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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. 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

  3. 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

  4. 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 ...

  5. CENTER FOR SARCOMA AND BONE ONCOLOGY EWING'S SARCOMA

    E-print Network

    Liu, Xiaole Shirley

    CENTER FOR SARCOMA AND BONE ONCOLOGY EWING'S SARCOMA RESEARCH DESCRIPTION In 2011, the Center for Sarcoma and Bone Oncology, facilitated the translation of a laboratory finding detected by colleagues of George Demetri, MD, director of the Center for Sarcoma and Bone Oncology, at Massachusetts General

  6. 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

  7. 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

  8. Ewing Sarcoma: An Eponym Window to History

    PubMed Central

    Cripe, Timothy P.

    2011-01-01

    Ewing sarcoma was named after James R. Ewing, an eminent American pathologist at Cornell who described the first cases in 1921. Although he is best remembered for this singular achievement, Ewing's contributions to the study of cancer were far more profound and influential. He essentially launched oncology as a discipline with the publication of his seminal textbook and founded the major American cancer societies that exist today. His vision of comprehensive cancer centers still drives our research infrastructure. Since his initial report, these organizations have helped us achieve numerous milestones in understanding and treating patients with Ewing sarcoma. PMID:21151695

  9. Optimal Learning for Drug Discovery in Ewing's Sarcoma

    E-print Network

    Powell, Warren B.

    Optimal Learning for Drug Discovery in Ewing's Sarcoma Diana M. Negoescu Peter I. Frazier Faculty, 2009 Diana M. Negoescu, Peter I. Frazier Optimal Learning for Drug Discovery in Ewing's Sarcoma #12;Outline I. Ewing Sarcoma and Our Problem II. Modeling Structure-Value Relationships III. Correlated

  10. Optimal Learning for Drug Discovery in Ewing's Sarcoma Diana Negoescu

    E-print Network

    Powell, Warren B.

    Optimal Learning for Drug Discovery in Ewing's Sarcoma Diana Negoescu Peter Frazier Faculty, and demonstrate the method on a problem with 87120 alternatives. 1 Introduction Ewing's sarcoma is a pediatric@georgetown.edu 1 #12;Ewing's sarcoma. If successful as a drug, this compound would improve the patients

  11. 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

  12. MicroRNAs in Ewing Sarcoma

    PubMed Central

    Dylla, Layne; Moore, Colin; Jedlicka, Paul

    2013-01-01

    MicroRNAs (miRs) have emerged recently as important regulators of gene expression in the cell. Frequently dysregulated in cancer, miRs have shed new light on molecular mechanisms of oncogenesis, and have generated substantial interest as biomarkers, and novel therapeutic agents and targets. Recently, a number of studies have examined miR biology in Ewing sarcoma. Findings indicate that alterations in miR expression in Ewing Sarcoma are widespread, involve both EWS/Ets oncogenic fusion-dependent and independent mechanisms, and contribute to malignant phenotypes. miRs with prognostic potential have been identified, and several preclinical studies suggest that miR manipulation could be therapeutically useful in this aggressive disease. These and future studies of miR biology stand to expand our understanding of Ewing sarcoma pathogenesis, and may identify new biomarkers and treatment options. PMID:23543617

  13. Multiple primary Ewing’s sarcomas in cerebral cranium of a child: a case report and review of the literature

    PubMed Central

    Wang, Dawei; Guo, Zongze

    2015-01-01

    Ewing’s sarcoma is the second most common pediatric bone tumor. Primary Ewing’s 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 Ewing’s sarcomas associated with the cranial bones, the first pediatric case report to date. We also review 71 cases Ewing’s sarcoma involving intracranial extension. The purpose of this article is to provide data concerning the clinical and therapeutic course of multiple primary Ewing’s sarcomas in associated with cerebral cranium. PMID:26261672

  14. 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.

  15. 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

  16. 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

  17. Is There a Predisposition Gene for Ewing's Sarcoma?

    PubMed Central

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

    2010-01-01

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

  18. 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

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

    ClinicalTrials.gov

    2015-09-28

    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

  20. 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.

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

    E-print Network

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

    2015-10-27

    Ewing’s sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing’s sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being...

  2. Ewing Sarcoma in a Patient With Cowden Syndrome.

    PubMed

    Chandhanayingyong, Mod C; Bernthal, Nicholas M; Ungarreevittaya, Piti; Nelson, Scott D; Chawla, Sant P; Singh, Arun S

    2015-11-01

    A 47-year-old woman, initially diagnosed in 1996 with Cowden syndrome (CS), PTEN-mutant bilateral breast cancer, a thyroid nodule, and uterine fibroids, presented to UCLA in 2013 with Ewing sarcoma of the pelvic bone. Her treatment course included mastectomies, hysterectomy/oophorectomy, and total thyroid resection, and chemotherapy, radiation, and hemipelvectomy for Ewing sarcoma. This case report illustrates the unusual presentation of Ewing sarcoma in a patient with PTEN-mutant CS, the probable underlying molecular pathogenesis, long-term management, and therapeutic considerations. PMID:26553762

  3. Ewing’s Sarcoma: An Uncommon Breast Tumor

    PubMed Central

    Meddeb, Sawsen; Rhim, Mohamed Salah; Kouira, Mouna; Mestiri, Sarra; Bibi, Mohamed; Yacoubi, Mohamed Tahar

    2014-01-01

    Ewing’s sarcoma/primitive neuroectodermal tumors (EWS/PNET) are rare malignant and aggressive tumors, usually seen in the trunk and lower limbs of children and young adults. They are uncommon in the breast. We report a case of a 43-year-old woman who developed a painless breast mass. An initial core needle biopsy concluded to a fibrocystic dystrophy contrasting with a rapidly growing mass; thus a large lumpectomy was done. Diagnosis of primary PNET of the breast was established, based on both histopathological examination and immunohistochemical findings. Surgical margins were positive, therefore, left modified radical mastectomy with axillary lymph nodes dissection was performed. The patient was given 6 cycles of adjuvant chemotherapy containing cyclophosphamide, adriamycin and vincristine. Twenty months later, she is in life without recurrence or metastasis. EWS/PNET may impose a diagnostic challenge. Indeed, mammography and ultrasonography features are non specific. The histopathological pattern is variable depending on the degree of neuroectodermal differentiation. Immuno-phenotyping is necessary and genetic study is the only confirmatory tool of diagnosis showing a characteristic cytogenetic anomaly; t (11; 22) translocation. PMID:25332765

  4. Ewing’s 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

    Ewing’s sarcoma is a highly malignant bone tumor found in children and adolescents, and the origin of this malignancy is not well understood. Here, we introduced a Ewing’s sarcoma–associated genetic fusion of the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ) of long bones collected from late gestational murine embryos. EWS-ETS fusions efficiently induced Ewing’s sarcoma–like small round cell sarcoma formation by these cells. Analysis of the eSZ revealed a fraction of a precursor cells that express growth/differentiation factor 5 (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS-ETS–dependent tumor induction. Genes downstream of the EWS-ETS fusion protein were quite transcriptionally active in eSZ cells, especially in regions in which the chromatin structure of the ETS-responsive locus was open. Inhibition of ?-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewing’s sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewing’s sarcoma and provide clues to the histogenesis of Ewing’s sarcoma in bone. PMID:24911143

  5. 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

  6. 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

  7. Atypical Presentation of Ewing’s 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 Ewing’s 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 Ewing’s sarcoma involving the orbit, skeleton, bone marrow and lymph nodes. PMID:26568777

  8. 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

  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 Ewing’s Sarcoma of the Spine with Paraplegia: A Case Report

    PubMed Central

    Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-01-01

    Ewing’s sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing’s sarcoma in the spine is very rare. Ewing’s sarcoma occurring in the spine is divided into two types, Ewing’s sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing’s sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing’s sarcoma and patient was started on combination chemotherapy and radiotherapy. PMID:25954672

  11. Antibody detection of translocations in Ewing sarcoma

    PubMed Central

    Luo, Wen; Milash, Brett; Dalley, Brian; Smith, Richard; Zhou, Holly; Dutrow, Natalie; Cairns, Bradley R; Lessnick, Stephen L

    2012-01-01

    The detection of chromosomal translocations has important implications in the diagnosis, prognosis and treatment of patients with cancer. Current approaches to translocation detection have significant shortcomings, including limited sensitivity and/or specificity, and difficulty in application to formalin-fixed paraffin-embedded (FFPE) clinical samples. We developed a new approach called antibody detection of translocations (ADOT) that avoids the shortcomings of current techniques. ADOT combines a transcriptional microarray-based approach with a novel antibody-based detection method. ADOT allows for the accurate and sensitive identification of translocations and provides exon-level information about the fusion transcript. ADOT can detect translocations in poor-quality unprocessed total ribonucleic acid (RNA). Furthermore, the technique is readily generalizable to detect any potential fusion transcript, including previously undescribed fusions. We demonstrate the feasibility of ADOT by examples in which both known and unknown Ewing sarcoma translocations are identified from cell lines, tumour xenografts and FFPE primary tumours. These results demonstrate that ADOT may be an effective approach for translocation analysis in clinical specimens with significant RNA degradation and may offer a novel diagnostic tool for translocation-based cancers. PMID:22419563

  12. Copy Number Alterations and Methylation in Ewing's Sarcoma

    PubMed Central

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

    2011-01-01

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

  13. Targeting Glutathione S-transferase M4 in Ewing sarcoma.

    PubMed

    Zhuo, Rupeng; Kosak, Kenneth M; Sankar, Savita; Wiles, Elizabeth T; Sun, Ying; Zhang, Jianxing; Ayello, Janet; Prestwich, Glenn D; Shami, Paul J; Cairo, Mitchell S; Lessnick, Stephen L; Luo, Wen

    2014-01-01

    Ewing sarcoma is a malignant pediatric bone and soft tissue tumor. Although the 5-year survival rate of localized disease approaches 75%, the prognosis of metastatic and/or therapy-resistant disease remains dismal despite the wide use of aggressive therapeutic strategies. We previously reported that high expression of glutathione S-transferase M4 (GSTM4) in primary tumors correlates with poor patient outcomes. GSTM4 is required for oncogenic transformation and mediates resistance to chemotherapeutic drugs in Ewing sarcoma cells. Here, we performed RNA-sequencing analyses of Ewing sarcoma cells and combined our results with publicly available datasets to demonstrate that GSTM4 is a major GST specifically expressed in Ewing sarcoma. Pharmacological inhibition of GSTM4 activity using a pan GST inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), significantly limited cellular proliferation and oncogenic transformation of Ewing sarcoma cells. Moreover, combined use of NBDHEX and etoposide synergistically increased cytotoxicity, suggesting a role for GSTM4 as an inhibitor of apoptosis. Mechanistic studies revealed that GSTM4 limits apoptosis owing to its ability to interact with Apoptosis Signal-regulating Kinase 1 (ASK1) and inhibit signaling via the c-Jun N-terminal Kinase axis. To exploit our observation that GSTM4 expression is specifically up-regulated in Ewing sarcoma, we tested the effect of a GSTM4-activated anti-cancer agent, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K, on tumor growth and survival. We found that JS-K robustly decreased Ewing sarcoma cell viability and xenograft tumor growth and improved overall survival of xenograft mice. Our data suggest that GSTM4 is a novel therapeutic target for the treatment of high GSTM4-expressing Ewing sarcoma. Strategies that combine standard chemotherapy with agents that inhibit GSTM4, that are activated by GSTM4, or that block GSTM4/ASK1 interactions, can potentially be more specific and/or efficacious than standard therapeutic approaches. PMID:25147782

  14. 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

  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. 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

    2015-03-31

    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

  17. 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

  18. Cytotoxicity of the saponin TTB2 on Ewing sarcoma cells

    PubMed Central

    HUANG, WENFENG; ZOU, KUN

    2015-01-01

    The steroidal saponin TTB2 can be isolated from the n-BuOH extracts of Trillium tschonoskii Maxim. The aim of the present study was to observe whether this saponin exerted any cytotoxic effects on malignant sarcoma cells, and to further investigate the possible underlying molecular mechanisms. The cell viability, cell cycle arrest and phosphorylation of certain important signal molecules in the sarcoma cell line were investigated. It was found that TTB2 inhibited the growth of the Ewing sarcoma cell line and arrested cells in the G2/M and S phases of the cell cycle in a dose- and time-dependent manner. Furthermore, the phosphorylation of extracellular signal-regulated kinase was inhibited by TTB2. In conclusion, the results showed that the saponin TTB2 isolated from T. tschonoskii Maxim exerts anticancer effects and may be a potential candidate for the development of anticancer drugs for use in the treatment of cancer. PMID:26622365

  19. 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

  20. 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

  1. 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

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

    PubMed Central

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

    2015-01-01

    Ewing’s sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing’s sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing’s sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing’s sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing’s sarcoma patients with PARP inhibitors. PMID:26505995

  3. 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

  4. Revision Surgical Treatment of a Second Lumbar Ewing Sarcoma

    PubMed Central

    Feng, Helin; Wang, Jin; Guo, Peng; Xu, Jianfa; Feng, Jiangang

    2015-01-01

    Abstract We report a case of a 58-year-old man who presented initially with lumbar pain. According to radiography, computed tomography, magnetic resonance imaging, and bone biopsy results, Ewing sarcoma (ES) was diagnosed. Tumor resection was performed, followed by chemotherapy and radiotherapy; pathology confirmed the diagnosis of ES. After surgery, the tumor recurred twice with progressive symptoms, meriting repeated excisional surgery. At the 4-year follow-up, the patient showed apparent improvement, with return of function and strength and resolution of pain. We discuss its clinical features and treatment in the light of the current knowledge. PMID:26222849

  5. 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.

  6. 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

  7. 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

  8. 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

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

    ClinicalTrials.gov

    2015-12-31

    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

  10. 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.

  11. 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

  12. 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

  13. 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, 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

  14. 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

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

    PubMed

    Renard, Caroline; Ranchère-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

  16. Salient features of mesenchymal stem cells—implications for Ewing sarcoma modeling

    PubMed Central

    Monument, Michael J.; Bernthal, Nicholas M.; Randall, R. Lor

    2013-01-01

    Despite a heightened appreciation of the many defining molecular aberrations in Ewing sarcoma, the cooperative genetic environment and permissive cell of origin essential for EWS/ETS-mediated oncogenesis remain elusive. Consequently, inducible animal and in vitro models of Ewing sarcoma from a native cellular context are unable to fully recapitulate malignant transformation. Despite these shortcomings, human, and murine mesenchymal stem cells (MSCs) are the closest working in vitro systems available. MSCs are tolerant of ectopic EWS/FLI expression, which is accompanied by a molecular signature most similar to Ewing sarcoma. Whether MSCs are the elusive cell of origin or simply a tolerant platform of the EWS/FLI transcriptome, these cells have become an excellent molecular tool to investigate and manipulate oncogenesis in Ewing sarcoma. Our understanding of the biological complexity and heterogeneity of human MSCs (hMSCs) has increased substantially over time and as such, appreciation and utilization of these salient complexities may greatly enhance the efficient use of these cells as surrogate models for Ewing sarcoma tumorigenesis. PMID:23443465

  17. Evaluation of Cytarabine Against Ewing Sarcoma Xenografts by the Pediatric Preclinical Testing Program

    PubMed Central

    Houghton, Peter J.; Morton, Christopher L.; Kang, Min; Reynolds, C. Patrick; Billups, Catherine A.; Favours, Edward; Payne-Turner, Debbie; Tucker, Chandra; Smith, Malcolm A.

    2015-01-01

    Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with down-regulation of the EWS-FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in vitro against a panel of 23 pediatric cancer cell lines and in vivo against 6 Ewing sarcoma xenografts. Acute lymphoblastic leukemia cell lines were the most sensitive to cytarabine in vitro (median IC50 9 nM), while Ewing sarcoma cell lines showed intermediate sensitivity (median IC50 232 nM). Cytarabine at a dose of 150 mg/kg administered daily 5× failed to significantly inhibit growth of five xenograft models, but reduced growth rate of the A673 xenograft by 50%. Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied. PMID:20979180

  18. Ewing sarcoma vs lymphoblastic lymphoma. A comparative immunohistochemical study.

    PubMed

    Lucas, D R; Bentley, G; Dan, M E; Tabaczka, P; Poulik, J M; Mott, M P

    2001-01-01

    To develop a practical immunohistochemistry panel for distinguishing lymphoblastic lymphoma from Ewing sarcoma (ES), we evaluated 17 ES and 27 lymphoblastic lymphoma and leukemia cases with antibodies to CD99, terminal deoxynucleotidyl transferase (TdT), leukocyte common antigen (LCA), CD43, CD79a, CD20, CD3, vimentin, and neuron-specific enolase (NSE). Three cases were bone lymphomas, 2 initially misdiagnosed as ES. All cases were CD99+. All lymphomas and leukemias were TdT+ compared to none of the ESs. None of the ESs expressed other lymphocytic markers, which were inconsistently expressed in the lymphomas and leukemias: CD43, 33%; LCA, 30%; CD79a, 19%; CD3, 19%; and CD20, 7%. Of the ESs, 88% were vimentin positive compared with 23% of lymphomas and leukemias. Vimentin was stronger and more diffuse in ES. NSE did not reliably stain any cases. When faced with the differential diagnosis of ES vs lymphoblastic lymphoma, an immunohistochemical panel that includes antibodies to CD99 and TdT is useful. Both epitopes are well preserved in fixed and decalcified tissue. A panel composed of antibodies to CD99 and TdT, in conjunction with other lymphocytic markers and vimentin, is highly sensitive and specific. PMID:11190795

  19. 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

  20. 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

  1. 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; Karlström, Åsa; 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

  2. 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

  3. ZEB2 Represses the Epithelial Phenotype and Facilitates Metastasis in Ewing Sarcoma

    PubMed Central

    Wiles, Elizabeth T.; Bell, Russell; Thomas, Dafydd; Beckerle, Mary

    2013-01-01

    The vast majority of cancer-related deaths are attributable to metastasis. Effective treatment of metastatic disease will be improved by a better understanding of the molecular mechanisms contributing to this phenomenon. Much of the work in this field has focused on metastasis of carcinomas, tumors of epithelial origin, while metastasis of sarcomas, tumors of mesenchymal origin, remains poorly understood. Experimental evidence from studies in carcinomas, coupled with clinical observations, highlights the importance of both epithelial and mesenchymal characteristics in these cancer cells that make them competent for metastasis. We set out to test if similar cellular plasticity contributes to sarcoma metastasis. We found that the transcription factor, ZEB2, repressed epithelial gene expression in Ewing sarcoma cells, and this, in turn, repressed the epithelial phenotype. When ZEB2 was experimentally reduced in these cells, epithelial characteristics including decreased migratory ability and cytoskeleton rearrangements were observed. Furthermore, ZEB2 reduction in Ewing sarcoma cells resulted in a decreased metastatic potential using a mouse metastasis model. Our data show that Ewing sarcoma cells may have more epithelial plasticity than previously appreciated. This coupled with previous data demonstrating Ewing sarcoma cells also have mesenchymal features primes these cells to successfully metastasize. This is clinically relevant for 2 important reasons. First, this may offer a therapeutic opportunity to induce characteristics of one cell type or the other depending on the stage of the disease. Second, and more broadly, this raises questions about the cell of origin in Ewing sarcoma and may inform future animal models of the disease. PMID:24386509

  4. 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

  5. Ewing Sarcoma Eswa Protein Regulates Chondrogenesis of Meckel's Cartilage through Modulation of Sox9 in Zebrafish

    E-print Network

    Merkes, Chris; Turkalo, Timothy K.; Wilder, Nicole; Park, Hyewon; Wenger, Luke W.; Lewin, Seth J.; Azuma, Mizuki

    2015-01-24

    Ewing sarcoma is the second most common skeletal (bone and cartilage) cancer in adolescents, and it is characterized by the expression of the aberrant chimeric fusion gene EWS/FLI1. Wild-type EWS has been proposed to play a role in mitosis, splicing...

  6. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis

    PubMed Central

    Marques Howarth, Michelle; Simpson, David; Ngok, Siu P.; Nieves, Bethsaida; Chen, Ron; Siprashvili, Zurab; Vaka, Dedeepya; Breese, Marcus R.; Crompton, Brian D.; Alexe, Gabriela; Hawkins, Doug S.; Jacobson, Damon; Brunner, Alayne L.; West, Robert; Mora, Jaume; Stegmaier, Kimberly; Khavari, Paul; Sweet-Cordero, E. Alejandro

    2014-01-01

    Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma. EWS-FLI1 alters gene expression through mechanisms that are not completely understood. We performed RNA sequencing (RNAseq) analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncoprotein. We determined that long noncoding RNA-277 (Ewing sarcoma–associated transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs. Inhibition of EWSAT1 expression diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar, whereas EWSAT1 inhibition had no effect on other cell types tested. Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a substantial fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1. Analysis of RNAseq data from primary human Ewing sarcoma further supported a role for EWSAT1 in mediating gene repression. We identified heterogeneous nuclear ribonucleoprotein (HNRNPK) as an RNA-binding protein that interacts with EWSAT1 and found a marked overlap in HNRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates in EWSAT1-mediated gene repression. Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes. PMID:25401475

  7. 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.; Gattenlöhner, Stefan; Ranft, Andreas; Dirksen, Uta; Jürgens, Heribert; Bräuninger, 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

  8. A link between basic fibroblast growth factor (bFGF) and EWS/FLI-1 in Ewing's sarcoma cells.

    PubMed

    Girnita, L; Girnita, A; Wang, M; Meis-Kindblom, J M; Kindblom, L G; Larsson, O

    2000-08-31

    The EWS/FLI-1 fusion gene is characteristic of most cases of Ewing's sarcoma and has been shown to be crucial for tumor transformation and cell growth. In this study we demonstrate a drastic down-regulation of the EWS/FLI-1 protein, and a growth arrest, following serum depletion of Ewing's sarcoma cells. This indicates that growth factor circuits may be involved in regulation of the fusion gene product. Of four different growth factors tested, basic fibroblast growth factor (bFGF) was found to be of particular significance. In fact, upon treatment of serum-depleted cells with bFGF, expression of the EWS/FLI-1 protein and growth of the Ewing's sarcoma cells were restored. In addition, a bFGF-neutralizing antibody, which was confirmed to inhibit FGF receptor (FGFR) phosphorylation, caused down-regulation of EWS/FLI-1. Experiments using specific cell cycle blockers (thymidine and colcemide) suggest that EWS/FLI-1 is directly linked to bFGF stimulation, and not indirectly to cell proliferation. We also demonstrated expression of FGFRs in several tumor samples of Ewing's sarcoma. Taken together, our data suggest that expression of FGFR is a common feature of Ewing's sarcoma and, in particular, that the bFGF pathway may be important for the maintenance of a malignant phenotype of Ewing's sarcoma cells through up-regulating the EWS/FLI-1 protein. Oncogene (2000) 19, 4298 - 4301 PMID:10980604

  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

    Kennedy, Alyssa L; Vallurupalli, Mounica; Chen, Liying; Crompton, Brian; Cowley, Glenn; Vazquez, Francisca; Weir, Barbara A; Tsherniak, Aviad; Parasuraman, Sudha; Kim, Sunkyu; Alexe, Gabriela; Stegmaier, Kimberly

    2015-10-01

    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. Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo

    E-print Network

    Azuma, Mizuki; Embree, Lisa J.; Sabaawy, Hatem; Hickstein, Dennis D.

    2007-10-03

    Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo Mizuki Azuma*, Lisa J. Embree, Hatem Sabaawy, Dennis D. Hickstein Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National... mitotic integrity and proneural cell survival in early zebrafish development. Citation: Azuma M, Embree LJ, Sabaawy H, Hickstein DD (2007) Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo. PLoS ONE...

  12. 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 EWS–down-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 translocation–based cancers. PMID:24069508

  13. 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

  14. 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

  15. 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

  16. Antagonizing Bcl-2 Family Members Sensitizes Neuroblastoma and Ewing’s 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 Ewing’s sarcomas (EWS) together cause 18% of all pediatric cancer deaths. Though there is growing interest in targeting the dysregulated metabolism of cancer as a therapeutic strategy, this approach has not been fully examined in NBL and EWS. In this study, we first tested a panel of metabolic inhibitors and identified the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) as the most potent chemotherapeutic across all NBL and EWS cell lines tested. Myc, a master regulator of metabolism, is commonly overexpressed in both of these pediatric malignancies and recent studies have established that Myc causes cancer cells to become “addicted” to glutamine. We found DON strongly inhibited tumor growth of multiple tumor lines in mouse xenograft models. In vitro, inhibition of caspases partially reversed the effects of DON in high Myc expressing cell lines, but not in low Myc expressing lines. We further showed that induction of apoptosis by DON in Myc-overexpressing cancers is via the pro-apoptotic factor Bax. To relieve inhibition of Bax, we tested DON in combination with the Bcl-2 family antagonist navitoclax (ABT-263). In vitro, this combination caused an increase in DON activity across the entire panel of cell lines tested, with synergistic effects in two of the N-Myc amplified neuroblastoma cell lines. Our study supports targeting glutamine metabolism to treat Myc overexpressing cancers, such as NBL and EWS, particularly in combination with Bcl-2 family antagonists. PMID:25615615

  17. Ewing’s sarcoma family of tumors of the maxillary sinus: a case report of multidisciplinary examination enabling prompt diagnosis

    PubMed Central

    Tajima, Shogo; Ohkubo, Aki; Yoshida, Matsumi; Koda, Kenji; Nameki, Ichirota

    2015-01-01

    There have been approximately 10 reports in English literature of cases of Ewing’s sarcoma family of tumors (EFT) arising in the maxillary sinus. In this location, some tumors mimic EFT, and are more frequently encountered. Herein, we present an additional case of an EFT originating in the maxillary sinus. The patient was a 15-year-old boy complaining of a non-tender swelling of the left cheek. Laboratory tests showed no abnormalities. Computed tomography and magnetic resonance imaging revealed a mass centered in the maxillary sinus with degeneration of the surrounding bones. Pathological examination along with flow cytometry and G-banding enabled the prompt diagnosis of EFT with the EWS/FLI1 fusion gene. The patient is planned to undergo chemotherapy. An origin in the head and neck and the presence of the typical EWS/FLI1, in conjunction with an opportunity for immediate treatment, may predict a relatively better prognosis for EFT in our case. PMID:25755803

  18. 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.

  19. 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

  20. The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.

    PubMed

    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

    2014-07-01

    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

  1. Fine-Needle Aspiration Cytology of Ewing's Sarcoma of Thoracic Spine with Extension into the Intradural Space

    PubMed Central

    Bordia, Sandhya; Meena, Sweta; Meena, Bijendar Kumar; Rajak, Vijay

    2014-01-01

    Ewing's sarcoma/peripheral primitive neuroectodermal tumor is a small, round, and blue cell malignancy that occurs most often in bone and soft tissues of children and young adults. The intraspinal manifestation of the disease is rare, and when present, this is often misdiagnosed with other varieties of primary spinal tumors. Fine-needle aspiration cytology (FNAC) plays important role in the early diagnosis of these cases. We report such a case of Ewing's sarcoma of thoracic spine with extension into the intradural space, which was initially suspected to be a case of metastatic lesion in an 18-year-old boy. PMID:24847440

  2. 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

  3. 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.

  4. Hypoxia shifts activity of neuropeptide Y in Ewing sarcoma from growth-inhibitory to growth-promoting effects

    E-print Network

    Lu, Congyi

    Ewing sarcoma (ES) is an aggressive malignancy driven by an oncogenic fusion protein, EWS-FLI1. Neuropeptide Y (NPY), and two of its receptors, Y1R and Y5R are up-regulated by EWS-FLI1 and abundantly expressed in ES cells. ...

  5. 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 Cécile; Bahrami, Armita; Zhang, Zhaojie; Lapouble, Eve; Grossetête-Lalami, Sandrine; Rusch, Michael; Reynaud, Stéphanie; 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, Valérie; Michon, Jean; Marec-Bérard, Perrine; Gut, Ivo; Downing, James; Dyer, Michael; Zhang, Jinghui; Delattre, Olivier

    2014-01-01

    Ewing sarcoma is a primary bone tumor initiated by EWSR1–ETS 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

  6. 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

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

    E-print Network

    Alhaddad, Anna; Botsoa, Jacques; Dantelle, Géraldine; Perruchas, Sandrine; Gacoin, Thierry; Mansuy, Christelle; Lavielle, Solange; Malvy, Claude; Treussart, François; Bertrand, Jean-Rémi

    2011-01-01

    We investigated the ability of diamond nanoparticles (nanodiamonds, NDs) to deliver small interfering RNA (siRNA) in Ewing sarcoma cells, in the perspective of in vivo anti-cancer nucleic acid drug delivery. siRNA was adsorbed onto NDs previously coated with cationic polymer. Cell uptake of NDs has been demonstrated by taking advantage of NDs intrinsic fluorescence coming from embedded color center defects. Cell toxicity of these coated NDs was shown to be low. Consistent with the internalization efficacy, we have shown a specific inhibition of EWS/Fli-1 gene expression at the mRNA and protein level by the ND vectorized siRNA in a serum containing medium.

  8. 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.

