These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Ewing sarcoma  

MedlinePLUS

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

2

Ewing's sarcoma.  

PubMed

Progress in the treatment of Ewing's sarcoma, the second most common bone tumour in children and adolescents, has improved survival from about 10% in the period before chemotherapy was introduced to about 75% today for patients with localised tumours. However, patients with metastases still fare badly, and the therapy carries short-term and long-term toxicities. Multidisciplinary care is indispensable for these patients. Molecular techniques and new imaging modalities are affecting the diagnosis and classification of patients with Ewing's sarcoma. Cooperative group studies have led to chemotherapy regimens using the same drugs (vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide), although the exact regimens differ in Europe and North America. The EWS-ETS family of gene fusions and their downstream effects in Ewing's sarcomas provide opportunities for new approaches to treatment. These include the inhibition of the fusion gene or its protein product, and pathways related to IGF1 and mTOR. Inhibition of tyrosine kinases, exploitation of non-apoptotic cell death, and interference with angiogenesis are promising new approaches. With many new approaches and relatively few patients, it will be challenging to integrate new and established treatments through clinical trials. PMID:20152770

Balamuth, Naomi J; Womer, Richard B

2010-02-01

3

Ewing's sarcoma.  

PubMed

Patients with Ewing's sarcoma should be transferred to a comprehensive cancer center for evaluation and management when the diagnosis is suspected. Proper biopsy technique is essential to preserve all therapeutic options, including limb preservation surgery. In addition to conventional histologic examination, biopsy tissue must be obtained for molecular biology studies. Demonstration of the consistent chromosomal translocation associated with Ewing's sarcoma is essential for diagnosis, and the specific type of fusion transcript has prognostic implications. Treatment must be intimately coordinated among oncologist, surgeon, and radiation oncologist. Successful treatment requires systemic, multi-agent chemotherapy and local control. The primary tumor can be treated with surgery, radiation therapy, or a combination of the two. The choice of modality should be dictated by the age of the patient, location of the primary tumor, functional consequences of the intervention, and concern about late effects, especially secondary malignancy. Treatment of the patient who presents with clinically detectable metastatic disease or who relapses after initial therapy remains unsatisfactory and controversial. PMID:12057167

Meyers, P A; Levy, A S

2000-08-01

4

Extraskeletal Ewings sarcoma.  

PubMed

A case of Ewings sarcoma arising in the soft tissue of the thumb is described. This appears to be the first case of digital extraskeletal Ewings sarcoma. The soft tissue location, the primary rather than metastatic nature, and the tumor type in this case were well documented. PMID:6855243

Chen, K T; Padmanabhan, A

1983-06-01

5

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

ClinicalTrials.gov

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

2013-06-20

6

Ewings' sarcoma of the mandible.  

PubMed

Ewings' sarcoma involving the facial bones is rare although it is the second most frequent bone malignancy. For the diagnosis a biopsy is needed. Currently the treatment is the combination of chemotherapy and radiotherapy with surgery indicated in only a few instances. We report a case of Ewing's sarcoma of the mandible and describe its clinicopathologic features and the treatment of this disease. PMID:14561368

Quesada, Juan L; Alcalde, Juan M; Espinosa, Juan M; García-Tapia, Rafael

2003-09-01

7

Ewing's Sarcoma of the Finger  

PubMed Central

Ewing's sarcoma is a mesenchymal cell tumor usually seen in long bones but very rarely seen in the bones of a finger. Swelling and pain are the most common complaints of the affected finger. In radiological imaging, it may be seen as permeative bone destruction accompanied by a soft tissue component or an expansile bone lesion. A 27-year-old right-hand dominant female patient presented with a swelling on the proximal phalanx of her right 3rd finger that had existed for 3 years. However, the mass started to gradually increase in size and the pain worsened over a period of 5 weeks. The mass was excised under regional intravenous anesthesia and Ewing's sarcoma was confirmed following a histopathological evaluation. No local recurrence or metastasis was detected 1 year after surgery. Since Ewing's sarcoma is rarely seen in the finger, we present this case with its radiological and clinical findings. PMID:25379350

Gökalp, Mehmet Ata; Kaplano?lu, Veysel; Ünsal, Seyyid ?erif; Erten, Remzi

2014-01-01

8

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

ClinicalTrials.gov

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

2015-02-04

9

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

ClinicalTrials.gov

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

2014-12-04

10

Ewing's sarcoma of scapula: a rare entity  

PubMed Central

Ewing's sarcoma is the second most common malignant bone tumour of childhood and adolescence. It may affect any bone, but it is frequent in the femur, ilium and the tibia. Here the authors are reporting a case of Ewing's sarcoma involving scapula in a 14-year-old boy presenting with pain and swelling around the shoulder. Swelling was removed which on histopathological examination showed solid sheets closely packed, poorly differentiated small cells that have a high nuclear-cytoplasmic ratio, fine chromatin and small nucleoli. A tentative diagnosis of Ewing's sarcoma was made which was confirmed by immunohistochemistry. PMID:22701069

Shahid, Mohammad; Varshney, Manoranjan; Maheshwari, Veena; Mubeen, Aysha; Siddiqui, Mohammed Azfar; Julfiqar, Julfiqar; Gaur, Kavita

