < 0.07). The progressive increase in the diameter of the external pudendal artery was significant (P < 0.001), but no significant differences were evident between the two groups (P > 0.35). Differences between group A and group B in all other haemodynamic parameters studied were not significant, neither throughout the last month of pregnancy (P > 0.25), nor during the first week of lactation (P > 0.06). However, their progressive changes during the last month of pregnancy were significant (P < 0.02). PMID:26130215

  3. Ewing Bank thrust: structural and sedimentological aspects

    SciTech Connect

    Huber, W.F.

    1989-03-01

    Compressional features observed as thrust faults occur in the Gulf of Mexico's upper slope area. A compressional feature manifested as a thrust can be seen in the Ewing Bank area in Block 988. This toe structure is initiated by upslope tensional forces via a type of large-scale slump. Wells that penetrate this thrust given no direct indications of repeat sections; however, well correlations tied via paleo and seismic data demonstrate the reverse nature of the fault's throw. The thrust feature can be seen clearly on a set of 3-D migrated extracted lines, which allow enhanced definition and increased confidence in the interpretation. Time slices through the area allow a plan view of the thrust. The Ewing Bank thrust fault zone trends east-west. Paleoreconstruction indicates the main thrust grew through time and suggests salt withdrawal beneath the decollement, which allowed the funneling of sediment. The compressional force apparently originated from the north due to normal faulting located at the front of a salt sheet; another possible origin is a more regional transmission of stress. The top and bottom of the salt sheet is appropriately imaged by 3-D data. By restoring salt thicknesses to depth, the interpreter can better appreciate the area's depositional and thrusting histories.

  4. Mast cell sarcoma: clinical management.

    PubMed

    Weiler, Catherine R; Butterfield, Joseph

    2014-05-01

    Mast cell sarcoma is a disorder that results in abnormal mast cells as identified by morphology, special stains, and in some publications, c-kit mutation analysis. It affects animal species such as canines more commonly than humans. In humans it is a very rare condition, with variable clinical presentation. There is no standard therapy for the disorder. It can affect any age group. It is occasionally associated with systemic mastocytosis and/or urticaria pigmentosa. The prognosis of mast cell sarcoma in published literature is very poor in humans. PMID:24745684

  5. Gallium scans in Paget's sarcoma

    SciTech Connect

    Yeh, S.D.; Rosen, G.; Benua, R.S.

    1982-12-01

    Bone and gallium scans were performed in twelve patients with Paget's sarcoma. Most of these patients had polyostotic Paget's disease. The lesions with sarcomatous changes were usually associated with less /sup 99m/Tc MDP uptake as compared with Pagetoid bone which was not sarcomatous. Gallium uptake in the tumor area was proportionally higher than the MDP uptake and appeared quite irregular. Follow-up scans were available in a limited number of patients. Temporary response to chemotherapy was reflected by the decreased gallium uptake in the tumor area. Gallium scans appear to be useful in confirming the diagnosis of Paget's sarcoma and may be valuable in monitoring therapeutic response.

  6. [Radiation induced sarcoma of the shoulder girdle].

    PubMed

    Steinke, N M; Ostgaard, S E; Jensen, O M; Nordentoft, A M; Sneppen, O

    1991-06-01

    A well-known complication after irradiation of tissue is development of postradiation sarcomas, and the shoulder girdle is in this connexion a frequent location, because it relatively often is exposured to x-rays. During the period 1956 to 1989 121 patients with sarcomas located to the shoulder girdle were referred to the Sarcoma centre in Arhus. Of these, six were postradiation sarcomas. The indication for the initial irradiation was in two cases cancer of the breast, in one malignant lymfogranulomatosis, in one a metastasis from malignant melanoma and finally two cases of peritendinitis humeroscapularis. In average 15 years (7-26 years) elapsed from irradiation to the diagnosis of the sarcomas. There were four bone sarcomas, two located in the clavicles and 2 in the humeri. Of these, three were osteogenic sarcomas and one a malignant fibrous histiocytoma. There were two soft tissue sarcomas, both located subcutaneously with involvement of deep fascia and muscle. Both tumors were extraskeletal osteogenic sarcomas. Three patients died of tumor on an average after 11 months. Two died without tumor from other causes, and one patient is alive without tumor 11 years after the treatment. If a patients presents with pain at the side of prior radiation, the diagnosis postradiation sarcoma must be considered and the patient referred to the Sarcoma centre. Radiation therapy should not be used in patients with benign lesions. PMID:2058030

  7. Gemcitabine Hydrochloride, Docetaxel, and Radiation Therapy in Treating Patients With Uterine Sarcoma That Has Been Removed By Surgery

    ClinicalTrials.gov

    2015-01-16

    Stage IA Uterine Sarcoma; Stage IB Uterine Sarcoma; Stage IC Uterine Sarcoma; Stage IIA Uterine Sarcoma; Stage IIB Uterine Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma

  8. Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

    SciTech Connect

    Kinsella, T.J.; Loeffler, J.S.; Fraass, B.A.; Tepper, J.

    1983-08-01

    A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. Local control was achieved in nine patients (90%) with a follow-up of 30 to 119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.

  9. Postradiation sarcoma involving the spine

    SciTech Connect

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

    1986-06-01

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

  10. Immunotherapy in Sarcoma: Future Horizons.

    PubMed

    Burgess, Melissa; Gorantla, Vikram; Weiss, Kurt; Tawbi, Hussein

    2015-11-01

    Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative regulatory signals from the innate immune system. Sarcomas are among the first tumors to be considered for immune interventions. From Coley's toxin to cytokine-based therapies to adoptive cell therapy, there have been numerous immunotherapeutic investigations in this patient population. A promising strategy includes adoptive T cell therapy which has been studied in small cohorts of synovial sarcoma, a subtype that is known to widely express the cancer testis antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal cell carcinoma demonstrate the utility and tremendous efficacy of immune checkpoint blockade with increased rates of durable responses compared to standard therapies. Responses in traditionally "non-immunogenic" tumors, such as lung and bladder cancers, provide ample rationale for the study of immune checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses in sarcomas, further research will help clarify optimal patient selection for future clinical trials and new combinatorial immunotherapeutic strategies. PMID:26423769

  11. Morel Receives 2005 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Schrag, Daniel P.; Morel, Franois M. M.

    2006-02-01

    Franois M. M. Morel received the Ewing Medal at the AGU Fall Meeting Honors Ceremony, which was held on 7 December 2005, in San Francisco, Calif. The medal is given for significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering, technology, and instrumentation; and for outstanding service to marine sciences. Franois Morel has led the search to understand the role of metals in the ocean, starting with a focus on inorganic processes and aquatic chemistry, and leading to a blend of geochemistry, microbiology, biochemistry, and genetics. His influence comes from his research and from the way he has educated an entire community of scientists with his textbooks, with his teaching, and through his former students and postdocs who hold faculty positions at universities throughout the world.

  12. Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-03-29

    High Grade Sarcoma; Metastatic Leiomyosarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Recurrent Leiomyosarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Synovial Sarcoma; Recurrent Undifferentiated Pleomorphic Sarcoma; Uterine Corpus Leiomyosarcoma

  13. CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor

    ClinicalTrials.gov

    2013-06-03

    Gastrointestinal Stromal Tumor; Recurrent Adult Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  14. What's New in Soft Tissue Sarcomas Research and Treatment?

    MedlinePLUS

    ... Topic Additional resources for soft tissue sarcoma What`s new in soft tissue sarcoma research and treatment? Research ... develop. This information is already being applied to new tests to diagnose and classify sarcomas. This is ...

  15. Soft Tissue Sarcomas of the Kidney

    PubMed Central

    Köhle, Olivia; Abt, Dominik; Rothermundt, Christian; Öhlschlegel, Christian; Brugnolaro, Christiane; Schmid, Hans-Peter

    2015-01-01

    Soft tissue sarcomas are rare mesenchymal tumors. Amongst others, primitive neuroectodermal tumors (PNET) of the kidney and synovial sarcoma of the kidney belong to the group of soft tissue sarcomas. Synovial sarcomas can occur almost anywhere in the body, most frequently, however, in the lower (62%) or upper extremities (21%). Metastases occur in 50-70% of cases, and thus the prognosis is poor. PNETs are rare, highly aggressive neoplastic lesions which mainly occur in the torso or axial skeleton in young adults. The prognosis is poor with a 5-year disease-free survival rate of 45-55%. The primary therapeutic approach is surgical resection. Most randomized studies assessing adjuvant chemotherapy for all types of localized soft tissue sarcomas did not show statistically significantly better overall survival times after chemotherapy, although they did show longer progression-free survival. We report on two cases of primary renal synovial sarcoma and one case of PNET of the kidney. PMID:25918607

  16. High-grade pelvic sarcoma after radiation therapy for low-grade endometrial stromal sarcoma

    SciTech Connect

    Chumas, J.C.; Patsner, B.; Mann, W.J. )

    1990-03-01

    A high-grade heterologous pelvic sarcoma arose in a 60-year-old woman 15 years after she received whole-pelvic radiation for a low-grade endometrial stromal sarcoma. This complication must be considered in determining therapy for low-grade endometrial sarcomas, which are usually inherently of indolent biological behavior.

  17. Radiation-induced sarcoma of the thyroid

    SciTech Connect

    Griem, K.L.; Robb, P.K.; Caldarelli, D.D.; Templeton, A.C. )

    1989-08-01

    A 23-year-old white man presented with a thyroid mass 12 years after receiving high-dose radiotherapy for a T2 and N1 lymphoepithelioma of the nasopharynx. Following subtotal thyroidectomy, a histopathologic examination revealed liposarcoma of the thyroid gland. The relationship between sarcomas and irradiation is described and Cahan and colleagues' criteria for radiation-induced sarcomas are reviewed. To our knowledge, we are presenting the first such case of a radiation-induced sarcoma of the thyroid gland.

  18. Cerebellar granulocytic sarcoma: a case report.

    PubMed

    Baytan, Birol; Evim, Melike Sezgin; Gne?, Adalet Meral; Kocaeli, Hasan; Balaban, Saduman; Korfal?, Ender; Tzner, Nkhet

    2012-06-01

    Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that is usually associated with acute myelogenous leukemia. Intraparenchymal cranial localization without skull, meningeal, or bone marrow invasion is extremely rare. The mechanisms of intraparenchymal cranial localization of GS remains unknown, as only 10 cases with cerebellar granulocytic sarcoma have been previously reported. Herein, we report a four year old boy with cerebellar localization of granulocytic sarcoma. PMID:24744651

  19. Cerebellar Granulocytic Sarcoma: A Case Report

    PubMed Central

    Baytan, Birol; Evim, Melike Sezgin; Gne?, Adalet Meral; Kocaeli, Hasan; Balaban, ?aduman; Korfal?, Ender; Tzner, Nkhet

    2012-01-01

    Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that is usually associated with acute myelogenous leukemia. Intraparenchymal cranial localization without skull, meningeal, or bone marrow invasion is extremely rare. The mechanisms of intraparenchymal cranial localization of GS remains unknown, as only 10 cases with cerebellar granulocytic sarcoma have been previously reported. Herein, we report a four year old boy with cerebellar localization of granulocytic sarcoma. PMID:24744651

  20. Primary pleuropulmonary synovial sarcoma: a case report

    PubMed Central

    Yuan, Lianfang; Guan, Zhiyu; Dai, Xuan; Xu, Jie

    2015-01-01

    Pleuropulmonary synovial sarcoma (PPSS) is an extremely rare malignant tumor, which is increasingly recognized as a subtype of sarcoma with a distinctive chromosomal translocation specific to synovial sarcoma. It is often presents like any thoracic tumor with symptoms such as chest pain or cough. Here we report a case of PPSS in a 49-year-old woman presenting with cough, shortness of breath and chest pain. And who were found upon histologic examination of the resection specimen to have cystic primary pleuropulmonary synovial sarcoma.

  1. Sarcomas of the distal extremities

    SciTech Connect

    Jenkin, R.D.T.

    1983-08-01

    This editorial focuses on sarcomas of bone or soft tissue at sites distal to the elbow or knee. These tumors are rare, so that it is not surprising that the best treatment is not clearly established. Whether or not systemic treatment is given to the patient with no evidence of metastatic disease, which is the common situation for sarcomas of the distal extremities, will be determined by results of adjuvant chemotherapy at the proximal limb and axial sites for the tumor entity in question. Necessarily the local treatment must be resection or irradiation or a combination of these treatments. The choice is determined by the relative effectiveness and morbidity of these treatments and is site-dependent.

  2. Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

    PubMed Central

    Fidler, M M; Frobisher, C; Guha, J; Wong, K; Kelly, J; Winter, D L; Sugden, E; Duncan, R; Whelan, J; Reulen, R C; Hawkins, M M

    2015-01-01

    Background: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Methods: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital status, alcohol and smoking habits, and educational qualifications were investigated for survivors who completed a questionnaire. Results: Survivors were seven times more likely to experience all-cause mortality than expected, and there were substantial differences in risk depending on tumour type. Beyond 25 years follow-up the risk of dying from all-causes was comparable to the general population. This is in contrast to dying before 25 years where the risk was 12.7-fold that expected. Survivors were also four times more likely to develop a SPN than expected, where the excess was restricted to 524 years post diagnosis. Increased health-care usage and poor health status were also found. Nonetheless, for some psychosocial outcomes survivors were better off than expected. Conclusions: Up to 25 years after 5-year survival, bone sarcoma survivors are at substantial risk of death and SPNs, but this is greatly reduced thereafter. As 95% of all excess deaths before 25 years follow-up were due to recurrences and SPNs, increased monitoring of survivors could prevent mortality. Furthermore, bone and breast SPNs should be a particular concern. Since there are variations in the magnitude of excess risk depending on the specific adverse outcome under investigation and whether the survivors were initially diagnosed with osteosarcoma or Ewing sarcoma, risks need to be assessed in relation to these factors. These findings should provide useful evidence for risk stratification and updating clinical follow-up guidelines. PMID:25989269

  3. Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

    ClinicalTrials.gov

    2015-08-26

    Childhood Acute Lymphoblastic Leukemia; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma; Ewing Sarcoma; Ewing Sarcoma of Bone; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Unspecified Childhood Solid Tumor, Protocol Specific; Wilms Tumor and Other Childhood Kidney Tumors

  4. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine the safety and efficacy of low-dose, subacute exposure of mature ewes to NaClO3 in the drinking water. Twenty-five ewes (BW = 62.5 7.3 kg) were placed indoors in individual pens with ad libitum access to water and feed. After 7 d of adaptation, ewes were assigned ran...

  5. Maurice Ewing Medalist: Xavier Le Pichon

    NASA Astrophysics Data System (ADS)

    Ewing, John I.; Le Pichon, Xavier

    1984-04-01

    Mr. President, fellow members of the American Geophysical Union, and members of the U.S. Navy, it gives me great pleasure to present the citation for the 1984 AGU/USN Maurice Ewing Medal, to be awarded to Dr. Xavier Le Pichon.After receiving diplomas in several disciplines of geology, physics, and geophysics from the University of Strasbourg during the 1950s, Xavier came to the Lamont-Doherty Geological Observatory as a visiting scientist where he put his knowledge to practice until 1968. In 1966 he received the Doctor of Sciences degree from the University of Strasbourg. Returning to France in 1968, Xavier spent the next five years at the Centre Ocanologique de Bretagne in Brest where he founded the Research Group. From Brest he moved to the headquarters of CNEXO in Paris for 5 years and then to the University of Paris to found the new Laboratoire de Godynamique. From his present position of professor at the university he will move next year to become director of the Geology Laboratory in the Ecole Normale Suprieure, one of the French Grandes Ecoles.

  6. AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-07-02

    Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Rhabdomyosarcoma; Dermatofibrosarcoma Protuberans; Endometrial Stromal Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  7. Adult human sarcomas. I. Basic science.

    PubMed

    Sinkovics, Joseph G

    2007-01-01

    When connective tissue undergoes malignant transformation, glioblastomas and sarcomas arise. However, the ancient biochemical mechanisms, which are now operational in sarcomas distorted by mutations and gene fusions in misaligned chromosomes, were originally acquired by those cells that emerged during the Cambrian explosion. Preserved throughout evolution up to the genus Homo, these mechanisms dictate the apoptosis- and senescence-resistant immortality of malignant cells. A 'retroviral paradox' distinguishes human sarcomas from those of the animal world. In contrast to the retrovirally induced sarcomatous transformation of animal (avian, murine, feline and simian) cells, human sarcomas have so far failed to yield a causative retroviral isolate. However, the proto-oncogenes/oncogenes transduced from their host cells by retroviruses of animals are the same that are active in human sarcomas. Since the encoded oncoproteins arise after birth, they are recognized frequently by the immune system of the host. Immune lymphocytes that kill autologous sarcoma cells in vitro commonly fail to do so in vivo. Sarcoma vaccines generate immune T- and natural killer cell reactions; even when vaccinated patients do not show a clinical response, their tumors become more sensitive to chemotherapy. The aim of this review is to lay a solid molecular biological foundation for the conclusion that targeting the sarcoma oncogenes will result in regression of the disease. PMID:17187519

  8. Subcutaneous Kaposi's sarcoma. Thallium scan demonstration

    SciTech Connect

    Lee, V.W.; Chen, H.; Panageas, E.; O'Keane, J.C.; Liebman, H.A. )

    1990-08-01

    A case of AIDS-related Kaposi's sarcoma involving subcutaneous tissues beyond the visible skin lesions is reported. In this case, the tumor was thallium avid. Thallium scintigraphy was able to demonstrate the true extent of the tumor and may be used to document the presence and extent of cutaneous and extracutaneous AIDS-related Kaposi's sarcoma.

  9. Clinical mastitis in ewes; bacteriology, epidemiology and clinical features

    PubMed Central

    Mrk, Tormod; Waage, Steinar; Tollersrud, Tore; Kvitle, Bjrg; Sviland, Stle

    2007-01-01

    Background Clinical mastitis is an important disease in sheep. The objective of this work was to identify causal bacteria and study certain epidemiological and clinical features of clinical mastitis in ewes kept for meat and wool production. Methods The study included 509 ewes with clinical mastitis from 353 flocks located in 14 of the 19 counties in Norway. Clinical examination and collection of udder secretions were carried out by veterinarians. Pulsed-field gel electrophoresis (PFGE) was performed on 92 Staphylococcus aureus isolates from 64 ewes. Results and conclusion S. aureus was recovered from 65.3% of 547 clinically affected mammary glands, coagulase-negative staphylococci from 2.9%, enterobacteria, mainly Escherichia coli, from 7.3%, Streptococcus spp. from 4.6%, Mannheimia haemolytica from 1.8% and various other bacteria from 4.9%, while no bacteria were cultured from 13.2% of the samples. Forty percent of the ewes with unilateral clinical S. aureus mastitis also had a subclinical S. aureus infection in the other mammary gland. Twenty-four of 28 (86%) pairs of S. aureus isolates obtained from clinically and subclinically affected mammary glands of the same ewe were indistinguishable by PFGE. The number of identical pairs was significantly greater than expected, based on the distribution of different S. aureus types within the flocks. One-third of the cases occurred during the first week after lambing, while a second peak was observed in the third week of lactation. Gangrene was present in 8.8% of the clinically affected glands; S. aureus was recovered from 72.9%, Clostridium perfringens from 6.3% and E. coli from 6.3% of the secretions from such glands. This study shows that S. aureus predominates as a cause of clinical ovine mastitis in Norway, also in very severe cases. Results also indicate that S. aureus is frequently spread between udder halves of infected ewes. PMID:17892567

  10. Evaluation of In Vitro Activity of the Class I PI3K Inhibitor Buparlisib (BKM120) in Pediatric Bone and Soft Tissue Sarcomas

    PubMed Central

    Anderson, Jennifer L.; Park, Ann; Akiyama, Ryan; Tap, William D.; Denny, Christopher T.; Federman, Noah

    2015-01-01

    Pediatric bone and soft tissue sarcomas often display increased Akt phosphorylation through up regulation of insulin-like growth factor (IGF1) signaling. Additionally, Akt signaling has been linked to resistance to IGF1 receptor (IGF1R) and mTOR (mammalian target of rapamycin) inhibitors in sarcoma, further demonstrating the role of Akt in tumor survival. This suggests targeting components of the PI3K/Akt pathway may be an effective therapeutic strategy. Here, we investigated the in vitro activity of the pan-class I PI3K inhibitor buparlisib (BKM120) in pediatric bone and soft tissue sarcomas. Buparlisib inhibited activation of Akt and signaling molecules downstream of mTORC1 (mTOR complex 1) in Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma cell lines. Anti-proliferative effects were observed in both anchorage dependent and independent conditions and apoptosis was induced within 24 hours of drug treatment. Buparlisib demonstrated cytotoxicity as a single agent, but was found to be more effective when used in combination. Synergy was observed when buparlisib was combined with the IGF1R inhibitor NVP-AEW541 and the mTORC1 inhibitor rapamycin. The addition of NVP-AEW541 also further reduced phospho-Akt levels and more potently induced apoptosis compared to buparlisib treatment alone. Additionally, the combination of buparlisib with the MEK1/2 inhibitor trametinib resulted in synergy in sarcoma cell lines possessing MAPK pathway mutations. Taken together, these data indicate buparlisib could be a novel therapy for the treatment of pediatric bone and soft tissue sarcomas. PMID:26402468

  11. Sarcomas other than Kaposi sarcoma occurring in immunodeficiency: interpretations from a systematic literature review

    PubMed Central

    Bhatia, Kishor; Shiels, Meredith. S.; Berg, Alexandra; Engels, Eric. A.