  9. Use of MR imaging to assess results of chemotherapy for Ewing sarcoma.

    PubMed

    Lemmi, M A; Fletcher, B D; Marina, N M; Slade, W; Parham, D M; Jenkins, J J; Meyer, W H

    1990-08-01

    MR imaging was used to monitor the results of initial chemotherapy of primary Ewing sarcoma of bone. The signal intensities of the soft-tissue and marrow components of the tumor were evaluated on T2-weighted images obtained in 10 patients (nine with responsive tumors) at presentation and during and immediately after completion of two cycles of chemotherapy. MR evidence of marrow and soft-tissue involvement was seen in all tumors at presentation. After treatment, the bone-marrow component of the nine drug-sensitive tumors showed an increase in signal intensity that in eight cases became comparable to that of water. Changes in signal intensity of the soft-tissue component were variable, consisting of increases in two of the responsive lesions, no change in three, a decrease in two, and complete resolution of the soft-tissue mass in two. There was no increase in signal intensity of either the bone-marrow or the soft-tissue component of the single nonresponsive tumor. All of the responsive tumors showed advanced healing, and abundant bony sclerosis was apparent on CT. Bone-marrow examinations, performed in seven of the nine patients with responsive lesions, disclosed no evidence of tumor in four. Two patients had residual extramedullary tumor; the nonresponsive lesion contained sheets of tumor cells. The increase in marrow signal intensity on T2-weighted images was associated with replacement of marrow elements by a loose, hypocellular myxoid matrix containing modest amounts of collagen, consistent with response to chemotherapy and eradication of disease. Therefore, an increase in the T2-weighted signal intensity of the bone-marrow component of Ewing sarcoma of bone reflected a favorable response to chemotherapy. MR signal changes, however, were not predictive of resolution of malignant disease within adjacent soft tissue. PMID:2115265

  10. 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

  11. Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line

    PubMed Central

    Moore, Joseph B.; Loeb, David M.; Hong, Kyung U.; Sorensen, Poul H.; Triche, Timothy J.; Lee, David W.; Barbato, Michael I.; Arceci, Robert J.

    2015-01-01

    Developmental reprogramming techniques have been used to generate induced pluripotent stem (iPS) cells from both normal and malignant cells. The derivation of iPS cells from cancer has the potential to provide a unique scientific tool to overcome challenges associated with the establishment of cell lines from primary patient samples and a readily expandable source of cells that may be used to model the initial disease. In the current study we developmentally reprogrammed a metastatic Ewing sarcoma (EWS) cell line to a meta-stable embryonic stem (ES)-like state sharing molecular and phenotypic features with previously established ES and iPS cell lines. EWS-iPS cells exhibited a pronounced drug resistant phenotype despite persistent expression of the oncogenic EWS-FLI1 fusion transcript. This included resistance to compounds that specifically target downstream effector pathways of EWS-FLI1, such as MAPK/ERK and PI3K/AKT, which play an important role in EWS pathogenesis. EWS-iPS cells displayed tumor initiation abilities in vivo and formed tumors exhibiting characteristic Ewing histopathology. In parallel, EWS-iPS cells re-differentiated in vitro recovered sensitivity to molecularly targeted chemotherapeutic agents, which reiterated pathophysiological features of the cells from which they were derived. These data suggest that EWS-iPS cells may provide an expandable disease model that could be used to investigate processes modulating oncogenesis, metastasis, and chemotherapeutic resistance in EWS. PMID:25806369

  12. 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

  13. An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma.

    PubMed

    Lamhamedi-Cherradi, Salah-Eddine; Menegaz, Brian A; Ramamoorthy, Vandhana; Aiyer, Ramani A; Maywald, Rebecca L; Buford, Adrianna S; Doolittle, Dannette K; Culotta, Kirk S; O'Dorisio, James E; Ludwig, Joseph A

    2015-07-01

    Ewing sarcoma is a transcription factor-mediated pediatric bone tumor caused by a chromosomal translocation of the EWSR1 gene and one of several genes in the ETS family of transcription factors, typically FLI1 or ERG. Full activity of the resulting oncogenic fusion protein occurs only after binding RNA helicase A (RHA), and novel biologically targeted small molecules designed to interfere with that interaction have shown early promise in the preclinical setting. Herein, we demonstrate marked preclinical antineoplastic activity of an orally bioavailable formulation of YK-4-279 and identify mechanisms of acquired chemotherapy resistance that may be exploited to induce collateral sensitivity. Daily enteral administration of YK-4-279 led to significant delay in Ewing sarcoma tumor growth within a murine model. In advance of anticipated early-phase human clinical trials, we investigated both de novo and acquired mechanism(s) by which Ewing sarcoma cells evade YK-4-279-mediated cell death. Drug-resistant clones, formed by chronic in vitro exposure to steadily increased levels of YK-4-279, overexpressed c-Kit, cyclin D1, pStat3(Y705), and PKC isoforms. Interestingly, cross-resistance to imatinib and enzastaurin (selective inhibitors of c-Kit and PKC-?, respectively), was observed and the use of YK-4-279 with enzastaurin in vitro led to marked drug synergy, suggesting a potential role for combination therapies in the future. By advancing an oral formulation of YK-4-279 and identifying prominent mechanisms of resistance, this preclinical research takes us one step closer to a shared goal of curing adolescents and young adults afflicted by Ewing sarcoma. PMID:25964201

  14. Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies

    PubMed Central

    Berger, Manfred; Dirksen, Uta; Braeuninger, Andreas; Koehler, Gabriele; Juergens, Heribert

    2013-01-01

    Chromosomal translocations between the EWS gene and members of the ETS gene family are characteristic molecular features of the Ewing sarcoma. The most common translocation t(11;22)(q24;q12) fuses the EWS gene to FLI1, and is present in 85–90% of Ewing sarcomas. In the present study, a specifically designed multiplex long-range PCR assay was applied to amplify genomic EWS-FLI1 fusion sites from as little as 100 ng template DNA. Characterization of the EWS-FLI1 fusion sites of 42 pediatric and young adult Ewing sarcoma patients and seven cell lines revealed a clustering in the 5? region of the EWS-breakpoint cluster region (BCR), in contrast to random distribution of breakpoints in the FLI1-BCR. No association of breakpoints with various recombination-inducing sequence motifs was identified. The occurrence of small deletions and duplications at the genomic junction is characteristic of involvement of the non-homologous end-joining (NHEJ) repair system, similar to findings at chromosomal breakpoints in pediatric leukemia and lymphoma. PMID:23441188

  15. 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.

  16. 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

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

    PubMed Central

    Carcaboso, Angel M.; Herrero-Martín, David; García-Macías, María del Carmen; Sevillano, Vicky; Alonso, Diego; Pascual-Pasto, Guillem; San-Segundo, Laura; Vila-Ubach, Monica; Rodrigues, Telmo; Fraile, Susana; Teodosio, Cristina; Mayo-Iscar, Agustín; Aracil, Miguel; Galmarini, Carlos María; Tirado, Oscar M.; Mora, Jaume; de Álava, 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

  18. 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

  19. 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

  20. Molecular Inversion Probe analysis detects novel copy number alterations in Ewing Sarcoma

    PubMed Central

    Jahromi, Mona S.; Putnam, Angelica R.; Druzgal, Colleen; Wright, Jennifer; Spraker, Holly; Kinsey, Michelle; Zhou, Holly; Boucher, Ken; Randall, R. Lor; Jones, Kevin B.; Lucas, David; Rosenberg, Andrew; Thomas, Dafydd; Lessnick, Stephen L.; Schiffman, Joshua D.

    2013-01-01

    Ewing sarcoma (ES) is the second most common bone tumor in children and young adults, with dismal outcomes for metastatic and relapsed disease. To better understand the molecular pathogenesis of ES and to identify new prognostic markers, we used molecular inversion probes (MIPs) to evaluate copy number alterations (CNAs) and loss of heterozygosity (LOH) in formalin-fixed paraffin-embedded (FFPE) samples which included 40 ES primary tumors and 12 ES metastatic lesions. CNAs were correlated with clinical features and outcome, and validated by immunohistochemistry (IHC). We identified previously reported CNAs, in addition to SMARCB1 (INI1/SNF5) homozygous loss and copy neutral LOH. IHC confirmed SMARCB1 protein loss in 7–10% of clinically-diagnosed ES tumors in three separate cohorts (University of Utah [N=40], Children’s Oncology Group [N=31], and University of Michigan [N=55]). A multifactor copy number (MCN)-index was highly predictive of overall survival (39% vs. 100%, P<0.001). We also identified RELN gene deletions unique to 25% of ES metastatic samples. In summary, we identified both known and novel CNAs using MIP technology for the first time in FFPE samples from patients with ES. CNAs detected by microarray correlate with outcome and may be useful for risk-stratification in future clinical trials. PMID:22868000

  1. 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.

  2. 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.

  3. 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

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

    PubMed

    Ordóñez, José Luis; Amaral, Ana Teresa; Carcaboso, Angel M; Herrero-Martín, David; del Carmen García-Macías, María; Sevillano, Vicky; Alonso, Diego; Pascual-Pasto, Guillem; San-Segundo, Laura; Vila-Ubach, Monica; Rodrigues, Telmo; Fraile, Susana; Teodosio, Cristina; Mayo-Iscar, Agustín; Aracil, Miguel; Galmarini, Carlos María; Tirado, Oscar M; Mora, Jaume; de Álava, Enrique

    2015-08-01

    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

  5. 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).

  6. Ewing Sarcoma Ewsa Protein Regulates Chondrogenesis of Meckel’s Cartilage through Modulation of Sox9 in Zebrafish

    PubMed Central

    Merkes, Chris; Turkalo, Timothy K.; Wilder, Nicole; Park, Hyewon; Wenger, Luke W.; Lewin, Seth J.; Azuma, Mizuki

    2015-01-01

    Ewing sarcoma is the second most common skeletal (bone and cartilage) cancer in adolescents, and it is characterized by the expression of the aberrant chimeric fusion gene EWS/FLI1. Wild-type EWS has been proposed to play a role in mitosis, splicing and transcription. We have previously shown that EWS/FLI1 interacts with EWS, and it inhibits EWS activity in a dominant manner. Ewing sarcoma is a cancer that specifically develops in skeletal tissues, and although the above data suggests the significance of EWS, its role in chondrogenesis/skeletogenesis is not understood. To elucidate the function of EWS in skeletal development, we generated and analyzed a maternal zygotic (MZ) ewsa/ewsa line because the ewsa/wt and ewsa/ewsa zebrafish appeared to be normal and fertile. Compared with wt/wt, the Meckel’s cartilage of MZ ewsa/ewsa mutants had a higher number of craniofacial prehypertrophic chondrocytes that failed to mature into hypertrophic chondrocytes at 4 days post-fertilization (dpf). Ewsa interacted with Sox9, which is the master transcription factor for chondrogenesis. Sox9 target genes were either upregulated (ctgfa, ctgfb, col2a1a, and col2a1b) or downregulated (sox5, nog1, nog2, and bmp4) in MZ ewsa/ewsa embryos compared with the wt/wt zebrafish embryos. Among these Sox9 target genes, the chromatin immunoprecipitation (ChIP) experiment demonstrated that Ewsa directly binds to ctgfa and ctgfb loci. Consistently, immunohistochemistry showed that the Ctgf protein is upregulated in the Meckel’s cartilage of MZ ewsa/ewsa mutants. Together, we propose that Ewsa promotes the differentiation from prehypertrophic chondrocytes to hypertrophic chondrocytes of Meckel’s cartilage through inhibiting Sox9 binding site of the ctgf gene promoter. Because Ewing sarcoma specifically develops in skeletal tissue that is originating from chondrocytes, this new role of EWS may provide a potential molecular basis of its pathogenesis. PMID:25617839

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

    PubMed

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

    2014-01-01

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

  8. 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; Schäfer, Karl L.; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C. W.; Athanasou, Nicholas A.; Noble, J. Alison; Hassan, A. Bassim

    2014-01-01

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

  9. 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

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

    PubMed

    Valsalan, Rejith Mannambeth; Zacharia, Balaji

    2015-10-18

    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

  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. 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

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

    PubMed Central

    Bouman, Lena; Sancéau, 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 [Sancéau, 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

  14. 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.

  15. 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.

  16. 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

  17. Synthesis and Structure–Activity Relationship Studies of Small Molecule Disruptors of EWS-FLI1 Interactions in Ewing’s Sarcoma

    PubMed Central

    2015-01-01

    EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing’s 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. 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)

  19. Ordering of probes surrounding the Ewing's sarcoma breakpoint on chromosome 22 using fluorescent in situ hybridization to interphase nuclei.

    PubMed

    Shipley, J M; Jones, T A; Patel, K; Kiely, F M; De Stavola, B L; Sheer, D

    1993-01-01

    Eight probes were localized by fluorescent in situ hybridization to the region surrounding the Ewing's sarcoma breakpoint on chromosome 22. Three of these were initially ordered by pair-wise hybridization to metaphase chromosomes with differential detection of the probes. These and the remaining probes were then ordered by hybridizing two or three probes simultaneously to interphase nuclei. In the two probe experiments and some of the three probe experiments, the order was derived by comparing mean interphase distances between signals from the probes. In the three probe experiments, either two probes were detected with one fluorochrome and the third with another or all three probes were individually distinguished by detecting one probe with fluorescein isothiocyanate (FITC), one with Texas Red, and one with both fluorochromes to give a mixed color. The order of the signals was then noted. Greater than 60 percent of configurations with a discrete order were shown or deduced to be correct. These approaches are assessed and we demonstrate a more obvious predominating order when all three probes are differentially detected. The order of the probes was deduced to be centromere: D22S271: D22S260: lambda S1: D22S262: cosK1831: Ewing's sarcoma breakpoint: cosLIF: D22S261: lambda S15: telomere. PMID:8404047

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

    PubMed

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

    2015-11-01

    Ewing's sarcoma (ES) is the second most common type of pediatric bone tumor, and is associated with a poor prognosis. Picropodophyllin (PPP), a novel selective inhibitor of insulin?like growth factor?1 receptor (IGF?1R), is able to strongly inhibit various types of cancers. However, the effect of IGF?1R on ES remains unclear. Following treatment with various concentrations of PPP for various times, cell viability was determined using an MTT assay. In addition, cell proliferation and apoptosis was investigated separately by bromodeoxyuridine staining and flow cytometry, respectively. The PPP?associated signaling pathway was also investigated. The results of the present study suggested that PPP inhibited cell proliferation and viability of A673 and SK?ES?1 human Ewing's sarcoma cells in a dose- and time?dependent manner. In addition, cell apoptosis rates were increased following treatment with PPP. Further investigation of the underlying mechanism revealed that PPP inhibited Akt phosphorylation. Fumonisin B1, an Akt?specific activator, reversed the inhibitory effects of PPP on cell growth. Furthermore, the results suggested that PPP decreased the expression levels of IGF?1R, a common activator of Akt signaling. PPP inhibited the growth of human Ewing's sarcoma cells by targeting the IGF?1R/Akt signaling pathway. Therefore, PPP may prove useful in the development of an effective strategy for the treatment of Ewing's sarcoma. PMID:26323364

  1. 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.

  2. A peculiar case of large primary cutaneous Ewing’s 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 Ewing’s 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 9.5 × 8 cm 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

  3. 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.

  4. Ewing's sarcoma family of tumors of the maxillary sinus: a case report of multidisciplinary examination enabling prompt diagnosis.

    PubMed

    Tajima, Shogo; Ohkubo, Aki; Yoshida, Matsumi; Koda, Kenji; Nameki, Ichirota

    2015-01-01

    There have been approximately 10 reports in English literature of cases of Ewing's sarcoma family of tumors (EFT) arising in the maxillary sinus. In this location, some tumors mimic EFT, and are more frequently encountered. Herein, we present an additional case of an EFT originating in the maxillary sinus. The patient was a 15-year-old boy complaining of a non-tender swelling of the left cheek. Laboratory tests showed no abnormalities. Computed tomography and magnetic resonance imaging revealed a mass centered in the maxillary sinus with degeneration of the surrounding bones. Pathological examination along with flow cytometry and G-banding enabled the prompt diagnosis of EFT with the EWS/FLI1 fusion gene. The patient is planned to undergo chemotherapy. An origin in the head and neck and the presence of the typical EWS/FLI1, in conjunction with an opportunity for immediate treatment, may predict a relatively better prognosis for EFT in our case. PMID:25755803

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

    PubMed

    Tardío, Juan C; Machado, Isidro; Navarro, Lara; Idrovo, Franklin; Sanz-Ortega, Julián; Pellín, 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

  6. Distinct Transcriptional Signature and Immunoprofile of CIC-DUX4–Fusion Positive Round Cell Tumors Compared to EWSR1-Rearranged Ewing Sarcomas – Further Evidence Toward Distinct Pathologic Entities

    PubMed Central

    Specht, Katja; Sung, Yun-Shao; Zhang, Lei; Richter, Günther H. S.; Fletcher, Christopher D.; Antonescu, Cristina R.

    2014-01-01

    Round cell sarcomas harboring CIC-DUX4 fusions have recently been described as highly aggressive soft tissue tumors of children and young adults. Due to partial morphologic and immunohistochemical overlap with Ewing sarcoma (ES), CIC-DUX4-positive tumors have generally been classified as Ewing sarcoma-like and managed similarly, however, a systematic comparison at the molecular and immunohistochemical levels between these two groups has not yet been conducted. Based on an initial observation that CIC-DUX4-positive tumors show nuclear immunoreactivity for WT1 and ETS transcription factors, FLI1 and ERG, we performed a detailed immunohistochemical and molecular analysis including these markers, to further investigate the relationship between CIC-DUX4 tumors and ES. The study group included 21 CIC-DUX4-positive sarcomas and 20 EWSR1-rearranged ES. Immunohistochemically, CIC-DUX4 sarcomas showed membranous CD99 positivity in 18 (86%) cases, but only 5 (24%) with a diffuse pattern, while WT1 and FLI1 were strongly positive in all cases. ERG was positive in 18% of cases. All ES expressed CD99 and FLI1, while ERG positivity was only seen in EWSR1-ERG fusion positive ES. WT1 was negative in all ES. Expression profiling validated by q-PCR revealed a distinct gene signature associated with CIC-DUX4 fusion, with upregulation of ETS transcription factors (ETV4, ETV1 and ETV5) and WT1, among top overexpressed genes compared to ES, other sarcomas and normal tissue. In conclusion, the distinct gene signature and immunoprofile of CIC-DUX4 sarcomas suggest a distinct pathogenesis from ES. The consistent WT1 expression may provide a useful clue in the diagnosis in the context of round cell sarcomas negative for EWSR1-rearrangement. PMID:24723486

  7. 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 20–26 GGAA motifs. Relative to white European and African controls, the NR0B1 GGAA-microsatellite in tumor cells demonstrated a strong bias for haplotypes containing 21–25 GGAA motifs suggesting a relationship between microsatellite function and disease susceptibility. This selection bias was not a product of microsatellite instability in tumor samples, nor was there a correlation between NR0B1 GGAA-microsatellite polymorphisms and survival outcomes. 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

  8. 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

  9. 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 Müllerian 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

  10. 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

  11. 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

  12. 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 ?mol/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

  13. 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

  14. Primary Ewing sarcoma of vulva, confirmed with molecular cytogenetic analysis: A rare case report with diagnostic and treatment implications.

    PubMed

    Rekhi, Bharat; Chinnaswamy, Girish; Vora, Tushar; Shah, Sneha; Rangarajan, Venkatesh

    2015-01-01

    Primary vulvar Ewing sarcoma (ES)/PNET is an uncommonly documented tumor, especially with molecular results. A 10-year-old girl presented with left vulvar swelling, a year ago. Her abdominopelvic ultrasound revealed a 12 cm × 8 cm sized, mixed echogenic blood-filled lesion in the left vulva; radiologically considered as a hematoma. Vulvectomy revealed a multinodular grey-brown tumor, microscopically comprising malignant round cells. Immunohistochemically, tumor cells diffusely expressed MIC2/CD99 and Fli1 and subsequently displayed EWSR1 rearrangement, confirming diagnosis of ES/PNET. Subsequently, PET-CT scan revealed residual local lesion with lung metastases. The patient was induced on EFT 2001 chemotherapy protocol. Three months after chemotherapy completion, there was no metabolically active disease on PET scan. Four months later, MRI disclosed recurrent primary and metastatic pulmonary lesions. She was planned for scar excision and adjuvant radiotherapy, but unfortunately defaulted further treatment. This forms the eighth case of primary vulvar ES/PNET confirmed with molecular cytogenetic result, underscoring therapeutic value of objective diagnosis in such cases. PMID:26275259

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

    PubMed Central

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

    2015-01-01

    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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Common Ewing sarcoma-associated antigens fail to induce natural T cell responses in both patients and healthy individuals.

    PubMed

    Altvater, Bianca; Kailayangiri, Sareetha; Theimann, Nadine; Ahlmann, Martina; Farwick, Nicole; Chen, Christiane; Pscherer, Sibylle; Neumann, Ilka; Mrachatz, Gabriele; Hansmeier, Anna; Hardes, Jendrik; Gosheger, Georg; Juergens, Heribert; Rossig, Claudia

    2014-10-01

    Disseminated or relapsed Ewing sarcoma (EwS) has remained fatal in the majority of patients. A promising approach to preventing relapse after conventional therapy is to establish tumor antigen-specific immune control. Efficient and specific T cell memory against the tumor depends on the expansion of rare T cells with native specificity against target antigens overexpressed by the tumor. Candidate antigens in EwS include six-transmembrane epithelial antigen of the prostate-1 (STEAP1), and the human cancer/testis antigens X-antigen family member 1 (XAGE1) and preferentially expressed antigen in melanoma (PRAME). Here, we screened normal donors and EwS patients for the presence of circulating T cells reactive with overlapping peptide libraries of these antigens by IFN-? Elispot analysis. The majority of 22 healthy donors lacked detectable memory T cell responses against STEAP1, XAGE1 and PRAME. Moreover, ex vivo detection of T cells specific for these antigens in both blood and bone marrow were limited to a minority of EwS patients and required nonspecific T cell prestimulation. Cytotoxic T cells specific for the tumor-associated antigens were efficiently and reliably generated by in vitro priming using professional antigen-presenting cells and optimized cytokine stimulation; however, these T cells failed to interact with native antigen processed by target cells and with EwS cells expressing the antigen. We conclude that EwS-associated antigens fail to induce efficient T cell receptor (TCR)-mediated antitumor immune responses even under optimized conditions. Strategies based on TCR engineering could provide a more effective means to manipulating T cell immunity toward targeted elimination of tumor cells. PMID:24973179

  1. 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, Géraldine; Le Cam, Eric; Malvy, Claude; Treussart, François; Bertrand, Jean-Rémi

    2012-01-01

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

  2. 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.

  3. Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation.

    PubMed

    Kawamura-Saito, Miho; Yamazaki, Yukari; Kaneko, Keiko; Kawaguchi, Noriyoshi; Kanda, Hiroaki; Mukai, Hiroyuki; Gotoh, Takahiro; Motoi, Tohru; Fukayama, Masashi; Aburatani, Hiroyuki; Takizawa, Toichiro; Nakamura, Takuro

    2006-07-01

    Ewing's family tumors (EFTs) are highly malignant tumors arising from bone and soft tissues that exhibit EWS-FLI1 or variant EWS-ETS gene fusions in more than 85% of the cases. Here we show that CIC, a human homolog of Drosophila capicua which encodes a high mobility group box transcription factor, is fused to a double homeodomain gene DUX4 as a result of a recurrent chromosomal translocation t(4;19)(q35;q13). This translocation was seen in two cases of soft tissue sarcoma diagnosed as Ewing-like sarcoma. CIC-DUX4 exhibits a transforming potential for NIH 3T3 fibroblasts, and as a consequence of fusion with a C-terminal fragment of DUX4, CIC acquires an enhanced transcriptional activity, suggesting that expression of its downstream targets might be deregulated. Gene expression analysis identified the ETS family genes, ERM/ETV5 and ETV1, as potential targets for the gene product of CIC-DUX4. Indeed, CIC-DUX4 directly binds the ERM promoter by recognizing a novel target sequence and significantly up-regulates its expression. This study clarifies the function of CIC and its role in tumorigenesis, as well as the importance of the PEA3 subclass of ETS family proteins in the development of EFTs arising through mechanisms different from those involving EWS-ETS chimeras. Moreover, the study identifies the role of DUX4 that is closely linked to facioscapulohumeral muscular dystrophy in transcriptional regulation. PMID:16717057

  4. Loss of pulp sensitivity and pain as the first symptoms of a Ewing's sarcoma in the right maxillary sinus and alveolar process: report of a case.

    PubMed

    Bornstein, Michael M; von Arx, Thomas; Altermatt, Hans Jörg

    2008-12-01

    This case report describes the diagnosis and treatment of a Ewing's sarcoma in the right maxillary sinus and alveolar bone of a 19-year-old female patient. The first clinical symptoms were a loss of sensitivity of the premolars and first molar in the right maxilla and acute pain located in the area of these teeth. Initially, the referring dentist had treated these findings as an acute apical periodontitis with root canal medication. Because swellings on the palatal and buccal aspects of the teeth occurred and could not be treated with incision and drainage, the dentist referred the patient. Cone-beam computed tomography revealed a proliferation of soft tissue in the right maxillary sinus, with a radiopaque material at the tip of the mesiobuccal root of the first molar and resorptive signs of the mesiobuccal and distobuccal roots of the first molar. The palatal cortical bone of the right alveolar process seemed to be intact. After explorative surgery with biopsies from the buccal, palatal, and sinus proliferation areas, the pathologist diagnosed the lesion as a Ewing's sarcoma. Treatment of the patient consisted of initial chemotherapy, hemimaxillectomy, and postsurgical chemoradiotherapy. PMID:19026893

  5. [Advances in tumor chemo-resistance regulated by MicroRNA].

    PubMed

    Lin, Gaoyang; Xu, Ke

    2014-10-20

    Chemotherapy is one of the primary treatment for malignant tumors. Tumor multidrug resistance (MDR) is a major cause of clinical failure of chemotherapy; however the mechanisms of chemo-resistance have not been fully elucidated. Recently, microRNA is one of the new hotspots in life science. MicroRNA regulates the expression of genes and plays roles a series of life events by post-transcriptional regulations, including cell proliferation, apoptosis, fat metabolism, nervous development, hormone secretion, tumor vessels generation, stem cell differentiation, tumor cell invasion and metastasis, and other physiological and pathological processes. Recent studies show that microRNA regulates the expression of multiple genes with high efficiency and specificity. The abnormal regulation of target genes by microRNA is responsible for tumor chemo-resistance, this may be an important component of the complexity of the regulation of chemo-resistance. Therefore, the study of microRNA and tumor drug resistance has profound practical significance. In this review, recent studies of tumor drug resistance, regulation of tumor drug resistance by microRNA, and microRNA as a potential target for tumor drug resistance therapy are reviewed. PMID:25342041

  6. A phase II study to determine the efficacy and safety of oral treosulfan in patients with advanced pre-treated Ewing sarcoma ISRCTN11631773.

    PubMed

    Michelagnoli, M; Whelan, J; Forsyth, S

    2015-01-01

    We report a prospective Phase II study of efficacy and toxicity for oral treosulfan in advanced Ewing sarcoma. Twenty patients, median age 19 years (range 7-39) from five UK sites, were treated with oral treosulfan 1 g/m(2) daily for 7 days in 28. Primary endpoint was objective response rate. Best response was stable disease in one patient. All patients died of progressive disease, after median 6.41 months. Median progression free survival was 1.8 months. Toxicity was minimal. No activity was demonstrated for treosulfan at this dose. Progression free survival data should be able to be used for comparison when planning future clinical trials. PMID:25284019

  7. 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) ...

  8. 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 Ewing’s sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing’s sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. PMID:24669185

  9. 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

  10. Fenretinide-dependent upregulation of death receptors through ASK1 and p38? enhances death receptor ligand-induced cell death in Ewing's sarcoma family of tumours

    PubMed Central

    White, D E; Burchill, S A

    2010-01-01

    Background: Sustained p38MAPK phosphorylation upregulates p75 neurotrophin (p75NTR) and induces apoptosis in Ewing's sarcoma family of tumours (ESFT). As fenretinide induces ESFT death through sustained p38MAPK phosphorylation, we hypothesised that this may be effected through upregulation of death receptors (DRs) and that treatment of fenretinide plus DR ligands may enhance apoptosis. Methods: DR expression was determined by flow cytometry. Trypan blue exclusion assays, caspase-8 flow cytometry and immunoblotting for Bid were used to measure cell death. Results: Fenretinide upregulated cell surface expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors, FAS and p75NTR, in an ASK1- and p38?-dependent manner. Cotreatment with fenretinide and DR ligands resulted in synergistic death compared with either agent alone; caspase-8 and Bid were cleaved in a time-dependent manner. Fenretinide did not increase DR expression in non-malignant cells. Furthermore, fenretinide, TRAIL or a combination of both agents was non-cytotoxic to non-malignant cells. Etoposide and actinomycin D increased expression of all DRs examined, whereas vincristine increased FAS alone. Only actinomycin D and TRAIL, and etoposide with TRAIL or FasL, enhanced death compared with either agent alone. Conclusion: The synergistic death observed with fenretinide and DR ligands suggests that this combination may be an attractive strategy for the treatment of ESFT. PMID:20877355

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

    PubMed

    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

    2014-09-15

    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

  12. 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

  13. 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.

