Sample records for chemo-resistant ewing sarcoma

  1. 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

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

    ClinicalTrials.gov

    2015-05-12

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

  3. Primary Ewings Sarcoma of the Lung

    PubMed Central

    Kunjir, Nana G; Ghorpade, Shivhari

    2015-01-01

    Extraosseous ewings sarcoma is an extremely rare neuroectodermal tumour. We report the case of a 30-year-old female who presented with right sided pulmonary mass. Radiology, histopathology and immunohistochemistry confirmed the diagnosis of primary pulmonary Ewings sarcoma. This case highlights the fact that Ewings sarcoma should be considered in differential diagnosis of patients presenting with pulmonary mass. PMID:25738070

  4. 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

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

    ClinicalTrials.gov

    2015-02-04

    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

  6. 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

  7. Extraskeletal Ewing's sarcoma arising in the larynx.

    PubMed

    Lynch, Michael C; Baker, Aaron; Drabick, Joseph J; Williams, Nicole; Goldenberg, David

    2014-06-01

    Extraskeletal Ewing's sarcoma (EES), or primitive neuroectodermal tumor, is an uncommon neoplasm with low incidence in the head and neck. Occurrences in the larynx are even more exceptional with only two previous reported cases of EES arising from the larynx. We report the case of a 45-year-old woman with a laryngeal Ewing's sarcoma treated with chemotherapy with radiotherapy to follow. Here we describe the histology, molecular diagnosis and treatment of this unusual tumor. PMID:24072589

  8. Diagnosis and Treatment of Ewing's Sarcoma

    Microsoft Academic Search

    Yukihide Iwamoto

    2007-01-01

    Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term

  9. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast

    PubMed Central

    Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

    2013-01-01

    Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis. PMID:23813511

  10. 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 and event-free survival in newly diagnosed patients with non-metastatic Ewing sarcoma of the bone or soft tissue (excluding the soft tissue of the skull).

  11. Perigastric extraskeletal Ewing's sarcoma: A case report

    Microsoft Academic Search

    Radoje B Colovic; Nikica M Grubor; Marjan T Micev; Slavko V Matic; Henry Dushan; Edward Atkinson; Stojan M Latincic; Colovic RB; Grubor NM; Micev MT; Matic SV; Atkinson HDE

    Ewing's sarcoma (ES) is a neoplasm of undifferentiated small round cells, which occurs in the bones and deep soft tissues of children and adolescents. We present a rare case of a 44-year-old woman with gastric ES presenting with epigastric pain and weight loss. Ultrasound and computed tomography scans indicated a solid\\/cystic mass in the pancreatic tail. At laparotomy, the tumor

  12. Systemic therapy for osteosarcoma and ewing sarcoma.

    PubMed

    Meyers, Paul A

    2015-01-01

    Curative therapy for both osteosarcoma and Ewing sarcoma requires the combination of effective systemic therapy and local control of all macroscopic tumors. Systemic therapy for osteosarcoma consists of multiagent chemotherapy. The most common regimen uses cisplatin, doxorubicin, and high-dose methotrexate. Addition of ifosfamide and etoposide to treatment for patients with poor initial response to therapy does not improve outcome. Addition of interferon to treatment for patients with favorable initial response does not improve outcome. Addition of liposomal muramyl tripeptide to chemotherapy may improve overall survival. Systemic therapy for Ewing sarcoma consists of multiagent chemotherapy including doxorubicin, vincristine, etoposide, and cyclophosphamide and/or ifosfamide. Increased dose intensity of therapy, either by shortening the intervals between cycles of chemotherapy or by increasing doses of chemotherapy, improves outcome. Regimens such as irinotecan/temozolomide or cyclophosphamide/topotecan have shown activity in metastatic recurrent Ewing sarcoma. Trials are ongoing to evaluate the addition of these drugs to existing multiagent regimens in order to test their ability to improve outcome. High-dose systemic therapy with autologous stem cell reconstitution is being tested for patients at high risk for recurrence; definitive results await completion of a prospective randomized trial. PMID:25993235

  13. Ewing sarcoma of the posterior fossa in an adolescent girl.

    PubMed

    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

  14. 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

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

    ClinicalTrials.gov

    2015-03-17

    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

  16. Ewing's sarcoma metastasis into the breast.

    PubMed

    Orgüç, Sebnem; Ba?ara, I??l; Poçan, Tecelli; Ozgüven, Ali Aykan; Ozkol, Mine

    2012-01-01

    The metastasis of extramammary malignancies into the breast is very unusual. Lymphoma, malignant melanoma, and rhabdomyosarcoma are the most common tumors that metastasize into breast tissue. The histological spectrum of breast masses in children and adolescents is different from that of adults. Imaging findings are useful for performing a diagnosis, but in a patient with a known malignancy, any enlarging breast mass, even one with a benign radiological appearance, should be investigated with a biopsy. In this article, we present the imaging findings of a 12-year-old female patient with breast metastasis of Ewing's sarcoma. PMID:21948698

  17. Primary Ewing's sarcoma of cervical vertebra: An uncommon presentation.

    PubMed

    Chhabra, Sonia; Singh, Sunita; Sethi, Divya; Mahapatra, Qury Sabita

    2014-04-01

    Ewing's sarcoma is a malignant primary bone tumor primarily seen in the long bones. Primary Ewing's sarcoma of the cranium is quite uncommon occurring in 1% of the cases. We report the occurrence of this rare lesion in a 24-year-old male presenting with progressively increasing swelling in left mastoid region mimicking a mastoid abscess which was later diagnosed on Fine needle aspiration cytology (FNAC) as a small round cell tumor as Ewing's sarcoma. Contrast enhanced computed tomography (CECT) revealed a typical moth eaten appearance in the first and second cervical vertebra. PMID:25126127

  18. [Epidural extraskeletal Ewing sarcoma. Case report and literature review].

    PubMed

    García-Moreno, Rafael; Bernal-García, Luis Miguel; Pineda-Palomo, Manuel; Botana-Fernández, Marcos; Gilete-Tejero, Ignacio Javier; Cabezudo-Artero, José Manuel

    2015-01-01

    Ewing sarcoma is a malignant tumour of the bone that sometimes presents extraskeletal involvement, with the epidural location being rare. We report the case of a 45-year-old woman with paresthesia, paresis and urinary retention. Magnetic resonance imaging showed an epidural mass from C6 to D3. Laminectomy from C7 to D2 and partial resection of the lesion was performed. Pathological analysis was consistent with Ewing sarcoma. The patient received chemotherapy and radiotherapy, without evidence of disease at 8 months follow-up. A review of the literature on all published cases of extraskeletal Ewing sarcoma with epidural involvement is presented. PMID:25497289

  19. Characterization of Cellular Signaling in Ewing Sarcoma Family of Tumors

    E-print Network

    Anderson, Jennifer Lynn

    2012-01-01

    and practice of pediatric oncology. Philadelphia: Lippincottpediatric patients with refractory solid tumors and Ewing sarcoma: a report from the Children's Oncologypediatric solid tumors (NCT00880282) and in combination with cytotoxic chemotherapy in a Children’s Oncology

  20. Primary paraesophageal Ewing’s sarcoma: an uncommon case report and literature review

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. Ewing's Sarcoma: An Uncommon Breast Tumor.

    PubMed

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

    2014-06-18

    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

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

    PubMed

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

    2015-06-01

    Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. Clinical presentation is usually dominated by local pain and a palpable mass. These symptoms justify imaging investigations: the first one, when an osseous lesion is suspected, is usually a conventional radiograph in two planes. Ewing sarcoma appears as a poorly defined osteolytic lesion that may frequently be associated with cortical erosion or laminar periosteal response ("onion skin"). However, this aspect is not pathognomonic and the definitive diagnosis is made by biopsy. Absence of pain or an unusual localization can lead to misdiagnosis. We report the case of a 7-year-old boy with Ewing sarcoma located in the mandible with a clinical picture including progressive mandibular swelling but no pain. PMID:25896628

  4. Suppression of the Ewing’s sarcoma phenotype by FLI1\\/ERF repressor hybrids

    Microsoft Academic Search

    Meropi Athanasiou; Lionel LeGallic; Dennis K Watson; Donald G Blair; George Mavrothalassitis

    2000-01-01

    Fusion of the 5? half of the Ewing’s sarcoma (ES) gene EWS with the DNA-binding domain of several transcription factors has been detected in many human tumors. The t(11;22)(q24;q12) chromosomal translocation is specifically linked to ES and primitive neuroectodermal tumors and results, in the majority of cases, in the fusion of the amino terminus of the EWS gene to the

  5. 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

  6. Ewing's sarcoma in mandibular similar to dental abscess

    PubMed Central

    Keshani, Forouz; Jahanshahi, Gholamreza; Attar, Bijan Movahedian; Kalantari, Mahsa; Razavi, Seyed Mohammad; Hashemzade, Zahra; Tavakoli, Payam

    2014-01-01

    Ewing's sarcoma is a rare malignant neoplasm that comprises approximately 4-6% of primary bone tumors. In most cases, femur and pelvis are affected, and less commonly the head and neck areas (in the jaws, usually the mandible). These tumors have been reported more frequently in males, mostly aged 5-20 years old. Systemic symptoms and signs such as fever, weight loss, anemia, leukocytosis, and elevated erythrocyte sedimentation rate (ESR) may be the first signs in oral Ewing's sarcoma. Such signs and symptoms are also seen in odontogenic infections and abscess. In one case, the patient went to a dentist with pain, swelling, and abscess similar to odontogenic infection and patient's tooth was pulled due to misdiagnosis. This tumor has an aggressive clinical behavior and is identified with rapid growth and high probability of metastasis at diagnosis. Thus, it is necessary to differentiate it from a dental abscess. As for the treatment of Ewing's sarcoma, first the tumor must undergo chemotherapy to reduce its size and, eventually, it undergoes extensive surgery. This case report deals with a 16-year-old patient wrongly diagnosed with odontogenic infection and abscess, and hospitalized. As the symptoms did not remit, biopsy was carried out and the patient was operated on with Ewing's sarcoma diagnosis. PMID:24627870

  7. Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

    PubMed Central

    Herrero-Martin, David; Fourtouna, Argyro; Niedan, Stephan; Riedmann, Lucia T.; Schwentner, Raphaela; Aryee, Dave N. T.

    2011-01-01

    Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease. PMID:22135504

  8. Ewing sarcoma of clavicle in children: report of 5 cases.

    PubMed

    Rodriguez Martin, Juan; Pretell Mazzini, Juan; Viña Fernandez, Rafael; Marti Ciruelos, Rafael; Curto de la Mano, Angel

    2009-11-01

    Ewing sarcoma accounts for about 2% to 3% of childhood tumors and can occur in any bone, but it is most often found in extremities and central axis. Ewing sarcoma affecting clavicle is uncommon. We report 5 cases of Ewing sarcoma of clavicle treated in our institution. The mean age at the time of diagnosis was 11.6 years (2 to 15 y). There were 3 males and 2 females. All patients received chemotherapy before and after the surgery. Likewise, radiotherapy was administrated after tumor excision in one patient. Different methods of surgical treatment were used and included: claviculectomy, claviculectomy and vascularized fibular autograft, and claviculectomy and clavicle allograft. One patient died during the follow-up because of the recurrence of the tumor and presence of metastatic disease. The remaining 4 patients had good functional outcomes with no pain of the shoulder at final follow-up. In conclusion, Ewing sarcoma of clavicle is a very rare tumor and different methods of surgical treatment can be used. Clavicle often can be resected with no need for reconstruction, especially in young children. Autografts or allografts can restore the normal anatomy of the shoulder. PMID:19801950

  9. 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

  10. Ewing sarcoma of the adrenal gland: a rare entity

    PubMed Central

    Blas, Joseph-Vincent V; Smith, Maxwell L; Wasif, Nabil; Cook, Curtiss B; Schlinkert, Richard T

    2013-01-01

    A 63-year-old man was referred to our office with an enlarging left adrenal mass found on work-up for prostate cancer. Imaging performed over the course of 6?months demonstrated an increasing left adrenal mass from 2.8 to 3.6?cm. Functional testing of the adrenal lesion was performed. The adrenal mass was non-functional. Owing to the enlarging size, the patient underwent a laparoscopic left adrenalectomy without complication and was discharged home the following day. Gross pathological evaluation demonstrated a 3.2?cm, well-encapsulated, partially cystic mass. Histological evaluation demonstrated a small round blue cell tumour suspicious of sarcoma. Immunohistochemical testing revealed strong CD99 positivity consistent with Ewing family of tumours. Reverse transcriptase PCR demonstrated the presence of the Ewing sarcoma fusion transcript. The patient is currently enrolled in an ongoing research chemotherapy protocol at our institution using vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. PMID:23853184

  11. Neglected primary Ewing's sarcoma of ethmoid presenting as surgical emergency

    PubMed Central

    Shukla, Dinesh; Rao, Vinjamuri Srinivas; Rajesh, Alugolu; Purohit, Aniruddh Kumar

    2013-01-01

    We present a male child with primary Ewing's sarcoma arising from ethmoid sinuses with intradural and extracranial extension (bilateral nasal cavities, orbits, and maxillary sinuses). This is a rare condition. He presented with recurrent episodes of epistaxis for 2 years, sudden onset rapidly progressive bilateral proptosis, with painful restriction of extraocular movements, and decreased visual acuity for 4 days. Sudden complete loss of vision following admission demanded emergency tumor decompression. PMID:23741264

  12. Short-term followup after surgical treatment of Ewing’s sarcoma

    PubMed Central

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

    2010-01-01

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

  13. Ewing sarcoma: phalangeal primary with fatal cardiac metastases.

    PubMed

    Wilson, K S; Nyssen, J; Alexander, S

    1979-01-01

    A 39-year-old man had pain and swelling of the terminal phalanx of a finger. Radiograph was interpreted as osteomyelitis, and amputation through the mid-phalanx was performed. Histology revealed Ewing sarcoma. Lung metastases rapidly developed. Right lung irradiation and systemic chemotherapy, including doxorubicin, were instituted. He developed progressive severe right ventricular failure which was attributed to effects of large pulmonary metastases. Autopsy showed massive right ventricular metastases, the primary pathological cause of the heart failure, without evidence of doxorubicin cardiomyopathy. PMID:547162

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

    SciTech Connect

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

    2012-03-01

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

  15. Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma.

    PubMed

    Ghisoli, Maurizio; Barve, Minal; Schneider, Reva; Mennel, Robert; Lenarsky, Carl; Wallraven, Gladice; Pappen, Beena O; LaNoue, John; Kumar, Padmasini; Nemunaitis, Derek; Roth, Alyssa; Nemunaitis, James; Whiting, Sam; Senzer, Neil; Fletcher, Frederick A; Nemunaitis, John

    2015-06-01

    We report on 12 consecutive patients with advanced/metastatic Ewing's sarcoma who were treated as a separate cohort of a phase 1 trial of FANG autologous immunotherapy (1?×?10(6)-2.5?×?10(7) cells/intradermal injection each month for minimum 4 months). Safety and clinical response were monitored. Patient immune response to unmodified autologous tumor cells was assessed by gamma interferon-enzyme-linked immunospot (?IFN-ELISPOT) assay using peripheral blood mononuclear cells from baseline (pretreatment) and multiple postvaccination time points. None of the 12 patients (47 vaccinations) developed grade 2/3/4 drug-related toxicity. Median product release granulocyte-macrophage colony-stimulating factor expression was 1,941 pg/10(6) cells, and TGF?1and TGF?2 knockdown were 99 and 100%, respectively. Eight patients were assessed for ELISPOT response to autologous tumor cells at baseline and all (100%) were negative. In contrast, follow-up ELISPOT response at month 1 or month 4 (one patient) after FANG was positive in all eight patients. One patient achieved a partial tumor response (38% tumor reduction, RECIST 1.1). The Kaplan-Meier estimated survival of these 12 patients at 1 year was 75%. In this phase 1 study in patients with Ewing's sarcoma, FANG immunotherapy was well tolerated, elicited a tumor-specific systemic immune response in all patients, and was associated with favorable 1-year survival. Further clinical testing is indicated. PMID:25917459

  16. Mutant screening for oncogenes of Ewing's sarcoma using yeast.

    PubMed

    Kitagawa, Takao; Okita, Hajime; Baron, Byron; Tokuda, Kazuhiro; Nakamura, Mikiko; Wang, Yufeng; Akada, Junko; Hoshida, Hisashi; Akada, Rinji; Kuramitsu, Yasuhiro; Nakamura, Kazuyuki

    2015-08-01

    Many fusion genes, which are the result of chromosomal translocation and work as an oncogene, have been recently identified, but their mode of actions is still unclear. Here, we performed a yeast mutant screening for oncogenes of Ewing's sarcoma to easily identify essential regions responsible for fusion protein functions using a yeast genetic system. Three kinds of oncogenes including EWS/FLI1, EWS/ERG, and EWS/E1AF exhibited growth inhibition in yeast. In this screening, we identified 13 single amino acid substitution mutants which could suppress growth inhibition by oncogenes. All of the point mutation positions of the EWS/ETS family proteins were located within the ETS domain, which is responsible for the interaction with a specific DNA motif. Eight-mutated residues within the ETS domain matched to 13 completely conserved amino acid residues in the human ETS domains. Moreover, mutants also showed reduced transcriptional activities on the DKK2 promoter, which is upregulated by the EWS/ETS family, compared to that of the wild type. These results suggest that the ETS domain in the EWS/ETS family proteins may be a primary target for growth inhibition of Ewing's sarcoma and that this yeast screening system can be applied for the functional screening of the oncogenes. PMID:25936378

  17. Combining PARP-1 inhibition and radiation in Ewing sarcoma results in lethal DNA damage.

    PubMed

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

    2013-11-01

    Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to an ETS transcription factor, most commonly Friend leukemia integration 1 (FLI1). The EWS-FLI1 fusion protein acts in a positive feedback loop to maintain the expression of PARP-1, which is involved in repair of DNA damage. Here, we examine the effects of PARP-1 inhibition and radiation therapy on Ewing sarcomas. In proliferation assays, the Ewing sarcoma cell lines RD-ES and SK-N-MC were much more sensitive than non-Ewing sarcoma cell lines to the PARP-1 inhibitor olaparib (Ola; IC50 0.5-1 ?mol/L vs. >5 ?mol/L) and to radiation (IC50 2-4 Gy vs. >6 Gy). PARP-1 inhibition with short hairpin RNA (shRNA) or Ola sensitized Ewing sarcoma cells, but not non-Ewing sarcoma cells, to radiation therapy in both proliferation and colony formation assays. Using the Comet assay, radiation of Ewing sarcoma cells with Ola, compared to without Ola, resulted in more DNA damage at 1 hour (mean tail moment 36-54 vs. 26-28) and sustained DNA damage at 24 hours (24-29 vs. 6-8). This DNA damage led to a 2.9- to 4.0-fold increase in apoptosis and a 1.6- to 2.4-fold increase in cell death. The effect of PARP-1 inhibition and radiation therapy on Ewing sarcoma cells was lost when EWS-FLI1 was silenced by shRNA. A small dose of radiation therapy (4 Gy), when combined with PARP-1 inhibition, stopped the growth of SK-N-MC flank tumors xenografts. In conclusion, PARP-1 inhibition in Ewing sarcomas amplifies the level and duration of DNA damage caused by radiation therapy, leading to synergistic increases in apoptosis and cell death in a EWS-FLI1-dependent manner. PMID:23966622

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

    ClinicalTrials.gov

    2015-06-01

    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

  19. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    ClinicalTrials.gov

    2015-07-03

    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

  2. Primary cervical spinal epidural Extra-osseous Ewing's sarcoma.

    PubMed

    Kogawa, M; Asazuma, T; Iso, K; Koike, Y; Domoto, H; Aida, S; Fujikawa, K

    2004-09-01

    Cases of primary spinal epidural Extra-osseous Ewing's sarcoma (EES) are rarely seen and a good prognosis for EES cannot be expected since a high incidence of local recurrence and metastasis frequently occur. We present a case of cervical spinal epidural EES in a 7-year-old girl with long survival after tumour resection. She also received adjuvant treatment with peripheral blood stem cell transplantation (PBSCT). This management successfully improved her condition and she was in complete remission without neurological deficit 60 months after surgery. Such a good prognosis of EES in the cervical spine is very rare. It is likely that magnetic resonance imaging (MRI) lead to a diagnosis of this rare type of EES at an early stage of the disease. PBSCT could be useful as an adjuvant to prolong the period of complete remission. PMID:15340820

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

    SciTech Connect

    Perez, C.A. (Washington Univ. School of Medicine, St. Louis, MO); Tefft, M.; Nesbit, M.; Burgert, E.O. Jr.; Vietti, T.; Kissane, J.; Pritchard, D.J.; Gehan, E.A.

    1981-02-01

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

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

    SciTech Connect

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

    1981-04-01

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

  5. 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

  6. Video-assisted Thoracic Surgery for Ewing's Sarcoma of the Mediastinum in a 3-year-old Girl

    Microsoft Academic Search

    Kiyoshi Koizumi; Shuji Haraguchi; Iwao Mikami; Hirotoshi Kubokura; Daisuke Okada; Shigeki Yamagishi; Hiroyasu Kinoshita; Yutaka Enomoto; Kazuo Shimizu; Miho Maeda

    We report of the experience of video-assisted thoracic surgery (VATS) for a Ewing's sarcoma at the posterior mediastinum in a 3 year old girl. The patient developed common cold like symp- toms and developed rapid lower limb paraplegia. A chest computed tomography (CT) showed a solid mass adjacent to the vertebrae. This was diagnosed as a Ewing's sarcoma histopathologi- cally

  7. Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report

    Microsoft Academic Search

    Bharat Rekhi; Sajid Qureshi; Ranjan Basak; Sangeeta B Desai; Seema Medhi; Purna Kurkure; Santosh Menon; Amita Maheshwari; Nirmala A Jambhekar

    2010-01-01

    INTRODUCTION: Primary Ewing's sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis. CASE PRESENTATION: We present an extremely rare case of Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old

  8. IDH Mutation Analysis in Ewing Sarcoma Family Tumors

    PubMed Central

    Na, Ki Yong; Noh, Byeong-Joo; Sung, Ji-Youn; Kim, Youn Wha; Santini Araujo, Eduardo; Park, Yong-Koo

    2015-01-01

    Background: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield ?-ketoglutarate (?-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of ?-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor ?, causing cells to be prone to tumorigenesis. Methods: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. Results: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. Conclusions: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs. PMID:26018518

  9. 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

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

    PubMed

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

    2015-01-01

    There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of MDM4 is frequently observed in sarcomas, this study examined the therapeutic potential of XI-006 for the treatment of Ewing and osteosarcoma. XI-006 treatment of Ewing and osteosarcoma cell lines (n?=?11) resulted in rapid and potent apoptosis at low micro-molar concentrations specifically in Ewing sarcoma cell lines (48?hr IC50 0.099-1.61??M). Unexpectedly, apoptotic response was not dependent on MDM4 mRNA/protein levels or TP53 status. Alkaline/neutral comet and ?H2AX immunofluorescence assays revealed that the cytotoxic effects of XI-006 could not be attributed to the induction of DNA damage. RNA expression analysis revealed that the mechanism of action of XI-006 could be accredited to the inhibition of cell division and cycle regulators such as KIF20A and GPSM2. Finally, potent synergy between XI-006 and olaparib (PARP inhibitor) were observed due to the down-regulation of Mre11. Our findings suggest that XI-006 represents a novel therapeutic intervention for the treatment of Ewing sarcoma. PMID:26095524

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

    PubMed Central

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

    2015-01-01

    There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of MDM4 is frequently observed in sarcomas, this study examined the therapeutic potential of XI-006 for the treatment of Ewing and osteosarcoma. XI-006 treatment of Ewing and osteosarcoma cell lines (n?=?11) resulted in rapid and potent apoptosis at low micro-molar concentrations specifically in Ewing sarcoma cell lines (48?hr IC50 0.099–1.61??M). Unexpectedly, apoptotic response was not dependent on MDM4 mRNA/protein levels or TP53 status. Alkaline/neutral comet and ?H2AX immunofluorescence assays revealed that the cytotoxic effects of XI-006 could not be attributed to the induction of DNA damage. RNA expression analysis revealed that the mechanism of action of XI-006 could be accredited to the inhibition of cell division and cycle regulators such as KIF20A and GPSM2. Finally, potent synergy between XI-006 and olaparib (PARP inhibitor) were observed due to the down-regulation of Mre11. Our findings suggest that XI-006 represents a novel therapeutic intervention for the treatment of Ewing sarcoma. PMID:26095524

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

    PubMed Central

    Parrish, JK; Sechler, M; Winn, RA; 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

  13. [Ewing's sarcoma. Retrospective study of 108 cases with review of the literature].

    PubMed

    Bouziani, A; Ben Rejeb, A; Mazabraud, A; Jagueux, M; Orcel, L

    1987-07-01

    108 cases of Ewing's Sarcoma are collected at the "Curie Institute" and studied by the authors using the modern Technics of electron microscopy, cytochemistry, immunohistochemistry and cytogenetics. They raise the histogenesis and etiological factors not entirely resolved yet at the light of literature review. PMID:3318749

  14. Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma

    PubMed Central

    Sankar, Savita; Bell, Russell; Stephens, Bret; Zhuo, Rupeng; Sharma, Sunil; Bearss, David J.; Lessnick, Stephen L.

    2014-01-01

    Ewing sarcoma provides an important model for transcription-factor mediated oncogenic transformation because of its reliance on the ETS-type fusion oncoprotein EWS/FLI. EWS/FLI functions as a transcriptional activator and transcriptional activation is required for its oncogenic activity. Here we demonstrate that a previously less-well characterized transcriptional repressive function of the EWS/FLI fusion is also required for the transformed phenotype of Ewing sarcoma. Through comparison of EWS/FLI transcriptional profiling and genome-wide localization data, we define the complement of EWS/FLI direct downregulated target genes. We demonstrate that LOX is a previously undescribed EWS/FLI-repressed target that inhibits the transformed phenotype of Ewing sarcoma cells. Mechanistic studies demonstrate that the NuRD co-repressor complex interacts with EWS/FLI, and that its associated histone deacetylase and LSD1 activities contribute to the repressive function. Taken together, these data reveal a previously unknown molecular function for EWS/FLI, demonstrate a more highly coordinated oncogenic transcriptional hierarchy mediated by EWS/FLI than previously suspected, and implicate a new paradigm for therapeutic intervention aimed at controlling NuRD activity in Ewing sarcoma tumors. PMID:23178492

  15. 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

  16. Ewing Sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions.

    PubMed

    Jedlicka, Paul

    2010-01-01

    Since its first description by James Ewing in 1921, Ewing Sarcoma has been a cryptic malignancy. A poorly differentiated tumor of uncertain histogenesis and aggressive biologic behavior, it is the second most common malignancy of bone and soft tissue affecting adolescents and young adults. Some two decades ago, the understanding of Ewing Sarcoma biology took a leap forward with the identification of recurrent EWS/Ets fusions, which drive onco-genesis in this disease. A further leap forward occurred over the last half decade with the application of gene silencing, global expression profiling and primary cell culture technologies to the study of this disease. Resulting work has revealed EWS/Ets fusions to be surprisingly versatile regulators of gene expression, and has narrowed the search for the elusive cell of origin. Improved understanding of EWS/Ets biology and relevant oncogenic pathways has in turn led to the development of targeted therapies, including, recently, small molecules targeting key complexes involving the oncogenic fusion itself. In many respects still remaining an enigma, Ewing Sarcoma is an important model for cancers originating in progenitor-type cells or manifesting progenitor-type cell features, and cancers containing recurrent oncogenic fusions, the latter a surprisingly expanding number. PMID:20490326

  17. 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

    Ewing Sarcoma Protein Ewsr1 Maintains 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... Survival in the Zebrafish Embryo. PLoS ONE 2(10): e979. doi:10.1371/journal.pone.0000979 INTRODUCTION The EWSR1 gene is involved in a number of different sarcomas as a result of chromosomal translocations. EWSR1 is fused to an ETS transcription factor (FLI...

  18. 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

    's Sarcoma tumorigenesis. Oncogene 24: 2715–2722. PMID: 15782144 3. Smith R, Owen LA, Trem DJ, Wong JS, Whangbo JS, et al. (2006) Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. Cancer Cell 9: 405–416. PMID...: 16697960 4. Zwerner JP, Joo J, Warner KL, Christensen L, Hu-Lieskovan S, et al. (2008) The EWS/FLI1 oncogenic transcription factor deregulates GLI1. Oncogene 27: 3282–3291. PMID: 18084326 5. Beauchamp E, Bulut G, Abaan O, Chen K, Merchant A, et al. (2009...

  19. Ewing's sarcoma of proximal phalanx of the hand with skip metastases to metacarpals.

    PubMed

    Shekhar, Anshu; Korlhalli, Suresh; Murgod, Gururaj

    2015-01-01

    Ewing's sarcoma is the second most common malignant primary bone tumor of childhood and adolescence affecting mainly the diaphysis of long bones and flat bones. This tumor is extraordinarily rare in small bones of the hand and presents as a swelling with atypical radiological features of cystic and lytic lesion with scant periosteal reaction. The common differential diagnosis include osteomyelitis, tuberculosis, enchondroma and benign tumors. Moreover, skip metastasis to adjacent bones is even rarer. The prognosis of this condition is greatly influenced by the presence of metastasis at presentation, further emphasizing the importance of early diagnosis. Multimodality treatment using surgery, radiotherapy and chemotherapy is currently recommended though no consensus exists. We report a case of Ewing's sarcoma of the little finger proximal phalanx which was initially missed and developed skip metastasis to several metacarpals within 4 months. PMID:26015641

  20. Primary orbital Ewing's sarcoma presenting with local recurrence to maxillary sinus shortly after tumor resection.

    PubMed

    Sendul, Selam Yekta; Ucgul, Cemile; Kabukcuoglu, Fevziye; Dirim, Burcu; Guven, Dilek

    2015-01-01

    Ewing's sarcoma (ES) is a malignant, small-round-cell neoplasm that normally affects the long bones of the limbs or the pelvis. Primary orbital ES of the skull has been considered extremely rare. We describe the case of a 19-year-old female patient with primary ES originating from the inferior orbital rime and, shortly after tumor resection, local recurrence to the maxillary sinus. PMID:26136562

  1. EWS-FLI1 Suppresses NOTCH-Activated p53 in Ewing's Sarcoma

    Microsoft Academic Search

    Jozef Ban; Max Kauer; Karl-Ludwig Schaefer; Christopher Poremba; Gunhild Jug; Raphaela Schwentner; Oskar Smrzka; Karin Muehlbacher; Dave N. T. Aryee; Heinrich Kovar

    2008-01-01

    Although p53 is the most frequently mutated gene in cancer, half of human tumors retain wild-type p53, whereby it is unknown whether normal p53 function is compromised by other cancer-associated alterations. One example is Ewing's sarcoma family tumors (ESFT), where 90% express wild-type p53. ESFT are characterized by EWS-FLI1 oncogene fusions. Studying 6 ESFT cell lines, silencing of EWS-FLI1 in

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

    PubMed Central

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

    2013-01-01

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

  3. Primary orbital Ewing's sarcoma presenting with local recurrence to maxillary sinus shortly after tumor resection

    PubMed Central

    Sendul, Selam Yekta; Ucgul, Cemile; Kabukcuoglu, Fevziye; Dirim, Burcu; Guven, Dilek

    2015-01-01

    Ewing's sarcoma (ES) is a malignant, small-round-cell neoplasm that normally affects the long bones of the limbs or the pelvis. Primary orbital ES of the skull has been considered extremely rare. We describe the case of a 19-year-old female patient with primary ES originating from the inferior orbital rime and, shortly after tumor resection, local recurrence to the maxillary sinus.

  4. Bone Marrow Metastasis in Ewing's Sarcoma and Peripheral Primitive Neuroectodermal Tumor: An Immunohistochemical Study

    Microsoft Academic Search

    E. J. Lazda; P. J. Berry

    1998-01-01

    Bone marrow metastases from small round cell tumors can present diagnostic difficulties. In this study, we assessed the value\\u000a of immunohistochemistry, using two monoclonal antibodies to CD99, for the diagnosis of metastatic disease in bone marrow trephine\\u000a specimens from patients with Ewing's sarcoma or primitive neuroectodermal tumor (PNET). The proportions of specimens showing\\u000a metastases were 10.3% with routine staining and

  5. Differentiating Lymphoblastic Lymphoma and Ewing's Sarcoma: Lymphocyte Markers and Gene Rearrangement

    Microsoft Academic Search

    Metin Ozdemirli; Julie C. Fanburg-Smith; Dan-Paul Hartmann; Norio Azumi; Markku Miettinen

    2001-01-01

    We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene

  6. CALLA positive acute lymphoblastic leukemia after etoposide-based therapy for Ewing's sarcoma

    Microsoft Academic Search

    G. Kapoor; S. Bajpai; C. N. Nair; Y. Badrinath; B. Gladstone; S. H. Advani

    1995-01-01

    This is an unusual and interesting case report concerning a 10 year old boy with an initial diagnosis of Ewing's sarcoma of the right tibia. He was successfully treated with a chemotherapy regimen consisting of vincristine, cyclophosphamide (cumulative dose 7200 mg\\/m2), doxorubicin, etoposide (cumulative dose 2700 mg\\/m2) and cisplatin and local radiotherapy to the tibia. After an interval of 37

  7. 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

  8. Auto-stimulatory action of secreted caveolin-1 on the proliferation of Ewing’s sarcoma cells

    PubMed Central

    Sengupta, Aniruddha; Mateo-Lozano, Silvia; Tirado, Oscar M.; Notario, Vicente

    2012-01-01

    Caveolin-1 (CAV1) is highly expressed in Ewing’s sarcoma (EWS). We previously showed that increased cellular CAV1 is associated with the regulation of the tumorigenicity, drug resistance and metastatic ability of EWS cells. Because several studies reported that melanoma and prostate cancer cells, which express relatively high CAV1 levels, secrete CAV1, and that secreted CAV1 is associated with tumor progression, our study explored the possibility that EWS cells also secreted CAV1 and that secreted CAV1 may contribute to EWS pathobiology. Results from experiments involving the ectopic expression of a Myc-tagged CAV1 protein in EWS cells as well as the supplementation of culture media with purified CAV1 protein followed by its intracellular localization using immunofluorescence demonstrated that EWS cells secrete CAV1, that they are able to take up the secreted protein, and that extracellular CAV1 enhances EWS cell proliferation. These findings strongly support the notion that secreted CAV1 may also contribute to the malignant properties of EWS. PMID:21373757

  9. 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

  10. 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

  11. Ewing's sarcoma and primitive neuroectodermal tumour (ES/PNET) presenting as a breast mass.

    PubMed

    Chuthapisith, Suebwong; Prasert, Wilairat; Warnnissorn, Malee; Pradniwat, Kanapon; Srimuninnimit, Vichien; Angsusinha, Tamnit

    2012-07-01

    Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) is a rare tumour usually detected in young individuals and uncommonly found within the breast tissue. In this case report, we examined a 46-year-old patient, who developed a lump on her breast and was later diagnosed with ES/PNET. Clinical presentation, age at development and radiological findings were of interest and were discussed. Diagnosis of the tumour was confirmed using various immunohistochemical studies and the presence of a translocation, t(11;22). A literature review of this rare condition was also included. PMID:22807962

  12. Ewing's sarcoma of the orbit with intracranial extension: A rare cause of unilateral proptosis

    PubMed Central

    Nair, Anup P.; Bettaswamy, Guruprasad; Jaiswal, Awdhesh K.; Garg, Pallav; Jaiswal, Sushila; Behari, Sanjay

    2011-01-01

    Ewing's sarcoma causing unilateral proptosis along with bifrontal extradural infiltration in a child is an unusual presentation. A female patient presented with features of painless proptosis of the left eye with visual deterioration. Her radiology revealed an infiltrating intraorbital, extraconal tumor with intracranial bifrontal extradural extension causing mass effect. Total excision of the intraorbital and intracranial part of the tumor along with postoperative chemo- and radiotherapy brought about a substantial relief. The clinicoradiological presentation and management of this rare entity are discussed. PMID:21977086

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

    SciTech Connect

    Yang, Min [Institute of Orthopaedics and Traumatology of PLA of China, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China)] [Institute of Orthopaedics and Traumatology of PLA of China, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China); Zhang, Rui [Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China)] [Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China); Yan, Ming; Ye, Zhengxu; Liang, Wei [Institute of Orthopaedics and Traumatology of PLA of China, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China)] [Institute of Orthopaedics and Traumatology of PLA of China, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China); Luo, Zhuojing, E-mail: luozhuojing@hotmail.com [Institute of Orthopaedics and Traumatology of PLA of China, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China)] [Institute of Orthopaedics and Traumatology of PLA of China, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032 (China)

    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.

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

    SciTech Connect

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

    1983-12-01

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

  15. Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration

    PubMed Central

    2014-01-01

    Background Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Methods Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 106 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 ?g/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. Results ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and ?9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. Conclusion These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs. PMID:24612486

  16. 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. ...

  17. Association of EWS-FLI1 Type 1 Fusion with Lower Proliferative Rate in Ewing’s Sarcoma

    PubMed Central

    de Alava, Enrique; Panizo, Angel; Antonescu, Cristina R.; Huvos, Andrew G.; Pardo-Mindán, F. Javier; Barr, Frederic G.; Ladanyi, Marc

    2000-01-01

    The Ewing’s sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90–95%) or ERG (5–10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher’s exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway. PMID:10702401

  18. 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.

  19. [Considerations of biomechanics after clavicular resection. Case report of rower with Ewing sarcoma].

    PubMed

    Gaulke, R; Schmitz, H G

    1998-02-01

    Because of poorly compartmentalized paraclavicular soft tissues, total extraperiostal claviculectomy in cases of malignoma with cortical destruction is always marginal. Due to different muscular compensation in the patients examined, literature disagrees on the biomechanical consequences of claviculectomy for the shoulder girdle. We present a case of total clavicula resection including chemotherapy and radiation in an 18-year-old rower with Ewing's sarcoma. Sixteen-month postoperative radiological and clinical examination revealed an excellent result. Thirty-six months postoperatively the patients is able to row symptom-free without any evidence of the disease. Biomechanical reflections on the significance of the trapezius muscle in compensating thoracoscapular instability provide information for rehabilitation. PMID:9553484

  20. Xenograft and genetically engineered mouse model systems of osteosarcoma and Ewing's sarcoma: tumor models for cancer drug discovery

    PubMed Central

    Sampson, Valerie B; Kamara, Davida F; Kolb, E Anders

    2014-01-01

    Introduction There are > 75 histological types of solid tumors that are classified into two major groups: bone and soft-tissue sarcomas. These diseases are more prevalent in children, and pediatric sarcomas tend to be highly aggressive and rapidly progressive. Sarcomas in adults may follow a more indolent course, but aggressive tumors are also common. Sarcomas that are metastatic at diagnosis, or recurrent following therapy, remain refractory to current treatment options with dismal overall survival rates. A major focus of clinical trials, for patients with sarcoma, is to identify novel and more effective therapeutic strategies targeted to genomic or proteomic aberrations specific to the malignant cells. Critical to the understanding of the potential for targeted therapies are models of disease that are representative of clinical disease and predictive of relevant clinical responses. Areas covered In this article, the authors discuss the use of mouse xenograft models and genetically engineered mice in cancer drug discovery. The authors provide a special focus on models for the two most common bone sarcomas: osteosarcoma (OS) and Ewing's sarcoma (ES). Expert opinion Predicting whether a new anticancer agent will have a positive therapeutic index in patients with OS and ES remains a challenge. The use of mouse sarcoma models for understanding the mechanisms involved in the response of tumors to new treatments is an important step in the process of drug discovery and the development of clinically relevant therapeutic strategies for these diseases. PMID:23844615

  1. Extraosseous Ewing sarcoma of the vagina 1 1 The views expressed herein are those of the authors and do not reflect the official policy or opinion of the Department of Defense, or the United States Army or Navy

    Microsoft Academic Search

    John Farley; John D O’Boyle; Jason Heaton; Stephen Remmenga

    2000-01-01

    Background: Ewing sarcoma is a highly malignant childhood bone neoplasm. Extraosseous presentations of Ewing sarcomas include the trunk, extremities, uterus, cervix, and vagina.Case: A 35-year-old woman, gravida 3, para 3, presented with a painless vaginal mass. After surgical excision, pathology results diagnosed an extraosseous Ewing sarcoma. Chemotherapy was given, followed by external beam and vaginal intracavitary brachytherapy, then more chemotherapy.

  2. Whole Lung Irradiation in Adults with Metastatic Ewing Sarcoma: Practice Patterns and Implications for Treatment

    PubMed Central

    Tanguturi, Shyam K.; George, Suzanne; Marcus, Karen J.; Demetri, George D.; Baldini, Elizabeth H.

    2015-01-01

    Background. Whole lung irradiation (WLI) is a standard treatment component for children with metastatic Ewing Sarcoma (ES), but data on WLI for adults are sparse. Design. An email survey was sent to expert sarcoma-dedicated oncologists worldwide: An adult with excellent performance status presents with primary ES in the leg and multiple pulmonary metastases. The patient achieves complete radiographic response after chemotherapy and resection of the primary. Would you give bilateral WLI to (1) this adult patient?, (2) this patient if 20 years old (yo)?, (3) this patient if 45 yo?, or (4) this patient if 60 yo? Results. 38 experts responded, including 24 adult, 1 adolescent young adult, and 13 pediatric oncologists. 63%, 63%, 62%, and 50% of respondents offered WLI to the adult, 20-year-old, 45-year-old, and 60-year-old, respectively. Pediatric oncologists more likely endorsed WLI across all ages including the adult (P = 0.01), 20-year-old (P = 0.005), 45-year-old (P = 0.01), and 60-year-old (P = 0.08). There were no significant differences between medical and radiation oncologists or between European/Australian and American providers. Conclusions. Almost two-thirds of experts surveyed supported WLI for adults with metastatic ES up to age 45 and half supported WLI for a 60-year-old. Continued collaboration across adult and pediatric oncology is needed to define evidence-based strategies across the age spectrum. PMID:26199562

  3. Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma

    PubMed Central

    Ambati, Srikanth R.; Lopes, Eloisi Caldas; Kosugi, Kohji; Mony, Ullas; Zehir, Ahmet; Shah, Smit K.; Taldone, Tony; Moreira, Andre L.; Meyers, Paul A.; Chiosis, Gabriela; Moore, Malcolm A.S.