    2012-01-01

    Purpose of review In immunodeficiency, an increased sarcoma risk is confirmed for Kaposis sarcoma. Whether rates of other sarcoma subtypes are elevated in the setting of immunodeficiency is not known. We therefore reviewed published case reports on HIV/AIDS patients and organ transplant recipients with sarcomas. For comparison, we assessed sarcomas in the U.S. general population using Surveillance Epidemiology End Results (SEER) data. Findings One hundred seventy-six non-KS sarcomas were identified, 75 in people with HIV/AIDS and 101 in transplant recipients. Leiomyosarcomas (n=101) were the most frequently reported sarcomas, followed by angiosarcomas (n=23) and fibrohistiocytic tumors (n=17). Leiomyosarcomas were reported with two age peaks, in children and young adults. Epstein-Barr virus (EBV) was detected in the tumor cells in 85% and 88% of leiomyosarcomas in HIV-infected people and transplant recipients, respectively. Angiosaromas and fibrohistiocytic tumors were most frequently reported in males. Among kidney transplant recipients, 20% of sarcomas arose at the site of an arteriovenous fistula. In comparison, leiomyoscarcomas, angiosarcomas, and fibrohistiocytic tumors comprised 16.9%, 3.8%, and 18.7% of sarcomas in the U.S. general population. Summary Leiomyosarcoma and angiosarcoma may occur disproportionately in immunodeficiency. Leiomyosarcomas appear etiologically linked to EBV while angiosarcomas might be correlated with an arteriovenous fistula. Additional studies are necessary to understand the contribution of immunodeficiency to the etiology of these sarcomas. PMID:22729152

  12. Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma

    PubMed Central

    De Sanctis, Rita; Marrari, Andrea; Marchetti, Silvia; Mussi, Chiara; Balzarini, Luca; Lutman, Fabio Romano; Daolio, Primo; Bastoni, Stefano; Bertuzzi, Alexia Francesca; Quagliuolo, Vittorio; Santoro, Armando

    2015-01-01

    Objective Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific subgroups of patients with soft tissue sarcomas (STS). Methods Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m2 every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS). Results Median age was 48 (range, 2075) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 05). Median number of trabectedin cycles was 3 (range, 117). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 223) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively. Conclusion Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma. PMID:26604682

  13. Mucin 1-mediated chemo-resistance in lung cancer cells.

    PubMed

    Ham, S Y; Kwon, T; Bak, Y; Yu, J-H; Hong, J; Lee, S K; Yu, D-Y; Yoon, D-Y

    2016-01-01

    Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial-mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and ?-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and ?-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers. PMID:26779808

  14. Mucin 1-mediated chemo-resistance in lung cancer cells

    PubMed Central

    Ham, S Y; Kwon, T; Bak, Y; Yu, J-H; Hong, J; Lee, S K; Yu, D-Y; Yoon, D-Y

    2016-01-01

    Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelialmesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and ?-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and ?-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers. PMID:26779808

  15. Diagnosis and treatment of Kaposi's Sarcoma. Oncology overview

    SciTech Connect

    Not Available

    1983-11-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Kaposi's sarcoma diagnosis; Kaposi's sarcoma clinical immunology; Kaposi's sarcoma chemotherapy; Kaposi's sarcoma radiotherapy; Kaposi's sarcoma other treatment modalities; Kaposi's sarcoma case reports; Kaposi's sarcoma etiology; Kaposi's sarcoma epidemiology; Kaposi's sarcoma relation to acquired immune deficiency syndrome; Kaposi's sarcoma reviews.

  16. Pazopanib in sarcomas: expanding the PALETTE

    PubMed Central

    Wilky, Breelyn A.; Meyer, Christian F.; Trent, Jonathan C.

    2014-01-01

    Purpose of review After failure of standard therapy, few effective treatment options exist for adult patients with metastatic sarcomas, and median survival remains dismal at approximately 1 year. Pazopanib, a multitargeted tyrosine kinase inhibitor, has recently been approved for nonadipocytic soft tissue sarcomas refractory to chemotherapy. In this review, we will revisit the efficacy of pazopanib in sarcomas, and present a patient case that illustrates two of many unanswered questions: which sarcoma patients are most likely to benefit from pazopanib therapy, and what criteria are best suited to accurately detect benefit in clinical trials? Recent findings Pazopanib has been tested in sarcoma patients in a phase II and phase III study, and was shown to prolong progression-free survival by 3 months relative to placebo. Although histology has been the primary stratification variable for subgroup analysis in large sarcoma trials, the PALETTE study did not demonstrate superior response within histologic cohorts. Ongoing trials seek to explore efficacy of pazopanib in previously excluded histologies, as well as include correlative studies to identify histologic and molecular biomarkers to predict patients likely to benefit. Summary Pazopanib has been proven to provide modest benefit overall to nonadipocytic soft tissue sarcoma patients, but we have yet to identify the molecular basis for those patients who derive exceptional benefit. PMID:23666473

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

    ClinicalTrials.gov

    2013-12-10

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

  18. Patterns of nonclinical intramammary infection in a ewe flock.

    PubMed

    Hueston, W D; Hartwig, N R; Judy, J K

    1986-01-15

    Coagulase-negative staphylococci were the most frequent bacterial isolates from nonclinical intramammary infections (NIMI) in a ewe flock. The prevalence of NIMI was 22.9% of the udder halves at lambing and decreased to 12.5% or less between week 2 and week 6 of lactation. The decrease was due mainly to the elimination of infections involving coagulase-negative staphylococci. The frequency of new NIMI in the first 6 weeks of lactation was less than 1% of the noninfected udder halves per week. The prevalence of NIMI increased steadily from 16.1% of the udder halves at the time of weaning the lambs to 29% at postweaning week 3. The new infection rate averaged 9.7% per week during the postweaning 3 weeks. The principal bacterial isolate in the new NIMI was coagulase-negative staphylococcus. Nonclinical intramammary infection in a ewe flock was monitored by bacteriologic cultural examinations of milk samples obtained from both udder halves of 24 ewes during early lactation and of 31 ewes in the same flock during the early postweaning period. The patterns of NIMI were similar to the patterns reported in cattle. PMID:3754546

  19. Ellen Thomas Receives 2012 Maurice Ewing Medal: Response

    NASA Astrophysics Data System (ADS)

    Thomas, Ellen

    2013-01-01

    I feel deeply honored to receive the Maurice Ewing Medal, especially because that means seeing my name on a list of medalists including some of my heroes in science. They not only influenced my scientific thinking, especially as to the complexities of the Earth's carbon cycle, but also helped me in my serendipitous career.

  20. UTERINE RESPONSE TO INFECTIOUS BACTERIA IN ESTROUS CYCLIC EWES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Luteal-phase uteri are susceptible to infections, and PGE2 and exogenous progesterone can down-regulate, whereas PGF2a can up-regulate, uterine immune functions. To study this phenomenon, uteri of follicular- or luteal-phase ewes were inoculated with either saline or bacteria (Arcanobacterium pyogen...

  1. Phase II Study of High-Dose Photon/Proton Radiotherapy in the Management of Spine Sarcomas

    SciTech Connect

    DeLaney, Thomas F. Liebsch, Norbert J.; Pedlow, Francis X.; Adams, Judith; Dean, Susan; Yeap, Beow Y.; McManus, Patricia; Rosenberg, Andrew E.; Nielsen, G. Petur; Harmon, David C.; Spiro, Ira J.; Raskin, Kevin A.; Suit, Herman D.; Yoon, Sam S.; Hornicek, Francis J.

    2009-07-01

    Purpose: Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of {>=}66 Gy are recommended. A Phase II clinical trial evaluated high-dose photon/proton XRT for spine sarcomas. Methods and Materials: Eligible patients had nonmetastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or postoperative photon/proton XRT with or without radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (Gy RBE) to subclinical disease, 70.2 Gy RBE to microscopic disease in the tumor bed, and 77.4 Gy RBE to gross disease at 1.8 Gy RBE qd. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 Gy RBE to surface/center. Intraoperative boost doses of 7.5 to 10 Gy could be given by dural plaque. Results: A total of 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). With 48 month median follow-up, 5-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence (p < 0.001). Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared after 77.12 to 77.4 Gy RBE. Conclusions: Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 Gy RBE are at risk for late toxicity.

  2. Incidence, and Gender, Age and Ethnic Distribution of Sarcomas in the Republic of Suriname from 1980 to 2008

    PubMed Central

    Mans, DRA; Lall, AE Budhu; Macnack, VL; van Tholl, JA; Zandveld, EB; Vrede, MA

    2014-01-01

    Objective: We report on the incidence and the gender, age and ethnic distribution of sarcomas diagnosed between 1980 and 2008 in the multi-ethnic Republic of Suriname. Methods: Total and average yearly number of cases, crude rates, as well as relevant population data were derived from the records of the Pathologic Anatomy Laboratory and the General Bureau of Statistics, respectively, and stratified according to gender, age groups 019, 2049 and 50+ years, and the largest ethnic groups (Hindustani, Creole, Javanese and Maroons). Results: Between 1980 and 2008, 258 sarcomas were diagnosed in Suriname, ie at a frequency of nine per year and an annual rate of two per 100 000. Overall, there was 0.9 male per female, two to four cases per year in each age group, and one to three patients in each ethnic group. Soft-tissue sarcomas comprised approximately 80% of overall cases, with a male/female ratio that was approximately 0.5; almost 90% of patients were older than 20 years; more than one-third was Creole. Leiomyosarcoma, fibrosarcoma and liposarcoma were most frequently encountered (90 cases), particularly above 20 years of age, while leiomyosarcomas seemed, additionally, more common in women and Creoles or Maroons. The most numerous bone tumours were primitive neuroectodermal tumour/Ewing tumour and osteosarcoma (37 cases). They were more common in males, the youngest age group, and Hindustanis and Creoles. Conclusions: The incidence of sarcomas in Suriname, and their gender, age and ethnic distribution in general, seemed comparable with international data. The main exception might be leiomyosarcoma which might have a predilection for Afro-Surinamese. PMID:25303244

  3. Induction of cervical dilation for transcervical embryo transfer in ewes

    PubMed Central

    2014-01-01

    Background A major limitation in the application of assisted reproductive technologies in sheep arises from the inability to easily traverse the uterine cervix. The cervix of the non-pregnant ewe is a narrow and rigid structure, with 5–7 spiral folds and crypts that block its lumen. The first two folds closest to the vagina appear to be the greatest obstacle for the instrument insertion into the sheep cervix. Therefore, the dilation of the distal part of the cervix could provide the conformational change necessary to perform non-invasive transcervical procedures. The present study set out to assess the efficacy of Cervidil®, a patented dinoprostone (PgE2)-containing vaginal insert with a controlled-release mechanism, to safely induce sufficient cervical dilation for the purpose of transcervical embryo transfer (TCET) in cyclic ewes. Methods The transfer of frozen-thawed ovine embryos was attempted in 22 cross-bred Rideau Arcott x Polled Dorset ewes, with or without the pre-treatment with Cervidil® for 12 or 24 h prior to TCET. Results Cervical penetration rate was significantly improved after Cervidil® pre-treatment, with 55% (6/11) of treated versus 9% (1/11) of control animals successfully penetrated (χ2-test, p < 0.05). Within the treated ewes that were penetrated, 67% (4/6) had been exposed to Cervidil(R) for 24 h and 33% (2/6) had had a 12-h exposure (p > 0.05). Variations in the age, weight, genotype, parity, lifetime lamb production (LLP) and post-partum interval (PPI) between penetrated and non-penetrated ewes were not significant (p > 0.05). The time taken to traverse the uterine cervix was negatively correlated (p < 0.05) with the age, parity, LLP and PPI. Progesterone assays and ultrasonographic examinations performed 25 days after ET confirmed pregnancy in 2 of 7 penetrated ewes, but no fetuses were detected ultrasonographically 55 days post-TCET. Conclusions The present results indicate a significant benefit of using Cervidil® for inducing cervical dilation during the mid-luteal phase in ewes but the reason(s) for impaired fertility after the transfer of frozen-thawed ovine embryos remains to be elucidated. PMID:24467737

  4. Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma

    ClinicalTrials.gov

    2015-03-25

    Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/PNET; Metastatic Osteosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/PNET; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  5. Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-12-03

    Fallopian Tube Cancer; Female Reproductive Cancer; Ovarian Carcinosarcoma; Ovarian Sarcoma; Recurrent Ovarian Epithelial Cancer; Recurrent Uterine Sarcoma; Stage III Ovarian Epithelial Cancer; Stage III Uterine Sarcoma; Stage IV Ovarian Epithelial Cancer; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  6. Treatment Option Overview (Adult Soft Tissue Sarcoma)

    MedlinePLUS

    ... cause signs or symptoms until they get very big. As the sarcoma grows bigger and presses on ... Caregivers About This PDQ Summary About PDQ Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) ...

  7. General Information about Adult Soft Tissue Sarcoma

    MedlinePLUS

    ... cause signs or symptoms until they get very big. As the sarcoma grows bigger and presses on ... Caregivers About This PDQ Summary About PDQ Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) ...

  8. Stages of Adult Soft Tissue Sarcoma

    MedlinePLUS

    ... cause signs or symptoms until they get very big. As the sarcoma grows bigger and presses on ... Caregivers About This PDQ Summary About PDQ Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) ...

  9. Treatment Options for Adult Soft Tissue Sarcoma

    MedlinePLUS

    ... cause signs or symptoms until they get very big. As the sarcoma grows bigger and presses on ... Caregivers About This PDQ Summary About PDQ Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) ...

  10. Biphasic synovial sarcoma in mandibular region

    PubMed Central

    Wadhwan, Vijay; Malik, Sangeeta; Bhola, Nitin; Chaudhary, Minal

    2011-01-01

    The term synovioma was coined by Smith in 1927, and later in 1936 Knox suggested the name synovial sarcoma. It occurs primarily in the paraarticular regions, usually in close association with tendon sheaths, bursae, and joint capsules. On rare occasions it may be seen in areas without any apparent relationship to synovial structures as in parapharyngeal region or the abdominal cavity. The first description of synovial sarcoma in the head and neck region was by Pack and Ariel in 1950. The majority of these tumors seem to take origin from paravertebral connective tissue spaces and manifest as solitary retropharyngeal or parapharyngeal masses near the carotid bifurcation. Synovial sarcoma has been reported in soft palate, tongue, maxillofacial region, angle of mandible, sternoclavicular region, scapular region, and the esophagus. We report a case of 28-year-old male patient with synovial sarcoma in mandibular region with biphasic pattern. PMID:22529590

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

    PubMed

    Neuville, Agns; Coindre, Jean-Michel; Chibon, Frdric

    2015-01-01

    Sarcomas are a heterogeneous group of tumors. Their diagnosis is based on morphology and immunohistochemical profile, with categories of tumors according to the type of tissue that they resemble. Nevertheless, for several tumors, cellular origin is unknown. Molecular analysis performed in recent years allowed, combining histophenotype and genomics, better classifying such sarcomas, individualizing new entities and grouping some tumors. Simple and recurrent genetic alterations, such as translocation, mutation, amplification, can be identified in one of two sarcomas and appear as new diagnostic markers. Their identification in specialized laboratories in molecular pathology of sarcomas is often useful and sometimes necessary for a good diagnosis, leading to a heavy and multidisciplinary multi-step treatment. PMID:25533919

  12. Myxoid sarcoma arising from the pulmonary trunk.

    PubMed

    Atari, E; Okudaira, M

    1987-02-01

    We reported a case of a myxoid sarcoma of the pulmonary trunk in a 40-year-old women. On light and immunohistochemical studies, spindle-shaped tumor cells revealed the nature of smooth muscle origin. PMID:3300161

  13. Gonadotropin stimulation using P.G. 600 on reproductive success of non-lactating anestrous ewes.

    PubMed

    D'Souza, K N; Rastle-Simpson, S L; Redhead, A K; Baptiste, Q S; Smith, B; Knights, M

    2014-08-01

    The effect of stimulation with a gonadotropin preparation with combined follicle stimulating and luteininzing hormone like activity on reproductive success in anestrous ewes was evaluated. In Experiment 1, ewes of mixed breeding were treated with CIDR inserts (0.3g progesterone) for 5 days and were assigned randomly to receive either gonadotropin stimulation (3mL i.m. injection of P.G. 600, 240IU eCG and 120IU hCG) at CIDR removal or no further treatment. Intact raddled rams were joined at insert removal for 30-35 days, and ewes were observed for indications of estrus after 4 days of ram exposure. Pregnancy diagnosis was conducted via transrectal ultrasonography at the time of ram removal and again 20-25 days. The second experiment was similar to Experiment 1, except treated ewes received the gonadotropin 1 day prior to insert removal. In Experiment 1, incidence of estrus was greater for treated ewes (P=0.01), and prolificacy tended to be greater in treated ewes (P=0.06). In Experiment 2, treated ewes had greater conception rates (P=0.01), pregnancy rates to first service (P=0.0007), and tended to have greater overall pregnancy rates than control ewes (P=0.07). A greater percentage of ewes lambed in the gonadotropin treated ewes than in ewes in the control group (P<0.0001), and overall lambing rates in treated ewes were greater than non-treated controls (P<0.0001). In conclusion, gonadotropin treatment 1 day prior to CIDR removal increased reproductive success in progesterone-treated anestrous ewes. PMID:24950998

  14. Acroangiodermatitis (Pseudo-Kaposi sarcoma).

    PubMed

    Singh, Satyendra Kumar; Manchanda, Kajal

    2014-07-01

    Acroangiodermatitis or Pseudo-Kaposi sarcoma is a rare angioproliferative entity, related to chronic venous insufficiency or certain other vascular anomalies. It is often associated with chronic venous insufficiency, arteriovenous malformation of the legs, chronic renal failure treated with dialysis, paralyzed legs and amputation stumps. We hereby describe a case of 45 year old female presenting with pitting pedal edema, multiple ulcers over bilateral lower limbs with irregular margins with erythema and hyperpigmentation of the surrounding skin. Color Doppler study of bilateral lower limbs was normal. Histopathological examination from one of the lesions showed hyperplastic epidermis, proliferation of capillaries in dermis, hemosiderin deposits and lymphocytic infiltrate. These features thus confirmed the diagnosis of Acroangiodermatitis. PMID:25165656

  15. Undifferentiated Embryonal Sarcoma of Liver

    PubMed Central

    Kallam, Avyakta; Krishnamurthy, Jairam; Kozel, Jessica

    2015-01-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant hepatic tumor. A 47 year old male presented with symptoms of sour taste in his mouth, occasional nausea, indigestion and 15-pound weight loss over two months. He had an unremarkable upper gastrointestinal endoscopy. Imaging showed a large liver mass in the left hepatic lobe that was resected and then reported as UESL. He went on to develop lung metastases and was initially treated with doxorubicin and ifosfamide followed by switching of therapy to gemcitabine and docetaxel due to progression of disease. He had a good response after two cycles and went on to receive four more cycles, achieving stable disease. We can therefore conclude that the combination of gemcitabine and docetaxel is a potential therapeutic option for patients with UESL. PMID:26788276

  16. Sarcoma botryoides in an infant.

    PubMed

    van Sambeeck, S J; Mavinkurve-Groothuis, A M C; Flucke, U; Dors, N

    2014-01-01

    A 17-month-old girl with no medical history presented at our emergency room with abnormal vaginal bleeding and vaginal tissue loss with a "grape bunch" appearance. Physical examination showed no abnormalities, but gynaecological examination showed abnormal vaginal tissue protruding through the vagina introitus. Given the typical clinical presentation, the age of the girl and the location and aspect of the lesion, there was a high suspicion of the botryoid variant of embryonal rhabdomyosarcoma of the vagina. Histology of a biopsy of the lesion was consistent with embryonal rhabdomyosarcoma. As no metastases were detected, the girl received chemotherapy. This case report describes the importance of early recognition of the typical clinical symptoms of sarcoma botryoides, since a rapid diagnosis followed by treatment is necessary to prevent death. PMID:25519859

  17. Surgical management of soft tissue sarcomas

    SciTech Connect

    Arlen, M.; Marcove, R.C.

    1987-01-01

    This volume reflects the latest thinking in surgical and adjuvant forms of therapy that can be offered to the sarcoma patient. Based on their analysis of sarcoma patients, the authors stress management based on site of origin, and discuss tumors on and about the shoulder girdle, hip joint, extremity, retroperitoneum, etc. Coverage includes methods for limb preservation; techniques for regional node resection; indications and methods for arterial perfusion, cryosurgery and isotope implantation; pre- and post-operative immunotherapy chemotherapy and radiation therapy.