  14. 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; Miñana, Belén; 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

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

    PubMed Central

    Kawano, Masanori; Tanaka, Kazuhiro; Itonaga, Ichiro; Iwasaki, Tatsuya; Tsumura, Hiroshi

    2015-01-01

    Myc oncogenic transcription factor is known to inhibit tumor suppressive microRNAs (miRNAs), resulting in greater expression of their target protein related to cell cycle, invasion or anti-apoptotic factors in human cancer cells. To explore possible oncogenic factors in Ewing’s sarcoma (ES), we conducted microarray-based approach to profile the changes in the expression of miRNAs and its downstream mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs). Three miRNAs, let-7a, miR-16 and miR-29b were significantly down-regulated, whereas c-Myc and cyclin D2 (CCND2) were significantly up-regulated in all tested ES cells compared with hMSCs. To verify that let-7a, miR-16 and miR-29b were the targets of c-Myc in ES cell lines, we transfected siRNA against c-Myc and confirmed the coordinate up-regulation of let-7a, miR-16 and miR-29b through the repression of c-Myc. The ES cells transfected with c-Myc-siRNA and let-7a, miR-16 and miR-29b exhibited the inhibition of the cell cycle progression. The increased expression of let-7a, miR-16 and miR-29b resulted in the reduction of CCND2 protein expression. We also demonstrated that c-Myc-siRNA treatment of ES cells was associated with the decreased expression of CCND2 as a down-stream of three miRNAs. Furthermore, the introduction of let-7a, miR-16 and miR-29b in ES cells could inhibit the c-Myc-mediated up-regulation of CCND2 resulted in the prevention of cell cycle progression. In addition, the transfection of let-7a, miR-16 and miR-29b in ES cells suppressed tumor growth ex vivo treatment. These findings suggests that the up-regulation of c-Myc inhibited the expression of let-7a, miR-16 and miR-29b subsequently induced CCND2 expression in ES cells. The present study might identify a novel oncogenic axis that c-Myc regulates the expression of CCND2 via let-7a, miR-16 and miR-29b, leading to the development new therapeutic targets for ES. PMID:26393798

  16. Combination of dasatinib and curcumin eliminates chemo-resistant colon cancer cells

    PubMed Central

    2011-01-01

    Metastatic colorectal cancer remains a serious health concern with poor patient survival. Although 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) is the standard therapy for colorectal cancer, it has met with limited success. Recurrence of the tumor after chemotherapy could partly be explained by the enrichment of the chemo-resistant sub-population of cancer stem cells (CSCs) that possess the ability for self-renewal and differentiation into different lineages in the tumor. Therefore development of therapeutic strategies that target CSCs for successful treatment of this malignancy is warranted. The current investigation was undertaken to examine the effectiveness of the combination therapy of dasatinib (a Src inhibitor) and curcumin (a dietary agent with pleiotropic effect) in inhibiting the growth and other properties of carcinogenesis of chemo-resistant colon cancer cells that are enriched in CSCs sub-population. Remnants of spontaneous adenomas from APCMin +/- mice treated with dasatinib and/or curcumin were analyzed for several cancer stem cell markers (ALDH, CD44, CD133 and CD166). Human colon cancer cells HCT-116 (p53 wild type; K-ras mutant) and HT-29 (p53 mutant; K-ras wild type) were used to generate FOLFOX resistant (referred to as CR) cells. The effectiveness of the combination therapy in inhibiting growth, invasive potential and stemness was examined in colon cancer CR cells. The residual tumors from APCMin +/- mice treated with dasatinib and/or curcumin showed 80-90% decrease in the expression of the CSC markers ALDH, CD44, CD133, CD166. The colon cancer CR cells showed a higher expression of CSCs markers, cell invasion potential and ability to form colonospheres, compared to the corresponding parental cells. The combination therapy of dasatinib and curcumin demonstrated synergistic interactions in CR HCT-116 and CR HT-29 cells, as determined by Calcusyn analysis. The combinatorial therapy inhibited cellular growth, invasion and colonosphere formation and also reduced CSC population as evidenced by the decreased expression of CSC specific markers: CD133, CD44, CD166 and ALDH. Our data suggest that the combination therapy of dasatinib and curcumin may be a therapeutic strategy for re-emergence of chemo-resistant colon cancer by targeting CSC sub-population. PMID:21774804

  17. 3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells.

    PubMed

    Ponnapakam, Adharsh P; Liu, Jiawang; Bhinge, Kaustubh N; Drew, Barbara A; Wang, Tony L; Antoon, James W; Nguyen, Thong T; Dupart, Patrick S; Wang, Yuji; Zhao, Ming; Liu, Yong-Yu; Foroozesh, Maryam; Beckman, Barbara S

    2014-02-15

    Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive as corresponding regular cancer cells under the exposure to anticancer ceramide analogs. In this work we designed five new ceramide analogs with different backbones, in order to test the hypothesis that extending the conjugated system in ceramide analogs would lead to an increase of their anticancer activity and selectivity towards resistant cancer cells. The analogs with the 3-ketone-4,6-diene backbone show the highest apoptosis-inducing efficacy. The most potent compound, analog 406, possesses higher pro-apoptotic activity in chemo-resistant cell lines MCF-7TN-R and NCI/ADR-RES than the corresponding chemo-sensitive cell lines MCF-7 and OVCAR-8, respectively. However, this compound shows the same potency in inhibiting the growth of another pair of chemo-sensitive and chemo-resistant cancer cells, MCF-7 and MCF-7/Dox. Mechanism investigations indicate that analog 406 can induce apoptosis in chemo-resistant cancer cells through the mitochondrial pathway. Cellular glucosylceramide synthase assay shows that analog 406 does not interrupt glucosylceramide synthase in chemo-resistant cancer cell NCI/ADR-RES. These findings suggest that due to certain intrinsic properties, ceramide analogs' pro-apoptotic activity is not disrupted by the normal drug-resistance mechanisms, leading to their potential use for overcoming cancer multidrug-resistance. PMID:24457089

  18. Ewing's sarcoma cells with CD57-associated increase of tumorigenicity and with neural crest-like differentiation capacity.

    PubMed

    Wahl, Joachim; Bogatyreva, Liubov; Boukamp, Petra; Rojewski, Markus; van Valen, Frans; Fiedler, Jörg; Hipp, Nora; Debatin, Klaus-Michael; Beltinger, Christian

    2010-09-01

    The Ewing family of tumors (EFT) is an important group of pediatric malignancies with a guarded prognosis. Little is known about the heterogeneity of EFT cells, and the cellular origin of EFT is disputed. We now add evidence that EFT are heterogeneous by showing that EFT cells from spheres growing in serum-free medium are markedly more tumorigenic than adherently growing EFT cells. Furthermore, EFT cells strongly expressing CD57 (HNK-1), a surface marker for migrating and proliferating neural crest cells, are more tumorigenic than cells with low expression of CD57, possibly mediated in part by enhanced adhesion and invasion. We contribute to the controversy about the cellular origin of EFT by clonal analysis, showing that EFT cells can differentiate similar to neural crest cells. These data increase our knowledge about the pathogenesis and heterogeneity of EFT. PMID:20104521

  19. Clinicopathological and molecular spectrum of ewing sarcomas/PNETs, including validation of EWSR1 rearrangement by conventional and array FISH technique in certain cases.

    PubMed

    Rekhi, Bharat; Vogel, Ulrich; Basak, Ranjan; Desai, Sangeeta B; Jambhekar, Nirmala A

    2014-07-01

    Over the years, a wide clinicopathological spectrum has been identified within Ewing family of tumors (EFTs). As these tumors are chemosensitive, their correct and timely identification is necessary. The aims of this study were (1) to present the diverse clinicopathological and molecular profile of EFTs in our settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially for application of ancillary techniques, namely RT-PCR for specific transcripts (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and (3) to show the utility of tissue microarray in establishing a new FISH test. Fifty-eight EFTs were identified in 38 males and 20 females within an age-range of 1-65 years (median, 16), mostly in lower extremities (14) (24.1 %). Therapeutically, most patients underwent neoadjuvant chemotherapy with subsequent surgery. Histopathologically, diagnosis of EFTs was initially offered in 41/58 (70.6 %) tumors. On review, 59 % tumors showed diffuse pattern, while 41 % displayed rosettes. Immunohistochemically, tumor cells were mostly diffusely positive for CD99 (48/52) (92.3 %); FLI-1 (17/18) (94.4 %); variably for BCL2 (16/18) (88.8 %), synaptophysin (6/20) (35 %), S100-P (2/7) (28.5 %), CD56 (2/5) (40 %), NSE (2/5) (40 %), calponin (3/4) (75 %), EMA (5/24) (20.8 %) and CK (3/24) (12.5 %), the latter two mostly focally. Fifty five tumors were EWS-FLI1 positive, while a single tumor was EWS-ERG positive. Sensitivity for PCR was 61 %. EWSR1 rearrangement was detected by FISH in 12/13 Ewing sarcomas/PNETs. Sensitivity for EWSR1 test was 92.3 % and specificity was 100 %. Thirty-eight tumors, including 14 molecular confirmed EFTs and 21 other tumors were tested for EWSR1 rearrangement. Among 21 unrelated tumors, EWSR1 rearrangement was detected in few myoepithelial tumors, occasional desmoplastic small round cell tumor and an extraskeletal myxoid chondrosarcoma. Further, a tissue microarray with a separate set of 8 EFTs, confirmed at another laboratory was analysed for validation of EWSR1 rearrangement test. 23/28 (82.1 %) tissue cores of the tissue microarray, stained by FISH were interpretable, including EWSR1 rearrangement, detected in 20/28 tissue cores; not detected in 3 liver cores and uninterpretable in 5 (17.8 %) cores. Classical EFTs can be diagnosed with diffuse, membranous CD99 positivity, intranuclear FLI1 positivity and LCA negativity in malignant round cells. In unconventional cases, it is indispensable to reveal the concomitant fusion m-RNA by RT-PCR. In case of negative molecular results, it is necessary to prove EWSR1 rearrangement by FISH. These tests should be interpreted with clinicopathological correlation. Tissue microarrays for FISH are useful during validation of a new test, especially when sarcomas like EFTs show less genetic heterogeneity within tumor cells. PMID:24293381

  20. 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

  1. Treatment Option Overview (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) ...

  2. 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) ...

  3. General Information about 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) ...

  4. 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

  5. Insulin-Like Growth Factor 1 Receptor as a Therapeutic Target in Ewing Sarcoma: Lack of Consistent Upregulation or Recurrent Mutation and a Review of the Clinical Trial Literature

    PubMed Central

    O'Neill, Alison; Shah, Nilay; Zitomersky, Naamah; Ladanyi, Marc; Shukla, Neerav; Üren, Aykut; Loeb, David; Toretsky, Jeffrey

    2013-01-01

    The insulin-like growth factor 1 receptor (IGF-1R) has been considered an important therapeutic target in Ewing sarcoma (ES), generating a need to identify the subset of patients most likely to respond to IGF-1R inhibitors. We assessed IGF-1R expression in ES cell lines and patient tumors to understand the variable clinical responses to anti-IGF-1R therapy. Using ligand-binding displacement, we measured between 13,000 and 40,000 receptors per cell in ES cell lines. We used ELISA to quantify IGF-1R in patient tumors, which expressed 4.8%??± 3.7 to 20.0%??± 0.2 of the levels in a positive control cell line overexpressing IGF-1R. Flow cytometry showed markedly reduced IGF-1R expression in ES cell lines compared to a standard positive control cell line. The IGF1R gene was sequenced in 47 ES tumor samples and 8 ES cell lines; only one tumor sample showed a nonsynonymous mutation, R1353H, in a region with low functional impact. Finally, we assessed IGF-1R pathway activity in the ES stem cell (ESSC) population, to characterize its potential for resistance to anti-IGF-1R therapy, using Luminex technology. We found no significant differences in IGF-1R pathway activity between ESSCs and the total cell population. Overall, our findings suggest that IGF-1R as a therapeutic target in this sarcoma may require reevaluation. PMID:23431249

  6. 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

  7. Uterine sarcoma

    MedlinePLUS

    Leiomyosarcoma; Endometrial stromal sarcoma; Undifferentiated sarcomas; Uterine cancer-sarcoma ... Past radiation therapy. A few women develop uterine sarcoma 5 to 25 years after they had radiation ...

  8. 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 (6 months) 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 with SFN. PMID:26648123

  9. Ewe Pronunciation.

    ERIC Educational Resources Information Center

    Schneeberg, Nan; Kpotufe, Prosper

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

  10. Targeted therapies for bone sarcomas

    PubMed Central

    Heymann, Dominique; Rédini, Françoise

    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

  11. 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; Sée, 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

  12. 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

  13. 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

  14. Friends of Ewing Cultural Center Ewing Cultural Center, which includes Ewing Manor, the Theatre at

    E-print Network

    Branoff, Theodore J.

    Friends of Ewing Cultural Center Ewing Cultural Center, which includes Ewing Manor, the Theatre annual summer productions; and public access to the garden pathways. Ewing Cultural Center Operational Cultural Center will: Purpose 1. Aid in the financial stability of Ewing Cultural Center; 2. Build the base

  15. Bone Sarcomas: From Biology to Targeted Therapies

    PubMed Central

    Gaspar, Nathalie; Di Giannatale, Angela; Geoerger, Birgit; Redini, Françoise; Corradini, Nadège; Enz-Werle, Natacha; Tirode, Franck; Marec-Berard, Perrine; Gentet, Jean-Claude; Laurence, Valérie; Piperno-Neumann, Sophie; Oberlin, Odile; Brugieres, Laurence

    2012-01-01

    Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours. In this paper, starting with the biology of these tumours, we will discuss potential therapeutic targets aimed at increasing local tumour control, limiting metastatic spread, and finally improving patient survival. PMID:23226965

  16. 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.

  17. 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

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

    PubMed

    Mariño-Enríquez, Adrián; 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

  19. What Is Kaposi Sarcoma?

    MedlinePLUS

    ... key statistics about Kaposi sarcoma? What is Kaposi sarcoma? Kaposi sarcoma (KS) is a cancer that develops ... lungs may cause trouble breathing. Types of Kaposi sarcoma The different types of KS are defined by ...

  20. What Is Uterine Sarcoma?

    MedlinePLUS

    ... key statistics about uterine sarcoma? What is uterine sarcoma? Uterine sarcoma is a cancer of the muscle ... type of cell they developed from: Endometrial stromal sarcomas develop in the supporting connective tissue ( stroma ) of ...

  1. Chemotherapy for Soft Tissue Sarcomas

    MedlinePLUS

    ... Chemotherapy for soft tissue sarcomas Targeted therapy for soft tissue sarcoma Clinical trials for soft tissue sarcomas Complementary and ... soft tissue sarcomas Next Topic Targeted therapy for soft tissue sarcoma Chemotherapy for soft tissue sarcomas Chemotherapy (chemo) is ...

  2. Uterine sarcoma.

    PubMed

    Belgrad, R; Elbadawi, N; Rubin, P

    1975-01-01

    Thirty-four cases of uterine sarcoma were studied with regard to their pathologic characteristics and response to treatment. Pathologic features did not always correlate with subsequent course. Combined therapy seems to enhance two-year survival in endometrial stromal sarcoma (ESS), although some patients may have low-grade tumors and hence represent a more favorable group. Adjuvant irradiation may improve local control rates in some mixed mesodermal sarcomas (MMS), but does not add appreciably to survival. It is of doubtful benefit in the leiomyosarcoma (LMS) group. When irradiation is employed, preoperative therapy is preferred except in the highly malignant mixed mesodermal sarcomas where prompt surgery seems indicated first. Supplemental brachytherapy may also be employed. PMID:1208858

  3. [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

  4. SYMPOSIUM: MOLECULAR GENETICS IN SARCOMA Synovial Sarcoma

    E-print Network

    Capecchi, Mario R.

    SYMPOSIUM: MOLECULAR GENETICS IN SARCOMA Synovial Sarcoma From Genetics to Genetic-based Animal Surgeons 2008 Abstract Synovial sarcomas are highly aggressive mesenchymal cancers that show modest protein in effectively all cases of synovial sarcoma suggests a role in the etiology. Other nonspecific

  5. Histiocytic sarcoma

    PubMed Central

    Machado, Eduardo Silva; de Miranda, Ana Carolina; Escopelli, Ticiane; Caron, Ruggero; Escopelli, Alessandra Cristhina

    2011-01-01

    A 59-year-old white woman, SC, after being treated for pneumonia, presented with an increase in the size of lymph nodes. The immunohistochemical examination diagnosed histiocytic sarcoma. Relapse occurred 12 months after starting chemotherapy. The patient evolved with febrile neutropenia, septic shock and death. PMID:23284265

  6. Kaposi Sarcoma

    Cancer.gov

    DCEG researchers conduct studies on Kaposi sarcoma (KS). Infection with KS-associated herpesvirus (KSHV, also known as human herpesvirus-8 [HHV-8]) is necessary for KS to occur, but other factors, such as HIV infection, greatly increase the risk of the disease.

  7. Uterine sarcoma

    PubMed Central

    Sait, Hesham K.; Anfinan, Nisrin M.; Sayed, Mohamed E. El; Alkhayyat, Shadi S.; Ghanem, Ahmed T.; Abayazid, Reem M.; Sait, Khalid H.

    2014-01-01

    Objectives: To investigate the clinical and histopathological characteristics, with the prognostic factors, treatment outcome, pattern of relapse, and survival analysis of uterine sarcoma patient Methods: All patients with histologically proven uterine sarcoma were identified using the database at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2000 and December 2012. Results: A total of 36 patients with uterine sarcoma were reviewed. The median age of all patients was 57 years, and the mean age was 57.72±13.17 years. Carcinosarcoma was reported in 21 patients (58%), leiomyosarcoma in 7 (19%), undifferentiated endometrial sarcoma in 6 (17%), and rhabdomyosarcoma in 2 (6%). Approximately half of the patients were stages III and IV (28% and 25%), while 15 patients (41%) were stage I; only 2 patients (6%) were stage II. The surgical treatment was hysterectomy and bilateral salpingoophorectomy (H+BSO) plus staging in 18 patients (50%), while in 4 patients (19%), H+BSO plus debulking was performed. Adjuvant chemotherapy was given in 24 (69%) and adjuvant radiotherapy in 5 (14%) cases, At a median follow-up period of 13.5 months, 8 patients (22%) relapsed. The 2-year disease-free survival (DFS) rate was 22% and the 5-year was 14%. In the multivariate analysis, the advanced stages (p=0.015) and lymph vascular invasion (p=0.0001) were associated with poor DFS, while the use of chemotherapy significantly improved the DFS (p=0.027). Conclusions: The poor outcome of high-grade uterine sarcoma patients was identified, and only one third of patients (30%) survived for 2 years. This finding necessitates the need for more aggressive tools to fight this disease. PMID:25316466

  8. 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 Ewing’s 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

  9. Sarcoma Immunotherapy

    PubMed Central

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

    2011-01-01

    Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis. PMID:24213130

  10. Novel histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in sarcoma cancer stem cells.

    PubMed

    Di Pompo, Gemma; Salerno, Manuela; Rotili, Dante; Valente, Sergio; Zwergel, Clemens; Avnet, Sofia; Lattanzi, Giovanna; Baldini, Nicola; Mai, Antonello

    2015-05-14

    Musculoskeletal sarcomas are aggressive malignancies of bone and soft tissues often affecting children and adolescents. Histone deacetylase inhibitors (HDACi) have been proposed to counteract cancer stem cells (CSCs) in solid neoplasms. When tested in human osteosarcoma, rhabdomyosarcoma, and Ewing's sarcoma stem cells, the new HDACi MC1742 (1) and MC2625 (2) increased acetyl-H3 and acetyl-tubulin levels and inhibited CSC growth by apoptosis induction. At nontoxic doses, 1 promoted osteogenic differentiation. Further investigation with 1 will be done in preclinical sarcoma models. PMID:25905694

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

    PubMed Central

    Pasello, Michela; Manara, Maria Cristina; Michelacci, Francesca; Fanelli, Marilù; 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

  12. 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

  13. 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, Ewing’s 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: 1.06–4.38; 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: 1.59–0.03; P<0.001), while no statistical significance was discovered in Ewing’s sarcoma (pooled HR =1.01, 95% CI: 0.45–2.27; P=0.99). Expression of IGF-1R could be a negative prognostic biomarker for patients suffering from BSTSs. PMID:26251617

  14. 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

  15. 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 ...

  16. Sarcoma Foundation of America

    MedlinePLUS

    ... season, don't forget that you can support sarcoma research by shopping through these links. App Now ... Join Donate Our Mission The mission of the Sarcoma Foundation of America (SFA) is to advocate for ...

  17. Soft Tissue Sarcoma

    MedlinePLUS

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

  18. 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

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

    ClinicalTrials.gov

    2015-12-31

    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

  20. 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.

  1. 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 tumor’s 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

  2. Can Kaposi Sarcoma Be Prevented?

    MedlinePLUS

    ... early? Can Kaposi sarcoma be prevented? Kaposi sarcoma (KS) is caused by the Kaposi sarcoma associated herpesvirus ( ... to protect people against KSHV. For now, preventing KS depends on reducing the chance of becoming infected ...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Determinants and consequences of age of primiparity in bighorn ewes

    E-print Network

    Festa-Bianchet, Marco

    752 Determinants and consequences of age of primiparity in bighorn ewes Julien G. A. Martin the reproductive performance of primiparous ewes. We then examined the consequences of delayed primiparity on adult ewes lost more mass in winter and gained less mass in summer than multiparous ewes. Small yearling ewes

  9. 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

  10. Influence of supplemental monensin on gestating and lactating ewes 

    E-print Network

    Peel, Richard Kraig

    1997-01-01

    Twenty-five multiparous Rambouillet ewes were used to determine the effects of feeding monensin during late gestation and early lactation on prepartum and postpartum ewe body weight, milk production, blood glucose levels, and lamb production. Ewes...

  11. 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

  12. What Is a Soft Tissue Sarcoma?

    MedlinePLUS

    ... soft tissue sarcomas? What is a soft tissue sarcoma? A sarcoma is a type of cancer that ... fibrosarcoma Solitary fibrous tumor Types of soft tissue sarcomas Adult fibrosarcoma usually affects fibrous tissue in the ...

  13. Translocation-related sarcomas.

    PubMed

    Mertens, Fredrik; Antonescu, Cristina R; Hohenberger, Peter; Ladanyi, Marc; Modena, Piergiorgio; D'Incalci, Maurizio; Casali, Paolo G; Aglietta, Massimo; Alvegård, Thor

    2009-08-01

    Sarcomas with chromosomal translocations represent only about one fourth of sarcoma diagnoses. However, like gastrointestinal stromal tumor (GIST), with its characteristic KIT or PDGFRA mutations, they are particularly interesting since they provide specific biological insights and mechanisms of action that may have an impact upon prognosis or therapy. These are mechanisms we are just beginning to exploit. In this section we will review the biology and clinical impact of translocation-associated sarcomas and review the clinical findings that have made a recent impact upon patients with these diverse diagnoses. PMID:19664492

  14. Kaposi's Sarcoma (KS)

    MedlinePLUS

    ... Select a Language: Fact Sheet 511 Kaposi's Sarcoma (KS) WHAT IS KS? HOW IS KS TREATED? CAN ... Skin lesions may come back after treatment. If KS has spread into internal organs , systemic (whole-body) ...

  15. 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.

  16. Fleming, Ewing, Macelwane awardees announced

    NASA Astrophysics Data System (ADS)

    AGU has announced that the 1986 John Adam Fleming Medal for original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, and related sciences will be presented to George E. Backus of the Scripps Institution of Oceanography (La Jolla, Calif.).In addition, as previously announced, John Imbrie of Brown University (Providence, R.I.) will receive the Maurice Ewing Award, and James B. Macelwane Awards will be presented to Edward M. Stolper of the California Institute of Technology (Pasadena) and Robert A. Weller of Woods Hole Oceanographic Institution (Woods Hole, Mass.).

  17. 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; López-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

  18. BCOR-CCNB3 Fusions Are Frequent in Undifferentiated Sarcomas of Male Children

    PubMed Central

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

    2014-01-01

    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 5 tumors prior to 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 6 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. 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-?, TNF-? and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-? 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

  20. Immunotherapeutic Intervention against Sarcomas

    PubMed Central

    Pedrazzoli, Paolo; Secondino, Simona; Perfetti, Vittorio; Comoli, Patrizia; Montagna, Daniela

    2011-01-01

    Advances in systemic therapy for sarcoma have produced, over the last two decades, relatively short-term benefits for the majority of patient. Among the novel biologic therapeutics that will likely increase our ability to cure human cancer in the years to come, immunotherapy is one of the most promising approaches. While past attempts to use immunotherapy have failed to dramatically shift the paradigm of care for the treatment of patients with sarcoma, major advances in basic and translational research have resulted, in more recent years, in clinical trial activity that is now beginning to generate promising results. However, to move from “proof of principle” to large scale clinical applicability, we need well-designed, multi-institutional clinical trials, along with continuous laboratory research to explore further the immunological characteristics of individual sarcoma subtypes and the consequent tailoring of therapy. PMID:21716856

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

    ClinicalTrials.gov

    2015-11-25

    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

  3. 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

  4. 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

  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. 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...

  7. 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.

  8. Survival by Stage of Soft Tissue Sarcoma

    MedlinePLUS

    ... sarcomas treated? Survival by stage of soft tissue sarcoma Survival rates are often used by doctors as ... relative 5-year survival rate of people with soft tissue sarcomas is around 50% according to statistics from the ...

  9. Can Soft Tissue Sarcomas Be Found Early?

    MedlinePLUS

    ... Signs and symptoms of soft tissue sarcomas Can soft tissue sarcomas be found early? People who have a strong ... conditions (see “ What are the risk factors for soft tissue sarcomas? ”) caused by defects in certain genes have an ...

  10. 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, ...

  11. 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

  12. 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

  13. 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

  14. Participation and Non-Participation in Mathematics Classrooms Bronwyn Ewing

    E-print Network

    Spagnolo, Filippo

    Participation and Non-Participation in Mathematics Classrooms Bronwyn Ewing Queensland University of Technology, Australia Bf.ewing@qut.edu.au Abstract Active student engagement in mathematics is promoted

  15. Multiphase Flows in Porous Media \\Lambda Richard E. Ewing y

    E-print Network

    Ewing, Richard E.

    Multiphase Flows in Porous Media \\Lambda Richard E. Ewing y Abstract The ability to numerically­Lagrangian techniques, MMOC (modified method of characteristics) described by Douglas and Russell [19] or Ewing et al

  16. ASPECTS OF NUMERICAL METHODS IN MULTIPHASE FLOWS Richard E. Ewing

    E-print Network

    Ewing, Richard E.

    ASPECTS OF NUMERICAL METHODS IN MULTIPHASE FLOWS Richard E. Ewing Texas A&M University Abstract by Douglas and Russell [15] or Ewing et al. [29], or ELLAM (Eulerian Lagrangian localized adjoint methods

  17. EWE-Forschungszentrum NEXT ENERGY im berblick Gemeinntziger

    E-print Network

    #12;EWE-Forschungszentrum NEXT ENERGY im Überblick Gemeinnütziger Trägervereinäge e e analog zur FhG unabhängiger Forschungsdienstleister An-Institut der Olden- burger Universität Finanzierung durch EWE, ergänzt durch Drittmittel Direktor: Prof. Dr. Carsten Agert EWE-Forschungszentrum für Energietechnologie e. V

  18. 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.

  19. www.yalecancercenter.org Learning About Sarcoma

    E-print Network

    O'Hern, Corey S.

    www.yalecancercenter.org Learning About Sarcoma Guest Expert: Gary Friedlaender, MD www sarcoma. Here is Francine Foss. Foss Could you start us off by explaining to our audience what a sarcoma. These include tumors arising in the breast, prostate, lung, or kidney. The sarcomas arise from the support

  20. www.yalecancercenter.org Understanding Sarcoma

    E-print Network

    O'Hern, Corey S.

    www.yalecancercenter.org Understanding Sarcoma Guest Expert: Gary Friedlaender, MD Wayne O in the treatment of sarcoma. Chu Why don't we start off by discussing what sarcoma is because I suspect many people are talking about are sarcomas, cancers of support tissues, such as connective tissues, bone, cartilage

  1. Purdy Awarded 2006 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Purdy, G. Michael; Detrick, Robert S.

    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.

  2. 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...

  3. Pedlosky receives 2011 Maurice Ewing Medal: Response

    NASA Astrophysics Data System (ADS)

    Pedlosky, Joseph

    2012-01-01

    Joseph Pedlosky was awarded the 2011 Maurice Ewing Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is 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 the marine sciences.”

  4. Pedlosky receives 2011 Maurice Ewing Medal: Citation

    NASA Astrophysics Data System (ADS)

    Liu, Zhengyu; Cessi, Paola

    2012-01-01

    Joseph Pedlosky was awarded the 2011 Maurice Ewing Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is 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 the marine sciences.”