2011-01-01

11

Surgical management of pelvic Ewing’s sarcoma  

PubMed Central

Background: Despite advances in adjuvant therapy, Ewing’s sarcoma of the pelvis remains an anatomic site with a poor prognosis due to its relative inaccessibility, complex anatomy, and limited reconstructive options available. This study evaluates the role of surgery in the management of patients with pelvic Ewing’s sarcoma who also have received conventional radiation therapy and chemotherapy. Materials and Methods: From July 1990 to July 2006, we received 10 patients with Ewing’s sarcoma of pelvis at our center. Nine patients were in stage II B and one in Stage III at the time of presentation to us. All patients underwent surgical resection after preoperative chemotherapy with or without radiotherapy, which was given at the discretion of the referral center. Reconstruction was attempted using plate osteosynthesis in four patients, SS wires and screws in three patients, free fibular strut graft in one patient, and none was done in two patients. Results: Functional outcome assessed by Enneking’s criteria revealed excellent outcome in two patients, good outcome in five patients, and poor outcome in two patients. At a mean followup of 10.3 years, seven patients remained free from the disease, and three patients died. The 5- and 10-year cumulative survival (Kaplan Meier method) was 63% and 34%, respectively. Conclusion: This study demonstrates that surgery plus chemotherapy and radiation therapy is helpful for treating patients with pelvic Ewing’s sarcoma, particularly in achieving local control. PMID:20924480

Natarajan, Mayil Vahanan; Sameer, M Mohamed; Bose, Jagdish Chandra; Dheep, Kunal

2010-01-01

12

Ewing’s sarcoma of the urogenital tract  

Microsoft Academic Search

This article reviews the current available information on Ewing’s sarcoma of the urogenital tract, focusing on the presentation,\\u000a diagnosis, and therapeutic management of this uncommon entity. Because of the rapid local growth of these tumors, an immediate\\u000a decision for treatment initiation is mandatory. The classical presentation depends mainly on the site of involvement of these\\u000a tumors, involving a palpable mass,

Amr Al-Najar; Markus Siggelkow; Carsten Maik Naumann; Moritz Franz Hamann; Peter-Klaus Jünemann; Christof van der Horst

2009-01-01

13

Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma  

Microsoft Academic Search

As a result of overlapping morphologic and immunohistochemical features, it can be difficult to distinguish synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma\\/primitive neuroectodermal tumor in core biopsies. To analyze and compare immunohistochemical profiles, we stained tissue microarrays of 23 synovial sarcomas, 23 malignant peripheral nerve sheath tumors, and 27 Ewing sarcomas with 22 antibodies potentially useful in

Stephen H Olsen; Dafydd G Thomas; David R Lucas

2006-01-01

14

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy  

PubMed Central

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months. PMID:23346500

Kim, Hyo-Sin; Min, Young-Don; Kee, Keun-Hong; Hong, Ran

2012-01-01

15

Primary Pulmonary Ewing’s Sarcoma: Rare Cause of Superior Vena Cava Syndrome in Children  

PubMed Central

Ewing’s sarcoma is a common malignant bone tumour presenting in children and young adults. Rarely extra- skeletal soft tissues and visceral organs can also be the site of origin of Ewing’s sarcoma. Primary pulmonary Ewing’s sarcoma is an extremely rare malignancy which occurs in the paediatric population. We report an unusual case of primary pulmonary Ewing’s sarcoma in a nine year old girl who presented with features of superior vena cava syndrome in the emergency department. The diagnosis was confirmed pathologically both by light microscopy and immunohistochemistry. The patient was put on chemotherapy and surgery was planned but the patient expired within three days of starting chemotherapy. PMID:25302247

Atwal, Swapndeep Singh; Garga, Umesh Chandra

2014-01-01

16

Anti-Epileptic Drug Targets Ewing Sarcoma  

PubMed Central

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

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

2014-01-01

17

Ewing Sarcoma of the Posterior Fossa in an Adolescent Girl  

PubMed Central

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

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

2014-01-01

18

Primary extraskeletal Ewing's sarcoma of the maxilla with intraorbital extension.  

PubMed

Extraskeletal Ewing's sarcoma is often described as a tumour involving the soft tissues of the lower extremities and the paravertebral region. Primary Ewing's sarcoma of the cranium is extremely rare, with only 17 cases reported so far [24]. Involvement of the paranasal sinus is a very rare entity. Involvement of facial bones is characterized by clinical and radiological features distinct from those commonly observed in other sites. Because of the above peculiarities a delay in diagnosis and thus in starting treatment is very probable in such cases. Primary Ewings sarcoma rarely arises in the facial skeleton and only occasionally in the maxilla. To date, there have been 22 cases of maxillary Ewing's sarcoma reported in the English-language literature [25]. We report here a new case of Ewing's sarcoma localized to the maxillary sinus, nose and the orbit, successfully treated by surgery, local high dosage radiotherapy and systemic chemotherapy. PMID:23120451