  18. Fine needle aspiration of Histiocytic sarcoma

    PubMed Central

    Mallya, Varuna; Bansal, Anju; Kapoor, Sujala

    2014-01-01

    Histiocytic sarcoma is derived from histiocytes and is among the rarest of the tumors affecting the lymphoid tissue. We report a case of a histiocytic sarcoma arising from the lymph node in a 35-year-old male who came for a fine needle aspiration cytology and a subsequent biopsy was conducted and the tissue subjected to hematoxylin and eosin and immunohistochemistry staining. PMID:25745287

  19. Genetic analysis of childhood sarcoma.

    PubMed

    Strong, L C; Williams, W R; Ferrell, R E; Tainsky, M A

    1989-01-01

    A survey of cancer in 159 3-year survivors of childhood soft tissue sarcoma and their relatives revealed a cancer excess in first-degree relatives primarily due to cancers occurring before the age of 35 years and a highly significant excess in relatives of patients with second malignant neoplasms. Tumors of soft tissue and bone, breast, and brain were in excess in relatives and as second malignant neoplasms in patients. To determine the most likely explanation for the observed cancer distribution, we applied segregation analysis under a unified version of the mixed model. The observed data were most compatible with a rare autosomal dominant gene with high penetrance (gene carriers had a 50% probability of cancer by age 30, increasing to 90% by age 60) as compared with a chance occurrence or a multifactorial explanation. We contrasted the relative odds of observing each pedigree under a sporadic, multifactorial, or major gene model, and identified 11 pedigrees in which familial clustering of cancer was significant, with the distribution of cancer strongly favoring a major gene in 9 pedigrees. The tumors in these kindreds have been associated with alterations in specific genetic loci by tumor-specific genetic analysis. In particular, we observed soft tissue sarcoma, osteosarcoma and premenopausal ductal breast carcinoma tumors, perhaps attributable to loss of the Rb-1 suppressor gene on chromosome 13q, in the same patients and families. Study of the cancer predisposition segregating in 10 families by genetic linkage with markers of chromosome 13q and the Rb-1 gene have to date given negative LOD scores at 0 = 0 of Z = -1.2 to -13.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2488230

  20. New Therapeutic Targets in Soft Tissue Sarcoma

    PubMed Central

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

    2012-01-01

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

  1. Potential Therapeutic Targets in Uterine Sarcomas

    PubMed Central

    Cuppens, Tine; Tuyaerts, Sandra; Amant, Frédéric

    2015-01-01

    Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Based on clinical reports, promising approaches for uterine leiomyosarcoma patients include inhibition of VEGF and mTOR signaling, preferably in combination with other targeted or cytotoxic compounds. Currently, the only targeted therapy approved in leiomyosarcoma patients is pazopanib, a multitargeted inhibitor blocking VEGFR, PDGFR, FGFR, and c-KIT. Additionally, preclinical evidence suggests effect of the inhibition of histone deacetylases, tyrosine kinase receptors, and the mitotic checkpoint protein aurora kinase A. In low-grade endometrial stromal sarcomas, antihormonal therapies including aromatase inhibitors and progestins have proven activity. Other potential targets are PDGFR, VEGFR, and histone deacetylases. In high-grade ESS that carry the YWHAE/FAM22A/B fusion gene, the generated 14-3-3 oncoprotein is a putative target, next to c-KIT and the Wnt pathway. The observation of heterogeneity within uterine sarcoma subtypes warrants a personalized treatment approach. PMID:26576131

  2. Technetium scanning in Kaposi's sarcoma and its simulators

    SciTech Connect

    Gunnoe, R.; Kalivas, J.

    1982-04-01

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

  3. Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas

    ClinicalTrials.gov

    2015-11-06

    Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Chordoma; Desmoid Tumor; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Recurrent Childhood Soft Tissue Sarcoma

  4. Isolated Limb Perfusion of Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Soft Tissue Sarcoma of the Arm or Leg

    ClinicalTrials.gov

    2012-03-14

    Stage IVB Adult Soft Tissue Sarcoma; Stage IIB Adult Soft Tissue Sarcoma; Stage IIC Adult Soft Tissue Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage IVA Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma

  5. Adult human sarcomas. II. Medical oncology.

    PubMed

    Sinkovics, Joseph G

    2007-02-01

    Human sarcoma cells can be killed by radio- and chemotherapy, but tumor cells acquiring resistance frequently kill the patient. A keen understanding of the intracellular course of oncogenic cascades leads to the discovery of small molecular inhibitors of the involved phosphorylated kinases. Targeted therapy complements chemotherapy. Oncogene silencing is feasible by small interfering RNA. The restoration of some of the mutated or deleted tumor-suppressor genes (p53, Rb, PTEN, hSNF, INK/ARF and WT) by demethylation or reacetylation of their histones has been accomplished. Genetically engineered or naturally oncolytic viruses selectively lyse tumors and leave healthy tissues intact. Adeno- or retroviral vectors deliver genes of immunological costimulators, tumor antigens, chemo- or cytokines and/or tumor-suppressor proteins into tumor (sarcoma) cells. Suicide gene delivery results in apoptosis induction. Genes of enzymes that target prodrugs as their substrates render tumor cells highly susceptible to chemotherapy, with the prodrug to be targeted intracellularly. It will be combinations of sophisticated surgical removal of the nonencapsulated and locally invasive primary sarcomas, advanced forms of radiotherapy to the involved sites and immunotherapy with sarcoma vaccines that will cure primary sarcomas. Adoptive immunotherapy with immune lymphocytes will be operational in metastatic disease only when populations of regulatory T cells are controlled. Targeted therapy with small molecular inhibitors of oncogene cascades, the driving forces of sarcoma cells, alteration of the tumor stroma from a supportive to a tumor-hostile environment, reactivation or replacement of wild-type tumor-suppressor genes, and radio-chemotherapy (with much reduced toxicity) will eventually accomplish the cure of metastatic sarcomas. PMID:17288529

  6. What Are the Key Statistics about Uterine Sarcoma?

    MedlinePLUS

    ... factors for uterine sarcoma? What are the key statistics about uterine sarcoma? The American Cancer Society's estimates ... uterine corpus. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  7. What Are the Key Statistics about Kaposi Sarcoma?

    MedlinePLUS

    ... what causes Kaposi sarcoma? What are the key statistics about Kaposi sarcoma? Before the AIDS epidemic, Kaposi ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  8. What's New in Kaposi Sarcoma Research and Treatment?

    MedlinePLUS

    ... Next Topic Additional resources for Kaposi sarcoma What’s new in Kaposi sarcoma research and treatment? A great ... once it has developed. Treatment Researchers are studying new and different ways to treat KS. Imiquimod (Aldara) ...

  9. What's New in Uterine Sarcoma Research and Treatment?

    MedlinePLUS

    ... Next Topic Additional resources for uterine sarcoma What`s new in uterine sarcoma research and treatment? Molecular pathology ... the chromosomes leads to the formation of a new gene, called JAZF1/JJAZ. This gene may help ...

  10. Reproductive performance in ewes fed varying levels of cut lucerne pasture around conception.

    PubMed

    Robertson, S M; Clayton, E H; Morgan, B; Friend, M A

    2015-07-01

    Elevated intakes of protein and energy may increase embryo mortality, but it is not clear whether fresh lucerne (Medicago sativa) pasture poses a risk. A two-year pen study using oestrous synchronised and artificially inseminated Merino ewes (n=175 in 2013 and 215 in 2014) evaluated whether feeding freshly cut lucerne pasture (mean crude protein 19.7%, metabolisable energy 9.4MJ/kg DM) at maintenance or ad libitum during different periods around insemination altered reproductive performance in comparison with ewes fed a Control diet (mean crude protein 7.8%, metabolisable energy 9.0MJ/kg DM) of pelleted faba bean hulls and oat grain hulls at maintenance. The proportion of pregnant ewes carrying multiple fetuses was reduced (P=0.026) when ewes were fed lucerne ad libitum between days 0 and 17 after insemination compared with the Control diet (0.18 and 0.34, respectively), but not when ewes were fed lucerne ad libitum between days 0 and 7 after insemination (0.22). Reproductive performance, including the proportion of ewes pregnant and the proportion with multiple fetuses, was not different (P>0.05) when ewes were fed lucerne at maintenance between days 0 and 7 compared with the Control diet. While reproductive performance was similar when ewes were fed lucerne at maintenance between 0 and 17 days after artificial insemination compared with pellets at maintenance, fetal numbers per pregnant ewe were reduced by feeding lucerne ad libitum after insemination. PMID:26024965

  11. Melatonin feeding decreases prolactin levels in the ewe.

    PubMed

    Symons, A M; Arendt, J; Laud, C A

    1983-10-01

    Three groups of Suffolk-cross ewes were kept in (A) summer photoperiod plus melatonin feeding in such a way as to mimic the plasma levels found in winter photoperiod, (B) winter photoperiod or (C) natural light/dark from mid-June onwards. Prolactin levels remained high in group C throughout July and August but were dramatically reduced in both groups A and B. The rise in prolactin levels associated with dusk, however, was still apparent in all three groups. Appropriate administration of melatonin can thus influence prolactin secretion in the same way as an extension of the dark phase. This effect is associated with an early onset of the breeding season in the ewe. PMID:6631305

  12. Targeted Therapies in Sarcomas: Challenging the Challenge

    PubMed Central

    Martn Liberal, Juan; Lagares-Tena, Laura; Sinz-Jaspeado, Miguel; Mateo-Lozano, Silvia; Garca del Muro, Xavier; Tirado, Oscar M.

    2012-01-01

    Sarcomas are a heterogeneous group of mesenchymal malignancies that very often lead to death. Nowadays, chemotherapy is the only available treatment for most sarcomas but there are few active drugs and clinical results still remain very poor. Thus, there is an imperious need to find new therapeutic alternatives in order to improve sarcoma patient's outcome. During the last years, there have been described a number of new molecular pathways that have allowed us to know more about cancer biology and tumorigenesis. Sarcomas are one of the tumors in which more advances have been made. Identification of specific chromosomal translocations, some important pathways characterization such as mTOR pathway or the insulin-like growth factor pathway, the stunning development in angiogenesis knowledge, and brand new agents like viruses have lead to the development of new therapeutic options with promising results. This paper makes an exhaustive review of preclinical and clinical evidence of the most recent targeted therapies in sarcomas and provides a future view of treatments that may lead to improve prognosis of patients affected with this disease. PMID:22701332

  13. Immunotherapy for Bone and Soft Tissue Sarcomas

    PubMed Central

    Uehara, Takenori; Fujiwara, Tomohiro; Takeda, Ken; Kunisada, Toshiyuki; Ozaki, Toshifumi; Udono, Heiichiro

    2015-01-01

    Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies. PMID:26167500

  14. Effects of neonatal progestin exposure on female reproductive tract structure and function in the adult ewe.

    PubMed

    Gray, C A; Bazer, F W; Spencer, T E

    2001-03-01

    Endometrial glands are present in all mammalian uteri and produce secretions that are hypothesized to support conceptus (i.e., embryo/fetus and placental membranes) survival and development. In sheep, endometrial gland morphogenesis occurs postnatally and can be epigenetically ablated by chronic neonatal exposure to a progestin from birth, thereby producing an adult uterine gland knock-out (UGKO) phenotype. This study determined the long-term effects of neonatal progestin exposure on adult ovine reproductive tract structure and function. Neonatal ewes were exposed to norgestomet (Nor) from birth to 32 wk of age. Unexposed ewes served as controls. After puberty, adult Nor-treated (n = 6) and control (n = 6) ewes were repeatedly bred at estrus (Day 0) to intact rams of proven fertility. In contrast to a pregnancy rate of 80% for control ewes, pregnancy was never detected on Day 25 after mating (or thereafter) in bred UGKO ewes. Control and Nor-treated ewes were then bred and necropsied on Day 9. Similar numbers of hatched blastocysts were present in uterine flushings from control and Nor-treated ewes. Weights of the ovaries and cervices were not affected by treatment. No histoarchitectural differences between control and Nor-treated ewes were detected for ovaries, oviducts, cervices, or vaginae. However, uterocervical and uterine weight as well as uterine horn length were less for Nor-treated ewes. The uteri of Nor-treated ewes were devoid of endometrial glands and lacked the stromal delineation characteristic of intercaruncular endometrium in control ewes. Endometrial width, area, and lumenal epithelial length were decreased in uteri from Nor-treated ewes, but myometrial width and morphology were not affected. Expression of a number of mRNAs that are expressed predominantly in the endometrial epithelia was not different between uteri from control and from Nor-treated ewes. Collectively, these results indicate that neonatal exposure of ewes to a progestin from birth appears to only affect development of the uterus and not any extrauterine reproductive tract tissues. The infertility of the UGKO ewes appears to result from a lack of endometrial glands and, by extension, of their secretions that are required to support growth and development of peri-implantation conceptuses. PMID:11207194

  15. Composition and sensory profiling of probiotic Scamorza ewe milk cheese.

    PubMed

    Albenzio, M; Santillo, A; Caroprese, M; Braghieri, A; Sevi, A; Napolitano, F

    2013-05-01

    The present study aimed to assess the effect of the addition of different usually recognized as probiotic bacterial strains on chemical composition and sensory properties of Scamorza cheese manufactured from ewe milk. To define the sensory profile of Scamorza cheese, a qualitative and quantitative reference frame specific for a pasta filata cheese was constructed. According to the presence of probiotic bacteria, cheeses were denoted S-BB for Scamorza cheese made using a mix of Bifidobacterium longum 46 and Bifidobacterium lactis BB-12, and S-LA for Scamorza cheese made using Lactobacillus acidophilus LA-5. The designation for control Scamorza cheese was S-CO. Analyses were performed at 15d of ripening. The moisture content of Scamorza ewe milk cheese ranged between 44.61 and 47.16% (wt/wt), showing higher values in S-CO and S-BB cheeses than in S-LA cheese; the fat percentage ranged between 25.43 and 28.68% (wt/wt), showing higher value in S-LA cheese. The NaCl percentage in Scamorza cheese from ewe milk was 1.75 ± 0.04% (wt/wt). Protein and casein percentages were the highest in Scamorza cheese containing a mix of bifidobacteria; also, the percentage of the proteose-peptone fraction showed the highest value in S-BB, highlighting the major proteolysis carried out by enzymes associated with B. longum and B. lactis strains. Texture and appearance attributes were able to differentiate probiotic bacteria-added cheeses from the untreated control product. In particular, S-BB and S-LA Scamorza cheeses showed higher color uniformity compared with S-CO cheese. Furthermore, the control cheese showed higher yellowness and lower structure uniformity than S-BB. The control product was less creamy and grainy than S-BB; conversely, the inclusion of probiotics into the cheese determined lower adhesivity and friability in S-BB and S-LA than in S-CO. This study allowed the definition of the principal composition and sensory properties of Scamorza ewe milk cheese. The specific quantitative vocabulary for sensory analysis and reference frame for assessor training also established in this study should be implemented to systematically monitor the quality of this new typology of ewe milk cheese. PMID:23522674

  16. Pathogenesis of reproductive failure induced by Trypanosoma vivax in experimentally infected pregnant ewes

    PubMed Central

    2013-01-01

    The present study was aimed at investigating the effect of experimental infection by Trypanosoma vivax in different stages of pregnancy, determining the pathogenesis of reproductive failure, and confirming transplacental transmission. We used 12 pregnant ewes distributed into four experimental groups: G1, was formed by three ewes infected with T. vivax in the first third of pregnancy (30 days); G2 comprised three infected ewes in the final third of pregnancy (100 days); G3 and G4 were composed of three non-infected ewes with the same gestational period, respectively. Each ewe of G1 and G2 was inoculated with 1.25 105 tripomastigotes. Clinical examination, determination of parasitemia, serum biochemistry (albumin, total protein, glucose, cholesterol, and urea), packed cell volume (PCV), serum progesterone, and pathological examination were performed. Placenta, amniotic fluid, blood and tissues from the fetuses and stillbirths were submitted to PCR. Two ewes of G1 (Ewe 1 and 3) presented severe infection and died in the 34th and 35th days post-infection (dpi), respectively; but both fetuses were recovered during necropsy. In G2, Ewe 5 aborted two fetuses on the 130th day (30 dpi) of pregnancy; and Ewe 6 aborted one fetus in the 140th day (40 dpi) of gestation. Ewes 2 and 4 delivered two weak lambs that died five days after birth. Factors possibly involved with the reproductive failure included high parasitemia, fever, low PCV, body score, serum glucose, total protein, cholesterol, and progesterone. Hepatitis, pericarditis, and encephalitis were observed in the aborted fetuses. The presence of T. vivax DNA in the placenta, amniotic fluid, blood, and tissues from the fetuses confirms the transplacental transmission of the parasite. Histological lesion in the fetuses and placenta also suggest the involvement of the parasite in the etiopathogenesis of reproductive failure in ewes. PMID:23289625

  17. Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

    ClinicalTrials.gov

    2016-02-11

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated Pleomorphic Sarcoma; Malignant Adult Hemangiopericytoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  18. [Soft tissue sarcomas and gastrointestinal stromal tumors].

    PubMed

    Reichardt, P

    2016-03-01

    Soft tissue sarcomas are rare tumors that represent a major challenge due to varying clinical presentations and often interdisciplinary treatment concepts. Gold standard for the treatment of localized resectable soft tissue sarcomas is complete surgical removal. In metastatic soft tissue sarcoma, systemic therapy is the treatment of choice. The most active drugs are anthracyclines and ifosfamide. Combination chemotherapy has improved both response rate and progression-free survival at the cost of increased toxicity. Imatinib at a dose of 400 mg/day is the gold standard for patients with advanced or metastatic gastrointestinal stromal tumors (GIST). In patients with a mutation in KIT exon 9, 800 mg/day is the recommended dose. In imatinib refractory or intolerant patients, sunitinib is recommended. Regorafenib has been approved for third-line therapy. PMID:26907871

  19. Phenotypic factors affecting coagulation properties of milk from Sarda ewes.

    PubMed

    Pazzola, M; Dettori, M L; Cipolat-Gotet, C; Cecchinato, A; Bittante, G; Vacca, G M

    2014-11-01

    In this study, milk-coagulation properties (MCP) were characterized in the Sarda sheep breed. Milk composition and MCP [rennet-coagulation time (RCT), curd-firming time [time to reach a curd firmness of 20mm (k20)], and curd firmness (a30), (a45), and (a60)] were obtained extending the lactodynamographic analysis from 30 to 60 min from a population of 1,121 ewes from 23 different farms. Managerial characteristics of farms and parity, individual daily milk yields and stage of lactation of ewes were recorded. Data were analyzed using a mixed-model procedure with fixed effects of days in milk, parity, daily milk yield, and flock size and the random effect of the flock/test day nested within flock size. Sampled farms were classified as small (<300 ewes) and medium (300 to 600 ewes), and these were kept by family operations, or as large (>600 ewes), often operated through hired workers. Daily milk yield was, on average, 1.58 0.79 L/d and variability for this trait was very high. The average content of fat, protein, and casein was respectively 6.41, 5.39, and 4.20%. The class of flock size had a significant effect only on curd firmness, whereas days in milk affected RCT and k20. The flock test day, parity, and daily milk yield were important sources of variation for all MCP. The mean value of RCT (8.6 min) and the low occurrence of noncoagulating samples (0.44%) confirmed the excellent coagulation ability of sheep milk compared with cattle milk. A more rapid coagulation was observed in mid-lactating, primiparous, and high-yielding ewes. The k20 was usually reached in less than 2 min after gelation, with the most favorable values at mid lactation. The mean value of curd firmness 30 min after rennet addition (a30) was, on average, 50mm and decreased to 46 and 42 mm respectively after 45 (a45) and 60 min (a60). The decreasing value of curd-firmness traits was likely to be caused by curd syneresis and whey expulsion. The correlation between RCT and a30 was much lower than in dairy cows and about null for a45 and a60. This means that curd firmness in dairy ewes is almost independent of gelation time and this can provide specific information for this species. In conclusion, this study showed that milk from Sarda sheep is characterized by an earlier gelation, a faster increase in curd firmness with time, and greater curd firmness after 30 min compared with dairy cows. Furthermore, correlations between MCP in sheep are much lower than in bovines and some of the assumptions and interpretations related to cows cannot be applied to sheep. PMID:25151884

  20. Biological characterization of soft tissue sarcomas.

    PubMed

    Hayashi, Takuma; Horiuchi, Akiko; Sano, Kenji; Kanai, Yae; Yaegashi, Nobuo; Aburatani, Hiroyuki; Konishi, Ikuo

    2015-12-01

    Soft tissue sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to mesenchymal transformation and the establishment of new therapies and diagnostic biomarker has been hampered by several critical factors. First, malignant soft tissue sarcomas are rarely observed in the clinic with fewer than 15,000 newly cases diagnosed each year in the United States. Another complicating factor is that soft tissue sarcomas are extremely heterogeneous as they arise in a multitude of tissues from many different cell lineages. The scarcity of clinical materials coupled with its inherent heterogeneity creates a challenging experimental environment for clinicians and scientists. Faced with these challenges, there has been extremely limited advancement in clinical treatment options available to patients as compared to other malignant tumours. In order to glean insight into the pathobiology of soft tissue sarcomas, scientists are now using mouse models whose genomes have been specifically tailored to carry gene deletions, gene amplifications, and somatic mutations commonly observed in human soft tissue sarcomas. The use of these model organisms has been successful in increasing our knowledge and understanding of how alterations in relevant oncogenic and/or tumour suppressive signal cascades, i.e., interferon-? (IFN-?), tumour protein 53 (TP53) and/or retinoblastoma (RB) pathway directly impact sarcomagenesis. It is the goal of many in the physiological community that the use of several mouse models will serve as powerful in vivo tools for further understanding of sarcomagenesis and potentially identify new diagnostic biomarker and therapeutic strategies against human soft tissue sarcomas. PMID:26807423

  1. Biological characterization of soft tissue sarcomas

    PubMed Central

    Horiuchi, Akiko; Sano, Kenji; Kanai, Yae; Yaegashi, Nobuo; Aburatani, Hiroyuki; Konishi, Ikuo

    2015-01-01

    Soft tissue sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to mesenchymal transformation and the establishment of new therapies and diagnostic biomarker has been hampered by several critical factors. First, malignant soft tissue sarcomas are rarely observed in the clinic with fewer than 15,000 newly cases diagnosed each year in the United States. Another complicating factor is that soft tissue sarcomas are extremely heterogeneous as they arise in a multitude of tissues from many different cell lineages. The scarcity of clinical materials coupled with its inherent heterogeneity creates a challenging experimental environment for clinicians and scientists. Faced with these challenges, there has been extremely limited advancement in clinical treatment options available to patients as compared to other malignant tumours. In order to glean insight into the pathobiology of soft tissue sarcomas, scientists are now using mouse models whose genomes have been specifically tailored to carry gene deletions, gene amplifications, and somatic mutations commonly observed in human soft tissue sarcomas. The use of these model organisms has been successful in increasing our knowledge and understanding of how alterations in relevant oncogenic and/or tumour suppressive signal cascades, i.e., interferon-γ (IFN-γ), tumour protein 53 (TP53) and/or retinoblastoma (RB) pathway directly impact sarcomagenesis. It is the goal of many in the physiological community that the use of several mouse models will serve as powerful in vivo tools for further understanding of sarcomagenesis and potentially identify new diagnostic biomarker and therapeutic strategies against human soft tissue sarcomas. PMID:26807423

  2. Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

    ClinicalTrials.gov

    2014-09-08

    Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  3. Evaluation of Dorper, Dorset, Katahdin, and Rambouillet crossbred ewes in high- and low-input production systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary objective was to evaluate wool (Dorset, Rambouillet) and hair (Dorper, Katahdin) dam breeds for their ability to complement Romanov germplasm as crossbred ewes managed in distinct production systems. Romanov ewes were mated with 18 rams of each dam breed to produce crossbred ewes for ev...