    2014-01-01

    Ewing sarcoma is characterized by multiple deregulated pathways that mediate cell survival and proliferation. Heat shock protein 90 (HSP90) is a critical component of the multi-chaperone complexes that regulate the disposition and activity of a large number of proteins involved in cell-signaling systems. We tested the efficacy of PU-H71, a novel HSP90 inhibitor in Ewing sarcoma cell lines, primary samples, benign mesenchymal stromal cells and hematopoietic stem cells. We performed cell cycle analysis, clonogenic assay, immunoblot analysis and reverse phase protein array in Ewing cell lines and in vivo experiments in NSG and nude mice using the A673 cell line. We noted a significant therapeutic window in the activity of PU-H71 against Ewing cell lines and benign cells. PU-H71 treatment resulted in G2/M phase arrest. Exposure to PU-H71 resulted in depletion of critical proteins including AKT, pERK, RAF-1, c-MYC, c-KIT, IGF1R, hTERT and EWS-FLI1 in Ewing cell lines. Our results indicated that Ewing sarcoma tumor growth and the metastatic burden were significantly reduced in the mice injected with PU-H71 compared to the control mice. We also investigated the effects of bortezomib, a proteasome inhibitor, alone and in combination with PU-H71 in Ewing sarcoma. Combination index (CI)-Fa plots and normalized isobolograms indicated synergism between PU-H71 and bortezomib. Ewing sarcoma xenografts were significantly inhibited when mice were treated with the combination compared to vehicle or either drug alone. This provides a strong rationale for clinical evaluation of PU-H71 alone and in combination with bortezomib in Ewing sarcoma. PMID:24388362

  4. 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. Mol Cancer Ther; 14(7); 1591-604. ©2015 AACR. PMID:25964201

  5. Overexpression of p53 protein in primary Ewing's sarcoma of bone: relationship to tumour stage, response and prognosis

    PubMed Central

    Abudu, A; Mangham, D C; Reynolds, G M; Pynsent, P B; Tillman, R M; Carter, S R; Grimer, R J

    1999-01-01

    Biopsy tissues of 52 patients with Ewing's sarcoma of bone treated between 1983 and 1993 were examined immunohistochemically to determine the significance of p53 protein in diagnosis and prognosis of Ewing's sarcoma. Mean age at diagnosis was 17 years (range 6–36) and minimum follow-up was 30 months. The tumours were located in the extremities and central bones in 35 and 17 patients respectively. Metastases were present in seven patients at diagnosis. Treatment consisted of chemotherapy, surgery and/or radiotherapy in all the patients. Overexpression of p53 protein was demonstrated in seven patients (14%). There was no relationship between expression of p53 and site of tumours. Patients who overexpressed p53 protein appeared to have more advanced diseases at diagnosis and poorer response to chemotherapy than those without p53 overexpression. The 5-year relapse-free survival and overall survival in patients without metastases at the time of diagnosis were 66% and 71%, respectively, in p53 protein-negative patients compared with 20% relapse-free and overall survival in those with p53 protein overexpression (P = 0.01). The poorer prognosis in p53 protein-positive patients was independent of site, local treatment or necrosis of the tumours (P < 0.05). Over-expression of p53 protein is an independent poor prognostic factor in Ewing's sarcoma of bone. © 1999 Cancer Research Campaign PMID:10098757

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

    SciTech Connect

    Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, and University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Keole, Sameer R. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, and University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Lagmay, Joanne P. [Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL (United States); Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, and the University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Gibbs, C. Parker; Scarborough, Mark T. [Department of Orthopedic Surgery, University of Florida College of Medicine, Gainesville, FL (United States); Islam, Saleem [Department of Surgery at the University of Florida College of Medicine, Gainesville, FL (United States); Marcus, Robert B. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, and the University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    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.

  7. 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

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

    PubMed Central

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

    2013-01-01

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

  9. Exenteration and Custom Implant Brachytherapy as a Treatment for Recurrent Primary Extraskeletal Orbital Ewing Sarcoma.

    PubMed

    Klufas, Michael A; Wolden, Suzanne L; Bohle, George C; Wexler, Leonard H; Abramson, David H

    2014-05-01

    A 6-year-old boy initially presented to an outside hospital with a right orbital mass with biopsy positive for translocation involving EWS RNA-binding protein 1 gene and imaging consistent with primary extraskeletal Ewing sarcoma (ES). There was no evidence of metastatic disease. Patient underwent gross tumor resection and adjuvant chemotherapy (VAdriaC/IE) followed by postoperative 45-Gy proton beam radiation. After 19 months, a solitary in-field local recurrence occurred, which was unsuccessfully surgically resected. Thereafter, treatment commenced with irinotecan and temozolomide, and the patient presented to the center of the authors. MRI showed locally recurrent disease without evidence of metastatic disease. Right orbital exenteration was performed, and an orbital mold was fashioned to deliver brachytherapy. There were no complications. The patient had no evidence of recurrent disease at 37-month follow up. This is the first report of orbital implant brachytherapy for recurrent primary ES of the orbit, and an additional report of primary extraskeletal ES of the orbit, which is a rare primary orbital tumor. PMID:24814278

  10. 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. (Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston (United States))

    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.

  11. 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.

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

    PubMed Central

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

    2013-01-01

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

  13. 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

  14. Ewing sarcoma-primitive neuroectodermal tumor of the uterus: a clinicopathologic, immunohistochemical and ultrastructural study of one case

    Microsoft Academic Search

    Ya-Li RenXiu-Ying; Xiu-Ying Tang; Ting Li

    2011-01-01

    Introduction  Ewing sarcoma-primitive neuroectodermal tumors (ES\\/PNET) constitute a family of neoplasms characterized by a continuum of\\u000a neuroectodermal differentiation. ES\\/PNET of the uterus is rare. There are 43 cases published in the English literature as\\u000a far as we know. We describe an additional case.\\u000a \\u000a \\u000a \\u000a \\u000a Case report  A 56-year-old woman presented with a 2-month history of irregular menopausal vaginal bleeding. After surgical excision, microscopic,

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

    PubMed

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

    2014-08-01

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

  16. 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

  17. Investigation of the Insulin-Like Growth Factor-1 Signaling Pathway in Localized Ewing Sarcoma

    PubMed Central

    Borinstein, Scott C.; Barkauskas, Donald A.; Krailo, Mark; Scher, Daniel; Scher, Lauren; Schlottmann, Silke; Kallakury, Bhaskar; Dickman, Paul S.; Pawel, Bruce R.; West, Daniel C.; Womer, Richard B.; Toretsky, Jeffrey A.

    2012-01-01

    BACKGROUND The insulin-like growth factor-1 (IGF-1) signaling pathway plays an important role in the pathology of Ewing sarcoma (ES). Retrospective studies have suggested that levels of IGF-1 and IGF binding protein 3 (IGFBP-3) are correlated with the outcome of patients with ES. METHODS The IGF-1 signaling pathway was investigated prospectively in 269 patients who had localized, previously untreated ES. Serum samples were obtained at diagnosis, and concentrations of IGF-1 and IGFBP-3 were determined by enzyme-linked immunosorbent assays. In addition, immunohistochemistry (IHC) was performed to assay for phosphorylated p70S6 kinase, protein kinase B (Akt), and forkhead box protein O1 (FOXO1) and to determine the presence of protein tyrosine phosphatase-L1 (PTPL1). IHC findings along with IGF-1 and IGFBP-3 concentrations were correlated with age, tumor location, sex, event-free survival, and overall survival. RESULTS Patients aged >18 years tended to have higher levels of IGF-1 (P =.10), lower levels of IGFBP-3 (P =.16), and decreased IGFBP-3:IGF-1 ratios (P =.01). No correlations were observed between sex, tumor location, or outcomes and concentrations of IGF-1 or IGFBP-3. Phosphorylation of p70S6 kinase, Akt, and FOXO1 was detected in the majority of patient tissues but was not associated with age, sex, or tumor location. PTPL1 was present in >80% of tumors and also was not correlated with age, sex, or tumor location. There was no difference in survival with respect to the presence of phosphorylated p70S6 kinase, phosphorylated FOXO1, phosphorylated Akt, or PTPL1. CONCLUSIONS The baseline IGFBP-3:IGF-1 ratio was correlated with age but did not affect the outcomes of patients with ES. The authors concluded that additional investigation of the IGF-1 pathway is warranted in patients with ES, and especially in those who have received treatment with IGF-1 receptor antibody inhibitors. PMID:21480204

  18. High-dose chemotherapy and autologous peripheral blood stem cell transplantation in adult patients with high-risk or advanced Ewing and soft tissue sarcoma

    Microsoft Academic Search

    M. Engelhardt; R. Zeiser; G. Ihorst; J. Finke; C. I. Müller

    2007-01-01

    Purpose  Despite the availability of combined-modality treatment for Ewing sarcoma (ES) and soft tissue sarcomas (STS), results from independent groups still indicate a poor prognosis for high-risk and metastasized patients. The benefit of high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (ASCT) as compared to standard treatment is not defined.Methods  Here, we report of HDCT in 35 consecutive adult patients

  19. 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)

  20. Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma

    PubMed Central

    Stegmaier, Kimberly; Wong, Jenny S; Ross, Kenneth N; Chow, Kwan T; Peck, David; Wright, Renee D; Lessnick, Stephen L; Kung, Andrew L; Golub, Todd R

    2007-01-01

    Background The presence of tumor-specific mutations in the cancer genome represents a potential opportunity for pharmacologic intervention to therapeutic benefit. Unfortunately, many classes of oncoproteins (e.g., transcription factors) are not amenable to conventional small-molecule screening. Despite the identification of tumor-specific somatic mutations, most cancer therapy still utilizes nonspecific, cytotoxic drugs. One illustrative example is the treatment of Ewing sarcoma. Although the EWS/FLI oncoprotein, present in the vast majority of Ewing tumors, was characterized over ten years ago, it has never been exploited as a target of therapy. Previously, this target has been intractable to modulation with traditional small-molecule library screening approaches. Here we describe a gene expression–based approach to identify compounds that induce a signature of EWS/FLI attenuation. We hypothesize that screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application. Methods and Findings A gene expression signature for the EWS/FLI off state was determined with microarray expression profiling of Ewing sarcoma cell lines with EWS/FLI-directed RNA interference. A small-molecule library enriched for FDA-approved drugs was screened with a high-throughput, ligation-mediated amplification assay with a fluorescent, bead-based detection. Screening identified cytosine arabinoside (ARA-C) as a modulator of EWS/FLI. ARA-C reduced EWS/FLI protein abundance and accordingly diminished cell viability and transformation and abrogated tumor growth in a xenograft model. Given the poor outcomes of many patients with Ewing sarcoma and the well-established ARA-C safety profile, clinical trials testing ARA-C are warranted. Conclusions We demonstrate that a gene expression–based approach to small-molecule library screening can identify, for rapid clinical testing, candidate drugs that modulate previously intractable targets. Furthermore, this is a generic approach that can, in principle, be applied to the identification of modulators of any tumor-associated oncoprotein in the rare pediatric malignancies, but also in the more common adult cancers. PMID:17425403

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

    Microsoft Academic Search

    Timothy J. Kinsella; James B. Mitchell; Scott McPherson; James Miser; Timothy Triche; Eli Glatstein

    1984-01-01

    Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and\\/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have

  2. Immunostaining of the p30\\/32 MIC2 antigen and molecular detection of EWS rearrangements for the diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumor

    Microsoft Academic Search

    Katia Scotlandi; Massimo Serra; Maria Cristina Manara; Stefania Benini; Manuela Sarti; Daniela Maurici; Pier-Luigi Lollini; Piero Picci; Franco Bertoni; Nicola Baldini

    1996-01-01

    The identification of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET) among other small round cell tumors (SRCTs) is a critical issue in musculoskeletal pathology because of the lack of clearly distinctive morphological features. In this study, the authors have compared advantages and limits of two procedures that were recently suggested as additional tools for the identification of ES\\/PNET, the

  3. Ewing Sarcoma tumor cells express CD34: implications for autologous stem cell transplantation

    Microsoft Academic Search

    I Yaniv; J Stein; D Luria; I J Cohen; E Liberzon; S Manor; A Grunshpan; Y Sverdlov; Y Kodman; J Issakov; M Feinmesser; R Zaizov; S Avigad

    2007-01-01

    The significance of tumor cell contamination in marrow and peripheral blood stem cell (PBSC) collections of patients with solid tumors remains controversial. Various methods have been developed to purge tumor cells from autologous stem cell products, including CD34+ selection. PBSC harvests from patients with Ewing family of tumors (EFT) were analyzed for contaminating tumor cells prior and after CD34+ selection

  4. Biomechanical aspects of claviculectomy – case report of a rower with Ewing's sarcoma

    Microsoft Academic Search

    R. Gaulke; H. G. Schmitz

    1998-01-01

    Summary  \\u000a Because of poorly compartmentalized paraclavicular soft tissues, total extraperiostal claviculectomy in cases of malignoma\\u000a with cortical destruction is always marginal. Due to different muscular compensation in the patients examined, literature\\u000a disagrees on the biomechanical consequences of claviculectomy for the shoulder girdle.\\u000a \\u000a \\u000a \\u000a We present a case of total clavicula resection including chemotherapy and radiation in an 18-year-old rower with Ewing's

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

    PubMed Central

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

    2015-01-01

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

  6. Chemotherapy-related toxicity in patients with non-metastatic Ewing sarcoma: influence of sex and age.

    PubMed

    Paioli, Anna; Luksch, Roberto; Fagioli, Franca; Tamburini, Angela; Cesari, Marilena; Palmerini, Emanuela; Abate, Massimo Eraldo; Marchesi, Emanuela; Balladelli, Alba; Pratelli, Loredana; Ferrari, Stefano

    2014-02-01

    Influence of age and sex on chemotherapy-related toxicity was evaluated in children (3-9 years), adolescents (10-17 years), and adults (up to 40 years) with localized Ewing sarcoma (ES) enrolled in the ISG/SSG III protocol. Treatment was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, dactinomycin, and etoposide. High-dose chemotherapy with busulfan and melphalan was given in poor responder patients. The analysis was based on 2191 courses of standard chemotherapy and 230 patients. A lower risk of G4 leukopenia and thrombocytopenia, hospitalization, febrile neutropenia, and red blood cell (RBC) transfusions was observed in males. Use of granulocyte colony-stimulating factor (G-CSF) was more frequent in adults, while children more often received RBC transfusions. A significant correlation between sex and chemotherapy-related toxicity was observed in the study, whereas no significant differences in terms of bone marrow toxicity can be expected according to patient age. Further studies should analyse the role of pharmacokinetics, pharmacogenomics, and clinical characteristics. PMID:24091100

  7. Synthesis and structure-activity relationship studies of small molecule disruptors of EWS-FLI1 interactions in Ewing's sarcoma.

    PubMed

    Tosso, Perrer N; Kong, Yali; Scher, Lauren; Cummins, Ryan; Schneider, Jeffrey; Rahim, Said; Holman, K Travis; Toretsky, Jeffrey; Wang, Kan; Üren, Aykut; Brown, Milton L

    2014-12-26

    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 (R(2) = 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

  8. 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

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

    PubMed Central

    Yamamoto, Yoshinari; Yamazaki, Kazuto; Ishida, Yasuo

    2015-01-01

    Renal Ewing sarcoma (ES) is a rare malignant tumor characterized by fusion of the EWSR1 gene with a member of the ETS family of oncogenes, arising at a specific chromosomal translocation. Diagnosis of ES can be problematic, especially from cytological or small bioptical specimens because the differential diagnoses comprising a diverse group of small round blue cell tumors (SRBCTs). We report a case of primary renal ES in a young male, which had a t(11;22) (q24;q12) chromosome translocation encoding a type2 EWSR1/FLI1 fusion transcript. The tumor cells showed diffuse cytoplasmic immunoreactivity for CD99 and diffuse nuclear immunoreactivity for NKX2.2, an important oncogenic transcriptional target of EWSR1/FLI1, not only in the histological, but also in the cytological specimens. From the results of this case, we speculate that NKX2.2, in combination with CD99, may be a useful immunocytochemical marker to distinguish renal ES from other SRBCTs of kidney. PMID:25948942

  10. Biomarkers in Ewing Sarcoma: The Promise and Challenge of Personalized Medicine. A Report from the Children’s Oncology Group

    PubMed Central

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

    2013-01-01

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

  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. 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.

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

    PubMed

    Li, Weihua; Li, Yuxia; Guo, Jiankuo; Pan, Huagang; Zhang, Yongle; Wang, Xiao

    2015-09-01

    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

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

    PubMed

    Tilan, Jason U; Lu, Congyi; Galli, Susana; Izycka-Swieszewska, Ewa; Earnest, Joshua Patrick; Shabbir, Asim; Everhart, Lindsay M; Wang, Shuo; Martin, Samantha; Horton, Meredith; Mahajan, Akanksha; Christian, David; O'Neill, Alison; Wang, Hongkun; Zhuang, Tingting; Czarnecka, Magdalena; Johnson, Michael D; Toretsky, Jeffrey A; Kitlinska, Joanna

    2013-12-01

    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. Paradoxically, NPY acting via Y1R and Y5R stimulates ES cell death. Here, we demonstrate that these growth-inhibitory actions of NPY are counteracted by hypoxia, which converts the peptide to a growth-promoting factor. In ES cells, hypoxia induces another NPY receptor, Y2R, and increases expression of dipeptidyl peptidase IV (DPPIV), an enzyme that cleaves NPY to a shorter form, NPY3-36. This truncated peptide no longer binds to Y1R and, therefore, does not stimulate ES cell death. Instead, NPY3-36 acts as a selective Y2R/Y5R agonist. The hypoxia-induced increase in DPPIV activity is most evident in a population of ES cells with high aldehyde dehydrogenase (ALDH) activity, rich in cancer stem cells (CSCs). Consequently, NPY, acting via Y2R/Y5Rs, preferentially stimulates proliferation and migration of hypoxic ALDHhigh cells. Hypoxia also enhances the angiogenic potential of ES by inducing Y2Rs in endothelial cells and increasing the release of its ligand, NPY3-36, from ES cells. In summary, hypoxia acts as a molecular switch shifting NPY activity away from Y1R/Y5R-mediated cell death and activating the Y2R/Y5R/DPPIV/NPY3-36 axis, which stimulates ES CSCs and promotes angiogenesis. Hypoxia-driven actions of the peptide such as these may contribute to ES progression. Due to the receptor-specific and multifaceted nature of NPY actions, these findings may inform novel therapeutic approaches to ES. PMID:24318733

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

    PubMed Central

    Galli, Susana; Izycka-Swieszewska, Ewa; Earnest, Joshua Patrick; Shabbir, Asim; Everhart, Lindsay M.; Wang, Shuo; Martin, Samantha; Horton, Meredith; Mahajan, Akanksha; Christian, David; O'Neill, Alison; Wang, Hongkun; Zhuang, Tingting; Czarnecka, Magdalena; Johnson, Michael D.; Toretsky, Jeffrey A.; Kitlinska, Joanna

    2013-01-01

    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. Paradoxically, NPY acting via Y1R and Y5R stimulates ES cell death. Here, we demonstrate that these growth-inhibitory actions of NPY are counteracted by hypoxia, which converts the peptide to a growth-promoting factor. In ES cells, hypoxia induces another NPY receptor, Y2R, and increases expression of dipeptidyl peptidase IV (DPPIV), an enzyme that cleaves NPY to a shorter form, NPY3-36. This truncated peptide no longer binds to Y1R and, therefore, does not stimulate ES cell death. Instead, NPY3-36 acts as a selective Y2R/Y5R agonist. The hypoxia-induced increase in DPPIV activity is most evident in a population of ES cells with high aldehyde dehydrogenase (ALDH) activity, rich in cancer stem cells (CSCs). Consequently, NPY, acting via Y2R/Y5Rs, preferentially stimulates proliferation and migration of hypoxic ALDHhigh cells. Hypoxia also enhances the angiogenic potential of ES by inducing Y2Rs in endothelial cells and increasing the release of its ligand, NPY3-36, from ES cells. In summary, hypoxia acts as a molecular switch shifting NPY activity away from Y1R/Y5R-mediated cell death and activating the Y2R/Y5R/DPPIV/NPY3-36 axis, which stimulates ES CSCs and promotes angiogenesis. Hypoxia-driven actions of the peptide such as these may contribute to ES progression. Due to the receptor-specific and multifaceted nature of NPY actions, these findings may inform novel therapeutic approaches to ES. PMID:24318733

  16. Dipeptidyl peptidases as survival factors in Ewing sarcoma family of tumors: implications for tumor biology and therapy.

    PubMed

    Lu, Congyi; Tilan, Jason U; Everhart, Lindsay; Czarnecka, Magdalena; Soldin, Steven J; Mendu, Damodara R; Jeha, Dima; Hanafy, Jailan; Lee, Christina K; Sun, Junfeng; Izycka-Swieszewska, Ewa; Toretsky, Jeffrey A; Kitlinska, Joanna

    2011-08-01

    Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs). Previously, we have shown that both exogenous NPY and endogenous NPY stimulate ESFT cell death via its Y1 and Y5Rs. Here, we demonstrate that this effect is prevented by dipeptidyl peptidases (DPPs), which cleave NPY to its shorter form, NPY(3-36), not active at Y1Rs. We have shown that NPY-induced cell death can be abolished by overexpression of DPPs and enhanced by their down-regulation. Both NPY treatment and DPP blockade activated the same cell death pathway mediated by poly(ADP-ribose) polymerase (PARP-1) and apoptosis-inducing factor (AIF). Moreover, the decrease in cell survival induced by DPP inhibition was blocked by Y1 and Y5R antagonists, confirming its dependence on endogenous NPY. Interestingly, similar levels of NPY-driven cell death were achieved by blocking membrane DPPIV and cytosolic DPP8 and DPP9. Thus, this is the first evidence of these intracellular DPPs cleaving releasable peptides, such as NPY, in live cells. In contrast, another membrane DPP, fibroblast activation protein (FAP), did not affect NPY actions. In conclusion, DPPs act as survival factors for ESFT cells and protect them from cell death induced by endogenous NPY. This is the first demonstration that intracellular DPPs are involved in regulation of ESFT growth and may become potential therapeutic targets for these tumors. PMID:21680731

  17. 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

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

    PubMed

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

    2012-12-01

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

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

    SciTech Connect

    McDermid, H.E. (Univ. of Alberta, Edmonton (Canada)); Budarf, M.L.; Emanuel, B.S. (Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States) Children's Hospital of Philadelphia, PA (United States))

    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.

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

    PubMed Central

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

    1996-01-01

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

  1. Pediatric soft tissue sarcomas.

    PubMed

    Stein-Wexler, Rebecca

    2011-10-01

    After a brief discussion of the rarity of soft tissue sarcomas in children and of the limited ability of magnetic resonance imaging to provide a tissue diagnosis, this article discusses the incidence, presentation, treatment, prognosis, and imaging characteristics of the more common and unusual pediatric soft tissue sarcomas. It begins with extensive discussion of rhabdomyosarcoma, synovial sarcoma, and congenital/infantile fibrosarcoma. It then presents a more abbreviated discussion of uncommon tumors such as alveolar soft part sarcoma, epithelioid sarcoma, extraosseous Ewing's sarcoma, granulocytic sarcoma, hemangiopericytoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, and undifferentiated sarcoma. PMID:21963167

  2. Proliferation Index: A Continuous Model to Predict Prognosis in Patients with Tumours of the Ewing's Sarcoma Family

    PubMed Central

    Brownhill, Samantha; Cohen, Dena; Burchill, Sue

    2014-01-01

    The prognostic value of proliferation index (PI) and apoptotic index (AI), caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT). Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100) of tumours with a median PI of 14 (range 0–87). Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79) of ESFT; the median AI was 3 (range 0–33). Caspase-8 protein expression was negative (0) in 14% (11/79), low (1) in 33% (26/79), medium (2) in 38% (30/79) and high (3) in 15% (12/79) of tumours, caspase-9 expression was low (1) in 66% (39/59) and high (3) in 34% (20/59), and caspase-10 protein was low (1) in 37% (23/62) and negative (0) in 63% (39/62) of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p?=?0.011) and overall survival (OS; p?=?<0.001) in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p?=?0.054, log rank test), although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p?=?0.003). Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p?=?0.028); patients with a pelvic tumour and a PI?20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT. PMID:25157404

  3. Stages of Ewing Sarcoma

    MedlinePLUS

    ... the bones and is detected by a scanner. Bone marrow aspiration and biopsy : The removal of bone marrow , blood , and a small piece of bone by ... removed from both hipbones. A pathologist views the bone marrow, blood, and bone under a microscope to see ...

  4. 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

  5. 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

  6. 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

  7. Suppression of FOXO1 is responsible for a growth regulatory repressive transcriptional sub-signature of EWS-FLI1 in Ewing sarcoma

    PubMed Central

    Niedan, S; Kauer, M; Aryee, D N T; Kofler, R; Schwentner, R; Meier, A; Pötschger, U; Kontny, U; Kovar, H

    2014-01-01

    The Ewing sarcoma (ES) EWS-FLI1 chimeric oncoprotein is a prototypic aberrant ETS transcription factor with activating and repressive regulatory functions. We report that EWS-FLI1-repressed promoters are enriched in forkhead box (FOX) recognition motifs, and identify FOXO1 as a EWS-FLI1-suppressed regulator orchestrating a major subset of EWS-FLI1-repressed genes. In addition to FOXO1 regulation by direct promoter binding of EWS-FLI1, its subcellular localization and activity is regulated by cyclin-dependent kinase 2- and AKT-mediated phosphorylation downstream of EWS-FLI1. Restoration of nuclear FOXO1 expression in ES cells impaired proliferation and significantly reduced clonogenicity. Gene-expression profiling revealed a significant overlap between EWS-FLI1-repressed and FOXO1-activated genes. As a proof of principle for a potential therapeutic application of our findings, the treatment of ES cell lines with methylseleninic acid (MSA) reactivated endogenous FOXO1 in the presence of EWS-FLI1 in a dose- and time-dependent manner and induced massive cell death dependent on FOXO1. In an orthotopic xenograft mouse model, MSA increased FOXO1 expression in the tumor paralleled by a significant decrease in ES tumor growth. FOXO1 reactivation by small molecules may therefore serve as a promising strategy for a future ES-specific therapy. PMID:23995784

  8. Soft tissue Ewing sarcoma--peripheral primitive neuroectodermal tumor with atypical clear cell pattern shows a new type of EWS-FEV fusion transcript.

    PubMed

    Llombart-Bosch, A; Pellín, A; Carda, C; Noguera, R; Navarro, S; Peydró-Olaya, A

    2000-09-01

    This study describes a new case of Ewing sarcoma (ES)-peripheral primitive neuroectodermal tumor (pPNET) with unusual phenotype and fusion gene structure. The tumor located in the inguinal area of a 15-year-old boy showed a highly aggressive behavior with hematogenous metastases after intensive chemotherapy and bone marrow transplant, causing death 28 months after diagnosis. The tumor displayed a clear cell pattern, and several neuroectodermal markers proved positive both in the original tumor and in xenografts. This neuroectodermal character was confirmed by electron microscopy. Moreover, cytogenetically the tumor has an unusual chromosomal rearrangement, t(2;22)(q13;q22,t(3;18)(p21;q23); representing a new EWS-FEV fusion type in which exon 7 of EWS gene is fused with exon 2 of FEV gene. This is the third published study of an ES-pPNET showing EWS-FEV fusion described, but it is the first study of a tumor with the aforementioned fusion points. These findings support the genetic and morphologic heterogeneity existing within the group of ES-pPNET tumors. PMID:10976720

  9. 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 [Section of Chemotherapy, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna (Italy)]. E-mail: gaetano.bacci@ior.it; Longhi, Alessandra [Section of Chemotherapy, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna (Italy); Briccoli, Antonio [Section of Thoracic Surgery, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna (Italy); Bertoni, Franco [Laboratory for Pathology, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna (Italy); Versari, Michela [Section of Chemotherapy, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna (Italy); Picci, Piero [Laboratory for Oncologic Research, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna (Italy)

    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.

  10. Cyclin D1 is a useful marker for soft tissue Ewing's sarcoma/peripheral Primitive Neuroectodermal Tumor in children and adolescents: A comparative immunohistochemical study with rhabdomyosarcoma.

    PubMed

    Magro, Gaetano; Brancato, Franca; Musumeci, Giuseppe; Alaggio, Rita; Parenti, Rosalba; Salvatorelli, Lucia

    2015-01-01

    Cyclin D1 amplification and/or overexpression contribute to the loss of the regulatory circuits that govern G1-S transition phase of the cell cycle, playing pivotal roles in different human malignant tumors, including breast, colon, prostate cancer, lymphoma, melanoma and neuroblastoma. In vitro studies have shown that cyclin D1 is overexpressed in Ewing's sarcoma (EWS)/peripheral Primitive Neuroectodermal Tumor (pPNET), but not in rhabdomyosarcoma cell lines. Only a few immunohistochemical studies are available on cyclin D1 expression in EWS/pPNET, which confirmed its expression only in a limited number of cases. The aim of the present study was a comparative immunohistochemical analysis of the expression and distribution of cyclin D1 in a large series of pediatric/adolescent soft tissue EWS/pPNETs and rhabdomyosarcomas (both embryonal and alveolar subtypes) to assess its potential usefulness in their differential diagnosis. Notably cyclin D1 was strongly and diffusely expressed in all cases (20/20) of EWS/pPNET, while it was lacked in all cases (15/15) of rhabdomyosarcomas. Immunohistochemical overexpression of cyclin D1 in EWS/pPNET is a novel finding which could be exploitable as a diagnostic immunomarker for this tumor. Although highly sensitive, cyclin D1 is not specific for EWS/pPNET, and thus it should not be evaluated alone but in the context of a wide immunohistochemical panel. Accordingly, we first emphasize that when pathologists are dealing with a small round blue cell tumor of soft tissues in pediatric/adolescent patients, a strong and diffuse nuclear expression of cyclin D1 is of complementary diagnostic value to CD99 and FLI-1 in confirming diagnosis of EWS/pPNET and in ruling out rhabdomyosarcoma. PMID:25765111

  11. Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group

    PubMed Central

    Malempati, Suman; Weigel, Brenda; Ingle, Ashish M.; Ahern, Charlotte H.; Carroll, Julie M.; Roberts, Charles T.; Reid, Joel M.; Schmechel, Stephen; Voss, Stephan D.; Cho, Steven Y.; Chen, Helen X.; Krailo, Mark D.; Adamson, Peter C.; Blaney, Susan M.

    2012-01-01

    Purpose A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES). Patients and Methods Pediatric patients with relapsed or refractory solid tumors were treated with cixutumumab as a 1-hour intravenous infusion once per week. Two dose levels—6 and 9 mg/kg—were evaluated using a standard three-plus-three cohort design. Patients with refractory ES were treated in an expanded phase II cohort at each dose level. Results Forty-seven eligible patients with a median age of 15 years (range, 4 to 28 years) were enrolled. Twelve patients were treated in the dose-finding phase. Hematologic and nonhematologic toxicities were generally mild and infrequent. Dose-limiting toxicities included grade 4 thrombocytopenia at 6 mg/kg and grade 3 dehydration at 9 mg/kg. Mean trough concentration (± standard deviation) at 9 mg/kg was 106 ± 57 ?g/mL, which exceeded the effective trough concentration of 60 ?g/mL observed in xenograft models. Three patients with ES had confirmed partial responses: one of 10 at 6 mg/kg and two of 20 at 9 mg/kg. Serum insulin-like growth factor I (IGF-I) levels consistently increased after one dose of cixutumumab. Tumor IGF-I receptor expression by immunohistochemistry did not correlate with response in patients with ES. Conclusion Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES. PMID:22184397

  12. Pericytes in sarcomas of bone.

    PubMed

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

    2015-07-01

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

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

    ClinicalTrials.gov

    2015-05-22

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

  14. Treatment Option Overview (Ewing Sarcoma)

    MedlinePLUS

    ... nurse specialist . Social worker . Rehabilitation specialist . Psychologist . Some cancer treatments cause side effects months or years after treatment has ... Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. ...

  15. General Information about Ewing Sarcoma

    MedlinePLUS

    ... the bones and is detected by a scanner. Bone marrow aspiration and biopsy : The removal of bone marrow , blood , and a small piece of bone by ... removed from both hipbones. A pathologist views the bone marrow, blood, and bone under a microscope to see ...

  16. Treatment Options for Ewing Sarcoma

    MedlinePLUS

    ... The RAS Initiative Progress Annual Report to the Nation Snapshots of Specific Types of Cancer Milestones in ... specific cancer type Progress Annual Report to the Nation Cancer Portfolio Snapshots Milestones in Cancer Research & Discovery ...

  17. Isolated mediastinal myeloid sarcoma successfully treated with chemoradiotherapy followed by unrelated allogeneic stem cell transplantation.

    PubMed

    Lee, Jeong Mi; Song, Haa-Na; Kang, Yeojin; Kim, Hosu; Min, Ji Hyun; Suh, Young Sun; Ahn, Jong-Hwa; Lee, Seung Hun; Jo, Yun-Won; Cheon, Yun-Hong; Kim, Moon Jin; Lee, Gyeong-Won

    2011-01-01

    A 22-year-old man was diagnosed with isolated mediastinal myeloid sarcoma which radiologically mimicked primary mediastinal lymphoma. Despite administration of standard remission induction chemotherapy with daunorubicin and cytarabine, and three cycles of intensive high-dose cytarabine-based consolidation, chemo-resistant hypermetabolic lesions were persistently detected in the highest mediastinum and in the supraclavicular area. However, complete remission and long-term survival were achieved by curative radiotherapy followed by unrelated allogeneic stem cell transplantation. PMID:22185993

  18. The Epidemiology of Sarcoma

    PubMed Central

    2012-01-01

    Sarcomas account for over 20% of all pediatric solid malignant cancers and less than 1% of all adult solid malignant cancers. The vast majority of diagnosed sarcomas will be soft tissue sarcomas, while malignant bone tumors make up just over 10% of sarcomas. The risks for sarcoma are not well-understood. We evaluated the existing literature on the epidemiology and etiology of sarcoma. Risks for sarcoma development can be divided into environmental exposures, genetic susceptibility, and an interaction between the two. HIV-positive individuals are at an increased risk for Kaposi’s sarcoma, even though HHV8 is the causative virus. Radiation exposure from radiotherapy has been strongly associated with secondary sarcoma development in certain cancer patients. In fact, the risk of malignant bone tumors increases as the cumulative dose of radiation to the bone increases (p for trend <0.001). A recent meta-analysis reported that children with a history of hernias have a greater risk of developing Ewing’s sarcoma (adjusted OR 3.2, 95% CI 1.9, 5.7). Bone development during pubertal growth spurts has been associated with osteosarcoma development. Occupational factors such as job type, industry, and exposures to chemicals such as herbicides and chlorophenols have been suggested as risk factors for sarcomas. A case-control study found a significant increase in soft tissue sarcoma risk among gardeners (adjusted OR 4.1, 95% CI 1.00, 14.00), but not among those strictly involved in farming. A European-based study reported an increased risk in bone tumors among blacksmiths, toolmakers, or machine-tool operators (adjusted OR 2.14, 95% CI 1.08, 4.26). Maternal and paternal characteristics such as occupation, age, smoking status, and health conditions experienced during pregnancy also have been suggested as sarcoma risk factors and would be important to assess in future studies. The limited studies we identified demonstrate significant relationships with sarcoma risk, but many of these results now require further validation on larger populations. Furthermore, little is known about the biologic mechanisms behind each epidemiologic association assessed in the literature. Future molecular epidemiology studies may increase our understanding of the genetic versus environmental contributions to tumorigenesis in this often deadly cancer in children and adults. PMID:23036164

  19. Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer.

    PubMed

    Toge, Masayoshi; Yokoyama, Satoru; Kato, Shinichiro; Sakurai, Hiroaki; Senda, Kazutaka; Doki, Yoshinori; Hayakawa, Yoshihiro; Yoshimura, Naoki; Saiki, Ikuo

    2015-04-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-?-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies. PMID:25647738

  20. Chemo-resistant melanoma sensitized by tamoxifen to low dose curcumin treatment through induction of apoptosis and autophagy.

    PubMed

    Chatterjee, Sudipa June; Pandey, Siyaram

    2011-01-15

    Melanoma is the deadliest form of skin cancer, which is notoriously aggressive and chemo-resistant, and for which there is little effective treatment available if it goes undetected. Curcumin from the turmeric spice (Curcuma longa) has long been used in Southeast Asian medicine to alleviate ailments and cure an array of diseases and disorders. It possesses anti-inflammatory, anti-oxidant and most importantly anti-carcinogenic activity. There have been contradictory reports discussing the efficacy of curcumin-induced death on melanoma. In this report we show that curcumin does induce apoptosis in A375 and the relatively resistant G361 malignant human melanoma cell lines at higher doses. Tamoxifen is an estrogen receptor (ER) blocker that is used for ER positive breast cancer treatment. Recently, tamoxifen has been shown to directly target the mitochondria. Given that curcumin is a pro oxidant and tamoxifen can act on mitochondria, we ask whether the combinatorial treatment could result in synergistic induction of apoptosis in chemo-resistant melanoma. Our results show a corresponding increase in phosphatidyl serine flipping, mitochondria depolarization and reactive oxygen species (ROS) generation by the combined treatment at lower doses. Interestingly, there was significant induction of autophagy along with apoptosis following the combined treatment. Importantly, non-cancerous cells are unaffected by the combination of these non-toxic compounds. However, once exposed to low doses of this co-treatment, melanoma cells still retain signals to commit suicide even after removal of the drugs. This combination provides a non-toxic option for combinatorial chemotherapy with great potential for future use. PMID:21088500

  1. Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones

    SciTech Connect

    Evans, R.; Nesbit, M.; Askin, F.; Burgert, O.; Cangir, A.; Foulkes, M.; Gehan, E.; Gilula, L.; Kissane, J.; Makley, J.

    1985-01-01

    This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) has a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regime I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients.

  2. 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

  3. Analysis of Prognostic Factors of Pediatric-Type Sarcomas in Adult Patients

    Microsoft Academic Search

    Hee Kyung Ahn; Ji Eun Uhm; Jeeyun Lee; Do Hoon Lim; Sung Wook Seo; Ki-Sun Sung; Su Jin Lee; Duk Joo Lee; Kyung Kee Baek; Won-Seog Kim; Joon Oh Park

    2011-01-01

    Objective: Pediatric-type sarcomas such as Ewing’s sarcoma (EWS)\\/primitive neuroectodermal tumor family and rhabdomyosarcoma are relatively uncommon in adult patients. Optimal treatment strategies for this population and prognosis in adult patients compared with pediatric patients remain controversial. Methods: We retrospectively reviewed pediatric-type sarcoma patients older than 15 years at a single institution. Results: A total of 84 consecutive patients between 1995

  4. Mononuclear cell-derived interleukin-1 beta confers chemo-resistance in pancreatic cancer cells by up-regulation of cyclooxygenase-2

    PubMed Central

    Angst, Eliane; Reber, Howard A.; Hines, Oscar J.; Eibl, Guido

    2008-01-01

    Background Pancreatic cancer is a very aggressive malignancy and efficient therapeutic options are still largely lacking. The importance of interactions between tumor cells and surrounding stromal elements, e.g. mononuclear cells, for chemo-resistance has been increasingly recognized. In addition, cyclooxygenase-2 is thought to be an important mediator of chemo-resistance in several malignancies. The aim of the present study was to explore the role of mononuclear cells in pancreatic cancer chemo-resistance. Methods U937 cells were differentiated into macrophage-like cells. The effect of U937 conditioned medium on drug-induced pancreatic cancer cell apoptosis was measured by ELISA. The contributions of interleukin-1? and cyclooxygenase-2 were evaluated by specific receptor antagonists and inhibitors. The importance of the extracellular signal-regulated kinase (ERK1/2) pathway was also determined. Results U937 conditioned culture medium protected pancreatic cancer cells from drug-induced apoptosis. This protective effect was abolished by an interleukin-1 receptor antagonist and cyclooxygenase-2 inhibitor. U937 conditioned medium and interleukin-1? stimulated expression of cyclooxygenase-2 and prostaglandin E2 production in pancreatic cancer cells, which was mediated by activation of the ERK1/2 pathway. Transfection of pancreatic cancer cells with cyclooxygenase-2 increased resistance to drug-induced cell death. Conclusions Mononuclear cells protect pancreatic cancer cells of drug-induced apoptosis in vitro by interleukin-1?-mediated expression of cyclooxygenase-2 and production of prostaglandins. This study highlights the importance of tumor-host interactions in pancreatic cancers and may provide the basis for novel therapeutic approaches to sensitize pancreatic cancers to chemotherapeutic agents. PMID:18571585

  5. Epidemiology and therapies for metastatic sarcoma

    PubMed Central

    Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

    2013-01-01

    Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

  6. Imaging of thoracic sarcomas of the chest wall, pleura, and lung.

    PubMed

    Foran, Paul; Colleran, Gabrielle; Madewell, John; O'Sullivan, Paul J

    2011-10-01

    Primary sarcomas of the thorax are uncommon. The purpose of this review is to describe the radiologic findings of sarcomas affecting the thorax, in particular the chest wall, pleura, and lungs. Most primary sarcomas affecting the thorax arise in the chest wall, and the most common sarcomas of the chest wall are chondrosarcoma, osteosarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, malignant fibrous histiocytoma, and fibrosarcoma. Primary pleural and pulmonary sarcomas are rare. Although histologic analysis is almost always required for accurate diagnosis, imaging is important for staging of these tumors, and several of these tumors have distinctive radiologic features, allowing the radiologist to narrow the differential diagnosis. PMID:21963160

  7. Uncommon sarcomas of the uterine cervix: a review of selected entities

    PubMed Central

    Fadare, Oluwole

    2006-01-01

    Sarcomas constitute less than 1% of all cervical malignancies. With over 150 reported cases, rhabdomyosarcomas represent the most commonly reported sarcoma at this location. In this report, a select group of the more uncommon sarcomas of the uterine cervix are reviewed, including all previously reported examples of leiomyosarcoma, liposarcoma, alveolar soft part sarcoma, Ewing sarcoma/primitive neuroectodermal tumor, undifferentiated endocervical sarcoma, and malignant peripheral nerve sheath tumor (MPNST). Emphasis is placed on any distinctive clinicopathologic features of these entities at this unusual location. PMID:16981999

  8. Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients

    Microsoft Academic Search

    Rolf D. Issels; Johann Mittermiiller; Arthur Gerl; Wolfgang Simon; Alfred Ortmaier; Claudio Denzlinger; Hansjoerg Sauer; Wolfgang Wilmanns

    1991-01-01

    Summary From July 1986 to 1990, 65 patients with deepseated, advanced sarcomas (43 soft-tissue sarcomas, 12 Ewing's sarcomas, 7 chondrosarcomas and 3 osteosarcomas) were entered in a protocol involving regional hyperthermia (RHT) combined with systemic ifosfamide and etoposide. RHT was produced by an electromagnetic deep regional heating device (BSD Medical Corporation, Salt Lake City, Utah). Of these patients, 62% (40

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

    ClinicalTrials.gov

    2015-07-02

    Childhood Solid Neoplasm; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Childhood Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma

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

    ClinicalTrials.gov

    2015-06-18

    Childhood Solid Neoplasm; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Childhood Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma

  11. Kaposi sarcoma

    MedlinePLUS

    Kaposi sarcoma is a cancerous tumor of the connective tissue, and is often associated with AIDS . ... Before the AIDS epidemic, Kaposi sarcoma was seen mainly in elderly Italian and Jewish men, and rarely, in elderly women. Among this group, the tumors ...