Varshney, Saurabh; Bist, S S; Gupta, Nitin; Bhatia, Rajat

2007-09-01

19

Ewing's sarcoma of the vertebral column  

SciTech Connect

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

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

1981-01-01

20

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

PubMed Central

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

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

2014-01-01

21

Ewing’s Sarcoma: An Uncommon Breast Tumor  

PubMed Central

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

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

2014-01-01

22

Ewing's sarcoma of maxilla: A rare case report  

PubMed Central

Ewing's sarcoma is uncommon malignancy of childhood, frequently involving the mandible. The occurrence in maxilla is rare. It is histopathologically characterized by sheets of round cells positive for CD99. Although the prognosis is poor but early diagnosis and long term follow up can improve the survival. This article presents a rare case of Ewing's sarcoma of maxilla in a 15 year old male patient showing excessive fibro-osseous response which is not a frequent presentation. A retrospective analysis of cases of Ewings sarcoma of maxilla published in the English litreture is reviewed. In our case, diagnosis was confirmed by immunohistochemistry where sheets of round tumor cells were positive for CD 99. Ewings sarcoma of maxilla is a rare and aggressive tumor. Hence early diagnosis, combined therapy and long term follow up is suggested in such cases. PMID:25328307

Jairamdas Nagpal, Deepak Kumar; Prabhu, Prashant Ramesh; Palaskar, Sangeeta Jayant; Patil, Swati

2014-01-01

23

Ewing's sarcoma of maxilla: A rare case report.  

PubMed

Ewing's sarcoma is uncommon malignancy of childhood, frequently involving the mandible. The occurrence in maxilla is rare. It is histopathologically characterized by sheets of round cells positive for CD99. Although the prognosis is poor but early diagnosis and long term follow up can improve the survival. This article presents a rare case of Ewing's sarcoma of maxilla in a 15 year old male patient showing excessive fibro-osseous response which is not a frequent presentation. A retrospective analysis of cases of Ewings sarcoma of maxilla published in the English litreture is reviewed. In our case, diagnosis was confirmed by immunohistochemistry where sheets of round tumor cells were positive for CD 99. Ewings sarcoma of maxilla is a rare and aggressive tumor. Hence early diagnosis, combined therapy and long term follow up is suggested in such cases. PMID:25328307

Jairamdas Nagpal, Deepak Kumar; Prabhu, Prashant Ramesh; Palaskar, Sangeeta Jayant; Patil, Swati

2014-05-01

24

Microarray-based DNA methylation study of Ewing’s sarcoma of the bone  

PubMed Central

Alterations in DNA methylation patterns are a hallmark of malignancy. However, the majority of epigenetic studies of Ewing’s sarcoma have focused on the analysis of only a few candidate genes. Comprehensive studies are thus lacking and are required. The aim of the present study was to identify novel methylation markers in Ewing’s sarcoma using microarray analysis. The current study reports the microarray-based DNA methylation study of 1,505 CpG sites of 807 cancer-related genes from 69 Ewing’s sarcoma samples. The Illumina GoldenGate Methylation Cancer Panel I microarray was used, and with the appropriate controls (n=14), a total of 92 hypermethylated genes were identified in the Ewing’s sarcoma samples. The majority of the hypermethylated genes were associated with cell adhesion, cell regulation, development and signal transduction. The overall methylation mean values were compared between patients who survived and those that did not. The overall methylation mean was significantly higher in the patients who did not survive (0.25±0.03) than in those who did (0.22±0.05) (P=0.0322). However, the overall methylation mean was not found to significantly correlate with age, gender or tumor location. GDF10, OSM, APC and HOXA11 were the most significant differentially-methylated genes, however, their methylation levels were not found to significantly correlate with the survival rate. The DNA methylation profile of Ewing’s sarcoma was characterized and 92 genes that were significantly hypermethylated were detected. A trend towards a more aggressive behavior was identified in the methylated group. The results of this study indicated that methylation may be significant in the development of Ewing’s sarcoma. PMID:25202378

PARK, HYE-RIM; JUNG, WOON-WON; KIM, HYUN-SOOK; PARK, YONG-KOO

2014-01-01

25

Poly(ADP-ribose) polymerase inhibitors in Ewing sarcoma  

PubMed Central

Purpose of review In 2012, two publications revealed a particular sensitivity of Ewing sarcoma cells to the inhibition of poly(ADP-ribose) polymerase (PARP). This review updates the reader on PARP function, the development of PARP inhibitors (PARPi) and the evidence for targeting PARP in Ewing sarcoma. It concludes with a description of ongoing/emerging PARPi clinical trials in patients with Ewing sarcoma. Recent findings PARP has a major role in DNA repair, and is a transcription regulator. The oncoprotein in Ewing sarcoma, EWS-FLI1, is proposed to interact with PARP-1, driving PARP-1 expression, which further promotes transcriptional activation by EWS-FLI1. Thus, there are two rationales for PARPi in the treatment of Ewing sarcoma: to disrupt the interaction between EWS-FLI1 and PARP, and for chemo-potentiation or radio-potentiation. The first clinical trial with a single agent PARPi failed to show significant responses, but preclinical evidence for combinations of PARPi with chemotherapy or radiotherapy is very promising. Summary Despite initial excitement for the potential of PARPi as single agent therapy in Ewing sarcoma, the emerging preclinical data now strongly support testing PARPi in combination with chemo/radiotherapy clinically. PMID:24840521

Vormoor, Britta; Curtin, Nicola J.

2014-01-01

26

Intradural extramedullary Ewing's sarcoma. Recurrence with acute clinical presentation and literature review.  