  4. Primary pulmonary monophasic synovial sarcoma: Evading diagnosis.

    PubMed

    Taylor, Marcus; Srinivasan, Lakshmi; Abid, Qamar

    2016-02-01

    Primary pulmonary synovial sarcoma is a very rare tumor, thus there is no consensus as to the most appropriate management. A 78-year-old man presented with nonspecific symptoms of weight loss and shortness of breath. Imaging confirmed a large right-sided mass and accompanying pleural effusion. Strong 18F-fluorodeoxyglucose uptake was found on positron-emission tomography. The preoperative work-up and intraoperative frozen section were inconclusive. Immunohistochemistry and molecular analysis confirmed the diagnosis of primary pulmonary monophasic synovial sarcoma. PMID:26612959

  5. Primary Renal Synovial Sarcoma: An Oncologic Surprise?

    PubMed Central

    Moorthy, H. Krishna; Pillai, Biju S.; Varghese, Jophy

    2014-01-01

    Primary renal synovial sarcoma is a rare tumor having a specific chromosomal translocation t(X; 18) (p11.2; q11.2). The clinical features of this tumor and radiologic appearances are quite similar to those of renal cell carcinoma. Confirmatory diagnosis requires fluorescent in situ hybridization or reverse transcriptase polymerase chain reaction validation for differentiating the tumors from sarcomatoid renal cell carcinoma. We present a case of primary renal synovial sarcoma that was diagnosed in a middle-aged man.

  6. Update for ASCO 2015 sarcoma sessions.

    PubMed

    Karakousis, Giorgos

    2015-12-01

    There were over 75 oral or poster presentations in last Spring's American Society for Clinical Oncology (ASCO) sarcoma sessions. These presentations included investigations studying new medical therapy regimens for soft tissue sarcoma (STS) patients with advanced disease, research studies on the relative value of aggressive local therapies for certain histologies of STS, and innovative investigations evaluating prognostic (and potentially therapeutic) implications of next generation sequencing of tumors and circulating tumor DNA. This paper serves to review select presentations from the sessions in the meeting. PMID:26298199

  7. Intrauterine bacterial inoculation and level of dietary methionine alter amino acid metabolism in nulliparous yearling ewes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using an intrauterine bacterial inoculation method, our objective was to determine the effects of acute sepsis and level of dietary metabolizable-methionine on splanchnic metabolism of amino acids in ewes. Twenty-five nulliparous yearling Rambouillet-cross ewes (initial BW = 65.1 ± 0.6 kg), surgical...

  8. Genetic evaluation of the probability of lambing in yearling Targhee ewes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the additive genetic control of lambing percentage in yearling Targhee ewes. The records of 3,103 ewe lambs born from 1989 to 2011 and mated at approximately 7.5 mo of age were analyzed. Records included sire, dam, weaning weight, breeding pen, age of dam...

  9. Ewe (for Togo). Special Skills Handbook. Peace Corps Language Handbook Series.

    ERIC Educational Resources Information Center

    Kozelka, Paul R., Comp.; Agbovi, Yao Ete, Comp.

    A book of language and cultural material for teachers and students of Ewe presents vocabulary lists and samples of Ewe language in various contexts, including letters, essays, and newspaper articles. Although not presented in lesson format, the material can be adapted by teachers or used by students for independent study. It is divided into two…

  10. Effect of vitamin E on the immune system of ewes during late pregnancy and lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present experiment was designed to determine the effects of a regimen of repeated, intramuscular (i.m.) injections of vitamin E (VE) on innate and humoral components of the immune response of pregnant and lactating ewes. Pregnant ewes were randomly assigned to two treatments consisting of i.m. i...

  11. RELATIONSHIP BETWEEN AGING AND NUTRITIONAL CONTROLLED GROWTH RATE ON HEAT PRODUCTION OF EWE LAMBS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine how reducing growth rate nutritionally alters the relationship between heat production per unit body weight and aging. Fasting heat production of 12 Dorset ewe lambs at 114 ± 2 d of age was determined, and ewes were assigned to treatments. Treatments co...

  12. Targeting protein kinases to reverse multidrug resistance in sarcoma.

    PubMed

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

    2016-02-01

    Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma. PMID:26827688

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

    SciTech Connect

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

    1988-12-01

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

  14. Genetic correlations between body weight change and reproduction traits in Merino ewes depend on age.

    PubMed

    Rose, G; Mulder, H A; van der Werf, J H J; Thompson, A N; van Arendonk, J A M

    2014-08-01

    Merino sheep in Australia experience periods of variable feed supply. Merino sheep can be bred to be more resilient to this variation by losing less BW when grazing poor quality pasture and gaining more BW when grazing good quality pasture. Therefore, selection on BW change might be economically attractive but correlations with other traits in the breeding objective need to be known. The genetic correlations (rg) between BW, BW change, and reproduction were estimated using records from approximately 7,350 fully pedigreed Merino ewes managed at Katanning in Western Australia. Number of lambs and total weight of lambs born and weaned were measured on approximately 5,300 2-yr-old ewes, approximately 4,900 3-yr-old ewes, and approximately 3,600 4-yr-old ewes. On a proportion of these ewes BW change was measured: approximately 1,950 2-yr-old ewes, approximately 1,500 3-yr-old ewes, and approximately 1,100 4-yr-old ewes. The BW measurements were for 3 periods. The first period was during mating period over 42 d on poor pasture. The second period was during pregnancy over 90 d for ewes that got pregnant on poor and medium quality pasture. The third period was during lactation over 130 d for ewes that weaned a lamb on good quality pasture. Genetic correlations between weight change and reproduction were estimated within age classes. Genetic correlations were tested to be significantly greater magnitude than 0 using likelihood ratio tests. Nearly all BW had significant positive genetic correlations with all reproduction traits. In 2-yr-old ewes, BW change during the mating period had a positive genetic correlation with number of lambs weaned (rg = 0.58); BW change during pregnancy had a positive genetic correlation with total weight of lambs born (rg = 0.33) and a negative genetic correlation with number of lambs weaned (rg = -0.49). All other genetic correlations were not significantly greater magnitude than 0 but estimates of genetic correlations for 3-yr-old ewes were generally consistent with these findings. The direction of the genetic correlations mostly coincided with the energy requirements of the ewes and the stage of maturity of the ewes. In conclusion, optimized selection strategies on BW changes to increase resilience will depend on the genetic correlations with reproduction and are dependent on age. PMID:24879756

  15. Melatonin can induce early onset of the breeding season in ewes.

    PubMed

    Arendt, J; Symons, A M; Laud, C A; Pryde, S J

    1983-06-01

    Patterns of plasma melatonin, similar in the duration of high levels to those found in winter, were induced in Suffolk-cross ewes kept in summer light (16 h light: 8 h darkness) by daily oral administration of melatonin (3 mg/13 mumol). The onset of oestrous cycles in these sheep occurred in August, 2-8 weeks before the onset of oestrous cycles in untreated ewes kept in natural light. The onset of oestrous cycles in a further group of ewes kept in winter light (8 h light: 16 h darkness) from mid-June was indistinguishable from that of the melatonin-treated ewes. Rams were excluded from the premises. These data indicate that melatonin alone in physiological quantities is sufficient to induce early onset of the breeding season in the ewe, and provide strong evidence for a hormonal role of melatonin in a short-day breeder. PMID:6683298

  16. Progesterone improves the maturation of male-induced preovulatory follicles in anoestrous ewes.

    PubMed

    Adib, Achraf; Freret, Sandrine; Touze, Jean-Luc; Lomet, Didier; Lardic, Lionel; Chesneau, Didier; Estienne, Anthony; Papillier, Pascal; Monniaux, Danielle; Pellicer-Rubio, Maria-Teresa

    2014-10-01

    The first ovulation induced by male effect in sheep during seasonal anoestrus usually results in the development of a short cycle that can be avoided by progesterone priming before ram introduction. In elucidating the involvement of the hypothalamic-pituitary-gonadal axis in the occurrence of short cycles, the effects of progesterone and the time of anoestrus on the development of male-induced preovulatory follicles were investigated in anoestrous ewes using morphological, endocrine and molecular approaches. Ewes were primed with progesterone for 2 (CIDR2) or 12 days (CIDR12) and untreated ewes used as controls during early (April) and late (June) anoestrus. The duration of follicular growth and the lifespan of the male-induced preovulatory follicles were prolonged by ?1.6 days in CIDR12 ewes compared with the controls. These changes were accompanied by a delay in the preovulatory LH and FSH surges and ovulation. Intra-follicular oestradiol concentration and mRNA levels of LHCGR and STAR in the granulosa and theca cells of the preovulatory follicles were higher in CIDR12 ewes than the control ewes. The expression of mRNA levels of CYP11A1 and CYP17A1 also increased in theca cells of CIDR12 ewes. CIDR2 ewes gave intermediate results. Moreover, ewes ovulated earlier in June than in April, without changes in the duration of follicular growth, but these effects were unrelated to the lifespan of corpus luteum. Our results give the first evidence supporting the positive effect of progesterone priming on the completion of growth and maturation of preovulatory follicles induced by male effect in seasonal anoestrous ewes, thereby preventing short cycles. PMID:25062803

  17. Instantánea del sarcoma

    Cancer.gov

    Información sobre las tendencias de incidencia, mortalidad y financiamiento del NCI sobre el sarcoma; así como ejemplos de actividades del NCI y adelantos en la investigación de este tipo de cáncer.

  18. Combination Therapy for Advanced Kaposi Sarcoma

    Cancer.gov

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  19. How Are Soft Tissue Sarcomas Diagnosed?

    MedlinePLUS

    ... Usually, the skin is first lubricated with gel. Ultrasound may be done before a biopsy to see if a lump is a cyst, ... sarcoma is present. Like FNA, CT scan and ultrasound can be used to guide the needle into tumors of internal organs. Surgical biopsy In a surgical biopsy, the entire tumor or ...

  20. Synovial sarcoma of the cauda equina.

    PubMed

    Yonezawa, Ikuho; Saito, Tsuyoshi; Nakahara, Daishi; Won, JongHwa; Wada, Takuro; Kaneko, Kazuo

    2012-02-01

    Primary synovial sarcoma originating from the cauda equina is extremely rare. Only one case, involving an 11-year-old girl, has been reported. The authors describe the case of a 23-year-old woman with a primary synovial sarcoma of the cauda equina. The patient visited a local hospital and described a 2-month history of low-back pain. She was referred to the authors' hospital for further evaluation. On physical examination, she had a straight-leg raising result of 70 bilaterally. Motor examination revealed Grade 4/5 strength in the bilateral extensor hallux longus muscles. There was normal sensation to light touch and vibration in the lower extremities. Sagittal Gd-enhanced T1-weighted MR imaging demonstrated an intradural, extramedullary, and uniformly enhancing mass that extended from L-3 to L-4. The mass was totally resected and adjuvant local radiation therapy was administered. Reverse transcriptase polymerase chain reaction (RT-PCR) of a paraffin-embedded tissue sample revealed SYT-SSX fusion transcripts, and the diagnosis of synovial sarcoma was confirmed. Five and a half years after surgery, the patient is free of local recurrence and metastatic disease. The RT-PCR detection of SYT-SSX fusion transcripts played a key role in establishing the diagnosis of synovial sarcoma of the cauda equina. Complete resection of the mass with adjuvant local radiation therapy proved to be effective. PMID:22098598

  1. Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

    PubMed Central

    2010-01-01

    Background Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy. Methods DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined. Results Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ? = 0.55 to ? = 0.80. Conclusions The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements. PMID:21190557

  2. Current management of pediatric soft tissue sarcomas

    PubMed Central

    Sangkhathat, Surasak

    2015-01-01

    Pediatric soft tissue sarcomas are a group of malignant neoplasms arising within embryonic mesenchymal tissues during the process of differentiation into muscle, fascia and fat. The tumors have a biphasic peak for age of incidence. Rhabdomyosarcoma (RMS) is diagnosed more frequently in younger children, whereas adult-type non-RMS soft tissue sarcoma is predominately observed in adolescents. The latter group comprises a variety of rare tumors for which diagnosis can be difficult and typically requires special studies, including immunohistochemistry and molecular genetic analysis. Current management for the majority of pediatric sarcomas is based on the data from large multi-institutional trials, which has led to great improvements in outcomes over recent decades. Although surgery remains the mainstay of treatment, the curative aim cannot be achieved without adjuvant treatment. Pre-treatment staging and risk classification are of prime importance in selecting an effective treatment protocol. Tumor resectability, the response to induction chemotherapy, and radiation generally determine the risk-group, and these factors are functions of tumor site, size and biology. Surgery provides the best choice of local control of small resectable tumors in a favorable site. Radiation therapy is added when surgery leaves residual disease or there is evidence of regional spread. Chemotherapy aims to reduce the risk of relapse and improve overall survival. In addition, upfront chemotherapy reduces the aggressiveness of the required surgery and helps preserve organ function in a number of cases. Long-term survival in low-risk sarcomas is feasible, and the intensity of treatment can be reduced. In high-risk sarcoma, current research is allowing more effective disease control. PMID:26566481

  3. Current management of pediatric soft tissue sarcomas.

    PubMed

    Sangkhathat, Surasak

    2015-11-01

    Pediatric soft tissue sarcomas are a group of malignant neoplasms arising within embryonic mesenchymal tissues during the process of differentiation into muscle, fascia and fat. The tumors have a biphasic peak for age of incidence. Rhabdomyosarcoma (RMS) is diagnosed more frequently in younger children, whereas adult-type non-RMS soft tissue sarcoma is predominately observed in adolescents. The latter group comprises a variety of rare tumors for which diagnosis can be difficult and typically requires special studies, including immunohistochemistry and molecular genetic analysis. Current management for the majority of pediatric sarcomas is based on the data from large multi-institutional trials, which has led to great improvements in outcomes over recent decades. Although surgery remains the mainstay of treatment, the curative aim cannot be achieved without adjuvant treatment. Pre-treatment staging and risk classification are of prime importance in selecting an effective treatment protocol. Tumor resectability, the response to induction chemotherapy, and radiation generally determine the risk-group, and these factors are functions of tumor site, size and biology. Surgery provides the best choice of local control of small resectable tumors in a favorable site. Radiation therapy is added when surgery leaves residual disease or there is evidence of regional spread. Chemotherapy aims to reduce the risk of relapse and improve overall survival. In addition, upfront chemotherapy reduces the aggressiveness of the required surgery and helps preserve organ function in a number of cases. Long-term survival in low-risk sarcomas is feasible, and the intensity of treatment can be reduced. In high-risk sarcoma, current research is allowing more effective disease control. PMID:26566481

  4. Effects of experimental Trypanosoma evansi infection on pregnancy in Yankasa ewes.

    PubMed

    Adeyeye, A A; Ate, I U; Lawal, A I; Adamu, S

    2016-03-15

    Twenty pregnant Yankasa ewes were assigned to three groups to determine the effect of Trypanosoma evansi infection on pregnancy. Groups A and B comprising seven ewes each were infected with approximately 1.0 × 10(6) cells of T evansi per ewe through venepuncture at the second and third trimesters of pregnancy, respectively. Group C comprising six ewes served as uninfected control. There was slight pyrexia in the infected groups (groups A and B) but was absent in group C. The mean body weight, glucose concentration, and packed cell volume of ewes in group A were not significantly different from those in group C throughout the study. There was also no significant difference in mean glucose concentration between groups B and C. However, in group B, mean body weight was significantly (P < 0.05) lower compared to group C at week 2 and from week 4 post infection (pi) till the end of the study; the packed cell volume also significantly (P < 0.05) decreased but at weeks 4 and 6 pi. The mean plasma protein of ewes in group A was significantly (P < 0.05) increased compared to those of group C at weeks 7, 11 pi and thereafter till the end of the study. On the contrary, the plasma protein of ewes in group B decreased significantly (P < 0.05) compared to those in group C at weeks 2 and 6 pi. There were no reproductive losses throughout the study. This was characterized by insignificant differences in the gestation length between ewes in the infected groups (groups A and B) compared with those in group C. However, there were significant (P < 0.05) decreases in lamb birth weights of ewes in group B compared with ewes in groups A and C. Mice inoculation with blood from infected ewes postpartum was parasitemic 18 to 25 days pi, for ewes in group B, whereas none of the mice in groups A and C were parasitemic. Lambs born from the infected groups (groups A and B) were also aparasitemic for 40 days postpartum. It was therefore concluded that the T evansi isolate used caused mild trypanosomosis when infected at third trimester, whereas ewes infected at second trimester were resistant. PMID:26643605

  5. Effect of selection for lifetime production of lamb weaned on hormonal factors that affect growth in Targhee ewes and lambs.

    PubMed

    Head, W A; Hatfield, P G; Hallford, D M; Fitzgerald, J A; Petersen, M K; Stellflug, J N

    1996-09-01

    Targhee ewes (n = 22, average age 5 yr) rearing twin lambs were used to investigate serum growth hormone (GH), IGF-I, triiodothyronine (T3), thyroxine (T4), and prolactin (PRL; ewes only) concentrations associated with selection pressure for lifetime production of kilograms of lamb weaned per ewe. Period 1 started on d 4 after birth and was conducted in confinement. Periods 2, 3, and 4 were conducted on fenced intermountain sagebrush-bunchgrass range starting at an average of 49, 84, and 112 d after birth, respectively. Blood samples were collected hourly for 6 h on d 4, 11, 18, 25, 49, 84, and 112 after lambing. Ewe models included the fixed effect for line, with ewe age, lambing date, and starting weight nested within line as potential covariables. Lamb models included fixed effects for line, sex, and sibling sex, with lamb age and birth weight nested within line tested as possible covariables. Growth hormone concentrations were greater (P = .06) for selected than for control ewes, but lamb GH concentrations did not differ (P = .90) between selected and control lambs. Ewe prolactin concentration tended (P = .13) to be greater for control than selected ewes. Ewe and lamb IGF-I did not differ (P > .55) between selected and control ewes and lambs. Ewe T3 and T4 concentrations did not differ (P > .19) between selected and control ewes; however, lamb T3 and T4 concentrations were greater (P < .01) for control than for selected lambs. Increased GH concentration in selected ewes seemed to be associated with greater milk production. Differences in selected and control lamb T3 and T4 concentrations could be an indicator of receptor sensitivity, metabolic activity, or seasonal reproductive transitions in ewe lambs. PMID:8880417

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

    ClinicalTrials.gov

    2016-03-18

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

  7. Transplacental transmission of Bluetongue virus serotype 8 in ewes in early and mid gestation.

    PubMed

    van der Sluijs, M; Timmermans, M; Moulin, V; Noordegraaf, C Vonk; Vrijenhoek, M; Debyser, I; de Smit, A J; Moormann, R

    2011-04-21

    The ability of Bluetongue virus serotype 8 (BTV-8) originating from the 2006 European outbreak to cross the ovine placenta during early and mid gestation was investigated in two separate experiments. In the first experiment, 16 ewes were infected with BTV-8 at 70-75 days gestation. The foetuses were collected at 18-19 days after infection (dpi). BTV-8 could be isolated from at least two organs of 19 out of 40 lambs and from 11 out of 16 infected ewes. In the second experiment, 20 BTV-8 infected ewes in early gestation (day 40-45) were euthanized at 10 days (10 ewes) or 30 days (10 ewes) after infection. The presence of BTV could be demonstrated in two foetuses from two ewes at 10 dpi and in 4 foetuses from four ewes at 30 dpi. The main pathological findings in the foetuses in mid gestation were meningo-encephalitis and vacuolation of the cerebrum. In the foetuses early at gestation, haemorrhages in various foetal tissues and necrosis and haemorrhages in the placentomes were found. These experiments demonstrate for the first time the presence of infectious BTV in lamb foetuses at different stages of gestation, combined with a difference in transmission rate depending on the gestation stage. The high transmission rate found at mid term gestation (69%) makes our model very suitable for further research into the mechanisms of transplacental transmission and for research into the reduction of this route of transmission through vaccination. PMID:21145670

  8. Thermoregulation and reproductive performance of grazing desert ewes (Ovis aries) as influenced by concentrate supplementation.