  12. 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

  13. Effect of Indirect Nonequilibrium Atmospheric Pressure Plasma on Anti-Proliferative Activity against Chronic Chemo-Resistant Ovarian Cancer Cells In Vitro and In Vivo

    PubMed Central

    Utsumi, Fumi; Kajiyama, Hiroaki; Nakamura, Kae; Tanaka, Hiromasa; Mizuno, Masaaki; Ishikawa, Kenji; Kondo, Hiroki; Kano, Hiroyuki; Hori, Masaru; Kikkawa, Fumitaka

    2013-01-01

    Purpose Nonequilibrium atmospheric pressure plasma (NEAPP) therapy has recently been focused on as a novel medical practice. Using cells with acquired paclitaxel/cisplatin resistance, we elucidated effects of indirect NEAPP-activated medium (NEAPP-AM) exposure on cell viability and tumor growth in vitro and in vivo. Methods Using chronic paclitaxel/cisplatin-resistant ovarian cancer cells, we applied indirect NEAPP-exposed medium to cells and xenografted tumors in a mouse model. Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in the above-mentioned EOC cells. Results We assessed the viability of NOS2 and NOS3 cells exposed to NEAPP-AM, which was prepared beforehand by irradiation with NEAPP for the indicated time. In NOS2 cells, viability decreased by approximately 30% after NEAPP-AM 120-sec treatment (P<0.01). The growth-inhibitory effects of NEAPP-AM were completely inhibited by N-acetyl cysteine treatment, while L-buthionine-[S, R]-sulfoximine, an inhibitor of the ROS scavenger used with NEAPP-AM, decreased cell viability by 85% after NEAPP-AM 60-sec treatment(P<0.05) and by 52% after 120 sec, compared to the control (P<0.01). In the murine subcutaneous tumor-formation model, NEAPP-AM injection resulted in an average inhibition of the NOS2 cell-inoculated tumor by 66% (P<0.05) and NOS2TR cell-inoculated tumor by 52% (P<0.05), as compared with the control. Conclusion We demonstrated that plasma-activated medium also had an anti-tumor effect on chemo-resistant cells in vitro and in vivo. Indirect plasma therapy is a promising treatment option for EOC and may contribute to a better patient prognosis in the future. PMID:24367486

  14. 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.

  15. 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 [Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul 130-701 (Korea, Republic of); Ha, Joohun [Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul 130-701 (Korea, Republic of); Park, Ock Jin [Department of Food and Nutrition, Hannam University, 133 Ojeong-dong Daedeok-gu, Daejeon 306-791 (Korea, Republic of)]. 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.

  16. Type II collagen as specific marker for mesenchymal chondrosarcomas compared to other small cell sarcomas of the skeleton

    Microsoft Academic Search

    Susanna Müller; Stephan Söder; André M Oliveira; Carrie Y Inwards; Thomas Aigner

    2005-01-01

    Mesenchymal chondrosarcoma is a rare, usually highly malignant chondrogenic neoplasm. The diagnosis of mesenchymal chondrosarcoma can be challenging, it nonetheless has important therapeutic and diagnostic implications. Thus, biopsies of mesenchymal chondrosarcomas without conspicuous cartilaginous differentiation cannot be safely distinguished from other small cell mesenchymal neoplasms such as Ewing's sarcoma and peripheral neuroendrocrine tumors, synovial sarcomas and hemangiopericytomas, because all of

  17. Advances in therapy for pediatric sarcomas.

    PubMed

    Weiss, Aaron; Gill, Jonathan; Goldberg, John; Lagmay, Joanne; Spraker-Perlman, Holly; Venkatramani, Rajkumar; Reed, Damon

    2014-01-01

    Pediatric sarcomas are relatively rare malignancies individually. As a group they are typically approached with combination chemotherapies in addition to local control. Fortunately, these malignancies have been approached through careful clinical trial collaboration to define risk groups and appropriately deliver local control measures and systemic therapies. Although local disease is typically approached with curative intent, therapy typically lasts over 6 months and has significant associated morbidities. It is more difficult to cure metastatic disease or induce sustained remissions. In this article, we discuss recent advances in the understanding of the disease process and highlight recent and future cooperative group trials in osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, nonrhabdomyosarcoma soft tissue sarcomas, and desmoid tumor as well as discuss promising therapeutic approaches such as epigenetics and immunotherapy. PMID:24894064

  18. Thoracic sarcomas in children.

    PubMed Central

    Andrassy, R J; Wiener, E S; Raney, R B; Lawrence, W; Lobe, T E; Corpron, C A; Maurer, H M

    1998-01-01

    OBJECTIVE: This study reviews the experience of the Intergroup Rhabdomyosarcoma Studies (IRS) II and III with thoracic sarcomas. SUMMARY BACKGROUND DATA: Thoracic sarcomas in children present special problems with histologic diagnosis, total resection of tumor, and local control. Previous studies have shown high rates of local and distant relapse. METHODS: Data from evaluable patients enrolled in IRS II and IRS III were reviewed. Progression-free and overall survival were estimated by the Kaplan-Meier method and statistical differences were calculated by the log-rank test. The multivariate regression analysis of data was performed using the Cox proportional hazards model. RESULTS: A total of 84 patients presented with thoracic sarcomas during IRS II (51 patients) and IRS III (33 patients). Of these, 76 were chest wall tumors, 3 were lung tumors, 4 were pleural tumors, and 1 arose from the heart. The average age at diagnosis was 8.5 years (range, 1 month-20.5 years). Thirty-three patients had alveolar histology, 17 had embryonal histology, and 12 had extraosseous Ewing's sarcoma, with indeterminate, undifferentiated, and pleomorphic histologies in the remaining 22 patients. Thirteen patients presented as group I (localized disease completely resected), 18 as group II (microscopic residual or nodal disease), 31 as group III (gross residual disease or biopsy only), and 22 as group IV (distant metastatic disease). Sixty patients (71%) achieved a complete response. Thirty-nine patients had a local relapse, and 22 had a distant relapse. Thirty-five patients (42%) survived with a mean follow-up of 1.8 years (range 0.7-11.7 years); 49 (58%) have died with an average survival of 1.1 years (range 0.3-11.7 years). Four patients (5%) died of infection or treatment complications. Progression-free survival was not significantly associated with histology, site, clinical group, or IRS study. Overall survival was significantly associated with clinical group, size, and local or distant recurrence, but not with histology or IRS study by univariate analysis. In a multivariate analysis, only clinical group and local and distant recurrence showed statistical significance (p < 0.002, < 0.006, and < 0.001, respectively). CONCLUSIONS: As expected, outcome was better for patients with totally resected or microscopically residual tumor after resection. A higher rate of recurrence in group I versus group II,although not statistically significant, suggests that identification of margin status may be difficult, and these patients may require more intensive efforts for local control. These patients continued to have a high rate of local and distant relapse, and new strategies for preventing these are under development. PMID:9488512

  19. Epithelioid Sarcoma

    PubMed Central

    Sobanko, Joseph F.; Meijer, Lindsay; Nigra, Thomas P.

    2009-01-01

    Epithelioid sarcoma is a rare, highgrade, soft tissue tumor that has a known propensity for local recurrence, regional lymph node involvement, and distant metastases. We review the clinical and histological presentations of epithelioid sarcoma. Because epithelioid sarcoma presents innocuously, it is often mistaken as a benign process, which can result in insufficient treatment. Therefore, we emphasize the need for clinicians to consider this diagnosis when a slowgrowing tumor is found on the distal extremity of a young male as the malignancy inherently portends a poor prognosis. Prognostic factors, such as local recurrence, regional metastatic disease, and tumor width, are discussed along with current treatment modalities, which include radical excision, sentinel lymph node biopsy, and radiation. PMID:20729965

  20. Blocking SDF-1?/CXCR4 downregulates PDGF-B and inhibits bone marrow derived pericyte differentiation and tumor vascular expansion in Ewing’s tumors

    PubMed Central

    Hamdan, Randala; Zhou, Zhichao; Kleinerman, Eugenie S.

    2014-01-01

    Bone marrow cells (BMCs) are critical to the expansion of the tumor vessel network that supports Ewing’s sarcoma growth. BMCs migrate to the tumor and differentiate into endothelial cells and pericytes. We recently demonstrated that stromal derived growth factor 1? (SDF-1?) regulates platelet derived growth factor B (PDGF-B) and that this pathway plays a critical role in BM-derived pericyte differentiation in vitro. We investigated the role of SDF-1?/PDGF-B in the tumor microenvironment in vivo in promoting BM-derived pericyte differentiation in Ewing’s tumors. The CXCR4 antagonist, AMD 3100, was used to disrupt the SDF-1?/CXCR4 axis in vivo in two xenograft Ewing’s tumor models. BMCs from green fluorescent protein (GFP+) transgenic mice were transplanted into lethally irradiated nude mice in order to track BMC migration to the tumor site. Following BMC engraftment, tumor-bearing mice received daily subcutaneous injections of either PBS or AMD 3100 for 3 weeks. Tumors were resected, and tumor sections were analyzed by immunohistochemistry. AMD 3100 inhibited BMC differentiation into desmin+ and NG2+ pericytes, affected the morphology of the tumor vasculature, decreased perfusion, and increased tumor cell apoptosis. We observed smaller vessels with tiny lumens and a decrease in the microvessel density. AMD 3100 also inhibited PDGF-B protein expression in vitro and in vivo. SDF-1? in the tumor microenvironment plays a critical role in promoting pericyte formation and Ewing’s sarcoma tumor neovascularization by regulating PDGF-B expression. Interfering with this pathway affects tumor vascular morphology and expansion. PMID:24282276

  1. 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.

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

    PubMed

    Anderson, Peter M; Pearson, Margaret

    2006-07-01

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

  3. Translational Activation of HIF1? by YB-1 Promotes Sarcoma Metastasis.

    PubMed

    El-Naggar, Amal M; Veinotte, Chansey J; Cheng, Hongwei; Grunewald, Thomas G P; Negri, Gian Luca; Somasekharan, Syam Prakash; Corkery, Dale P; Tirode, Franck; Mathers, Joan; Khan, Debjit; Kyle, Alastair H; Baker, Jennifer H; LePard, Nancy E; McKinney, Steven; Hajee, Shamil; Bosiljcic, Momir; Leprivier, Gabriel; Tognon, Cristina E; Minchinton, Andrew I; Bennewith, Kevin L; Delattre, Olivier; Wang, Yuzhuo; Dellaire, Graham; Berman, Jason N; Sorensen, Poul H

    2015-05-11

    Metastatic dissemination is the leading cause of death in cancer patients, which is particularly evident for high-risk sarcomas such as Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma. Previous research identified a crucial role for YB-1 in the epithelial-to-mesenchymal transition (EMT) and metastasis of epithelial malignancies. Based on clinical data and two distinct animal models, we now report that YB-1 is also a major metastatic driver in high-risk sarcomas. Our data establish YB-1 as a critical regulator of hypoxia-inducible factor 1? (HIF1?) expression in sarcoma cells. YB-1 enhances HIF1? protein expression by directly binding to and activating translation of HIF1A messages. This leads to HIF1?-mediated sarcoma cell invasion and enhanced metastatic capacity in vivo, highlighting a translationally regulated YB-1-HIF1? axis in sarcoma metastasis. PMID:25965573

  4. Iatrogenic lidocaine toxicosis in ewes.

    PubMed

    Scarratt, W K; Troutt, H F

    1986-01-15

    Lidocaine intoxication developed inadvertently in a group of ewes. Six ewes used in a student laboratory session on laparotomy procedures were anesthetized locally with lidocaine hydrochloride (20 mg/kg) prior to simultaneous bilateral laparotomy. Shortly after the administration of lidocaine hydrochloride, the ewes developed muscle tremors and became recumbent, with a variety of neurologic signs including dullness, opisthotonos, odontoprisis, mydriasis, blindness, extensor rigidity, and convulsions. The ewes were given intravenous fluid therapy, and 90 minutes after the onset of signs, the ewes were standing, dull, and appetent. The laboratory session was rescheduled 2 weeks later, using the same ewes and a reduced dosage of lidocaine hydrochloride (10 mg/kg). There were no adverse effects and the simultaneous bilateral laparotomy procedure was completed without complications. The authors recommend the use of lidocaine hydrochloride at a dosage not exceeding 10 mg/kg for ewes requiring extensive local anesthesia. PMID:3700216

  5. Mesenchymal progenitors expressing TRAIL induce apoptosis in sarcomas.

    PubMed

    Grisendi, Giulia; Spano, Carlotta; D'souza, Naomi; Rasini, Valeria; Veronesi, Elena; Prapa, Malvina; Petrachi, Tiziana; Piccinno, Serena; Rossignoli, Filippo; Burns, Jorge S; Fiorcari, Stefania; Granchi, Donatella; Baldini, Nicola; Horwitz, Edwin M; Guarneri, Valentina; Conte, Pierfranco; Paolucci, Paolo; Dominici, Massimo

    2015-03-01

    Sarcomas are frequent tumors in children and young adults that, despite a relative chemo-sensitivity, show high relapse rates with up to 80% of metastatic patients dying in 5 years from diagnosis. The real ontogeny of sarcomas is still debated and evidences suggest they may derive from precursors identified within mesenchymal stromal/stem cells (MSC) fractions. Recent studies on sarcoma microenvironment additionally indicated that MSC could take active part in generation of a supportive stroma. Based on this knowledge, we conceived to use modified MSC to deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) targeting different sarcoma histotypes. Gene modified MSC expressing TRAIL were cocultured with different osteosarcoma, rhabdomyosarcoma, and Ewing's Sarcoma (ES) cell lines assessing viability and caspase-8 activation. An in vivo model focused on ES was then implemented considering the impact of MSC-TRAIL on tumor size, apoptosis, and angiogenesis. MSC expressing TRAIL induced significantly high apoptosis in all tested lines. Sarcoma death was specifically associated with caspase-8 activation starting from 8 hours of coculture with MSC-TRAIL. When injected into pre-established ES xenotransplants, MSC-TRAIL persisted within its stroma, causing significant tumor apoptosis versus control groups. Additional histological and in vitro studies reveal that MSC-TRAIL could also exert potent antiangiogenic functions. Our results suggest that MSC as TRAIL vehicles could open novel therapeutic opportunities for sarcoma by multiple mechanisms. PMID:25420617

  6. New drug developments for patients with metastatic soft tissue sarcoma

    Microsoft Academic Search

    Jörg Thomas Hartmann; Shreyaskumar Patel

    2005-01-01

    For the subgroup of patients with inoperable gastrointestinal stromal tumors, progress has been made by the rapid development\\u000a and approval of the targeted therapy imatinib mesylate. Small round cell sarcomas (SRCT), such as Ewing\\/primitive neuroectodermal\\u000a tumor, desmoplastic SRCT, and rhabdomyosarcoma, are chemotherapy-sensitive and potentially curable malignancies that are treated\\u000a with multimodality dose-intensive neoadjuvant protocols regardless of size or overt metastatic

  7. Sarcoma Foundation of America

    MedlinePLUS

    ... asking ... Sarcoma Foundation of America Awarded Prestigious 4-Star Rating from Charity Navigator SARCOMA FOUNDATION OF AMERICA AWARDED PRESTIGIOUS 4-STAR RATING FROM CHARITY NAVIGATOR DAMASCUS, Md. – June 23, ...

  8. Neurologic Complications of Sarcoma

    Microsoft Academic Search

    Santosh Kesari; Lara J. Kunschner

    Sarcomas are a heterogeneous group of tumors that rarely involve the nervous system. Neurologic effects of sarcoma are more\\u000a often due to tumors outside of the central nervous system. However, as long-term survival rates in childhood sarcoma improves,\\u000a reports of late neurologic complications have increased. With recent advances in treating local sarcomas with targeted molecular\\u000a therapies, the incidence of late

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

    PubMed

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

    2015-06-01

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

  10. Ewing Marion Kauffman Foundation

    NSDL National Science Digital Library

    Founded in 1966, the Kauffman Foundation was the brainchild of Ewing Kauffman who displayed a great curiosity about the world and who also happened to be a great believer in the importance of philanthropy. Over the past forty years, the Foundation has worked on a variety of initiatives, including work on supporting early education, entrepreneurship, and school reform. On the homepage, visitors will find five primary sections, including "Advancing Innovation", "Education", and "Research & Policy". The first place to start is the "Research & Policy" area. Here, visitors can find data reports and analysis papers on national entrepreneurship trends and technology innovation strategies. In each section, visitors can also view media clips featuring commentary from Kauffman Foundation scholars and experts. Moving on, the "Grants" area is a great way to learn about grant opportunities and recipients listed by date and name. Finally, the "Stay Connected" area contains a place where visitors can sign up to receive their various e-newsletters.

  11. Hyperplastic cardiac sarcoma recurrence.

    PubMed

    Shariff, Masood A; Abreu, Juan A; Durrani, Farida; Daniele, Eddie; Bowman, Kimberly C; Sadel, Scott; Asgarian, Kourosh T; McGinn, Joseph T; Nabagiez, John P

    2015-01-01

    Primary cardiac sarcomas are rare tumors with a median survival of 6-12 months. Data suggest that an aggressive multidisciplinary approach may improve patient outcome. We present the case of a male who underwent resection of cardiac sarcoma three times from the age of 32 to 34. This report discusses the malignant nature of cardiac sarcoma and the importance of postoperative multidisciplinary care. PMID:25861508

  12. Mechanisms of sarcoma development

    Microsoft Academic Search

    Lee J. Helman; Paul Meltzer

    2003-01-01

    Sarcomas are a rare and diverse group of tumours that are derived from connective tissues, including bone, muscle and cartilage. Although there are instances of hereditary predisposition to sarcomas, the overwhelming majority of such tumours are sporadic. In the past decade, we have gained much insight into the genetic abnormalities that seem to underlie the pathogenesis of these tumours. This

  13. Molecular Alterations in Pediatric Sarcomas: Potential Targets for Immunotherapy

    PubMed Central

    Goletz, Theresa J.; Mackall, Crystal L.; Berzofsky, Jay A.

    1998-01-01

    Purpose/results/discussion. Recurrent chromosomal translocations are common features of many human malignancies. While such translocations often serve as diagnostic markers, molecular analysis of these breakpoint regions and the characterization of the affected genes is leading to a greater understanding of the causal role such translocations play in malignant transformation. A common theme that is emerging from the study of tumor-associated translocations is the generation of chimeric genes that, when expressed, frequently retain many of the functional properties of the wild-type genes from which they originated. Sarcomas, in particular, harbor chimeric genes that are often derived from transcription factors, suggesting that the resulting chimeric transcription factors contribute to tumorigenesis. The tumor-specific expression of the fusion proteins make them likely candidates for tumor-associated antigens (TAA) and are thus of interest in the development of new therapies. The focus of this review will be on the translocation events associated with Ewing's sarcomas/PNETs (ES), alveolar rhabdomyosarcoma (ARMS), malignant melanoma of soft parts (MMSP) (clear cell sarcoma), desmoplastic small round cell tumor (DSRCT), synovial sarcoma (SS), and liposarcoma (LS), and the potential for targeting the resulting chimeric proteins in novel immunotherapies. PMID:18521238

  14. Cutaneous Metastatic Undifferentiated Pleomorphic Sarcoma from a Mediastinal Sarcoma

    PubMed Central

    Jeong, Do Seon; Park, Dong Hwa

    2015-01-01

    Undifferentiated pleomorphic sarcoma, known as malignant fibrous histiocytoma, is a malignant neoplasm that arises in both soft tissue and bones. In 2002, the World Health Organization declassified malignant fibrous histocytoma as a formal diagnostic entity and renamed it 'undifferentiated pleomorphic sarcoma not otherwise specified.' It most commonly occurs in the lower extremities and rarely metastasizes cutaneously. We report a case of cutaneous metastatic undifferentiated pleomorphic sarcoma of the buttocks occurring in a 73-year-old man diagnosed with mediastinal sarcoma 4 years previously. He first noticed the mass approximately 2 months previously. Histological findings with immunomarkers led to a final diagnosis of cutaneous metastatic sarcoma from mediastinal undifferentiated pleomorphic sarcoma. PMID:26082589

  15. Hairy cell sarcoma

    PubMed Central

    Waxman, Jonathan H. Y.

    1983-01-01

    The first case of a hairy cell sarcoma is presented. Subsequent to surgical resection and post-operative radiotherapy the patient has survived two years without systemic evidence of hairy cell leukaemia. ImagesFig. 1 PMID:6866872

  16. What Is Uterine Sarcoma?

    MedlinePLUS

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

  17. 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...

  18. Treatment Options for Kaposi Sarcoma

    MedlinePLUS

    ... type of cancer being treated. Liposomal chemotherapy uses liposomes (very tiny fat particles) to carry anticancer drugs. ... doxorubicin is used to treat Kaposi sarcoma. The liposomes build up in Kaposi sarcoma tissue more than ...

  19. Orbital granulocytic sarcoma

    PubMed Central

    Stockl, F.; Dolmetsch, A.; Saornil, M; Font, R.; Burnier, M.

    1997-01-01

    AIM—Orbital granulocytic sarcoma is a localised tumour composed of cells of myeloid origin. Histological diagnosis can be difficult in patients with poorly differentiated orbital tumours and no evidence of systemic leukaemia. The naphthol AS-D chloracetate esterase (Leder stain) and immunohistochemical stains for lysozyme and MAC387 were used to determine the staining characteristics of these tumours. A case series of seven patients with orbital granulocytic sarcoma is presented.?METHODS—Seven patients with orbital granulocytic sarcoma were studied. Haematoxylin and eosin, Leder, and lysozyme stained sections were available in seven cases. Unstained formalin fixed paraffin embedded sections of seven cases were available for immunohistochemical evaluation using the avidin-biotin-complex technique for MAC387.?RESULTS—The mean age of presentation of the orbital tumour was 8.8 years. Four patients presented with an orbital tumour before any systemic manifestations of leukaemia. In two cases the diagnosis of the orbital tumour and systemic leukaemia was made simultaneously. There was one case of established systemic myeloid leukaemia in remission with the subsequent development of orbital granulocytic sarcoma. Six of seven cases (86%) were positive for the Leder stain. Five of seven cases (71%) showed positive immunoreactivity with lysozyme. The immunohistochemical stain for MAC387 was positive in all seven cases (100%) including one case that was negative for both lysozyme and Leder stains.?CONCLUSIONS—Orbital granulocytic sarcoma is a tumour that affects children and can present with rapidly progressive proptosis. This tumour may develop before, during, or after the occurrence of systemic leukaemia. The combination of Leder and lysozyme stains is useful in the diagnosis of orbital granulocytic sarcoma. MAC387 may be a more reliable marker for orbital granulocytic sarcoma.?? PMID:9497470

  20. Primary hepatic sarcomas: CT findings

    Microsoft Academic Search

    Ri-Sheng Yu; Ying Chen; Biao Jiang; Liu-Hong Wang; Xiu-Fang Xu

    2008-01-01

    Primary hepatic sarcomas are rare tumors that are difficult to diagnose clinically. Different primary hepatic sarcomas may\\u000a have different clinical, morphologic, and radiological features. In this pictorial review, we summarized computed tomography\\u000a (CT) findings of some relatively common types of hepatic sarcomas, including angiosarcoma, epithelioid hemangioendothelioma\\u000a (EHE), liposarcoma, undifferentiated embryonal sarcoma (UES), leiomyosarcoma, malignant fibrous histiocytoma (MFH), and carcinosarcoma\\u000a (including

  1. Multicentric myofibroblastic sarcoma.

    PubMed

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

    2014-01-01

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

  2. 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

  3. 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

  4. 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

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

    ClinicalTrials.gov

    2014-08-11

    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

  8. Gene therapy for sarcoma.

    PubMed

    Fruehauf, S; Veldwijk, M R; Berlinghoff, S; Basara, N; Baum, C; Flasshove, M; Hegewisch-Becker, S; Kröger, N; Licht, T; Moritz, T; Hengge, U R; Zeller, W J; Laufs, S

    2002-01-01

    Soft tissue sarcomas are mesenchymal tumors which respond poorly to systemic therapy. Recent studies suggest a higher response rate with an increased doxorubicin dosage. However, this was parallel with a profound hematotoxicity in 75% of patients. Transfer of the human multidrug resistance 1 (MDR1) gene to normal hematopoietic stem cells and transplantation may significantly reduce the hematotoxicity of anthracyclin-based chemotherapy. To test this concept of supportive gene therapy in advance of a clinical study, we transduced mobilized peripheral blood progenitor cells (PBPC) with the retroviral vector SF91m3 containing the human MDR1 gene, transplanted these cells to immune-deficient mice, allowed 6 weeks for engraftment to occur and treated the animals with MDR1-based chemotherapy. In the MDR1-transduced group the human leukocytes were significantly protected from the toxicity of chemotherapy (p < 0.05). While the gene transfer rate was in the range of 10% and thus comparable to recent clinical trials, the gene expression was 59% of transduced cells and thus significantly higher than previously reported for less-advanced vectors. On the other hand, ifosfamide, a drug which has been used successfully for stem cell mobilization, is active in soft tissue sarcoma. Due to these favorable characteristics sarcoma is an attractive target to test the efficacy of MDR1 gene therapy in a clinical setting. Gene therapeutic strategies may also be used to directly target sarcoma cells, e.g. by transfer of suicide genes. We found that adenoassociated virus 2 (AAV-2) vectors efficiently transduce human HS-1 and HT1080 sarcoma cells (>90%) while other tumor cell lines and primary human PBPC were less susceptible. The thymidine kinase (TK) suicide gene was cloned into an AAV-2 vector and a complete kill of TK-transduced HS-1 and HT1080 cells was observed following exposure to aciclovir or ganciclovir (GCV), while >90% of mock-transduced HS-1 cells survived at these dosages. Transplantation of those sarcoma cells to nonobese diabetic (NOD)/LtSz-severe-combined immunodeficient (scid)/scid (NOD/SCID) mice resulted in a survival of >5 months in the AAV-TK-transduced/GCV-treated group, while the mice in the mock-transduced/GCV-treated group had died after 3 weeks. These data show that soft tissue sarcomas are a particularly suitable model system for the development and clinical testing of new gene therapeutic concepts. PMID:12426490

  9. Immunoreactivity using anti-ERG monoclonal antibodies in sarcomas is influenced by clone selection.

    PubMed

    Machado, Isidro; Mayordomo-Aranda, Empar; Scotlandi, Katia; Picci, Piero; Llombart-Bosch, Antonio

    2014-08-01

    The aim of the present study was to explore ERG immunoreactivity in a series of sarcomas, GIST and malignant rhabdoid tumor (MRT), considering the not fully elucidated specificity and sensitivity of this antibody. Paraffin-embedded tissue microarrays from those tumors were stained with anti-ERG against the C-terminus [(EPR3864(2)] and N-terminus (Clone 9FY). EPR3864(2) was positive in almost all angiosarcomas, and MRT.GIST were positive in a large proportion of cases (38.4%), and more than half the synovial sarcomas (52.7%) revealed EPR3864(2) staining. Several chondrosarcomas, osteosarcomas, rhabdomyosarcoma and Ewing's sarcoma family of tumors (ESFT) presented EPR3864(2) expression in a lower number of cases. 9FY was positive in most of the angiosarcomas; however, only sporadic ESFT and synovial sarcoma were positive and the other tumors tested were negative. Fourteen ESFT with EWSR1/Fli-1 gene fusion presented positive nuclear staining for EPR3864(2). Similarly, 5 ESFT with EWSR1/Fli-1 gene fusion presented positive staining for 9FY. We must stress that the difference between the present and previous studies may be due to the source of the anti-ERG employed, anti-ERG against C or N-terminus, protein cross-reactivity and dilution. In conclusion, specificity for ERG staining in sarcomas should be considered with caution and the immunoexpression is undoubtedly influenced by clone and antibody selection. PMID:24906228

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

    PubMed

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

    2015-02-01

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

  11. Biomaterial-Induced Sarcoma

    PubMed Central

    Kirkpatrick, C. James; Alves, Antonio; Köhler, Holger; Kriegsmann, Jörg; Bittinger, Fernando; Otto, Mike; Williams, David F.; Eloy, Rosy

    2000-01-01

    In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence. PMID:10751369

  12. Spinal and Paraspinal Ewing Tumors

    SciTech Connect

    Indelicato, Daniel J., E-mail: dindelicato@floridaproton.or [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Keole, Sameer R. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Shahlaee, Amir H. [Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL (United States); Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Gibbs, C. Parker; Scarborough, Mark T. [Department of Orthopedic Surgery, University of Florida College of Medicine, Gainesville, FL (United States); Pincus, David W. [Department of Neurosurgery, University of Florida College of Medicine, Gainesville, FL (United States); Marcus, Robert B. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    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.

  13. [Intraosseous highly differentiated osteogenic sarcoma].

    PubMed

    Petrovichev, N N; Khmelev, O N; Luk'ianchenko, A B; Karapetian, R M

    1988-01-01

    A man of 20 developed well-differentiated intraosseous osteogenic sarcoma of the femur. Clinico-roentgenologic, computed tomography and histological findings revealed a number of features uncommon for the tumor: (1) a torpid course, (2) histological appearance typical for parosteal sarcoma, (3) low malignant potential. PMID:3196181

  14. 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 [Department of Radiotherapy, University Hospital of Muenster, Muenster (Germany)]. E-mail: schuck@uni-muenster.de; Ahrens, Susanne [Department of Pediatric Oncology and Hematology, University Hospital of Muenster, Muenster (Germany); Schorlemer, Ines von [Department of Radiotherapy, University Hospital of Muenster, Muenster (Germany); Kuhlen, Michaela [Department of Pediatric Oncology and Hematology, University Hospital of Muenster, Muenster (Germany); Paulussen, Michael [Department of Pediatric Oncology and Hematology, University Hospital of Muenster, Muenster (Germany); Hunold, Andrea [Department of Pediatric Oncology and Hematology, University Hospital of Muenster, Muenster (Germany); Gosheger, Georg [Department of Orthopedics, University Hospital of Muenster, Muenster (Germany); Winkelmann, Winfried [Department of Orthopedics, University Hospital of Muenster, Muenster (Germany); Dunst, Juergen [Department of Radiotherapy, University Hospital of Halle, Halle (Germany); Willich, Normann [Department of Radiotherapy, University Hospital of Muenster, Muenster (Germany); Juergens, Heribert [Department of Pediatric Oncology and Hematology, University Hospital of Muenster, Muenster (Germany)

    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.

  15. Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2015-06-08

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

  16. 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.

  17. Esthesioneuroblastoma is not a member of the primitive peripheral neuroectodermal tumour-Ewing’s group

    PubMed Central

    Mezzelani, A; Tornielli, S; Minoletti, F; Pierotti, M A; Sozzi, G; Pilotti, S

    1999-01-01

    Esthesioneuroblastoma (ENB) is a rare, site-specific, locally aggressive neuronal malignancy so far thought to belong to primitive peripheral neuroectodermal tumour-Ewing's tumour (pPNETs-ETs). Its anatomical location, in addition to morphologic, immunophenotypic and ultrastructural features, suggests its origin in the neuronal or neuroendocrine cells of the olfactory epithelium. However, the cytogenetic and molecular data currently available appear controversial on the presence of the typical translocation t(11;22)(q24;q12) and of trisomy 8, chromosomal changes that characterize the tumours belonging to the pPNETs-ETs. Herein we have analysed five ENB tumour specimens for trisomy 8 by fluorescence in situ hybridization (FISH), for the presence of EWS gene rearrangements by FISH, reverse transcription polymerase chain reaction and Southern blot analyses, as well as for the expression of the Ewing sarcoma-associated MIC2 antigen by immunohistochemistry. Neither EWS/FLI-I, EWS/ERG and EWS/FEV fusion genes nor MIC2 expression were found in any tumour, whereas trisomy 8 was found in one case only. Moreover, DNA from three cases analysed by Southern blot did not show EWS gene rearrangements. Our results support the evidence that ENB is not a member of the pPNETs-ETs. © 1999 Cancer Research Campaign PMID:10574242

  18. [Sarcoma neurogenes of the larynx].

    PubMed

    Szmeja, Z; Kruk-Zagajewska, A; Wierzbicka, M; Majewski, P

    1998-01-01

    Malignant nonepithelial neoplasms of the larynx are rare, and tumors of mesenchymal origin constitute 4-6% of all malignant neoplasms of the larynx. Sarcoma neurogenes vel malignant schwannoma make up 10% of all soft tissue sarcomas. In this paper a case of the extremely rare malignant schwannoma of the larynx is presented. In world literature we have met four case reports describing tumors of this histological morphology and location. PMID:9591428

  19. 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.”

  20. Kastner Receives 2008 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Elderfield, Henry; Kastner, Miriam

    2009-02-01

    Miriam Kastner was awarded the 2008 Maurice Ewing Medal at the AGU Fall Meeting Honors Ceremony, held 17 December 2008 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.''

  1. 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.”

  2. Ewing Memorial Scholarship Family & Consumer Sciences

    E-print Network

    Karonis, Nicholas T.

    Ewing Memorial Scholarship Family & Consumer Sciences Two Scholarships, of $1,000.00 each, may in Family & Consumer Sciences Currently enrolled in an accredited Illinois college or university of the following information: Why are you pursuing a degree in Family and Consumer Sciences? What are your future

  3. Adenovirus E1A and Ewing tumors

    Microsoft Academic Search

    E. de Alava; R. Sanchez-Prieto; S. Ramon y Cajal

    2000-01-01

    In the December 1999 issue of Nature Medicine, Melot and Delattre and Kovar, challenged the Sanchez-Prieto et al . September 1999 article proposing that the adenoviral E1A gene induces the Ewing tumor fusion transcript EWS–FLI1. Here Sanchez-Prieto et al. respond…Ed.

  4. 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 ...

  5. [KAPOSI'S SARCOMA OF THE VULVA].

    PubMed

    Chokoeva, Aa; Tchernev, G; Wollina, U

    2015-01-01

    Kaposi's sarcoma represents multiple idiopathic hemorrhagic sarcoma--a mesenchymal tumor that affects the blood and lymph vessels. Its performance is associated with an infection with human herpes virus type 8--the so called KSHV (Kaposi's sarcoma -associated virus), and with the human immunodeficiency virus. Kaposi's sarcoma is considered as a typical clinical manifestation in male homosexuals suffering from acquired immune deficiency syndrome (AIDS), while his performance in HIV-positive women is unusual, with a ratio of men to women--10-15: 1. Vulvar localization is much rarer. It is up to 5 times more frequent in HIV- positive patients. It is clinically represented in most of the cases by the clinical picture of nonspecific tumor mass. Biopsy and further virological testing for establishing KSHV in lesional tissue is essential for confirming the diagnosis. Serological testing for HIV/AIDS in affected patients is required. Local treatment includes surgical excision of solitary lesions, cryotherapy as well as radiotherapy. The use of interferon alpha resulted in complete remission in approximately 40% of the affected patients. New trends in treatment tend to be pathogenetically directed as in the process of studies to date are inhibitors of angiogenesis. Due to the rarity of the occurrence, non-specific clinical picture and histological findings, Kaposi's sarcoma should be considered in the differential diagnosis of tumor masses with vulvar localization, especially in HIV-positive patients. PMID:26137776

  6. Conditioning ewes and lambs to increase consumption of spotted knapweed

    Microsoft Academic Search

    Travis Raymond Whitney; Bret Eugene Olson

    2006-01-01

    Spotted knapweed (Centaurea maculosa Lam.) is an invasive plant that alters species composition and grazing value of rangelands in the northwestern United States. The spread of invasive plants may be reduced by using livestock as a biological control. We determined if mature ewes and their lambs (n=34ewe\\/lamb pairs) consume more spotted knapweed when ewes and\\/or lambs are conditioned to fresh-cut

  7. Serum protein pattern in ewe with pregnancy toxemia

    Microsoft Academic Search

    Gul Fatma Yarim; Gulay Ciftci

    2009-01-01

    Pregnancy toxemia is a metabolic disease of pregnant ewes which causes significant economic losses in sheep industry. The\\u000a pathophysiology and metabolic changes of this disorder remain poorly understood. We conducted this study to describe the serum\\u000a protein pattern associated with the pregnancy toxemia in ewes. In this study, the electrophoretic pattern of serum proteins\\u000a of 15 ewes with naturally occuring

  8. Granulocytic sarcoma of the testis.

    PubMed

    Eggener, S E; Abrahams, A; Keeler, T C

    2004-03-01

    Granulocytic sarcoma is a rare tumor composed of neoplastic blood cells, typically occurring during the course of, or before the onset of, acute nonlymphoblastic leukemia. We present a case of a 37-year-old man with acute testicular pain who was found to have a testicular mass diagnosed as granulocytic sarcoma (GS). Because GS virtually always progresses to leukemia, he underwent postoperative radiotherapy and chemotherapy. He was free of disease 6 months after treatment. This case highlights a rare hematologic cancer that urologists and pathologists should be aware of because it can present as a testicular mass. PMID:15028471

  9. Mast cell sarcoma: clinical management.

    PubMed

    Weiler, Catherine R; Butterfield, Joseph

    2014-05-01

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

  10. 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

  11. Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors

    Microsoft Academic Search

    C J Fraser; B J Weigel; J P Perentesis; K E Dusenbery; T E DeFor; K S Baker; M R Verneris

    2006-01-01

    The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose–response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these

  12. Chromosomal translocations highlighted in Primitive Neuroectodermal Tumors (PNET) and Ewing sarcoma

    PubMed Central

    Tranc?u, IO

    2014-01-01

    Almost 200 molecular markers in oncology, very important in the diagnosis, prognostic and treatment were identified. The cell and tissue markers and also the circulating (sanguine) ones are genetic markers of the hereditary and non-hereditary tumors. Also extremely important are the regulatory ways of cell growth and differentiation, of the cell “senescence” and cell death (apoptosis). The term of “tumor marker” concerns a variety of molecules or processes that are different in the normal cell compared with the malign cell. The tumor markers may include modifications to the genetic level (mutations, deletions or genes amplifications) to the transcription level (super expression or sub-expression), to the translation level (high or low quantities of proteins, abnormal glycosylation of proteins) and/or to the functional level (the level of cell differentiation or presence of neo-vascularisation). Cancer is a genetic disease. There is a deregulation at the genes level that controls the cell division and withdrawal from the cell cycle or there is a genetic susceptibility. In other words, cancer is an end point for several phases in which the oncogenes and stimulatory signals and inhibitors produced and controlled by the products of these oncogenes are involved. PMID:25870694

  13. Molecular Approaches to Sarcoma Therapy

    PubMed Central

    Olsen, R. J.; Tarantolo, S. R.

    2002-01-01

    Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed. PMID:18521343

  14. 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.

  15. Expression of the LIM homeobox domain transcription factor ISL1 (Islet-1) is frequent in rhabdomyosarcoma but very limited in other soft tissue sarcoma types.