PubMed

The intradural extramedullary space is an extremely unusual site for the onset of Ewing's sarcoma. We describe a case of recurrence of intradural extramedullary Ewing's sarcoma and review the literature available on this topic. PMID:24007736

Bazzocchi, Alberto; Bacci, Antonella; Serchi, Elena; Salerno, Angela; Salizzoni, Eugenio; Leonardi, Marco

2013-08-01

27

Ewing’s sarcoma arising from the adrenal gland in a young male: a case report  

PubMed Central

Background Ewing’s sarcoma uncommonly arises from extraosseous soft tissue or parenchymal organs. Primary adrenal Ewing’s Sarcoma, although very rare, is extremely aggressive and commonly fatal. Case presentation A 17 year old Pakistani male was referred to the outpatient oncology clinic at our center with a three month history of concomitant pain, swelling and dragging sensation in the right hypochondrium. Abdominal examination revealed a large, firm mass in the right hypochondrium extending into the right lumbar region and epigastrium. His genital exam was unremarkable and there were no stigmata of hepatic or adrenal disease. Computed tomography scans revealed a large peripherally enhancing mass in the hepatorenal area, biopsy of which showed a neoplastic lesion composed of small round blue cells which exhibited abundance of glycogen and stained diffusely positive for CD99 (MIC2 antigen). Fluorescence in situ hybridization demonstrated gene rearrangement at chromosome 22q12 which confirmed the diagnosis of Ewing’s sarcoma. Staging scans revealed pulmonary metastasis and hence he was commenced on systemic chemotherapy. Conclusion This case report highlights the importance of keeping Ewing’s sarcoma in mind when a young patient presents with a large non-functional adrenal mass. PMID:24330865

2013-01-01

28

Ewing's sarcoma cancer stem cell targeted therapy.  

PubMed

Ewing`s sarcoma (ES) family of tumors (ESFTs) are round cell tumors of bone and soft tissues, afflicting children and young adults. This review summarizes the present findings about ES cancer stem cell (CSC) targeted therapy: prognostic factors, chromosomal translocations, initiation, epigenetic mechanisms, candidate cell of ES origin (Mesenchymal stem cells (MSCs) and Neural crest stem cells (NCSCs)). The ES CSC model, histopathogenesis, histogenesis, pathogenesis, ES mediated Hematopoietic stem progenitor cells (HSPCs) senescence are also discussed. ESFTs therapy is reviewed concerning CSCs, radiotherapy, risk of subsequent neoplasms, stem cell (SC) support, promising therapeutic targets for ES CSCs (CSC markers, immune targeting, RNAi phenotyping screens, proposed new drugs), candidate EWS-FLI1 target genes and further directions (including human embryonic stem cells (hESCs)). Bone marrow-derived human MSCs are permissive for EWS-FLI1 expression with transition to ESFT-like cellular phenotype. ESFTs are genetically related to NCSC, permissive for EWS-FLI1 expression and susceptible to oncogene-induced immortalization. Primitive neuroectodermal features and MSC origin of ESFTs provide a basis of immune targeting. The microRNAs profile of ES CSCs is shared by ESCs and CSCs from divergent tumor types. Successful reprogramming of differentiated human somatic cells into a pluripotent state allows creation of patient- and disease-specific SCs. The functional role of endogenous EWS at stem cell level on both senescence and tumorigenesis is a link between cancer and aging. The regulatory mechanisms of oncogenic activity of EWS fusions could provide new prognostic biomarkers, therapeutic opportunities and tumor-specific anticancer agents against ESFTs. PMID:24294922

Todorova, Roumiana

2014-01-01

29

Ewings sarcoma of the hand-a case report.  

PubMed

Ewings sarcoma of the hand is relatively rare. Ewings sarcoma can present with minimal pain and swelling of the affected digit. The Erythrocyte sedimentation rate and C-reactive protein may be high. Radiologically, Ewings sarcoma can present with a plethora of features from permeative bone destruction to expansile lesions with or without periosteal reaction. Because of these features, this can be confused with Tuberculosis especially in a country like ours where Tuberculosis is endemic. This leads to starting of inappropriate treatment and delay in diagnosis. We report a case of an 18 year old boy who was initially diagnosed as Tuberculous dactylytis of the proximal phalanx of the little finger. He was started on anti-tuberculous treatment and did not respond to it. Subsequent investigation in our centre which also included an open biopsy, confirmed the diagnosis of Ewings sarcoma. He was treated with ray excision, and chemotherapy. This case is being presented for its rarity and also to emphasize the fact that an open biopsy in suspected cases would be appropriate to confirm the diagnosis. This would prevent delay in diagnosis of rare conditions like Ewings sarcoma. PMID:22282674

Rajappa, Srinivasan; Menon, P Gopinath; Sundaram, Sandhya

2010-12-01

30

Primary Ewing's sarcoma of the spine presenting as acute paraplegia  

PubMed Central

Ewing's sarcoma is a primary bone malignancy with the highest incidence in the second decade of life. Although it mostly affects the metaphyseal region of long growing bones, involvement of spine is not very uncommon especially the sacrum. Nonsacral spinal Ewing's sarcoma is rarer and often mimics a benign condition before spreading extensively. They present with neurologic deficits due to spinal cord compression, but acute onset paraplegia has not been previously reported. A high index of clinical suspicion can clinch the diagnosis early in the course of the disease. A prompt intervention is required to keep neurological damage to a minimum, and a correct combination of surgery, chemotherapy, and radiotherapy is required for better long-term patient outcome. We report a 16-year-old female who presented with acute paraplegia and had an excellent postoperative outcome after radical excision of a D9 Ewing's sarcoma. PMID:22837785

Gopalakrishnan, C. V.; Shrivastava, Adesh; Easwer, H. V.; Nair, Suresh

2012-01-01

31

Extraskeletal Ewings sarcoma of the small bowel: case report and literature review.  