    PubMed

    Elnageeb, Mohammed E; Abdelatif, Abdalla M; Makawi, Sharaf Eldin A

    2008-09-15

    Twenty sexually mature Desert ewes were used to study the effects of concentrate supplementation on thermoregulation and reproductive traits. The ewes were divided into two equal groups, control and supplemented; the supplemented group received daily 500 g of concentrate mixture (crushed sorghum grain and cotton seed cake). In both groups, oestrus was synchronized with hormonal method and the ewes were naturally inseminated. Pregnancy was diagnosed by the ultra-sonography technique. Dietary supplementation resulted in a shorter time of oestrus onset, higher rates of conception, lambing and a significant decrease in gestation length. The fertility and fecundity of ewes were also improved. Supplementations also increased significantly the pre-and post lambing weight of ewes and the birth and weaning weights of the lambs. The body weight, rectal temperature and respiratory rate increased significantly with the advance of pregnancy in both groups of ewes. These indices decreased significantly with the progress of lactation. The supplemented ewes maintained higher values of these indices during pregnancy and lactation. PMID:19137829

  9. Improvement of fertility in artificially inseminated ewes following vaginal treatment with misoprostol plus terbutaline sulphate.

    PubMed

    Horta, A E M; Barbas, J P; Marques, C C; Baptista, M C; Vasques, M I; Pereira, R M; Mascarenhas, R D; Cavaco-Gonalves, S

    2010-12-01

    The effect of vaginal administration of misoprostol plus terbutaline sulphate 6?h prior to artificial insemination (AI) upon the site of AI (vaginal or cervical) and fertility was studied using a total of 87 estrous synchronized Serra da Estrela ewes (control n?=?42 and treated n?=?45). Artificial insemination was performed using refrigerated semen at 54-55?h after sponge removal. Lambing rate (fertility) and prolificacy were compared between control and treated ewes. The effect of the site of semen deposition on fertility was also evaluated. Prolificacy rate was not different between control (1.5) and treated (1.59) ewes. The proportion of cervical AI achieved in control (45.2%) and treated (37.8%) ewes was not significantly different. Overall, fertility was significantly lower in control than in treated ewes (42.9% vs 64.4%; p?ewes (30.4% vs 60.7%; p?ewes. Although needing confirmation, it was hypothesized that drugs might have induced local secretory modifications leading to an increase of cervical ability to retain more viable spermatozoa for fertilization. PMID:20210884

  10. Uterine vascular effects of estetrol in nonpregnant ewes.

    PubMed

    Levine, M G; Miodovnik, M; Clark, K E

    1984-03-15

    Estetrol is produced by the fetal liver and has been suggested to be a sensitive indicator of fetal well-being. Although the uterine vascular effects of estrogens (17 beta-estradiol, estriol, and estrone) have been extensively investigated in our laboratory and those of others, the ability of estetrol to dilate the ovine uterine vasculature is not presently known. The present experiment was designed to compare the vasoactivity of estetrol to that of a second pregnancy-associated estrogen, estriol. Five nonpregnant oophorectomized ewes were chronically instrumented with catheters in the femoral artery, femoral vein, uterine arteries, and electromagnetic flow probes on both uterine arteries. Upon recovering from operation, animals received unilateral intra-arterial (uterine) injections of either estriol (0.1, 0.3, 1, and 3 micrograms) or estetrol (1, 3, 10, and 30 micrograms). Ewes received only one dose of either estetrol or estriol daily and all doses were given in a randomized order. Uterine blood flow responses were continuously monitored and the time of onset, peak, and duration were recorded. The time of onset (38 +/- 2 minutes), time of peak response (75 +/- 1 minute), and duration (189 +/- 7 minutes) were approximately equal to those observed for estriol. On the basis of the data obtained in the present study we have determined that estetrol is 15 to 30 times less potent than estriol as a uterine vasodilator. PMID:6702941

  11. Pregnancy toxemia and ketosis of ewes and does.

    PubMed

    Marteniuk, J V; Herdt, T H

    1988-07-01

    Pregnancy toxemia of ewes and does appears to occur when the animal cannot meet the glucose demands of the fetal-placental unit and hypoglycemia develops. There is individual variation in susceptibility, and there may be basic differences in glucose metabolism between susceptible animals and nonsusceptible animals. Increased serum NEFA and ketone body concentrations accompany the disease, but clinical signs do not appear to develop in the absence of hypoglycemia. The diagnosis is based on history, clinical signs, and the finding of ketone bodies in the urine. Numerous metabolic abnormalities develop subsequent to hypoglycemia and hyperketonemia, and these affect the prognosis. Important secondary abnormalities include acidosis, dehydration, and renal failure. Therapy is frequently unsuccessful, but frequent administration of small doses of glucose appears to be beneficial, if the other abnormalities, such as acidosis and dehydration, are controlled. Prevention can be readily achieved by nutritional means and is far more rewarding than therapy. Ewes and does must be fed in relation to their changing energy needs throughout the reproductive cycle. PMID:3264753

  12. Contrasting epidemiology of childhood osteosarcoma, Ewing's tumor, and rhabdomyosarcoma

    SciTech Connect

    Miller, R.W.

    1981-04-01

    Marked dissimilarities in the epidemiology of osteosarcoma, Ewing's tumor, and rhabdomyosarcoma indicate differences in their origins. A major clue to the genesis of Ewing's tumor comes not from defining persons at high risk but from the observation that blacks are at unusually low risk. The neoplasm does not aggregate in families and is not part of any known syndrome. No environmental causes have been identified. By contrast, osteosarcoma may be caused by external or internal ionizing radiation, and it aggregated in families with the same tumor or with dissimilar tumors and in certain genetic disorders of bone. In man and in dogs, the frequency of the neoplasm is related to bone mass and growth. Rhabdomyosarcoma of the upper versus the lower limbs seems related to muscle mass. Age peaks in the occurrence of the tumor elsewhere vary with the anatomic site; head and neck tumors develop in early childhood and urogenital tumors both in early years and in adolescence. The sex ratio (male to female) also varies with the site affected. Rhabdomyosarcoma aggregates with certain other tumors in families and overlaps with osteosarcoma in some of these relationships but is distinguished from that tumor by its excessive occurrence in neurofibromatosis.

  13. Vitamin E supplementation of undernourished ewes pre- and post-lambing reduces weight loss of ewes and increases weight of lambs.

    PubMed

    Rosales Nieto, César Augusto; Meza-Herrera, César Alberto; Moron Cedillo, Felipe de Jesús; Flores Najera, Manuel de Jesús; Gámez Vázquez, Hector Guillermo; Ventura Pérez, Felipe de Jesús; Liu, Shimin

    2016-03-01

    The aim of this study was to test if vitamin E supplementation during late gestation and early lactation would affect the weight of ewes under nutritional restriction and the performance of their lambs. Mature Rambouillet ewes (n = 37) were fed a diet that supplied 70 % of the energy and 80 % of recommended protein requirements and randomly assigned to either vitamin E (vit E, n = 20, 4 IU of α-tocopherol kg(-1) of live weight) or control (n = 17, without vitamin E supplementation). During the experimental period, the mean weight of ewes decreased from 74.6 ± 2.4 to 58.1 ± 2.2 kg. Weight loss of ewes was slightly less for the vit E than the control (-65 vs -124 g day(-1), SEM = 46; P = 0.07). Lambs born from vit E-supplemented ewes were heavier than lambs from the control and grew significantly faster (239 vs 195 g day(-1), SEM = 29.3, P < 0.05) with heavier weights at weaning (16.5 vs 13.5 kg, SEM = 1.8, P < 0.05). Besides, birth weight, weaning weight and daily weight gain favoured to single lambs and to male lambs (P < 0.05). Weaning weight was positively correlated to birth weight (P < 0.05) and weight gain (P < 0.001). When the nutrient requirements for ewes are not met, supplementation of vitamin E during late gestation and early lactation might be an effective strategy to minimise ewe weight loss as well as to increase lamb growth. PMID:26894501

  14. Organic and inorganic selenium: IV. passive transfer of immunoglobulin from ewe to lamb.

    PubMed

    Stewart, W C; Bobe, G; Vorachek, W R; Stang, B V; Pirelli, G J; Mosher, W D; Hall, J A

    2013-04-01

    Newborn lambs depend on their dams for passive transfer of immunoglobulins, primarily IgG, for protection from harmful pathogens until their own immunological defenses have developed. Previous studies have suggested that supplementation with Se results in a modest increase in IgG concentration in serum of newborn calves and lambs. To evaluate the effect of the Se source and supplementation rate in ewes during pregnancy on passive transfer of IgG to their lambs, 210 Polypay, Suffolk, or Suffolk Polypay cross ewes were divided into 7 treatment groups (n = 30 each) and drenched weekly with no Se, at the maximum FDA-allowed concentration with inorganic Na-selenite or organic Se-yeast (4.9 mg Se/wk), or with inorganic Na-selenite and organic Se-yeast at supranutritional concentrations (14.7 and 24.5 mg Se/wk). Ewe serum IgG concentrations were measured within 30 d of parturition, ewe colostrum and lamb serum IgG concentrations were measured at parturition before suckling, and lamb serum IgG concentrations were measured again at 48 h postnatal. Ewes receiving 24.5 mg Se/wk tended to have or had, independent of Se source, greater colostral IgG concentrations than ewes receiving 4.9 mg Se/wk overall (81.3 vs. 66.2 mg/mL; P = 0.08) and for Polypay ewes only (90.1 vs. 60.7 mg/mL; P = 0.03). Polypay ewes receiving Se-yeast at 24.5 mg Se/wk transferred a greater calculated total IgG amount to their lambs than Polypay ewes receiving Se-yeast at 4.9 mg Se/wk (15.5 vs. 11.6 g; P = 0.02), whereas the converse was true (interaction between Se source and dose concentration; P = 0.03) for Polypay ewes receiving inorganic Na-selenite at 24.5 mg Se/wk vs. Na-selenite at 4.9 mg/wk (11.6 vs. 15.7 g; P = 0.08). Our results suggest that supranutritional Se supplementation of Polypay ewes during pregnancy increases colostral IgG concentrations but that the optimal supplementation rate for IgG transfer from ewe to lamb may differ for Na-selenite and Se-yeast. PMID:23408818

  15. Harvey Sarcoma Virus: A Second Murine Type C Sarcoma Virus with Rat Genetic Information

    PubMed Central

    Scolnick, Edward M.; Parks, Wade P.

    1974-01-01

    The nucleic acid sequences found in the Harvey strain of murine sarcoma virus have been analyzed by RNA[3H]DNA and [3H]RNADNA hybridization techniques. The Harvey strain of murine sarcoma virus has been found to possess at least two sets of nucleic acid sequences. One set of sequences is contained in the Moloney strain of mouse type-C virus, and the other set is contained in DNA transcripts synthesized in endogenous reactions containing rat type-C virus(es). The nucleic acid sequences that are detected in the Harvey sarcoma virus with the DNA probes synthesized from the rat type-C virus(es) are related to the rat sequences detected in the Kirsten strain of murine sarcoma virus. The results support the model that both Kirsten and Harvey sarcoma viruses arose through a process of recombination or reassortment between mouse type-C viruses and sequences in rat cells and suggest that the information for transformation of fibroblasts may be contained in the rat type-C or cellular genome. PMID:4364897

  16. Familial Kaposi's Sarcoma: A Report of Five Cases from Greece.

    PubMed

    Armyra, Kalliopi; Kouris, Anargyros; Xanthinaki, Arsinoi; Stratigos, Alexandros; Potouridou, Irene

    2014-01-01

    Introduction. Familial cases of Kaposi's sarcoma have rarely been reported. Kaposi's sarcoma is not uncommon in Greece; its incidence is estimated at 0.20 per 100.000 habitants, showing an increased predominance in the Peloponnese, in Southern Greece. Case Report. We describe five cases of familial clustering of KS originating from Greece. Discussion. The pathogenesis of familial Kaposi's sarcoma is still far from being completely understood. Genetic, environmental, and infectious factors have been incriminated. PMID:25093124

  17. Familial Kaposi's Sarcoma: A Report of Five Cases from Greece

    PubMed Central

    Armyra, Kalliopi; Kouris, Anargyros; Xanthinaki, Arsinoi; Stratigos, Alexandros; Potouridou, Irene

    2014-01-01

    Introduction. Familial cases of Kaposi's sarcoma have rarely been reported. Kaposi's sarcoma is not uncommon in Greece; its incidence is estimated at 0.20 per 100.000 habitants, showing an increased predominance in the Peloponnese, in Southern Greece. Case Report. We describe five cases of familial clustering of KS originating from Greece. Discussion. The pathogenesis of familial Kaposi's sarcoma is still far from being completely understood. Genetic, environmental, and infectious factors have been incriminated. PMID:25093124

  18. Radiation-induced prostatic sarcoma: A case report

    SciTech Connect

    Scully, J.M.; Uno, J.M.; McIntyre, M.; Mosely, S. )

    1990-09-01

    A 64-year-old man had a prostatic sarcoma 8 years after transurethral prostatectomy and radical bilateral pelvic lymph node dissection with insertion of 125-iodine implants for stage B1N carcinoma of the prostate. Therapy for the sarcoma consisted of isolated pelvic perfusion and then pelvic exenteration with creation of an ileal conduit and colostomy. The pathology report showed well encapsulated grade 2 spindle cell sarcoma of the prostate. Multiple small metallic particles were embedded in the tumor specimen.

  19. Isolated myeloid sarcoma presenting in all four eyelids.

    PubMed

    Thomas, Scott A; Durairaj, Vikram D

    2007-01-01

    Myeloid sarcoma is an unusual manifestation of acute leukemia. These leukemic tumors have been described in multiple organ systems. Leukemia is almost always present, but may be undiagnosed when the myeloid sarcoma comes to medical attention. We present a clinicopathologic report of a previously healthy young woman with conjunctival myeloid sarcomas of all 4 eyelids without evidence of an underlying hematologic disorder over 15 months' follow-up, despite refusal of consolidation chemotherapy. Isolated, multifocal myeloid sarcoma of the periorbital region is a very rare manifestation of acute leukemia. PMID:17667120

  20. Radiation-induced sarcoma following radiotherapy for testicular tumor

    SciTech Connect

    Lynch, D.F. Jr.; Herr, H.W.

    1981-12-01

    We report 4 cases of soft tissue sarcoma following radiation therapy for testicular tumor. The tumors included leiomyosarcoma, fibroxanthosarcoma, reticulum cell sarcoma and spindle cell sarcoma. Each malignancy arose within the irradiated area after a long latent period (mean 12 years) and each was histologically proved. Total radiation doses ranged from 3,500 to 9,000 rad. Three patients died as a result of the second neoplasm. Radiation-induced sarcomas are rare but must be considered in the differential diagnosis of new tumor growth in patients treated previously with radiotherapy. Full evaluation of such new tumor growth, including tissue diagnosis, is necessary before additional therapy is prescribed.

  1. Polypoid uterine lesions mimicking endometrial stromal sarcoma.

    PubMed Central

    McCluggage, W G; Alderdice, J M; Walsh, M Y

    1999-01-01

    Two polypoid submucosal uterine lesions were examined histologically and immunohistochemically with monoclonal antibodies to desmin and alpha smooth muscle actin. One case comprised a leiomyoma and the other a polypoid form of adenomyosis. Both polyps had prolapsed through the external cervical os. The lesions had an ulcerated surface with focal areas of marked increased cellularity and pronounced vascularity throughout, such that they mimicked a low grade endometrial stromal sarcoma infiltrating the myometrium. The cellular areas showed diffuse positivity for desmin and alpha smooth muscle actin, confirming them to be of smooth muscle origin. The changes of marked hypercellularity and pronounced vascularity within polypoid submucosal uterine lesions have not been emphasised in published reports up to now. Pathologists should be aware of these morphological features in order to avoid misdiagnosis of such cases as endometrial stromal sarcomas. The changes described here are likely to be secondary to trauma associated with a polypoid lesion prolapsing through the external cervical os. Images PMID:10605413

  2. Emerging therapies for adult soft tissue sarcoma.

    PubMed

    Radaelli, Stefano; Stacchiotti, Sivia; Casali, Paolo G; Gronchi, Alessandro

    2014-06-01

    Soft tissue sarcoma (STS) are a broad group of rare tumors. Cornerstone of treatment is surgery. Complementary radiotherapy is recommended in high-risk STS arising from extremities. Doxorubicine ifosfamide based cytotoxic chemotherapy, explored in few randomized trials, showed a certain degree of activity, playing an established role only in unresectable disease. Since peculiar chemosensitivity towards alternative drugs was described for different metastatic subtypes in second or further lines, the modern concept of 'histology-driven chemotherapy' has been accepted and employed: gemicitabine dacarbazine, trabectedin and taxanes used respectively in patients with leiomyosarcoma, solitary fibrous tumor, myxoid/round cell liposarcoma, angiosarcoma. Recent discoveries about molecular pathways involved in STS tumorogenesis led to develop molecular targeted agents such as imatinib used in advanced dermatofibrosarcoma protuberans (DFSP) or metastatic DFSP-related fibrosarcoma, pazopanib, approved as second line regimen in advanced non-adipocitic STS and recently sunitinib in solitary fibrous tumors, alveolar soft part sarcoma and extraskeletal myxoid chondrosarcoma. PMID:24555529

  3. Utility of characteristic 'Weak to Absent' INI1/SMARCB1/BAF47 expression in diagnosis of synovial sarcomas.

    PubMed

    Rekhi, Bharat; Vogel, Ulrich

    2015-07-01

    Recently, very few studies have shown value of immunohistochemical (IHC) expression of INI1/SMARCB1 in diagnosis of synovial sarcomas (SSs). This study was aimed at testing reproducibility and utility of this finding. Sixty-eight SSs and 147 other tumours, in the form of various biopsies, were tested for IHC expression of INI1. Twenty-six SSs were further confirmed with positive SS18 rearrangement. Forty monophasic spindle cell type (58.8%), 13 biphasic (19.1%), 12 poorly differentiated (17.6%) and three calcifying SSs (4.4%) were positive for epithelial membrane antigen (EMA) (46/62) (74.1%), pan cytokeratin (AE1/AE3) (31/47) (65.9%), cytokeratin (CK7) (20/31) (64.5%), BCL2 (62/66) (93.9%), MIC2 (61/63) (96.8%), transducin-like enhancer of split 1 (TLE1) (29/31) (93.5%) and CK19 (14/24) (58.3%). INI1 expression was 'weak to absent' in 60/68 (88.2%) SSs; in 1/3 atypical ossifying fibromyxoid tumours (AOFMTs) and in 3/10 (30%) malignant peripheral nerve sheath tumours (MPNSTs) of various types. INI1 was completely absent in 10/10 (100%) epithelioid sarcomas (ESs), 4/4 (100%) malignant rhabdoid tumours, single paediatric undifferentiated sarcoma, 5/19 (26.3%) myoepithelial carcinomas and in 2/4 (50%) epithelioid-subtype of MPNSTs. Remaining 100 tumours, including 12 Ewing sarcomas, 15 carcinomas, eight solitary fibrous tumours (SFT), seven extraskeletal myxoid chondrosarcomas, three fibrosarcomas and other tumours retained INI1 expression. A unique 'weak to absent' IHC expression of INI1 is highly sensitive (88.2%) and specific (97.3%) for a SS, irrespective of its subtypes and types of biopsies. This can be considered useful in diagnosing SSs, especially in settings lacking molecular and/or cytogenetic analysis. A similar INI1 expression is shared by certain AOFMTs and MPNSTs. PMID:25912315

  4. Management of soft tissue and bone sarcomas

    SciTech Connect

    Van Oosterom, A.T.; Van Unnik, J.A.M.

    1986-01-01

    This book contains 32 papers. Some of the titles are: Adjuvant Treatment for Osteosarcoma of the Limbs; Trial 20781 of the SIOP and the EORTC Radiotherapy/Chemotherapy; Application of Magnetic Resonance Imaging (MRI) in Diagnosis and Follow-up During Treatment of Bone Tumors; Radiological Assessment of Local Involvement in Bone Sarcomas; and Prevention of Lung Metastases by Irradiation Alone or Combined with Chemotherapy in an Animal Model.