  5. Follicular Dendritic Cell Sarcoma

    PubMed Central

    Udayakumar, Achandira M.; Al-Bahri, Maiya; Burney, Ikram A.; Al-Haddabi, Ibrahim

    2015-01-01

    Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation further complicated by the difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence and metastasis. Unlike other soft tissue sarcomas or histiocytic and dendritic cell neoplasms, cytogenetic studies are very limited in FDCS cases. Although no specific chromosomal marker has yet been established, complex aberrations and different ploidy types have been documented. We report the case of a 39-year-old woman with FDCS who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in February 2013. Ultrastructural, immunophenotypical and histological findings are reported. In addition, karyotypic findings showed deletions of the chromosomes 1p, 3q, 6q, 7q, 8q and 11q. To the best of the authors’ knowledge, these have not been reported previously in this tumour. Techniques such as spectral karyotyping may help to better characterise chromosomal abnormalities in this type of tumour. PMID:26355964

  6. Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2015-12-23

    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

  7. 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

  8. 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.

  9. Instantánea del sarcoma de Kaposi

    Cancer.gov

    Información sobre las tendencias de incidencia, mortalidad y financiamiento del NCI sobre el sarcoma de Kaposi; así como ejemplos de actividades del NCI y adelantos en la investigación de este tipo de cáncer.

  10. 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.

  11. 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.

  12. 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

  13. 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 ...

  14. 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

  15. www.yalecancercenter.org Understanding Sarcoma

    E-print Network

    O'Hern, Corey S.

    www.yalecancercenter.org Understanding Sarcoma Guest Expert: Gary Friedlaender, MD The Wayne Southwick Professor of Orthopaedics Director, Yale Cancer Center Sarcoma Program www.wnpr.org #12;Barber I Miller, will discuss sarcomas and explain about the various types and treatment options. Dr. Chu

  16. CENTER FOR SARCOMA AND BONE ONCOLOGY ANGIOSARCOMAS

    E-print Network

    Liu, Xiaole Shirley

    CENTER FOR SARCOMA AND BONE ONCOLOGY ANGIOSARCOMAS RESEARCH DESCRIPTION An effective method Demetri, MD, director of the Center for Sarcoma and Bone Oncology, and collaborating investigators at other leading sarcoma centers worldwide completed a definitive phase III clinical trial of a new

  17. CENTER FOR SARCOMA AND BONE ONCOLOGY LIPOSARCOMA

    E-print Network

    Liu, Xiaole Shirley

    CENTER FOR SARCOMA AND BONE ONCOLOGY LIPOSARCOMA RESEARCH DESCRIPTION Reliable research models had not been effectively modeled. However, investigators at the Center for Sarcoma and Bone Oncology trials testing different MDM2 inhibitors. The Center for Sarcoma and Bone Oncology's leadership

  18. CENTER FOR SARCOMA AND BONE ONCOLOGY LEIOMYOSARCOMA

    E-print Network

    Liu, Xiaole Shirley

    CENTER FOR SARCOMA AND BONE ONCOLOGY LEIOMYOSARCOMA RESEARCH DESCRIPTION Defining the genomic for Sarcoma and Bone Oncology, collaborated with investigators at the Broad Institute of MIT and Harvard types of uterine leiomyosarcoma ­ but may not work against other types of sarcoma ­ helps physicians

  19. INTRODUCTION Kaposi's sarcoma-associated herpesvirus

    E-print Network

    Damania, Blossom

    INTRODUCTION Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, was originally isolated from Kaposi's sarcoma lesions using representational difference analysis (1). KSHV has been linked to the development of Kaposi's sarcoma (2­4) and lymphoproliferative disorders

  20. The Truth about Sarcomas Guest Expert

    E-print Network

    O'Hern, Corey S.

    The Truth about Sarcomas Guest Expert: Dieter Lindskog, MD Associate Professor of Orthopedics at 888-234-4YCC. This week you will hear a conversation about sarcomas with Dr. Dieter Lindskog. Dr and Clinical Research Program Director for the Sarcoma Program at Yale Cancer Center. Here is Steven Gore. Gore

  1. 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

  2. Ewing's Sarcoma EWS protein regulates skeletogenesis by modulation of SOX9

    E-print Network

    Merkes, Christopher Michael

    2013-05-31

    ). In addition, there were reduced intervertebral discs and asymmetrical vertebrae leading to curved spines in MZ ewsa/ewsa mutants. MZ ewsa/ewsa mutants display disorganized alignment of Sox9 expressing neural crest cells at 27hpf. Because both craniofacial...

  3. 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

  4. 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...

  5. Desegregation in Ewing Township, New Jersey: A Case Study.

    ERIC Educational Resources Information Center

    Cotton, Oscar D.; And Others

    In January 1974, a research team from Teachers College, Coloumbia University spent four days in Ewing Township, New Jersey studying and documenting the efforts made by the school district and community in bringing about a desegregated system. Ewing School District was one of four districts to be included in the Comparative Desegregation Project…

  6. 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

  7. [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

  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. How Is Kaposi Sarcoma Diagnosed?

    MedlinePLUS

    ... further tests will be needed to confirm the diagnosis. Medical history and physical exam If your doctor suspects ... tissues, such as skin, lungs, or intestines. Last Medical Review: 08/08/2014 Last Revised: ... Detection, Diagnosis, and Staging Treating Kaposi Sarcoma Talking With Your ...

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

    ClinicalTrials.gov

    2015-12-17

    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

  12. 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

  13. 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

  14. 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.

  15. What Are the Key Statistics about Soft Tissue Sarcoma?

    MedlinePLUS

    ... A LIST » What is cancer? What is a soft tissue sarcoma? What are the key statistics about soft tissue sarcomas? Previous Topic What is a soft tissue sarcoma? Next Topic What are the risk factors for ...

  16. 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 ...

  17. Do We Know What Causes Soft Tissue Sarcomas?

    MedlinePLUS

    ... sarcomas be prevented? Do we know what causes soft tissue sarcomas? Scientists still don't know exactly what causes ... there is also an increased risk of developing soft tissue sarcomas (these were noted in “ What are the risk ...

  18. The Clone Wars – Revenge of the Metastatic Rogue State: The Sarcoma Paradigm

    PubMed Central

    Spraker, Holly L.; Price, Shawn L.; Chaturvedi, Aashi; Schiffman, Joshua D.; Jones, Kevin B.; Lessnick, Stephen L.; Beckerle, Mary; Randall, R. Lor

    2011-01-01

    Ewing sarcoma (ES) is the second most common bone tumor affecting primarily adolescents and young adults. Despite recent advances in biological understanding, intensification of chemotherapeutic treatments, and progress in local control with surgery and/or radiation therapy, patients with metastatic or recurrent ES continue to have a dismal prognosis with less than 20% overall survival. All ES is likely metastatic at diagnosis although our methods of detection and classification may not account for this. Progressive disease may arise via a combination of: (1) selection of chemotherapy-resistant clones in primary tumor, (2) signaling from bone or lung microenvironments that may attract tumor cells to distant locations, and/or (3) genetic changes within the ES cells themselves due to DNA-damaging chemotherapeutic agents or other “hits.” These possibilities and the evidence base to support them are explored. PMID:22649772

  19. 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.

  20. 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.

  1. 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 5–24 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

  2. Undernutrition affects embryo quality of superovulated ewes.

    PubMed

    Abecia, J A; Forcada, F; Palacín, I; Sánchez-Prieto, L; Sosa, C; Fernández-Foren, A; Meikle, A

    2015-02-01

    To determine the effect of undernutrition on embryo production and quality in superovulated sheep, 45 ewes were allocated into two groups to be fed diets that provided 1.5 (control, C; n = 20) or 0.5 (low nutrition, L; n = 25) times daily requirements for maintenance, from oestrous synchronization with intravaginal sponges to embryo collection. Embryos were collected 7 days after the onset of oestrus (day 0). Low nutrition resulted in lower live weight and body condition at embryo collection (P < 0.05). Diet (P < 0.01) and day of sampling (P < 0.001) significantly affected plasma non-esterified fatty acid (NEFA) and insulin concentrations. Plasma leptin concentrations decreased on day 7 only in L ewes. A significant effect of dietary treatment (P < 0.05) and day (P < 0.0001) was observed on plasma insulin-like growth factor (IGF)-I concentrations. The number of recovered oocytes and embryos did not differ between the groups (L: 15.4 ± 0.4; C: 12.4 ± 0.4). Recovery rate was lower (P < 0.05) in the L (60%) than in the C group (73%). The total number of embryos and number of viable-transferable embryos (5.0 ± 0.3 and 3.4 ± 0.3 embryos, respectively) of the L group were lower (P < 0.1) when compared with controls (8.4 ± 0.4 and 6.2 ± 0.4 embryos, respectively). Undernutrition during the period of superovulation and early embryonic development reduced total and viable number of embryos. These effects might be mediated by disruption of endocrine homeostasis, oviduct environment and/or oocyte quality. PMID:24103562

  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. 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

  5. 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.

  6. ASPECTS OF UPSCALING IN SIMULATION OF FLOW IN POROUS MEDIA Richard E. Ewing

    E-print Network

    Ewing, Richard E.

    ASPECTS OF UPSCALING IN SIMULATION OF FLOW IN POROUS MEDIA Richard E. Ewing Institute­Lagrangian techniques, MMOC (modified method of characteristics) described by Douglas and Russell, 32, 76 Ewing et al

  7. Modeling intragranular diffusion in low-connectivity granular media Robert P. Ewing,1

    E-print Network

    Hu, Qinhong "Max"

    Modeling intragranular diffusion in low-connectivity granular media Robert P. Ewing,1 Chongxuan Liu of intragranular diffusion. Citation: Ewing, R. P., C. Liu, and Q. Hu (2012), Modeling intragranular diffusion

  8. 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

  9. 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.

  10. 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, 20–75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0–5). Median number of trabectedin cycles was 3 (range, 1–17). 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, 2–23) 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

  11. Escalating topotecan in combination with treosulfan has acceptable toxicity in advanced pediatric sarcomas.

    PubMed

    Bauer, F; Filipiak-Pittroff, B; Wawer, A; von Luettichau, I; Burdach, S

    2013-05-01

    Patients with advanced pediatric sarcomas have a poor prognosis and novel combination therapies are needed to improve the response rates. Hematological and organ related toxicities have been observed when administering topotecan in combination with, e.g., high dose thiotepa. This study evaluates the toxicity of escalating doses of topotecan alone or in combination with thiotepa or treosulfan. We compared the toxicity including death of complication (DOC) of topotecan alone or in combination with thiotepa or treosulfan in advanced pediatric sarcomas (n = 12). Ten of 12 patients (0.83) suffered from advanced tumors of the Ewing family (i.e., bone or marrow metastases or relapse <24 month after diagnosis, including one neuroepithelial tumor of the kidney) and two from alveolar rhabdomyosarcoma stage IV (0.17). Median age was 15 years (range 5-28). Ratio of female to male was 1:1. Two patients received topotecan alone (1.25 mg/m(2) q 5d and 1.5 mg/m(2) q 5d), three patients received four courses of topotecan (2 mg/m(2) q d 1-5) in combination with thiotepa (100 mg/m(2) q d 1-5), and seven patients received topotecan (2 mg/m(2) q d 1-5) in combination with treosulfan (10g/m(2) q d 3-5). Overall toxicity was not different between all three groups; mean scores were 1.6, 1.8, and 1.7 according to WHO grading (Scale 0-4). Organ related toxicity ranged between 0 and 4 and was not different as well. DOC was 0/2, 1/3, and 0/7 patients respectively. Escalating therapy with topotecan in combination with treosulfan has acceptable toxicity and warrants further investigation in advanced pediatric sarcomas. PMID:23509879

  12. Individual Differences, Parasites, and the Costs of Reproduction for Bighorn Ewes (Ovis canadensis)

    E-print Network

    Lazzaro, Brian

    Individual Differences, Parasites, and the Costs of Reproduction for Bighorn Ewes (Ovis canadensis-795 INDIVIDUAL DIFFERENCES, PARASITES, AND THE COSTSOF REPRODUCTIONFOR BIGHORN EWES (OVIS CANADENSIS) BY MARCO marked bighorn ewes (Ovis canadensis)were examined over 8 years in south-western Alberta, Canada. (2

  13. vol. 176, no. 4 the american naturalist october 2010 Bighorn Ewes Transfer the Costs of

    E-print Network

    Festa-Bianchet, Marco

    vol. 176, no. 4 the american naturalist october 2010 Bighorn Ewes Transfer the Costs canadensis) ewes at Ram Mountain, Alberta, we studied how reproductive effort varied with environmental and ma- ternal conditions. During summer, lactating ewes should gain enough mass to survive the winter

  14. Mass-dependent reproductive strategies in wild bighorn ewes: a quantitative genetic approach

    E-print Network

    Festa-Bianchet, Marco

    Mass-dependent reproductive strategies in wild bighorn ewes: a quantitative genetic approach D. REÂ Mountain bighorn sheep (Ovis canadensis) population, ewes differing by more than 30% in body mass weaned expenditure that varied according to ewe mass. We performed a quantitative genetic analysis to assess genetic

  15. Model-based approach for analysis of transcriptome perturbation reveals Ewing oncogene interaction network

    E-print Network

    Tichit, Laurent

    Model-based approach for analysis of transcriptome perturbation reveals Ewing oncogene interaction of the response. We apply it to oncogene induction experiments in Ewing tumor cell-lines. From non-linear fit of time series to annotated network of EWS/FLI1 in Ewing tumor cell-lines To characterize numerically

  16. Rainfall limit of the N cycle on Earth Stephanie A. Ewing,1,2

    E-print Network

    Macalady, Jenn

    Rainfall limit of the N cycle on Earth Stephanie A. Ewing,1,2 Greg Michalski,3 Mark Thiemens,4. Citation: Ewing, S. A., G. Michalski, M. Thiemens, R. C. Quinn, J. L. Macalady, S. Kohl, S. D. Wankel, C clearly preserves soluble salts in these soils [Ewing et al., 2006], the specific relationship between

  17. Diazepam facilitates acceptance of alien lambs by postparturient ewes.

    PubMed

    Ferreira, A; Carrau, A; Rodas, E; Rubianes, E; Benech, A

    1992-06-01

    The aim of this study was to determine the effect of diazepam on the behavior of parturient ewes towards alien lambs. There is evidence that benzodiazepines cause behavioral changes during the lactation period in rats. In two independent experiments, it was found that the ewes acceptance of alien lambs significantly increased following a single injection of the benzodiazepine, diazepam, given either 1 or 12 h after parturition. In a third experiment, in which the alien lamb was not permitted to suckle during a period of 2 h after the injection, the diazepam treatment did not provoke significant differences in maternal behavior of the ewes, although in the ewes treated with diazepam, suckling clearly tended to increase. At the dose employed (20 mg), administered 1 h after birth, diazepam caused no signs of sedation as assessed in an open-field test carried out 3 h after parturition. This doesn't eliminate the possibility of diazepam having a sedative effect in the period of 2 h immediately after its administration and before the test and, in this way, facilitating suckling which could be responsible for the maternal behavior observed after this period. As diazepam gives rise to an enhanced GABAergic activity in the brain, these observations suggest that a GABAergic mechanism could also play a role in the process whereby ewes form a selective bond with their own offspring. PMID:1641413

  18. Seasonal Fluctuations of Nematode Populations in Breeding Ewes and Lambs

    PubMed Central

    Ayalew, L.; Gibbs, H. C.

    1973-01-01

    The seasonal changes in nematode populations of a flock of sheep in the Montreal area were determined using serial fecal egg counts, fecal culture of larvae and necropsy worm counts. It was found that Ostertagia spp.,Nematodirus spp., Trichostrongylus agei, Trichostrongylus spp. and Chabertia ovina over-wintered on pasture and could initiate patent infections the following spring. The development of populations of H. contortus was typical of that seen with most of the other species and was characterized by the following series of events. In early winter when the study was started with stabled pregnant ewes, most of the populations were immature and the egg counts were low and remained so throughout the entire winter. However, in the spring, following lambing, large numbers of adult worms were seen with a consequent decrease in immatures and a sudden increase in egg counts. When the ewes and lambs were pastured together, the egg counts in ewes dropped consequent to “self-cure”, the “spring-rise” providing the major source of overwhelming infections for lambs with deaths by the end of July. As the season progressed larvae taken in by both ewes and lambs did not mature, and by early fall, most of the worm population consisted of immature forms. It appeared that H. contortus could not have more than two generations in ewes or lambs in a single grazing season. PMID:4265556

  19. 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

  20. 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 Océanologique 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 Géodynamique. 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 Supérieure, one of the French Grandes Ecoles.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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 0–19, 20–49 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

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

    PubMed Central

    Mørk, Tormod; Waage, Steinar; Tollersrud, Tore; Kvitle, Bjørg; Sviland, Ståle

    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

  7. 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

  8. [Computed tomography of primary pulmonary sarcomas].

    PubMed

    König, R; Steinbächer, M; Merkle, N

    1986-06-01

    CT findings of 4 patients with primary pulmonary sarcomas are presented. In all cases there was a more than 5 cm large solid, circular configured, intrapulmonary growth without enlarged hilar and mediastinal lymph nodes and also without atelectasis. PMID:3731692

  9. General Information about Adult Soft Tissue Sarcoma

    MedlinePLUS

    ... tissue sarcoma is a disease in which malignant (cancer) cells form in the soft tissues of the body. ... diagnosed, tests are done to find out if cancer cells have spread within the soft tissue or to ...

  10. Drugs Approved for Soft Tissue Sarcoma

    Cancer.gov

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

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

    PubMed

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

    2015-01-01

    Sarcomas are a heterogeneous group of tumors. Their diagnosis is based on morphology and immunohistochemical profile, with categories of tumors according to the type of tissue that they resemble. Nevertheless, for several tumors, cellular origin is unknown. Molecular analysis performed in recent years allowed, combining histophenotype and genomics, better classifying such sarcomas, individualizing new entities and grouping some tumors. Simple and recurrent genetic alterations, such as translocation, mutation, amplification, can be identified in one of two sarcomas and appear as new diagnostic markers. Their identification in specialized laboratories in molecular pathology of sarcomas is often useful and sometimes necessary for a good diagnosis, leading to a heavy and multidisciplinary multi-step treatment. PMID:25533919

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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...

  19. Recent Developments in Reservoir Simulation Richard E. Ewing \\Lambda

    E-print Network

    Ewing, Richard E.

    Recent Developments in Reservoir Simulation Richard E. Ewing \\Lambda Abstract Three basic problem areas have dominated much of the recent research in reservoir simulation. First, one must obtain processes. This includes the problem of obtaining accurate reservoir descriptions at various length scales

  20. Ellen Thomas Receives 2012 Maurice Ewing Medal: Citation

    NASA Astrophysics Data System (ADS)

    Bralower, Timothy J.

    2013-01-01

    Ellen Thomas was awarded the 2012 Maurice Ewing Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is 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 the marine sciences".

  1. William J. Jenkins Receives 2010 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Doney, Scott C.; Kurz, Mark; Jenkins, William J.

    2011-02-01

    William J. Jenkins was awarded the 2010 Maurice Ewing Medal at the AGU Fall Meeting Honors Ceremony, held on 15 December 2010 in San Francisco, Calif. The medal is 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 the marine sciences.”

  2. H. Thomas Rossby Receives 2009 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Rhines, Peter B.; Rossby, H. Thomas

    2010-02-01

    H. Thomas Rossby was awarded the 2009 Maurice Ewing Medal at the AGU Fall Meeting Honors Ceremony, held on 16 December 2009 in San Francisco, Calif. The medal is for “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.”

  3. 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.

  4. 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 (?2-test, p?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?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

  5. 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 ...

  6. 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) ...

  7. 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

  8. Cancer Cell A Conditional Mouse Model of Synovial Sarcoma

    E-print Network

    Capecchi, Mario R.

    Cancer Cell Article A Conditional Mouse Model of Synovial Sarcoma: Insights into a Myogenic Origin.01.016 SUMMARY Synovial sarcoma is an aggressive soft-tissue malignancy marked by a unique t(X;18) translocation sarcoma based on conditional expression of the human SYT-SSX2. Using this model, we have identified

  9. CENTER FOR SARCOMA AND BONE ONCOLOGY GASTROINTESTINAL STROMAL TUMOR (GIST)

    E-print Network

    Liu, Xiaole Shirley

    CENTER FOR SARCOMA AND BONE ONCOLOGY GASTROINTESTINAL STROMAL TUMOR (GIST) RESEARCH DESCRIPTION that continue to make a tangible difference in the lives of people with GIST ­ the most common form of sarcoma, as with most drugs, patient response can vary; George Demetri, MD, director of the Center for Sarcoma and Bone

  10. Targeted Therapies in Sarcomas: Challenging the Challenge

    PubMed Central

    Martín Liberal, Juan; Lagares-Tena, Laura; Sáinz-Jaspeado, Miguel; Mateo-Lozano, Silvia; García 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

  11. Metastatic undifferentiated pleomorphic sarcoma causing intraoperative stroke.

    PubMed

    Spaulding, Reed; Koumoundouros, Theodoros; Parker, Joseph C

    2013-01-01

    Malignant Fibrous Histiocytoma was historically the most commonly diagnosed soft tissue sarcoma of adults. In 2002, the World Health Organization declassified malignant fibrous histiocytoma as a formal diagnostic entity. They recommended renaming the disease "Pleomorphic Undifferentiated Sarcoma". Current thoughts about the origin of this tumor are being debated. We report a case of a dedifferentiated liposarcoma that metastasized to the lung within one year. The histologic morphology of the metastasis was more aggressive than the primary lesion, and was consistent with a pleomorphic undifferentiated sarcoma. Following surgical resection of the metastatic pulmonary lesion, the patient never fully regained consciousness. He expired the day following his surgery. At autopsy, the patient was found to have died from a massive hemorrhagic stroke involving almost the entire left cerebrum. Tumor emboli from the pulmonary metastasis were seen in the left middle cerebral artery, causing the cerebral infarct. The embolic lesion was consistent with a pleomorphic undifferentiated sarcoma. This case illustrates the evolution that soft tissue sarcomas can undergo as they metastasize and become increasingly undifferentiated, and confirms the surgical risk of resecting such lesions. PMID:23694792

  12. Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-06-24

    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

  13. 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

  14. Reproductive performance of ewes grazing lucerne during different periods around mating.

    PubMed

    Robertson, S M; Clayton, E H; Friend, M A

    2015-11-01

    High intake of lucerne pastures or feeding of other high quality diets during early pregnancy may increase embryo mortality, negating any benefit of improved nutrition on ovulation rate in ewes. This study was conducted to determine whether grazing ewes on lucerne (Medicago sativa) pastures for 7 days prior to and throughout joining would result in greater foetal numbers than if ewes were removed 7 days after the commencement of joining, or if ewes grazed senescent pasture throughout the joining period. Merino ewes (300) were allocated to two replicates of three treatments, grazing pastures between Days -7 and 36 of an unsynchronised, natural autumn joining. Grazing lucerne to Day 7 of joining resulted in 30% more (P<0.05) foetuses per ewe than grazing senescent pasture (1.60±0.07 and 1.31±0.07, respectively), and 19% more lambs marked per ewe joined. Extending grazing of lucerne past Day 7 of joining did not result in additional foetuses per ewe (1.61±0.06) in comparison with only grazing lucerne to Day 7 of joining. Greater than 80% of ewes mated during the first 14 days of joining, and the proportions of ewes returning to oestrus and re-mating (0.18±0.022) and of non-pregnant (0.09±0.017) ewes were similar (P>0.05) among all treatment groups, suggesting no differences between treatments in embryo mortality. Grazing naturally cycling ewes on lucerne prior to and during joinings in autumn is recommended as a means to increase the number of lambs born, although additional gains may not be obtained by grazing past day seven of joining. PMID:26454684

  15. Multimodality therapy for metastatic sarcomas confined to the lung

    PubMed Central

    GOLLARD, RUSSELL P.; TURNER, J. FRANCIS

    2012-01-01

    Metastectomy or resection of sarcomas which have metastasized to the lung from other sites has a long and established history. At present, there are more than forty different drugs with activity in soft tissue sarcomas. A number of sarcomas demonstrate differential sensitivities to chemotherapy and targeted agents. Intimate knowledge of the biological behavior of each distinct type of sarcoma should predicate what treatment or protocol is most suitable. Certain patients might benefit from either neoadjuvant or adjuvant therapy following the resection of metastatic lesions. Much remains to be learned about the differential sensitivities of various sarcomas to different treatment regimens. PMID:23205068

  16. 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

  17. 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.

  18. Prions in Milk from Ewes Incubating Natural Scrapie

    PubMed Central

    Lacroux, Caroline; Simon, Stéphanie; Benestad, Sylvie L.; Maillet, Séverine; Mathey, Jacinthe; Lugan, Séverine; Corbière, Fabien; Cassard, Hervé; Costes, Pierrette; Bergonier, Dominique; Weisbecker, Jean-Louis; Moldal, Torffin; Simmons, Hugh; Lantier, Frederic; Feraudet-Tarisse, Cécile; Morel, Nathalie; Schelcher, François; Grassi, Jacques; Andréoletti, Olivier

    2008-01-01

    Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species. PMID:19079578

  19. TCGA Benchmark 4: Evaluating SV and SNV Calls Using Cell Line Genomes - Adam Ewing, TCGA Scientific Symposium 2012

    Cancer.gov

    Home News and Events Multimedia Library Videos TCGA Benchmark 4: Evaluating SV and SNV Calls Using Cell Line Genomes - Adam Ewing TCGA Benchmark 4: Evaluating SV and SNV Calls Using Cell Line Genomes - Adam Ewing, TCGA Scientific Symposium 2012 You

  20. Legume silage to sheep Growing lambs, as well as ewes in late pregnancy and early lactation, have high requirements

    E-print Network

    Legume silage to sheep Growing lambs, as well as ewes in late pregnancy and early lactation, have/clover-silage as onlu forage in diets for ewes and for lambs of different ages. In conclusion, the results show some

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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...

  6. Many eyes or many ewes: vigilance tactics in female bighorn sheep Ovis canadensis vary according to reproductive status

    E-print Network

    Festa-Bianchet, Marco

    Many eyes or many ewes: vigilance tactics in female bighorn sheep Ovis canadensis vary according patterns in bighorn sheep Ovis canadensis ewes. We also test whether the observed vigilance patterns with increasing group size, vigilance tactics differed between barren and lactating females. Lactating ewes relied

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

    ClinicalTrials.gov

    2015-09-10

    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

  8. Tissue Microarray Validation of Epidermal Growth Factor Receptor and SALL2 in Synovial Sarcoma

    E-print Network

    Botstein, David

    Tissue Microarray Validation of Epidermal Growth Factor Receptor and SALL2 in Synovial Sarcoma,§ Stanford University School of Medicine, Stanford, California Histological diagnosis of synovial sarcoma can levels in synovial sarcoma than in other soft tissue tumors, representing excellent candidates

  9. ORF57 Overcomes the Detrimental Sequence Bias of Kaposi's Sarcoma-Associated Herpesvirus Lytic Genes

    E-print Network

    Mandel-Gutfreund, Yael

    ORF57 Overcomes the Detrimental Sequence Bias of Kaposi's Sarcoma-Associated Herpesvirus Lytic Hannover, Hanover, Germanya ; Technion Institute, Haifa, Israelb ABSTRACT Kaposi's sarcoma and cellular mRNAs. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus

  10. Effects of level and source of copper on copper status of ewes and newborn lambs 

    E-print Network

    Eckert, Gregory Evan

    1997-01-01

    Experiment one was conducted to determine the Cu status of mature ewes fed two sources Of CU (CUS04 VS CU proteinate) at one of three levels (10, 20 and 30 mg/kg). Ewes were fed a basal diet containing cottonseed hulls, cottonseed meal, and cracked...

  11. 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...

  12. 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...

  13. A LOCAL APPROACH TO THE FINITENESS OBSTRUCTION JOHN EWING, PETER LOFFLER, AND ERIK KJR PEDERSEN

    E-print Network

    Pedersen, Erik Kjær

    A LOCAL APPROACH TO THE FINITENESS OBSTRUCTION JOHN EWING, PETER L¨OFFLER, AND ERIK KJÆR PEDERSEN 0 the localization square Z // Z(p) Z(1/p) // Q 1 #12;2 JOHN EWING, PETER L¨OFFLER, AND ERIK KJÆR PEDERSEN If we

  14. 78 FR 338 - CSX Transportation, Inc.; Abandonment Exemption-in Ewing Township, Mercer County, NJ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-03

    ...CSX Transportation, Inc.; Abandonment Exemption--in Ewing Township, Mercer County, NJ CSX Transportation, Inc. (CSXT...Drive, and the end of the track at milepost QAT 34.49, in Ewing Township, Mercer County, N.J. (the Line). The Line...

  15. Primary granulocytic sarcoma of meninges and mediastinum as diagnostic dilemma.

    PubMed

    Samanta, Dipti Rani; Mohanty, Kirti Ranjan; Roopesh, K; Senapati, Surendra Nath

    2013-06-01

    Granulocytic sarcoma is a rare hematological neoplasm which is often misdiagnosed. We report two patients of primary granulocytic sarcoma, one at meninges who was diagnosed radiologically as meningioma and on histopathology as langerhans cell histiocytosis. The second patient presented with an ulcerated chest wall swelling, who on histopathology revealed malignant round cell tumour. Both the patients subsequently proved as primary granulocytic sarcoma on immunohistochemistry. These two cases are reported here due to their rarity. PMID:24426349

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Thyroid carcino-sarcoma in a dog.