    PubMed

    Erlenbach-Wünsch, Katharina; Haller, Florian; Taubert, Helge; Würl, Peter; Hartmann, Arndt; Agaimy, Abbas

    2014-06-01

    The transcription factor ISL1 (islet-1) has emerged as a useful marker for metastatic pancreatic well differentiated neuroendocrine neoplasms, but recent studies showed wider expression in poorly differentiated neuroendocrine carcinomas from different sites as well as poorly differentiated neuroblastoma. Expression of ISL1 in soft tissue sarcomas has not been studied before.We evaluated ISL1 expression in 249 soft tissue tumour specimens from 249 patients and 17 precursor cell lymphoblastic lymphomas (ALL). ISL1 was not detected in any of 63 liposarcomas of different subtypes, 55 leiomyosarcomas, 22 solitary fibrous tumours, 20 undifferentiated pleomorphic/spindle cell sarcomas, 13 small cell synovial sarcomas and 17 ALL cases. Variable nuclear expression was detected in rhabdomyosarcoma (15/25, 60%), rhabdomyoblastic areas of malignant müllerian mixed tumours (5/5), Ewing sarcoma (2/12, very weak) and monophasic fibrous synovial sarcoma (2/29). More extensive staining (moderate to strong) was restricted to rhabdomyosarcoma. Taken by histological subtype, ISL1 was expressed more frequently in alveolar (9/11, 82%) versus non-alveolar (6/14, 43%) rhabdomyosarcoma. ISL1 is commonly expressed in rhabdomyosarcoma, particularly the alveolar subtype and should be distinguished from poorly differentiated neuroendocrine and neuroblastic neoplasms. Awareness of this finding helps to avoid misinterpretation as neuroendocrine neoplasms that would result in inappropriate therapeutic and prognostic consequences. PMID:24751901

  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. Effect of Interferon  Administration on Endometrium of Nonpregnant Ewes: A Comparison with Pregnant Ewes

    Microsoft Academic Search

    Yizhen Chen; Jonathan A. Green; Eric Antoniou; Alan D. Ealy; Nagappan Mathialagan; Angela M. Walker; Mary P. Avalle; Cheryl S. Rosenfeld; Leonard B. Hearne; R. Michael Roberts

    2006-01-01

    In ruminants, conceptus interferon- (IFNT) alters maternal physiology to accommodate a pregnancy. We hypothesized that the effectiveness of IFNT on extending corpus luteum (CL) life span in nonpregnant ewes would depend upon the dose and manner of administration and would be correlated with the response in gene expression in endometrium. We anticipated that IFNT, whether administered im or by uterine

  18. MATERNAL INGESTION OF LOCOWEED. I. EFFECTS ON EWE-LAMB BONDING AND BEHAVIOUR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated whether exposure of ewes to locoweed (Oxytropis sericea Nutt. In T. & G.; Leguminosae) during gestation would affect ewe behavior during parturition, ewe-lamb bonding and related behaviors post partum, and maternal responsiveness of ewes to alien and own lambs. Twenty-nine n...

  19. The bacterial flora in the teat duct of ewes can protect against and can cause mastitis

    Microsoft Academic Search

    Ilectra A. Fragkou; Vasia S. Mavrogianni; Peter J. Cripps; Dimitris A. Gougoulis; George C. Fthenakis

    2007-01-01

    We studied the possible effects of bacterial populations within the teat duct, in the pathogenesis of ovine mastitis. In experiment I, 32 ewes were allocated into group A (ewes from which we isolated (+++ growth) coagulase-negative staphylococci), B (ewes from whose duct we isolated (+ growth) coagulase-negative staphylococci) or C (ewes from which we isolated Bacillus spp.) and subdivided into

  20. Erythroblastic sarcoma, an extremely rare variant of myeloid sarcoma.

    PubMed

    Cornfield, Dennis B

    2012-11-01

    A 79-year-old man was admitted to the hospital because of a 20-lb weight loss, low back pain, and leg weakness. He had a 1-year history of fibrotic myelodysplasia, possibly therapy related, with a highly complex chromosome karyotype. Radiologic evaluation showed extensive destructive bone lesions, retroperitoneal lymphadenopathy, and evidence for thoracic spinal cord compression. Core biopsies of a retroperitoneal lymph node showed groups of large, immature-appearing mononuclear cells which, on Wright-stained touch preparation, appeared similar to dysplastic erythroid precursors noted on recent marrow aspirate smears. Immunohistochemical staining showed negativity of neoplastic cells to an extensive panel of nonhematopoietic and myeloid markers, and positivity for CD117, glycophorin A, and CD71, consistent with a diagnosis of erythroblastic sarcoma. This lesion is a very unusual variant of myeloid sarcoma and has been described only rarely in the medical literature. PMID:22795354

  1. An HIV-negative penil Kaposi's sarcoma.

    PubMed

    Demir, A; Temiz, Y; Bozkurt, S U; Erbarut, I; Ilker, Y

    2004-01-01

    Kaposi's sarcoma is a tumour of reticuloendothelial system. Non-epidemic Kaposi's sarcoma limited to the penile involvement should be aggressively treated because it is rarely associated with diffuse organ involvement localized surgical excision or small-field external beam or electron beam radiation has been effective. In this case, we presented a man 53 years old, who presents with a papular indolent lesion on the glans penis, which is reported as a Kaposi sarcoma after excision of the lesion. PMID:15787336

  2. NY-ESO-1-specific T Cells in Treating Patients With Advanced NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation Therapy

    ClinicalTrials.gov

    2015-07-14

    Mast Cell Sarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma

  3. Growth curve analysis of Rambouillet ewes 

    E-print Network

    Mathenge, James Mwai

    1981-01-01

    51 53 VITA 59 LIST OF TABLES TABLE PAGE NUMBER OF EWES BY YEARS, AGE OF DAM AND TYPE OF BIRTH/REARING SUBCLASSES LEAST-SQUARES MEANS FOR BREEDING WEIGHTS 3, 4 AND 5 BY YEAR OF BIRTH. . . . . . . . . ~ ~ ~ ~ ~ ~ 18 LEAST-SQUARES MEANS FOR AGE... and Whiteman (1975) reported single-reared lambs were heavier at birth (4. 2 vs. 3. 7 kg), gained faster to weaning (. 34 vs. . 25 kg/day) and were heavier at 70 days (25. 9 vs. 21. 4 kg) than the twin-reared lambs. Holtman and Bernard (1969) reported lambs...

  4. Growth curve analysis of Rambouillet ewes

    E-print Network

    Mathenge, James Mwai

    1981-01-01

    for this study. However, most of the results were reported for 152 observations; a subset of the 283 records that contained the smst complete set of weighted' Type of birth and rearing was the single most significant source of variation for preweaning body... weights and growth rates. Estimation of mature weight obtained for 184 records was 59. 6 + . 77 kilograms. Based upon analysis of yearly weights, ewes had reached maturity by 42 months of age. Birth and 120-day weight were lower than those reported...

  5. Proton Radiotherapy for Pediatric Sarcoma

    PubMed Central

    Ladra, Matthew M.; Yock, Torunn I.

    2014-01-01

    Pediatric sarcomas represent a distinct group of pathologies, with approximately 900 new cases per year in the United States alone. Radiotherapy plays an integral role in the local control of these tumors, which often arise adjacent to critical structures and growing organs. The physical properties of proton beam radiotherapy provide a distinct advantage over standard photon radiation by eliminating excess dose deposited beyond the target volume, thereby reducing both the dose of radiation delivered to non-target structures as well as the total radiation dose delivered to a patient. Dosimetric studies comparing proton plans to IMRT and 3D conformal radiation have demonstrated the superiority of protons in numerous pediatric malignancies and data on long-term clinical outcomes and toxicity is emerging. In this article, we review the existing clinical and dosimetric data regarding the use of proton beam radiation in malignant bone and soft tissue sarcomas. PMID:24424260

  6. Pulmonary Kaposi's sarcoma in Africa.

    PubMed Central

    Pozniak, A L; Latif, A S; Neill, P; Houston, S; Chen, K; Robertson, V

    1992-01-01

    BACKGROUND: A study was carried out to identify the main clinical radiological and bronchoscopic features of HIV related Kaposi's sarcoma of the lung in African patients. METHODS: Forty seven HIV positive patients with epidemic Kaposi's sarcoma who had clinical or radiological respiratory changes were investigated by simple lung function tests and fibreoptic bronchoscopy. RESULTS: The most common respiratory symptoms in the 47 patients were persistent cough in 42, haemoptysis in 23, and breathlessness in 38. A restrictive spirometric pattern was most common. The mean (SD) forced expiratory volume in one second (FEV1) was 1.88 (0.62) 1 with a forced vital capacity (FVC) of 2.66 (0.87) 1 and a FEV1/FVC% of 73.2 (7.5). On the chest radiograph 26 patients had diffuse reticulonodular shadows, 11 focal nodular shadows, seven a pleural effusion, and one a substantial increase in vascular markings; in two the radiograph was normal. At bronchoscopy characteristic discrete lesions were easily visible in 37 patients and were often bright red. Multiple nodules were seen in 11, flat or early plaque lesions in 12 (14 had both), proximal flat lesions and diffuse infiltration in three, diffuse infiltration alone in four, and masses in two; one had normal appearances at bronchoscopy. One patient had Pneumocystis carinii and two had a single bacterial pathogen cultured from the bronchoalveolar lavage fluid. Only two of 29 bronchoscopic biopsies showed classical histological Kaposi's sarcoma. After cytotoxic treatment 20 patients have died, with an overall median survival of 70 days. CONCLUSION: In this African population symptomatic pulmonary Kaposi's sarcoma was common, with lesions seen in all but one patient at bronchoscopy. Coexistent infection was uncommon. Prognosis was poor despite treatment. PMID:1440469

  7. Synovial sarcoma of the foot.

    PubMed

    Bekarev, Mikhail; Elsinger, Elisabeth C; Villanueva-Siles, Esperanza; Borzykowski, Ross M; Geller, David S

    2013-01-01

    We report the case of a 75-year-old male who underwent lung lobectomy for presumed lung cancer. Thereafter, he presented with a painful mass between the third and fourth metatarsal heads in the foot that was assumed to be Morton's neuroma. After extensive oncologic evaluation, the foot mass was diagnosed as a synovial sarcoma. In retrospect, his lung lesion was understood to be metastatic disease. PMID:23632071

  8. Vaccinia necrosum complicating immunoblastic sarcoma.

    PubMed

    Turkel, S B; Overturf, G D

    1977-07-01

    A 59-year-old man is presented who had immunoblastic lymphadenopathy which evolved over a three-year period into immunoblastic sarcoma. His course was complicated by vaccinia necrosum, which necessitated prolonged therapy with Marboran and vaccinia-immune globulin. The persistence of virus was documented at autopsy by positive viral culture and ultra-structural examination. This case illustrates the potential hazards of administration of live viral vaccines to an immune compromised host presumed to be in remission and suggests that the continued activity of viral infection may signal the unsuspected persistence of underlying disease. PMID:880554

  9. [Isolated myeloid sarcoma involving the mediastinum].

    PubMed

    Jeli?-Puskari?, Biljana; Kardum-Skelin, Ika; Susterci?, Dunja; Pazur, Marina; Vrhovac, Radovan; Radi?-Kristo, Delfa; Gredelj-Simec, Njetocka; Kovacevi?, Dragica Obad; Plas?ak, Jasmina; Gasparov, Slavko; Jaksi?, Branimir

    2011-09-01

    Myeloid sarcoma is a rare extramedullary solid tumor consisting of immature myeloid cells and most commonly involving the bone, skin, lymph nodes, soft tissue, gastrointestinal tract and testis. Mediastinal myeloid sarcoma is very rare. There are two major types of myeloid sarcoma: granulocytic sarcoma and monoblastic sarcoma, according to immature cell type. Myeloid sarcoma is found in 2%-8% of patients with acute myeloid leukemia (AML). Myeloid sarcoma may develop before or concurrently with AML, or may be the initial manifestation of AML relapse in previously treated patients. Blast transformation of some form of myeloproliferative neoplasm or myelodysplastic syndrome may also manifest as myeloid sarcoma. A major differential diagnostic problem is isolated primary myeloid sarcoma without bone marrow and peripheral blood involvement, which may precede leukemic stage for months or years, and which is frequently misdiagnosed, mostly as malignant lymphoma. A case is presented of a 56-year-old female patient complaining of weakness, vertigo, dry cough and breathing difficulties. Clinical examination revealed enhanced vascular pattern on the right chest and right arm edema. Computed tomography (CT) of the thorax showed an expansive growth measuring 11 cm craniocaudally in the anterior mediastinum. Fine needle aspiration cytology of tumor mass yielded a scarcely cellular sample with individual atypical immature cells, fine chromatin structure and scarce cytoplasm with occasional granules and Auer rods. Considering the morphological, cytochemical and immunocytochemical characteristics of immature cells, the diagnosis of myeloid sarcoma was made and verified by histopathology of tumor biopsy sample. Immature cells were not found by analysis of bone marrow puncture sample, immunophenotyping of bone marrow cells and bone biopsy analysis. As immature cell proliferation was not detected in bone marrow and peripheral blood, while spread of the disease beyond the mediastinum was ruled out by imaging methods (CT, ultrasonography), it was decided to be a primary non-leukemic form of mediastinal myeloid sarcoma. Myeloid sarcoma should be taken in consideration on differential diagnosis of solid tumors because making an accurate diagnosis is necessary for timely initiation of appropriate therapy. Weakly expressed or lacking clear signs of myeloid differentiation may hamper morphological diagnosis. As isolated myeloid sarcoma is a very rare entity frequently resembling lymphoma in clinical presentation, it poses a major diagnostic challenge for both morphologists and clinicians. PMID:23126041

  10. 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

  11. Uterine sarcomas: clinical presentation and MRI features

    PubMed Central

    Santos, Pedro; Cunha, Teresa Margarida

    2015-01-01

    Uterine sarcomas are a rare heterogeneous group of tumors of mesenchymal origin, accounting for approximately 8% of uterine malignancies. They comprise leiomyosarcoma, endometrial stromal sarcoma, undifferentiated endometrial sarcoma, and adenosarcoma. Compared with the more common endometrial carcinomas, uterine sarcomas behave more aggressively and are associated with a poorer prognosis. Due to their distinct clinical and biological behavior, the International Federation of Gynecology and Obstetrics introduced a new staging system for uterine sarcomas in 2009, categorizing uterine carcinosarcoma as a variant of endometrial carcinoma, rather than a pure sarcoma. Magnetic resonance imaging (MRI) has a developing role in the assessment of these malignancies. Features such as tumor localization, irregular or nodular margins, necrosis, rapid growth, intense contrast enhancement, and restriction at diffusion-weighted imaging can suggest the diagnosis and help differentiate from more common leiomyomas and endometrial carcinoma. MRI is therefore extremely useful in preoperative detection and staging and, consequently, in determination of appropriate management. This pictorial review aims to discuss the clinical features of uterine sarcomas, as well as their most common appearances and distinct characteristics in MRI. PMID:25347940

  12. Mesenchymal stem cell transformation and sarcoma genesis

    PubMed Central

    2013-01-01

    MSCs are hypothesized to potentially give rise to sarcomas after transformation and therefore serve as a good model to study sarcomagenesis. Both spontaneous and induced transformation of MSCs have been reported, however, spontaneous transformation has only been convincingly shown in mouse MSCs while induced transformation has been demonstrated in both mouse and human MSCs. Transformed MSCs of both species can give rise to pleomorphic sarcomas after transplantation into mice, indicating the potential MSC origin of so-called non-translocation induced sarcomas. Comparison of expression profiles and differentiation capacities between MSCs and sarcoma cells further supports this. Deregulation of P53- Retinoblastoma-, PI3K-AKT-and MAPK pathways has been implicated in transformation of MSCs. MSCs have also been indicated as cell of origin in several types of chromosomal translocation associated sarcomas. In mouse models the generated sarcoma type depends on amongst others the tissue origin of the MSCs, the targeted pathways and genes and the differentiation commitment status of MSCs. While some insights are glowing, it is clear that more studies are needed to thoroughly understand the molecular mechanism of sarcomagenesis from MSCs and mechanisms determining the sarcoma type, which will potentially give directions for targeted therapies. PMID:23880362

  13. Alveolar soft part sarcoma causing perianal abscess.

    PubMed

    Sullivan, Niall; McCulloch, Tom; Leverton, David

    2011-07-01

    A 34-year-old woman presented with a perianal abscess that communicated with the vagina. There was a background of a one-year history of a conservatively treated, traumatic, paravaginal haematoma. Histology of the fistula tract showed alveolar soft part sarcoma and subsequent imaging identified a large soft tissue mass in the pelvis with lung metastases. Alveolar soft part sarcoma is a rare soft tissue sarcoma of unknown cellular origin affecting predominantly young women, often in deep soft tissues and lower extremities. PMID:21943444

  14. Phase II Study of High-Dose Photon/Proton Radiotherapy in the Management of Spine Sarcomas

    SciTech Connect

    DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States)], E-mail: tdelaney@partners.org; Liebsch, Norbert J. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Pedlow, Francis X. [Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Adams, Judith; Dean, Susan [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Yeap, Beow Y. [Department of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); McManus, Patricia [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Rosenberg, Andrew E.; Nielsen, G. Petur [Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Harmon, David C. [Department of Medicine, Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Spiro, Ira J. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Raskin, Kevin A. [Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Suit, Herman D. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Yoon, Sam S. [Department of Surgery (Section of Surgical Oncology), Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Hornicek, Francis J. [Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States)

    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.

  15. Synovial sarcoma in a premature newborn.

    PubMed

    Köse, Do?an; Annagür, Ali; Erol, Cengiz; U?ra?, Serdar; Köksal, Yavuz

    2014-06-01

    Synovial sarcoma is rarely detected in infants, with an annual incidence of 0.5 per million. Synovial sarcoma occurs more frequently in adolescents and young adults, with the majority of patients presenting between 15 and 40 years of age. It is extremely rare, however, in pediatric patients under 2 years of age. In the present study we examined a 3-day-old male infant born at 32 weeks who had a mass on his left arm. Synovial sarcoma was identified on histopathological and immunohistochemical analysis of biopsy material acquired from the mass. On whole body magnetic resonance imaging, diffuse metastases were detected in the bilateral lungs in the retroperitoneal zone, in bilateral suprarenal glands, the right liver lobe, the right kidney, and the brain. To our knowledge this is the youngest patient to be diagnosed with synovial sarcoma in the literature. PMID:24894940

  16. Primary clear cell sarcoma of the tongue.

    PubMed

    Kraft, Stefan; Antonescu, Cristina R; Rosenberg, Andrew E; Deschler, Daniel G; Nielsen, G Petur

    2013-11-01

    Clear cell sarcoma shares features with melanoma, but frequently shows EWSR1 rearrangements. It is an aggressive tumor typically occurring in the soft tissues of the extremities, with a gastrointestinal variant with less consistent melanocytic differentiation. It is extremely rare in the head and neck region, with no reported cases in the oral cavity. We report a case of an 82-year-old woman with a clear cell sarcoma arising in the tongue, with cervical lymph node metastases. Histologically, the tumor showed some features of gastrointestinal clear cell sarcoma. No osteoclast-type giant cells were present. The tumor cells were positive for S100 protein and negative for other melanocytic markers. Fluorescence in situ hybridization showed rearrangements of EWSR1 and ATF1. This case expands the spectrum of clear cell sarcoma with a gastrointestinal-like variant in a novel site, emphasizing the need to consider it as a differential diagnosis to melanoma in mucosal sites. PMID:24168510

  17. Treatment Options for Childhood Soft Tissue Sarcoma

    MedlinePLUS

    ... followed by adjuvant chemotherapy . Blood Vessel Tumors Angiosarcoma (deep) Treatment of angiosarcoma may include the following: Surgery ... about clinical trials is available from the NCI Web site . Recurrent and Progressive Childhood Soft Tissue Sarcoma ...

  18. 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.

  19. Postirradiation sarcomas of the head and neck

    SciTech Connect

    Maisel, R.H.; Manivel, J.C.; Porto, D.P.; Stanley, M.

    1989-09-01

    We discuss four cases of postirradiation sarcomas of the head and neck. Two cases were metachronous sarcomas that appeared after operation and irradiation for primary sarcomas, 1 case was a mandibular malignant fibrous histiocytoma that developed on the opposite side of the jaw from a malignant histiocytic neoplasm that was irradiated 8 years previously, and 1 case was a laryngeal tumor that appeared 5 years after combined operative and radiation therapy for a laryngeal squamous carcinoma. Immunohistochemical studies more precisely defined and classified these tumors, and assisted in determining a therapeutic protocol. The therapy for postirradiation sarcomas includes extirpative operation when possible, but the role of chemotherapy is uncertain. The aggressive behavior of these neoplasms was attested to by the death of three patients within 18 months of their operations.

  20. Yellow grease as an alternative energy source for nursing Awassi ewes and their suckling lambs

    Microsoft Academic Search

    M. S. Awawdeh; B. S. Obeidat; R. T. Kridli

    2009-01-01

    Thirty Awassi ewes with an initial body weight (BW) of 52.0kg (SD=8.4) nursing single lambs with an initial BW of 6.2kg (SD=1.0) were utilized to study yellow grease, by partially replacing barley, as an alternative energy source. The ewes aged 3–7 years and parity ranged from 2 to 6. All ewes gave birth 6–8 days before starting the experiment. Ewes

  1. Genomic characteristics of soft tissue sarcomas

    Microsoft Academic Search

    Fredrik Mertens; Ioannis Panagopoulos; Nils Mandahl

    2010-01-01

    Studies on the molecular mechanisms behind soft tissue sarcoma development have disclosed that these malignancies are as genetically\\u000a heterogeneous as they are clinically and morphologically diverse. Much of the genetic information on soft tissue sarcomas\\u000a is still limited to the genomic level, as detected by chromosome banding analysis or comparative genomic hybridization. Based\\u000a on the results of such studies, soft

  2. Technetium scanning in Kaposi's sarcoma and its simulators

    SciTech Connect

    Gunnoe, R.; Kalivas, J.

    1982-04-01

    The clinical picture of ulcerated purple plaques on the legs often suggests several diagnoses: Kaposi's sarcoma, stasis dermatitis, atrophie blanche (livedoid vasculitis), and a poorly understood condition called acroangiodermatitis of Favre-Chaix (pseudo-Kaposi's sarcoma). Even the skin biopsy may not always be conclusive. We describe our experience with three patients with pseudo-Kaposi's sarcoma, one with true Kaposi's sarcoma and two with atrophie blanche. Clinical and histopathologic similarities among these three conditions pointed up the need for additional confirmatory studies, i.e., isotope scanning. The technetium scan was positive in both Kaposi's sarcoma and pseudo-Kaposi's sarcoma but negative in atrophie blanche.

  3. 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. New therapeutic targets in soft tissue sarcoma.

    PubMed

    Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C; Lazar, Alexander J

    2012-05-01

    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 underlying mechanisms. 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 on 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 biological agents currently in preclinical and early phase I/II trials. This will provide the reader with the context for understanding the current state of this field and a sense of where it may be headed in the coming years. PMID:22498582

  5. Application of Proteomics to Soft Tissue Sarcomas

    PubMed Central

    Kondo, Tadashi; Kubota, Daisuke; Kawai, Akira

    2012-01-01

    Soft tissue sarcomas are rare and account for less than 1% of all malignant cancers. Other than development of intensive therapies, the clinical outcome of patients with soft tissue sarcoma remains very poor, particularly when diagnosed at a late stage. Unique mutations have been associated with certain soft tissue sarcomas, but their etiologies remain unknown. The proteome is a functional translation of a genome, which directly regulates the malignant features of tumors. Thus, proteomics is a promising approach for investigating soft tissue sarcomas. Various proteomic approaches and clinical materials have been used to address clinical and biological issues, including biomarker development, molecular target identification, and study of disease mechanisms. Several cancer-associated proteins have been identified using conventional technologies such as 2D-PAGE, mass spectrometry, and array technology. The functional backgrounds of proteins identified were assessed extensively using in vitro experiments, thus supporting expression analysis. These observations demonstrate the applicability of proteomics to soft tissue sarcoma studies. However, the sample size in each study was insufficient to allow conclusive results. Given the low frequency of soft tissue sarcomas, multi-institutional collaborations are required to validate the results of proteomic approaches. PMID:22778956

  6. Original article Iodine nutrition in ewes. 2. Effects of low to high iodine

    E-print Network

    Boyer, Edmond

    Original article Iodine nutrition in ewes. 2. Effects of low to high iodine intake by ewes on the iodine (I) levels. Dietary I contents (mg/kg dry matter [DM]) in pregnancy and lactation, respectively inorganic iodine (PII) of lambs from birth to d42 of life was affected by ewe I intake, except for groups

  7. The effect of milking frequency on the milk production of Chios ewes and Damascus goats

    E-print Network

    Paris-Sud XI, Université de

    The effect of milking frequency on the milk production of Chios ewes and Damascus goats C milking caused a significant reduction (21.6 p. 100) in the milk production of Chios ewes during the first of the ewes milked twice daily were switched to one daily milking. The total reduction in the milk yield

  8. Effects of trenbolone acetate and propylene glycol on pregnancy toxaemia in ewes

    Microsoft Academic Search

    A Wierda; J Verhoeff; S van Dijk; J Dorresteijn; T Wensing

    1985-01-01

    Eleven ewes with pregnancy toxaemia were monitored clinically and biochemically after daily treatment with trenbolone acetate (30 mg) and propylene glycol (twice daily 100 ml), for at least one week. The clinical signs of pregnancy toxaemia at first examination were less severe than those described in ewes in other countries. After the first treatment, the appetite improved in nine ewes,

  9. 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.

  10. 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 ...

  11. 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) ...

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

    MedlinePLUS

    ... for soft tissue sarcomas? What are the key statistics about soft tissue sarcomas? The American Cancer Society's ... in the United States for 2015 are (these statistics include both adults and children): About 11,930 ...

  13. What Are the Key Statistics about Kaposi Sarcoma?

    MedlinePLUS

    ... what causes Kaposi sarcoma? What are the key statistics about Kaposi sarcoma? Before the AIDS epidemic, Kaposi ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  14. What Are the Key Statistics about Uterine Sarcoma?

    MedlinePLUS

    ... factors for uterine sarcoma? What are the key statistics about uterine sarcoma? The American Cancer Society's estimates ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  15. Establishment of a novel clear cell sarcoma cell line (Hewga-CCS), and investigation of the antitumor effects of pazopanib on Hewga-CCS

    PubMed Central

    2014-01-01

    Background Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines. Methods Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo. Results Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling. Conclusions CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism. PMID:24946937

  16. 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

  17. Immunotherapy for Bone and Soft Tissue Sarcomas

    PubMed Central

    Uehara, Takenori; Fujiwara, Tomohiro; Takeda, Ken; Kunisada, Toshiyuki; Ozaki, Toshifumi; Udono, Heiichiro

    2015-01-01

    Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

  18. Gastric myeloid sarcoma without acute myeloblastic leukemia

    PubMed Central

    Huang, Xiao-Li; Tao, Jin; Li, Jian-Zhong; Chen, Xiao-Liang; Chen, Jian-Ning; Shao, Chun-Kui; Wu, Bin

    2015-01-01

    Myeloid sarcomas (MS) involve extramedullary blast proliferation from one or more myeloid lineages that replace the original tissue architecture, and these neoplasias are called granulocytic sarcomas, chloromas or extramedullary myeloid tumors. Such tumors develop in lymphoid organs, bones (e.g., skulls and orbits), skin, soft tissue, various mucosae, organs, and the central nervous system. Gastrointestinal (GI) involvement is rare, while the occurrence of myeloid sarcomas in patients without leukemia is even rare. Here, we report a case of a 38-year-old man who presented with epigastric pain and progressive jaundice. An upper GI endoscopy had shown extensive multifocal hyperemic fold thickening and the spread of nodular lesions in the body of the stomach. Biopsies from the gastric lesions indicated myeloid sarcoma of the stomach. However, concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia. For diagnosis, the immunohistochemical markers must be checked when evaluating a suspected myeloid sarcoma case. Accurate MS diagnosis determines the appropriate therapy and prognosis. PMID:25717265

  19. 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

  20. 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

  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. 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.

  3. 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.”

  4. 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".

  5. KINETICS OF EXPERIMENTAL SALMONELLA ABORTUS OVIS INFECTION IN EWES

    E-print Network

    Paris-Sud XI, Université de

    KINETICS OF EXPERIMENTAL SALMONELLA ABORTUS OVIS INFECTION IN EWES F LANTIER Station de Pathologie/12/86 / accepted 15/03/87 Résumé CINÉTIQUE D'UNE INFECTION EXPÉRIMENTALE PAR SALMONELLA ABORTUS OVlS CHEZ LA BRE- BIS. - La multiplication et la dissémination de Salmonella abortus ovis, un sérotype de salmonella spé

  6. Fault Tolerance in MPI Programs ? William Gropp and Ewing Lusk

    E-print Network

    Gropp, Bill

    Fault Tolerance in MPI Programs ? William Gropp and Ewing Lusk Mathematics and Computer Science examines the topic of writing fault-tolerant MPI applications. We discuss the meaning of fault tolerance in general and what the MPI Standard has to say about it. We survey several approaches to this problem

  7. Fault Tolerance in MPI Programs William Gropp and Ewing Lusk

    E-print Network

    Gropp, Bill

    Fault Tolerance in MPI Programs William Gropp and Ewing Lusk Mathematics and Computer Science examines the topic of writing fault-tolerant MPI applications. We discuss the meaning of fault tolerance in general and what the MPI Standard has to say about it. We survey several approaches to this problem

  8. Mixed grazing trial with suckling cows and dry pregnant ewes

    E-print Network

    Paris-Sud XI, Université de

    , winter weight loss and sex of suckled calf. The same management was applied each year with each group : 1 for 3 months at turn out and allocated to groups on the basis of parity, calving date, live weight more weight in the mixed group. Weight and body condition of the ewes and subsequently birth weight

  9. 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...

  10. Effect of Freezing on Fossomatic Cell Counting in Ewe Milk

    Microsoft Academic Search

    J. R. Martínez; C. Gonzalo; J. A. Carriedo; F. San Primitivo

    2003-01-01

    Using the Fossomatic method, a total of 10,072 ana- lytical somatic cell count (SCC) observations were car- ried out on 4760 aliquots taken from 70 individual ewe milk samples with the objective of studying whether freezing showed significant differences of SCC in com- parison with refrigeration, according to different ana- lytical conditions. These conditions were four preserva- tion procedures (without

  11. Molecular piracy of Kaposi's sarcoma associated herpesvirus.

    PubMed

    Choi, J; Means, R E; Damania, B; Jung, J U

    2001-01-01

    Kaposi's Sarcoma associated Herpesvirus (KSHV) is the most recently discovered human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and Multicentric Casttleman's disease. KSHV contains numerous open reading frames with striking homology to cellular genes. These viral gene products play a variety of roles in KSHV-associated pathogenesis by disrupting cellular signal transduction pathways, which include interferon-mediated anti-viral responses, cytokine-regulated cell growth, apoptosis, and cell cycle control. In this review, we will attempt to cover our understanding of how viral proteins deregulate cellular signaling pathways, which ultimately contribute to the conversion of normal cells to cancerous cells. PMID:11325605

  12. Clear cell sarcoma of the stomach.

    PubMed

    Lagmay, Joanne P; Ranalli, Mark; Arcila, Maria; Baker, Peter

    2009-08-01

    Clear cell sarcoma (CCS) is a high grade soft tissue sarcoma with a distinct molecular profile. Gastrointestinal CCS is very rare and most reported cases are in adults. We describe a 10-year-old female with a 4-month history of anemia who later developed fever, weight loss and abdominal pain. She was subsequently found to have a large infiltrative gastric mass. A diagnosis of CCS was confirmed by molecular and cytogenetic studies. This case illustrates the necessity of a multimodal approach, particularly the use of molecular studies, in the diagnostic evaluation of rare tumors presenting in unusual sites. PMID:19350639

  13. Epigenetic Regulators: New Therapeutic Targets for Soft Tissue Sarcoma

    PubMed Central

    Zhang, Pingyu; Pollock, Raphael E

    2015-01-01

    Soft tissue sarcoma is a malignancy that develops from human soft tissues such as muscle, nerve, fat, and blood vessels. The World Health Organization classification comprises about 50 different histologic types of soft tissue sarcoma. Soft tissue sarcoma is treated most often with surgery. Chemotherapy and radiotherapy have shown only minor effects on patient survival in this disease. The overall 5-year survival rate of soft tissue sarcoma is 50%; it has not changed for the past several decades. A new class of therapeutic targets for soft tissue sarcoma was identified recently. Epigenetic regulators, such as DNA methyltransferases, histone deacetylases, and histone-modifying enzyme enhancer of zeste homolog 2, have been found to be involved in pathogenesis of various soft tissue sarcomas. Small-molecule inhibitors of these epigenetic regulators may provide a new targeted therapy approach to soft tissue sarcomas in the future.

  14. 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.

  15. 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

  16. Serum-cell interactions in transmission of sarcoma in the soft shell clam, Mya arenaria L.

    PubMed

    Sunila, I

    1992-08-01

    1. Serum proteins from sarcomatous soft shell clams, Mya arenaria L., enhanced transmission of sarcoma. 2. Sarcoma cells were isolated and administered to the recipients at the same cell density in different sarcoma-protein-free diluents: seawater, serum from normal clams, heat-treated sarcoma serum or protease-digested sarcoma serum. 3. Transmission in these groups was significantly slower than in the group where cells were administered in intact sarcoma serum, demonstrating that the tumor promoting factors in the serum were heat-sensitive proteins. 4. Normal hemocytes administered in sarcoma serum caused mortality but not sarcoma transmission, suggesting the presence of cytotoxic factors in sarcoma serum. PMID:1355037

  17. CENTER FOR SARCOMA AND BONE ONCOLOGY OSTEOSARCOMA

    E-print Network

    Liu, Xiaole Shirley

    , MD, chair of Dana'-Farber's Department of Pediatric Oncology, and investigators at the BroadCENTER FOR SARCOMA AND BONE ONCOLOGY OSTEOSARCOMA RESEARCH DESCRIPTION Dana-Farber is advancing osteosarcoma research and care with investigations led by Katherine Janeway, MD, a pediatric hematologist

  18. Pulmonary histiocytic sarcoma in a rabbit.

    PubMed

    Leissinger, Mary; Brandão, João; Wakamatsu, Nobuko; Le Roux, Alexandre; Rich, Gregory; Gaunt, Stephen

    2013-09-01

    An approximately 8-year-old male castrated Dutch rabbit was evaluated for a 6-day history of respiratory signs, which began as sneezing and progressed to tachypnea with anorexia. On physical examination, tachypnea and pale mucous membranes were noted. Thoracic radiographs revealed a soft tissue pulmonary mass, fine-needle aspirates of which confirmed a neoplasia with malignant features suspicious for a histiocytic sarcoma. The rabbit was discharged and due to a rapidly deteriorating condition, the owner declined chemotherapy with Lomustine and elected euthanasia of the rabbit. The affected lung was submitted for histopathology. Histologic sections of the lung were characterized by clusters of histiocytic cells and multinucleated giant cells with occasional invasion of blood and lymphatic vessels. The histologic diagnosis was histiocytic sarcoma. To the authors' knowledge, this is the first case report of histiocytic sarcoma in a rabbit. Based on the clinical and radiologic findings in this case, histiocytic sarcoma should be included in the list of differentials for rabbits presenting with respiratory signs and evidence of a pulmonary mass. PMID:23909927

  19. 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 receive bevacizumab alone every 3 weeks for a maximum of 11 treatments.

  20. Postirradiation sarcoma of bone. A perspective

    Microsoft Academic Search

    Apostolos A. Tountas; Victor L. Fornasier; A. R. Hardwood; Philip M. K. Leung

    1979-01-01

    Ten cases of irradiation induced sarcoma of bone which fulfilled Cahan's criteria were seen in a twenty year period at the Princess Margaret Hospital. The overall incidence of this complication is 0.035% of all irradiated five year survivors. Combining our data with three other large series presented in the literature, a dose complication curve could be deduced. On the basis

  1. Prostatic stromal sarcoma with neuroectodermal differentiation

    PubMed Central

    2012-01-01

    Abstract Prostatic stromal sarcoma is a fairly rare tumor that constitutes approximately 0.1–0.2% of all prostatic cancers. Detailed characteristics of the tumor are still unclear due to its rarity. We describe a case of prostatic stromal sarcoma in a 63 year-old man who suffered from urinary obstructive symptoms. Palliative transuterine resection was performed and the preliminary histopathological diagnosis was neuroendocrine carcinoma. After chemotherapy, total pelvic exenteration was performed. Histopathologically, the tumor was composed of monotonously proliferating small to medium-sized round cells, which existed in compact islands with loose or dense fibrovascular networks. Immunohistochemically, the tumor cells were widely positive for vimentin, CD56, CD99 and focally positive for synaptophysin, CD10, progesterone receptor, desmin and CD34, but negative for EMA, cytokeratin, estrogen receptor, S-100 and myoglobin. Most of the previously reported tumors exhibited positive stainability for CD10 and progesterone receptor. In addition to these markers, expressions of CD56, CD99 and synaptophysin were characteristically detected in our case. To the best of our knowledge, we present the first case of prostatic stromal sarcoma with characteristic immunohistochemical staining properties. Although the biological characteristics of this rare tumor have not yet been elucidated, these findings suggest prostatic stromal sarcoma can potentially show neuroectodermal differentiation. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7291874028051262 PMID:23217062

  2. General Information about Adult Soft Tissue Sarcoma

    MedlinePLUS

    ... is available from the NCI Web site . To Learn More About Adult Soft Tissue Sarcoma For more information from the ... regularly and updated as needed, by the PDQ Adult Treatment Editorial ... what has been learned in the laboratory. Each trial answers certain scientific ...

  3. Stages of Adult Soft Tissue Sarcoma

    MedlinePLUS

    ... is available from the NCI Web site . To Learn More About Adult Soft Tissue Sarcoma For more information from the ... regularly and updated as needed, by the PDQ Adult Treatment Editorial ... what has been learned in the laboratory. Each trial answers certain scientific ...

  4. Kaposi's Sarcoma Treated with Topical Alitretinoin

    Microsoft Academic Search

    A. González de Arriba; S. Pérez-Gala; R. Goiriz-Valdés; L. Ríos-Buceta; A. García-Díez

    2007-01-01

    Kaposi's sarcoma is a multifocal neoplastic process with four clinical variants, all of them induced by human herpes virus 8. Currently there is no treatment of choice and it depends on the extension and location of the lesions as well as on the clinical type of the disease. Alitretinoin gel 0.1% is approved for the treatment of cutaneous lesions of

  5. Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes

    Microsoft Academic Search

    Ramanathan K Kasimanickam; Vanmathy R Kasimanickam; Jacobo S Rodriguez; Kevin D Pelzer; Philip D Sponenberg; Craig D Thatcher

    2010-01-01

    BACKGROUND: Tocopherols have biphasic, proangiogenic and antiangiogenic therapeutic effects. The objective of this clinical trial was to clarify tocopherol's placental angiogenic potential in late pregnant ewes following oral supplementation. METHODS: Eighteen pregnant ewes during late gestation were selected for this study. Ewes were given oral supplementation of 500 mg of alpha-tocopherol (aT; N = 6) or 1000 mg of gamma-tocopherol

  6. RUMEN-PROTECTED BYPASS FAT FOR DAIRY EWE COMMERCIAL MILK PRODUCTION

    Microsoft Academic Search

    Brett C. McKusick; Yves M. Berger; David L. Thomas

    The effects of fat supplementation and weaning system on commercial milk yield and milk composition were determined on 129 East Friesian crossbred ewes. Prior to lambing, ewes were randomly assigned to one of two weaning systems. The DY1 system involved weaning of ewes from their lambs within 24 to 36 hr post-partum and then twice-daily machine milking. In the MIX

  7. Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

    PubMed Central

    2010-01-01

    Background Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy. Methods DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined. Results Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ? = 0.55 to ? = 0.80. Conclusions The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements. PMID:21190557

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

    ClinicalTrials.gov

    2015-03-03

    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

  9. Reproductive performance in ewes fed varying levels of cut lucerne pasture around conception.

    PubMed

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

    2015-07-01

    Elevated intakes of protein and energy may increase embryo mortality, but it is not clear whether fresh lucerne (Medicago sativa) pasture poses a risk. A two-year pen study using oestrous synchronised and artificially inseminated Merino ewes (n=175 in 2013 and 215 in 2014) evaluated whether feeding freshly cut lucerne pasture (mean crude protein 19.7%, metabolisable energy 9.4MJ/kg DM) at maintenance or ad libitum during different periods around insemination altered reproductive performance in comparison with ewes fed a Control diet (mean crude protein 7.8%, metabolisable energy 9.0MJ/kg DM) of pelleted faba bean hulls and oat grain hulls at maintenance. The proportion of pregnant ewes carrying multiple fetuses was reduced (P=0.026) when ewes were fed lucerne ad libitum between days 0 and 17 after insemination compared with the Control diet (0.18 and 0.34, respectively), but not when ewes were fed lucerne ad libitum between days 0 and 7 after insemination (0.22). Reproductive performance, including the proportion of ewes pregnant and the proportion with multiple fetuses, was not different (P>0.05) when ewes were fed lucerne at maintenance between days 0 and 7 compared with the Control diet. While reproductive performance was similar when ewes were fed lucerne at maintenance between 0 and 17 days after artificial insemination compared with pellets at maintenance, fetal numbers per pregnant ewe were reduced by feeding lucerne ad libitum after insemination. PMID:26024965

  10. What regulates placental steroidogenesis in 90-day pregnant ewes?

    Microsoft Academic Search

    Yoshie S. Weems; Laurie Kim; Vicki Tsuda; Chaoquan Yin; Charles W. Weems

    2007-01-01

    By day-90, the placenta secretes half of the circulating progesterone and 85% of the circulating estradiol-17? [Weems YS, Vincent D, Tanaka Y, et al. Effects of prostaglandin F2? on sources of progesterone and pregnancy in intact, ovariectomized, and hysterectomized 90–100 day pregnant ewes. Prostaglandins 1992;43:203–22; Weems YS, Vincent DL, Nusser K, et al. Effects of prostaglandin F2? (PGF2?) on secretion

  11. Luteogenesis in cyclic ewes: echotextural, histological, and functional correlates.

    PubMed

    Duggavathi, R; Bartlewski, P M; Pierson, R A; Rawlings, N C

    2003-08-01

    To date, it has not been possible to detect corpus luteum (CL) by ultrasonography, immediately following ovulation, in the ewe. Early CL detection is essential to be able to relate luteal outcome to the developmental pattern of the ovulated follicle and to confirm ovulation. Image analysis of the CL may be useful in providing a noninvasive picture of CL differentiation and function. The present study was designed to use high-resolution ultrasonography to monitor and to correlate the echotextural, histological, and functional attributes of the developing ovine CL from Days 1 to 3 after ovulation. Ten ewes underwent twice-daily transrectal ultrasonography and blood sampling from the day of synchronized estrus. Ewes were ovariectomized at 12-24, 36-48, and 60-72 h after ovulation. Ovaries collected were scanned in a water bath before processing for histology. Ultrasonographic images of CL were analyzed for echotexture. Histological sections were analyzed for the percentage area of the CL occupied by blood clot or luteal tissue. Serum samples were analyzed for progesterone concentration. Numerical pixel value, heterogeneity, and percentage of the CL occupied by blood clot declined (P<0.05) from 12-24 to 60-72 h after ovulation. Luteal area and serum progesterone concentration increased (P<0.05) from 12-24 to 60-72 h. The results indicated that it was possible to visualize developing CL as early as 12-24 h after ovulation in the ewe. Echotexture of the CL was closely associated with its morphological and functional characteristics; image analysis holds promise for noninvasive monitoring of CL differentiation and growth. PMID:12724274

  12. Dairy and suckled milk production of Dorset ewes

    Microsoft Academic Search

    K. G. Geenty

    1980-01-01

    Two experiments were carried out (1976–77 and 1977–78) to measure both dairy and suckled milk production of Dorset ewes by machine milking. Dairy production was 71% of suckled yield during the corresponding 10 weeks of lactation in 1976–77 and 75% during 14 weeks of lactation in 1977–78. In the 1976–77 experiment varying lamb suckling regimes, which involved partial or complete

  13. [Correlation between epithelioid sarcoma and poorly differentiated fibroblastic synovialosarcoma].