  5. Metastatic pleomorphic sarcoma to left atrium

    PubMed Central

    Hawasli, Ammar H; Cayce, Rachael; Luong, Trung; Taiwo, Evelyn; Feliciano, Michael N; Reimold, Sharon C; DiMaio, John M; Haley, Barbara B

    2009-01-01

    Although several thousand patients are diagnosed with sarcoma annually in the United States, metastases to the heart are very uncommon. In this case report, an overall low frequency cancer presents masquerading with common cardiac symptomology. This case illustrates the importance for detailed diagnostic cardiac evaluations and heightened suspicion by physicians to consider metastatic disease to the heart in cancer patients with cardiovascular complications. Also discussed is a review of surgical and chemotherapeutic options for this problem. PMID:21139880

  6. Multimodality Local Therapy for Retroperitoneal Sarcoma

    SciTech Connect

    Paryani, Nitesh N.; Zlotecki, Robert A.; Swanson, Erika L.; Morris, Christopher G.; Grobmyer, Stephen R.; Hochwald, Steven N.; Marcus, Robert B.; Indelicato, Daniel J.

    2012-03-01

    Purpose: Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival. Methods and Materials: Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era. Results: The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%). Conclusion: For retroperitoneal sarcoma, local control remains a challenge and combined-modality therapy may be associated with significant acute and late morbidity. Our patterns of failure data suggest that improvements in local control may translate into a survival benefit.

  7. Hormonal profiles of late gestation ewes following intra-uterine inoculation with and without lux-modified Escherichia coli.

    PubMed

    Moulton, Keesla; Ryan, Peter; Christiansen, David; Hopper, Richard; Klauser, Chad; Bennett, William; Rodts-Palenik, Sheryl; Willard, Scott

    2009-02-01

    The objectives of these investigations were to develop an ovine model for Escherichia coli (E. coli)-induced preterm delivery, and monitor ewe hormonal response. EXP 1: Ewes (105 +/- 13 days of gestation) were allotted to the following intra-uterine inoculations: Saline-(CON; n=5); 1 x 10(6) CFU/ml (Low Treatment, LT; n=6); or 1 x 10(7) CFU/ml (High Treatment, HT; n=6) E. coli. Twenty-four h after inoculation, the HT ewes had increased (P<0.05) cortisol compared to LT and CON ewes, and HT and LT ewes had increased (P<0.05) progesterone compared to CON ewes. Preterm delivery was 33% for LT ewes and 0% for HT and CON ewes. EXP 2: Ewes (124 +/- 18 days of gestation) were allotted to the following intra-uterine inoculations using lux-modified E. coli: Trial-1: Luria Broth (LB; CT1; n=5); 4.0 x 10(6) CFU (n=5), 20.0 x 10(6) CFU (n=5); and Trial-2: LB (CT2; n=5), 1.2 x 10(6) CFU (n=5), and 5.6 x 10(6) CFU (n=5) E. coli-lux. Preterm delivery occurred between 48 and 120 h post-inoculation in 60, 25, 60 and 75% of ewes infected with 1.2, 4.0, 5.6, and 20 x 10(6) CFU, respectively. Serum cortisol and progesterone did not differ (P>0.05) between CT1 or CT2 and inoculated ewes. In summary, 25 to 75% of ewes inoculated preterm delivered. However, variable results in cortisol and progesterone profiles between Control and inoculated ewes were observed between the two studies. PMID:18997446

  8. In vivo radiolocalization of antiosteogenic sarcoma monoclonal antibodies in osteogenic sarcoma xenografts

    SciTech Connect

    Nakamura, T.; Sakahara, H.; Hosoi, S.; Yamamuro, T.; Higashi, S.; Mikawa, H.; Endo, K.; Toyama, S.

    1984-05-01

    Monoclonal antibodies Ost6 and Ost7 (mouse Immunoglobulin G1) to human osteogenic sarcoma were isolated from ascitic fluid and labeled with radioiodine. After injection into athymic nu/nu mice with s.c. xenografts of human osteogenic sarcoma, the uptake of radioactivity in tumors, visceral organs, and blood was determined. Five days after injection, Ost6 and Ost7 showed preferential accumulation in tumors (tumor:blood ratio, 4.3). Furthermore, with testicular and bladder tumors, both unreactive with Ost7, there was no localization of radiolabeled Ost7 in xenograft growths. When Ost7 was labeled with /sup 131/I, its accumulation into human osteogenic sarcoma could be clearly visualized by whole-body gamma-scintigraphy without computer-assisted data processing.

  9. Metachronous Bilateral Extremity Soft Tissue Sarcomas

    PubMed Central

    Nowrasteh, Ghodratollah; Aziz, Tanim; Assas, Mohammed Al; Nuaimi, Lateefa Al; Marzouqi, Saeeda; Quadri, Asif A.M.; Alrawi, Sadir

    2016-01-01

    Case series Patient: Male, 44 • Male, 58 Final Diagnosis: Soft tissue sarcomas Symptoms: Discomfort • swelling Medication: — Clinical Procedure: Image guided biopsy • metastatic work up • neoadjuvant radiotherapy • radical resection Specialty: Surgery Objective: Rare disease Background: Soft tissue sarcomas (STS) account for approximately 1% of adult malignancies, with 50 to 60% occurring in the extremities. Liposarcoma is the most common type of STS and represent about 20% of total adult sarcomas. There are rare syndromes associated with increased risk of developing STS. Further, chemical compounds such as chlorinated phenols and a few chemotherapeutic drugs have been linked to STS, along with ionizing radiation. Nevertheless, the etiology is uncertain for most of these lesions. Case Report: This report details 2 cases of metachronous bilateral STS of the lower extremities. The first of these presented as a local recurrence of a previously resected right thigh liposarcoma and a new liposarcoma in the left thigh. As mentioned above, among the different subtypes of STS, liposarcoma has the highest tendency for multifocality. The second patient had multifocal metachronous leiomyosarcoma with lung metastases occurring simultaneously with the second presentation. Leiomyosarcoma is another subtype reported to present with multi-focal disease. Conclusions: Despite the rarity of bilateral lesions, their occurrence should not be overlooked in the initial diagnosis and follow-up of the initially detected tumor. Early detection can affect patient survival because their presence predicts unfavorable outcomes. PMID:26744032

  10. Tumor-specific immunity in sarcoma patients.

    PubMed

    Rella, W; Kotz, R; Arbes, H; Leber, H

    1977-01-01

    Stimulatory responses of 40 patients with bone [33] and soft tissue [7] sarcomas to autologous tumor cells were correlated with clinical data and prognosis. Although conclusive judgments for individual patients cannot be made, some genral features emerge: patients with stimulation indices greater than 1.5 have a 50 percent relapse-free interval after surgery of 22 months, patients with indices, below 1.5 have a 50 percent relapse-free interval of 5 months. 7 out of 10 responder patients are tumor-free 1 year after surgery as compared to 5 out of 19 (26 percent of non-responder pateints (p less than 0.05). Removal of the tumor is followed by an increase in the stimulatory response and by the dissappearance of blocking serum factors in patients with favourable prognosis. Responses return to baseline levels in tumor free patients 9-12 months after surgery. The results suggest that tumor-associated immune responses play a role in the development of human sarcomas. In addition, 47 lymphocyte samples of 25 patients were tested for stimulation by autologous tumor cells and for cell-mediated cytotoxicity against allogeneic sarcoma cell lines. Similar results were obtained in both test systems when pre-therapy lymphocytes were used. Discordant results were frequently seen at times after surgery. Both test systems may complement each other and may help clarify the tumor-specificity of certain lymphocytotoxic activities. PMID:144262

  11. Sarcoma Immunotherapy: Past Approaches and Future Directions

    PubMed Central

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

    2014-01-01

    Sarcomas are heterogeneous malignant tumors of mesenchymal origin characterized by more than 100 distinct subtypes. Unfortunately, 2550% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease. PMID:24778572

  12. Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.

    PubMed

    Manes, Jorgelina; Ríos, Glenda; Fiorentino, María Andrea; Ungerfeld, Rodolfo

    2016-03-15

    The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P < 0.0001, and P < 0.0001, respectively). The percentage of sperm with progressive motility was lower after incubation with vaginal mucus collected from estrous ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P < 0.0001, respectively). The sample incubated for 30 minutes with mucus from ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P < 0.0001). The percentage of sperm with functional membrane was significantly lower in the sample incubated for 30 minutes with vaginal mucus from ewes treated with IS than in the other three treatments (P < 0.0001). After 90 minutes, the percentage was still lower than that in the sample collected from ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P < 0.0001 and P = 0.008, respectively). The percentage of apoptotic spermatozoa was greater in samples incubated during 30 minutes with vaginal mucus collected from ewes treated with IS than in the other three groups (P = 0.0005). The functionality and the viability of ram sperm is negatively affected by the cervical mucus of ewes pretreated with progestagen-impregnated IS used in estrous synchronization treatments. This may partially explain the decrease in conception rate obtained with treatments with IS. PMID:26627933

  13. Effect of early and late exposure to estrual ewes on ram sexual performance classifications.

    PubMed

    Stellflug, J N; Lewis, G S

    2007-02-01

    This study was conducted to determine whether exposure of ram lambs to estrual ewes during their first autumn and again as adults just before serving capacity tests (SCT) affected the outcome of the sexual performance tests. Treatments were either early exposure of Polypay ram lambs (i.e., 7-8-mo-old rams with ewes for 17 d [n=30] or no early exposure [n=30]), and late exposure (i.e., 16-19-mo-old rams with estrual ewes for 3 d) or no exposure to estrual ewes in a 2x2 factorial arrangement. Three serving capacity tests were conducted immediately after the early exposure period for individual ram lambs that were exposed to ewes early. Three sham sexual performance tests (i.e., four ram lambs placed in test pens for 30-min without ewes) were conducted with ram lambs that were not exposed to ewes early. All rams were evaluated during nine 30-min serving capacity tests over a 2-mo period at 16-19 mo of age to determine sexual performance. Prior to serving capacity tests, one half of the rams from each early exposure treatment were exposed to estrual-induced ewes for 3 d. Specific sexual behaviors (e.g., sniffs, flehmens, foreleg kicks, vocalizations, mount attempts, mounts, and ejaculations) were recorded during serving capacity tests. Number of sniffs, flehmens, foreleg kicks, vocalizations, and mount attempts were summed without estimating the value of importance and analyzed as courtship behaviors. Sexual performance data were analyzed with Mixed model procedures for repeated measures. During serving capacity tests, the early exposed rams exhibited more courtships (40.3+/-8.0 versus 23.4+/-4.6; P<0.05; LSM+/-estimated SE), mounts (11.3+/-1.0 versus 7.7+/-0.9; P<0.01), and ejaculations (3.3+/-0.2 or 2.4+/-0.2; P<0.01) than rams not exposed to ewes as ram lambs, respectively. We conclude that early exposure of 7-8-mo-old ram lambs to estrual ewes improves sexual performance in serving capacity tests at 16-19 mo of age in most rams whereas, late exposure to estrual ewes for 3 d prior to serving capacity tests did not improve sexual performance scores. PMID:16533578

  14. Effects of supplementary treatment with bovine growth hormone on hormonal and ovulatory responses to inhibin immunization in ewes.

    PubMed

    Tannetta, D S; Fray, M D; Wrathall, J H; Bleach, E C; Glencross, R G; Knight, P G

    1997-07-01

    The aim of this study was to determine whether supplementary treatment with recombinant bovine growth hormone(rbGH) can enhance the ovulatory response of ewes to inhibin immunization. Crossbred ewes (n = 20) were actively immunized against bovine inhibin a1-29 peptide conjugate while 20 ewes served as controls. Oestrus was synchronized using progestagen sponges and ewes were allocated to four groups: control ewes (n = 10); control ewes given rbGH (n = 10); inhibin-immunized ewes (n = 10) and inhibin-immunized ewes given rbGH (n = 10). A single s.c. dose of rbGH (50 mg) was given 7 days before sponge removal. Blood was collected for measurement of inhibin antibody titre, and concentrations of insulin-like growth factor I (IGF-I), FSH, oestradiol and progesterone. Ovulation, pregnancy and lambing rates were also recorded. All inhibin-immunized ewes produced antibodies that bound 125I-labelled (32 kDa) inhibin. The concentration of FSH in the plasma of the ewes after the second booster inhibin immunization was higher than that in control ewes (P < 0.005). Treatment with rbGH promoted a 2-3-fold increase in plasma concentration of IGF-I (P < 0.001); the response was less (P < 0.01) in immunized compared with control ewes. Treatment with rbGH alone had no significant effect on the concentration of FSH or oestradiol or on ovulation rate or litter size. Overall, inhibin-immunized ewes had higher mean FSH concentrations (P < 0.002), higher preovulatory oestradiol surges (P < 0.05) and higher progesterone concentrations in the luteal phase (P < 0.0001). Treatment with rbGH reduced the effects of immunization on FSH (P < 0.01) and progesterone (P < 0.02) concentrations. Immunized ewes showed a threefold increase in ovulation rate (P < 0.001) and a 1.8-fold increase in litter size (P < 0.05) compared with control ewes. In immunized ewes given rbGH, ovulation rate was increased by a factor of 2.2 and litter size by a factor of 1.8. In conclusion, these data do not support the hypothesis that supplementary treatment of ewes with rbGH to raise plasma IGF-I concentrations (and presumably intraovarian IGF-I) can enhance the ovulatory response to inhibin immunization. PMID:9306979

  15. Effect of selenium yeast supplementation on naturally acquired parasitic infection in ewes.

    PubMed

    Hooper, Kathryn J; Bobe, Gerd; Vorachek, William R; Bishop-Stewart, Janell K; Mosher, Wayne D; Pirelli, Gene J; Kent, Michael L; Hall, Jean A

    2014-12-01

    Gastrointestinal parasites cause substantial economic losses in pasture-based sheep production systems. Supranutritional organic selenium (Se) supplementation may be beneficial because it improves immune responses to pathogens. To evaluate the effect of Se-yeast supplementation on gastrointestinal parasite load, 30 ewes per treatment group were drenched weekly with no Se, 4.9mg Se/week as Se yeast (maximum FDA-allowed concentration), or supranutritional concentrations of Se yeast (14.7 and 24.5mg Se/week) starting early fall for 85weeks. Fecal samples were collected at weeks 63, 66, 78, and 84 and counted for total trichostrongyle-type eggs and Haemonchus contortus eggs (in samples with ?200 trichostrongyle eggs/g feces). During breeding season (fall), ewes were kept on pasture; ewes receiving 24.5mg Se/week had lower fecal trichostrongyle egg counts (93??40 eggs/g feces) compared with ewes receiving no Se (537??257 eggs/g feces; P?=?0.007) or ewes receiving 4.9mg Se/week as Se yeast (398??208 eggs/g feces; P?=?0.03). In winter, fecal trichostrongyle egg counts decreased, and group differences were not apparent. During lambing season (spring), ewes were kept in the barn and fecal trichostrongyle egg counts increased, although no group differences were observed. However, none of the ewes receiving supranutritional Se yeast, and with trichostrongyle egg counts ?200 eggs/g of feces, but four of the ewes receiving lower Se dosages had H. contortus egg counts ?1,000 eggs/g feces (P?=?0.04). Our results suggest that supranutritional Se-yeast supplementation may enhance resistance to naturally occurring H. contortus gastrointestinal parasitism in sheep. PMID:25256922

  16. Equine chorionic gonadotrophin administration to rams improves their effectiveness to stimulate anoestrous ewes (the "ram effect").

    PubMed

    Ungerfeld, Rodolfo; Clemente, Neftali; Bonjour, Lorena; Orihuela, Agustin

    2014-10-01

    Ewes' response to ram effect is related to the strength of androgen-dependent ram signals. Experiment 1 aimed to determine if the administration of a single dose of 1000IU of eCG to rams three days before joining them with ewes enhance their ability to stimulate females. Based on the results of Experiment 1, in a second experiment rams received two doses seven and three days before their introduction to females. In Experiment 1, rams treated or not with eCG were joined with ewes, and estrous was recorded until Day 5 (Day 0=rams and ewes were joined), and from Day 15 to Day 23. In addition, serum testosterone concentration was measured in all rams in the first recorded period. Testosterone values were greater in eCG-E1 than in Con-E1 rams on Days 0 and 2. The percentage of ewes in estrus was similar in both groups. In Experiment 2, rams were treated with two doses of eCG on Days -7 and -3 or remained as untreated controls. Estrous was recorded until Day 5, and pregnancy rate on Day 46; testosterone was measured in samples collected from all rams. Testosterone concentration was greater in eCG-E2 than Con-E2 rams from Day -5 to Day 1, and tended to do so on Day 2. More eCG-E2 than Con-E2 ewes came into estrus and became pregnant. It was concluded that treatment of rams with two high doses of eCG before joining them with anestrous ewes, enhanced their ability to induce ewes' cyclic activity (the "ram effect"). PMID:25059200

  17. The Ewes Reproductive Performance, Growth Rate and Carcass Quality of Lambs Kept in a Barn vs Those Kept under an Overhead Shelter

    PubMed Central

    Ku?nicka, Ewa; Rant, Witold

    2013-01-01

    A herd of polish lowland local sheep was divided into two equal groups: the first group was kept under an overhead shelter, and the second group was kept in a warm barn. The effect of maintenance on ewes reproductive performance, survival as well as the growth rate of lambs, and their carcasses quality was investigated. The lack of differences in fertility and prolificacy of ewes as well as in the survival and growth rate between the groups confirmed a good adaptation of ?ela?nie?ska sheep to low temperature. Harsh environmental conditions did not cause a significant decrease of the body weight growth; however, they brought in an (insignificant) reduction of subcutaneous fat thickness and meatiness of the loin part of a lambs body. The fat content of carcasses obtained from lambs reared under the overhead shelter was significantly lower, with no differences of meat and bones contribution between the groups. PMID:25049778

  18. Cervical versus intrauterine insemination of ewes using fresh or frozen semen diluted with aloe vera gel.

    PubMed

    Rodriguez, F; Baldassarre, H; Simonetti, J; Aste, F; Ruttle, J L

    1988-01-01

    This study was conducted at Belen de Escobar, Argentina, in March and April 1987. Experimental work on synchronization of estrus, deep-freeze conservation of ram semen and small fertility trials involving cervical and intrauterine (i.u.) insemination methods was undertaken. A total of 80 Corriedale ewes were used in seven insemination trials. Insemination trials were grouped into two experimental groups for comparison of 1) frozen semen diluted with an experimental extender and a control diluent inseminated cervically or i.u. in synchronized/superovulated ewes and 2) cervical insemination of fresh diluted or frozen semen in ewes inseminated at natural estrus or in ewes that were synchronized/superovulated. An overall ovulation rate of 8.7 +/- 0.5 was obtained by using a superovulatory regimen consisting of 3 mg Norgestomet implants and a total dose of 18 mg follicle stimulating hormone-pituitary (FSH-P). Numbers of ova recovered per ewe following superovulation ranged from 4.3 to 5.4. In experimental Group I, fertilization rates improved when laparoscopic intrauterine AI was used compared with cervical insemination (P<0.05). Fertility rates of i.u. and cervical insemination of frozen semen diluted with the experimental extender showed satisfactory fertilizing capacity. In experimental Group II, a lower number of fertilized ova were recovered from ewes inseminated with frozen semen (P<0.02), irrespective of their estrus manipulation. PMID:16726526

  19. Effect of selective anthelmintic treatments on health and production parameters in Pelibuey ewes during lactation.

    PubMed

    Arece-García, Javier; López-Leyva, Yoel; González-Garduño, Roberto; Torres-Hernández, Glafiro; Rojo-Rubio, Rolando; Marie-Magdeleine, Carine

    2016-02-01

    A study was conducted from December to April 2013, with the aim of evaluating a system of selective antiparasitic treatments using the FAMACHA© color chart compared with a conventional suppressive deworming system every 30 days in Pelibuey ewes during lactation. For the study, 54 ewes were used. They were randomly divided into two groups: FAMACHA and chemical treatments. The ewes in the first group received selective treatment depending on the ocular mucosa coloration (FAMACHA) and body condition score (BCS), while in the second group (chemical) all the animals remained under routine deworming every 30 days. Fecal nematode egg counts, proportion of third-stage trichostrongylid larvae, body condition, coloration of the ocular mucosa, and packed cell volume in the ewes were determined, while in lambs only body weight (BW) was recorded. No significant differences (p > 0.05) were observed in any of the studied variables between groups; however, the use of antiparasitic drugs was reduced during the experimental period in the FAMACHA group and no deaths of lambs or ewes were recorded. The results indicate that during the lactation of ewes, a strategy of selective treatments can be implemented without showing deterioration in major health and productive parameters of these animals. PMID:26563269

  20. Skeletal lesions of histiocytic sarcoma in nineteen dogs.

    PubMed

    Schultz, Ryan M; Puchalski, Sarah M; Kent, Michael; Moore, Peter F

    2007-01-01

    The purpose of this study was to describe the clinical and radiographic findings in dogs with bone lesions secondary to histiocytic sarcoma. Nineteen dogs with radiographically identified bone lesions that were histologically diagnosed as histiocytic sarcoma were assessed. The medical records, all available radiographs and histologic sections were reviewed retrospectively. Dogs were subcategorized into localized or disseminated histiocytic sarcoma groups. Golden Retrievers or Rottweilers greater than 5 years of age, with a history of lameness or neurologic deficits localized to the spinal cord was the most common presentation. Fifteen of 19 dogs had a radiographically detectable soft tissue mass associated with bone destruction. The bone lesions had aggressive characteristics and the sites of involvement included periarticular bones (n = 11), vertebrae (n = 6), proximal humerus (n = 5), and rib (n = 2). Fifteen of 19 dogs had disseminated histiocytic sarcoma, and four had localized histiocytic sarcoma. All Rottweilers had disseminated histiocytic sarcoma. Histiocytic sarcoma should be considered as a differential diagnosis for aggressive periarticular, vertebral, or proximal humeral bone lesions identified on radiographs. The index of suspicion should be increased in greater than 5-year-old Golden Retrievers and Rottweilers when a soft tissue mass is associated with the bone lesion on radiographs or myelography. Bone involvement with histiocytic sarcoma, and the Rottweiler breed, was associated with the disseminated form of the disease. PMID:18018725

  1. An unusual pleomorphic sarcoma in a hybrid mallard

    USGS Publications Warehouse

    Roffe, Thomas J.