PubMed

Extraskeletal Ewings sarcoma is a tumour of neuroectodermal origin sharing close similarities with Ewings sarcoma of bone. We report the case of a 21 year old 16 week pregnant woman presenting with vomiting and weight loss and found to have an extraskeletal Ewings sarcoma of the small bowel. In a review of the literature there are no previous reports of extraskeletal Ewings sarcoma occurring in the small bowel. The diagnosis of extraskeletal Ewings sarcoma and the complicated management of a young pregnant woman with a malignant tumour are described. PMID:11768578

Adair, A; Harris, S A; Coppen, M J; Hurley, P R

2001-12-01

32

Ewing Sarcoma of the Kidney: A Rare Entity  

PubMed Central

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

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

2014-01-01

33

Is time of the essence? Delayed diagnosis of Ewing's sarcoma.  

PubMed

Rarely in modern medicine are we able to observe the natural history of a patient with a sarcoma. This unusual case provides that opportunity. A CT scan was performed on the leg of a 15-year-old boy with a tender soft tissue mass on the lateral aspect of his left calf. Despite showing a lesion consistent with a sarcoma, neither the patient nor his family was informed. Almost a year and a half later, the patient returned and was diagnosed with Ewing's sarcoma. A staging work up showed no metastatic disease. After undergoing chemotherapy and a complete surgical resection of the tumour, the patient remains disease-free 10?years later, indicating that the biology of Ewing's sarcoma may be more important than time to diagnosis in determining outcome. PMID:25628326

Edwards, Madeline; Halton, Jacqueline; Ramphal, Raveena; Johnston, Donna

2015-01-01

34

A Molecular Function Map of Ewing's Sarcoma  

PubMed Central

Background EWS-FLI1 is a chimeric ETS transcription factor that is, due to a chromosomal rearrangement, specifically expressed in Ewing's sarcoma family tumors (ESFT) and is thought to initiate the development of the disease. Previous genomic profiling experiments have identified EWS-FLI1–regulated genes and genes that discriminate ESFT from other sarcomas, but so far a comprehensive analysis of EWS-FLI1–dependent molecular functions characterizing this aggressive cancer is lacking. Methodology/Principal Findings In this study, a molecular function map of ESFT was constructed based on an integrative analysis of gene expression profiling experiments following EWS-FLI1 knockdown in a panel of five ESFT cell lines, and on gene expression data from the same platform of 59 primary ESFT. Out of 80 normal tissues tested, mesenchymal progenitor cells (MPC) were found to fit the hypothesis that EWS-FLI1 is the driving transcriptional force in ESFT best and were therefore used as the reference tissue for the construction of the molecular function map. The interrelations of molecular pathways were visualized by measuring the similarity among annotated gene functions by gene sharing. The molecular function map highlighted distinct clusters of activities for EWS-FLI1 regulated genes in ESFT and revealed a striking difference between EWS-FLI1 up- and down-regulated genes: EWS-FLI1 induced genes mainly belong to cell cycle regulation, proliferation, and response to DNA damage, while repressed genes were associated with differentiation and cell communication. Conclusions/Significance This study revealed that EWS-FLI1 combines by distinct molecular mechanisms two important functions of cellular transformation in one protein, growth promotion and differentiation blockage. By taking MPC as a reference tissue, a significant EWS-FLI1 signature was discovered in ESFT that only partially overlapped with previously published EWS-FLI1–dependent gene expression patterns, identifying a series of novel targets for the chimeric protein in ESFT. Our results may guide target selection for future ESFT specific therapies. PMID:19404404

Kofler, Reinhard; Walker, Bob; Davis, Sean; Meltzer, Paul; Kovar, Heinrich

2009-01-01

35

Primary Ewings sarcoma of the spine: case report.  

PubMed

Primary malignant sarcomas of the spine are extremely rare. Because of biological heterogeneity, these tumors have variable sensitivity to radiation and chemotherapy. Adequate local control through complete tumor removal is an important therapeutic goal. However, aggressive resection of tumors in the spinal column must be coupled with restoration of spinal column stability and minimization of neural deficits. The balance of these factors makes treatment of primary sarcomas of the spine challenging, and dictates an individual approach to treatment. We report on a 18 years old man with primary Ewing's sarcoma of the nonsacral spine. The clinical picture and imaging characteristics were analyzed as well as the management modalities and outcome. PMID:17119813

Dini, Leandro I; Mendonça, Rodrigo; Gallo, Pasquale

2006-09-01

36

Appearance of extraosseous pelvic Ewing sarcoma on triphasic bone scan.  