    PubMed

    Giuliano, Antonio; Grant, Jessica; Benoit, Jerome

    2013-01-01

    An adult male greyhound was diagnosed with a thyroid carcino-sarcoma by means of histopathology and positive immuno-histochemistry staining for cytokeratin and vimentin. Surgery and radiotherapy of the area were successful in local tumour control. Adjuvant chemotherapy was recommended to treat and prevent further metastasis. The use of carboplatin, metronomic cyclophosphamide chemotherapy and toceranib failed to control the progression of distant metastasis. The survival time was seven months from the time of diagnosis. This is the eighth case of carcino-sarcoma of the thyroid documented in veterinary medicine and the first one treated with a multimodal approach based on surgery, radiotherapy and chemotherapy. As documented in human medicine, chemotherapy appeared to be ineffective to prevent or delay the progression of the metastatic disease in this case. PMID:23718201

  2. 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.

  3. 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

  4. 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.

  5. Undifferentiated uterine sarcoma metastatic to the brain

    PubMed Central

    Stofko, Douglas L

    2013-01-01

    Background: Undifferentiated uterine sarcoma (UUS) is a rare tumor with an aggressive growth pattern. They occur in women from 40 to 60 years and are generally characterized by poor prognosis, a high rate of local recurrence, and distant metastases. UUS accounts for 0.2% of all gynecological malignancies. Possible treatments include surgery, radiotherapy, and chemotherapy. Case Description: A 65-year-old female with postmenopausal bleeding was found to have a uterine mass for which she underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The pathologic evaluation was consistent with undifferentiated endometrial sarcoma. She began experiencing headaches with associated visual disturbances. Magnetic resonance imaging (MRI) of the brain showed a homogenous enhancing occipital dural-based mass measuring 1.6 × 1.8 × 1.7 cm. Due to the rarity of metastatic uterine sarcoma to the brain, this was believed to represent a meningioma and subsequently observed. Interval MRI scan revealed a significant increase in size of the right occipital mass to 2.3 cm with increased edema and mass effect. She underwent right occipital image guided craniotomy for resection of the mass. Histopathology confirmed UUS metastases. Conclusion: Randomized trials analyzing these treatment options are limited due to the rarity of this disease; therefore, a standard therapy is not established. Based on a review of the literature, this is only the fourth case reported of UUS metastatic to the brain. PMID:24231690

  6. 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, 25–50% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease. PMID:24778572

  7. Hypofractionated accelerated radiotherapy in osteogenic sarcoma.

    PubMed

    Lombardi, F; Gandola, L; Fossati-Bellani, F; Gianni, M C; Rottoli, L; Gasparini, M

    1992-01-01

    A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients. PMID:1429102

  8. 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-Gonçalves, 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

  9. Vaginal histological changes after using intravaginal sponges for oestrous synchronization in anoestrous ewes.

    PubMed

    Manes, J; Campero, C; Hozbor, F; Alberio, R; Ungerfeld, R

    2015-04-01

    To characterize the histological and cytological vaginal changes generated by the use of intravaginal sponge (IS) applied in oestrous synchronization treatments in ewes during mid-non-breeding season. Thirty-five multiparous ewes were allocated to three experimental groups according to the moment in which the samples were taken: (i) ewes treated with IS containing 60 mg of medroxyprogesterone acetate for 14 days, sampled the day of IS removal (group ISR; n = 10), (ii) or after sponge removal at time of oestrus or 72 h after removal (group AR; n = 14) and (iii) ewes without sponge treatment that were sampled at the day of IS removal of the other groups (group CG; n = 11). Vaginal biopsies and cytological samples were taken from the anterior vaginal fornix area. The vagina of the CG group had a stratified squamous epithelium with a moderate degree of cellular infiltration with lymphocytes and plasma cells in the lamina propia. Treated ewes (ISR and AR) had epithelial hyperplasia and hypertrophy. ISR ewes had haemorrhage and perivascular infiltrate and an increased number of epithelial cells, neutrophils, macrophages and erythrocytes at IS removal. The use of IS generated histological and cytological alterations in the vaginal wall when used for oestrous synchronization in anoestrous ewes. PMID:25604995

  10. 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.

  11. 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

  12. Key odorants of Oscypek, a traditional Polish ewe's milk cheese.

    PubMed

    Majcher, Ma?gorzata A; Jele?, Henryk H

    2011-05-11

    The unique flavor of Oscypek, a Polish ewe's milk smoked cheese, is described as slightly sour, piquant, salted, and smoked. In this paper with the application of gas chromatography-olfactometry (GC-O) and combination of aroma extract dilution analysis (AEDA) 20 potent odorants of this cheese have been identified within the flavor dilution factor (FD) range of 4-2048. Among them, 2-methoxyphenol, 2-methoxy-4-methylphenol, 4-methylphenol, and butanoic acid showed the highest FD factors. Quantification results based on labeled standard addition followed by calculation of odor activity values (OAV) of 13 compounds with the highest FD factors revealed that 11 compounds were present at concentrations above their odor threshold values and therefore mostly contribute to the overall aroma of smoked ewe's milk cheese. Six of those compounds were represented by phenolic derivatives, with the highest OAV for 2-methoxyphenol (1280). Analysis of key odorants of an unsmoked cheese sample showed that the smoking process had a fundamental influence on Oscypek aroma formation. PMID:21456615

  13. 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

  14. 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.

  15. [Follicular dendritic cell sarcoma in head and neck region].

    PubMed

    Cerda, T; Sun, X S; Cazorla, A; Laurent, C; Floret, F; Haudebourg, J; Thyss, A; Thariat, J

    2014-01-01

    Follicular dendritic cell sarcomas are a recently described entity, with biphenotypic characteristics of lymphomas and sarcomas. The treatment is hardly consensual in the literature. We report two head and neck cases, of favorable outcome after surgery and radiotherapy. Histopathology and differential diagnoses are discussed as well as the therapeutic strategies used. PMID:24373643

  16. 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.

  17. 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

  18. 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

  19. 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

  20. [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

  1. Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-12-07

    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

  2. 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

  3. Ewing, R. Transportation Service Standards As if People Matter. Transportation Research Record 1400: 10-17.

    E-print Network

    County TSM (transportation system management)/TDM indexes (including auto, transit, and nonEwing, R. Transportation Service Standards ­ As if People Matter. Transportation Research Record County will be using congestion indexes rather than LOS, Bellevue has mobility management areas

  4. Effects of prenatal shearing of ewes and calf genotype on cold tolerance of newborn ruminants 

    E-print Network

    Falck, Stephanie Joy

    2001-01-01

    Weather-related losses are the second leading cause of death for both calves and lambs. One management practice used to reduce lamb losses due to cold exposure is shearing pregnant ewes. Research has shown that lambs ...

  5. The roles of estradiol-17 beta and prolactin in uterine gland development in the neonatal ewe 

    E-print Network

    Carpenter, Karen Denise

    2005-11-01

    Endometrial glands are required for adult uterine function and develop post-natally in mammalian species. Therefore, studies were conducted using neonatal ewes as a model to determine: 1) the roles of estradiol-17-alpha and estrogen receptor-alpha...

  6. The effect of maternal nutritional status during mid-gestation on placental characteristics in ewes.

    PubMed

    Sen, U; Sirin, E; Kuran, M

    2013-02-01

    The aim of this study was to determine the effects of maternal nutritional status during mid-gestation on placental characteristics in ewes. Time of estrus of 3-5 years old Karayaka breed ewes was synchronized and mating was monitored to determine the day 0 of gestation. The ewes had similar body weights (47.8±0.7kg) and loin eye muscle values (thickness; 20.9±1.0mm and fat thickness; 4.7±0.5mm) at mating. The ewes were allocated into two treatment groups at day 30 of gestation; under-fed (UF; n=12) and well-fed (WF; n=13) groups. The ewes in UF group were fed with a diet to provide 50% of their daily requirement from day 30 to day 80 of gestation and 100% of their daily requirement during the rest of the gestation period. The ewes in WF group were fed at least 100% of their daily requirement throughout gestation. The singleton bearing ewes in the UF group had a lesser (P<0.05) placental weight (354.1 compared with 378.3g), average cotyledon weight (1.50 compared with 1.82g) and lamb birth weight (3.8 compared with 4.2kg) than singleton bearing ewes in the WF group. There were positive correlations between placental weight and lamb birth weight (r=.469; P<0.05), placental weight and average cotyledon weight (r=.695; P<0.01), average cotyledon weight and lamb birth weight (r=.742; P<0.01) and placental efficiency and cotyledon density (r=.853; P<0.01) for ewes in WF group. Additionally, the pattern of weight gain/loss was different (P<0.05) between the two groups. Ewes in UF group lost body weight progressively from day 30 of gestation until day 80. The results of present study show that under-feeding of ewes during mid-gestation may cause an insufficient placental development and hence alter fetal development resulting in a reduced birth weight from singleton pregnancies. PMID:23273533

  7. Continuous exposure to sexually active rams extends estrous activity in ewes in spring.

    PubMed

    Abecia, J A; Chemineau, P; Flores, J A; Keller, M; Duarte, G; Forcada, F; Delgadillo, J A

    2015-12-01

    Sexual activity in sheep is under photoperiodic control, which is the main environmental factor responsible for the seasonality of reproduction. However, other natural environmental factors such as presence of conspecifics can slightly influence the timing of onset and offset of the breeding season. In goats, we have found that the continuous presence of bucks that were rendered sexually active out of season by previous exposure to long days, prevented goats from displaying seasonal anestrus, which suggests that the relative contribution of photoperiod in controlling seasonal anestrus should be reevaluated in small ruminant species. The aim of this study was to assess whether the presence of sexually active rams that had been stimulated by artificial photoperiod and melatonin implants, reduces seasonal anestrus in sheep, by prolonging ovulatory activity in spring. Ewes were assigned to one of two groups (n = 16 and 15), which were housed in two separate barns, and kept in contact, either with the treated or the control rams between March and July. Vasectomized rams were either exposed to 2 months of long days followed by the insertion of three subcutaneous melatonin implants (treated rams, n = 8), or exposed to natural light conditions (control rams, n = 2). Estrus was monitored daily, and weekly plasma progesterone analyses indicated ovulatory activity. Ewes that were exposed to treated rams exhibited a higher proportion of monthly estrus than ewes exposed to the control rams (P < 0.05). Thirteen of 15 ewes (one ewe was not considered because of the presence of persistent CL) exposed to stimulated rams exhibited estrous behavior in a cyclic manner. In contrast, all ewes exposed to control rams stopped estrous activity for a period of time during the study, such that this group exhibited a significantly longer anestrous season (mean ± standard error of the mean 89 ± 9 days) than did the ewes housed with treated rams (26 ± 10 days; P < 0.0001). Among 15 ewes housed with treated rams, 13 of them exhibited continuous ovulatory activity between March and July, whereas one stopped in June and two in July. All ewes kept with control rams stopped ovulating for some time; consequently, those ewes had a longer anovulation period than did the group exposed to treated rams (3 ± 3 vs. 18 ± 7 days, respectively; P < 0.05). In conclusion, continuous exposure to sexually activated rams induced by artificial photoperiod and melatonin implants in spring extended the ovarian activity of ewes in spring, which results in an increase in estrous expression. PMID:26329664

  8. Head and Neck Sarcomas: The UCLA Experience

    PubMed Central

    Tajudeen, Bobby A.; Fuller, Jennifer; Lai, Chi; Grogan, Tristan; Elashoff, David; Abemayor, Elliot; St. John, Maie

    2014-01-01

    Purpose To profile the clinical presentation, subtype distribution, and treatment results of sarcomas of the head and neck at a single tertiary academic center over an 11-year period. Materials and Methods A retrospective review was performed by examining the records and reviewing the pathology of 186 patients with head and neck sarcomas treated at UCLA Medical Center from 2000 to 2011. Results The mean age of the study population was 49 +/? 22 years. 58% of the patients were male and 42% were female. Median duration of follow-up for the entire group was 18.5 months. The most common presenting symptom was a mass lesion in 59.9% of patients. The nasal cavity/sinus was the most common presenting site seen in 22% of patients. Solitary fibrous tumor/hemangiopericytoma was the most common subtype. 15% of patients had evidence of prior radiation exposure. 26.3% of tumors were greater than 5cm and 35.5% were high-grade. Margins were positive in 31.2% of patients. Lymph node metastasis was rare at 6.5%. Perineural invasion was identified in 6.5%. Among all subtypes, 5-yr recurrence-free survival and overall survival were 50% and 49%, respectively. Multivariate analysis demonstrated that grade and margin status were predictors of recurrence-free survival while grade and age affected overall survival. Conclusions Head and neck sarcomas are a rare entity frequently presenting as a mass lesion. In our series, lesions tended to be high-grade with a significant portion of surgical specimens having positive margins. Grade and margin status were the most important predictors of survival. PMID:24721744

  9. 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

  10. 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, 4.9 mg Se/week as Se yeast (maximum FDA-allowed concentration), or supranutritional concentrations of Se yeast (14.7 and 24.5 mg Se/week) starting early fall for 85 weeks. 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 24.5 mg 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 4.9 mg 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

  11. Novel genes induce uterine receptivity: the characterization of a specific gene product in the ewe uterus 

    E-print Network

    De Graauw, Jennifer Ann

    2013-02-22

    -1 NOVEL GENES INDUCE UTERINE RECEPTIVITY: THF. CHARACTERIZATION OF A SPECIFIC GENE PRODUCT IN THE EWE UTERUS A Senior Honors Thesis By JENNIFER ANN DE GRAAUW Submitted to the Office of Honors Programs 4 Academic Scholarships Texas A&M University... In partial fulfillment of the requirements of the UNIVERSITY UNDERGRADUATE RESEARCH FELLOWS APRIL 2000 Group: Molecular Genetics NOVEL GENES INDUCE UTERINE RECEPTIVITY: THE CHARACTERIZATION OF A SPECIFIC GENE PRODUCT IN THE EWE UTERUS A Senior Honors...

  12. [Sarcoma of the hand and wrist].

    PubMed

    Steinau, H U; Farzaliyev, F; Stricker, I; Hauser, J; Podleska, L E

    2015-04-01

    Sarcomas of the hand and wrist are rare malignancies, which should be referred to high-volume comprehensive cancer centres providing multidisciplinary treatment options. The tumour board should propose patient-oriented oncological pathways as well as sophisticated hand and plastic reconstructive procedures. In Addition, isolated limb perfusion with TNF-alpha and melphalan is likely to lead to preoperative tumour shrinkage allowing for R0 resection in sano. Our clinical results in long-term survivors demonstrate reduced amputation rates and salvage of basic hand function when a risk-adapted treatment rationale is applied. PMID:25761400

  13. 100 years of Rous sarcoma virus

    PubMed Central

    2011-01-01

    The discovery of Rous sarcoma virus, which was reported by Peyton Rous in the Journal of Experimental Medicine 100 years ago, opened the field of tumor virology. It showed that some cancers have infectious etiology, led to the discovery of oncogenes, and laid the foundation for the molecular mechanisms of carcinogenesis. Rous spent his entire research career at The Rockefeller Institute, and he was the JEM’s longest serving editor. Here, we comment briefly on the life of this remarkable scientist and on the importance of his discoveries. PMID:22110182

  14. 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

  15. Gastrointestinal Nematode Populations in Stabled Ewes of Rimouski Region

    PubMed Central

    Ayalew, L.; Fréchette, J. L.; Malo, R.; Beauregard, C.

    1973-01-01

    Nematode populations is stabled ewes of the Rimouski region were studied by means of fecal worm egg counts, fecal culture of larvae, and worm counts at necropsy. It was found that during the winter strongyle egg counts were low, Trichostrongylus eggs being most numerous, The stronglye egg counts increased following lambing and reached peak in June. Ostertagia spp was the principal contributor to this “spring-rise”, with substantial contribution from Trichostrongylus and Haemonchus contortus. The bulk of adult worm populations in winter, however, was made up of Trichostrongylus, whereas the great majority of the populations of Ostertagia spp, H. contortus and Nematodirus spp were inhibited in development at the fourth larval stage. All the worms recovered at necropsy in spring were adults, coinciding with the “spring-rise”. PMID:4270807

  16. Induction of ovulation in anestrus ewes using a dopamine receptor antagonist.

    PubMed

    Saxena, Vijay Kumar; De, Kalyan; Kumar, Davendra; Naqvi, Syed Mohammad Khursheed; Krishnaswamy, Narayanan; Tiwari, Ashok Kumar

    2015-11-01

    Estradiol decreases the pulse frequency of LH during the nonbreeding season through dopaminergic neurons that results in anestrus in the ewe. Long-term administration of sulpiride, a dopamine antagonist, induced ovulation in seasonally anestrus mares. Accordingly, we tested whether sulpiride would induce ovulatory estrus in seasonally anestrus Malpura ewes. A total of 12 Malpura ewes were divided into sulpiride (at 0.6 mg/kg b.i.d.) or control groups. Anestrus was defined on the basis of the absence of heat signs for 2 months through twice-a-day heat detection during the nonbreeding season (October-November) and progesterone level of less than 1 ng/mL. Rates of estrus induction, ovulation, multiple ovulations, and lambing in the sulpiride-treated ewes were 83.3%, 100%, 16.6%, and 66.7%, respectively. The mean interval from treatment to estrus was 5.25 ± 1.49 days. Progesterone levels were elevated after ovulation significantly on Days 5 and 7 after estrus as compared to Day 0 after sulpiride treatment (P < 0.05). In contrast, none of the control group ewes showed either estrus or ovulation. There was a significant association between sulpiride treatment and estrus induction rate as well as ovulation rate (P < 0.05). It is concluded that the result provides proof of concept that the dopamine antagonist can induce ovulation in seasonally anestrus ewes. PMID:26275500

  17. 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

  18. 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; µm(2) ), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (Dmin ; µm) and maximum nuclear diameter (Dmax ; µm). 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

  19. 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

  20. 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

  1. [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

  2. 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

  3. Assessing the usefulness of prostaglandin E2 (Cervidil) for transcervical 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 12 hours or 24 hours 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 12 hours) 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

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

    PubMed

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

    2015-01-01

    Current therapies for sarcomas are often inadequate. This study sought to identify actionable gene targets by selective targeting of the molecular networks that support sarcoma cell proliferation. Silencing of asparagine synthetase (ASNS), an amidotransferase that converts aspartate into asparagine, produced the strongest inhibitory effect on sarcoma growth in a functional genomic screen of mouse sarcomas generated by oncogenic Kras and disruption of Cdkn2a. ASNS silencing in mouse and human sarcoma cell lines reduced the percentage of S phase cells and impeded new polypeptide synthesis. These effects of ASNS silencing were reversed by exogenous supplementation with asparagine. Also, asparagine depletion via the ASNS inhibitor amino sulfoximine 5 (AS5) or asparaginase inhibited mouse and human sarcoma growth in vitro, and genetic silencing of ASNS in mouse sarcoma cells combined with depletion of plasma asparagine inhibited tumor growth in vivo. Asparagine reliance of sarcoma cells may represent a metabolic vulnerability with potential anti-sarcoma therapeutic value. PMID:26499495

  5. : Enhancement of Autophagy during Lytic Replication by the Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Activator

    E-print Network

    Huang, Ching-Tsan

    : Enhancement of Autophagy during Lytic Replication by the Kaposi's Sarcoma-Associated Herpesvirus Classroom (autophagy) KSHV KSHV Kaposi's sarcoma-associated herpesvirus (KSHV (autophagy) UV (autophagosome) (lysosome)(autolysosome)[1] [2] Kaposi's sarcoma-associated herpesvirus

  6. [Prognostic factors in soft tissue sarcomas. Experiences from the Sarcoma Center in Aarhus].

    PubMed

    Vraa, S; Keller, J O; Nielsen, O S; Sneppen, O; Jurik, A G; Jensen, O M

    2000-02-14

    In the present study, the outcome, patterns of local recurrence and survival, as well as prognostic factors, were evaluated in patients surgically treated for soft tissue sarcomas. Between January 1979 and July 1993, 316 consecutive patients were referred to the Sarcoma Centre in Aarhus with localised malignant soft tissue sarcoma of the extremities or trunk. There were 161 men (51%) and 155 women (49%), the median age was 56 years (1-94). Histologically 52 patients (16%) had a grade I, 60 patients (19%) a grade 2 and 204 patients (65%) a grade 3A or 3B tumour. The five-year local recurrence rate was 18% and the five-year survival rate was 75%. Multivariate analysis indicated the following variables as independent unfavourable factors for local recurrence: extracompartmental location, histological high-grade (i.e. histologically highly malignant) local excision, no adjuvant radiotherapy and intralesional/marginal excision. Independent unfavourable factors for survival were advanced age, extracompartmental location, histological high-grade, lower extremity location and large tumour size. Based on these variables, a prognostic model was made. PMID:10740435

  7. The effect of shearing on the energy metabolism of the pregnant ewe.

    PubMed

    Symonds, M E; Bryant, M J; Lomax, M A

    1986-11-01

    1. Metabolizable energy (ME) intakes, heat production, non-protein respiratory quotient (NPRQ) and the plasma concentrations of glucose, non-esterified fatty acids (NEFA), 3-hydroxybutyrate, insulin, growth hormone (GH) and cortisol were measured in shorn and unshorn pregnant ewes. 2. Lamb birth-weight was 17% higher from shorn ewes despite similar ME intakes in the two groups. Shearing resulted in a significant decrease in the digestibility of dry matter and energy. 3. Both shorn and unshorn ewes were found to be in positive nitrogen balance and negative energy balance. Heat production was 28% higher in shorn ewes. This increase in heat production in the shorn group could be completely accounted for by an increase in the oxidation of fatty acids as measured using the NPRQ values. 4. Despite an apparent increase in the use of fat as an energy source there were no effects of shearing on the mean plasma concentrations of NEFA, 3-hydroxybutyrate, GH and cortisol. 5. Measurements made at 1 h intervals for 24 h indicated a tendency for the concentrations of glucose to be increased and insulin decreased in shorn ewes, particularly, between 6 and 11 h after feeding. 6. It is concluded that shearing pregnant ewes at 8 weeks before lambing results in a chronic increase in energy requirements which are met by oxidizing body fat depots. The cold stress induced by shearing may also inhibit insulin secretion resulting in increased plasma glucose concentrations. The effects of shearing on energy metabolism in the ewe are discussed in relation to the nutrient supply for the developing fetus. PMID:3314982

  8. Walker, J. S., Carruthers, A. E., Orr-Ewing, A. J., & Reid, J. P. (2013). Measurements of Light Extinction by Single Aerosol Particles. The Journal

    E-print Network

    Subramanian, Sriram

    2013-01-01

    Walker, J. S., Carruthers, A. E., Orr-Ewing, A. J., & Reid, J. P. (2013). Measurements of Light. Carruthers, Andrew J. Orr-Ewing* and Jonathan P. Reid* School of Chemistry, University of Bristol, Bristol

  9. What Are the Key Statistics about Uterine Sarcoma?

    MedlinePLUS

    ... are the key statistics about uterine sarcoma? The American Cancer Society's estimates for cancer of the uterine corpus (body ... Health On The Net National Health Council © 2015 American Cancer Society, Inc. All rights reserved. The American Cancer Society ...

  10. Extraosseous osteogenic sarcoma of the breast: mammographic and pathologic findings

    SciTech Connect

    Watt, A.C.; Haggar, A.M.; Krasicky, G.A.

    1984-01-01

    An unusual primary extraosseous osteogenic sarcoma is described. The tumor's mammographic appearance was highly suggestive of the correct histologic diagnosis. This case supports the theory that these tumors originate from a totipotent cell.

  11. What Are the Risk Factors for Soft Tissue Sarcoma?

    MedlinePLUS

    ... the section “ What is a soft tissue sarcoma ?”). Li-Fraumeni syndrome Li-Fraumeni syndrome is caused by inherited defects in ... area. The area may be examined closely, and x-rays or other imaging studies may be obtained. ...

  12. Sarcoma de tejido blando—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del sarcoma de tejido blando, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  13. Sarcoma de tejido blando—Versión para profesionales de salud

    Cancer.gov

    Información del Instituto Nacional del Cáncer para profesionales de salud sobre el tratamiento del sarcoma de tejido blando, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados con este tipo de cáncer.

  14. A Comparative Study between Carcinoma and Sarcoma Using Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Dehghani-Bidgoli, Z.; Baygi, M. H. Miran; Kabir, E.; Malekfar, R.

    2014-01-01

    The purpose of this study was to find discriminating Raman spectral features between two major types of cancer, i.e., carcinoma and sarcoma. To this end, Raman spectra from adenocarcinoma, liposarcoma and fibrosarcoma samples were compared. A Raman system was used for the tissue Raman spectroscopic measurements at 785-nm laser excitation. After pre-processings, the Raman spectra were investigated, in major bands associated with protein and lipids, in the adenocarcinoma, liposarcoma, and fibrosarcoma groups. Principal component analysis and nonnegative matrix factorization were performed for finding most significant features in discriminating the spectra of carcinoma from those of sarcoma samples. The findings of this study show that the lipid content in the sarcoma samples decreases compared with the carcinoma samples. The achieved accuracy in discriminating carcinoma from sarcoma by linear discriminant analysis is 93.75 % and 90.63 % using the first nine principal components and nonnegative matrix factorization analysis, respectively.

  15. [Morphology and histogenesis of soft tissue chordoid sarcoma].

    PubMed

    Galil-Ogly, G A; Poroshin, K K; Krylov, L M

    1981-01-01

    The data of examinations of 6 chordoid-sarcomas of soft tissues which, owing to myxomatosis of the interstitial substance and vesicle-like cells containing glycogen, are similar in structure with skeletal chordoma are presented. It is emphasized that choroidsarcoma, unlike chordoma, has the ultrastructural features of cartilage differentiation: collagenization of the matrix, similarity of some tumour cells to chondrocytes. These data suggest that chordoid-sarcoma is histogenetically associated with rudiments of mesenchyma responsible for cartilage formation. PMID:7213084

  16. Postirradiation sarcoma (malignant fibrous histiocytoma) following cervix cancer

    SciTech Connect

    Pinkston, J.A.; Sekine, I.

    1982-02-01

    A case of postirradiation sarcoma is described. The tumor, a malignant fibrous histiocytoma, occurred in the radiation field 11 years following postoperative external beam radiation therapy (7000 rad) for carcinoma of the cervix. Reports of postirradiation malignant fibrous histiocytoma are rare, and the occurrence of this neoplasm following treatment of cervix cancer has not previously been described. The literature concerning postirradiation bone and soft tissue sarcomas is briefly reviewed, with special attention to malignant fibrous histiocytomas.

  17. Clinical exuberance of classic Kaposi's sarcoma and response to radiotherapy*

    PubMed Central

    Trujillo, Jeniffer Muñoz; Alves, Natália Ribeiro de Magalhães; Medeiros, Paula Mota; Azulay-Abulafia, Luna; Alves, Maria de Fátima Guimarães Scotelaro; Gripp, Alexandre Carlos

    2015-01-01

    Kaposi's sarcoma (KS) is a multicentric vascular neoplasm, with cutaneous and extracutaneous involvement. Different clinical and epidemiological variants have been identified. The classic form is manifested mainly in elderly men with indolent and long-term evolution, with lesions localized primarily in the lower extremities. We present two cases of classic Kaposi's sarcoma (CKS) in two female patients with extensive, exuberant skin involvement and rapid evolution, with good response to radiotherapy.

  18. Kaposi Sarcoma, CSR 1975-2005

    Cancer.gov

    Under 65 54.2 54.5 43.2f 56.6 56.5 62.9f 43.1 44.2 19.7f 65 and over 85.9 87.0 78.5f 87.7 87.5 81.2f 75.3g 64.4g - Table X-6 KAPOSI SARCOMA SURVIVAL RATES, BY RACE, SEX, DIAGNOSIS YEAR, STAGE AND AGE SEER Cancer Statistics Review 1975-2005 National Cancer Institute a Survival rates are relative rates expressed as percents. b Rates are from the SEER 9 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta).

  19. Kaposi Sarcoma, CSR 1975-2004

    Cancer.gov

    Under 65 53.2 53.4 44.9f 55.3 55.2 63.6f 42.3 43.1 25.7f 65 and over 84.0 86.4f 77.3f 85.9 87.4f 80.8f 66.5g 39.8g - Table X-6 KAPOSI SARCOMA SURVIVAL RATES, BY RACE, SEX, DIAGNOSIS YEAR, STAGE AND AGE SEER Cancer Statistics Review 1975-2004 National Cancer Institute a Survival rates are relative rates expressed as percents. b Rates are from the SEER 9 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta).