    PubMed

    Bouziani, A; Khlil, A; Zarrouk, H; Kammoun, N; Debbiche, A; Doss, N; Cheikh, R; Ben Ayed, M

    1991-01-01

    The authors report an original case of tendosynovial sarcoma localizated in the side of the palm of the hand of an eight year old child. This tumor has two morphological forms. One is characteristic of undifferentiated synovialosarcoma, and the other of epitheloid sarcoma. The immuno-histochemical study confirms the diagnosis of undifferentiated synovialosarcoma. On the basis of this case and with reference to the literature, the authors suggest that epithelioid sarcoma and synovialosarcoma constitute the same entity. PMID:1647752

  14. Radiation-induced prostatic sarcoma: A case report

    SciTech Connect

    Scully, J.M.; Uno, J.M.; McIntyre, M.; Mosely, S. (Bay Area Hospital, Coos Bay, OR (USA))

    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.

  15. 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

  16. Effects of service sire on prenatal mortality and prolificacy in ewes.

    PubMed

    Holler, T L; Dean, M; Taylor, T; Poole, D H; Thonney, M L; Thomas, D L; Pate, J L; Whitley, N; Dailey, R A; Inskeep, E K

    2014-07-01

    Ability to select service sires that minimize partial or complete losses of pregnancy could have major economic impacts in sheep production systems. This study tested the null hypothesis that survival of potential progeny did not vary with breed type of service sire or among individual rams. Data included 980 ewes on 10 farms; each ewe was pregnant to 1 of 67 rams of 12 breeds. Number of conceptuses was estimated once during pregnancy by ultrasonography, either transrectal (embryos) or transabdominal (fetuses), and was compared with number of lambs born to estimate losses. Data were examined first for number of lambs born and second for documented losses. Individual service sires affected number born (P < 0.001), which varied from 0.70 to 2.45 lambs per pregnant ewe. The main effects of breed type on lambs born were not significant, but breed types of both service sires (P < 0.0002) and ewes (P < 0.001) interacted with diagnosed number of conceptuses. Lambs born varied with ewe age (P < 0.0001) and among farms (P < 0.0001), and statistically, farms interacted with number of diagnosed conceptuses (P < 0.0001); season had no effect. In documented losses, there were both main effects of individual service sire and a service sire × number of diagnosed embryos interaction (P < 0.005). Thus, ewes bred to some rams were more apt to lose single pregnancies, whereas ewes bred to other rams were more apt to lose 1 or more embryos or fetuses from multiple pregnancies. Breed type of service sire affected (P < 0.05) prenatal death. Complete losses of single conceptuses tended to be greater in ewes bred to black-faced or hair-type rams (service sire breed type × number of diagnosed conceptuses; P < 0.09). Breed type of ewes also varied in incidence of complete losses (P < 0.05); hair-type ewes (46%) lost more (P < 0.02) documented conceptuses from examination to birth than black-faced (27%), white-faced (20%), or dairy-type (25%) ewes. Greater losses of singles than of multiples occurred in black-faced (37% vs. 18%) and hair-type (64% vs. 27%) ewes than in other breeds (ewe breed type × number of conceptuses; P < 0.03) per ewe. Surprisingly, purebred conceptuses were lost less often (24%) than crossbreds (36.4%; P < 0.002). Selection of rams based on records of prenatal losses in ewes they serviced may be a method to decrease embryonic and fetal wastage. However, further study to determine repeatability of differences among service sires from year to year will be required. PMID:24778333

  17. Extremely rare case of vulvar myxoid epithelioid sarcoma.

    PubMed

    Rego, Joana Lima; Cintra, Georgia Fontes; Netto, Ana Karina Junqueira; Abrahão-Machado, Lucas Faria; Tsunoda, Audrey

    2015-01-01

    Epithelioid sarcoma is a distinct sarcoma type with specific morphology and immunophenotype. An epithelioid sarcoma of the vulva is an extremely rare and aggressive tumor and most commonly occurs on the labia majora in women of reproductive age. Only few cases have been reported, especially with the presence of focal myxoid changes. Early diagnosis is difficult because of its benign appearance as a painless subcutaneous nodule. Optimal treatment is not well established due to its rarity. We report a successfully approached case of vulvar epithelioid sarcoma that occurred in a 34-year-old female patient, treated with wide local excision, and review of the current medical literature. PMID:25737787

  18. Somatic cell counts in milk of Welsh-Mountain, Dorset-Horn and Chios ewes throughout lactation

    Microsoft Academic Search

    G. C. Fthenakis

    1996-01-01

    During four experiments the somatic cell counts (SCC) of 2642 milk samples were determined. SCC were studied in the milk of healthy Welsh-Mountain and Dorset-Horn ewes (experiment I), healthy Chios ewes (experiment II), Welsh-Mountain ewes subjected to intramammary inoculation with Staphylococcus simulans (experiment III) or Dorset-Horn ewes similarly inoculated (experiment IV). SCC of less than 1.0 × 106 cells ml?1

  19. An unusual breast mass: primary synovial sarcoma

    PubMed Central

    Doyle, Victoria J; Bateman, Adrian C; Theaker, Jeffery M

    2013-01-01

    We describe a 54-year-old woman presenting with mastalgia and a 6?mm breast lesion on imaging. Core biopsy revealed a lesion characterised by a predominant epithelioid and a minor spindle cell component. Our differential diagnosis included intraduct papilloma/adenoma and adenomyoepithelioma. However, initial immunohistochemistry did not support these diagnoses and further immunohistochemistry raised the possibility of a synovial sarcoma. This was confirmed with the finding, using fluorescence in-situ hybridisation, of the characteristic translocation t(x; 18) (p11.2; q11.2). Establishing a diagnosis of synovial sarcoma at unusual sites may be difficult, especially when limited tissue is available, for example, within a core biopsy. In this case, immunohistochemistry was useful, but cytogenetics was the key additional investigation. It is important to consider the possibility of rare tumours when the morphological and immunohistochemical features of a lesion initially appear conflicting or inconclusive. PMID:23784772

  20. Endometrial stromal sarcoma: a rare entity.

    PubMed

    Jabeen, Salma; Anwar, Shahnaz; Fatima, Naheed

    2015-03-01

    Endometrial Stromal Sarcoma (ESS) is a hormone sensitive tumor. It is a rare gynecological tumor and is considered to occur more often in pre-menopausal women. A proper pre-operative diagnosis is difficult and confirmed in most cases after hysterectomy for a presumed benign disease. Endometrial sampling, ultrasound, and magnetic resonance imaging can provide diagnostic clues. For early disease complete surgical cure is possible, however, adjuvant therapy is available for recurrence. This case of Low Grade Endometrial Stromal Sarcoma (LGESS) in a 21 years old woman was presented as irregular vaginal bleeding. Clinical diagnosis of fibroid was made but analysis of endometrium showed ESS confirmed on hysterectomy specimen. One should consider it in any case with rapid fibroid enlargement. PMID:25772965

  1. Soft tissue sarcoma of the extremity.

    PubMed Central

    Cooper, T. M.; Sheehan, M.; Collins, D.; O'Connor, T. P.

    1996-01-01

    A retrospective review of 33 cases of soft tissue sarcoma of the extremity presenting over a 10 year period was undertaken. The history, patterns of referral, diagnostic investigations, procedures undertaken and outcomes were studied. We found there was a frequent delay in diagnosis and sometimes misinterpretation of biopsy specimens. Patients were seen by a variety of specialists from disciplines such as general surgery, plastic surgery, orthopaedic surgery and rheumatology. Considerable progress has been made in the treatment of soft tissue sarcomas, often allowing local control of the tumour without amputation. We believe there should be early referral of patients having these tumours to a centre where a combined multidisciplinary approach can be undertaken. PMID:8881731

  2. Extragenital endometrial stromal sarcoma arising in endometriosis.

    PubMed

    Alcázar, Juan Luis; Guerriero, Stefano; Ajossa, Silvia; Parodo, Giuseppina; Piras, Bruno; Peiretti, Michele; Jurado, Matías; Idoate, Miguel Ángel

    2012-01-01

    The diagnosis rate of deep pelvic endometriosis is increasing. Endometrial stromal sarcoma (ESS) is a rare neoplasm. Extragenital ESS is an extremely uncommon event. Very few cases of extragenital ESS have been reported to date. The diagnosis of this entity is very difficult in some instances. Knowledge about its management is also limited. In this paper, we review the current literature on the clinical management, histology, immunohistochemistry, treatment and outcome of ESS arising in pelvic endometriosis. PMID:22538201

  3. Diagnosis and Management of Synovial Sarcoma

    Microsoft Academic Search

    R. Lor Randall; Kathryn L. S. Schabel; Ying Hitchcock; David E. Joyner; Karen H. Albritton

    2005-01-01

    Opinion statement  Synovial sarcoma is a unique tumor with substantial promise for biologically targeted therapy. Although it demonstrates moderate\\u000a chemosensitivity, with approximately 50% response rates to ifosfamide- and doxorubicin-containing regimens, it has a diagnostic\\u000a translocation and a potentially informative chimeric protein product. Although surgical management remains the cornerstone\\u000a to effect local control, therapeutic advancements are unlikely to occur by continuing to

  4. Therapeutic effectiveness of selected protoporphyrin derivatives in treatment of lung sarcoma (sarcoma L1)

    NASA Astrophysics Data System (ADS)

    Pirozynska, E.; Kalczak, M.; Stanowski, Edward; Kupsc, M.; Graczyk, Alfreda; Konarski, Jerzy

    1995-03-01

    The effectiveness of two preparations used as photosensitizers in the photodynamic method for neoplasm treatment was examined. The material consisted of Balb/c strain mice with transplanted lung sarcoma, Sarcoma L1. Arginine derivative HpDArg2 (hematoporphyrin derivatives -- arginine) and PP(Phen2Arg2, i.e., 1-arginine di(N- phenylalanyl) protoporphyrinate, were used as photosensitizers. Animals were administered the photosensitizer in a dose of 10 mg/kg body weight. After 24 hrs they were irradiated with He-Ne laser; total energy of 150 J/cm2 was applied in three portions of 50 J/cm2 each, at 24-h intervals. The results showed that PP(Phen)2Arg2 destroyed Sarcoma L1 much more effectively than the conventionally used mixture of hematoporphyrin derivatives, customarily named HpD.

  5. Phenotypic factors affecting coagulation properties of milk from Sarda ewes.

    PubMed

    Pazzola, M; Dettori, M L; Cipolat-Gotet, C; Cecchinato, A; Bittante, G; Vacca, G M

    2014-11-01

    In this study, milk-coagulation properties (MCP) were characterized in the Sarda sheep breed. Milk composition and MCP [rennet-coagulation time (RCT), curd-firming time [time to reach a curd firmness of 20mm (k20)], and curd firmness (a30), (a45), and (a60)] were obtained extending the lactodynamographic analysis from 30 to 60 min from a population of 1,121 ewes from 23 different farms. Managerial characteristics of farms and parity, individual daily milk yields and stage of lactation of ewes were recorded. Data were analyzed using a mixed-model procedure with fixed effects of days in milk, parity, daily milk yield, and flock size and the random effect of the flock/test day nested within flock size. Sampled farms were classified as small (<300 ewes) and medium (300 to 600 ewes), and these were kept by family operations, or as large (>600 ewes), often operated through hired workers. Daily milk yield was, on average, 1.58 ± 0.79 L/d and variability for this trait was very high. The average content of fat, protein, and casein was respectively 6.41, 5.39, and 4.20%. The class of flock size had a significant effect only on curd firmness, whereas days in milk affected RCT and k20. The flock test day, parity, and daily milk yield were important sources of variation for all MCP. The mean value of RCT (8.6 min) and the low occurrence of noncoagulating samples (0.44%) confirmed the excellent coagulation ability of sheep milk compared with cattle milk. A more rapid coagulation was observed in mid-lactating, primiparous, and high-yielding ewes. The k20 was usually reached in less than 2 min after gelation, with the most favorable values at mid lactation. The mean value of curd firmness 30 min after rennet addition (a30) was, on average, 50mm and decreased to 46 and 42 mm respectively after 45 (a45) and 60 min (a60). The decreasing value of curd-firmness traits was likely to be caused by curd syneresis and whey expulsion. The correlation between RCT and a30 was much lower than in dairy cows and about null for a45 and a60. This means that curd firmness in dairy ewes is almost independent of gelation time and this can provide specific information for this species. In conclusion, this study showed that milk from Sarda sheep is characterized by an earlier gelation, a faster increase in curd firmness with time, and greater curd firmness after 30 min compared with dairy cows. Furthermore, correlations between MCP in sheep are much lower than in bovines and some of the assumptions and interpretations related to cows cannot be applied to sheep. PMID:25151884

  6. Comparison of Weigh-Suckle-Weigh and Machine Milking for Measuring Ewe Milk Production1,2

    Microsoft Academic Search

    M. E. Benson; M. J. Henry; R. A. Cardellino

    Thirteen crossbred ewes were used to compare weigh-suckle-weigh (WSW) and machine milking (MM) methods for determining milk produc- tion of ewes that were rearing single or twin lambs. At parturition, ewes were 13 mo of age and produced six single lambs and seven pairs of twin lambs. Milk production estimates were initiated on d 6 of lactation and a 3-d

  7. Endometrial stromal sarcoma - the new genetic paradigm.

    PubMed

    Lee, Cheng-Han; Nucci, Marisa R

    2015-07-01

    Endometrial stromal sarcoma (ESS) is a gynaecological sarcoma that is composed of cells that resemble those of proliferative-phase endometrial stroma. The 2014 World Health Organization tumour classification system separates ESS into low-grade and high-grade types, which are histologically, genetically and clinically distinct from undifferentiated uterine sarcoma (UUS). Low-grade ESSs frequently contain chromosomal rearrangements that result in JAZF1-SUZ12 fusion or equivalent genetic fusions. Although most low-grade ESSs show classic histological features that closely resemble those of proliferative-phase endometrial stroma, there are several histological variants that are associated with the same genetic fusions as seen in the classic type. High-grade ESS is defined by the presence of YWHAE-NUTM2A/B (YWHAE-FAM22A/B) fusions. High-grade ESSs are clinically more aggressive than low-grade ESSs, but are associated with a lower mortality rate than UUSs. The histological and immunophenotypic features of these different types of ESS, and their diagnostic considerations, are the subjects of this review. PMID:25355621

  8. 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

  9. Histiocytic sarcoma with fatal duodenal ulcers.

    PubMed

    Akishima, Yuri; Akasaka, Yoshikiyo; Yih-Chang, Ger; Ito, Kinji; Ishikawa, Yukio; Lijun, Zhang; Kiguchi, Hideko; Lipscomb, Gary; Strong, Jack P; Ishii, Toshiharu

    2004-01-01

    Histiocytic sarcoma is an uncommon neoplasm of mature histiocytes with very poor outcome. We report an autopsy case of a true histiocytic sarcoma with characteristic symptoms of so-called "malignant histiocytosis of the intestine". The liver and spleen were enlarged, with remarkable tumor cell infiltration in the hepatic sinusoids and splenic sinuses. Tumor cells aggregated to form sporadic nodular lesions in the liver, which often showed coagulative necrosis. Infarcted lesions also occurred at the splenic subcapsular area. In addition, tumor cell infiltration was noted in the sinuses of bone marrow and lymph node. Tumor cells often demonstrated moderate pleomorphism with multinucleated giant cells. They were positive for CD68 and negative for T- and B-cell lineage markers, megakaryocytic markers, and CD30. Various examinations were done to rule out infection-associated hemophagocytic syndrome, and the absence of infectious diseases was revealed. Thus, the diagnosis of histiocytic sarcoma was made. Apart from these lesions, multiple ulcerations, some with fatal perforation, were found in the esophagus and duodenum. They showed only non-specific inflammatory changes without tumor cell involvement. The ulcers probably derived from ischemic condition through an embolic process caused by tumor cell infiltration elsewhere in the blood vessels at the periphery of the ulcers. PMID:15310151

  10. 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

  11. Original article Iodine nutrition in ewes : effects of low to high iodine

    E-print Network

    Boyer, Edmond

    Original article Iodine nutrition in ewes : effects of low to high iodine intake on iodine content; In a first experiment, 2 groups of 46 and 47 multiparous ewes received diets which provided an iodine intake inorganic iodine (Pit) was less affected by the I intake during lactation than during preg- nancy

  12. 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...

  13. LOW FERTILITY IN NURSING EWES DURING THE NON-BREEDING SEASON

    E-print Network

    Paris-Sud XI, Université de

    LOW FERTILITY IN NURSING EWES DURING THE NON-BREEDING SEASON Y. COGNIE, M. HERNANDEZ-BARRETO J, regardless of the month of the year. However, the fertility after artificial insemination at the induced-lambings-per-year programme the lowest fertility is found in nursing ewes during the period of lactation anoestrus. When

  14. Responses of dairy ewes before and after parturition to different nutritional regimes during pregnancy.

    E-print Network

    Paris-Sud XI, Université de

    pregnancy. III. — The concentration of some metabolites in the blood during pregnancy D. STERN, J. H of several metabolites in the blood of ewes in late pregnancy are described. The ewes were included in a 3 x during late pregnancy was positively correlated with glucose and negatively correlated with FFA

  15. Salmonella Indiana as a cause of abortion in ewes: Genetic diversity and resistance patterns

    Microsoft Academic Search

    I. Luque; A. Echeita; J. León; S. Herrera-León; C. Tarradas; R. González-Sanz; B. Huerta; R. J. Astorga

    2009-01-01

    Salmonella enterica subspecies enterica Indiana, a food-borne serovar uncommon in most countries, was responsible for an outbreak of abortion in a flock of Lacaune dairy ewes in southern Spain. Drinking water and feedstuff samples were analysed in an attempt to determine the source of the infection. Pigeons (Columba livia) and turtledoves (Streptopelia turtur) in close contact with the ewes were

  16. 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 born to shorn ewes have...

  17. Effect of propylene glycol on pre- and postpartum performance by dairy ewes

    Microsoft Academic Search

    V. Chiofalo; M. Todaro; L. Liotta; S. Margiotta; T. Manzo; G. Leto

    2005-01-01

    This study was carried out in order to determine the effects, after feeding propylene glycol to Valle del Belice ewes 30 days prepartum and 30 days postpartum, on metabolic profiles, body-condition score, milk yield, milk composition, milk clotting ability and the performance of suckling lambs. Ewes were blocked by parity, body-condition score and previous milk production, and assigned randomly to

  18. Fetal and maternal lesions in pregnant ewes ingesting locoweed (Astragalus lentiginosus).

    PubMed

    Hartley, W J; James, L F

    1975-06-01

    Locoweed (Astragalus lentiginosus) was fed to ewes from 70 to 100 days of pregnancy. Ewes were killed at 100, 115, 130, and 145 days, and selected tissues were collected from both the dam and the fetus for histologic examination. Neurovisceral cytoplasmic vacuolation and neuroaxonal dystrophy decreased in dam and fetus with time after the feeding of locoweed was discontinued. PMID:1147336

  19. Effect of dietary animal fat and methionine on dairy ewes milk yield and milk composition

    Microsoft Academic Search

    C Goulas; G Zervas; G Papadopoulos

    2003-01-01

    The effect of supplemental animal fat, or animal fat and rumen protected methionine, on lactating dairy ewes production was evaluated in the present study. Twelve dairy pregnant ewes of the Karagouniko breed, with two embryos, were allocated to three groups (treatments), in order to examine the effect of three diets: control (C), diet with animal fat at 7% of concentrates’

  20. Genetic correlations between body weight change and reproduction traits in Merino ewes depend on age.

    PubMed

    Rose, G; Mulder, H A; van der Werf, J H J; Thompson, A N; van Arendonk, J A M

    2014-08-01

    Merino sheep in Australia experience periods of variable feed supply. Merino sheep can be bred to be more resilient to this variation by losing less BW when grazing poor quality pasture and gaining more BW when grazing good quality pasture. Therefore, selection on BW change might be economically attractive but correlations with other traits in the breeding objective need to be known. The genetic correlations (rg) between BW, BW change, and reproduction were estimated using records from approximately 7,350 fully pedigreed Merino ewes managed at Katanning in Western Australia. Number of lambs and total weight of lambs born and weaned were measured on approximately 5,300 2-yr-old ewes, approximately 4,900 3-yr-old ewes, and approximately 3,600 4-yr-old ewes. On a proportion of these ewes BW change was measured: approximately 1,950 2-yr-old ewes, approximately 1,500 3-yr-old ewes, and approximately 1,100 4-yr-old ewes. The BW measurements were for 3 periods. The first period was during mating period over 42 d on poor pasture. The second period was during pregnancy over 90 d for ewes that got pregnant on poor and medium quality pasture. The third period was during lactation over 130 d for ewes that weaned a lamb on good quality pasture. Genetic correlations between weight change and reproduction were estimated within age classes. Genetic correlations were tested to be significantly greater magnitude than 0 using likelihood ratio tests. Nearly all BW had significant positive genetic correlations with all reproduction traits. In 2-yr-old ewes, BW change during the mating period had a positive genetic correlation with number of lambs weaned (rg = 0.58); BW change during pregnancy had a positive genetic correlation with total weight of lambs born (rg = 0.33) and a negative genetic correlation with number of lambs weaned (rg = -0.49). All other genetic correlations were not significantly greater magnitude than 0 but estimates of genetic correlations for 3-yr-old ewes were generally consistent with these findings. The direction of the genetic correlations mostly coincided with the energy requirements of the ewes and the stage of maturity of the ewes. In conclusion, optimized selection strategies on BW changes to increase resilience will depend on the genetic correlations with reproduction and are dependent on age. PMID:24879756

  1. Progesterone improves the maturation of male-induced preovulatory follicles in anoestrous ewes.

    PubMed

    Adib, Achraf; Freret, Sandrine; Touze, Jean-Luc; Lomet, Didier; Lardic, Lionel; Chesneau, Didier; Estienne, Anthony; Papillier, Pascal; Monniaux, Danielle; Pellicer-Rubio, Maria-Teresa

    2014-10-01

    The first ovulation induced by male effect in sheep during seasonal anoestrus usually results in the development of a short cycle that can be avoided by progesterone priming before ram introduction. In elucidating the involvement of the hypothalamic-pituitary-gonadal axis in the occurrence of short cycles, the effects of progesterone and the time of anoestrus on the development of male-induced preovulatory follicles were investigated in anoestrous ewes using morphological, endocrine and molecular approaches. Ewes were primed with progesterone for 2 (CIDR2) or 12 days (CIDR12) and untreated ewes used as controls during early (April) and late (June) anoestrus. The duration of follicular growth and the lifespan of the male-induced preovulatory follicles were prolonged by ?1.6 days in CIDR12 ewes compared with the controls. These changes were accompanied by a delay in the preovulatory LH and FSH surges and ovulation. Intra-follicular oestradiol concentration and mRNA levels of LHCGR and STAR in the granulosa and theca cells of the preovulatory follicles were higher in CIDR12 ewes than the control ewes. The expression of mRNA levels of CYP11A1 and CYP17A1 also increased in theca cells of CIDR12 ewes. CIDR2 ewes gave intermediate results. Moreover, ewes ovulated earlier in June than in April, without changes in the duration of follicular growth, but these effects were unrelated to the lifespan of corpus luteum. Our results give the first evidence supporting the positive effect of progesterone priming on the completion of growth and maturation of preovulatory follicles induced by male effect in seasonal anoestrous ewes, thereby preventing short cycles. PMID:25062803

  2. 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.

  3. The structure of the Rous sarcoma virus glycoprotein complex

    Microsoft Academic Search

    G. Pauli; W. Rohde; E. Harms

    1978-01-01

    Summary The viral envelope glycoprotein gp85 is released from purified Rous sarcoma virus by treatment with 2-mercaptoethanol, while the second surface antigen gp35 remains associated with the membrane of intact virus particles. The data represented substantiate and extend previous observations on the Rous sarcoma virus glycoprotein complex.

  4. Sirolimus for Kaposi's Sarcoma in Renal-Transplant Recipients

    Microsoft Academic Search

    Giovanni Stallone; Antonio Schena; Barbara Infante; Salvatore Di Paolo; Antonella Loverre; Giulio Maggio; Elena Ranieri; Loreto Gesualdo; Francesco Paolo Schena; Giuseppe Grandaliano

    2005-01-01

    background Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treat- ment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects. methods We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy- proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an exci- sional biopsy of the lesion and one

  5. Significance of Circulating Tumor Cells in Soft Tissue Sarcoma

    PubMed Central

    Nicolazzo, Chiara; Gradilone, Angela

    2015-01-01

    Circulating tumor cells can be detected from the peripheral blood of cancer patients. Their prognostic value has been established in the last 10 years for metastatic colorectal, breast, and prostate cancer. On the contrary their presence in patients affected by sarcomas has been poorly investigated. The discovery of EpCAM mRNA expression in different sarcoma cell lines and in a small cohort of metastatic sarcoma patients supports further investigations on these rare tumors to deepen the importance of CTC isolation. Although it is not clear whether EpCAM expression might be originally present on tumor sarcoma cells or acquired during the mesenchymal-epithelial transition, the discovery of EpCAM on circulating sarcoma cells opens a new scenario in CTC detection in patients affected by a rare mesenchymal tumor. PMID:26167450

  6. Superficial soft tissue sarcomas (S-STS): A study of 367 patients from the French Sarcoma Group (FSG) database

    Microsoft Academic Search

    Sébastien Salas; Eberhard Stoeckle; Françoise Collin; Binh Bui; Philippe Terrier; Louis Guillou; Martine Trassard; Dominique Ranchere-Vince; Fleur Gregoire; Jean-Michel Coindre

    2009-01-01

    AimThe specific natural history of superficial soft tissue sarcomas (S-STS) has been rarely considered. We describe the clinical characteristics of a large series of S-STS (N=367) from the French Sarcoma Group (GSF-GETO) database and analyse the prognostic factors affecting outcome.

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

    ClinicalTrials.gov

    2015-06-08

    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

  8. Case of clear cell sarcoma in the left buttock in which serum neuron-specific enolase was a useful marker for monitoring disease progression.

    PubMed

    Takamura, Saori; Teraki, Yuichi

    2015-06-01

    We report a case of clear cell sarcoma (CCS) in the left buttock in which serum neuron-specific enolase (NSE) was useful as a biomarker of CCS progression. A 40-year-old man had a subcutaneous tumor, 1.7 cm in diameter, in the left buttock. Histopathology revealed that the tumor consisted of nests of polygonal or spindle-shaped cells with abundant clear cytoplasm delineated by fibrous septa in the subcutaneous tissue. There was cellular atypia but no melanin deposits. Immunohistochemically, the tumor cells were positive for HMB-45, Melan-A, S-100 protein and NSE. Reverse transcription polymerase chain reaction demonstrated Ewing's sarcoma oncogene-activating transcription factor 1 fusion transcripts in the tumor cells. CCS was diagnosed. There was no metastasis to the lymph nodes and viscera, and the patient was treated by surgical wide resection. The serum NSE levels increased before detection of distant metastasis and further increased in parallel with the expansion of metastasis. The present case suggests that serum NSE could be used as a biochemical marker in the clinical follow up of patients with CCS. PMID:25809881

  9. Outcome analysis in patients with uterine sarcoma

    PubMed Central

    Yu, Tosol; Wu, Hong-Gyun; Ha, Sung Whan; Song, Yong-Sang; Park, Noh-Hyun; Kim, Jae-Won

    2015-01-01

    Purpose To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. Materials and Methods We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). Results The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. Conclusion The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns. PMID:25874175

  10. Energy and protein metabolism in sarcoma patients.

    PubMed Central

    Shaw, J H; Humberstone, D M; Wolfe, R R

    1988-01-01

    We have performed a series of isotopic infusions both in normal volunteers (N = 16) and in sarcoma patients (N = 7). Using the primed-constant infusion of stable or radioisotopes we have determined the rates of glucose turnover, glucose oxidation, glucose recycling, and net protein catabolism (NPC). In addition, we have measured VO2 and VCO2. The values for VCO2 and VO2 were higher in the patients than in the volunteers (mean VO2 values in volunteers and patients: 107 +/- 13 and 158 +/- 13 mumol/kg/min, respectively). The basal rate of glucose appearance in the sarcoma patients was twice the value seen in the volunteers (28.3 +/- 3.5 vs. 13.9 +/- 0.3 mumol/kg/min). Glucose infusion in the volunteers resulted in virtually total suppression of endogenous glucose production, while in the patients glucose infusion induced only a 30% suppression of endogenous glucose production (p less than 0.01). The rate of glucose clearance in the patients was approximately twice the value seen in the volunteers [5.4 +/- 1.0 vs. 2.7 +/- 0.1 mL/kg/min (p less than 0.01)]. The per cent of glucose uptake oxidized in the patients was significantly less than in the volunteers [22% vs. 36% (p less than 0.05)], and the per cent of glucose uptake that was recycled was significantly higher in the patients [55% vs. 10% (p less than 0.01)]. In addition, the basal rate of net protein loss was increased twofold in the patients [3.2 +/- 0.5 vs. 1.4 +/- 0.4 g (protein)/kg/d (p less than 0.01)], and in contrast to the situation in the volunteers there was no suppression in the rate of net protein loss when the patients were infused with glucose. The basal insulin concentration and the insulin response to glucose infusion in the patients were similar to that of the volunteers, but the plasma cortisol level was similar in volunteers and in the patients (p less than 0.05). We conclude from these studies the following: (1) Sarcoma patients have significantly elevated rates of glucose production and glucose clearance, but they have an impaired capacity to directly oxidize either endogenous or infused glucose, coupled with an increased rate of glucose recycling. (2) Sarcoma patients have an elevated metabolic rate and are catabolic. In addition, in contrast with normal volunteers, glucose infusion does not result in a suppression of protein loss. PMID:3422801

  11. 100 years of Rous sarcoma virus.

    PubMed

    Weiss, Robin A; Vogt, Peter K

    2011-11-21

    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

  12. Fifty-one Kaposi sarcoma patients

    Microsoft Academic Search

    Mutlu Dogan; Lutfi Dogan; Feyyaz Ozdemir; Nuriye Yildirim Ozdemir; Hasan Senol Coskun; Ulku Yalcintas Arslan; Guze Ozal; Gungor Utkan; Ahmet Demirkazik; Fazil Aydin; Nurullah Zengin; Fikri Icli

    2010-01-01

    Introduction  Kaposi sarcoma (KS) is a mesenchymal tumor originating from lymphatic endothelial cells. Immunsupressive patients have higher\\u000a risk for KS. HHV-8 has a role in immunpathogenesis of KS.\\u000a \\u000a \\u000a \\u000a \\u000a Aim  Evaluation of demographical properties with tumor characteristics and treatment modalities of KS.\\u000a \\u000a \\u000a \\u000a Material and method  Histopathologically documented KS patients were evaluated retrospectively. Anti-HIV seroprevalence was also evaluated with\\u000a patient and tumor characteristics besides treatment

  13. The radiotherapeutic management of chordoid sarcoma

    SciTech Connect

    Hitchon, H.; Nobler, M.P.; Wohl, M.; Levy, W. (Albert Einstein Medical Center, Philadelphia, PA (USA))

    1990-06-01

    Chordoid sarcoma is a rare neoplasm, with only 13 cases reported. In the past, the treatment of choice was excision or amputation, with radiation therapy reserved for metastases. This case report demonstrates the persistent nature and indolent course the tumor may have and its good response to high-dose irradiation. External beam irradiation, both photons and electrons, intraoperative radiation therapy, and 192-iridium implantation have all been successfully utilized for treatment of multiple recurrences in this patient. Doses of 6,000 cGy or greater were necessary to control the tumor in our patient, and this dose is recommended as adjuvant treatment following conservative (gross) tumor removal.

  14. Effects of residual feed intake classification and method of alfalfa processing on ewe intake and growth.

    PubMed

    Redden, R R; Surber, L M M; Grove, A V; Kott, R W

    2014-02-01

    The objective of this research was to evaluate the effects of residual feed intake (RFI) determined under ad libitum feeding conditions on DMI and performance of yearling ewes fed either chopped or pelleted alfalfa hay. In Exp. 1, 45 ewe-lambs had ad libitum access to a pelleted grower diet for 63 d and individual DMI was determined using an electronic feed delivery system. Residual feed intake values were assigned to each ewe-lamb as a measure of feed efficiency. Sixteen ewe-lambs with the most positive RFI values were classified as high RFI (inefficient) and 16 ewe-lambs with the most negative RFI values were classified as low RFI (efficient). In Exp. 2, half of the ewes from each efficiency group were placed into 1 of 2 pens and provided ad libitum access to either pelleted or chopped alfalfa hay. Individual DMI was again determined using an electronic feed delivery system. Body weight, LM area (LMA), and 12th-rib back fat thickness (BF) were measured at the beginning and end of both experiments. In Exp. 1, DMI by ewe-lambs in the low RFI group was 9% less (P = 0.01) than by ewe-lambs in the high RFI group (2.21 vs. 2.43 kg/d); however, ADG and initial and final BW, LMA, and BF did not differ (P > 0.27) among RFI groups. In Exp. 2, there were no feed processing × RFI group interactions (P > 0.14) for any trait. By design, RFI values were lower (P < 0.01) by yearling ewes in the low than high RFI group (-0.27 vs. 0.27); however, RFI values did not differ (P = 1.0) between yearling ewes fed chopped versus pelleted alfalfa. Dry matter intake was 22% less (P < 0.01) by yearling ewes in the low than high RFI group (2.5 vs. 3.2 kg/d) and 59% less (P < 0.01) by yearling ewes fed chopped versus pelleted alfalfa (2.2 vs. 3.5 kg/d). Initial and final BW, ADG, and G:F did not differ (P > 0.45) between RFI groups but were greater (P < 0.01) by yearling ewes fed pelleted alfalfa compared to chopped alfalfa. Final LMA did not differ (P = 0.77) between RFI groups, but final BF tended to be greater (P = 0.06) for high than low RFI yearling ewes (0.63 vs. 0.57 cm). Final LMA and BF were greater (P < 0.01) by yearling ewes fed pelleted than chopped alfalfa. Low RFI ewes had lower DMI and BF compared to high RFI ewes. Ewe efficiency as determined by RFI was repeatable on subsequent forage based diets; however, differences in intake and efficiency were more apparent when alfalfa was pelleted. PMID:24664570

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Ram mating behavior after long-term selection for reproductive rate in Rambouillet ewes.

    PubMed

    Stellflug, J N; Berardinelli, J G

    2002-10-01

    Mating behavior is known to be heritable in several species, but it is not known if selection schemes for ewe reproductive traits affect mating behavior of rams. Therefore, our objectives were to determine if divergent (high vs low index) selection of a female reproductive trait (lambs born divided by age of ewe minus one) affects mating behavior patterns of male offspring during training to service an artificial vagina (AV) in a less than natural setting (Exp. 1) or during serving capacity tests (SCT) in simulated natural mating conditions (Exp. 2). The method for evaluating male mating behavior was a series of serving capacity tests to estimate sexual performance. For Exp. 1, five, 30-min observations were conducted to assess the mating behavior of 29 rams (22 mo old) being trained to service an AV. In Exp. 1, percentages of rams mounting (73 vs 36%) and ejaculating (67 vs 29%) differed (P < 0.05) between rams from high and low Rambouillet ewe selection lines, respectively. In Exp. 2, ram classification consisted of exposing each 22- to 24-mo-old ram (n = 48) to three unrestrained ewes in estrus for 18, 30-min tests. Any ram that had not mounted or ejaculated during SCT was evaluated for sexual orientation in a 30-min preference test in which each ram had access to both restrained estrual ewes and restrained rams. In Exp. 2, there was no difference (P > 0.2) in percentages of rams mounting (92 vs 78%) and ejaculating (88 vs 74%) between rams from high and low Rambouillet ewe selection lines, respectively. There was no difference (P > 0.33) between high and low ewe selection line rams for mounts or ejaculations for 18 SCT. Only one male-oriented ram was identified, which was from the high line. In Exp. 2, six SCT were necessary to obtain 95% reliability in sexual performance scores. Results of these studies indicate that long-term selection of ewes for litter size did not alter ram sexual performance after SCT under simulated natural mating conditions or affect incidence of male-oriented rams. Mating behavior observed during training to service an AV was lower for rams from ewes of the low selection line than for rams from ewes of the high selection line. We concluded that long-term selection for reproductive rate in ewes did not alter mating behavior patterns of male offspring; however, test conditions, such as restrained and unrestrained ewes and number of serving capacity tests, may affect conclusions in studies that evaluate sexual performance of rams. PMID:12413080

  20. Prognostic factors in patients with jaw sarcomas.

    PubMed

    Vadillo, Rafael Morales; Contreras, Sonia Julia Sacsaquispe; Canales, Janet Ofelia Guevara

    2011-01-01

    The aim of this study was to identify the prognostic factors related to the survival of patients with sarcomas of the jaw treated in the Dr. Eduardo Caceres Graziani National Institute for Neoplastic Diseases, Lima, Peru. Age, gender, delay in consultation, diagnostic delay, therapeutic delay, tumor size, tumor location, facial asymmetry, pain, treatment type, and histopathological diagnosis were all evaluated as possible prognostic factors that would influence survival in those with jaw sarcomas. In the analysis, the following was used: mortality tables, Kaplan-Meier's product-limit method, log-rank, and Breslow and Tarone-Ware tests; for the prognostic factors, Cox's Regression Model was used. The overall survival rate, with the patient being free from disease at two years, was 55%, and that at five years was 45%. In the independent analysis of the prognostic factors, four variables were statistically significant in influencing survival: gender (p = 0.043), histopathologic diagnosis (p = 0.019), tumor location (p = 0.019), and treatment type (p = 0.030). According to Cox's Regression Model for the multivariate analysis, statistically significant prognostic factors were: gender (p = 0.086), tumor location (p = 0.020), and treatment type (p = 0.092). Thus, the variables of gender, tumor location, and treatment type were determined to be predictive factors for prognosis of survival. PMID:22031055

  1. Endometrial stromal sarcoma arising in vagina.

    PubMed

    Liu, Zhaoxia; Ding, Jiao; Li, Xia; Yu, Kehan

    2013-01-01

    Endometrial stromal sarcoma (ESS) arising in the vagina is an extremely rare extrauterine endometrial stroma sarcoma, with only 4 cases reported in the literature up to date. Here we report a case of neoplasm originating from vagina. A 32-year-old woman complained of intermittent vaginal bleeding especially after intercourse. A mass with a diameter of 1.0 cm was found in the middle and upper segments of the right posterior vaginal wall. Biopsy showed ESS. Total abdominal hysterectomy, unilateral salpingo-oophorectomy (right) and partial vaginectomy were performed. No ESS lesion was found in endometrium. The patient received six courses of platinum-containing combination chemotherapy after surgery and was free of tumor 18 months after the diagnosis of ESS. The diagnosis of ESS relies on pathologic examination. CD10 is the most useful immunohistochemical marker for the diagnosis of this tumor. The mainstay treatment of ESS is surgery. Local excision and ovarian retaining may be considered in premenopausal women. PMID:24294390

  2. Multiple granulocytic sarcomas in essential thrombocythemia.

    PubMed

    Tanaka, Yasuhiro; Nagai, Yuya; Mori, Minako; Fujita, Haruyuki; Togami, Katsuhiro; Kurata, Masayuki; Matsushita, Akiko; Maeda, Akinori; Nagai, Kenichi; Tanaka, Kyoko; Takahashi, Takayuki

    2006-12-01

    A 59-year-old woman was diagnosed with essential thrombocythemia in 1988 and had been treated with hydroxyurea, mitobronitol, busulfan, and ranimustine, in that order. Hepatosplenomegaly, low-grade fever, and body weight loss manifested, and a few blasts were noted in the peripheral blood studied in March 2002. A biopsied specimen of the bone marrow showed myelofibrosis but not a leukemia in August 2004. An abnormal karyotype with der(1; 13) appeared for the first time. She was treated with low-dose prednisolone. In January 2005, she experienced left hip joint pain, and magnetic resonance scanning showed a tumoral lesion in the femoral head. Histological diagnosis of the biopsied mass revealed that it was a granulocytic sarcoma, and radiotherapy was performed. In April 2005, bone scintigraphy showed multiple lesions. She became febrile and red blood cell transfusion-dependent with hepatosplenomegaly and a small number of circulating blasts. Intravenous cytarabine (low dose) and etoposide relieved the fever and hepatosplenomegaly; however, she developed a pathologic fracture of the right humerus. An additional karyotypic abnormality (7q22 deletion) was noted. She subsequently died of infection. Granulocytic sarcoma is very rare in essential thrombocythemia, and this patient may be the first reported case of essential thrombocythemia that developed multiple lesions and a pathologic fracture without transformation to overt leukemia. PMID:17189221

  3. Multidisciplinary Management of Soft Tissue Sarcoma

    PubMed Central

    Nystrom, Lukas M.; Reimer, Nickolas B.; Reith, John D.; Dang, Long; Zlotecki, Robert A.; Scarborough, Mark T.; Gibbs, C. Parker

    2013-01-01

    Soft tissue sarcoma is a rare malignancy, with approximately 11,000 cases per year encountered in the United States. It is primarily encountered in adults but can affect patients of any age. There are many histologic subtypes and the malignancy can be low or high grade. Appropriate staging work up includes a physical exam, advanced imaging, and a carefully planned biopsy. This information is then used to guide the discussion of definitive treatment of the tumor which typically involves surgical resection with a negative margin in addition to neoadjuvant or adjuvant external beam radiation. Advances in imaging and radiation therapy have made limb salvage surgery the standard of care, with local control rates greater than 90% in most modern series. Currently, the role of chemotherapy is not well defined and this treatment is typically reserved for patients with metastatic or recurrent disease and for certain histologic subtypes. The goal of this paper is to review the current state of the art in multidisciplinary management of soft tissue sarcoma. PMID:23983648

  4. Adjuvant chemotherapy for soft tissue sarcoma.

    PubMed

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  5. [Experience in the treatment of breast sarcomas].