    1987-01-01

    An unusual pleomorphic sarcoma from a hybrid mallard (Anas platyrhynchos) is described. Rhabdomyosarcoma was considered in the original differential diagnoses but rejected due to lack of specific characteristics generally seen in these tumors. The histologic characteristics described are consistent with mammalian sarcomas recorded in the literature as malignant fibrous histiocytoma.

  2. Kaposi's sarcoma involving the thyroid in a patient with AIDS

    SciTech Connect

    Krauth, P.H.; Katz, J.F.

    1987-11-01

    A 30-year-old man with acquired immune deficiency syndrome (AIDS) and Kaposi's sarcoma had a palpable thyroid mass and cervical lymphadenopathy. Nuclear medicine and ultrasound scans revealed multiple thyroid nodules. Results of biopsy showed Kaposi's sarcoma metastatic to the thyroid.

  3. Primary pulmonary synovial sarcoma: Diagnosis on squash smears.

    PubMed

    Yaseen, Syed Besina; Mustafa, Farhat; Rafiq, Danish; Makhdoomi, Rumana; Chanda, Nassima

    2015-01-01

    Synovial sarcomas are rare tumors accounting for approximately 5-10% of soft tissue sarcomas. They occur predominantly in the extremities, followed by head and neck. Primary pulmonary sarcomas are very rare and comprise only 0.5% of all primary lung malignancies. The diagnosis is established only after sarcomas like primary lung malignancies, and metastatic sarcomas have been excluded. For synovial sarcomas that arise at unusual locations, a definitive diagnosis is challenging and requires the use of ancillary diagnostic procedures such as immunohistochemistry (IHC) and molecular genetic techniques for confirmation of diagnosis. We report a case of 29-year-old male who had right lower lobe lung mass. He underwent right lower lobectomy. Intraoperative squash smears revealed spindle cell sarcoma. Subsequent histopathology and IHC confirmed the diagnosis as synovial sarcoma. We report this case on account of its rarity and to emphasize the utility of intraoperative squash smears in the diagnosis of such cases, which has been under-utilized in clinical practice. PMID:25948950

  4. Melanoma and soft tissue sarcoma in seven patients.

    PubMed

    Garber, J E; Liepman, M K; Gelles, E J; Corson, J M; Antman, K H

    1990-12-01

    Seven patients with both melanoma and sarcoma were seen at the Dana Farber Cancer Institute (Boston, MA) over a 4-year period. Three had additional malignant neoplasms; one of these patients also had the hereditary cutaneous malignant melanoma, dysplastic nevus syndrome. These observations suggest the possibility of a biologic relationship between melanoma and sarcoma, the nature of which remains unknown. PMID:2245401

  5. Significance of Circulating Tumor Cells in Soft Tissue Sarcoma

    PubMed Central

    Nicolazzo, Chiara; Gradilone, Angela

    2015-01-01

    Circulating tumor cells can be detected from the peripheral blood of cancer patients. Their prognostic value has been established in the last 10 years for metastatic colorectal, breast, and prostate cancer. On the contrary their presence in patients affected by sarcomas has been poorly investigated. The discovery of EpCAM mRNA expression in different sarcoma cell lines and in a small cohort of metastatic sarcoma patients supports further investigations on these rare tumors to deepen the importance of CTC isolation. Although it is not clear whether EpCAM expression might be originally present on tumor sarcoma cells or acquired during the mesenchymal-epithelial transition, the discovery of EpCAM on circulating sarcoma cells opens a new scenario in CTC detection in patients affected by a rare mesenchymal tumor. PMID:26167450

  6. Rearrangement of the p53 gene in human osteogenic sarcomas.

    PubMed Central

    Masuda, H; Miller, C; Koeffler, H P; Battifora, H; Cline, M J

    1987-01-01

    p53 is a 53-kDa nuclear protein that is associated with malignant transformation in several tumor model systems. In a survey of 134 human carcinomas, sarcomas, leukemias, and lymphomas obtained at surgery or from peripheral blood, we found rearrangements of the p53 gene only in osteogenic sarcomas (3 of 6 osteogenic sarcomas examined). Normal tissue from one of these patients had an unrearranged gene, indicating that the genetic abnormality in the tumor was acquired. Two of the sarcomas with rearranged genes expressed levels of p53 protein that were elevated relative to other tumors. Rearranged p53 genes were also found in human osteogenic sarcoma cell lines. Images PMID:2823272

  7. Synovial Sarcoma of the Buccal Mucosa: A Rare Case Report

    PubMed Central

    Mahesh, Kumar T. S.; Ponnuswamy, Indira Annamalai; David, Maria Priscilla; Shivhare, Peeyush; Puttaranganayak, Mahalakshmi Ikkanur; Sinha, Pooja

    2013-01-01

    Synovial sarcoma (SS) is a rare malignant neoplasm that arises most commonly in joint capsules and articular tendons, but its relationship to the synovium is not always obvious. Synovial sarcoma is a malignant soft tissue tumor representing 5.6% to 10% of all soft tissue sarcomas. They are termed SS because of their histologic resemblance to the synovium, but they rarely involve a synovial structure and are thought to arise from pluripotential mesenchymal cells. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the para-articular regions of the extremities, with approximately 9% occurring in the head and neck region. Synovial sarcoma has been reported rarely in the oral cavity. We report a very rare case of Synovial sarcoma of the buccal mucosa in a 24-year-old male patient. PMID:23762651

  8. [Incidence of malignant soft tissue tumors (sarcomas) after previous radiotherapy].

    PubMed

    Hernandez-Richter, T; Heiss, M M; Bubb, C; Jauch, K W

    1996-01-01

    The causal agent for sarcomas is mostly unknown. Unlike solid epithelial carcinomas, the correlation to the exposition to carcinogenic agents is unknown. Besides hereditary neurofibromatosis ("Recklinghausen"), radiation therapy has been reported to induce malignant tumors. In this retrospective study during the last 10 years we observed that in 7 of 356 (approximately 2%) patients treated for sarcomas in our Department of Surgery, the sarcoma was located in the area where radiation therapy had been given earlier for another primary malignant tumor. The interval between this radiation therapy and the diagnosis of sarcoma was 9 to 30 years, corroborated by findings in the literature based on approximately 100 radiation-induced tumors. The median survival time after diagnosis of sarcoma was 3 years. Because radiation therapy is often used in the treatment of malignant tumors this late complication is a clinically relevant problem in long-time survival. PMID:9064470

  9. Assessing the usefulness of prostaglandin E2 (Cervidil) fortranscervical artificial insemination in ewes.

    PubMed

    Bartlewski, Pawel M; Candappa, Ivanka B R

    2015-12-01

    The underlying theme of this study involved the evaluation of the dilatory effects of prostaglandin E2 on the ovine cervix and thus the assessment of its potential applicability to transcervical artificial insemination (TCAI) in ewes. A novel method of prostaglandin E2 administration (controlled slow-release vaginal inserts) was examined, and the practical implications of this approach including cervical penetrability and posttreatment pregnancy rates were evaluated. The Guelph method of TCAI was performed during the seasonal anestrus (n=40) and the breeding season (n=40) on multiparous Rideau Arcott Polled Dorset ewes, with or without the pretreatment with Cervidil (for a duration of 12hours or 24hours before TCAI). Cervical penetration rates averaged 82.5% (66 of 80), and they varied neither (P>0.05) between the two seasons nor between Cervidil-treated ewes and their respective controls. Cervidil priming significantly reduced the total time required for TCAI during the breeding season in comparison with controls (54 vs. 98 seconds), especially after the 24-hour exposure (38 vs. 108 seconds). The time taken to traverse the uterine cervix was negatively correlated (P<0.05) with the breed (percentage of Rideau Arcott genotype) and lifetime lamb production in seasonally anestrous ewes. Four out of 36 (11%) successfully penetrated ewes in the breeding season (three ewes allocated to the 12-hour control group and one ewe that had received Cervidil for 12hours) became pregnant and carried the lambs to term. Vaginal mucus impedance at TCAI was significantly and positively correlated with the total time required to complete the procedure in cyclic ewes, and the negative correlation between vaginal mucus impedance and total time values at the time of controlled intravaginal drug release device removal approached to significance in anestrous ewes. The present results indicate a moderate benefit of using Cervidil for inducing cervical dilation before TCAI in ewes, mainly in the breeding season. The specific reason(s) for impaired fertility after the TCAI using frozen-thawed ram semen remains to be elucidated. PMID:26349412

  10. Endocrine and reproductive function in ewes exposed to the organochlorine pesticides lindane or pentachlorophenol.

    PubMed

    Beard, A P; Bartlewski, P M; Rawlings, N C

    1999-01-01

    The effects of lindane (LIN, gamma-hexachlorocyclohexane) and pentachlorophenol (PCP) on reproduction and general endocrine function were examined in breeding ewes as a model for wild and domestic ungulates, which may be exposed to low levels of pesticides that are potential endocrine-disrupting chemicals. Ewes (n = 13/group) were fed either a control untreated diet (CON), or a diet treated with LIN (1 mg/kg/d) or PCP (1 mg/kg/d) during the 5 wk prior to mating and throughout pregnancy and lactation. Mating response, ovulation rate, follicle and corpus luteum size, gestation length, pregnancy rate, lambing rate, and lamb birth weight were recorded. After weaning, 6 ewes from each group were bled at 15-min intervals for 8 h during the day and night and for 1 h before and 5 h after i.v. administration of gonadotropin-releasing hormone, thyroid-stimulating hormone (TSH), and adrenocorticotropin, to measure serum concentrations of luteinizing hormone, follicle-stimulating hormone, thyroxine (T4), and cortisol. Ewes were then killed and endocrine tissues examined histologically. Pregnancy rate as a result of matings taking place at the synchronized estrus was significantly decreased by the lindane treatment However, PCP and lindane did not markedly affect any other aspect of reproductive function studied. In PCP-treated ewes, serum concentrations of T4 were significantly reduced compared to control ewes during the day and night; however, the T4 response to TSH was not altered by PCP treatment. No other measured endocrine parameters were consistently affected by lindane or PCP. Thyroid follicle size was significantly increased in the LIN and PCP ewes compared to the control ewes. Low serum concentrations of T4 in the PCP ewes may have resulted in increased TSH secretion and increased thyroid follicle size. In conclusion, although pesticide treatments had no serious adverse effects on reproductive function in breeding ewes, PCP reduced T4 concentration, which in the long term could influence reproductive and general performance. PMID:9923752

  11. Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors

    ClinicalTrials.gov

    2015-10-28

    Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Rhabdoid Tumor; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Germ Cell Tumors; Ewings Sarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma; Osteosarcoma; Rhabdomyosarcoma

  12. [SURGERY FOR SARCOMA OF THE PULMONARY ARTERY].

    PubMed

    Parshin, V D; Motus, I Ya; Belov, Yu V; Chernyavsky, A M; Neretin, A V; Rusinov, V V

    2015-01-01

    Sarcoma of the pulmonary artery is a rare tumor. At present the literature describes single cases. However the number of publications increases in recent time due to improved diagnostics. There are appeared papers, which provide a series of observations of surgical treatment for this kind of tumor exceeded more than 10 cases. It can be assumed that today the number of these cases in the literature contains several hundreds. Thus despite the rarity of this tumor there is a certain understanding of the clinical picture of this disease and treatment that we tried to do in this paper being studied the available literature and bringing four of our observation. PMID:26242161

  13. Undifferentiated pleiomorphic sarcoma simultaneously occuring with thymoma

    PubMed Central

    Tsolakis, Nikolaos

    2014-01-01

    We report here a case of thymoma simultaneously associated with neuroendocrine tumor. A 65-year-old male, presented with cough. Radiographic studies showed a mediastinal mass. On fine needle aspiration cytology and histopathological examination, a diagnosis of thymoma with coexisting undifferentiated pleomorphic sarcoma was made. Although thymoma is associated with many extrathymic malignancies, its association with neuroendocrine tumor is rare. This case is being reported on to reinforce that clinicians should bear in mind the possibility of extrathymic malignancies in patients with thymoma. PMID:25276394

  14. Epithelioid sarcoma resembling benign fibrous histiocytoma.

    PubMed

    Lynch, Michael C; Graber, Emmy M; Johnson, T Shane; Clarke, Loren E

    2015-02-01

    Epithelioid sarcoma (ES) is a rare malignancy notorious for its tendency to histologically mimic granuloma annulare and other palisading granulomatous processes. We report a case of ES on the right hand of a 23-year-old man that histopathologically resembled a benign fibrous histiocytoma. Superficial portions of the tumor were well differentiated, exhibiting spindled and ovoid cells with scant cytoplasm that surrounded sclerotic collagen bundles. More obvious atypia including greater cellularity, nuclear pleomorphism, and mitotic activity were mostly confined to the deep-seated regions of the tumor. In addition to palisading granulomatous processes, ES can mimic benign fibrous histiocytoma, and the superficial portions of ES may appear deceptively benign. PMID:25750961

  15. Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2016-03-10

    Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

  16. ChildSeq-RNA: A next-generation sequencing-based diagnostic assay to identify known fusion transcripts in childhood sarcomas.

    PubMed

    Qadir, Mohammed A; Zhan, Shing H; Kwok, Brian; Bruestle, Jeremy; Drees, Becky; Popescu, Oana-Eugenia; Sorensen, Poul H

    2014-05-01

    Childhood sarcomas can be extremely difficult to accurately diagnose on the basis of morphological characteristics alone. Ancillary methods, such as RT-PCR or fluorescence in situ hybridization, to detect pathognomonic gene fusions can help to distinguish these tumors. Two major deficiencies of these assays are their inability to identify gene fusions at nucleotide resolution or to detect multiple gene fusions simultaneously. We developed a next-generation sequencing-based assay designated ChildSeq-RNA that uses the Ion Torrent platform to screen for EWSR1-FLI1 and EWSR1-ERG, PAX3-FOXO1 and PAX7-FOXO1, EWSR1-WT1, and ETV6-NTRK3 fusions of Ewing sarcoma (ES), alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, and congenital fibrosarcoma, respectively. To rapidly analyze resulting data, we codeveloped a bioinformatics tool, termed ChildDecode, that operates on a scalable, cloud-computing platform. Total RNA from four ES cell lines plus 33 clinical samples representing ES, alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, and congenital fibrosarcoma tumors was subjected to ChildSeq-RNA. This accurately identified corresponding gene fusions in each tumor type, with no examples of false positive fusion detection in this proof-of-concept study. Comparison with previous RT-PCR findings demonstrated high sensitivity (96.4%; 95% CI, 82.3%-99.4%) and specificity (100%; 95% CI, 56.6%-100%) of ChildSeq-RNA to detect gene fusions. Herein, we propose ChildSeq-RNA as a novel tool to detect gene fusions in childhood sarcomas at single-nucleotide resolution. PMID:24517889

  17. Transcervical artificial insemination of Australian Merino ewes with frozen-thawed semen.

    PubMed

    Windsor, D P; Szll, A Z; Buschbeck, C; Edward, A Y; Milton, J T; Buckrell, B C

    1994-01-01

    We compared conventional methods for laparoscopic and cervical artificial insemination (AI) to a transcervical AI procedure (Guelph System for Transcervical AI; GST-AI) for use with frozen semen in Merino ewes. The GST-AI procedure was performed by an experienced operator in Experiment 1 (771 ewes) and by 2 inexperienced operators in Experiment 2 (555 ewes). In Experiment 1, intrauterine insemination by GST-AI was achieved in 76% of the ewes. The pregnancy rate at Day 70 for ewes inseminated by laparoscopy (48%, 120 251 ) was higher (P<0.01) than for ewes inseminated by either intrauterine GST-AI (32%, 64 201 ) or cervical AI (9%, 24 256 ). The overall (intrauterine and intracervical) pregnancy rate for GST-AI was 26% (68 264 ) and was unaffected by depth of insemination within the cervix. Pregnancy rates were unaffected by ram or day of insemination. In Experiment 2, the operators achieved intrauterine inseminations by GST-AI in 43% (78 182 ) of the ewes, with a significant operator effect (P<0.01) on depth of cervical penetration. The pregnancy rate to intrauterine GST-AI (40%, 31 78 ) did not differ from that to laparoscopic insemination. The total pregnancy rate for GST-AI in Experiment 2 (19%, 34 182 ) was lower (P<0.05) than that for laparoscopic AI (39%, 72 187 ) but superior (P<0.05) to that for cervical AI (1%, 1 186 ). The GST-AI pregnancy rates were affected by depth of AI (P<0.01) and by operator (P<0.05). It is concluded that GST-AI is superior to cervical AI, and may have application in Merinos if cervical penetration rates can be improved. PMID:16727521

  18. Short-term nutritional treatments grazing legumes or feeding concentrates increase prolificacy in Corriedale ewes.

    PubMed

    Violes, C; Meikle, A; Martin, G B

    2009-07-01

    We tested whether short periods of increased nutrition will improve ovulation rate and prolificacy, irrespective of the method used to synchronise the cycles of the ewes. In Experiment 1, we used 138 Corriedale ewes to evaluate two factors: synchronization treatment (sponges versus a single injection of prostaglandin) and type of pasture (native versus improved with Lotus corniculatus). Ewes were mated at the end of the grazing period and prolificacy was evaluated at lambing. Grazing Lotus corniculatus for 12 days tended to increase the number of twin lambs born (P=0.09). The percentage of ewes showing oestrus during a 9-day period was similar among synchronization treatments. Animals in Experiments 2 (n=282) and 3 (n=288) were allocated to a control group or a group fed a supplement of corn grain and soybean meal for 7 days. Ewes received 2 prostaglandin injections and the supplement was fed from Days 11 to 17 after the second prostaglandin. Ovulation rate was measured in 65 (Experiment 2) and 61 (Experiment 3) ewes that were confirmed to have consumed the supplement and showed oestrus in a 4-day period. The supplement increased ovulation rate by 14% in both experiments (P<0.05). We conclude that Corriedale ewes can respond with increases in prolificacy to a 12-day period grazing Lotus corniculatus and in ovulation rate to 7 days feeding with a supplement rich in energy and protein. Moreover, in these studies, prostaglandin was as effective as sponges for synchronising oestrus, an important factor in future decisions about hormonal management of fertility. PMID:18639397

  19. Primary Synovial Sarcoma of the Pharynx: A Series of Five Cases and Literature Review.

    PubMed

    Fatima, Syeda Samia; Din, Nasir Ud; Ahmad, Zubair

    2015-12-01

    Synovial sarcoma comprises approximately 10% of all soft tissue sarcomas. Although synovial sarcoma has been reported in practically every organ, the extremities are the commonest site of occurrence followed by the head and neck. Primary synovial sarcoma of the pharynx is rare and only case reports have been published. We report a series of five cases of primary synovial sarcoma involving the pharynx. PMID:26022274

  20. RELATIVE RESISTANCE OF DORPER CROSSBRED EWES IN GASTRO-INTESTINAL NEMATODE INFECTION COMPARED WITH ST. CROIX AND KATAHDIN EWES IN THE SOUTHEASTERN UNITED STATES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to evaluate relative resistance of Dorper crossbred (DO), Katahdin (KA), St. Croix (SC), and Hampshire (HA) ewes to natural and experimental gastro-intestinal (GI) nematode infection over a 20 month period. The objective of Experiment 1 was to evaluate breeds for resistance to...