  20. Imaging Techniques for Kaposi Sarcoma (KS)

    PubMed Central

    O’Mahony, Deirdre; Gandjbakhche, Amir H; Hassan, Moinuddin; Vogel, Abby; Yarchoan, Robert

    2008-01-01

    Kaposi’s sarcoma (KS) is a multicentric tumor that most frequently involves the skin but can involve other tissues as well. Clinicians treating patients with KS or conducting clinical trials in this disease can benefit from imaging studies to document the extent of disease, to document changes with therapy, and to assess the extent of visceral and lymphatic involvement. A number of conventional techniques can be of use in meeting these needs, such as conventional light photography to assess skin or mucosal lesions, computerized tomography of the chest to assess pulmonary disease, and magnetic resonance imaging. In addition, a number of techniques are being developed with the goals of providing improved differentiation of KS from other diseases or providing information about the degree of angiogenesis in the lesions and other physiologic factors. We present here an overview of both established and experimental modalities of imaging in KS. PMID:19039297

  1. [Epitheloid sarcoma--an overlooked diagnosis?].

    PubMed

    Jensen, D B; Nielsen, N H; Nielsen, P L; Krag, C

    1991-06-24

    Epitheloid sarcoma (ES) is a malignant soft-tissue tumour which occurs particularly on the hand and forearm in young adults. The tumour grows slowly and metastasizes relatively late but has, nevertheless, a considerable mortality and morbidity because it is frequently erroneously diagnosed, both clinically and pathologically, either as a benign tumour or as a reactive inflammatory process. Two typical cases with diagnostic delays of 12 and 15 years, respectively, which required amputations through the upper arm or forearm are described. Even although ES is a rare tumour form, clinicians and pathologists should be aware of this possibility as, in the early stages, the tumour can frequently be treated effectively and radically by wide local excision without amputation. PMID:1862573

  2. Epithelioid inflammatory myofibroblastic sarcoma: a case report

    PubMed Central

    Clevenger, Jessica A.; Masters, Gregory A.; Bauer, Thomas L.; Nam, Brian T.

    2015-01-01

    Inflammatory myofibroblastic tumor (IMT) of the lung is a rare malignancy with few cases reported in the literature. Histologically, it is composed by spindle cells and an infiltrate of inflammatory cells. Children and young, non-smoking adults constitute the majority of cases, the clinical behavior ranges from a benign entity to a malignant process with rapid recurrence and metastatic progression. We present a case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) of the pleura, a malignant variant of IMT, which was initially treated with debulking surgical resection followed by systemic chemotherapy. The tumor was found to have an anaplastic lymphoma kinase (ALK) gene rearrangement. An ALK directed tyrosine kinase inhibitor was used with an impressive response, the patient remains in remission nearly 1 year after presentation. The pathogenesis, pathologic findings, clinical behavior and imaging of pulmonary EIMS are discussed.

  3. Hypoxia-Dependent Modification of Collagen Networks Promotes Sarcoma Metastasis

    PubMed Central

    Eisinger-Mathason, T.S. Karin; Zhang, Minsi; Qiu, Qiong; Skuli, Nicolas; Nakazawa, Michael S.; Karakasheva, Tatiana; Mucaj, Vera; Shay, Jessica E.S.; Stangenberg, Lars; Sadri, Navid; Puré, Ellen; Yoon, Sam S.; Kirsch, David G.; Simon, M. Celeste

    2013-01-01

    Intratumoral hypoxia and expression of Hypoxia Inducible Factor 1? (HIF1?) correlate with metastasis and poor survival in sarcoma patients. We demonstrate here that hypoxia controls sarcoma metastasis through a novel mechanism wherein HIF1? enhances expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). We show that loss of HIF1? or PLOD2 expression disrupts collagen modification, cell migration and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSLKrasG12D/+; Trp53fl/fl murine sarcoma models. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF1?-deficient tumors, and analysis of human sarcomas reveal elevated HIF1? and PLOD2 expression in metastatic primary lesions. Pharmacological inhibition of PLOD enzymatic activity suppresses metastases. Collectively, these data indicate that HIF1? controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors. We conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination. PMID:23906982

  4. Wiki-based clinical practice guidelines for the management of adult onset sarcoma: a new paradigm in sarcoma evidence.

    PubMed

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

    2015-01-01

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

  5. Kaposi sarcoma can also involve the heart

    PubMed Central

    Lababidi, Mohamad Hani; Alhawasli, Hazem; Iroegbu, Nkemakolam

    2015-01-01

    Kaposi sarcoma (KS) is a low-grade angioproliferative tumor associated with infection with human herpes virus 8 (HHV-8). The disease was named after Moritz Kaposi, a Hungarian dermatologist who first described it in 1872 as ‘idiopathic multiple pigmented sarcoma of the skin.’ HHV-8 infection is required for the development of KS, but not all infected persons develop the disease. KS is also considered an acquired immune deficiency syndrome (AIDS)-defining illness by the Centers for Disease Control and Prevention guidelines. According to data from the United States AIDS and cancer registries, both KS and non-Hodgkin lymphoma are the most common malignancies associated with human immunodeficiency virus (HIV) infection. However, the incidence of both malignancies has decreased dramatically since 1996 following the widespread utilization of highly active antiretroviral therapies. HIV-associated KS can involve virtually any site in the body including lymph nodes, gastrointestinal tract, respiratory system, heart, pericardium, bone marrow, and other visceral organs. However, cutaneous disease is the most common and is the usual initial presentation for KS. KS-related pericardial effusion can be a life-threatening emergency and should be considered in HIV/AIDS patients who present with signs and symptoms of pericardial effusion. The importance of diagnosing and differentiating KS-related pericardial effusion from other causes of pericardial effusion lies in the differences in the treatment and management in comparison to other etiologies of pericardial effusion. We report a case of a 54-year old man who presented to our hospital with a large pericardial effusion and was subsequently diagnosed to have HIV-related KS pericardial effusion. A brief review of the literature on the diagnosis and management is also presented. PMID:26653688

  6. Soft tissue sarcoma and occupational exposures

    SciTech Connect

    Wingren, G.; Fredrikson, M.; Brage, H.N.; Nordenskjoeld, B.A.; Axelson, O. )

    1990-08-15

    The associations between soft tissue sarcoma (STS) and occupational exposures were studied in a case-referent study in the southeast of Sweden. Exposure information was obtained through mailed questionnaires to 96 cases, 450 randomly selected population referents, and 200 cancer referents. Odds ratios (OR), were calculated for various occupational groups, and particularly, for occupations with potential exposure to chlorinated phenoxy herbicides and chlorophenols. In the analyses based on population referents, increased risks for soft tissue sarcoma were seen for especially gardeners (OR = 4.1), but also railroad workers (OR = 3.1); construction workers with exposure to impregnating agents (OR = 2.3), asbestos (OR = 1.8), or pressure impregnating agents (OR = 1.7); and unspecified chemical workers with potential exposure to phenoxy herbicides and/or chlorophenols (OR = 1.6). A similar pattern appeared when cancer referents were used although the numerical values of the odds ratios became different. A grouping of jobs resulted in Mantel-Haensel OR from 1.5 to 1.9 for farmers and forestry workers, dependent on referents used and even more increased OR for railroad workers and unspecified chemical workers with potential exposure to phenoxy herbicides and chlorophenols. The results of the study confirm rather than refute that phenoxy herbicides and chlorophenols could be of etiologic importance for STS; the high risk for gardeners, although based on a small number of individuals, was unexpected and remains unclear. Also, since other cancers were used as referents, no definite problems of recall bias should obtain in this material. None of the exposed groups had a higher proportion of smokers than the unexposed group.

  7. Broadband calibration of R//V Ewing seismic sources M. Tolstoy, J. B. Diebold, S. C. Webb, D. R. Bohnenstiehl, E. Chapp,

    E-print Network

    Bohnenstiehl, Delwayne

    Broadband calibration of R//V Ewing seismic sources M. Tolstoy, J. B. Diebold, S. C. Webb, D. R to obtain broad frequency band measurements of seismic sources used by the R/V Maurice Ewing. Received. Holmes, and M. Rawson (2004), Broadband calibration of R/V Ewing seismic sources, Geophys. Res. Lett., 31

  8. The Relationship between Selenium and T3 in Selenium Supplemented and Nonsupplemented Ewes and Their Lambs

    PubMed Central

    Hefnawy, Abd Elghany; Youssef, Seham; Aguilera, P. Villalobos; Rodríguez, C. Valverde; Pérez, J. L. Tórtora

    2014-01-01

    Twenty pregnant ewes were selected and classified into two groups. The first group received subcutaneous selenium supplementation (0.1 mg of sodium selenite/kg BW) at the 8th and 5th weeks before birth and 1st week after birth while the other was control group without selenium injection. Maternal plasma and serum samples were collected weekly from the 8th week before birth until the 8th week after birth and milk samples were taken from ewes weekly, while plasma and serum samples were collected at 48 hours, 1st, 2nd, 3rd, 5th, and 8th weeks after birth from the newborn lambs. Results demonstrated significant positive relationship between maternal plasma selenium and serum T3 in supplemented and control ewes (r = 0.69 to 0.72, P < 0.05). There was significant (P < 0.001) increase in T3 in supplemented ewes and their lambs until the 8th week after birth. There was positive relationship between milk, selenium concentration, and serum T3 in the newborn lambs of the supplemented group (r = 0.84, P < 0.01), while the relationship was negative in the control one (r = ?0.89, P < 0.01). Muscular and thyroid pathological changes were independent of selenium supplementation. Selenium supplementation was important for maintaining T3 in ewes and newborn lambs until the 8th week after birth. PMID:24660087

  9. Coenurus cerebralis cyst in the orbit of a ewe.

    PubMed

    Haridy, Mohie; Sadan, Madeh; Omar, Mosab; Sakai, Hiroki; Yanai, Tokuma

    2014-01-01

    A 4-year-old Rahmani breed ewe was presented for surgery to the Veterinary Teaching Hospital, South Valley University, Egypt with enlargement and protrusion of the eye ball, blepharitis and congestion of the conjunctiva. On examination, a cyst 2.5 cm x 3.5 cm in diameter containing sandy fluid was detected in the perioptic nerve fat. Histopathological examination revealed that the epithelial lining of the conjunctiva was necrotic and severely infiltrated by neutrophils. The underlying connective tissue was oedematous, hyperaemic and severely infiltrated by neutrophils. Desquamation of the corneal epithelium was seen, together with oedema of the stroma. The tissue surrounding the cyst was compressed and the lacrimal glands revealed pressure atrophy. The muscular tissue was atrophied and infiltrated by fat cells. The cyst wall was lined with white scolices protruding from the inner wall. Based on the gross and histopathological characteristics of the cyst observed, the cyst was diagnosed as Coenurus cerebralis. This is the first report of orbital coenurosis in a sheep. PMID:25686102

  10. 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.

  11. 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 ...

  12. Comparison of the post-parturient rise in faecal egg counts of indigenous and cross-bred ewes.

    PubMed

    Singh, S; Yadav, C L; Banerjee, D P

    1997-09-01

    The breed differences in post-parturient rise (PPR) in faecal egg counts in lambing ewes of different breeds naturally infected with Haemonchus contortus were compared. The ewes of Nali, 50% Nali x 50% Russian Merino/Corriedale and 37.5% Nali x 62.5% Russian Merino/Corriedale were treated with fenbendazole while ewes of the above three breeds as well as 25% Nali x 75% Russian Merino/Corriedale, were kept untreated. Observations from 3 weeks before lambing to 12 weeks post-lambing at weekly intervals revealed that in treated ewes, egg counts of Nali did not differ significantly with 50% Nali whereas 37.5% Nali had significantly higher egg counts than those of Nali and 50% Nali. In untreated ewes egg counts of 50% Nali were significantly higher than that of Nali on some occasions, while 25% Nali had significantly higher egg counts than the other three breeds. None of the ewes from the Nali breed showed signs of haemonchosis, whereas few lambing ewes of the three Nali crosses (50%, 37.5% and 25% Nali) showed signs of haemonchosis and one ewe of the latter breed died. PMID:9271473

  13. Nutritional plane and selenium supply during gestation impact yield and nutrient composition of colostrum and milk in primiparous ewes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to investigate effects of nutritional plane and Se supply during gestation on yield and nutrient composition of colostrum and milk in first parity ewes. Rambouillet ewe lambs (n = 84, age = 240 +/- 17 d, BW = 52.1 +/- 6.2 kg), were allocated to 6 treatments in a 2 x 3 factorial array...

  14. Radiation-associated sarcoma: A review of 23 patients with postradiation sarcoma over a 50-year period

    SciTech Connect

    Amendola, B.E.; Amendola, M.A.; McClatchey, K.D.; Miller, C.H. Jr. )

    1989-10-01

    Between 1934 and 1983, 23 patients with well-documented diagnosis of radiation-associated sarcoma (RAS) were seen at the University of Michigan Medical Center. The median latent period from irradiation to diagnosis of RAS was 13 years with a minimum latent period of 3 and a maximum of 34 years. All sarcomas originated in previously normal tissues within the irradiated field. Pathology slides available in all patients were reviewed by the same pathologist for the purpose of the study, and the diagnosis of sarcoma was confirmed histologically. There were five bone sarcomas and 18 soft tissue sarcomas. Thirteen patients developed radiation-associated sarcoma following megavoltage treatment with a minimum total radiation dose of 25 Gy in 2 1/2 weeks. The other 10 patients received orthovoltage and/or brachytherapy irradiation alone or combined with external beam radiation. In this group, the radiation doses ranged from 25 Gy to 72 Gy except for one patient who received 8 Gy delivered by orthovoltage irradiation as treatment of knee arthritis. Four patients were originally treated for benign conditions. All the other patients (n = 19) received radiation therapy for a variety of primary malignancies including carcinoma of the cervix (n = 4), brain gliomas (n = 13), Wilm's tumors (n = 2) and retinoblastomas (n = 2), among others.

  15. Interferon-? expression in trophoblast cells in pregnant ewes challenged with Chlamydophila abortus.

    PubMed

    Worrall, S; Sammin, D J; Bassett, H F; Reid, C R; Gutierrez, J; Marques, P X; Nally, J E; O'Donovan, J; Williams, E J; Proctor, A; Markey, B K

    2011-08-01

    Pregnant ewes were challenged with Chlamydia abortus at 91-98 days of gestation and euthanised at 14, 21 and 28 days post-challenge. IFN? mRNA labelling appeared to be co-localised with Chlamydial lipopolysaccharide within trophoblast cells in discrete areas lining the primary villi in the limbus and hilar zone of the placentomes from challenged sheep on days 21 and 28 post-infection. The presence of IFN? was also demonstrated by immunohistochemistry. No labelling was seen in tissues from the non-infected ewes. The presence of IFN? in trophoblast cells from infected ewes may indicate an attempt to restrict the replication of the organism and be an important trigger for the inflammatory responses that develop on the fetal side of the placenta in enzootic abortion. PMID:21722966

  16. Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma

    E-print Network

    Jacks, Tyler E.

    Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-Kras[superscript ...

  17. Motivation to obtain a food reward of pregnant ewes in negative energy balance: behavioural, metabolic and endocrine considerations.

    PubMed

    Verbeek, E; Waas, J R; Oliver, M H; McLeay, L M; Ferguson, D M; Matthews, L R

    2012-07-01

    Low food availability often coincides with pregnancy in grazing animals. This study investigated how chronic reductions in food intake affected feeding motivation, and metabolic and endocrine parameters in pregnant sheep, which might be indicative of compromised welfare. Ewes with an initial Body Condition Score of 2.7±0.3 (BCS; 0 indicates emaciation and 5 obesity) were fed to attain low (LBC 2.0±0.0,), medium (MBC 2.9±0.1) or high BCS (HBC 3.7±0.1) in the first trimester of pregnancy. A feeding motivation test in which sheep were required to walk a set distance for a palatable food reward was conducted in the second trimester. LBC and MBC ewes consumed more rewards (P=0.001) and displayed a higher expenditure (P=0.02) than HBC ewes, LBC ewes also tended to consume more rewards than MBC ewes (P=0.09). Plasma leptin and glucose concentrations were inversely correlated to expenditure (both P<0.05) and appear to be associated with hunger in sheep. LBC ewes were in negative energy balance, with lower muscle dimensions, plasma glucose, leptin, insulin, cortisol, and insulin-like growth factor-1 concentrations and higher free fatty acids concentrations compared to HBC ewes; metabolic and endocrine parameters of the MBC ewes were intermediate. The high feeding motivation and negative energy balance of low BCS ewes suggested an increased risk of compromised welfare. Imposing even a small cost on a food reward reduced motivation substantially in high BCS ewes (despite high intake when food was freely available). Assessment of a willingness to work for rewards, combined with measures of key metabolic and endocrine parameters, may provide sensitive barometers of welfare in energetically-taxed animals. PMID:22789465

  18. [Thoraco-scapular amputation in sarcomas of the shoulder girdle].

    PubMed

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

    1991-09-01

    A total of 121 patients with sarcomas localized to the shoulder girdle were referred to the Sarcoma Centre in Arhus. Of these, 17 (14%) underwent interscapulothoracic amputation. At the time of treatment, the average age was 51 years (17-82 years). Eleven of these patients had sarcomas of bone and six had soft tissue sarcomas. Late diagnosis or previous surgical interventions contributed to the indication for the mutilating procedure. At the time of referral, six of the 11 cases of bone sarcomas were complicated by a pathological fracture and all six soft tissue sarcomas had been submitted to incisional biopsy or non-radical treatment. The soft tissue sarcomas were usually large with an average maximum diameter of 10 cm (4-15 cm). Postoperative recovery was uncomplicated in all cases. Local recurrence occurred in three patients (18%). Eight patients (47%) developed metastases and died from the tumour on an average of 32 months (7-94 months) after operation. Two patients died from other causes without tumour. Seven patients (41%) were tumourfree and alive for an average of 69 months (21-128 months) after operation. Only three of these seven patients wore their shoulder-arm prosthesis regularly while the remainder preferred to be either without a prosthesis or to use a lightweight shoulder prosthesis. None of the seven patients still experienced phantom pain necessitating analgetics. All of the patients were self-reliant in everyday life and the five patients who had been occupationally active until the time of operation had returned to work. The prognosis after interscapulothoracic amputation depends upon the primary malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1949256

  19. Uterine involution and progesterone level during the postpartum period in Barbary ewes in north Libya

    PubMed Central

    Medan, M.S.; EL-Daek, T.

    2015-01-01

    The objectives of the present study were to determine the time of uterine involution and ovarian activity using ultrasound examination and progesterone assay. Weekly progesterone levels were measured starting one week postpartum until two weeks after the 1st postpartum estrus in Barbary ewes lambed during winter in AL-Bayda city, north of Libya. A total of 15 Barbary ewes were used in the present study distributed in three groups according to the month of lambing as group 1 (lambed in January), group 2 (lambed in February) and group 3 (lambed in March). Ewes were examined weekly by trans-rectal ultrasound to check involution of the uterus starting one week after lambing until complete uterine involution. Blood samples were collected from the jugular vein, and serum was separated and stored at -20 °C until measuring progesterone using ELISA. Results showed that uterine involution completed at day 35 postpartum in groups 1 and 2, while it occurred at day 28 in group 3. The mean progesterone level was basal (less than 1 ng/ml) for a long period and started to increase at days 119, 99 and 77 postpartum in group 1, 2 and 3, respectively. One ewe did not show estrus at all during the period of study in group 2 and there were no growing follicles on their ovaries. The obtained results indicate that, uterine involution as determined by ultrasound completed earlier in ewes lambed in March than those lambed in February or January. Also, progesterone level and ultrasound examination showed that there was no ovarian activity for a longtime after parturition indicating that reproduction in Barbary ewes tends to be seasonal in AL-Bayda city, north Libya. PMID:26623357

  20. Controlled trials of the anthelmintic oxfendazole in ewes and lambs naturally infected with gastrointestinal nematodes.

    PubMed

    Downey, N E

    1977-09-24

    Oxfendazole doses at a rate of 5 mg per kg, before or after lambing, reduced nematode egg output to insignificant levels in ewes, most of which were not exposed to re-infection. Ewes treated with oxfendazole had a significantly lower egg output than those treated with levamisole, although the latter anthelmintic was also highly effective. In lambs, oxfendazole at a dose rate of 5 mg per kg, showed 100 per cent efficacy for Ostertagia circumcincta, O trifurcata, Teledorsagia davtiani, Trichostrongylus axei, T vitrinus, T colubriformis, Nematodirus battus, N filicollis, immature Nematodirus, Chabertia ovina, and 93 per cent efficacy for Trichuris spp. Levamisole showed similar efficacies but did not remove Trichuris. PMID:335633

  1. Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma

    ClinicalTrials.gov

    2015-07-22

    Basal Cell Carcinoma of the Skin; Eccrine Carcinoma of the Skin; Recurrent Adult Soft Tissue Sarcoma; Recurrent Melanoma; Recurrent Skin Cancer; Squamous Cell Carcinoma of the Skin; Stage III Adult Soft Tissue Sarcoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Melanoma

  2. Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral

    E-print Network

    Ronquist, Fredrik

    Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid Abstract Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid-Tegument Complexes

  3. The development of Kaposi sarcoma, a highly vascular tumour of endothe-

    E-print Network

    Damania, Blossom

    The development of Kaposi sarcoma, a highly vascular tumour of endothe- lial cell origin, is associated with a herpes virus, KSHV (Kaposi sarcoma- associated herpesvirus). Individual KSHV genes have be beneficial for treating Kaposi sarcoma in the clinic. Katharine H. Wrighton ORIGINAL RESEARCH PAPER Wang, L

  4. Characterization of Kaposi's sarcoma-associated herpesvirus (KSHV) K1 promoter activation by Rta

    E-print Network

    Damania, Blossom

    Characterization of Kaposi's sarcoma-associated herpesvirus (KSHV) K1 promoter activation by Rta Abstract The K1 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a 46-kDa transmembrane. Keywords: KSHV; HHV8; K1; Rta; Orf50; Transcription Introduction Kaposi's sarcoma-associated herpesvirus

  5. Intratumor versus Intertumor Heterogeneity in Gene Expression Profiles of Soft-Tissue Sarcomas

    E-print Network

    Lunds Universitet,

    Intratumor versus Intertumor Heterogeneity in Gene Expression Profiles of Soft-Tissue Sarcomas,Lund University,Lund,Sweden 4 Departmentof Pathology,Lund University,Lund,Sweden Soft-tissue sarcomas (STSs from a large STS. VVC 2005 Wiley-Liss, Inc. INTRODUCTION Soft-tissue sarcomas (STSs) of the extremities

  6. Mini-review Kaposi sarcoma-associated herpesvirus (KSHV): Molecular biology

    E-print Network

    Damania, Blossom

    Mini-review Kaposi sarcoma-associated herpesvirus (KSHV): Molecular biology and oncogenesis Kwun-related malignancies Viral latency Lytic replication a b s t r a c t Kaposi sarcoma-associated herpesvirus (KSHV with the develop- ment of three neoplastic diseases: Kaposi sarcoma (KS), primary effusion lymphoma (PEL

  7. Avian sarcoma leukosis virus receptor-envelope system for simultaneous dissection of multiple

    E-print Network

    Miyashita, Yasushi

    Avian sarcoma leukosis virus receptor-envelope system for simultaneous dissection of multiple screened all receptor­envelope pairs result- ing from the combination of four avian sarcoma leukosis virus analysis of diverse neuronal systems. avian sarcoma leukosis virus | pseudotyped lentiviral vector

  8. Antagonism of Host Antiviral Responses by Kaposi's Sarcoma-Associated Herpesvirus Tegument Protein

    E-print Network

    Ronquist, Fredrik

    Antagonism of Host Antiviral Responses by Kaposi's Sarcoma-Associated Herpesvirus Tegument Protein responses. Kaposi's sarcoma-associated herpesvirus (KSHV) is demonstrated in this report to be able by Kaposi's Sarcoma-Associated Herpesvirus Tegument Protein ORF45. PLoS ONE 5(5): e10573. doi:10

  9. Cytokine & Growth Factor Reviews 12 (2001) 245257 Molecular piracy of Kaposi's sarcoma associated herpesvirus

    E-print Network

    Damania, Blossom

    2001-01-01

    Cytokine & Growth Factor Reviews 12 (2001) 245­257 Survey Molecular piracy of Kaposi's sarcoma6ard medical school, 1 Pine Hill Dri6e, Southborough, MA 01772, USA Abstract Kaposi's Sarcoma with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and Multicentric Casttleman's disease. KSHV

  10. NEW OCCURRENCE OF EPIZOOTIC SARCOMA IN CHESAPEAKE BAY SOFT SHELL CLAMS, MYA ARENARIA

    E-print Network

    NEW OCCURRENCE OF EPIZOOTIC SARCOMA IN CHESAPEAKE BAY SOFT SHELL CLAMS, MYA ARENARIA C. A FARLEY 1983 and May 1984 revealed peak prevalences of42-65% in clams from five sites. Sarcomas in laboratory disease has been observed in a wild molluscan population which was previously documented to be sarcoma

  11. Primary synovial sarcoma of the abdominal wall: a case report and literature review

    PubMed Central

    Kritsaneepaiboon, Supika; Sangkhathat, Surasak; Mitarnun, Winyou

    2015-01-01

    Synovial sarcoma (SS) is the fourth most common type of soft tissue sarcoma, following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma. It usually occurs in the extremities near the large joints of middle-aged patients. We describe a case of synovial sarcoma of the anterior abdominal wall (SSAW) in an adolescent girl and undertake a review of the literature. PMID:26629297

  12. Reproductive and productive performances of Santa Inês ewes submitted to breeding in different periods of the Amazonian humid tropical climate.

    PubMed

    Soares, Felipe Nogueira; Oliveira, Maria Emilia Franco; Padilha-Nakaghi, Luciana Cristina; de Oliveira, Luís Guilherme; Feliciano, Marcus Antônio Rossi; de Oliveira, Felipe Brener Bezerra; Teixeira, Pedro Paulo Maia; Vicente, Wilter Ricardo Russiano; Faturi, Cristian; Rodrigues, Luiz Fernando de Souza

    2015-12-01

    The objective of this study was to evaluate the reproductive and productive performance of Santa Inês ewes bred at different times of the year in humid tropical climate. One hundred and forty-eight Santa Inês ewes were grouped according to the time of the year of their breeding season (i.e., mating period) (dry/wet, wet, wet/dry, and dry season). The service type was natural mating and the ewes and rams were kept together every night for 45 days. Reproductive efficiency was assessed by service, pregnancy, lambing, prolificacy, twinning, pregnancy loss, weaning, and lamb mortality rates. Ewes were weighed at the beginning and at the end of the breeding season and before and after parturition, and sequential weighing of the lambs was performed (at birth, 15, 30, 60, and 90 days). Reproductive efficiency index (number of lambs weaned/total of served ewes) and productive efficiency (kg of weaned lamb/kg of served or lambed ewes) were calculated. All ewes expressed estrus early in the breeding season; however, a higher percentage (53.5 and 7.1 % at 30 and 45 days, respectively) of ewes returned to estrus during the wet/dry period. The lower rates (13.9 %) of return to estrus at 30 days were during the wet season (P??0.05) effects of breeding seasons on the remaining reproductive rates. Ewes that lambed during the wet/dry transition period weighted less, before (40.5?±?2.5 kg) and after (38.6?±?1.6 kg) parturition, than those of other groups (P?ewes, respectively; P?ewes served in the dry season. The reproductive performance of Santa Inês ewes was not significantly influenced by the period of the year in which the breeding seasons took place, allowing for four breeding seasons a year in the Amazon region. Variations between periods in return to estrus rates, weight of ewes close to parturition and lamb weight at weaning indicate that climate changes can also affect reproductive rates. PMID:26224599

  13. Spinal Myeloid Sarcoma "Chloroma" Presenting as Cervical Radiculopathy: Case Report.

    PubMed

    Hu, Xiaobang; Shahab, Imran; Lieberman, Isador H

    2015-06-01

    Study Design?Case report. Objective?Myeloid sarcoma (also known as chloroma) is a rare, extramedullary tumor composed of immature granulocytic cells. It may occur early in the course of acute or chronic leukemia or myeloproliferative disorders. Spinal cord invasion by myeloid sarcoma is rare. The authors report a rare case of spinal myeloid sarcoma presenting as cervical radiculopathy. Methods?A previously healthy 43-year-old man presented with progressive neck, right shoulder, and arm pain. Cervical magnetic resonance imaging (MRI) revealed a very large enhancing extradural soft tissue mass extending from C7 through T1, with severe narrowing of the thecal sac at the T1 level. The patient underwent posterior cervical open biopsy, laminectomy, and decompression. Histologic examination of the surgical specimen confirmed the diagnosis of myeloid sarcoma. Postoperatively, a bone marrow biopsy was done, which showed myeloproliferative neoplasm with eosinophilia. The patient then received systemic chemotherapy and radiotherapy. Results?At the 10-month follow-up, the patient reported complete relief of arm pain and neck pain. X-rays showed that the overall cervical alignment was intact and there was no evidence of a recurrent lesion. MRI showed no evidence of compressive or remnant lesion. Conclusions?Spinal myeloid sarcoma presenting as cervical radiculopathy is rare, and it may be easily misdiagnosed. Knowledge of its clinical presentation, imaging, and histologic characterization can lead to early diagnosis and appropriate treatment. PMID:26131394

  14. Immunoglobulin G Locus Events in Soft Tissue Sarcoma Cell Lines

    PubMed Central

    Chen, Zhengshan; Li, Jing; Xiao, Yanna; Zhang, Junjun; Zhao, Yingying; Liu, Yuxuan; Ma, Changchun; Qiu, Yamei; Luo, Jin; Huang, Guowei; Korteweg, Christine; Gu, Jiang

    2011-01-01

    Recently immunoglobulins (Igs) have been found to be expressed by cells other than B lymphocytes, including various human carcinoma cells. Sarcomas are derived from mesenchyme, and the knowledge about the occurrence of Ig production in sarcoma cells is very limited. Here we investigated the phenomenon of immunoglobulin G (IgG) expression and its molecular basis in 3 sarcoma cell lines. The mRNA transcripts of IgG heavy chain and kappa light chain were detected by RT-PCR. In addition, the expression of IgG proteins was confirmed by Western blot and immunofluorescence. Immuno-electron microscopy localized IgG to the cell membrane and rough endoplasmic reticulum. The essential enzymes required for gene rearrangement and class switch recombination, and IgG germ-line transcripts were also identified in these sarcoma cells. Chromatin immunoprecipitation results demonstrated histone H3 acetylation of both the recombination activating gene and Ig heavy chain regulatory elements. Collectively, these results confirmed IgG expression in sarcoma cells, the mechanism of which is very similar to that regulating IgG expression in B lymphocytes. PMID:21731691

  15. Rous sarcoma virus transforming protein tyrosine kinase is expressed and active in sarcoma-free avian embryos microinjected with Rous sarcoma virus

    SciTech Connect

    Howlett, A.R.; Carter, V.C.; Martin, G.S.; Bissell, M.J. )

    1988-10-01

    Early embryonic avian tissue is resistant to transformation by Rous sarcoma virus. To determine the nature of this resistance, the authors examined the expression and properties of the Rous sarcoma virus transforming protein pp60{sup v-src}, in infected embryonic chicken limbs in ovo. Lysates from Rous sarcoma virus-infected limbs contained the viral structural protein p19{sup gag}, as detected by immunoblot analysis and showed pp60{sup v-src} kinase activity in vitro. Immunoblot analysis of lysates with anti-phosphotyrosine antibodies revealed a number of phosphotyrosine-containing proteins present in lysates of Rous sarcoma virus-infected embryos but not in lysates of control, uninfected embryos. These studies demonstrate that pp60{sup v-src} is co-expressed with viral structural determinants in infected embryonic avian tissue. The localization pattern of the major src gene substrate p36 (calpactin I) was compared with that of p19{sup gag} by double-label immunofluorescence and found to be generally nonoverlapping. These observations are consistent with the concept that the induction of tumors in ovo requires complementation between viral determinants and host factors. These host factors, which may be critical substrates of pp60{sup src}, are subject to developmental regulation in the avian embryo.