    PubMed

    Farkas, E; Orosz, Z; Kovács, T; Köves, I

    1997-01-26

    Authors operated on 6339 malignant breast tumors at the Department of Surgery, National Institute on Oncology between 1980 and 1994. The records of 14 patients with sarcomas of the breast were analyzed. These included 2 malignant phyllodes tumors, 3 malignant fibrous histiocytomas, 2-2 fibrosarcomas and carcinosarcomas and liposarcoma, angiosarcoma, leiomyosarcoma, osteosarcoma and dermatofibrosarcoma protuberans one of each. During this period 5 patients died, 9 are living without evidence of tumor. Analysing these 14 cases authors present their policy in surgical therapy of breast sarcomas compared with literature data. They emphasise the importance of wide resection margins for prevention of tumor progression. The above mentioned principle is valid for local recurrences so radicalization of the previous conservative breast surgery may be necessary in selected cases. Intraoperative histological examination is recommended to verify that the resection margins are tumor free. Axillary block dissection is not necessary except in cases when palpable, firm lymph nodes are present in the region. Depending on the histological grade adjuvant radiotherapy could be considered but its effectiveness is not proven. PMID:9072752

  6. Follicular dendritic cell sarcoma of the neck with pulmonary metastases.

    PubMed

    Fareed, Muhammad Mohsin; Memon, Muhammad Ali; Rashid, Azhar; Furrukh, Muhammad; Ahmed, Shoaib; Ghouri, Abdul Rauf; Khan, Amjad; Asghar, Abdul Shaheed

    2011-09-01

    We present a case of follicular dendritic cell sarcoma in a 48 years old Saudi female who reported with slowly progressive right sided extranodal neck mass associated with pulmonary metastasis. Clinical examination, histopathologic features including distinct immunostains combine together to make the rare diagnosis of follicular dendritic cell sarcoma. This entity is often misdiagnosed due to non-consideration in differential diagnosis of sarcoma. It carries a significant potential for regional as well as distant spread and hence categorized as intermediate risk malignancy. Clinical, histopathological and immunohistochemical aspects and therapeutic options of this unusual case are discussed. PMID:21914416

  7. Testicular granulocytic sarcoma, a source of diagnostic confusion.

    PubMed

    Constantinou, J; Nitkunan, T; Al-Izzi, M; McNicholas, T A

    2004-10-01

    We report a case of granulocytic sarcoma of the testis without hematologic manifestations. The patient was disease free 7 years after the initial presentation. The initial pathology interpretation favored a diagnosis of high-grade non-Hodgkin's lymphoma but additional histologic staining confirmed the diagnosis of granulocytic sarcoma. Only 2 cases of testicular granulocytic sarcoma without an associated hematologic disorder have been described. To our knowledge, this is the third reported case. The diagnosis of this rare tumor is difficult and should be in the differential diagnosis when non-Hodgkin's lymphoma is considered. PMID:15491733

  8. Biological Extremity Reconstruction after Sarcoma Resection: Past, Present, and Future

    PubMed Central

    Holzer, Lukas A.; Leithner, Andreas

    2013-01-01

    In sarcoma surgery besides a wide local resection, limb salvage became more and more important. Reconstruction of bone and soft tissue defects after sarcoma resection poses a major challenge for surgeons. Nowadays a broad range of reconstructive methods exist to deal with bony defects. Among these are prostheses, bone autografts, or bone allografts. Furthermore a variety of plastic reconstructive techniques exist that allow soft tissue reconstruction or coverage after sarcoma resection. Here we discuss the historical highlights, the present role, and possible future options for biological reconstruction. PMID:23840167

  9. 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

  10. Radiotherapy to Improve Local Control Regardless of Surgical Margin and Malignancy Grade in Extremity and Trunk Wall Soft Tissue Sarcoma: A Scandinavian Sarcoma Group Study

    Microsoft Academic Search

    Nina L. Jebsen; Clement S. Trovik; Henrik C. F. Bauer; Anders Rydholm; Odd R. Monge; Kirsten Sundby Hall; Thor Alvegård; Øyvind S. Bruland

    2008-01-01

    Purpose: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. Methods and Materials: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers

  11. 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 ...

  12. EFFECTS OF INFECTION ON PLASMA LEVELS OF COPPER AND ZINC IN EWES

    E-print Network

    Paris-Sud XI, Université de

    examen de la cuprémie et des paramètres traduisant l'inflammation. Une hypozincémie d'inflam- mation ne chronic metritis, mastitis or age. The ewes were fed ad libitum a good quality hay con- #12;taining 9 mg

  13. 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

    A homogeneous group of thirty-one crossbred ewes was used to determine the effect of administering a progesterone Controlled Intravaginal Drug Releasing Device (CIDR) on circulating levels of progesterone in the subsequent cycle following CIDR...

  14. ELIMINATION OF (14C) HEPTACHLOR FROM BODY STORES OF LACTATING EWES TREATED WITH OVINE GROWTH HORMONE

    Microsoft Academic Search

    D. W. Holcombe; G. S. Smith; M. F. Khan; D. M. Hallford; K. Rozman

    2010-01-01

    Elimination of ( 14 C) heptachlor from body burdens of sheep was measured using mature ewes nursing single offspring, and the influence of exogenous ovine growth hormone (oGH) on elimination was studied. Six ewes (62 -+ 2.5 kg BW) were dosed (i.p.) once with ( 14C) hep- tachlor (2.04 mg\\/kg BW; .88 gCi\\/mg heptachlor) and three were treated additionally with

  15. Parenteral administration of L-arginine prevents fetal growth restriction in undernourished ewes.

    PubMed

    Lassala, Arantzatzu; Bazer, Fuller W; Cudd, Timothy A; Datta, Sujay; Keisler, Duane H; Satterfield, M Carey; Spencer, Thomas E; Wu, Guoyao

    2010-07-01

    Intrauterine growth restriction (IUGR) is a major health problem worldwide that currently lacks an effective therapeutic solution. This study was conducted with an ovine IUGR model to test the hypothesis that parenteral administration of l-arginine (Arg) is effective in enhancing fetal growth. Beginning on d 28 of gestation, ewes were fed a diet providing 100% (control-fed) or 50% (underfed) of NRC-recommended nutrient requirements. Between d 60 of gestation and parturition, underfed ewes received i.v. infusions of saline or 155 micromol Arg-HCl/kg body weight 3 times daily, whereas control-fed ewes received only saline. The birth weights of lambs from saline-infused underfed ewes were 23% lower (P < 0.01) than those of lambs from control-fed dams. Administration of Arg to underfed ewes increased (P < 0.01) concentrations of Arg (69%), ornithine (55%), proline (29%), methionine (37%), leucine (36%), isoleucine (35%), cysteine (19%), and FFA (43%) in maternal serum, decreased maternal circulating levels of ammonia (18%) and triglycerides (32%), and enhanced birth weights of lambs by 21% compared with saline-infused underfed ewes. There was no difference in birth weights of lambs between the control-fed and the Arg-infused underfed ewes. These novel results indicate that parenteral administration of Arg to underfed ewes prevented fetal growth restriction and provide support for its clinical use to ameliorate IUGR in humans. The findings also lay a new framework for studying cellular and molecular mechanisms responsible for the beneficial effects of Arg in regulating conceptus growth and development. PMID:20505020

  16. Scopolamine impairs the ability of parturient ewes to learn to recognise their lambs

    Microsoft Academic Search

    F. Lévy; Ph. Richard; M. Meurisse; N. Ravel

    1997-01-01

    Within a 4-h period after parturition, the ewe learns the odor of her lamb that will later allow recognition of her offspring\\u000a from an alien lamb. This study investigated the involvement of the cholinergic system in this olfactory learning. At parturition\\u000a and 2?h later, ewes received IM injections of saline (C group, n?=?21), scopolamine methylbromide (METSCOP group, 100??g\\/kg, n?=?14) a

  17. Radiation-Induced Changes of Telomerase Activity in a Human Ewing Xenograft Tumor

    Microsoft Academic Search

    Andreas Schuck; Christopher Poremba; Claudia Lanvers; Stefan Könemann; Tobias Schleifer; Daniel Wai; Kirsten Horn; Stefan Hesselmann; Yvonne Braun; Bernd Frodermann; Karl-Ludwig Schäfer; Raihanatou I. Diallo; Claudia E. Rübe; Christian Rübe; Barbara Dockhorn-Dworniczak; Normann Willich

    2002-01-01

    Aim: The effect of ionizing irradiation on telomerase activity and further associated biological factors was evaluated in a human Ewing tumor xenograft model on nude mice. Material and Methods: The human Ewing tumor cell line STA-ET-1 was established in a nude mouse model. Initially, the dose-response relationship for the tumor model was established. For the radiation experiments two dose levels

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

    MedlinePLUS

    ... soft tissue sarcoma. Exposure to dioxin and to herbicides that contain phenoxyacetic acid at high doses (such ... known for certain. There is no evidence that herbicides (weed killers) or insecticides, at levels encountered by ...

  19. Molecular diagnostics in soft tissue sarcomas and gastrointestinal stromal tumors.

    PubMed

    Smith, Stephen M; Coleman, Joshua; Bridge, Julia A; Iwenofu, O Hans

    2015-04-01

    Soft tissue sarcomas are rare malignant heterogenous tumors of mesenchymal origin with over fifty subtypes. The use of hematoxylin and eosin stained sections (and immunohistochemistry) in the morphologic assessment of these tumors has been the bane of clinical diagnosis until recently. The last decade has witnessed considerable progress in the understanding and application of molecular techniques in refining the current understanding of soft tissue sarcomas and gastrointestinal stromal tumors beyond the limits of traditional approaches. Indeed, the identification of reciprocal chromosomal translocations and fusion genes in some subsets of sarcomas with potential implications in the pathogenesis, diagnosis and treatment has been revolutionary. The era of molecular targeted therapy presents a platform that continues to drive biomarker discovery and personalized medicine in soft tissue sarcomas and gastrointestinal stromal tumors. In this review, we highlight how the different molecular techniques have enhanced the diagnosis of these tumors with prognostic and therapeutic implications. PMID:25772665

  20. Undifferentiated Pleomorphic Sarcoma of the Male Breast Causing Diagnostic Challenges

    PubMed Central

    Jeong, Young Ju; Oh, Hoon Kyu

    2011-01-01

    Undifferentiated pleomorphic sarcoma of the breast are uncommon and often present diagnostic challenges. Herein, we report a case of the undifferentiated pleomorphic sarcoma occurring in the male breast. A 76-year-old man presented with a palpable bean-sized mass in his left breast for two months. Core needle biopsy revealed the presence of atypical cells in a fibrous proliferative lesion, which was removed by wide excision. Based on examination of the excised tumor, the initial pathologic diagnosis was atypical spindle cell lesion with uncertain malignant potential. One year later, the patient returned with a recurrent mass atthe previous surgical site. The mass was again surgically removed using wide excision. Based on histological findings with immunomarkers, the final diagnosis was undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma of the breast can cause genuine diagnostic difficulty and appropriate immunohistochemistry is mandatory for differential diagnosis. PMID:22031808

  1. [Hemodynamics of right circulation in ewes: normal values].

    PubMed

    Martinot, S; Robin, J; Vedrinne, C; Franck, M; Champsaur, G

    1996-01-01

    The right cardiac pressure was measured on 24 anesthetized adult ewes (Halothane) with a Swan Ganz catheter. After a review of the catheterization technique, the results (mean +/- standard deviation) in mmHg were: right auricle 17 +/- 5, right ventricle 30 +/- 6 (systolic) and 12 +/- 6 (telediastolic), pulmonary artery 29 +/- 6 (systolic), 13 +/- 6 (diastolic) and 20 +/- 6 (mean), capillary pressure 17 +/- 7. We observed slight variations in the pressure curve morphology compared to those found for man and the pressures were 5-10 mmHg higher than what is observed in man and slightly higher than those observed in dogs. These results also demonstrate a great variation between animals. PMID:8620190

  2. Biopsy techniques for soft tissue and bowel sarcomas.

    PubMed

    Tuttle, Rebecca; Kane, John M

    2015-04-01

    There is overlap in the clinical presentation of benign soft tissue tumors and soft tissue sarcomas. A preoperative sarcoma diagnosis would allow for consideration for neoadjuvant therapy, including preoperative radiation, as well as optimal surgical treatment planning, and patient counseling. Image guided core needle biopsy is a low morbidity, cost-effective, highly accurate approach for obtaining a definitive pathologic diagnosis. Any biopsy approach should minimize the potential for tumor seeding of otherwise uninvolved anatomic structures. PMID:25663366

  3. Molecular virology of Kaposi's sarcoma-associated herpesvirus

    Microsoft Academic Search

    Patrick S. Moore; Yuan Chang

    2001-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), the most recently discovered human tumour virus, is the causative agent of Kaposi's sarcoma, primary e¡usion lymphoma and some forms of Castleman's disease. KSHV is a rhadinovirus, and like other rhadinoviruses, it has an extensive array of regulatory genes obtained from the host cell genome. These pirated KSHV proteins include homologues to cellular CD21, three di¡erent

  4. Contemporary Management of Retroperitoneal Soft Tissue Sarcomas.

    PubMed

    Olimpiadi, Yuliya; Song, Suisui; Hu, James S; Matcuk, George R; Chopra, Shefali; Eisenberg, Burton L; Sener, Stephen F; Tseng, William W

    2015-08-01

    Management of retroperitoneal soft tissue sarcomas (RP STS) can be very challenging. In contrast to the more common extremity STS, the two predominant histologic subtypes encountered in the retroperitoneum are well-differentiated/dedifferentiated liposarcoma and leiomyosarcoma. Surgery remains the mainstay of treatment for RP STS. Preoperative planning and anticipation of the need for resection of adjacent organs/structures are critical. The extent of surgery, including the role of compartmental resection, is still controversial. Radiation therapy may be an important adjunct to surgery to provide locoregional disease control; this is currently being evaluated in the preoperative setting in the EORTC STRASS trial. Systemic therapy, tailored to the specific histologic subtype, may also be of benefit for the management of RP STS. Further investigation of novel therapies (e.g., targeted therapies, immunotherapy) is needed. Overall, multi-institutional collaboration is important moving forward, to continue to better understand and optimize management of this disease. PMID:26092408

  5. Granulocytic sarcoma: report of three cases.

    PubMed

    Mwanda, W O; Rajab, J A

    1999-10-01

    Granulocytic sarcoma (GS) is a rare extramedullary solid tumour composed of malignant immature cells of the granulocytic series. It may herald, accompany or signal acute myeloid leukaemia (AML) or chronic granulocytic leukaemia (CGL). GS may also occur in patients with myelodysplastic syndromes (MDS) where it is a sign of imminent disease progression. Three cases of GS are presented; the first one involving the pancreas and preceding AML, the second case affecting uterine cervix in stable phase CGL and the third case is GS of the breast accompanying AML. Any site of the body may be involved by the GS, and morbidity depends on the local organ/tissue affected in addition to the attending primary leukaemia or MDS. Treatment of GS involves surgery, radiotherapy and chemotherapy. The objective of this communication is to enhance awareness in personnel providing health care. Further, early diagnosis and treatment affects overall outcome. PMID:10734514

  6. Soft tissue sarcoma and occupational exposures

    SciTech Connect

    Wingren, G.; Fredrikson, M.; Brage, H.N.; Nordenskjoeld, B.A.; Axelson, O. (University Hospital, Linkoeping (Sweden))

    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. Metabolic adaptations to pregnancy and lactation in German Blackheaded Mutton and Finn sheep ewes with different susceptibilities to pregnancy toxaemia

    Microsoft Academic Search

    R. Duehlmeier; I. Fluegge; B. Schwert; N. Parvizi; M. Ganter

    2011-01-01

    The metabolic adaptations for pregnancy and lactation were evaluated in ewes with a higher and a lower risk of being affected by pregnancy toxaemia. Plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA) and ?-hydroxybutyrate (?-HB) were determined in 7 pregnant, 4.5- to 6.5-year-old German Blackheaded Mutton ewes (higher risk=HR) and 5 pregnant, 2.5-year-old Finn sheep ewes (lower risk=LR) 8

  8. A cytological study of the maturation process of the ovum of the ewe during normal and induced ovulations 

    E-print Network

    Savery, Harry P.

    1954-01-01

    period. Most of the eight ewes not ovulating when injected with the pituitary gonadotropins were in poor healtha One ewe when slaughtered showed an infantile reproductive tract, while another possessed a tract which exhibited a very pale color... A CYTOLOGICAL STUDY OP THE MATURATION PROCESS OF THE OVUM OP THE EWE DURING NORMAL AND INDUCED OVULATIONS A Dissertation By Harry P. Savery Approved as to style and content by: Chairman of Committee Head of department of Animal Husbandry...

  9. The effects of metabolizable energy intake on body fat depots of adult Pelibuey ewes fed roughage diets under tropical conditions

    Microsoft Academic Search

    A. J. Chay-Canul; A. J. Ayala-Burgos; J. C. Ku-Vera; J. G. Magaña-Monforte; L. O. Tedeschi

    2011-01-01

    The objective of this work was to evaluate the effect of metabolizable energy intake (MEI) on changes in fat depots of adult\\u000a Pelibuey ewes fed roughage diets under tropical conditions. Eighteen 3-year-old Pelibuey ewes with similar body weight (BW)\\u000a of 37.6?±?4.0 kg and body condition score (BCS) of 2.5?±?0.20 were randomly assigned to three groups of six ewes each in a

  10. Novel p53 tumour suppressor mutations in cases of spindle cell sarcoma, pleomorphic sarcoma and fibrosarcoma in cats

    Microsoft Academic Search

    B. Mayr; M. Reifinger; K. Alton; G. Schaffner

    1998-01-01

    Twenty feline neoplasms were sequenced in the region from exons 5 to 8 for the presence of tumour suppressor gene p53 mutations. In a spindle cell sarcoma of the bladder, a missense mutation (codon 164 AAG?GAG, lysine?glutamic acid) in exon 5 was detected. In a pleomorphic sarcoma, a 23 bp deletion involving the splicing junction between intron 5 and exon

  11. Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

    Microsoft Academic Search

    Teiyu Izumi; Yoshinao Oda; Tadashi Hasegawa; Yukihiro Nakanishi; Hiroshi Iwasaki; Hiroshi Sonobe; Hiroaki Goto; Hidenari Kusakabe; Tomonari Takahira; Chikashi Kobayashi; Ken-ichi Kawaguchi; Tsuyoshi Saito; Hidetaka Yamamoto; Sadafumi Tamiya; Yukihide Iwamoto; Masazumi Tsuneyoshi

    2006-01-01

    Dysadherin is a cancer-associated cell membrane glycoprotein, which downregulates E-cadherin and promotes metastasis. We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases. In addition, we compared dysadherin mRNA expression between epithelioid

  12. A case of relapsed visceral Kaposi's sarcoma with bilateral chylothoraces successfully treated with paclitaxel.

    PubMed

    Natarajan, Pavithra; Miller, Alastair

    2015-07-01

    Chylothorax is a rare complication of visceral Kaposi's sarcoma. We report a case with bilateral chylothoraces secondary to relapsed visceral Kaposi's sarcoma who was successfully treated with paclitaxel chemotherapy. PMID:25122577

  13. Primary breast sarcoma: A review of 33 cases with immunohistochemistry and prognostic factors

    Microsoft Academic Search

    Ph. Terrier; M. J. Terrier-Lacombe; H. Mouriesse; S. Friedman; M. Spielmann; G. Contesso

    1989-01-01

    The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas).

  14. Primary synovial sarcoma of the parotid gland in 15-year-old boy

    Microsoft Academic Search

    Ivica Lukši?; Mišo Virag; Spomenka Manojlovi?; Bojan Obradovi?; Darko Macan; Jasminka Stepan

    2011-01-01

    Synovial sarcoma (SS) is a malignant mesenchymal tumour, predominantly found in the deep soft tissues of lower extremities, whereas only 3% occur in the head and neck region. Primary synovial sarcoma of the parotid gland is exceptionally uncommon. This is a report of a 15-year-old boy with a synovial sarcoma arising in the parotid gland, and, to the best of

  15. Effect of solar radiation and flaxseed supplementation on milk production and fatty acid profile of lactating ewes under high ambient temperature

    Microsoft Academic Search

    M. Caroprese; M. Albenzio; A. Bruno; V. Fedele; A. Santillo; A. Sevi

    2011-01-01

    The objectives of this study were to evaluate the effects of protection from solar radiation and whole flaxseed supplementation on milk yield and milk fatty acid profile in lactating ewes exposed to high ambient temperature. The experiment was conducted during summer and involved 40 ewes divided into 4 groups. The ewes were either exposed (not offered shade) or protected from

  16. Influence of weaning age, milking frequency, and udder stimulation on dairy milk production and post-partum oestrus interval of Dorset ewes

    Microsoft Academic Search

    K. G. Geenty; P. G. Davison

    1982-01-01

    The dairy milk production of Dorset ewes was measured in a 2 × 2 × 2 factorial experiment. Factors were: machine milking of ewes from parturition or following the weaning of lambs at 4 weeks of age; once- or twice-daily milking from Week 6 of lactation; and udder stimulation or no stimulation. Ewes milked from parturition had a mean total

  17. 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. (Lawrence Berkeley Lab., CA (USA))

    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.

  18. [Kaposi's sarcoma--classic form. A rare familial case].

    PubMed

    Invernizzi, R; Ubiali, P; Barcella, A; Bonzanini, C

    1993-03-15

    Although Kaposi's sarcoma became very well-known with the outbreak of AIDS, this pathology in the classic Mediterranean form is still unusual and obscure. Nowadays we identify four types of Kaposi's sarcoma: 1) the classic Mediterranean form, 2) the endemic African one, 3) the therapeutical in immunosuppressed patients, 4) the epidemic AIDS-related one. We report a very rare case of familial Kaposi's sarcoma: the father (72 y.o.) manifested Kaposi's sarcoma in 1989 with several angiomatoid nodules on the penis and hands; the son (31 y.o.) presented in 1991 only one little nodule on the penis. The right therapy in these cases (patients with a small number of localizations) was to remove all the tumors and to wait: whereas in other cases it's preferable to use radio- or chemo-therapy or immunomodulator agents. We studied the patients and identified their form of Kaposi like the classic one not completely related (the son) to the HLA DR5, which is the HLA-phenotype most frequent in this sarcoma. Moreover we stress the rarity of genital localization in the classic form, instead it is very common (20%) in the AIDS-related one. PMID:8506043

  19. Spinal Myeloid Sarcoma “Chloroma” Presenting as Cervical Radiculopathy: Case Report

    PubMed Central

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

    2015-01-01

    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

  20. 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

  1. Assessing the reading level of online sarcoma patient education materials.

    PubMed

    Patel, Shaan S; Sheppard, Evan D; Siegel, Herrick J; Ponce, Brent A

    2015-01-01

    Cancer patients rely on patient education materials (PEMs) to gather information regarding their disease. Patients who are better informed about their illness have better health outcomes. The National Institutes of Health (NIH) recommends that PEMs be written at a sixth- to seventh-grade reading level. The purpose of this study was to evaluate the readability of online PEMs of bone and soft-tissue sarcomas and related conditions. We identified relevant online PEMs from the following websites: American Academy of Orthopaedic Surgeons, academic training centers, sarcoma specialists, Google search hits, Bonetumor.org, Sarcoma Alliance, Sarcoma Foundation of America, and Medscape. We used 10 different readability instruments to evaluate the reading level of each website's PEMs. In assessing 72 websites and 774 articles, we found that none of the websites had a mean readability score at or below 7 (seventh grade). Collectively, all websites had a mean readability score of 11.4, and the range of scores was grade level 8.9 to 15.5. None of the PEMs in this study of bone and soft-tissue sarcomas and related conditions met the NIH recommendation for PEM reading levels. Concerted efforts to improve the reading level of orthopedic oncologic PEMs are necessary. PMID:25566558

  2. Classic Kaposi's sarcoma treated with topical rapamycin.

    PubMed

    Díaz-Ley, Blanca; Grillo, Emiliano; Ríos-Buceta, Luis; Paoli, John; Moreno, Carmen; Vano-Galván, Sergio; Jaén-Olasolo, Pedro

    2015-01-01

    Kaposi's sarcoma (KS) is an angioproliferative disorder caused by human herpesvirus 8 (HHV-8). Current research efforts have focused on the study of the relative role of KSHV-encoded genes in Kaposi's sarcomagenesis in order to identify novel mechanism-based therapies for patients suffering from this tumor. Although several viral genes have potential for KS pathogenesis, compelling data point to the KSHV-encoded G protein-coupled receptor (vGPCR) as a leading candidate viral gene for the initiation of KS. Interestingly, the oncogenic potential of vGPCR seems to correlate with its capacity to activate the mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin, the prototypical inhibitor of the mTOR signaling pathway, has recently emerged as an effective treatment for KS when administered orally. In this case report, we present an immunocompetent patient with KS lesions treated with topical rapamycin achieving clinical and histologic healing after 16 weeks of treatment. The topical application of rapamycin could be a novel therapeutic option for the treatment of KS. PMID:25314592

  3. Multiagent PET for Risk Characterization in Sarcoma

    PubMed Central

    Eary, Janet F.; Link, Jeanne M.; Muzi, Mark; Conrad, Ernest U.; Mankoff, David A.; White, Jedediah K.; Krohn, Kenneth A.

    2015-01-01

    A major goal of molecular imaging in cancer is to evaluate patient tumors for risk of treatment resistance and poor outcome using biologically specific PET agents. This approach was investigated using a multiagent imaging protocol for which patients were imaged in a single session to minimize changes in tumor parameters caused by multiple-day and -setting observation differences. Methods We present data from a pilot study in 10 soft-tissue sarcoma patients imaged with 11C-thymidine for cellular proliferation, 18F-fluoromisonidazole (FMISO) for tissue hypoxia, and 11C-verapamil for P-glycoprotein activity, in comparison with 15O-water for blood flow and 11C-CO2 for metabolite analysis and 18F-FDG clinical scans. Several patients underwent repeated imaging after adriamycin-based chemotherapy. Results Quantitative imaging results showed that tumor uptake parameters vary between patients and with respect to each other in individual patients, suggesting that each patient’s tumor biologic profile is unique. Specific tumor characteristics such as variable cellular proliferation, hypoxic volume, and upregulated P-glycoprotein activity were identified. Conclusion This study shows that multiagent PET is feasible and yields unique and potentially complementary biologic information on individual tumors. PMID:21421714

  4. Differential effects of mineralocorticoid blockade on the hypothalamo-pituitary-adrenal axis in pregnant and nonpregnant ewes

    PubMed Central

    Lingis, Melissa; Richards, Elaine M.

    2011-01-01

    During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus. PMID:21205934

  5. Effects of nutritional plane and selenium supply during gestation on ewe and neonatal offspring performance, body composition, and serum selenium.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate effects of nutritional plane and Se supply during gestation on ewe and offspring performance and body composition, 84 Rambouillet ewe lambs (age = 240 ± 17 d, BW = 52.1 ± 6.2 kg), were allocated to a 2 x 3 x 2 factorial design. Factors included adequate (ASe) vs. supranutritional (HSe...

  6. Sources of variation in the reproductive performance of ewes inseminated with frozen-thawed ram semen by laparoscopy

    Microsoft Academic Search

    J. Eppleston; W. M. C. Maxwell

    1995-01-01

    Fertility data from 8 artificial insemination programs, involving more than 5000 ewes and 110 rams in 3 flocks, were analyzed to determine variation due to individual AI program and ram in the reproductive performance of ewes inseminated with frozen-thawed semen by laparoscopy. The semen had been previously frozen by commercial AI centers in either pellets or straws. Both AI program

  7. Foetal cross-protection experiments between type 1 and type 2 bovine viral diarrhoea virus in pregnant ewes

    Microsoft Academic Search

    D. J Paton; G Sharp; G Ibata

    1999-01-01

    A flock of 82 non-pregnant ewes was split into three immunisation groups and given an intranasal dose of either cell culture medium, or a type 1 or a type 2 bovine viral diarrhoea virus (BVDV-1 or BVDV-2). Two months later the flock was reconstituted and after a further three weeks, the ewes were bred to pestivirus negative rams after synchronisation

  8. 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...

  9. Effects of high-dose prepartum injections of Se and vitamin E on milk and serum concentrations in ewes

    Microsoft Academic Search

    P. A. Cuesta; L. R. McDowell; W. E. Kunkle; N. S. Wilkinson; F. G. Martin

    1995-01-01

    An experiment was conducted to evaluate the effects of relatively high-dose Se and vitamin E injections to pregnant ewes on serum Se and ?-tocopherol concentrations of the dam and their offspring, the Se concentrations of colostrum and milk, and the relative lasting effects of these nutrients in the body. Ewes were randomly assigned to seven experimental groups that included treatment

  10. Quantification of progesterone binding in mammary tissue of pregnant ewes

    SciTech Connect

    Smith, J.J.; Capuco, A.V.; Akers, R.M.

    1987-06-01

    Progestin-binding sites in mammary tissue from 14 prepartum, multiparous ewes at 50, 80, 115, and 140 d of gestation were demonstrated by the binding of (/sup 3/H) R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) to ovine mammary cytosol in the presence of sodium molybdate and excess cortisol. Homogenization extracted 89% of total mammary receptors (nuclear) into cytosol. Binding was specific for progestins and was of high affinity. The average dissociation constant for (/sup 3/H) R5020 specifically bound to receptors extracted into mammary cytosol was 1.9 (+/- .4) x 10/sup -9/ M (n = 14) and did not change significantly over the test period. However, binding capacities (fmol/mg cytosolic protein) differed according to stage of gestation with averages of 125 +/- 53, 149 +/- 26, 656 +/- 216, 57 +/- 22 at 50, 80, 115, and 140 d of pregnancy, respectively. Increased number of progestin-binding sites at 115 d of gestation (whether data are expressed per unit of tissue weight, DNA, or cytosolic protein) suggests that an increase per mammary epithelial cell may be necessary to produce the full lobuloalveolar proliferation observed at this stage of gestation.

  11. Broadband calibration of R/V Ewing seismic sources

    NASA Astrophysics Data System (ADS)

    Tolstoy, M.; Diebold, J. B.; Webb, S. C.; Bohnenstiehl, D. R.; Chapp, E.; Holmes, R. C.; Rawson, M.

    2004-07-01

    The effects of anthropogenic sound sources on marine mammals are of increasing interest and controversy [e.g., Malakoff, 2001]. To understand and mitigate better the possible impacts of specific sound sources, well-calibrated broadband measurements of acoustic received levels must be made in a variety of environments. In late spring 2003 an acoustic calibration study was conducted in the northern Gulf of Mexico to obtain broad frequency band measurements of seismic sources used by the R/V Maurice Ewing. Received levels in deep water were lower than anticipated based on modeling, and in shallow water they were higher. For the marine mammals of greatest concern (beaked whales) the 1-20 kHz frequency range is considered particularly significant [National Oceanic Atmospheric Administration and U. S. Navy, 2001; Frantzis et al., 2002]. 1/3-octave measurements show received levels at 1 kHz are ~20-33 dB (re: 1 ?Pa) lower than peak levels at 5-100 Hz, and decrease an additional ~20-33 dB in the 10-20 kHz range.

  12. 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.

  13. Primary spindle cell sarcoma of the breast masquerading as necrotizing fasciitis.

    PubMed

    Gesakis, Kanellos; Tanos, Grigorios; Onyekwelu, Obi; Gaitis, Anastasios; Gudur, Laxminarayan; Agarwal, Anil

    2014-01-01

    Breast sarcomas are rare neoplasms arising from the few epithelial elements of the gland. It represents much <1% of all breast cancer. Of the heterogeneous group of sarcomas, the more common subtypes include spindle cell sarcoma. The main risk factor for the development of breast sarcomas is previous radiation therapy following breast-conservation surgery for breast cancer or non-Hodgkin's lymphoma. We report on an idiopathic presentation of spindle cell sarcoma in an otherwise healthy middle-aged woman. An emphasis is made on the rare occurrence of lymphatic metastasis. We discuss our recommended management strategy with particular reference to the benefit of multidisciplinary team decision-making. PMID:24876317

  14. Ultrasonographic imaging to monitor fetal and placental developments in ewes fed locoweed (Astragalus lentiginosus).

    PubMed

    Panter, K E; Bunch, T D; James, L F; Sisson, D V

    1987-04-01

    Ultrasonographic imaging was used to monitor the effects of locoweed (Astragalus lentiginosus) on fetal, placental, and cotyledonary developments in pregnant ewes and proved to be a useful noninvasive method of monitoring the effects of locoweed poisoning on fetal and placental development. Ultrasonographic imaging may be a good research technique to observe the effects of toxicants on fetal movement, fetal heart action, and growth and development of the fetus and placenta. Known effects of locoweed poisoning in pregnant ewes, such as fluid accumulation in the placenta (hydrops allantois, hydrops amnii), altered cotyledonary development, and fetal death were observed with ultrasonographic imaging. A previously unknown effect of locoweed on fetal heart action also was observed. Locoweed decreased fetal heart rates, caused cardiac irregularity, and decreased the strength of heart contractions. All ewes, except No. 3525, fed locoweed aborted. At necropsy, aborted fetuses had hypertrophy of the heart, right ventricular dilatation, rounded at the apex of the heart, and generalized edema. PMID:3296887

  15. Clear cell sarcoma of the penis: a case report

    PubMed Central

    Ito, Timothy; Melamed, Jonathan; Perle, Mary Ann; Alukal, Joseph

    2015-01-01

    Clear cell sarcoma of the penis is exceedingly rare with only one prior case involving the penis reported in the literature. We present the case of a 32 year old male who presented with an infiltrative neoplasm at the base of the penis as well as extensive metastatic disease to the lymph nodes and bone. Morphologic, immunohistochemical and cytogenetic findings established the diagnosis of clear cell sarcoma. Despite chemotherapy the patient’s disease was rapidly progressive and the patient died of disease within 8 months of diagnosis.

  16. 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.

  17. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia.

    PubMed

    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L; West, Daniel C

    2003-02-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. PMID:12557072

  18. Focus Formation by a Murine Sarcoma-Leukemia Virus Complex

    PubMed Central

    Declève, A.; Lieberman, M.; Hahn, G. M.; Kaplan, H. S.

    1970-01-01

    A quantitative study has been made of the interactions between radiation leukemia virus (RadLV), its murine sarcoma virus pseudotype, and their C57BL host cells. The elimination of interference phenomena by delayed infection of cells with RadLV made possible the quantitative determination of the pseudotype in terms of defective sarcoma and endogenous RadLV particles. This in turn permitted the quantitative assessment of RadLV helper activity and of the various factors which influence the accuracy and sensitivity of the helper assay. PMID:4318086

  19. Refractoriness to inductive day lengths terminates the breeding season of the Suffolk ewe.

    PubMed

    Robinson, J E; Karsch, F J

    1984-11-01

    The ambient photoperiod was recorded over an 8-yr period at the beginning and end of the breeding season in a flock of Suffolk ewes maintained outdoors. The transition into the breeding season in this short-day breeder occurred at a day length which was much longer (14.0 h, Sept. 3 +/- 5 days) than that at the onset of anestrus (11.5 h, Feb. 15 +/- 3 days). This produced a marked asymmetry of the annual cycles of photoperiod and reproduction. In an attempt to explain this asymmetry, we determined if ewes enter anestrus because increasing day lengths curtail breeding or because ewes lose the ability to respond to prevailing short day lengths (i.e., become photorefractory). On the winter solstice, 3 groups of 6 ovariectomized ewes bearing s.c. Silastic implants of estradiol were placed on different day length treatments: 1) natural environment; 2) artificial day length which simulated natural photoperiod; or 3) artificial day length equivalent to that of the winter solstice (10L). Transition into anestrus was determined from the precipitous drop in serum luteininzing hormone (LH) concentrations. The breeding season was not prolonged in ewes held on the winter solstice day length; LH did not remain elevated beyond the time that it plummeted in the other groups. These findings lead to the conclusion that Suffolk ewes normally cease breeding, not because they are actively inhibited by increasing day lengths, but because they become photorefractory. This can account, at least in part, for the asymmetry between the annual cycle of photoperiod and reproduction in this short-day breeder. PMID:6542427

  20. Recurrent lower gastrointestinal bleeding due to primary colonic Kaposi's sarcoma in a patient with AIDS.

    PubMed

    Ling, Jie; Coron, Roger; Basak, Prasanta; Jesmajian, Stephen

    2013-11-01

    Epidemic Kaposi's sarcoma remains the most common cancer in patients with human immunodeficiency virus and is associated with significant morbidity and mortality in AIDS patients. Primary visceral Kaposi's sarcoma (Kaposi's sarcoma without cutaneous lesions) presenting with lower gastrointestinal bleeding (LGIB) has rarely been reported. Though Kaposi's sarcoma can occur anywhere in gastrointestinal tract, gastrointestinal symptoms are often non-specific such as chronic blood loss anaemia, vomiting, diarrhoea, intestinal obstruction. In these patients, severe gastrointestinal bleeding requiring repeated blood transfusions is extremely rare. Clinicians should be aware of gastrointestinal tract Kaposi's sarcoma since visceral Kaposi's sarcoma can present in the absence of cutaneous involvement. Endoscopy with biopsy is useful in the diagnosis for severe LGIB in patients with AIDS. Furthermore, gastrointestinal Kaposi's sarcoma should be considered in the differential diagnosis of GI bleeding. We report a case of primary colonic KS who presented with recurrent GI bleeding which was eventually diagnosed by sigmoidoscopy and confirmed pathologically. PMID:23970616

  1. The induction of breeding activity in lactating ewes during anestrus by the use of hormones

    E-print Network

    Ahmed, Shams Uddin

    1963-01-01

    and content by: gg. ~ Chairman of Committee Head of Departxnent January, 1963 855502 BIO GRAPH Y Shams Uddin Ahmed was born on August 1, 1934 at Paik Para, P. S. Shaila Kupa in the district of Jessore, East Pakistan. He obtained the Bachelor... as well as save labor. The purposes of this study were to induce estrus in lactating anestrous ewes by the use of hormones, to determine the ovarian re- sponse in ewes which failed to exhibit estrus after hormonal treatment, and to determine the gross...

  2. Cediranib for Metastatic Alveolar Soft Part Sarcoma

    PubMed Central

    Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

    2013-01-01

    Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

  3. Radiation Therapy for Chloroma (Granulocytic Sarcoma)

    SciTech Connect

    Bakst, Richard; Wolden, Suzanne [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    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.