  1. Kaposi sarcoma incidence in Mozambique: national and regional estimates.

    PubMed

    Meireles, Paula; Albuquerque, Gabriela; Vieira, Mariana; Foia, Severiano; Ferro, Josefo; Carrilho, Carla; Lunet, Nuno

    2015-11-01

    Kaposi sarcoma is expressed in four clinical variants, all associated with human herpes virus type 8 infection, namely, classic, endemic, immunosuppression-related and AIDS-related. The latter currently accounts for most of the burden of Kaposi sarcoma in sub-Saharan Africa, reflecting the frequency of HIV infection and its management. We aimed to estimate the incidence of Kaposi sarcoma in Mozambique and in its provinces. We estimated the number of incident cases of Kaposi sarcoma by adding up the expected number of endemic and AIDS-related cases. The former were estimated from the rates observed in Kyandondo, Uganda (1960-1971). The latter were computed from the number of AIDS-related deaths in each region, assuming that the ratio between the AIDS-related Kaposi sarcoma incident cases and the number of AIDS-related deaths observed in the city of Beira applies to all regions. A total of 3862 Kaposi sarcoma cases were estimated to have occurred in Mozambique in 2007, mostly AIDS-related, in the age group 25-49 years, and in provinces from South/Centre. The age-standardized incidence rates were 36.1/100?000 in men and 11.5/100?000 in women, with a more than three-fold variation across provinces. We estimated a high incidence of Kaposi sarcoma in Mozambique, along with large regional differences. These results can be used to improve disease management and to sustain political decisions on health policies. PMID:25494288

  2. The biology of uterine sarcomas: A review and update

    PubMed Central

    KOBAYASHI, HIROSHI; UEKURI, CHIAKI; AKASAKA, JURIA; ITO, FUMINORI; SHIGEMITSU, AIKO; KOIKE, NATSUKI; SHIGETOMI, HIROSHI

    2013-01-01

    Uterine sarcoma is a rare neoplasm, accounting for only 5% of uterine malignancies. The pathogenesis of uterine sarcoma remains largely unknown, although recent basic science and pre-clinical animal models have provided a better understanding of tumor biology. The aim of this study was to review the clinical features, imaging characteristics, genetic aberrations and therapeutic approaches in uterine sarcoma. This study reviewed the English-language literature on clinical and basic studies on uterine sarcoma. The common variants of uterine sarcoma are carcinosarcoma, leiomyosarcoma and endometrial stromal sarcoma (ESS). Genetic profiling efforts have identified amplification, overexpression and mutation, while the molecular mechanisms of tumorigenesis driven by these genomic and genetic aberrations have yet to be fully elucidated yet. Recent genome-wide studies have also identified complex chromosomal rearrangements as oncogenic mechanisms. The cell cycle regulators, p16 and p53, are frequently over-expressed and appear to be involved in key modifications of sarcomagenesis. Molecular-targeted therapy has now been evaluated in clinical trials for certain subtypes. In conclusion, aberrations of cell cycle control would be a critical step in the development of uterine sarcoma. This review has provided new areas of study targeting molecular and genetic pathways. PMID:24649216

  3. Quantitative morphology in canine cutaneous soft tissue sarcomas.

    PubMed

    Simeonov, R; Ananiev, J; Gulubova, M

    2015-12-01

    Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n?=?8), liposarcoma (n?=?8) and haemangiopericytoma (n?=?8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n?=?12) and dermal fibrosis (n?=?12)] were analysed by computer-assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; m(2) ), mean nuclear perimeter (MNP; m), mean nuclear diameter (MND mean; m), minimum nuclear diameter (Dmin ; m) and maximum nuclear diameter (Dmax ; m). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for Dmax ) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour-like fibrous lesions in dogs. PMID:24890665

  4. Advances in the diagnosis and management of sarcomas.

    PubMed

    Elias, A D

    1992-08-01

    Cytogenetic alterations that characterize different histologic subtypes of soft tissue sarcomas have been identified. In a few situations, more precise chromosomal mapping has allowed identification of certain genes that may be involved in the development or tumor progression of sarcomas. Careful family histories must be elicited in sarcoma patients. While "cancer families" are rarely identified when screening close relatives of sarcoma patients, the discovery of the currently known tumor suppressor gene syndromes associated with germ line retinoblastoma gene and p53 gene defects were made possible by their association with sarcomas. Optimal management of primary sarcomas includes function-sparing complete resection and radiotherapy. Innovative radiotherapy, utilizing radiation sensitizers or brachytherapy, may increase local control in patients with unresectable tumors. New drugs are needed. Epirubicin and other anthracycline analogues do have significant activity; however, no other novel drugs have documented efficacy. Dose intensity is being explored with sarcoma trials providing the "vehicle" to evaluate new cytokines. Several mechanisms of doxorubicin resistance have been identified in cell lines and fresh tumors, including alterations in glutathione peroxidase activity and MDR-1 gene expression. These observations need to be taken to the clinic. PMID:1511024

  5. A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes

    PubMed Central

    Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

    2015-01-01

    Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST. PMID:26839509

  6. Metachronous Bilateral Extremity Soft Tissue Sarcomas.

    PubMed

    Nowrasteh, Ghodratollah; Aziz, Tanim; Al Assas, Mohammed; Al Nuaimi, Lateefa; Marzouqi, Saeeda; Quadri, Asif A M; Alrawi, Sadir

    2016-01-01

    BACKGROUND Soft tissue sarcomas (STS) account for approximately 1% of adult malignancies, with 50 to 60% occurring in the extremities. Liposarcoma is the most common type of STS and represent about 20% of total adult sarcomas. There are rare syndromes associated with increased risk of developing STS. Further, chemical compounds such as chlorinated phenols and a few chemotherapeutic drugs have been linked to STS, along with ionizing radiation. Nevertheless, the etiology is uncertain for most of these lesions. CASE REPORT This report details 2 cases of metachronous bilateral STS of the lower extremities. The first of these presented as a local recurrence of a previously resected right thigh liposarcoma and a new liposarcoma in the left thigh. As mentioned above, among the different subtypes of STS, liposarcoma has the highest tendency for multifocality. The second patient had multifocal metachronous leiomyosarcoma with lung metastases occurring simultaneously with the second presentation. Leiomyosarcoma is another subtype reported to present with multifocal disease. CONCLUSIONS Despite the rarity of bilateral lesions, their occurrence should not be overlooked in the initial diagnosis and follow-up of the initially detected tumor. Early detection can affect patient survival because their presence predicts unfavorable outcomes. PMID:26744032

  7. [Alveolar soft part sarcoma in pediatric patients].

    PubMed

    Paillard, Catherine; Coulomb, Aurore; Helfre, Sylvie; Orbach, Daniel

    2015-09-01

    Alveolar soft part sarcoma, ASPS, is a rare malignant tumor, with preferential primary localization in limbs, usually occurring in adolescents and young adults. This sarcoma, well defined histologically and at molecular level, has an indolent course, but a high potential metastatic pulmonary and cerebral evolution, sometimes late. ASPS is characterized by an almost specific translocation t(X, 17)(p11;25) which creates a fusion protein, APSL-TFE3, acting as an aberrant transcription factor. An in-bloc resection of the primary tumor is the treatment of choice in cases of localized disease. Conventional chemotherapy is generally ineffective. The role of radiotherapy is discussed in case of micro- or macroscopical incomplete residue. It seems to reduce local recurrence, but did not influence overall survival. The 5 years survival rate in children, adolescents and young adults is close to 80% in case of localized disease but poorer in presence of metastases. Recently, systemic anti-tumoral treatments have been focused on the use of targeted therapies. Anti-angiogenic drugs and tyrosine kinase inhibitors are the most promising approaches, but require further study. Prognostic risk factors in the literature are age (>10Y), tumor size (>5cm) and presence of metastases. This article reviews the clinical manifestations, diagnosis modalities, radiographic characteristics and therapeutic strategy of this disease in the pediatric population. PMID:26235420

  8. Systemic Therapy for Advanced Soft Tissue Sarcomas

    PubMed Central

    Riedel, Richard F

    2012-01-01

    Soft tissue sarcomas (STS) are a rare, heterogeneous group of solid tumors in need of improved therapeutic options. First-line chemotherapy is considered the current standard of care for patients with advanced, symptomatic STS, but the median survival is only 8 to 12 months. Efforts to increase response rates by using combination or dose-dense regimens have largely failed to improve patient outcomes. However, increasing evidence supports the use of specific treatments for certain histological subtypes of STS, and novel therapies, including tyrosine kinase and mammalian target of rapamycin inhibitors, are currently under active investigation. In addition, novel treatment approaches (such as maintenance therapy) designed to prolong the duration of response to chemotherapy and delay disease progression are being explored. This article provides an overview of current systemic therapies for patients with advanced STS and discusses ongoing efforts designed to improve patient outcomes through the use of novel therapeutic agents and treatment strategies. Cancer 2011;. 2011 American Cancer Society. Soft tissue sarcomas (STS) are a rare, heterogeneous group of solid tumors in need of improved therapeutic options. This article provides an overview of current systemic therapies for patients with advanced STS and discusses ongoing efforts designed to improve patient outcomes through the use of novel therapeutic agents and treatment strategies. PMID:21837668

  9. Multidisciplinary Management of Soft Tissue Sarcoma

    PubMed Central

    Nystrom, Lukas M.; Reimer, Nickolas B.; Reith, John D.; Dang, Long; Zlotecki, Robert A.; Scarborough, Mark T.; Gibbs, C. Parker

    2013-01-01

    Soft tissue sarcoma is a rare malignancy, with approximately 11,000 cases per year encountered in the United States. It is primarily encountered in adults but can affect patients of any age. There are many histologic subtypes and the malignancy can be low or high grade. Appropriate staging work up includes a physical exam, advanced imaging, and a carefully planned biopsy. This information is then used to guide the discussion of definitive treatment of the tumor which typically involves surgical resection with a negative margin in addition to neoadjuvant or adjuvant external beam radiation. Advances in imaging and radiation therapy have made limb salvage surgery the standard of care, with local control rates greater than 90% in most modern series. Currently, the role of chemotherapy is not well defined and this treatment is typically reserved for patients with metastatic or recurrent disease and for certain histologic subtypes. The goal of this paper is to review the current state of the art in multidisciplinary management of soft tissue sarcoma. PMID:23983648

  10. Estrus response and fertility of Menz and crossbred ewes to single prostaglandin injection protocol.

    PubMed

    Mekuriaw, Zeleke; Assefa, Habtemariam; Tegegne, Azage; Muluneh, Dagne

    2016-01-01

    Natural lambing in sheep in Ethiopia occurs throughout the year in a scattered manner negatively affecting survival and growth rates of the lambs born during the unfavorable season of the year. Thus, controlling the time of mating artificially using exogenous source of hormones is considered as one of the ways to mitigated problems related to haphazard lambing. To this end, an experiment was conducted to evaluate efficacy of prostaglandin-based estrus synchronization protocol in local and crossbred ewes. A total of 160 ewes (80 local and 80 crossbreds) which lambed at least once and aged 3-5years were used. Lutalyse (dinoprost tromethamine sterile solution equivalent to 5mg dinoprost per ml) and its analog, Synchromate (cloprostenol sodium equivalent to 0.250mg cloprostenol per ml), were tested at different doses. The treatments used were intramuscular injection of (1) 2.50ml of Lutalyse (12.5mg dinoprost tromethamine), (2) 2ml of Lutalyse (10.0mg dinoprost tromethamine), (3) 1ml of Synchromate (0.25mg of cloprostenol Sodium), and (4) 0.8ml of Synchromate (0.20mg of cloprostenol Sodium). Forty ewes (20 local and 20 crossbreds) were allocated per treatment. Following injection of the respective hormones, rams of known fertility were introduced into the flock for the duration of 96h at the ratio of one ram to 10 ewes. All estrus synchronization protocols except treatment 4 (0.8ml of Synchromate) induced estrus (heat) in majority (55-65%) of local and crossbred ewes within 96h post-hormone injection. The time interval from hormone administration to onset of estrus was also more or less similar for all treatment groups except for treatment group 4 which showed heat quicker. The highest lambing rate was recorded in local ewes (84.62% (11/13) treated with 2.5ml of Lutalyse, whereas the least was obtained in crossbreds (33.33% (3/9) treated with 0.8ml Synchromate. In conclusion, even though 2.5ml and 2ml of Lutalyse or 1ml of Synchromate were able to induce heat in majority of local and crossbred ewes, the highest lambing percentage was obtained from ewes treated with 2.5ml of Lutalyse. Therefore, the use of 2.5ml Lutalyse is recommended to synchronize estrus in local and crossbred ewes under Ethiopian smallholder sheep production system for the benefit of improved lambing rate. PMID:26439244

  11. Effect of prostaglandin E2 on cervical compliance in pregnant ewes.

    PubMed

    Stys, S J; Dresser, B L; Otte, T E; Clark, K E

    1981-06-15

    Cervical compliance increases dramatically at parturition in sheep independent of uterine activity. Recently, in vitro production of prostaglandin E2 (PGE2) by the cervix has been shown to increase at parturition. This study investigated the effects of PGE2 on cervical compliance and uterine blood flow in pregnant ewes. Eight animals were chronically instrumented with pressure balloons within the cervical os and amniotic cavity, an electromagnetic flow probe on a uterine artery, and catheters in the maternal cervical os, femoral artery, femoral, uterine, and cervical veins, and fetal hindlimb vein. PGE2 (10 mg) was administered in a water-soluble gel into the cervical os every 4 hours times three doses at least 5 days after surgical preparation (124 to 142 days' gestation). In all eight ewes, cervical compliance increased within 8 to 12 posttreatment hours to levels comparable to that seen at spontaneous parturition. Five of the ewes did not progress into labor; compliance in these ewes returned to baseline 24 to 72 hours after the peak. Uterine blood flow was measured in five ewes during the PGE2 treatment and demonstrated no significant alterations. Maternal cardiovascular and fetal respiratory parameters were monitored throughout the experiment and remained stable. The present data suggest that PGE2 may be an important regulatory of the biochemical and physical changes which occur in the cervix at parturition. PMID:7246656

  12. Population subdivision among desert bighorn sheep (Ovis canadensis) ewes revealed by mitochondrial DNA analysis.

    PubMed

    Boyce, W M; Ramey, R R; Rodwell, T C; Rubin, E S; Singer, R S

    1999-01-01

    We used behavioural observations and mitochondrial DNA (mtDNA) sequence analysis to examine demographic and genetic structure within and among home-range groups of desert bighorn sheep (Ovis canadensis) ewes in the Peninsular Ranges of southern California, USA. We identified substantial genetic variation in the first 515 bp of the mtDNA control region and determined that seven haplotypes were distributed in a nonrandom fashion among these ewe subpopulations. Although a significant (P < 0.01) amount of mtDNA variation (33%) was partitioned among home-range groups, we did not find strong evidence for matrilineal substructuring within these groups. Based on analyses of molecular variance, and comparisons of behavioural associations and distances between centres of activity, we concluded that within a given home-range group, bighorn sheep ewes generally associate with other ewes based on their availability rather than their matrilineal relationships. Our results also supported the conclusion that multiple ewe subpopulations exist within the Peninsular Ranges, and that these subpopulations are the most basic demographic and genetic units. PMID:9919700

  13. Biological Extremity Reconstruction after Sarcoma Resection: Past, Present, and Future

    PubMed Central

    Holzer, Lukas A.; Leithner, Andreas

    2013-01-01

    In sarcoma surgery besides a wide local resection, limb salvage became more and more important. Reconstruction of bone and soft tissue defects after sarcoma resection poses a major challenge for surgeons. Nowadays a broad range of reconstructive methods exist to deal with bony defects. Among these are prostheses, bone autografts, or bone allografts. Furthermore a variety of plastic reconstructive techniques exist that allow soft tissue reconstruction or coverage after sarcoma resection. Here we discuss the historical highlights, the present role, and possible future options for biological reconstruction. PMID:23840167

  14. Advances in sarcoma genomics and new therapeutic targets

    PubMed Central

    Taylor, Barry S.; Barretina, Jordi; Maki, Robert G.; Antonescu, Cristina R.; Singer, Samuel; Ladanyi, Marc

    2012-01-01

    Preface Increasingly, human mesenchymal malignancies are classified by the abnormalities that drive their pathogenesis. While many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities and in many cases are resistant to adjuvant therapies. In this Review, we discuss the core molecular determinants of sarcomagenesis and emphasize the emerging genomic and functional genetic approaches that, coupled to novel therapeutic strategies, have the potential to transform the care of patients with sarcoma. PMID:21753790

  15. A rare case of myeloid sarcoma presenting as anal fissure

    PubMed Central

    VECCHIO, R.; INTAGLIATA, E.; FIUMARA, P.F.; VILLARI, L.; MARCHESE, S.; CACCIOLA, E.

    2015-01-01

    Myeloid sarcoma is a tumor composed of myeloblasts occurring at an extramedullary site. It may develop in patients with acute myeloid leukemia, myeloproliferative or myelodysplastic syndrome, sometimes preceding onset of the systemic disease. Frequent sites of myeloid sarcoma are bones or various soft tissues. Gastrointestinal involvement is very rare. We report a unique case of myeloid sarcoma presenting as a painful anal fissure, in a patient with a history of acute myeloid leukemia. The diagnosis was achieved by a surgical excisional biopsy and immunoistochemical staining. PMID:26712260

  16. Pseudo-Kaposi sarcoma (acroangiodermatitis): occurring after bullous erysipelas.

    PubMed

    Kutlubay, Zekayi; Yardimci, Gürkan; Engin, Burhan; Demirkesen, Cuyan; Aydin, Övgü; Khatib, Rashid; Tuzun, Yalçın

    2015-05-01

    Pseudo-Kaposi sarcoma is a benign reactive vascular proliferative disorder, which can be seen at any age. It occurs when the chronic venous pressure changes result in vascular proliferation in the upper and mid dermis. This disease is divided into two subtypes: the most frequent subtype is the Mali type and seen in early ages. The Mali type is seen in chronic venous insufficiency and in those patients with arteriovenous shunts. The rare subtype is the Stewart-Bluefarb type. This disease must be distinguished from Kaposi sarcoma because of their clinical resemblance. Herein, we present a patient with pseudo-Kaposi sarcoma, which developed after bullous erysipelas. PMID:26295854

  17. Follicular dendritic cell sarcoma of the neck with pulmonary metastases.

    PubMed

    Fareed, Muhammad Mohsin; Memon, Muhammad Ali; Rashid, Azhar; Furrukh, Muhammad; Ahmed, Shoaib; Ghouri, Abdul Rauf; Khan, Amjad; Asghar, Abdul Shaheed

    2011-09-01

    We present a case of follicular dendritic cell sarcoma in a 48 years old Saudi female who reported with slowly progressive right sided extranodal neck mass associated with pulmonary metastasis. Clinical examination, histopathologic features including distinct immunostains combine together to make the rare diagnosis of follicular dendritic cell sarcoma. This entity is often misdiagnosed due to non-consideration in differential diagnosis of sarcoma. It carries a significant potential for regional as well as distant spread and hence categorized as intermediate risk malignancy. Clinical, histopathological and immunohistochemical aspects and therapeutic options of this unusual case are discussed. PMID:21914416

  18. Electromagnetic Dissociation Cross Sections using Weisskopf-Ewing Theory

    NASA Technical Reports Server (NTRS)

    Adamczyk, Anne M.; Norbury, John W.

    2011-01-01

    It is important that accurate estimates of crew exposure to radiation are obtained for future long-term space missions. Presently, several space radiation transport codes exist to predict the radiation environment, all of which take as input particle interaction cross sections that describe the nuclear interactions between the particles and the shielding material. The space radiation transport code HZETRN uses the nuclear fragmentation model NUCFRG2 to calculate Electromagnetic Dissociation (EMD) cross sections. Currently, NUCFRG2 employs energy independent branching ratios to calculate these cross sections. Using Weisskopf-Ewing (WE) theory to calculate branching ratios, however, is more advantageous than the method currently employed in NUCFRG2. The WE theory can calculate not only neutron and proton emission, as in the energy independent branching ratio formalism used in NUCFRG2, but also deuteron, triton, helion, and alpha particle emission. These particles can contribute significantly to total exposure estimates. In this work, photonuclear cross sections are calculated using WE theory and the energy independent branching ratios used in NUCFRG2 and then compared to experimental data. It is found that the WE theory gives comparable, but mainly better agreement with data than the energy independent branching ratio. Furthermore, EMD cross sections for single neutron, proton, and alpha particle removal are calculated using WE theory and an energy independent branching ratio used in NUCFRG2 and compared to experimental data.

  19. Quantification of progesterone binding in mammary tissue of pregnant ewes

    SciTech Connect

    Smith, J.J.; Capuco, A.V.; Akers, R.M.

    1987-06-01

    Progestin-binding sites in mammary tissue from 14 prepartum, multiparous ewes at 50, 80, 115, and 140 d of gestation were demonstrated by the binding of (/sup 3/H) R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) to ovine mammary cytosol in the presence of sodium molybdate and excess cortisol. Homogenization extracted 89% of total mammary receptors (nuclear) into cytosol. Binding was specific for progestins and was of high affinity. The average dissociation constant for (/sup 3/H) R5020 specifically bound to receptors extracted into mammary cytosol was 1.9 (+/- .4) x 10/sup -9/ M (n = 14) and did not change significantly over the test period. However, binding capacities (fmol/mg cytosolic protein) differed according to stage of gestation with averages of 125 +/- 53, 149 +/- 26, 656 +/- 216, 57 +/- 22 at 50, 80, 115, and 140 d of pregnancy, respectively. Increased number of progestin-binding sites at 115 d of gestation (whether data are expressed per unit of tissue weight, DNA, or cytosolic protein) suggests that an increase per mammary epithelial cell may be necessary to produce the full lobuloalveolar proliferation observed at this stage of gestation.

  20. Maternal and fetal tissue selenium loads in nulliparous ewes fed supranutritional and excessive selenium during mid to late pregnancy.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives were to describe the effects of Se on fetal and maternal Se load when fed supranutritionally as Se-enriched wheat grain, and supranutritionally and excessively as sodium selenate to nulliparous pregnant ewes during pregnancy. Pregnant, whitefaced-cross, nulliparous ewes (n = 32; 45.6 ...