  16. Breaking the Rules: Increased Invasive Agression in Chemo-Resistant Lymphoma 

    E-print Network

    Cherry, Evan M

    2012-07-11

    for many therapies, including treatment for cancer and gout. Physiological levels for cytoskeletal drugs vincristine (Fig. 2A), colchicine (Fig. 2B), and paclitaxel (Fig. 2C) have been determined from HPLC [14-16] and will be used...

  17. Epithelioid Sarcoma: Diagnostic Features and Genetics.

    PubMed

    Thway, Khin; Jones, Robin L; Noujaim, Jonathan; Fisher, Cyril

    2016-01-01

    Epithelioid sarcoma (ES) is a rare, aggressive soft-tissue neoplasm of uncertain differentiation, characterized by nodular aggregates of epithelioid cells, which are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen, and often for CD34. It has a propensity for multifocal disease at presentation, local recurrence, and regional metastasis. These are aggressive neoplasms with particularly poor prognosis after regional or distant metastatic disease, for which surgical resection is still the mainstay of treatment, and options for patients with metastatic disease remain undefined. There are 2 distinct variants: classic ES, which typically presents as a subcutaneous or deep dermal mass in the distal extremities of young adults and comprises nodular distributions of relatively uniform epithelioid cells with central necrosis, and the proximal variant, which has a predilection for proximal limbs and limb girdles and the midline of the trunk, which is composed of sheets of larger, more atypical cells with variable rhabdoid morphology. Both classic and proximal-type ESs are associated with the loss of SMARCB1/INI1 protein expression, but appear otherwise molecularly relatively heterogeneous. We review classic and proximal-type ES, discussing morphology, immunohistochemical and genetic findings, the differential diagnosis, and the future potential for targeted therapies. PMID:26645461

  18. Myxoinflammatory fibroblastic sarcoma: morphologic and genetic updates.

    PubMed

    Ieremia, Eleni; Thway, Khin

    2014-10-01

    Myxoinflammatory fibroblastic sarcoma (MIFS) is a malignant mesenchymal neoplasm most frequently arising in the distal extremities of adults, which usually behaves in a low-grade manner but is capable of metastasizing to local and distant sites, rarely leading to death. It is a rare tumor whose unusual morphology can lead to erroneous histologic diagnosis, either as a nonneoplastic (infectious or inflammatory) process or as a variety of neoplastic diseases. While its exact origin is uncertain, ultrastructural studies have shown at least some of the constituent cells to be modified fibroblasts. Distinct and reproducible genetic abnormalities identified in MIFS are translocation t(1;10)(p22:q24), with rearrangements of the TGFBR3 and MGEA5 genes associated with increased levels of FGF8, and formation of marker/ring chromosome 3, with amplification of the VGLL3 locus. Because these genetic abnormalities are shared by both MIFS and hemosiderotic fibrohistiocytic lipomatous tumor, it is thought that these 2 morphologically distinct neoplasms may comprise a spectrum of disease defined by these genetics. We review the literature on MIFS and discuss morphology (including that of MIFS/hemosiderotic fibrohistiocytic lipomatous tumor hybrid lesions), immunohistochemistry, the differential diagnosis, and recent molecular genetic developments. PMID:25268202

  19. Serum hormone profiles, pregnancy rates, and offspring performance of Rambouillet ewes treated with recombinant bovine somatotropin before breeding.

    PubMed

    Camacho, L E; Benavidez, J M; Hallford, D M

    2012-08-01

    An experiment was conducted to examine effects of bovine ST (bST) on serum hormone concentrations, pregnancy rates, and offspring performance. Before initiation of a fall breeding period, 75 Rambouillet ewes (68.8 ± 1.5 kg) received an intravaginal insert containing 0.3 g of progesterone (P4) to synchronize onset of estrus. After 12 d, inserts were removed (d 0), and ewes (stratified by BW and age) received either 0 (control, n = 37) or 250 (n = 38) mg of recombinant bST (Posilac, Monsanto, St. Louis, MO, subcutaneously). Ewes were joined with fertile rams 24 h after insert removal. Blood samples were collected from 12 ewes in each treatment group daily from d 0 to 20 after insert removal. Serum IGF-I concentrations were 315 and 437 (± 58) ng/mL in control and bST-treated ewes 2 d after receiving bST (P = 0.02) and remained increased (P < 0.03) in bST-treated ewes throughout the 13-d period (P < 0.05). Serum prolactin (P > 0.10) and estradiol (P = 0.65) were similar between treatments. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were similar (P > 0.20) between treatments from d 0 through 8. Controls had greater (P < 0.04) serum T3 and T4 concentrations than treated ewes did until d 18. Serum P4 was similar (P > 0.10) in control and bST-treated ewes from d 0 through 3 but was increased (P < 0.05) from d 4 to 8 in control ewes. Serum P4 was again similar (P > 0.10) between treatments from d 9 to 20. Serum insulin concentrations were 0.44 and 1.74 (± 0.19) ng/mL in control and bST-treated ewes, respectively, 1 d after receiving bST (P < 0.001) and remained increased (P < 0.03) in bST-treated ewes through d 9 (P < 0.03). Serum glucose was increased (P = 0.003) from d 0 to 10 in bST-treated ewes compared with controls. Thirty-three of 37 (89%) control ewes were pregnant, whereas 27 of 38 (71%) bST-treated ewes were pregnant (P = 0.05). As a percentage of ewes lambing, 61% and 39% of control ewes produced single and twin lambs, respectively, compared with 41% and 59% of bST-treated ewes (P = 0.12). Lamb 60-d adjusted weaning weights were 23.0 and 21.2 (± 0.65) kg for offspring produced by control and bST-treated dams, respectively (P = 0.04). In conclusion, serum IGF-I, insulin, and glucose were greater whereas serum T3, T4, and P4 were less in bST-treated ewes than in controls. Pregnancy rates and offspring adjusted weaning weights were decreased by bST treatment immediately before breeding. PMID:22785164

  20. Ad libitum Pasture Feeding in Late Pregnancy Does Not Improve the Performance of Twin-bearing Ewes and Their Lambs

    PubMed Central

    Corner-Thomas, R. A.; Back, P. J.; Kenyon, P. R.; Hickson, R. E.; Ridler, A. L.; Stafford, K. J.; Morris, S. T.

    2015-01-01

    The present study evaluated the effect of controlled ryegrass-white clover herbage availability from day 128 until day 142 of pregnancy in comparison to unrestricted availability, on the performance of twin-bearing ewes of varying body condition score (BCS; 2.0, 2.5, or 3.0) and their lambs. It was hypothesised that under conditions of controlled herbage availability, the performance of lambs born to ewes with a greater BCS would be greater than those born to ewes with a lower BCS. During the period that the nutritional regimens were imposed, the pre- and post-grazing herbage masses of the Control regimen (1,070±69 and 801±30 kg dry matter [DM]/ha) were lower than the ad libitum regimen (1,784±69 and 1,333±33 kg DM/ha; p<0.05). The average herbage masses during lactation were 1,410±31 kg DM/ha. Nutritional regimen had no effect on ewe live weight, BCS and back fat depth or on lamb live weight, indices of colostrum uptake, maximal heat production, total litter weight weaned or survival to weaning (p>0.05). The difference in ewe BCSs and back fats observed among body condition groups was maintained throughout pregnancy (p<0.05). At weaning, ewes from the BCS2.0 group had lower BCS and live weight (2.4±0.2, 74.3±2.6 kg) than both the BCS2.5 (2.6±0.2, 78.6±2.4 kg) and BCS3.0 ewes (2.7±0.2, 79.0±2.6 kg; p<0.05), which did not differ (p>0.05). Ewe BCS group had no effect on lamb live weight at birth or weaning or on maximal heat production (p>0.05). Serum gamma glutamyl transferase concentrations of lambs born to BCS3.0 ewes were higher within 36 hours of birth than lambs born to BCS2.0 ewes and BCS2.5 ewes (51.8±1.9 vs 46.5±1.9 and 45.6±1.9 IU/mL, respectively [p<0.05]). There was, however, no effect of ewe body condition on lamb plasma glucose concentration (p>0.05). Lamb survival was the only lamb parameter that showed an interaction between ewe nutritional regimen and ewe BCS whereby survival of lambs born to BCS2.5 and BCS3.0 ewes differed but only within the Control nutritional regimen ewes (p<0.05). These results indicate farmers can provide twin-bearing ewes with pre- and post-grazing ryegrass-white clover herbage covers of approximately 1,100 and 800 kg DM/ha in late pregnancy, provided that herbage covers are 1400 in lactation, without affecting lamb performance to weaning. The present results also indicate that under these grazing conditions, there is little difference in ewe performance within the BCS range of 2.0 to 3.0 and therefore they do not need to be managed separately. PMID:25656209

  1. Synovial Sarcoma of the Tongue: Report of a Case.

    PubMed

    Basile, Lauren E; Hoch, Benjamin; Dillon, Jasjit K

    2016-01-01

    This report outlines the workup and management of a 55-year-old woman with a synovial sarcoma of the lateral border of the tongue that was initially diagnosed as a glomus tumor. A review was performed of the literature on synovial sarcomas of the oral cavity and current National Comprehensive Cancer Network guidelines. Synovial sarcomas of the tongue are rare neoplasms, with variable morphologic microscopic types and immunohistochemical profiles. Fluorescence in situ hybridization analysis of the known gene translocation also can be used in diagnosis. According to the literature, resection of the tumor is the current treatment of choice; however, owing to the rarity of this entity, diagnosis and management prove challenging for the oral and maxillofacial surgeon. PMID:26212094

  2. Intraneural Extension of Synovial Sarcoma: Exceptional, or Simply Underrecognized?

    PubMed

    Ng, Wen; Thway, Khin

    2015-12-01

    Intraneural extension of soft tissue sarcomas is uncommon; it is most frequently seen in malignant peripheral nerve sheath tumor, but its occurrence is exceptional in synovial sarcoma. We describe a case arising extraneurally within the deep soft tissues of the forearm, which recurred and resulted in above-elbow amputation, revealing an unexpected finding of diffuse intraneural extension of tumor within a macroscopically normal major nerve. Despite macroscopic and microscopically clear soft tissue margins, the neoplasm had "traveled" a significant distance intraneurally to involve the neural resection margin. This feature does not appear to have been described before; it highlights the issue of whether intraneural spread of synovial sarcoma might have been previously underrecognized, and we discuss briefly some practical implications. PMID:26215219

  3. Rhabdomyosarcoma and other soft tissue sarcomas of childhood.

    PubMed

    Diller, L

    1992-08-01

    Childhood rhabdomyosarcoma and the other soft tissue sarcomas of childhood are a heterogeneous group of tumors with many histologic subtypes, affecting multiple anatomic locations and requiring the care of subspecialists from a variety of disciplines. Epidemiologic studies of childhood sarcomas indicate that a familial predisposition to malignancy may contribute to tumorigenesis in a proportion of patients. Diagnosis of these tumors may be difficult; immunohistochemical and cytogenetic analysis is clearly important. Large cooperative group studies have answered important treatment questions in past years; these studies are now being analyzed for clues to effective treatment of specific histologic and anatomic subgroups. The Intergroup Rhabdomyosarcoma Study IV is now open and the questions addressed are reviewed. New developments in late effects of therapy for childhood sarcoma are considered. PMID:1511025

  4. Formation of reticuloendotheliosis virus pseudotypes of Rous sarcoma virus.

    PubMed

    Sawyer, R C; Hanafusa, H

    1977-06-01

    Superinfection of chicken embryo fibroblasts transformed by the defective Bryan strain of Rous sarcoma virus (BH-RSV) with two different reticuloendotheliosis viruses (REVs), REV strain T (REV-T) or spleen necrosis virus (SNV), resulted in the production of infectious sarcoma virus pseudotypes. These pseudotypes were neutralized by antiserum prepared against SNV and were unable to infect chicken cells preinfected with either REV-T or SNV. These results suggest that defective BH-RSV is able to use the glycoprotein from REV to form infectious pseudotypes. On the other hand, neither REV-T nor SNV was able to supply a functional reverse transcriptase to the polymerase-negative mutant BH-RSValpha, nor was REV-T or SNV able to complement the defect in the internal protein gene of the temperature-sensitive avian sarcoma virus mutant NY45. PMID:195082

  5. Adamantinoma-like Ewing family tumors of the head and neck: a pitfall in the differential diagnosis of basaloid and myoepithelial carcinomas.

    PubMed

    Bishop, Justin A; Alaggio, Rita; Zhang, Lei; Seethala, Raja R; Antonescu, Cristina R

    2015-09-01

    Ewing sarcoma family tumors (EFTs) of the head and neck are rare and may be difficult to diagnose, as they display significant histologic overlap with other more common undifferentiated small blue round cell malignancies. Occasionally, EFTs may exhibit overt epithelial differentiation in the form of diffuse cytokeratin immunoexpression or squamous pearls, resembling the so-called adamantinoma-like EFTs and being challenging to distinguish from bona fide carcinomas. Furthermore, the presence of EWSR1 gene rearrangement correlated with strong keratin expression may suggest a myoepithelial carcinoma. Herein, we analyze a series of 7 adamantinoma-like EFTs of the head and neck, most of them being initially misdiagnosed as carcinomas because of their anatomic location and strong cytokeratin immunoexpression, and subsequently reclassified as EFT by molecular techniques. The tumors arose in the sinonasal tract (n=2), parotid gland (n=2), thyroid gland (n=2), and orbit (n=1), in patients ranging in age from 7 to 56 years (mean, 31 y). Microscopically, they departed from the typical EFT morphology by growing as nests with peripheral nuclear palisading and prominent interlobular fibrosis, imparting a distinctly basaloid appearance. Moreover, 2 cases exhibited overt keratinization in the form of squamous pearls, and 1 sinonasal tumor demonstrated areas of intraepithelial growth. All cases were positive for CD99, pancytokeratin, and p40. A subset of cases showed synaptophysin, S100 protein, and/or p16 reactivity, further confounding the diagnosis. Fluorescence in situ hybridization assays showed EWSR1 and FLI1 rearrangements in all cases. Our results reinforce that a subset of head and neck EFTs may show strong cytokeratin expression or focal keratinization, and are therefore histologically indistinguishable from more common true epithelial neoplasms. Thus, CD99 should be included in the immunopanel of a round cell malignancy regardless of strong cytokeratin expression or anatomic location, and a strong and diffuse CD99 positivity should prompt molecular testing for the presence of EWSR1 gene rearrangements. PMID:26034869

  6. Head and Neck Sarcomas: Analysis of the SEER Database

    PubMed Central

    Peng, Kevin A.; Grogan, Tristan; Wang, Marilene B.

    2015-01-01

    Objective To summarize the epidemiology of sarcomas occurring in the head and neck and identify prognostic factors for patient survival. Study Design and Setting Cross-sectional analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program. Methods The SEER 18 registries, comprising sarcoma diagnoses made from 1973 to 2010, were queried for sarcomas arising in the head and neck. Pediatric and adult patients were analyzed separately, and multivariate and propensity-matched analyses were performed to identify predictors of disease-specific survival. Results In all, 11,481 adult cases and 1244 pediatric cases were identified. In adults, the most common histologic subtypes were malignant fibrous histiocytoma (MFH), Kaposi sarcoma, and hemangiosarcoma, while in the pediatric cohort, the most common histologic subtypes were rhabdomyosar-coma, MFH, and osteosarcoma. Cause-specific 2-, 5-, and 10-year survival rates were 76%, 66%, and 61% for adults and 84%, 73%, and 71% for pediatric patients. Multivariate analysis performed for adults revealed that male gender, absence of radiation therapy, and stage I disease were associated with improved cause-specific survival reaching statistical significance. However, a propensity-matched model demonstrated no significant difference in cause-specific survival between patients who received radiation and those who did not. Conclusion Sarcomas, a heterogeneous group of malignant mesenchymal tumors, are uncommonly found in the head and neck. This study represents the largest analysis of patients with head and neck sarcomas in the literature and demonstrates the impact of age, gender, primary site, histology, and radiation status on overall prognosis. PMID:25135525

  7. Evaluation of the effect of progesterone CIDR Devices on circulating levels of progesterone in cyclic ewes 

    E-print Network

    Satterfield, Michael Carey

    2005-02-17

    and progesterone administered to ewes in spring and summer. J Anim Sci 1990; 68:923-930. 12. Welch RAS, Andrews WD, Barnes DR, Bremmer K, Harvey TG. CIDR dispenser for oestrus and ovulation control in sheep. Proc 10 th Int Congr on Anim Reprod Artif Insem...

  8. Effect of feeding flax or linseed meal on progesterone clearance rate in ovariectomized ewes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovariectomized ewes (n = 22; 68.76 ± 2.34 kg initial body weight; 2.9 ± 0.1 initial body condition score) were individually fed one of three diets: 1) Control (phytoestrogen-free; n = 7), 2) Flax containing diet (n = 8), or 3) linseed meal (LSM) containing diet (n =7) to investigate the rate of prog...

  9. Grazing Deferment Effects On Forage Diet Quality And Ewe Performance Following Summer Rangeland Fire

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Complete rest or grazing deferment is a general recommendation following fire in the western U.S. to encourage vegetative recovery. However, effects of grazing deferments on animal performance have not been determined. Forage quality and ewe performance were evaluated for grazing trials with deferme...

  10. MATHEMATICAL ANALYSIS FOR RESERVOIR MODELS ZHANGXIN CHEN AND RICHARD E. EWING \\Lambda

    E-print Network

    Ewing, Richard E.

    physically reasonable hypotheses on the data. Then in the second part of this paper, it is proven how (usually gas or oil in petroleum engineering, or water in groundwater hydrology). The usual equations@dragon.math.smu.edu. R. Ewing, Institute for Scientific Computation, Texas A&M University, College Station, Texas 77843

  11. Numerical Methods for Contaminant Transport in Porous Media Richard E. Ewing

    E-print Network

    Ewing, Richard E.

    Abstract. The transport of contaminants in porous media is a com­ plex process that may involve from one plume is determined, one needs accurate models to design and optimize a remediation strategies of characteristics) described by Dou­ glas and Russell [18] or Ewing et al. [36] or ELLAM (Eulerian

  12. A case report describing detection of Rhodoturola minuta fungemia in an ewe lamb

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An eight-month-old crossbred ewe that was normal upon physical examination was humanely euthanized for tissue collection. Prior to euthanasia, whole blood was collected via jugular venipuncture into 60-ml syringes containing EDTA anticoagulant. After sacrifice, the brain was removed and the choroi...

  13. Evidence that the Arcuate Nucleus Is an Important Site of Progesterone Negative Feedback in the Ewe

    PubMed Central

    Holaskova, Ida; Nestor, Casey C.; Connors, John M.; Billings, Heather J.; Valent, Miro; Lehman, Michael N.; Hileman, Stanley M.

    2011-01-01

    There is now considerable evidence that dynorphin neurons mediate the negative feedback actions of progesterone to inhibit GnRH and LH pulse frequency, but the specific neurons have yet to be identified. In ewes, dynorphin neurons in the arcuate nucleus (ARC) and preoptic area (POA) are likely candidates based on colocalization with progesterone receptors. These studies tested the hypothesis that progesterone negative feedback occurs in either the ARC or POA by determining whether microimplants of progesterone into either site would inhibit LH pulse frequency (study 1) and whether microimplants of the progesterone receptor antagonist, RU486, would disrupt the inhibitory effects of peripheral progesterone (study 2). Both studies were done in ovariectomized (OVX) and estradiol-treated OVX ewes. In study 1, no inhibitory effects of progesterone were observed during treatment in either area. In study 2, microimplants of RU486 into the ARC disrupted the negative-feedback actions of peripheral progesterone treatments on LH pulse frequency in both OVX and OVX+estradiol ewes. In contrast, microimplants of RU486 into the POA had no effect on the ability of systemic progesterone to inhibit LH pulse frequency. We thus conclude that the ARC is one important site of progesterone-negative feedback in the ewe. These data, which are the first evidence on the neural sites in which progesterone inhibits GnRH pulse frequency in any species, are consistent with the hypothesis that ARC dynorphin neurons mediate this action of progesterone. PMID:21693677

  14. Judicial Responses to Adverse Academic Decisions Affecting Public Postsecondary Institution Students since "Horowitz" and "Ewing".

    ERIC Educational Resources Information Center

    Ford, Deborah L.; Strope, John L., Jr.

    1996-01-01

    The "Horowitz" and "Ewing" decisions defined the rights to due process in academic matters on the public postsecondary campus. This study bring the law forward since the 1978 and 1985 Supreme Court decisions by identifying and analyzing 59 cases. (142 footnotes) (MLF)

  15. Ovarian consequences of low dose peroral Fusarium (T-2) toxin in a ewe and heifer model.

    PubMed

    Huszenicza, G; Fekete, S; Szigeti, G; Kulcsár, M; Fébel, H; Kellems, R O; Nagy, P; Cseh, S; Veresegyházy, T; Hullár, I

    2000-05-01

    The effect of low dose peroral Fusarium produced T-2 toxin intake upon the ovarian function was evaluated in ewes (n = 30; Trial 1) and heifers (n = 7; Trial 2). Half of the ewes and all of the heifers were fed rich, acidosis-inducing concentrate. The 30 ewes were divided into 6 groups of 5 animals each. They were given 0, 0.3 or 0.9 mg/day (0, 5 or 15 ug/kg) purified T-2 toxin per os for 21 days (3x2 factorial design). Four of the 7 heifers were fed 9 mg/day (25 ug/kg) of the same purified T-2 toxin for 20 days while 3 remained untreated. The estrus cycles in all animals were synchronized prior to the trials and the T-2 exposure was started in the mid-luteal phase. The acidic condition in the rumen was estimated by the determination of urinary net acid-base excretion. The ovarian activity was followed with blood sampling for progesterone on alternate days (Trial 1) or with ultrasonography and sampling for progesterone daily (Trial 2). All of the heifers and concentrate-fed ewes showed a compensated acidosis, during first two thirds of T-2 exposure. In Trial 1, ovarian malfunction manifested as lower P4 peak concentration in the midluteal phase, shortening of the CL lifespan and prolonged follicular phases. These malfunctions were detected in 3 and 3 ewes fed concentrate and 0.3 mg and 0.9 mg T-2 toxin. Lower P4 peak concentration was observed in 1 ewe fed regular diet and 0.9 mg T-2 toxin. None of the control and acidotic groups (0 mg T-2), or ewes fed regular diet with 0.3 mg T-2 showed any ovarian malfunction. In Trial 2, after PGF2, administration the ovulation occured later and the plasma progesterone level remained low (< 3 nmol/l) for a longer period in T-2 treated heifers, than their untreated control mates (5.0+/-0.7 vs 3.7+/-0.5 d, P<0.05 and 8.3+/-0.4 vs 6.3+/-0.9 d, P<0.01, respectively). These results show that the peroral T-2 intake can significantly retard the folliculus maturation and ovulation and perhaps the subsequent luteinisation also in ruminants kept on concentrate-rich diet. PMID:10883849

  16. Epithelioid Sarcoma in the Cervical Spine: A Case Report

    PubMed Central

    Lee, Chungnam; Kim, Nara

    2015-01-01

    Epithelioid sarcoma is a rare and highly malignant soft tissue neoplasm that most commonly occurs in the long bones. This uncommon tumor has a poor clinical outcome, and the modality of its treatment has not yet been fully established. The authors report an extremely rare presentation of epithelioid sarcoma in the cervical spine, along with its clinical progression, imaging, and pathology. The patient underwent three surgical procedures and adjuvant radiochemical management. He survived for 25 months with a good general condition and adapted well to his social activity. Systemic metastasis was not found, but the patient died of respiratory failure due to direct tracheal invasion of the tumor. PMID:26512275

  17. Results of Pulmonary Resection: Sarcoma and Germ Cell Tumors.

    PubMed

    Ceppa, DuyKhanh P

    2016-02-01

    Pulmonary metastasis occurs in as many as 88% and 80% of stage IV patients with sarcoma and germ cell tumors, respectively. Pulmonary metastatectomy may be the only means of rendering a patient disease free. Sublobar resection (wedge or segmentectomy), lobectomy, and pneumonectomy achieve complete resection. Bilateral disease can be resected via staged thoracoscopy/thoracotomy, median sternotomy, or clamshell thoracotomy. Multiple resections and re-resections have resulted in improved survival. Five-year survival rates as high as 35% to 52% for sarcoma and 80% for germ cell tumor can be realized. PMID:26611510

  18. SARC: Development and Support of a Sarcoma Research Consortium Infrastructure

    SciTech Connect

    Arkison, Jim

    2007-10-29

    SARC is a non-for-profit organization whose mission and vision is to advocate for the collaboration on the design of clinical trials on sarcoma, to further the knowledge regarding the diagnosis and treatment of sarcoma and provide accurate and up to date information to physicians, patients and families. The objectives are to assist in the development of the infrastructure for the continued growth and spectrum of clinical research, to facilitate biannual meeting of investigators, and to develop a preclinical research base that would design and conduct research that would improve the process of drug treatments selected for clinical research trials.

  19. Semiquantitative gallium scintigraphy in patients with osteogenic sarcoma

    SciTech Connect

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

    1984-04-01

    Sequential gallium scans were performed in 37 patients with newly diagnosed osteogenic sarcoma. High gallium uptake was found more often in males in the 10 to 19 age group and in femoral lesions. High uptake was also seen in patients who had predominantly osteoblastic or mixed changes on radiographs and in those who had a soft tissue mass. Following chemotherapy, significant decrease of tumor to nontumor ratio occurred in the patients who responded to treatment as shown by a Grade III or IV response on histologic examinations at the time of en bloc resection. It is concluded that semiquantitative gallium scintigraphy is useful in monitoring therapeutic response in patients with osteogenic sarcoma.

  20. Langerhans cell sarcoma: case report and review of world literature.

    PubMed

    Zwerdling, Ted; Won, Eric; Shane, Lisa; Javahara, Ramin; Jaffe, Ronald

    2014-08-01

    Langerhans cell sarcoma is a rare malignancy with only 1 pediatric case (less than 15 y of age) reported. Here, we report the second case of Langerhans cell sarcoma in a child who presented with cord compression. This patient was treated with extensive surgical resection, postoperative chemotherapy, and involved-field radiation therapy. She completed therapy and remains in remission for 27 months. A review and analysis of all 53 cases published in the world literature is provided to help guide physicians treating this disease. Recently discovered genetic mutation involving BRAF is also discussed. PMID:24942035

  1. [Molecular targeted drugs for soft tissue sarcoma and neuroendocrine tumor].