  4. TRIM8 anti-proliferative action against chemo-resistant renal cell carcinoma.

    PubMed

    Caratozzolo, Mariano Francesco; Valletti, Alessio; Gigante, Margherita; Aiello, Italia; Mastropasqua, Francesca; Marzano, Flaviana; Ditonno, Pasquale; Carrieri, Giuseppe; Simonnet, Hélène; D'Erchia, Anna Maria; Ranieri, Elena; Pesole, Graziano; Sbisà, Elisabetta; Tullo, Apollonia

    2014-09-15

    In some tumours, despite a wild-type p53 gene, the p53 pathway is inactivated by alterations in its regulators or by unknown mechanisms, leading to resistance to cytotoxic therapies. Understanding the mechanisms of functional inactivation of wild-type p53 in these tumours may help to define prospective targets for treating cancer by restoring p53 activity. Recently, we identified TRIM8 as a new p53 modulator, which stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. In this paper we demonstrated that TRIM8 deficit dramatically impairs p53-mediated cellular responses to chemotherapeutic drugs and that TRIM8 is down regulated in patients affected by clear cell Renal Cell Carcinoma (ccRCC), an aggressive drug-resistant cancer showing wild-type p53. These results suggest that down regulation of TRIM8 might be an alternative way to suppress p53 activity in RCC. Interestingly, we show that TRIM8 expression recovery in RCC cell lines renders these cells sensitive to chemotherapeutic treatments following p53 pathway re-activation. These findings provide the first mechanistic link between TRIM8 and the drug resistance of ccRCC and suggest more generally that TRIM8 could be used as enhancer of the chemotherapy efficacy in cancers where p53 is wild-type and its pathway is defective. PMID:25277184

  5. TRIM8 anti-proliferative action against chemo-resistant renal cell carcinoma

    PubMed Central

    Gigante, Margherita; Aiello, Italia; Mastropasqua, Francesca; Marzano, Flaviana; Ditonno, Pasquale; Carrieri, Giuseppe; Simonnet, Hélène; D'Erchia, Anna Maria; Ranieri, Elena; Pesole, Graziano; Sbisà, Elisabetta; Tullo, Apollonia

    2014-01-01

    In some tumours, despite a wild-type p53 gene, the p53 pathway is inactivated by alterations in its regulators or by unknown mechanisms, leading to resistance to cytotoxic therapies. Understanding the mechanisms of functional inactivation of wild-type p53 in these tumours may help to define prospective targets for treating cancer by restoring p53 activity. Recently, we identified TRIM8 as a new p53 modulator, which stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. In this paper we demonstrated that TRIM8 deficit dramatically impairs p53-mediated cellular responses to chemotherapeutic drugs and that TRIM8 is down regulated in patients affected by clear cell Renal Cell Carcinoma (ccRCC), an aggressive drug-resistant cancer showing wild-type p53. These results suggest that down regulation of TRIM8 might be an alternative way to suppress p53 activity in RCC. Interestingly, we show that TRIM8 expression recovery in RCC cell lines renders these cells sensitive to chemotherapeutic treatments following p53 pathway re-activation. These findings provide the first mechanistic link between TRIM8 and the drug resistance of ccRCC and suggest more generally that TRIM8 could be used as enhancer of the chemotherapy efficacy in cancers where p53 is wild-type and its pathway is defective. PMID:25277184

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

    E-print Network

    Cherry, Evan M

    2012-07-11

    Diffuse Large B Cell Lymphoma (DLBCL) is a common form of cancer, accounting for 30% of all lymphoma diagnoses. Patient survival rates of DLBCL are roughly 30-40% with the standard chemotherapeutic cocktail consisting of cyclophosphamide...

  7. Restoration of Sensitivity in ChemoResistant Glioma Cells by Cold Atmospheric Plasma

    PubMed Central

    Köritzer, Julia; Boxhammer, Veronika; Schäfer, Andrea; Shimizu, Tetsuji; Klämpfl, Tobias G.; Li, Yang-Fang; Welz, Christian; Schwenk-Zieger, Sabina; Morfill, Gregor E.; Zimmermann, Julia L.; Schlegel, Jürgen

    2013-01-01

    Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Despite multimodal treatments including surgery, chemotherapy and radiotherapy the prognosis remains poor and relapse occurs regularly. The alkylating agent temozolomide (TMZ) has been shown to improve the overall survival in patients with malignant gliomas, especially in tumors with methylated promoter of the O6-methylguanine-DNA-methyltransferase (MGMT) gene. However, intrinsic and acquired resistance towards TMZ makes it crucial to find new therapeutic strategies aimed at improving the prognosis of patients suffering from malignant gliomas. Cold atmospheric plasma is a new auspicious candidate in cancer treatment. In the present study we demonstrate the anti-cancer properties of different dosages of cold atmospheric plasma (CAP) both in TMZ-sensitive and TMZ-resistant cells by proliferation assay, immunoblotting, cell cycle analysis, and clonogenicity assay. Importantly, CAP treatment restored the responsiveness of resistant glioma cells towards TMZ therapy. Concomitant treatment with CAP and TMZ led to inhibition of cell growth and cell cycle arrest, thus CAP might be a promising candidate for combination therapy especially for patients suffering from GBMs showing an unfavorable MGMT status and TMZ resistance. PMID:23704990

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

    E-print Network

    Cherry, Evan M

    2012-07-11

    Diffuse Large B Cell Lymphoma (DLBCL) is a common form of cancer, accounting for 30% of all lymphoma diagnoses. Patient survival rates of DLBCL are roughly 30-40% with the standard chemotherapeutic cocktail consisting of cyclophosphamide...

  9. Effect of freezing on Fossomatic cell counting in ewe milk.

    PubMed

    Martínez, J R; Gonzalo, C; Carriedo, J A; San Primitivo, F

    2003-08-01

    Using the Fossomatic method, a total of 10,072 analytical somatic cell count (SCC) observations were carried out on 4760 aliquots taken from 70 individual ewe milk samples with the objective of studying whether freezing showed significant differences of SCC in comparison with refrigeration, according to different analytical conditions. These conditions were four preservation procedures (without preservation, potassium dichromate, azidiol, and bronopol), two storage temperatures (refrigeration and freezing), five milk ages within storage (24 h postcollection in refrigeration, and 24 h, 15, 30, and 60 d postcollection in freezing), two thawing types (rapid and slow), and two analytical temperatures (40 and 60 degrees C). Preservation, storage, and analytical temperature, type of thawing and milk age within storage, and most of the interactions showed a significant effect on the SCC variation. On average, the SCC was lower after freezing than in refrigeration. This effect depended specifically on type of preservation and analytical temperature of milk. The SCC of milk unpreserved or preserved with bronopol or potassium dichromate, and analyzed at 40 degrees C, was not affected by freezing; however, use of azidiol as a preservative before freezing, and heating the milk to 60 degrees C following thawing resulted in significantly decreased SCC. Milk age had little quantitative influence on SCC of thawed milk. The type of thawing (rapid and slow) did not significantly influence SCC of milk analyzed at 40 degrees C. As a result, when using properly handled samples, the Fossomatic method could be used to enumerate SCC in samples frozen over the 60 d. PMID:12939082

  10. Thoracoscopic resection of bilateral metastatic sarcomas causing spontaneous pneumothorax.

    PubMed

    Jones, D R; Tanguilig, G G; Graeber, G M

    1994-10-01

    Pulmonary metastases from soft tissue sarcomas may present with spontaneous pneumothorax. Metastatectomy via thoracotomy or median sternotomy has been the procedure of choice. We present a patient with bilateral spontaneous pneumothorax secondary to metastatic angiosarcoma where staged video-assisted thoracic surgery using the thoracoscope was used to successfully resect the tumors. PMID:7924513

  11. Sarcomas arising after radiotherapy for peptic ulcer disease

    Microsoft Academic Search

    Michael R. Lieber; Charles S. Winans; Melvin L. Griem; Rahim Moossa; Victor M. Elner; Wilbur A. Franklin

    1985-01-01

    Summary Therapeutic gastric irradiation has been used to reduce peptic juice secretion in patients with peptic ulcer disease. Between 1937 and 1968 a total of 2049 patients received such therapy at the University of Chicago. Three of these patients are known to have developed sarcomas in the field of radiation. Two gastric leiomyosarcomas of the stomach were diagnosed 26 and

  12. Nature of the Causative Agent of the Rous Fowl Sarcoma

    Microsoft Academic Search

    E. M. Fraenkel; C. A. Mawson

    1937-01-01

    THE opinions of workers in the field of Rous sarcoma are divided into two schools, one of which uses as a working hypothesis the suggestion of Fraenkel1 that the agent is a pure chemical substance or a `virus-enzyme', while the other considers it to be a particle resembling a virus. These opinions are represented by two quotations from recent publications.

  13. Synovial sarcoma in cerebellum: a case report and literature review.

    PubMed

    Xiao, Guan-ying; Pan, Bin-cai; Tian, Xiao-ying; Li, Yang; Li, Bin; Li, Zhi

    2014-01-01

    Synovial sarcoma is a tumor of unknown origin and is extremely rare in the central nervous system. We present a case involving an unusual cerebellar synovial sarcoma in a male infant. Neuroimaging revealed a large, solid, gadolinium-enhancing mass located in the parenchyma of the right cerebellar hemisphere and associated with multiple cyst formation. Histologically, the tumor was composed of uniform spindle cells with indistinct borders and numerous mitotic figures. The tumor cells were observed to form dense cellular sheets, but in some areas the tumor showed a hemangiopericytomatous vascular pattern consisting of tumor cells arranged around dilated, thin-walled blood vessels. Immunohistochemistry showed that vimentin, CD99 and Bcl-2 were diffusely positive in most cells, and focal reactivity for cytokeratin (AE1/AE3) and S-100 protein was also observed. The tumor cells were, however, negative for CK19, EMA, CD34, synaptophysin, GFAP, desmin, myogenin, and smooth muscle actin. Cytogenetic analysis using fluorescence in situ hybridization demonstrated the translocation t(X;18)(p11;q11). A diagnosis of primary cerebellar monophasic synovial sarcoma was made. To our knowledge, this is the first report of a synovial sarcoma in brain parenchyma. The present case indicates that it is essential to select the appropriate immunohistochemical panel and-especially-perform molecular analysis to accurately diagnose intracranial spindle cell tumors. PMID:23223956

  14. Endometrial stromal sarcoma: a population-based analysis

    Microsoft Academic Search

    J K Chan; N M Kawar; J Y Shin; K Osann; L-m Chen; C B Powell; D S Kapp

    2008-01-01

    To determine independent prognostic factors for the survival of patients with endometrial stromal sarcoma (ESS), data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute from 1988 to 2003. Kaplan–Meier and Cox proportional hazards models were used for analyses. Of 831 women diagnosed with ESS, the median age was 52 years (range: 17–96

  15. [Radiotherapy for sarcoma: hadrontherapy, for whom and what for?].

    PubMed

    Pommier, P; Sunyach, M-P; Hu, Yi; Amsalem, E; Claude, L; Moncort-Boulch, D; Toutenu, P; Balosso, J

    2010-06-01

    The radiobiological properties of the hadrons (neutrons, protons, carbon ions) led to their therapeutic use in sarcomas, as a referent therapy or as an alternative to photon therapy. An extensive review of the literature has been conducted to assess the present indications and the perspectives for hadrontherapy. Compared to photons, neutrons are characterized by a higher biological efficiency that is on particular importance for these tumours usually considered as radio-resistant. Neutrons have been considered as a standard therapy for sarcoma' patients, contra-indicated for surgery or with a definitive R2 resection, but their indications and use have been restricted due to the occurrence of late severe toxicities related to their poor ballistic' properties. Thanks to their physical properties (Bragg Peak), protons are characterized by a higher conformity index compared to photons (and neutrons) with optimal organs at risk preservation that permits a dose escalation. Protontherapy is to date the standard of care for base of skull, spinal and paraspinal sarcomas. Carbon ions combined both advantages from protons and neutrons. Literature data permits to consider this radiation modality as a referent therapy for unresectable sarcomas. The ongoing diffusions of protons and carbon ions radiotherapy facilities will permit to offer these therapies to more patients and to conduct studies that are warranted to determine their indications and their results. PMID:20547480

  16. Prognostic Impact of Lymphocytes in Soft Tissue Sarcomas

    Microsoft Academic Search

    Sveinung W. Sorbye; Thomas Kilvaer; Andrej Valkov; Tom Donnem; Eivind Smeland; Khalid Al-Shibli; Roy M. Bremnes; Lill-Tove Busund; Niels Olsen Saraiva Câmara

    2011-01-01

    PurposeThe purpose of this study was to clarify the prognostic significance of lymphocyte infiltration in soft tissue sarcomas (STS). Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of tumor infiltrating lymphocytes is controversial as the immune system has conflicting roles during

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

    PubMed

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

    2015-03-01

    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

  18. 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

  19. Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes.

    PubMed

    Souza, C J H; McNeilly, A S; Benavides, M V; Melo, E O; Moraes, J C F

    2014-10-01

    Litter size (LS) in sheep is determined mainly by ovulation rate (OR). Several polymorphisms have been identified in the growth differentiation factor 9 (GDF9) gene that result in an increase in OR and prolificacy of sheep. Screening the databank of the Brazilian Sheep Breeders Association for triplet delivery, we identified flocks of prolific Ile de France ewes. After resequencing of GDF9, a point mutation (c.943C>T) was identified, resulting in a non-conservative amino acid change (p.Arg315Cys) in the cleavage site of the propeptide. This new allele was called Vacaria (FecG(v) ). A flock of half-sib ewes was evaluated for OR in the first three breeding seasons, and Vacaria heterozygotes had higher OR (P < 0.001), averaging 2.1 ± 0.1 when compared to 1.2 ± 0.1 in wild-type ewes. The OR was also influenced by age, increasing in the second and third breeding seasons (P < 0.001). In flocks segregating this allele, the LS was higher in mutant sheep (P < 0.001), averaging 1.61 ± 0.07 in heterozygotes and 1.29 ± 0.03 in wild-type ewes. Analysis of homozygote reproductive tract morphology revealed uterine and ovarian hypoplasia. Ovarian follicles continue to develop up to small antral stages, although with abnormal oocyte morphology and altered arrangement of granulosa cells. After the collapse of the oocyte in most follicles, the remaining cells formed clusters that persisted in the ovary. This SNP is useful to improve selection for dam prolificacy and also as a model to investigate GDF9 post-translation processing and the fate of the follicular cells that remain after the oocyte demise. PMID:25039891

  20. Performance of dairy ewes fed diets with a fibrolytic enzyme product included in the concentrate during the suckling period.

    PubMed

    Flores, C; Caja, G; Casals, R; Albanell, E; Such, X

    2008-06-01

    Seventy-two multiparous ewes from two dairy breeds (Manchega, n = 36 and Lacaune, n = 36) were used in a replicated 2 × 2 factorial design to evaluate the effects of diet supplementation with an exogenous fibrolytic enzyme product on lactation performance and feed intake during the suckling period (weeks 1 to 4) according to breed. Ewes were blocked in groups of nine and fed ad libitum after lambing a diet based on 70% forage and 30% concentrate to which the enzyme was added after pelleting. Experimental concentrates were: control (without enzyme) and enzyme (fibrolytic enzyme complex, included at 0.47% volume to weight of concentrate). Twenty-four dry and open ewes (Manchega, n = 12 and Lacaune, n = 12) were also grouped by breed and used to measure the fill value of the ration used. During the suckling period, milk yield, milk composition, dry matter intake, lamb growth, as well as body weight change and body condition score change were not affected by enzyme supplementation. Breed effect was significant for milk yield, the Manchega ewes yielding less milk with a higher content of milk components than the Lacaune ewes. The opposite was observed for dry matter intake. Enzyme supplementation reduced intake by 9% in the dry ewes, resulting in a greater fill value of the diet. In conclusion, no lactational effects were detected when the fibrolytic enzyme product was added to the concentrate fed to dairy ewes. PMID:22443676

  1. Effects of addition of different vegetable oils to lactating dairy ewes' diet on meat quality characteristics of suckling lambs reared on the ewes' milk.

    PubMed

    Vieira, Ceferina; Fernández-Diez, Ana; Mateo, Javier; Bodas, Raul; Soto, Sergio; Manso, Teresa

    2012-07-01

    The effect of different vegetable oils used in the diet of lactating ewes on the meat quality of their suckling lambs has been evaluated. Lambs (males and females) were slaughtered at 11 kg. Fortyeight lactating Churra ewes (prolificacy 1.5) and their suckling lambs were assigned to four treatments according to the oil added (3% on weight basis) to the ewes' daily ration: palm oil as control (CON); olive oil (OLI); soybean oil (SOY); and linseed oil (LIN). Analyses of pH, colour, thiobarbituric acid reactive substances (TBARS), tocopherol levels, volatile compounds and a sensory evaluation were carried out on suckling lambs' meat. Results showed no substantial effect on pH, colour, TBARS and tocopherol levels. Volatiles typically derived from lipid oxidation were higher in SOY group. However, panellists were only able to correctly identify samples from LIN group. Furthermore, the meat from LIN group showed lower scores towards odour and flavour quality and overall liking than that from the rest of treatments. PMID:22381704

  2. Elimination of (/sup 14/C)heptachlor from body stores of lactating ewes treated with ovine growth hormone

    SciTech Connect

    Holcombe, D.W.; Smith, G.S.; Khan, M.F.; Hallford, D.M.; Rozman, K.

    1988-09-01

    Elimination of (14C)heptachlor from body burdens of sheep was measured using mature ewes nursing single offspring, and the influence of exogenous ovine growth hormone (oGH) on elimination was studied. Six ewes (62 +/- 2.5 kg BW) were dosed (i.p.) once with (14C)heptachlor (2.04 mg/kg Bw; .88 microCi/mg heptachlor) and three were treated additionally with oGH (oGH; 5 mg/d) for 21 d. Three additional ewes served as controls. Excreta were collected each day for 21 d. Milk and blood were collected every 3rd d until ewes were euthanized at d 21. 14C activity was measured in excreta, milk, blood and tissues. Total cumulative activity of (14C)heptachlor and(or) metabolites in excreta (21 d) did not differ (P greater than .20) in ewes given oGH (25 +/- 2%) vs none (23 +/- 2%). Milk yield and protein content were unaffected (P greater than .10) by oGH. Ewes given oGH eliminated 2.2 +/- 2% of total 14C dosage into milk during 21 d, whereas ewes untreated with oGH eliminated 1.3 +/- .2% (P less than .10); total 14C activity eliminated into milk plus excreta was similar for ewes given oGH or none (P greater than .10). For all six ewes, half-times (T1/2) for distribution and elimination of 14C activity (heptachlor and metabolites) were 1.5 d and 11.7 d, respectively. Blood concentrations of 14C activity during 21 d yielded elimination half-time as 23 d. Unlike bovines, which eliminate heptachlor slowly (T1/2 approximately 70 to 80 d) and mainly into milk fat, lactating ovines eliminated heptachlor and(or) metabolites mainly into excreta and about sixfold faster than bovines.

  3. The effect of oestrus synchronization and mating season on the productivity of Pelibuey ewes

    E-print Network

    Boyer, Edmond

    Note The effect of oestrus synchronization and mating season on the productivity of Pelibuey ewes J for meat production in developing countries ». Observations carried out on our sheep at the experimental and in July, March and October, respectively. Also significant effects were found for the synchronization

  4. UDDER CONFORMATION, MILK YIELD AND MILK FRACTIONATION IN THE DAIRY EWE

    E-print Network

    Paris-Sud XI, Université de

    milking parlour systems (as for example in dairy cows) and in this way may prove to be a decisive factor type and milk frac- tionation. (1) Dr M. MORAG died (24-4-73) shortly after summarizing this paper. #12UDDER CONFORMATION, MILK YIELD AND MILK FRACTIONATION IN THE DAIRY EWE R. SAGI M. MORAG Faculty

  5. Lead and cadmium in raw buffalo, cow and ewe milk from west Azerbaijan, Iran.

    PubMed

    Najarnezhad, Vahid; Jalilzadeh-Amin, Ghader; Anassori, Ehsan; Zeinali, Vahid

    2015-06-01

    In this study, 300 raw buffalo, cow and ewe milk samples from five townships in west Azerbaijan, Iran, were analysed. Lead and cadmium were determined using atomic absorption spectrophotometry. Mean concentration of lead and cadmium in buffalo milk samples was 0.018 ± 0.001 and 0.003 ± 0.001 mg/kg, respectively. Mean concentration of lead and cadmium in cow milk samples was 0.007 ± 0.001 and 0.001 ± 0.001 mg/kg, respectively, and in ewe milk, these mean values were 0.010 ± 0.001 and 0.002 ± 0.001 mg/kg, respectively. Statistical analyses showed that lead and cadmium concentrations in buffalo milk were significantly higher than those in cow and ewe milk. Moreover, the concentration of these heavy metals in ewe milk was significantly higher than that in cow milk. It was also found that concentration of these selected toxic metals in milk increased with increasing age of the animals. PMID:25588978

  6. A. Gonzlez-Bulnes et al.Embryo degeneration in superovulated ewes Original article

    E-print Network

    Paris-Sud XI, Université de

    A. González-Bulnes et al.Embryo degeneration in superovulated ewes Original article Influence of maternal environment on the number of transferable embryos obtained in response to superovulatory FSH-Madrid, Spain (Received 30 January 2002; accepted 10 June 2002) Abstract -- In a first experiment, embryo

  7. Kiss1 Gene Expression and the Effects of Kisspeptin During Pubertal Development in the Ewe Lamb 

    E-print Network

    Redmond, Jeremy Scott

    2012-02-14

    . Brain tissue was collected from ewes at 25, 30, and 35 wk of age (n=6/group). Patterns of LH release in circulation were determined on the day before euthanasia and cells containing Kiss1-mRNA were identified by in situ hybridization. Mean concentrations...

  8. Pregnancy rates after ewes were treated with estradiol-17beta and oxytocin.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cervical dilation may improve transcervical sheep embryo-transfer procedures, if the cervical dilation method does not reduce pregnancy rates. This experiment was conducted to determine whether estradiol-17beta-oxytocin treatment, which dilates the cervix in luteal-phase ewes, affects pregnancy rat...

  9. 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...

  10. Protein supplementation for severely undernourished ewes P Kabr, M Petit, H Tournadre

    E-print Network

    Paris-Sud XI, Université de

    nutrients (such as amino acids) which promoted microbial activity and fiber digestion. Ortigues I, Smith T the effects of protein supplementation on the digesti- bility of a medium-quality forage and on body weight loss when energy supply was severely restricted. During the first 26 d of the trial, all ewes were fed

  11. Improving the Performance of MPI Derived Datatypes William D. Gropp, Ewing Lusk, and Debbie Swider

    E-print Network

    Gropp, William D.

    Improving the Performance of MPI Derived Datatypes #3; William D. Gropp, Ewing Lusk, and Debbie Abstract The Message Passing Interface (MPI) standard provides a powerful mechanism for describing non­contiguous mem­ ory locations: derived datatypes. In addition, MPI de­ rived datatypes have a key role in the MPI

  12. PVM and MPI Are Completely Different William Gropp and Ewing Lusk

    E-print Network

    Gropp, William D.

    PVM and MPI Are Completely Different William Gropp and Ewing Lusk Mathematics and Computer Science Division Argonne National Laboratory Abstract PVM and MPI are often compared. These comparisons usually start with the un­ spoken assumption that PVM and MPI represent different solutions to the same problem

  13. Milk fatty acid composition of indigenous goat and ewe breeds from Sindh, Pakistan

    Microsoft Academic Search

    Farah N. Talpur; M. I. Bhanger; Nusrat N. Memon

    2009-01-01

    The present study was undertaken to evaluate the breed influence on milk fatty acid (FA) composition, particularly on the concentration of conjugated linoleic acid (CLA) from two different indigenous breeds of goats (Pateri and Kamori; n=30 for each breed) and ewes (Kachi and Kooka; n=25 for each) from Sindh, Pakistan. All animals were managed together and received the same diet.

  14. Mammary Pathogens and Their Relationship to Somatic Cell Count and Milk Yield Losses in Dairy Ewes

    Microsoft Academic Search

    C. Gonzalo; A. Ariznabarreta; J. A. Carriedo; F. San Primitivo

    2002-01-01

    A total of 9592 samples of half udder milk were col- lected monthly throughout lactation for bacteriological and somatic cell count (SCC) study from 1322 Churra ewe lactations from seven separate flocks enrolled in the recording scheme of the National Association of Spanish Churra Breeders in the Castile-Leon region of Spain. Statistical analyses were carried out from a mixed model

  15. Effects of undernutrition during late pregnancy on gluconeogenesis and ketogenesis in twin-pregnant ewes

    E-print Network

    Paris-Sud XI, Université de

    Effects of undernutrition during late pregnancy on gluconeogenesis and ketogenesis in twin on gluco- neogenesis and ketogenesis after dietary restriction of ewe at the end of pregnancy. Two weeks or the last 4 to 6 weeks of pregnancy, depending on the lot (80 to 100 p. 100 of maintenance needs

  16. Influence of the stage of pregnancy on gentamicin disposition in the ewe

    E-print Network

    Paris-Sud XI, Université de

    Short note Influence of the stage of pregnancy on gentamicin disposition in the ewe M Oukessou PL ― The influence of the state of pregnancy (mid- and end of pregnancy) on the kinetic disposition from mid to end of pregnancy (from 0.09 I.kg-1 to 0.194 I.kg-1).). Similarly, plasma clearance

  17. Responses of dairy ewes before and after parturition, to different nutritional regimes during pregnancy

    E-print Network

    Paris-Sud XI, Université de

    pregnancy 1. - Ewe body weight, uterine contents, and lamb birth weight (1) D. STERN J. H. ADLER H. TAGARI E (maintenance) levels and three levels of late pregnancy allowance (steaming up) were compared. During the last three weeks of pregnancy inappetance appeared in the high steaming-up groups, mainly among those which

  18. The Estrous Cycle of the Ewe Is Resistant to Disruption by Repeated, Acute Psychosocial Stress1

    PubMed Central

    Wagenmaker, Elizabeth R.; Breen, Kellie M.; Oakley, Amy E.; Tilbrook, Alan J.; Karsch, Fred J.

    2010-01-01

    Five experiments were conducted to test the hypothesis that psychosocial stress interferes with the estrous cycle of sheep. In experiment 1, ewes were repeatedly isolated during the follicular phase. Timing, amplitude, and duration of the preovulatory luteinizing hormone (LH) surge were not affected. In experiment 2, follicular-phase ewes were subjected twice to a “layered stress” paradigm consisting of sequential, hourly application of isolation, restraint, blindfold, and predator cues. This reduced the LH pulse amplitude but did not affect the LH surge. In experiment 3, different acute stressors were given sequentially within the follicular phase: food denial plus unfamiliar noises and forced exercise, layered stress, exercise around midnight, and transportation. This, too, did not affect the LH surge. In experiment 4, variable acute psychosocial stress was given every 1–2 days for two entire estrous cycles; this did not disrupt any parameter of the cycle monitored. Lastly, experiment 5 examined whether the psychosocial stress paradigms of experiment 4 would disrupt the cycle and estrous behavior if sheep were metabolically stressed by chronic food restriction. Thirty percent of the food-restricted ewes exhibited deterioration of estrous cycle parameters followed by cessation of cycles and failure to express estrous behavior. However, disruption was not more evident in ewes that also encountered psychosocial stress. Collectively, these findings indicate the estrous cycle of sheep is remarkably resistant to disruption by acute bouts of psychosocial stress applied intermittently during either a single follicular phase or repeatedly over two estrous cycles. PMID:20164438

  19. RAM MATING BEHAVIOR AFTER LONG-TERM SELECTION FOR REPRODUCTIVE RATE IN RAMBOUILLET EWES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mating behavior is heritable in several species, but it is not known if selection for ewe traits affect ram mating behavior. Our objectives were to determine if divergent (high vs low) selection of a female trait (lambs born) affects mating behavior of male offspring when trained to service an artif...

  20. CLINICAL EVALUATION OF A COMMERCIAL VACCINE AGAINST CHLAMYDIAL ABORTION OF EWES

    E-print Network

    Paris-Sud XI, Université de

    CLINICAL EVALUATION OF A COMMERCIAL VACCINE AGAINST CHLAMYDIAL ABORTION OF EWES Annie RODOLAKIS A Tours-Nouzilly - 37380 Nouzilly Résumé MESURE DE L'EFFICACITE D'UN VACCIN CONTRE LA CHLAMYDIOSE ABORTIVE isolées dans les écouvillons vaginaux de 7 de ces 9 brebis vacci- nées. Chlamydial abortion is the main

  1. Involution and regeneration of the endometrium following parturition in the ewe

    Microsoft Academic Search

    J. D. O'Shea; P. J. Wright

    1984-01-01

    Involution and regeneration of the endometrium after parturition in the ewe, were studied by light- and electron microscopy. The luminal epithelium in intercaruncular regions of the endometrium remained intact at all stages, but degeneration and death of many glandular epithelial cells were observed on the day after parturition. Glandular regeneration had commenced by 8 d post partum, and the glands

  2. 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

  3. 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)

  4. THE EFFECT OF VARYING THE DAILY MILKING FREQUENCY ON THE MILK YIELD OF THE EWE

    E-print Network

    Paris-Sud XI, Université de

    THE EFFECT OF VARYING THE DAILY MILKING FREQUENCY ON THE MILK YIELD OF THE EWE AND EVIDENCE ON THE NATURE OF THE INHIBITION OF MILK EJECTION BY HALF-UDDER MILKING M. MORAG Negev Institute for Arid Zone of daily milking is derived from both survey and experimental data. HANSSONand BONNIER, (1947) have pointed

  5. Contribution of body reserves to milk production in underfed dairy ewes

    E-print Network

    Paris-Sud XI, Université de

    Contribution of body reserves to milk production in underfed dairy ewes A Agus F Bocquier1 IINRA ruminants can mobilize body reserves, mainly lipids, to maintain milk production. This ability to sustain milk production through body energy mobilization is well documented in dairy cows, but little is known

  6. Administration of distillate thyme leaves into the diet of Segureña ewes: effect on lamb meat quality.

    PubMed

    Nieto, G; Bañón, S; Garrido, M D

    2012-12-01

    The effect of including thyme by-products from the distillation industry into the diet of pregnant ewes on the final quality of lamb meat was evaluated during meat storage in modified atmosphere. A total of 36 Segureña ewes were randomly assigned to three homogeneous groups. One group was fed a basal diet (BD) as control (C), whereas the diet of the other two groups was modified by substituting 10% (T 1) and 20% (T 2) of the BD with pellets made from 50% barley and 50% distilled thyme leaves (DTL). Meat spoilage (total viable, psychrotroph (PSY), moulds and yeasts, Enterobacteriaceae and lactic acid bacteria), thiobarbituric acid reactive substances (TBARS), colour (CIELab coordinates, metmyoglobin) and sensory characteristics of fresh lamb meat packed in modified atmosphere packaging (70% O2 : 30% CO2) were analysed after storage at 0, 7, 14 and 21 days. In general, the DTL-containing diet inhibited lipid and pigment oxidation in fresh lamb meat. Lower PSY counts and content of secondary oxidation product (TBARS) as a result of adding DTL to the ewe diet, whereas surface redness (a* values) was significantly higher on days 7 and 14. It can be concluded that thyme by-products from the distillation industry could be used as a source of natural antioxidant and antimicrobial in the feed for ewes. PMID:23031660

  7. Creating aversion to toxic plants in ewe lambs: The example of Ferula communis

    Microsoft Academic Search

    S. Landau; A. Egber; A. Shlosberg; M. Belaich; A. Perevolotsky

    SUMMARY - The circum-Mediterranean perennial Ferula communis (giant fennel) contains anticoagulant constituents. The value of conditioned feed aversion (CFA) - building up temporal contiguity between ingestion of the plant and post-ingestive malaise in order to elicit rejection at later encounters - as a means to minimize intake of F. communis was investigated. Because most casualties are ewe-lambs, within 30 days

  8. Analysis Time and Lactation Stage Influence on Lactoperoxidase System Components in Dairy Ewe Milk

    Microsoft Academic Search

    R. L. Althaus; M. P. Molina; M. Rodríguez; N. Fernández

    2001-01-01

    To study the effect of time elapsed from the moment of taking samples on lactoperoxidase system compo- nents, we analyzed the activity of the lactoperoxidase enzyme and the concentrations of thiocyanate and hy- drogen peroxide in 46 individual samples of Manchega ewe milk. Samples were maintained at a temperature of 4°C until analysis, which took place at 6, 12, 24,

  9. Grant Title: EWING MARION KAUFFMAN FOUNDATION GRANTS Funding Opportunity Number: N/A

    E-print Network

    Farritor, Shane

    Grant Title: EWING MARION KAUFFMAN FOUNDATION GRANTS Funding Opportunity Number: N/A Agency in science, technology, engineering and math (STEM). Release and Expiration: N/A Application Deadline programs and activities nationally and within the Kansas City area. The majority of the education grants go

  10. The effect of a split feeding regimen and breed on body temperature of hair sheep ewes in the tropics.

    PubMed

    Godfrey, R W; Vinson, M C; Ketring, R C

    2013-11-01

    Lactating St. Croix White and Dorper×St. Croix White ewes were used to evaluate the effect of breed and feeding a split ration on body temperature during the cool (March-April) and warm (July-August) seasons in the U.S. Virgin Islands. Within each season ewes were assigned to treatments (n=8/treatment) based on breed, age, and number of lambs. Treatments consisted of individually feeding ewes daily 0.9 kg concentrate (16.4% CP and 68% TDN) in the morning (AM) or afternoon (PM), 0.45 kg in the morning and afternoon (AM-PM), or no feed (Control) for 56 d beginning on d 7 (lambing=d 0). Ewes were fitted with intravaginal temperature data loggers, set to record vaginal temperature (VT) at 5-min intervals, for 48 h in wk 2 (d 8-14), 5 (d 29-35), and 8 (d 50-56) postpartum. Repeated measures analysis of VT was conducted using a model including treatment, season, and breed as fixed effects. There was no effect of season so data were pooled across season. The interaction of breed with treatment or season was not significant so breed comparisons were made using data pooled across treatments and season. The mean temperature, relative humidity, and temperature-humidity index during the cool and warm seasons were 25.8°C, 85.9%, and 76.1 and 28.3°C, 86.7%, and 80.6, respectively. There was no effect of season or the breed×treatment×season interaction on VT (P>0.10) so all data were pooled across season and breed for analysis of the treatment effect. During wk 2 there was no difference (P>0.10) in VT among treatment groups. During wk 5 the AM-PM ewes had higher (P<0.01) VT than AM, PM, or Control ewes. During wk 8 the AM-PM and PM ewes had higher VT (P<0.01) than either the AM or Control ewes. To evaluate breed effect, data were pooled across treatments and seasons and analyzed using breed as the single main effect. Dorper×St. Croix White ewes had higher (P<0.0001) VT than St. Croix White ewes. The results show that body temperature of ewes can be influenced by time of feeding and breed. The local breed of sheep, St. Croix White, had a lower body temperature than Dorper×St. Croix White sheep. Ewes that were fed in the afternoon for an extended time during the postpartum period developed elevated body temperatures, which could make them more susceptible to heat stress. PMID:24045495

  11. Green leaf allowance and dairy ewe performance grazing on tropical pasture.

    PubMed

    De Souza, J; Batistel, F; Ticiani, E; Sandri, E C; Pedreira, C G S; Oliveira, D E

    2014-06-01

    The objective of this study was to explain the influence of green leaf allowance levels on the performance of dairy ewes grazing a tropical grass. Seventy-two lactating ewes grazed Aruana guineagrass (Panicum maximum Jacq. cv. Aruana) for 80 d. The treatments were 4 daily levels of green leaf allowance (GLA) on a DM basis corresponding to 4, 7, 10, and 13 kg DM/100 kg BW, which were named low, medium-low, medium-high, and high level, respectively. The experimental design was completely randomized with 3 replications. During the experimental period, 4 grazing cycles were evaluated in a rotational stocking grazing method (4 d of grazing and 16 d of rest). There was a linear effect of GLA on forage mass, and increasing GLA resulted in increased total leaf mass, reaching an asymptotic plateau around the medium-high GLA level. The stem mass increased with increased GLA, and a pronounced increase was observed between medium-high and high GLAs. Increasing GLA increased both forage disappearance rate and postgrazing forage mass. Leaf proportion increased with GLA, peaking at the medium-high level, and the opposite occurred for stem proportions, which reduced until medium-high GLA level, followed by an increase on high GLA. Forage CP decreased linearly with GLA, and increasing GLA from low to high reduced CP content by 31%. On the other hand, NDF increased 14% and ADF increased 26%, both linearly in response to greater GLA levels. Total digestible nutrients decreased linearly by 8% when GLA increased from low to high level. Milk yield increased, peaking at medium-high GLA (1.75 kg ewe(-1) d(-1)) and decreased at high GLA level (1.40 kg ewe(-1) d(-1)). Milk composition was not affected by the GLA levels. There was a reduction in stocking rate from 72 to 43 ewes/ha when GLA increased from low to high level. Productivity (milk yield kg ha(-1) d(-1)) increased as GLA increased, peaking at medium-low level (115 kg ha(-1) d(-1)). Although this tropical grass showed the same pattern in responses to GLA levels as reported in the literature with temperate pastures, the magnitude of the process changed and the maximum response in milk yield from lactating dairy ewes grazing a tropical pasture would be achieved with higher forage allowances than in temperate pastures. Overall, Aruana guineagrass grazed by lactating dairy ewes should be managed to provide 7 to 10 GLA in kg DM/100 kg BW according to the production goals. PMID:24671589

  12. RADIOTHERAPY TO IMPROVE LOCAL CONTROL REGARDLESS OF SURGICAL MARGIN AND MALIGNANCY GRADE IN EXTREMITYAND TRUNK WALL SOFT TISSUE SARCOMA: A SCANDINAVIAN SARCOMA GROUP STUDY

    Microsoft Academic Search

    NINA L. JEBSEN; CLEMENT S. TROVIK; C. F. BAUER; ANDERS RYDHOLM; ODD R. MONGE; THOR ALVEGARD; ØYVIND S. BRULAND

    Purpose: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of local- ized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scan- dinavia between 1986 and 2005. Methods and Materials: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian

  13. R/V EWING seismic source array calibrations: 2003

    NASA Astrophysics Data System (ADS)

    Diebold, J.; Webb, S.; Tolstoy, M.; Rawson, M.; Holmes, C.; Bohnenstiehl, D.; Chapp, E.

    2003-12-01

    In the Northern Gulf of Mexico, May, 2003, an NSF-funded effort was carried out to obtain calibrated measurements of the various airgun arrays deployed by R/V EWING during its seismic surveys. The motivations for this were several: to ground-truth the modeling upon which safety radii for marine mammal mitigation are established; to obtain broadband digitized signals which will accurately define the full spectral content of airgun signatures; to investigate the effects of seafloor interactions and their contribution to the acoustic noise levels from seismic sources. For this purpose, a digital, remotely telemetering spar buoy was designed and assembled; affording interactive control over the choice of two hydrophone channels, four fixed gain settings and four digitizing rates [6,250 - 50,000 Hz.] Three deployments were planned: a deep-water site, suitable for comparison of actual signals with modeled results; a shallow-water [25 - 50m] site where the effects of bottom interaction would be strongest; and a continental-slope site, which represents the favored habitat of many cetacean species. Methodology was developed which enabled the sequential discharge of four subarrays of 6, 10, 12 and 20 airguns. A separate run was made with two "GI" airguns, the favored high resolution survey source. An Incidental Harassment Authorization and a Biological Opinion, including an Incidental Take Statement were issued for the project by National Marine Fisheries, and a suite of marine mammal observation and mitigation procedures was followed. The deep and shallow water sites were occupied, and some 440 airgun signals were recorded. The slope site work was cancelled due to weather too poor for accurate marine mammal observation, but calibration was subsequently carried out with an exploration industry source vessel in a similar environment. Preliminary results indicate that the mitigation modeling is accurate, though somewhat conservative; that the radiated energy from airgun arrays, known to be strongest at very low frequencies, continues to diminish as frequencies increase up to 25 kHz, and that interactions with the seafloor, while complex, are understandable.