PubMed

A 24-year-old man with extraosseous Ewing sarcoma in the pelvis underwent a triphasic bone scintigraphy to rule out bone metastases and local bone infiltration before chemotherapy. The bone scintigraphy showed tracer uptake in the tumor in all 3 phases. PMID:24566405

Muckle, Marianne; Habibi, Elham; Simon, Birgit; Zipfel, Matthias; Biersack, Hans Jürgen; Ahmadzadehfar, Hojjat

2014-04-01

37

Ewing's sarcoma in mandibular similar to dental abscess  

PubMed Central

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

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

2014-01-01

38

Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma  

PubMed Central

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

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

2011-01-01

39

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

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

2014-01-22

40

Targeting the p53 Pathway in Ewing Sarcoma  

PubMed Central

The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53. PMID:21197471

Neilsen, Paul M.; Pishas, Kathleen I.; Callen, David F.; Thomas, David M.

2011-01-01

41

Ewing sarcoma/peripheral primitive neuroectodermal tumor and related tumors.  

PubMed

Ewing sarcoma/peripheral primitive neuroectodermal tumor (EWS/pPNET) and other tumors with EWS gene rearrangements encompass a malignant and intermediate neoplasm with a broad anatomic distribution and a wide age range but a predilection for soft tissue in children, adolescents, and young adults. The overlapping histologic, immunohistochemical and cytogenetic and molecular genetic features create diagnostic challenges despite significant clinical and prognostic differences. Ewing sarcoma is the 3rd most common sarcoma in children and adolescents, and desmoplastic small round cell tumor is a rare neoplasm that occurs more often in older children, adolescents, and young adults. Pathologic examination is complemented by immunohistochemistry, cytogenetics, and molecular genetics. This article reviews the clinicopathologic features of EWS/pPNET and desmoplastic small round cell tumor in the spectrum of tumors with EWS gene rearrangements. Other tumors with different histopathologic features and an EWS gene rearrangement are discussed elsewhere in this volume. PMID:22420726

Tsokos, Maria; Alaggio, Rita D; Dehner, Louis P; Dickman, Paul S

2012-01-01

42

Ewing's Sarcoma of the Zygomatic Arch Presenting in a 69-Year Old: An Unusual Case Report  

PubMed Central

Objective. We report a rare case of Ewing's sarcoma of the zygomatic arch presenting in a 69-year-old patient. Method. Case report and a review of the world literature on Ewing's sarcoma incidence and management. Results. Ewing's sarcoma is a malignant round cell tumour of neuroectodermal origin that typically presents in the pelvis and long bones of children and adolescent boys. This report is the first to document the presentation of ewing's sarcoma of the zygomatic arch in a 69-year-old lady. Our patient underwent surgical excision and radiotherapy and at 4-year followup has no signs of recurrence or metastasis. Conclusion. To our knowledge this is the first case report to document Ewing's sarcoma of this location in a 69-year-old patient. This case report highlights the importance of diagnostic investigations in Ewing's sarcoma and discusses the management issues that this rare presentation raises. PMID:22937369

Mennie, Joanna C.; Reid, Robin; Cowie, Fiona; Hilmi, Omar

2011-01-01

43

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

PubMed Central

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

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

2013-01-01

44

Review of therapeutic strategies for osteosarcoma, chondrosarcoma, and Ewing’s sarcoma  

PubMed Central

Summary The most prevalent forms of bone cancer are osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. Although chemotherapy and radiotherapy have replaced traditional surgical treatments, survival rates have undergone only marginal improvements. Current knowledge of the molecular pathways involved in each type of cancer has led to better approaches in cancer treatment. A number of cell signaling molecules are involved in tumorigenesis, and specific targets have been identified based on these signal transducers. This review highlights some of the important cellular pathways and potential therapeutic targets, tumor site-specific irradiation techniques, and novel drug delivery systems used to administer these drugs. PMID:21804475

Dai, Xing; Ma, Wei; He, Xijing; Jha, Rajiv Kumar

2011-01-01

45

RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma  

PubMed Central

Background Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Results Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. Conclusion In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma. PMID:20718987

2010-01-01

46

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

PubMed Central

Background. The origin of Ewing's sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better prognosis when confined between periosteum and bone. Is it the same for periosteal Ewing's sarcoma? Methods. We describe two new cases and comprehensively review the literature consisting of 18 documented cases since the condition was first described in 1986 (S.M. Bator.Cancer 58:1781– 4). Results. Periosteal Ewing's sarcoma differs from the other forms of Ewing's sarcoma in terms of sex predominance, location of tumor, surgical stage at presentation and typical imaging studies. Eighteen out of the 20 patients were reported to be alive with no evidence of disease. Conclusions. It seems that the prognosis of this rare variant of Ewing's sarcoma family of tumors might be better but the small number of cases precludes such a firm conclusion. PMID:18521268

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

1999-01-01

47

The First European Interdisciplinary Ewing Sarcoma Research Summit  

PubMed Central

The European Network for Cancer Research in Children and Adolescents (ENCCA) provides an interaction platform for stakeholders in research and care of children with cancer. Among ENCCA objectives is the establishment of biology-based prioritization mechanisms for the selection of innovative targets, drugs, and prognostic markers for validation in clinical trials. Specifically for sarcomas, there is a burning need for novel treatment options, since current chemotherapeutic treatment protocols have met their limits. This is most obvious for metastatic Ewing sarcoma (ES), where long term survival rates are still below 20%. Despite significant progress in our understanding of ES biology, clinical translation of promising laboratory results has not yet taken place due to fragmentation of research and lack of an institutionalized discussion forum. To fill this gap, ENCCA assembled 30 European expert scientists and five North American opinion leaders in December 2011 to exchange thoughts and discuss the state of the art in ES research and latest results from the bench, and to propose biological studies and novel promising therapeutics for the upcoming European EWING2008 and EWING2012 clinical trials. PMID:22662320