    PubMed

    Kato, Shunsuke

    2015-08-01

    Both the soft tissue sarcomas and the neuroendocrine tumors are rare diseases. Therefore the recruiting of these patients was more difficult than other cancer species, and the development of the new therapy for these diseases did not readily advance. However, the identification of driver molecules for each sub-type enabled us to the development of the molecular targeted drugs. As for the GIST, several TKIs are used, but in late years it is found that susceptibility of TKIs varies according to difference in second mutation. In this chapter, the molecular target drug for the soft tissue sarcoma and the neuroendocrine tumor is reviewed. PMID:26281696

  2. Ewes Direct Most Maternal Attention towards Lambs that Show the Greatest Pain-Related Behavioural Responses

    PubMed Central

    Futro, Agnieszka; Mas?owska, Katarzyna; Dwyer, Cathy M.

    2015-01-01

    Although neonatal farm animals are frequently subjected to painful management procedures, the role of maternal behaviour in pain coping, has not been much studied. We investigated whether ewes were able to distinguish between lambs in pain and those that were not, and whether their behaviour altered depending on the severity of lamb pain. Eighty male lambs were allocated to one of 4 pain treatments within 24 hours of birth. Lambs were either handled only (C), bilaterally castrated with tight rubber rings (RR), as for RR but with the application of a Burdizzo clamp immediately proximal to the ring (Combined) or subjected to short scrotum castration (SSC) where the testicles were retained within the abdomen and only the scrotum removed. The behaviour of the ewe, treated lamb and untreated sibling where present (n = 54) were recorded for 30 minutes after treatment. Castration treatment increased the expression of abnormal standing and lying postures, specific pain-related behaviours (head-turning, stamping/kicking, easing quarters, tail wagging) and composite pain scores (P<0.001 for all). The greatest expression of pain-related behaviours was shown by lambs in the RR group, which were the only group to show rolling responses indicative of severe pain, followed by the SSC group. Ewes expressed more licking/sniffing responses to the RR and SSC lambs than towards the Combined and C lambs (P<0.05), and oriented most to RR lambs and least to C lambs (P<0.001). Ewes with two lambs also directed more attention towards the treated than the untreated lamb (P<0.001). The quantity of maternal care directed towards the lamb was positively correlated with the expression of active pain behaviours. The data demonstrate that ewes are able to discriminate between lambs in pain and those that are not, and that their response is increased with a greater severity of pain. PMID:26217942

  3. Prevalence and etiology of subclinical mastitis in dairy ewes in two seasons in Semnan province, Iran.

    PubMed

    Narenji Sani, Reza; Mahdavi, Ali; Moezifar, Melika

    2015-10-01

    Twenty-one dairy ewe flocks selected by stratified random sampling were subjected to study the prevalence and etiology of subclinical intramammary infections and to assess the influence of parity on the prevalence of intramammary infections. Also, spontaneous cure rates were determined over study period. A total of 1192 milk samples were collected at 2 weeks after lambing until tenth-week postpartum. All flocks had hand milking; those which were classified by bacterial culture and California Mastitis Test (CMT) as positive were deemed to have glands with subclinical mastitis (SCM). Of 1192 halves examined, 791 samples were collected during spring and 401 samples were collected during summer. Prevalence rate of SCM in spring was 14.7 %; and spontaneous cure that occurred in this season was 88.8 %; coagulase-negative staphylococci (CNS) were the most common isolates (66.6 %). Samples collected in spring showed higher prevalence rate of SCM than summer samples. This rate was 8.9 % in summer. Spontaneous cure rate in this season was 69.4 %, and Staphylococcus aureus (72.2 %) was the most common isolates. SCM was seen at significantly lower rates in left half than in right one (p?ewes had significantly higher (p?ewes. The incidence of clinical mastitis (defined as number of clinical cases per 100 ewe-months) was 0.21 and 0.74 in spring and summer, respectively. The isolates from clinical cases in spring were fungi and, from summer, were S. aureus. Also, S. aureus SCM cases were not significantly severe than other SCM cases. In conclusion, multiparous ewes were most at risk, and severity of infection was higher in summer. PMID:26041046

  4. Radiation Therapy for Chloroma (Granulocytic Sarcoma)

    SciTech Connect

    Bakst, Richard; Wolden, Suzanne; Yahalom, Joachim

    2012-04-01

    Objectives: Chloroma (granulocytic sarcoma) is a rare, extramedullary tumor of immature myeloid cells related to acute nonlymphocytic leukemia or myelodysplastic syndrome. Radiation therapy (RT) is often used in the treatment of chloromas; however, modern studies of RT are lacking. We reviewed our experience to analyze treatment response, disease control, and toxicity associated with RT to develop treatment algorithm recommendations for patients with chloroma. Patients and Methods: Thirty-eight patients who underwent treatment for chloromas at our institution between February 1990 and June 2010 were identified and their medical records were reviewed and analyzed. Results: The majority of patients that presented with chloroma at the time of initial leukemia diagnosis (78%) have not received RT because it regressed after initial chemotherapy. Yet most patients that relapsed or remained with chloroma after chemotherapy are in the RT cohort (90%). Thirty-three courses of RT were administered to 22 patients. Radiation subsite breakdown was: 39% head and neck, 24% extremity, 9% spine, 9% brain, 6% genitourinary, 6% breast, 3% pelvis, and 3% genitourinary. Median dose was 20 (6-36) Gy. Kaplan-Meier estimates of progression-free survival and overall survival in the RT cohort were 39% and 43%, respectively, at 5 years. At a median follow-up of 11 months since RT, only 1 patient developed progressive disease at the irradiated site and 4 patients developed chloromas at other sites. RT was well tolerated without significant acute or late effects and provided symptom relief in 95% of cases. Conclusions: The majority of patients with chloromas were referred for RT when there was extramedullary progression, marrow relapse, or rapid symptom relief required. RT resulted in excellent local disease control and palliation of symptoms without significant toxicity. We recommend irradiating chloromas to at least 20 Gy, and propose 24 Gy in 12 fractions as an appropriate regimen.

  5. Fast neutron therapy for soft tissue sarcoma

    SciTech Connect

    Pickering, D.G.; Stewart, J.S.; Rampling, R.; Errington, R.D.; Stamp, G.; Chia, Y.

    1987-10-01

    Seventy-nine patients with soft tissue sarcoma were treated with fast neutron therapy at the Hammersmith Hospital, MRC Cyclotron Unit. Sixty-six of these, treated between 1971 and 1983 were assessable. The histology was reviewed and graded in 82% of cases and tumors divided into groups according to maximum diameter. In sixteen patients, who were irradiated following complete macroscopic removal of tumor, there was 94% local control and 86% survived 5 years. Of the 50 patients who had gross tumors present 62% were greater than 10 cm in diameter, and 20 were recurrent after previous radiotherapy or surgery or both. Sixty-eight per cent of gross tumors completely regressed and local control was 52%. The main cause of death was metastatic spread, and median survival was 63 months for Grade 1 patients, 9 months for Grade 2, and 7 months for Grade 3. Thus, there was a significant advantage to patients with Grade 1 tumor but little difference between Grades 2 and 3. Twenty-seven patients experienced late complications of treatment, 67% of which involved the skin predominantly and were related to the low energy of neutrons used. Seventeen of the 27 had received previous radiotherapy. Neutron therapy given in this dose and fractionation produced a higher local control rate than photon therapy, but complications were more frequent. Since these mainly involved the skin a lower level of complications may be anticipated using higher energy neutrons which will have a more even distribution of dose and lower skin dosage. Forty-eight per cent of patients developed metastatic disease, indicating the need for effective systemic therapy, especially in Grades 2 and 3 tumors.

  6. Decline in faecal worm egg counts in lambs suckling ewes treated with lipophilic anthelmintics: implications for hastening development of anthelmintic resistance.

    PubMed

    Dever, M L; Kahn, L P

    2015-04-30

    The aim for this experiment was to look for evidence of milk transfer of anthelmintic actives from ewes to their suckling lambs by reference to lambs' faecal worm egg count (WEC). The hypothesis was that WEC will decline in lambs suckling ewes treated with anthelmintics known to be lipophilic. One group of lactating Border Leicester×Merino ewes were treated (TX) with a combination of short (2.5mg/kg monepantel) and long-acting (1mg/kg moxidectin long-acting injection and a sustained release of 4.62g albendazole over 100 days) anthelmintics to remove gastrointestinal nematode (GIN) burden on day 0. The other group of lactating ewes (UTX) and all lambs (White Suffolk sires) were not treated. Ewes and lambs grazed as a single group and were exposed to GIN (predominately Haemonchus contortus) infection from pasture. Measurements were taken on days 0 and 7. WEC of lambs suckling UTX ewes increased from 6441 to 10,341 eggs per gram (epg) between days 0 and 7, while there was a 51% reduction in WEC for lambs suckling TX ewes. Packed cell volume (PCV) was significantly higher for lambs suckling TX ewes on day 7 compared to lambs suckling UTX ewes (28.5% vs. 24.9%, p=0.039). These results suggest that lambs suckling ewes treated with lipophilic anthelmintics received a sub-therapeutic dose via milk which would increase selection within the GIN (H. contortus) population for anthelmintic resistance. PMID:25754351

  7. Prognostic factors in soft tissue sarcoma.

    PubMed

    Maretty-Nielsen, Katja

    2014-11-01

    Despite major advances in the knowledge of soft tissue sarcoma (STS) during the last decades, no significant improvement in survival has been observed. Detailed data on the prognosis of STS are crucial in order to identify patients who might benefit from more aggressive treatment. Such data can be obtained from properly designed databases; however, the validation of data is crucial in order to obtain valid, reliable results. Furthermore, the majority of prognostic studies in STS have been limited by potential selection bias, low power, and biased estimates due to the statistical methods used, e.g., dichotomizing continuous variables, censoring competing events, as well as not adjusting for important confounders. The overall aim of this thesis was to investigate the prognosis of STS patients using data from the Aarhus Sarcoma Registry (ASR), covering western Denmark in the period from 1979 to 2008. In study I, we systematically validated data in the ASR and evaluated the validity, including completeness of patient registration and accuracy of data. In study II, we investigated the prognostic impact of patient-, tumor-, and treatment-related factors on local recurrence and disease-specific mortality. These were analyzed in a competing risk model in which continuous variables were included as cubic splines and possible confounders were selected based on directed acyclic graphs. In study III, we examined the impact of comorbidity on overall and disease-specific mortality. In study IV, we compared mortality in patients with abnormal biomarkers to those with normal values, assessed the significance of adjusting for comorbidity, as well as constructed a prognostic biomarker score. In study V, we described the relative mortality, i.e., the mortality in STS patients compared with the mortality in a general population, and compared relative and disease-specific estimates. The mortality in the general population was determined using an individually age- and sex-matched comparison cohort. All five studies were conducted in western Denmark within a population of approximately 2.5 million. Individual linkage between the ASR and national registries was made possible by the unique Danish civil registration number. The National Patient Registry and the LABKA research database were used to obtain data on comorbidity and biomarkers. In studies II to V we used a time-to-event-analysis approach that included cumulative incidence functions as well as crude and confounder adjusted Cox proportional hazard regression. In study I, we established that the overall validity of data in the ASR, after validation, was satisfactory and that the ASR included 85.3% of sarcoma patients from western Denmark between 1979 and 2008. In study II, we found a five-year local recurrence and disease-specific mortality of 16% and 24%, respectively. We excluded depth as a prognostic factor, and established that age, duration of symptoms, tumor size, anatomical and compartmental location, as well as radiotherapy were important prognostic factors for disease-specific mortality. In study III, we found that the level of comorbidity before or at diagnosis was an independent prognostic factor for both overall and disease-specific mortality, even after adjustment for age. In study IV, we showed that pretreatment levels of albumin, hemoglobin, and neutrophil to lymphocyte ratios were independently correlated with disease-specific mortality, and that adjusting for comorbidity was significant. In study V, we found five- and ten-year relative mortalities of 32.8% and 36.0%, respectively. The mortality in patients with low-grade STS was not significantly increased compared with the general population. The five- and ten-year disease-specific mortalities were underestimated by 3.1 and 1.9 percentage points compared to the relative mortality, respectively. We showed that relative mortality provided an accurate method to differentiate between cancer-specific and non-cancer-specific deaths. In conclusion, we showed that the ASR is a valid source of population-based data on STS. Impro

  8. Clear Cell Sarcoma of Kidney in a Neonate

    PubMed Central

    Jain, Sanjay; Tuteja, Neeraj; Agrawal, Leeladhar

    2014-01-01

    A neonate presented with abdominal mass in left flank was investigated and operated upon. Histopathology confirmed the diagnosis of clear cell sarcoma of the kidney. Post-operatively, chemotherapy was given according to the NWTS-5 protocol. During follow-up, the patient has shown good recovery after 7 months of surgery. PMID:26023506

  9. National Sarcoma Awareness Month (H. Res.150; 114th Congress)

    Cancer.gov

    The resolution expresses support for the designation of July as National Sarcoma Awareness Month. H. Res. 150 was introduced by Rep. Kathy Castor (D-FL) on 3/16/2015 and referred to the Committee on Oversight and Government Reform.

  10. Pazopanib and HDAC inhibitors interact to kill sarcoma cells

    PubMed Central

    Tavallai, Seyedmehrad; Hamed, Hossein A; Grant, Steven; Poklepovic, Andrew; Dent, Paul

    2014-01-01

    The present studies were to determine whether the multi-kinase inhibitor pazopanib interacted with histone deacetylase inhibitors (HDACI: valproate, vorinostat) to kill sarcoma cells. In multiple sarcoma cell lines, at clinically achievable doses, pazopanib and HDACI interacted in an additive to greater than additive fashion to cause tumor cell death. The drug combination increased the numbers of LC3-GFP and LC3-RFP vesicles. Knockdown of Beclin1 or ATG5 significantly suppressed drug combination lethality. Expression of c-FLIP-s, and to a lesser extent BCL-XL or dominant negative caspase 9 reduced drug combination toxicity; knock down of FADD or CD95 was protective. Expression of both activated AKT and activated MEK1 was required to strongly suppress drug combination lethality. The drug combination inactivated mTOR and expression of activated mTOR strongly suppressed drug combination lethality. Treatment of animals carrying sarcoma tumors with pazopanib and valproate resulted in a greater than additive reduction in tumor volume compared with either drug individually. As both pazopanib and HDACIs are FDA-approved agents, our data argue for further determination as to whether this drug combination is a useful sarcoma therapy in the clinic. PMID:24556916

  11. Incidence of sarcoma in patients treated with fast neutrons

    SciTech Connect

    MacDougall, R. Hugh . E-mail: medical.dean@st-andrews.ac.uk; Kerr, Gillian R.; Duncan, William

    2006-11-01

    Purpose: The aim of this study is to report the incidence of soft tissue sarcoma in a large group of patients treated with fast neutrons. Methods: A systematic review was conducted of long-term follow-up after trials of fast neutron therapy for cancers at various sites. The study took place at Edinburgh Cancer Centre, Western General Hospital, Edinburgh, Scotland, United Kingdom. From 1977 to 1984, 620 patients were treated using fast neutrons in the MRC cyclotron unit in Edinburgh. Most of these were treated within randomized controlled trials. Follow-up was maintained in all except 2 patients, who left the area to return abroad. The main outcome measure was the incidence of new soft-tissue sarcomas during long-term follow-up. Results: Three cases of sarcoma, developing within the treatment volume, were observed in a small group of patients treated some years earlier using fast neutrons. This incidence was 111 times what would have been expected in the normal population and 15 times the incidence in a comparable photon-treated group of patients. Conclusion: The long-term incidence of sarcomas in patients previously treated with fast neutrons is significant.

  12. Intravenous maternal -arginine administration to twin-bearing ewes during late pregnancy enhances placental growth and development.

    PubMed

    van der Linden, D S; Sciascia, Q; Sales, F; Wards, N J; Oliver, M H; McCoard, S A

    2015-10-01

    This study aimed to investigate if intravenous maternal Arg administration to well-fed twin-bearing ewes, from 100 to 140 d of gestation or birth, could enhance placental development and placental nutrient transport. Ewes received intravenous infusions of saline (control) or 345 ?mol Arg HCl/kg of BW 3 times daily from d 100 of pregnancy (P100) to d 140 of pregnancy (P140; cohort 1) or from P100 to birth (cohort 2). At P140, ewes in cohort 1 were euthanized and individual placentae per fetus were dissected and placentomes were classed per type (A to D) and size (light to heavy). Placentome number and individual weight were recorded. As an indicator of placental nutrient transport, blood plasma was collected from the uterine ovarian vein (UOV), uterine artery (UA), and umbilical vein and artery at the time of euthanasia and analyzed for metabolites and free AA concentrations. The ewes in cohort 2 were allowed to lamb and lambs were weighed at birth. The expelled placenta was dissected and number of cotyledons and weights of total cotyledons, remaining fetal membranes, and total placenta were recorded. At P140, Arg-infused ewes had a 63% ( = 0.03) greater number of unoccupied caruncles than control ewes. No differences were observed for placental weight at P140. At birth, lambs from Arg-infused ewes tended to have 11% ( = 0.09) greater placental weight and 34% ( = 0.03) greater total cotyledon weight compared with control lambs. Arginine-infused ewes (Arg-infused) had increased concentrations of Arg ( = 0.0001) and ornithine (Orn; = 0.004) but decreased concentrations of Met ( = 0.01) and His ( = 0.02 and = 0.09, respectively) compared with control ewes in plasma UOV and UA. Fetuses from Arg-infused ewes had increased concentrations of Orn ( = 0.005) and decreased concentrations of His ( = 0.006), Met ( = 0.003), and Lys ( = 0.01) but no differences in Arg ( > 0.10) concentrations were found compared with control fetuses in umbilical artery and vein plasma. This study showed that maternal Arg administration of well-fed twin-bearing ewes during late pregnancy tended to improve placental growth and development. PMID:26523584

  13. Effect of Moxidectin Treatment at Peripartum on Gastrointestinal Parasite Infections in Ewes Raised under Tropical Andes High Altitude Conditions

    PubMed Central

    Vargas-Duarte, J. J.; Lozano-Márquez, H.; Grajales-Lombana, H. A.; Manrique-Perdomo, C.; Martínez-Bello, D. A.; Saegerman, C.; Raes, M.; Kirschvink, N.

    2015-01-01

    This study tested the impact of moxidectin at peripartum on nematode fecal egg count (FEC) and clinical parameters on ewes in the high altitude tropical Andes of Colombia. FEC and clinical evaluations were performed on 9 occasions in 43 naturally infected ewes before and during gestation and after lambing. Moxidectin (Mox, 200?µg?kg?1) was applied at late pregnancy (T1, n = 15) or 48 hours after parturition (T2, n = 14). 14 untreated ewes served as controls (C). Suckling lambs (n = 58) remained untreated and underwent four clinical and parasitological evaluations until 8 weeks after birth. Mox efficacy equaled 99.3% (T1) and 96.9% (T2). Highest mean FEC value reflecting periparturient nematode egg rise (PPER) was recorded in C ewes at 4–6 weeks after lambing. Significant FEC reductions were found in T1 (94.8%) and T2 (96.7%) ewes (p < 0.05). All lambs showed a significant and ewes-group independent increase in FEC before weaning (p < 0.05). Clinical parameters (anemia and diarrhea) showed time- and treatment-related differences (p < 0.05). Monitoring of FEC and clinical parameters linked to gastrointestinal parasite infections allowed demonstrating that postpartum or preweaning are two critical periods to nematode infection for sheep raised under tropical Andes high altitude conditions. Use of Mox as anthelmintic treatment prevented PPER. PMID:26078913

  14. Maternal dietary intake alters organ mass and endocrine and metabolic profiles in pregnant ewe lambs.

    PubMed

    Vonnahme, K A; Neville, T L; Perry, G A; Redmer, D A; Reynolds, L P; Caton, J S

    2013-10-01

    To determine the impacts of Se supply and maternal dietary intake on ewe organ mass and endocrine and metabolic changes throughout gestation, pregnant first parity ewes (n=77) were allocated to 6 treatments in a 2×3 factorial array. Factors included Se [adequate Se (ASe; 9.5?g/kg BW) vs. high Se (HSe; 81.8?g/kg BW)] initiated at breeding and dietary intake [60% (RES), 100% (CON), or 140% (EXC) of requirements] initiated on d 50 of gestation. Ewes were individually fed and blood samples from the jugular vein were obtained approximately every 14 d from d 50 until parturition. Maternal Se supply did not impact endocrine or metabolic status. There was a nutritional intake by day interaction for NEFA, blood urea nitrogen (BUN), insulin, triiodothyronine (T3), thyroxine (T4), progesterone (P4), and estradiol-17? (E2). As expected, with increased maternal intake, NEFA concentrations were reduced. During the last weeks of gestation, BUN and insulin were elevated in EXC compared with RES ewes. Although the pattern of T3 and T4 differed throughout gestation within a treatment group, as maternal intake increased, circulating T3 and T4 were increased. For P4 and E2, as maternal dietary intake increased, there was a reduction in the steroid concentrations in jugular blood. There was only a main effect of maternal nutrition (P<0.001) for cortisol concentrations with EXC ewes having greater concentrations than RES and CON ewes, which did not differ. Although Se is known to influence thyroid hormone metabolism, supranutritional levels during pregnancy did not alter circulating T3 and T4 concentrations. Alterations in maternal endocrine status may have influenced placental transport of nutrients to the developing fetus, which we have shown previously is affected by maternal dietary Se and intake. In addition, the alterations in mammary gland weight that we observed may explain the impact of maternal nutrition on mammary gland function and colostrum production, thereby further impairing growth of developing neonates. PMID:23981299

  15. Extrapolated withdrawal-interval estimator (EWE) algorithm: a quantitative approach to establishing extralabel withdrawal times.

    PubMed

    Martín-Jiménez, Tomás; Baynes, Ronald E; Craigmill, Arthur; Riviere, Jim E

    2002-08-01

    The extralabel use of drugs can be defined as the use of drugs in a manner inconsistent with their FDA-approved labeling. The passage of the Animal Medicinal Drug Use Clarification Act (AMDUCA) in 1994 and its implementation by the FDA-Center for Veterinary Medicine in 1996 has allowed food animal veterinarians to use drugs legally in an extralabel manner, as long as an appropriate withdrawal period is established. The present study introduces and validates with simulated and experimental data the Extrapolated Withdrawal-Period Estimator (EWE) Algorithm, a procedure aimed at predicting extralabel withdrawal intervals (WDIs) based on the label and pharmacokinetic literature data contained in the Food Animal Residue Avoidance Databank (FARAD). This is the initial and first attempt at consistently obtaining WDI estimates that encompass a reasonable degree of statistical soundness. Data on the determination of withdrawal times after the extralabel use of the antibiotic oxytetracycline were obtained both with simulated disposition data and from the literature. A withdrawal interval was computed using the EWE Algorithm for an extralabel dose of 25 mg/kg (simulation study) and for a dose of 40 mg/kg (literature data). These estimates were compared with the withdrawal times computed with the simulated data and with the literature data, respectively. The EWE estimates of WDP for a simulated extralabel dose of 25 mg/kg was 39 days. The withdrawal time (WDT) obtained for this dose on a tissue depletion study was 39 days. The EWE estimate of WDP for an extralabel intramuscular dose of 40 mg/kg in cattle, based on the kinetic data contained in the FARAD database, was 48 days. The withdrawal time experimentally obtained for similar use of this drug was 49 days. The EWE Algorithm can obtain WDI estimates that encompass the same degree of statistical soundness as the WDT estimates, provided that the assumptions of the approved dosage regimen hold for the extralabel dosage regimen. Population models could be fitted to fragmentary data to predict residue concentrations in tissues, validate the EWE estimates, and obtain WDI estimates. PMID:12383725

  16. Comparative pathology of canine soft tissue sarcomas: possible models of human non-rhabdomyosarcoma soft tissue sarcomas.

    PubMed

    Milovancev, M; Hauck, M; Keller, C; Stranahan, L W; Mansoor, A; Malarkey, D E

    2015-01-01

    Comparative analyses of canine and human soft tissue sarcomas (STSs) are lacking. This study compared the histological and immunohistochemical (labelling for desmin, smooth muscle actin [SMA], CD31, pancytokeratin, S100 and CD34) appearance of 32 archived, formalin-fixed, paraffin wax-embedded canine STS tumour specimens by board-certified veterinary and medical pathologists, both blinded to the other's interpretations. Comparison between the veterinary and human diagnoses revealed a generally consistent pattern of interpretation with few notable variations. Most tumours (13/32) were judged to display similar histomorphological appearance to human low-grade spindle cell sarcomas, appearing non-distinctive and morphologically of a fibroblastic/myofibroblastic type. Five canine cases resembled human liposarcoma, but with atypical desmin-positive epithelioid cells present. Five canine cases resembled human spindle cell sarcoma with myxoid features and two additional cases resembled human myxofibrosarcoma. Seven canine cases were noted to resemble human undifferentiated sarcoma. Findings in the present study demonstrate that canine STSs display histological and immunohistochemical features similar to their human equivalents. Because of these cross-species similarities, a particular opportunity exists to understand the biology and treatment of human STS by potentially including dogs as clinical models. PMID:25435513

  17. Anti-angiogenic therapy, a new player in the field of sarcoma treatment.

    PubMed

    Versleijen-Jonkers, Yvonne M H; Vlenterie, Myrella; van de Luijtgaarden, Addy C M; van der Graaf, Winette T A

    2014-08-01

    Sarcomas encompass a heterogeneous family of mesenchymal malignancies. In metastatic disease improvement in outcome has been limited and there is a clear need for the development of new therapies. One potential target is angiogenesis, already an accepted target for treatment of more prevalent cancers. Multiple (pre)clinical studies focused on the role of angiogenesis and anti-angiogenic treatment in sarcomas. However, getting significant results is complicated due to the relatively small number of patients and the broad range of sarcoma subtypes. Recently, pazopanib has been approved for the treatment of advanced soft tissue sarcoma patients, which is an important step forward and paves the way for the introduction of anti-angiogenic treatment in sarcomas. However, more studies are needed to understand the biological mechanisms by which patients respond to angiogenic inhibitors and to detect markers of response. This review covers the knowledge that has been gained on the role of angiogenesis and anti-angiogenic therapy in sarcomas. PMID:24613529

  18. MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics.

    PubMed

    Varshney, Jyotika; Subramanian, Subbaya

    2015-01-01

    Sarcomas are highly aggressive heterogeneous tumors that are mesenchymal in origin. There have been vast advancements on identifying diagnostic markers for sarcomas including chromosomal translocations, but very little progress has been made to identify targeted therapies against them. The tumor heterogeneity, genetic complexity and the lack of drug studies make it challenging to recognize the potential targets and also accounts for the inadequate treatments in sarcomas. In recent years, microRNAs that are a part of small non-coding RNAs have shown promising results as potential diagnostic and prognostic biomarkers in multiple sarcoma types. This review focuses on the current knowledge of the microRNAs that are deregulated in sarcomas, and an insight on the strategies to target these microRNAs that are essential for developing improved therapies for various human sarcomas. PMID:26137468

  19. Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis.

    PubMed

    Eisinger-Mathason, T S Karin; Mucaj, Vera; Biju, Kevin M; Nakazawa, Michael S; Gohil, Mercy; Cash, Timothy P; Yoon, Sam S; Skuli, Nicolas; Park, Kyung Min; Gerecht, Sharon; Simon, M Celeste

    2015-06-30

    Genetic aberrations responsible for soft-tissue sarcoma formation in adults are largely unknown, with targeted therapies sorely needed for this complex and heterogeneous family of diseases. Here we report that that the Hippo pathway is deregulated in many soft-tissue sarcomas, resulting in elevated expression of the effector molecule Yes-Associated Protein (YAP). Based on data gathered from human sarcoma patients, a novel autochthonous mouse model, and mechanistic analyses, we determined that YAP-dependent expression of the transcription factor forkhead box M1 (FOXM1) is necessary for cell proliferation/tumorigenesis in a subset of soft-tissue sarcomas. Notably, FOXM1 directly interacts with the YAP transcriptional complex via TEAD1, resulting in coregulation of numerous critical pro-proliferation targets that enhance sarcoma progression. Finally, pharmacologic inhibition of FOXM1 decreases tumor size in vivo, making FOXM1 an attractive therapeutic target for the treatment of some sarcoma subtypes. PMID:26080399

  20. MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics

    PubMed Central

    Varshney, Jyotika; Subramanian, Subbaya

    2015-01-01

    Sarcomas are highly aggressive heterogeneous tumors that are mesenchymal in origin. There have been vast advancements on identifying diagnostic markers for sarcomas including chromosomal translocations, but very little progress has been made to identify targeted therapies against them. The tumor heterogeneity, genetic complexity and the lack of drug studies make it challenging to recognize the potential targets and also accounts for the inadequate treatments in sarcomas. In recent years, microRNAs that are a part of small non-coding RNAs have shown promising results as potential diagnostic and prognostic biomarkers in multiple sarcoma types. This review focuses on the current knowledge of the microRNAs that are deregulated in sarcomas, and an insight on the strategies to target these microRNAs that are essential for developing improved therapies for various human sarcomas. PMID:26137468