  14. Effect of feeding calcium salts on performance of nursing Awassi ewes.

    PubMed

    Obeidat, Belal S; Awawdeh, Mofleh S; Titi, Hosam H; AbuGhazaleh, Amer A; Al-Lataifeh, Fatima A; Alawneh, Ibrahim A; Abu Ishmais, Majdi A; Qudsieh, Rasha I; Subih, Hadil S

    2011-08-01

    Twenty nursing Awassi ewes (BW?=?50?±?2.35 kg, age?=?4.5?±?1.2 years) with their lambs were used to evaluate the effects of feeding calcium salts in lactation diets on performance and pre-weaning growth of their lambs. Treatments were 0% calcium salts (CON) or 5% calcium salts (FAT). At the end of the study, a digestibility experiment was performed. Milk yield was greater (P?ewes fed the FAT diet than the CON diet. Milk composition was similar (P?>?0.05) between diets. However, milk energy value (kcal/day) tended to be greater (P?=?0.07) for the FAT diet than the CON diet. Concentrations of milk C18:1c9 and C20:0 were greater (P?ewes fed the FAT diet than the CON diet. However, concentration of trans-10, cis-12 CLA was lower (P?=?0.05) in the FAT diet than in the CON diet. No differences in feed intake and body weight change were detected between diets. Digestibility of dry matter, organic matter, crude protein, ether extract, neutral detergent fiber, and acid detergent fiber were similar (P?>?0.05) for diets. For lambs, weaning weight was not affected by treatments. However, average daily gain and total gain were greater (P?=?0.053) for the FAT diet than the CON diet. Results suggest that supplementing lactating ewes with calcium salts at the beginning of lactation phase improves daily milk yield of ewes and pre-weaning growth of their lambs with no major negative impact on feed intake and digestibility. PMID:21448779

  15. Scopolamine impairs the ability of parturient ewes to learn to recognise their lambs.

    PubMed

    Lévy, F; Richard, P; Meurisse, M; Ravel, N

    1997-01-01

    Within a 4-h period after parturition, the ewe learns the odor of her lamb that will later allow recognition of her offspring from an alien lamb. This study investigated the involvement of the cholinergic system in this olfactory learning. At parturition and 2 h later, ewes received IM injections of saline (C group, n = 21), scopolamine methylbromide (METSCOP group, 100 micrograms/kg, n = 14) a peripherally acting muscarinic antagonist, a low dose of scopolamine hydrobromide (SCOP32 group, 32 micrograms/kg, n = 15) or a higher dose of scopolamine hydrobromide (SCOP100 group, 100 micrograms/kg, n = 18). Maternal behavior was observed at parturition and selective behavior was tested after 4 h of mother-young contact. No differences in maternal behavior at parturition were found between groups. By contrast, the proportion of ewes showing selectivity was significantly lower in the SCOP100 group (7/18) than in the METSCOP group (12/14, P = 0.01), SCOP32 group (12/15, P = 0.03), or C group (17/21, P = 0.01). In addition, saline-treated ewes, after having established their selective bond, received 100 micrograms/kg scopolamine and were again tested for selectivity 20 min later. Only one out of the 17 tested ewes failed to recognize their lambs after this treatment. These results indicate that intact central muscarinic transmission of the brain is required for the learning of individual lamb odor at parturition but not for the recall of this information. PMID:9122368

  16. 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

  17. 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

  18. Universal marker and detection tool for human sarcoma circulating tumor cells.

    PubMed

    Satelli, Arun; Mitra, Abhisek; Cutrera, Jeffry J; Devarie, Marcos; Xia, Xueqing; Ingram, Davis R; Dibra, Denada; Somaiah, Neeta; Torres, Keila E; Ravi, Vinod; Ludwig, Joseph A; Kleinerman, Eugenie S; Li, Shulin

    2014-03-15

    To date, no specific marker exists for the detection of circulating tumor cells (CTC) from different types of sarcomas, though tools are available for detection of CTCs in peripheral blood of patients with cancer for epithelial cancers. Here, we report cell-surface vimentin (CSV) as an exclusive marker on sarcoma CTC regardless of the tissue origin of the sarcoma as detected by a novel monoclonal antibody. Utilizing CSV as a probe, we isolated and enumerated sarcoma CTCs with high sensitivity and specificity from the blood of patients bearing different types of sarcoma, validating their phenotype by single cell genomic amplification, mutation detection, and FISH. Our results establish the first universal and specific CTC marker described for enumerating CTCs from different types of sarcoma, thereby providing a key prognosis tool to monitor cancer metastasis and relapse. PMID:24448245

  19. The boy who refused an IV: a case report of subcutaneous clodronate for bone pain in a child with Ewing Sarcoma

    Microsoft Academic Search

    Harold Siden

    2007-01-01

    BACKGROUND: Bone pain in malignancy can be challenging to treat. Bisphosphonates have been found to be useful in adults with bone pain, but there are no reports of their use in children for this indication. In pediatric palliative medicine there are hurdles in translating knowledge gained primarily in adult studies into application in children. Obstacles exist in initially determining whether

  20. Follicular dynamics and dominance in Booroola x Finnish Landrace and Booroola x Suffolk ewes heterozygous for the F gene.

    PubMed

    Castonguay, F; Dufour, J J; Minvielle, F; Estrada, R

    1990-05-01

    To study the influence of the F gene on follicular dynamics and dominance, 2-year-old Booroola x Finnish Landrace (BFL, N = 17) and Booroola x Suffolk (BS, N = 18) ewes were compared with contemporary purebred Finn (FL, N = 18) and Suffolk (S, N = 18) ewes. In Exp. 1, oestrous cycles of ewes were synchronized during the breeding season with progestagen-impregnated sponges. At sponge removal (Day 0), 14 days after insertion, ewes of each of the 4 genetic groups were assigned to Group 1 in which all follicles visible on both ovaries were destroyed by electrocauterization except for the largest (F1) which was marked, Group 2 in which all visible follicles on both ovaries were destroyed, or Group 3 in which the 3 largest follicles of both ovaries were identified as F1, F2 and F3 and marked. At 48 h after treatment (Day 2), follicular growth was evaluated. At Day 0, the mean number of small follicles (1-3 mm) was higher (P less than 0.05) for BS, S and BFL (35.8, 35.1 and 32.9) than FL (24.9) ewes. Large follicles (greater than or equal to 4 mm) were more numerous (P less than 0.05) in FL (3.5) than in BS (2.1) ewes, BFL and S ewes being intermediate. Diameter of the F1 follicle was larger (P less than 0.05) for S (7.6 mm) than FL, BS and BFL (5.8, 5.1 and 5.1 mm) ewes. In Group 1, all F1 follicles marked at Day 0 ovulated at oestrus after sponge removal for BFL, BS and S ewes while in FL ewes, 2 of 6 F1 follicles regressed. In ewes ovulating, only the F1 follicle ovulated except for one S ewe which shed one more ovum. In Group 2, there were no follicles greater than or equal to 4 mm at Day 2 and no ewes ovulated after treatment. In Group 3, the proportion of marked follicles that ovulated was higher for S ewes than in those of the prolific genotypes. The number of follicles not marked at Day 0 but ovulating (compared to the total number of ovulations) was higher in BFL, BS and FL (8/11, 9/13 and 9/13) than S (3/10) ewes. In Exp. 2, prolific (BFL + BS) and non-prolific (S) ewes were compared following destruction of follicles greater than or equal to 3 mm with the F1 left intact (Treatment 1) or destroyed (Treatment 2), 12 days after sponge insertion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2374114

  1. Isolated Kaposi Sarcoma of the Tonsil: A Case Report and Review of the Scientific Literature

    PubMed Central

    Pittore, Barbara; Pelagatti, Carlo Loris; Deiana, Francesco; Ortu, Francesco; Maricosu, Elena; Cossu, Sergio; Sotgiu, Giovanni

    2015-01-01

    Kaposi sarcoma is a tumour caused by human herpes virus 8, also known as Kaposi sarcoma-associated herpes virus. It usually affects the skin and oral mucosa; however, it can also sometimes affect the lungs, the liver, the stomach, the bowel, and lymph nodes. Several body sites may be affected simultaneously. The involvement of the tonsils is rare. We described an isolated localization of Kaposi's sarcoma of the right tonsil in a HIV-positive patient. PMID:25755902

  2. Human herpesvirus-like nucleic acid in various forms of Kaposi's sarcoma

    Microsoft Academic Search

    Y. Q. Huang; J. J. Li; W. C. Zhang; D. Feiner; A. E. Friedman-Kien; M. H. Kaplan; B. Poiesz; Ke Katabira

    1995-01-01

    The association between a new human herpesvirus-like agent and various forms of Kaposi's sarcoma was examined by PCR. The DNA sequences of this agent were detected in 7 of 8 classic Kaposi's sarcoma specimens, 12 of 12 AIDS-associated specimens from the United States, and 7 of 10 specimens from African endemic Kaposi's sarcoma. Polymorphism of the herpesvirus-like DNA in the

  3. Risk Assessment Based on FDG-PET Imaging in Patients with Synovial Sarcoma

    Microsoft Academic Search

    Jennifer W. Lisle; Janet F. Eary; Janet O’Sullivan; Ernest U. Conrad

    2009-01-01

    Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent\\u000a not all synovial sarcomas share the same tumor biology. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We\\u000a therefore assessed the clinical value of 18F-FDG-PET-derived maximum standard uptake value (SUVmax) for predicting survival in patients

  4. Isolated kaposi sarcoma of the tonsil: a case report and review of the scientific literature.

    PubMed

    Pittore, Barbara; Pelagatti, Carlo Loris; Deiana, Francesco; Ortu, Francesco; Maricosu, Elena; Cossu, Sergio; Sotgiu, Giovanni

    2015-01-01

    Kaposi sarcoma is a tumour caused by human herpes virus 8, also known as Kaposi sarcoma-associated herpes virus. It usually affects the skin and oral mucosa; however, it can also sometimes affect the lungs, the liver, the stomach, the bowel, and lymph nodes. Several body sites may be affected simultaneously. The involvement of the tonsils is rare. We described an isolated localization of Kaposi's sarcoma of the right tonsil in a HIV-positive patient. PMID:25755902

  5. Cross-sectional imaging of primary thoracic sarcomas with histopathologic correlation: a review for the radiologist.

    PubMed

    Dillman, Jonathan R; Pernicano, Perry G; McHugh, Jonathan B; Attili, Anil K; Mourany, Bassem; Pinsky, Renee W; Strouse, Peter J; Kazerooni, Ella A

    2010-01-01

    Numerous forms of primary sarcoma can arise from the heart, pericardium, great vessels, lungs, chest wall, and breasts. Magnetic resonance imaging and computed tomography currently play important roles in determining the extent of primary thoracic sarcoma involvement, potential for resectability, and response to therapy. The purpose of this article is to review the various forms of primary sarcoma that may affect the thorax as well as illustrate pertinent cross-sectional radiologic findings with histopathologic correlation. PMID:19931110

  6. Cytologic diagnosis of undifferentiated high grade pleomorphic sarcoma of breast presenting with brain metastasis

    PubMed Central

    Chakrabarti, Indranil; Ghosh, Nilanjana; Giri, Amita

    2013-01-01

    Primary sarcoma of breast are rare. Diagnosis by aspiration cytology is difficult due to nonspecific cytomorphologic features. An initial presentation with neurological symptoms due to metastasis of breast sarcoma to the brain has not been previously reported. Here, we describe a case of a 60-year-old female who presented with headache, dizziness and convulsion and was subsequently diagnosed with undifferentiated high grade pleomorphic sarcoma of breast with cerebellar metastasis. PMID:23914101

  7. Postradiation osteogenic sarcoma of bone and soft tissues. A clinicopathologic study of 66 patients

    Microsoft Academic Search

    Andrew G. Huvos; Helen Q. Woodard; William G. Cahan; Norman L. Higinbotham; Fred W. Stewart; Avital Butler; Sara S. Bretsky

    1985-01-01

    Sixty-six patients with well-documented osteogenic sarcomas arising in bones and soft tissues after exposure to x-rays, which represent approximately 5.5 percent of all osteogenic sarcomas registered since 1921 at this institution, were studied. These secondary sarcomas occurred in equal proportion in both sexes, with the sixth decade of life being the most common age. In 42 patients, the bone had

  8. Sodium chlorate reduces presence of Escherichia coli in feces of lambs and ewes managed in shed-lambing systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to establish doses of orally-administered NaClO3 that reduced presence of generic Escherichia coli in intestines of ewes and neonatal lambs managed in a shed-lambing system. Neonatal lambs (n = 32; age = 7.1 ± 1.2 d; BW = 6.8 ± 1.0 kg) and yearling ewes (n = 44; BW = 74.8 ± 5.6 kg)...

  9. Effect of willow supplementation upon plasma amino acid concentration in ewes grazing drought pastures of low nutritive value

    Microsoft Academic Search

    D. W. Pitta; T. N. Barry; N. Lopez-Villalobos; G. T. Attwood

    2009-01-01

    Effects of supplementing willow stem cuttings to ewes grazing drought pastures upon plasma amino acid (AA) concentrations was studied on Massey University's Riverside Farm, near Masteron, on the East Coast of New Zealand. Ewes of similar age and weight (i.e., 59.0±2.22kg) were assigned to two groups of 7 each, either with (supplemented) or without (control) supplementation of willow, and experimental

  10. Safety of an amino-acetonitrile derivative (AAD), monepantel, in ewes and their offspring following repeated oral administration

    Microsoft Academic Search

    N Malikides; K Spencer; R Mahoney; K Baker; K Vanhoff; C Hall; R Debenedetti; GA Strehlau

    2009-01-01

    AIM: To demonstrate the clinical and reproductive safety in ewes and their offspring of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire reproductive cycle.METHODS: A randomised controlled blinded study design was used. One hundred and twelve primi- or multi-parous ewes and 28 rams were randomly

  11. Relationship between beta-lactoglobulin polymorphism and milk fatty acid composition in milk of Massese dairy ewes

    Microsoft Academic Search

    M. Mele; G. Conte; A. Serra; A. Buccioni; P. Secchiari

    2007-01-01

    The influence of milk beta-lactoglobulin phenotype on the content of fat, total protein, whey protein, casein, and fatty acids of 163 individual milk samples from Massese ewes was determined. Sampling was conducted randomly on five dairy ewe farms located in the area of origin of the Massese breed (North-West Tuscany, Italy). Three beta-lactoglobulin phenotypes were detected: their frequencies were AA

  12. Synovial sarcoma of the abdominal wall: Imaging findings and review of the literature

    PubMed Central

    de Haas, Robbert J.; Bonenkamp, Johannes J.; Flucke, Uta E.; de Rooy, Jacky W.J.

    2015-01-01

    Synovial sarcoma is the fourth most common type of soft-tissue sarcoma (following undifferentiated pleomorphic sarcoma, liposarcoma, and rhabdomyosarcoma), and should be considered a high-grade neoplasm with a high number of local recurrences and late metastases. Synovial sarcoma predominantly occurs in adolescents and young adults, and typically arises near the joints of the lower extremity. However, this tumor can also occur at uncommon sites such as the abdominal wall, which is illustrated in this article. Furthermore, we reviewed the available literatures on the clinical, pathological and radiological appearances, as well as the current knowledge concerning treatment options and prognosis. PMID:25926925

  13. Walleye Dermal Sarcoma Virus: Molecular Biology and Oncogenesis

    PubMed Central

    Rovnak, Joel; Quackenbush, Sandra L.

    2010-01-01

    Retroviruses have been detected in most vertebrate species and are etiologic agents of a variety of neoplastic diseases. The study of retroviruses has been instrumental in uncovering the molecular mechanisms responsible for oncogenesis. Retroviruses have been isolated from three neoplastic diseases in fish, two of which affect the dermis and regress naturally coincident with spawning. This feature provides a unique model to study mechanisms of tumor development and regression. Three complex retroviruses, isolated from walleye (Sander vitreus) with dermal sarcoma and epidermal hyperplasia, are the members of the newest retroviral genus, Epsilonretrovirus. Three accessory proteins, encoded by walleye dermal sarcoma virus (WDSV), function in the regulation of host and viral gene expression and cell cycle, alter cell-signaling pathways to promote cell proliferation and block apoptosis, and, finally, induce apoptosis through dissipation of the mitochondrial membrane potential. PMID:21994717

  14. Walleye dermal sarcoma virus: molecular biology and oncogenesis.

    PubMed

    Rovnak, Joel; Quackenbush, Sandra L

    2010-09-01

    Retroviruses have been detected in most vertebrate species and are etiologic agents of a variety of neoplastic diseases. The study of retroviruses has been instrumental in uncovering the molecular mechanisms responsible for oncogenesis. Retroviruses have been isolated from three neoplastic diseases in fish, two of which affect the dermis and regress naturally coincident with spawning. This feature provides a unique model to study mechanisms of tumor development and regression. Three complex retroviruses, isolated from walleye (Sander vitreus) with dermal sarcoma and epidermal hyperplasia, are the members of the newest retroviral genus, Epsilonretrovirus. Three accessory proteins, encoded by walleye dermal sarcoma virus (WDSV), function in the regulation of host and viral gene expression and cell cycle, alter cell-signaling pathways to promote cell proliferation and block apoptosis, and, finally, induce apoptosis through dissipation of the mitochondrial membrane potential. PMID:21994717

  15. Establishment of productively infected walleye dermal sarcoma explant cells

    PubMed Central

    Rovnak, Joel; Casey, Rufina N.; Brewster, Connie D.; Casey, James W.; Quackenbush, Sandra L.

    2012-01-01

    Walleye dermal sarcoma virus (WDSV) is a complex retrovirus associated with dermal sarcomas in walleye fish. Virus expression is tightly regulated and limited to accessory gene transcripts throughout tumour development. During tumour regression, this regulation is lost and the replication of virus is greatly enhanced. Cultured walleye fibroblasts infected in vitro do not produce significant quantities of infectious virus. Tissue culture cells established by explantation of tumour cells were found to harbour WDSV provirus and to express accessory and structural proteins. The sequence of the provirus showed little variation from a previous WDSV isolate. Retroviral particles were isolated from supernatants from these cells and were able to transfer infection to uninfected walleye fibroblasts. In addition to the virus present in supernatants, much of the virus was cell associated and liberated only by sonication. This virus was found at internal cellular membranes, including mitochondria, and was infectious. PMID:17698670

  16. Bone sarcoma in humans induced by radium: A threshold response?

    SciTech Connect

    Rowland, R.E.

    1996-08-01

    The radium 226 and radium 228 have induced malignancies in the skeleton (primarily bone sarcomas) of humans. They have also induced carcinomas in the paranasal sinuses and mastoid air cells. There is no evidence that any leukemias or any other solid cancers have been induced by internally deposited radium. This paper discuses a study conducted on the dial painter population. This study made a concerted effort to verify, for each of the measured radium cases, the published values of the skeletal dose and the initial intake of radium. These were derived from body content measurements made some 40 years after the radium intake. Corrections to the assumed radium retention function resulted in a considerable number of dose changes. These changes have changed the shape of the dose response function. It now appears that the induction of bone sarcomas is a threshold process.

  17. Quality of life measures in soft tissue sarcoma.

    PubMed

    Gundle, Kenneth R; Cizik, Amy M; Jones, Robin L; Davidson, Darin J

    2015-01-01

    The assessment of health-related quality of life (HRQL) via patient-reported outcomes has the potential to answer critical questions and improve the care of soft tissue sarcoma (STS). This review outlines the rationale for quality of life measures in sarcoma, and details various instrument types: disease- and anatomic-specific, provider-generated, generic HRQL and health state utilities. Prior usage in STS populations, relative advantages of specific patient-reported outcome measures and a framework for selecting appropriate measures are discussed. Uniform incorporation of validated HRQL measures in STS clinical research would further the understanding of patient wellbeing beyond traditional clinical measures, and more widespread use of health state utilities measures in particular has the potential to facilitate comparative effectiveness research. PMID:25377073

  18. Imaging of soft tissue and osseous sarcomas of the extremities.

    PubMed

    Colleran, Gabrielle; Madewell, John; Foran, Paul; Shelly, Martin; O'Sullivan, Paul J

    2011-10-01

    Soft tissue and osseous sarcomas of the extremities are uncommon malignancies that represent very important diagnostic entities because of their aggressive nature. Radiologic investigations, including plain film, computed tomography, contrast-enhanced magnetic resonance imaging; scintigraphy, ultrasound, and positron emission tomography-computed tomography, play critical roles in providing a differential, establishing the diagnosis, demonstrating prognostic characteristics, and tailoring tumor treatment. The purpose of this review is to describe the most common soft tissue and osseous sarcomas of the extremities, with emphasis on their plain film and magnetic resonance imaging characteristics with the aim of aiding the reader to accurately describe the important imaging features and generate an appropriate differential diagnosis to aid the referring clinician with prompt appropriate management and treatment. PMID:21963165

  19. [A case of stromal sarcoma with multiple local recurrences].

    PubMed

    Murakami, Eriko; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2014-11-01

    A 53-year-old woman presented with a right breast lump identified approximately 6 months previously on palpation. Because the lump gradually increased in size, she initially visited a general practitioner who referred her to our hospital. Mammography and breast ultrasonography revealed a lesion in the right breast. Biopsy indicated a case of stromal sarcoma. Three months later, another lesion was detected, and simple mastectomy was performed. A recurrent lesion was detected after 1 month, and lumpectomy was performed. Another mass developed 1 month later, and extirpation was performed. After 1 month, another mass was detected, and extirpation was performed again. The stump was negative for lesions and recurrences. A thorough examination did not reveal metastasis to remote organs. There are no established therapies for stromal sarcoma. Surgical excision is undoubtedly indicated, as observed in this patient who showed multiple recurrent lesions despite the surgeries performed. PMID:25731369

  20. Systemic therapy in soft tissue sarcomas: past, present and future.

    PubMed

    Purohit, Samit; Bhise, Rohan; Appachu, Sandhya; Lakshmaiah, K C; Govindbabu, K

    2011-12-01

    Soft tissue sarcomas (STS) comprise 1% of all cancers diagnosed worldwide with more than 40 different histological subtypes each with distinct underlying biology, natural history and response to treatment. Due to the differential chemosensitivity it is imperative to have a correct histological diagnosis for optimal treatment of these patients. Even though surgery remains the primary modality of treatment there is increasing specialization of chemotherapy with respect to histological subtype. In general there is no place for "one size fits all strategy". To correctly define the role of chemotherapy, an extensive search was carried out online and offline for all relevant articles concerning chemotherapy in soft tissue sarcoma. This review aims to discuss the evolution of chemotherapy, its present role in neoadjuvant, adjuvant, metastatic settings and exciting trends with the advent of targeted therapies. PMID:23204790

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

    PubMed

    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 (T 1, n = 15) or 48 hours after parturition (T 2, 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% (T 1) and 96.9% (T 2). 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 T 1 (94.8%) and T 2 (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

  2. Fertility Rates of Ewes Treated with Medroxyprogesterone and Injected with Equine Chorionic Gonadotropin plus Human Chorionic Gonadotropin in Anoestrous Season.

    PubMed

    Santos, I W; Binsfeld, L C; Weiss, R R; Kozicki, L E

    2010-01-01

    The aim of the present paper was to investigate the efficiency of the equine chorionic gonadotropin (eCG) plus human chorionic gonadotropin (hCG) associated with medroxyprogesterone acetate (MAP) to estrous ewes synchronization. Ninety Texel ewes were investigated during seasonal anoestrous. The ewes received intravaginal sponges containing MAP (60?mg) for nine days. At the time of sponges' withdrawal, the ewes were divided into three groups (G): (1) receiving 2?mL of saline i.m. (n = 30), (2) receiving eCG 400?IU i.m. (n = 30), and (3) receiving eCG 400?IU plus hCG 200?IU i.m. (n = 30). Twelve h after sponges' removal, teaser rams were used to estrus check and remained with the ewes for 96?h. The artificial insemination was made with fresh semen 10?h after estrus detection. The effect of the treatment was not significant for the estrous rates among the groups: 73%, 90%, and 86%, respectively. The main effect was observed in the pregnancy and lambing rates among the groups: 70%, 86%, 56%, and 80%, 120%, 56%, respectively. Based on these results from our study, the use of the MAP-eCG is the best choice to improve the fertility rate on ewes. PMID:20953333

  3. Sources of variation in the reproductive performance of ewes inseminated with frozen-thawed ram semen by laparoscopy.

    PubMed

    Eppleston, J; Maxwell, W M

    1995-03-01

    Fertility data from 8 artificial insemination programs, involving more than 5000 ewes and 110 rams in 3 flocks, were analyzed to determine variation due to individual AI program and ram in the reproductive performance of ewes inseminated with frozen-thawed semen by laparoscopy. The semen had been previously frozen by commercial AI centers in either pellets or straws. Both AI program and individual ram affected the proportion of ewes pregnant and the number of fetuses per ewe inseminated, but not the number of fetuses per pregnant ewe. Semen samples from 97 of the rams used were analyzed on a Hamilton Thorn HTM 2000 image analyzer for sperm concentration, percentage of motile and progressively motile spermatozoa, mean progressive velocity, and mean linear index. The correlations between these traits and reproductive performance obtained after insemination were calculated. There was large variation in the quantity and quality of the frozen semen, but only the number of total and motile spermatozoa inseminated per ewe was correlated with fertility (0.25 and 0.26, respectively). Regression analysis showed that none of the traits measured were useful for predicting fertility. PMID:16727668

  4. Fertility Rates of Ewes Treated with Medroxyprogesterone and Injected with Equine Chorionic Gonadotropin plus Human Chorionic Gonadotropin in Anoestrous Season

    PubMed Central

    Santos, I. W.; Binsfeld, L. C.; Weiss, R. R.; Kozicki, L. E.

    2010-01-01

    The aim of the present paper was to investigate the efficiency of the equine chorionic gonadotropin (eCG) plus human chorionic gonadotropin (hCG) associated with medroxyprogesterone acetate (MAP) to estrous ewes synchronization. Ninety Texel ewes were investigated during seasonal anoestrous. The ewes received intravaginal sponges containing MAP (60?mg) for nine days. At the time of sponges' withdrawal, the ewes were divided into three groups (G): (1) receiving 2?mL of saline i.m. (n = 30), (2) receiving eCG 400?IU i.m. (n = 30), and (3) receiving eCG 400?IU plus hCG 200?IU i.m. (n = 30). Twelve h after sponges' removal, teaser rams were used to estrus check and remained with the ewes for 96?h. The artificial insemination was made with fresh semen 10?h after estrus detection. The effect of the treatment was not significant for the estrous rates among the groups: 73%, 90%, and 86%, respectively. The main effect was observed in the pregnancy and lambing rates among the groups: 70%, 86%, 56%, and 80%, 120%, 56%, respectively. Based on these results from our study, the use of the MAP—eCG is the best choice to improve the fertility rate on ewes. PMID:20953333

  5. 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.

  6. Follow-up of the soft tissue sarcoma patient.

    PubMed

    Tseng, William W; Amini, Behrang; Madewell, John E

    2015-04-01

    Despite optimal treatment, patients with soft tissue sarcoma are at risk for recurrence and therefore appropriate surveillance is critical. At minimum, regularly scheduled clinical assessments and chest X-rays are necessary. Consensus guidelines are available; however, surveillance strategies must be personalized based on the risk for recurrence and inherent disease biology. Further research is needed on a number of issues, including the impact of surveillance on clinical outcome and the utility of molecular surveillance. PMID:25322963

  7. Disseminated Kaposi sarcoma in a HIV negative patient

    PubMed Central

    Lin, Guoshu; Wang, Hongyan; Fan, Xing; Li, Hui; Wang, Zaixing; Lin, Da; Yang, Sen; Zhang, Xuejun

    2015-01-01

    Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vascular nodules on the skin and other organs. It is a systemic, malignant and multifactor disease and has a variable course. We describe an elderly Chinese man who had a rapidly growing maroon nodule on his right foot, both arms and cheekbones. KS in HIV-negative patients has only been reported sporadically. PMID:26045873

  8. Undifferentiated sarcoma of the orbit with angiomyxoid features.

    PubMed

    De Niro, Jennifer E; Cham, Elaine M; Silkiss, Rona Z

    2014-01-01

    A 7-month-old female infant developed a grade 3 un-differentiated sarcoma with angiomyxoid features of the right orbit. The tumor expanded rapidly 2 months after an initial sub-total resection and extended posteriorly toward the right cavernous sinus. After treatment with ifosphamide, doxorubicin, and proton beam radiation, there was no discernible residual tumor 20 months after starting chemotherapy. PMID:25314104

  9. Disseminated Kaposi sarcoma in a HIV negative patient.

    PubMed

    Lin, Guoshu; Wang, Hongyan; Fan, Xing; Li, Hui; Wang, Zaixing; Lin, Da; Yang, Sen; Zhang, Xuejun

    2015-01-01

    Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vascular nodules on the skin and other organs. It is a systemic, malignant and multifactor disease and has a variable course. We describe an elderly Chinese man who had a rapidly growing maroon nodule on his right foot, both arms and cheekbones. KS in HIV-negative patients has only been reported sporadically. PMID:26045873

  10. Structural Characterization of the Rous Sarcoma Virus RNA Stability Element

    Microsoft Academic Search

    Jason E. Weil; Michalis Hadjithomas; Karen L. Beemon

    2009-01-01

    In eukaryotic cells, an mRNA bearing a premature termination codon (PTC) or an abnormally long 3 untranslated region (UTR) is often degraded by the nonsense-mediated mRNA decay (NMD) pathway. Despite the presence of a 5- to 7-kb 3 UTR, unspliced retroviral RNA escapes this degradation. We previously identified the Rous sarcoma virus (RSV) stability element (RSE), an RNA element downstream

  11. Radiation-induced sarcomas of the head and neck

    PubMed Central

    Thiagarajan, Anuradha; Iyer, N Gopalakrishna

    2014-01-01

    With improved outcomes associated with radiotherapy, radiation-induced sarcomas (RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stage-matched sarcomas that arise independent of irradiation and surgical resection with clear margins seems to offer the best chance for cure. PMID:25493233

  12. Sarcoma of the thyroid gland: a case report.

    PubMed

    Marteil-Oudrer, A M; Friess, Ph; Vix, M; Gasser, B; Jeandidier, N; Pinget, M

    2002-06-01

    Sarcoma of the thyroid gland is a very uncommon malignant tumor (<1% of thyroid cancers) characterized by severe local course and rapid metastatic dissemination and very poor prognosis. We report the case of an 84-year-old woman hospitalized for expiratory dyspnea, severe malnutrition and swallowing disorders leading to bronchial infection. She had a voluminous (20 cm) extra-thoracic right-neck goiter with a considerable superficial venous pattern that had developed on an old goiter before growing recently. CEA and calcitonin levels were normal. The cervical-thoracic CT demonstrated a partially necrosed heterogeneously hypodense tumor compressing the esophagus and the trachea with displacement of adjacent structures which were not directly invaded. Large areas of necrosis and a probable metastatic image measuring 3 cm in the right median pulmonary lobe were observed. Macrobiopsy disclosed grade 3 sarcoma. Complete resection delivered a 3.170 kg tumor. Histology confirmed the diagnosis of sarcoma without neoplastic extension. Apart from right recurrent palsy, the initial post-operative period was satisfactory and the patient was discharged. Four and a half months later she was rehospitalized with local recurrence with a large metastatis in the right lung. She died two weeks later. PMID:12193877

  13. Bone sarcomas as second malignant neoplasms following childhood cancer

    SciTech Connect

    Newton, W.A. Jr.; Meadows, A.T.; Shimada, H.; Bunin, G.R.; Vawter, G.F. (Children's Hospital of Columbus, OH (USA))

    1991-01-01

    This study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood. Sarcomas of bone were the most common second malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13-institution consortium consisting of pediatric oncology centers from western Europe, Canada, and the United States. The authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import. The literature concerning the subtypes of bone tumors, clinical and experimental, is also reviewed. The authors also investigated the effect of several factors on the time interval from the first diagnosis to the SMN (i.e., the bone sarcoma). Anthracyclines significantly shortened the interval by about 3 years. The primary diagnosis also significantly affected the interval, with leukemia/lymphomas having the shortest interval and retinoblastoma the longest. The authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions. However, lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the SMN developed.

  14. V-ATPase as an effective therapeutic target for sarcomas

    SciTech Connect

    Perut, Francesca, E-mail: francesca.perut@ior.it [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Avnet, Sofia; Fotia, Caterina; Baglìo, Serena Rubina; Salerno, Manuela [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Hosogi, Shigekuni [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Kusuzaki, Katsuyuki [Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Baldini, Nicola [Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna (Italy); Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy)

    2014-01-01

    Malignant tumors show intense glycolysis and, as a consequence, high lactate production and proton efflux activity. We investigated proton dynamics in osteosarcoma, rhabdomyosarcoma, and chondrosarcoma, and evaluated the effects of esomeprazole as a therapeutic agent interfering with tumor acidic microenvironment. All sarcomas were able to survive in an acidic microenvironment (up to 5.9–6.0 pH) and abundant acidic lysosomes were found in all sarcoma subtypes. V-ATPase, a proton pump that acidifies intracellular compartments and transports protons across the plasma membrane, was detected in all cell types with a histotype-specific expression pattern. Esomeprazole administration interfered with proton compartmentalization in acidic organelles and induced a significant dose-dependent toxicity. Among the different histotypes, rhabdomyosarcoma, expressing the highest levels of V-ATPase and whose lysosomes are most acidic, was mostly susceptible to ESOM treatment. - Highlights: • Osteosarcoma, rhabdomyosarcoma, and chondrosarcoma survive in acidic microenvironment. • At acidic extracellular pH, sarcoma survival is dependent on V-ATPase expression. • Esomeprazole administration induce a significant dose-dependent toxicity.

  15. Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells

    PubMed Central

    Hettmer, Simone; Liu, Jianing; Miller, Christine M.; Lindsay, Melissa C.; Sparks, Cynthia A.; Guertin, David A.; Bronson, Roderick T.; Langenau, David M.; Wagers, Amy J.

    2011-01-01

    Soft-tissue sarcomas are heterogeneous cancers that can present with tissue-specific differentiation markers. To examine the cellular basis for this histopathological variation and to identify sarcoma-relevant molecular pathways, we generated a chimeric mouse model in which sarcoma-associated genetic lesions can be introduced into discrete, muscle-resident myogenic and mesenchymal cell lineages. Expression of Kirsten rat sarcoma viral oncogene [Kras(G12V)] and disruption of cyclin-dependent kinase inhibitor 2A (CDKN2A; p16p19) in prospectively isolated satellite cells gave rise to pleomorphic rhabdomyosarcomas (MyoD-, Myogenin- and Desmin-positive), whereas introduction of the same oncogenetic hits in nonmyogenic progenitors induced pleomorphic sarcomas lacking myogenic features. Transcriptional profiling demonstrated that myogenic and nonmyogenic Kras; p16p19null sarcomas recapitulate gene-expression signatures of human rhabdomyosarcomas and identified a cluster of genes that is concordantly up-regulated in both mouse and human sarcomas. This cluster includes genes associated with Ras and mechanistic target of rapamycin (mTOR) signaling, a finding consistent with activation of the Ras and mTOR pathways both in Kras; p16p19null sarcomas and in 26–50% of human rhabdomyosarcomas surveyed. Moreover, chemical inhibition of Ras or mTOR signaling arrested the growth of mouse Kras; p16p19null sarcomas and of human rhabdomyosarcoma cells in vitro and in vivo. Taken together, these data demonstrate the critical importance of lineage commitment within the tumor cell-of-origin in determining sarcoma histotype and introduce an experimental platform for rapid dissection of sarcoma-relevant cellular and molecular events. PMID:22135462

  16. Pattern of loss of spermatozoa from the vagina of the ewe.

    PubMed

    Tilbrook, A J; Pearce, D T

    1986-01-01

    In a series of experiments spermatozoa were inseminated blindly into the vagina of ewes and then recovered at varying times after insemination. Most of the spermatozoa inseminated were lost by drainage through the vulva. The rate of loss was not affected by the motility of spermatozoa or oestrous state of the ewe. Initially after insemination the loss was not rapid with 82% of the insemination 18% of spermatozoa remained and by 12 h 10% remained. Spermatozoa were removed from the vagina during withdrawal of the penis after intromission and the extent of this loss varied between rams and with the volume of semen already in the vagina. Up to half the inseminate was lost in this way when there was 0.5 ml of semen in the vagina but only 11% was lost when the volume of inseminate was 0.1 ml. The unavoidable loss of spermatozoa may influence the quantity available for fertilizing ova. PMID:3827743

  17. Expression of seasonality in Merinos d'Arles ewes of different genotypes at the MT1 melatonin receptor gene.

    PubMed

    Teyssier, J; Migaud, M; Debus, N; Maton, C; Tillard, E; Malpaux, B; Chemineau, P; Bodin, L

    2011-03-01

    Spontaneous ovulatory activity (SOA) in spring has been used to study the out-of-season breeding ability of Merinos d'Arles (MA) ewes. Within this breed, an association was found between more intense seasonality and genotype -/- at a MnlI restriction site (allele - for its absence v. + for its presence) in Exon II of the MT1 receptor gene. This study was designed to ascertain whether this association results in a direct effect of the MT1 genotype on the expression of seasonality in MA ewes. In the first year of the study, genotyping of 314 MA ewes at locus MnlI was carried out and resulted in frequencies of 43.0%, 44.9% and 12.1% for genotypes +/+, +/- and -/-, respectively. The SOA of these ewes was determined in early April of two consecutive years by assaying plasma progesterone concentrations in two blood samples taken 9 days apart. Groups of 30 ewes of each homozygous genotype (+/+ and -/-) were identified from this population and their SOA was followed by taking blood samples at regular intervals between January and mid-April of the second and third year of the study. In the second year, groups of ewes were managed together on rangelands, whereas in the third year each group was split into two subgroups given differential feed levels. The results clearly showed that genotype had no significant effect on SOA during the 2- to 3-month period preceding the introduction of rams for spring mating. In the second year of the study, in which the experimental procedure allowed a fair comparison of the fertility of ewes in spring mating, fertility was similar for both genotypes. The reciprocity of the association was not demonstrated and the MnlI polymorphic site could not be used as a genetic marker of selection for out-of-season breeding ability, at least not in the MA breed. The percentage of cycling ewes significantly decreased between January and April, and older ewes (5 or 6 years old depending on the year of the study) were more cyclic than younger ones (2 and 3 years old, respectively). The differential feeding level of ewes from early February did not significantly affect their SOA during the time period studied in the third year of the study. PMID:22445399

  18. Immune competence of the mammary gland as affected by somatic cell and pathogenic bacteria in ewes with subclinical mastitis.

    PubMed

    Albenzio, M; Santillo, A; Caroprese, M; Ruggieri, D; Ciliberti, M; Sevi, A

    2012-07-01

    Immune competence of the ewe mammary gland was investigated by monitoring the leukocyte differential count, cytokine pattern, and endogenous proteolytic enzymes in milk samples with different somatic cell counts (SCC) and pathogenic bacteria. Furthermore, the leukocyte differential count and T-lymphocyte populations were evaluated in ewe blood. A total of 1,500 individual milk samples were randomly selected from the pool of the samples collected during sampling and grouped into 5 classes of 300 samples each, on the basis of SCC. Classes were <300,000 cells/mL, from 300,000 to 500,000 cells/mL, from 501,000 to 1,000,000 cells/mL, from 1,001,000 to 2,000,000 cells/mL, and >2,000,000 cells/mL. Microbiological analyses of ewe milk were conducted to detect mastitis-related pathogens. Sheep whose udders were without clinical abnormalities, and whose milk was apparently normal but with at least 10(3)cfu/mL of the same pathogen were considered to have subclinical mastitis and therefore defined as infected. Polymorphonuclear neutrophilic leukocytes (PMNL) and macrophages increased with SCC, whereas lymphocytes decreased. Milk samples with SCC >1,000,000 cells/mL showed differences in leukocyte populations between uninfected and infected ewes, with higher percentages of PMNL and macrophages and lower percentages of lymphocytes in infected animals. Nonviable PMNL levels were the highest in ewe milk samples with SCC <300,000 cells/mL; starting from SCC >500,000 cells/mL, nonviable PMNL were higher in uninfected ewes than in infected ones. In infected animals giving milk with SCC >1,000,000 cells/mL, a higher CD4(+)/CD8(+) ratio was observed, suggesting that the presence of pathogens induced an activation of both CD4(+) and CD8(+). The levels of tumor necrosis factor-? and IL-12 were higher in infected than uninfected ewes, irrespective of SCC. Plasmin activity increased along with SCC and was always higher in infected than uninfected animals; cathepsin D increased starting from 1,001,000 cells/mL in milk samples from noninfected ewes and starting from 301,000 cells/mL in milk samples from infected animals. The associations between somatic cells, cytokines, endogenous proteolytic enzymes, and pathogenic bacteria can be used to better understand the pathogenesis of subclinical mastitis in ewes and the effect on the immune response of ewe mammary gland. PMID:22720942

  19. Growth and metabolic characteristics of Suffolk and Gulf Coast Native yearling ewes supplemented with chromium tripicolinate

    Microsoft Academic Search

    C. D. Forbes; J. M. Fernandez; L. D. Bunting; D. L. Thompson; L. R. Gentry; A. M. Chapa

    1998-01-01

    An experiment was conducted to investigate differences in production and physiological criteria in yearling ewe lambs from two distinct breeds fed a concentrate–base diet (13.5% CP) supplemented with 0 (BAS) or 370 ppb (CRP) chromium tripicolinate. The breeds used were Suffolk (SFK, n=8, BW 58.9±1 kg), representing a breed selected for meat production, and Gulf Coast Native sheep (GCN, n=8,

  20. A field study of reproductive performance and productivity of Pelibuey ewes in Southeastern Mexico.

    PubMed

    Magaña-Monforte, Juan Gabriel; Huchin-Cab, Miguel; Ake-López, Ricardo Jesus; Segura-Correa, Jose Candelario

    2013-11-01

    The objective was to evaluate the reproductive performance and productivity of Pelibuey ewes in two flocks in Southeastern Mexico. Animals grazed on irrigated star grass (Cynodon plectostachyus). In flock 1, lambs grazed with their mothers from 7 to 70 days of age (weaning age), whereas in flock 2, they were confined and offered chopped grass, a commercial concentrated and managed under restricted suckling until weaning at 60 days of age.. The statistical model included the fixed effects of flock, year and season of lambing, parity number, litter size at weaning, first order interactions and the random effects of ewe and the error term. The means ± SD for age at first lambing, prolificacy, lambing interval (LI), weaning weight, and productivity were 477?±?85.5 days, 1.41?±?0.51 lambs, 255.9?±?51.8 days, 16.5?±?4 kg, and 18.1?±?4.42 kg of lamb weaned, respectively. Repeatability estimates for the latter four traits were 0.09, 0.07, 0.11, and 0.13, respectively. All main effects in the models were significant (P?Ewes with two or three lambs produced 8 and 14 kg of lamb more at weaning than single lamb ewes. In conclusion, reproductive performance and productivity could be improved, and the low repeatability estimates suggest that management should be used in a short term rather than genetic approaches. PMID:23765552