Kovar, Heinrich; Alonso, Javier; Aman, Pierre; Aryee, Dave N. T.; Ban, Jozef; Burchill, Sue A.; Burdach, Stefan; De Alava, Enrique; Delattre, Olivier; Dirksen, Uta; Fourtouna, Argyro; Fulda, Simone; Helman, Lee J.; Herrero-Martin, David; Hogendoorn, Pancras C. W.; Kontny, Udo; Lawlor, Elizabeth R.; Lessnick, Stephen L.; Llombart-Bosch, Antonio; Metzler, Markus; Moriggl, Richard; Niedan, Stephan; Potratz, Jenny; Redini, Françoise; Richter, Günther H. S.; Riedmann, Lucia T.; Rossig, Claudia; Schäfer, Beat W.; Schwentner, Raphaela; Scotlandi, Katia; Sorensen, Poul H.; Staege, Martin S.; Tirode, Franck; Toretsky, Jeffrey; Ventura, Selena; Eggert, Angelika; Ladenstein, Ruth

2012-01-01

48

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

ClinicalTrials.gov

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

2015-01-07

49

Variable Expression of PIK3R3 and PTEN in Ewing Sarcoma Impacts Oncogenic Phenotypes  

PubMed Central

Ewing Sarcoma is an aggressive malignancy of bone and soft tissue affecting children and young adults. Ewing Sarcoma is driven by EWS/Ets fusion oncoproteins, which cause widespread alterations in gene expression in the cell. Dysregulation of receptor tyrosine kinase signaling, particularly involving IGF-1R, also plays an important role in Ewing Sarcoma pathogenesis. However, the basis of this dysregulation, including the relative contribution of EWS/Ets-dependent and independent mechanisms, is not well understood. In the present study, we identify variable expression of two modifiers of PI3K signaling activity, PIK3R3 and PTEN, in Ewing Sarcoma, and examine the consequences of this on PI3K pathway regulation and oncogenic phenotypes. Our findings indicate that PIK3R3 plays a growth-promotional role in Ewing Sarcoma, but suggest that this role is not strictly dependent on regulation of PI3K pathway activity. We further show that expression of PTEN, a well-established, potent tumor suppressor, is lost in a subset of Ewing Sarcomas, and that this loss strongly correlates with high baseline PI3K pathway activity in cell lines. In support of functional importance of PTEN loss in Ewing Sarcoma, we show that re-introduction of PTEN into two different PTEN-negative Ewing Sarcoma cell lines results in downregulation of PI3K pathway activity, and sensitization to the IGF-1R small molecule inhibitor OSI-906. Our findings also suggest that PTEN levels may contribute to sensitivity of Ewing Sarcoma cells to the microtubule inhibitor vincristine, a relevant chemotherapeutic agent in this cancer. Our studies thus identify PIK3R3 and PTEN as modifiers of oncogenic phenotypes in Ewing Sarcoma, with potential clinical implications. PMID:25603314

Niemeyer, Brian F.; Parrish, Janet K.; Spoelstra, Nicole S.; Joyal, Teresa; Richer, Jennifer K.; Jedlicka, Paul

2015-01-01

50

N-(4-Hydroxyphenyl) Retinamide Potentiated Anti-tumor Efficacy of Genistein in Human Ewing’s Sarcoma Xenografts  

PubMed Central

Background Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. New therapeutic strategies are urgently needed for treatment of Ewing’s sarcoma. We examined for the first time the efficacy of N-(4-hydroxyphenyl) retinamide (4-HPR) and genistein (GST) alone and also in combination for controlling growth of human Ewing’s sarcoma SK-N-MC and RD-ES xenografts. Methods Efficacy of combination therapy was evaluated using histopathological parameters. Molecular mechanisms of combination therapy were detected using Western blotting and immunofluorescence microscopy. Results Histopathological examination of tumor sections showed that control group maintained characteristic growth of tumors, 4-HPR alone caused differentiation of tumor cells, GST alone induced apoptosis to some extent, and combination of 4-HPR and GST significantly induced apoptosis in both Ewing’s sarcoma xenografts. Time-dependent reductions in body weight, tumor volume, and tumor weight were also found. Combination therapy increased Bax:Bcl-2 ratio to trigger mitochondrial release of Smac/Diablo into the cytosol to down regulate the baculovirus inhibitor-of-apoptosis repeat containing (BIRC) proteins such as BIRC-2 and BIRC-3 and thereby promote apoptosis. Activation of caspase-3 and mitochondrial release of apoptosis-inducing factor (AIF) occurred in course of apoptosis. Down regulation of the survival factor NF-?B and the angiogenic factors VEGF and FGF2 and increase in caspase-3 activity controlled tumor growth. In situ immunofluorescent labelings showed overexpression of calpain, caspase-12, and caspase-3, and AIF in xenografts, indicating induction of cysteine proteases and AIF for apoptosis. Conclusions Results revealed that combination of 4-HPR and GST could be highly effective treatment for inhibiting Ewing’s sarcomas in vivo. PMID:21822457

Karmakar, Surajit; Choudhury, Subhasree Roy; Banik, Naren L.; Ray, Swapan K.

2011-01-01

51

Structure-Function Based Molecular Relationships in Ewing's Sarcoma  

PubMed Central

Ewing's Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing's sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer.

2015-01-01

52

Extraskeletal Ewing’s sarcoma/primitive neuroectodermal tumor of the mediastinum: Significant response to chemoradiotherapy  

PubMed Central

Primary mediastinal extraskeletal Ewing’s sarcoma (EES) is quite rare. To the best of our knowledge, only five cases have been reported. Given the paucity of data, there is consequently no optimal treatment strategy available. The current study presents the case of a 51-year-old female with unresectable EES of the posterior mediastinum. Chemoradiotherapy achieved near complete remission without severe side-effects. The literature associated with EES is also reviewed. The present case highlights the possibility of the diagnosis of EES for a mediastinal mass. Chemoradiotherapy may be a good option for unresectable cases. In the future, large-scale collaborative clinical trials should be initiated to provide an improved understanding of the characteristics of EES and the best treatment strategy.

LIU, MIN; LIU, BAILONG; DONG, LIHUA; HAN, TAO; ZHANG, LEI

2015-01-01

53

Vaginal metastasis of a Ewing sarcoma five years after resection of the primary tumor  

PubMed Central

A 35-year-old female presented with pain and swelling of the distal left radius. A diagnosis of Ewing sarcoma was made and she underwent neoadjuvant chemotherapy and surgery. Macroscopic viable areas remained on the map of the surgical specimen; as such, she was classified as a poor responder and received high dose adjuvant chemotherapy. She remained disease-free for five years, until age 40. A vaginal polyp was then detected during a routine gynaecologic examination. It was removed and histopathology revealed metastatic Ewing sarcoma. To our knowledge, this is the first reported case of a vaginal metastasis of Ewing sarcoma. PMID:22612902

2011-01-01

54

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

PubMed

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

Apostolopoulos, Kostas; Ferekidis, Eleftherios

2003-01-01

55

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

PubMed Central

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

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

2013-01-01

56

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

ClinicalTrials.gov

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

2015-02-11

57

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

ClinicalTrials.gov

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

2015-01-05

58

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

PubMed Central

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

2012-01-01

59

Rare case of extraskeletal Ewings sarcoma of the sinonasal tract.  

PubMed

Ewings sarcoma (ES) and primitive neuroectodermal tumor are closely related family of small round cell tumors seen in childhood and adolescence. The incidence of these tumors occurring in the head and neck region is just 2-7%. Mandible and maxilla are the most common sites, whereas involvement of the sinonasal tract is very rare. We report a case of extraskeletal ES of the sinonasal tract in a 29-year-old female who presented with nasal obstruction and epistaxis. The patient was treated with 14 cycles of chemotherapy, combined with surgery and radiotherapy with complete recovery. We present this case due to its rarity, to analyze the clinical, histopathological and immunohistochemical findings, so as to differentiate from other small round cell tumors of the sinonasal tract for appropriate treatment. PMID:22531536

Yeshvanth, Sunil Kumar; Ninan, Kurian; Bhandary, Sathish Kumar; Lakshinarayana, Kishan Prasad H; Shetty, Jayaprakash K; Makannavar, Jagdish H

2012-01-01

60

The many faces of atypical Ewing's sarcoma. A true entity mimicking sarcomas, carcinomas and lymphomas.  

PubMed

Ewing's sarcoma family of tumours (ESFT) comprises a group of small round cell tumours (SRCT) genetically defined by specific chromosomal translocations resulting in a fusion of the EWSR1 gene with a member of the ETS family of transcription factors. Atypical ESFT are the most challenging of the ESFT subtypes, and the differential diagnosis with other SRCT of bone and soft tissue is difficult since these subtypes can resemble other neoplasms. The present article describes nine cases of genetically confirmed, atypical ESFT, having unusual alterations at morphological and immunohistochemical (IHC) levels associated with atypical clinical presentation mimicking sarcomas, carcinomas and lymphomas. Present results demonstrate that ESFT showing overlapping morphological and immunohistochemical features with other SRCT of soft tissue and bone, or even with carcinomas or lymphoma, can be differentiated using molecular techniques. In SRCT with EWSR1 translocation demonstrated by FISH, the RT-PCR analysis of specific sarcoma-related gene fusion can offer important clues for the diagnosis of specific entities, especially in tumours with unusual histopathology and/or IHC findings. Thus, we confirm that the integration of clinical, histopathological, IHC and genetic data becomes decisive in the diagnosis of bone and soft tissue sarcomas. PMID:21181413

Machado, Isidro; Noguera, Rosa; Mateos, Eduardo Alcaraz; Calabuig-Fariñas, Silvia; López, F Ignacio Aranda; Martínez, Antonio; Navarro, Samuel; Llombart-Bosch, Antonio

2011-03-01

61

Primary Ewings sarcoma of cavernous sinus in an infant: a case report and review of literature.  

PubMed

Ewing's / peripheral primitive neuroectodermal tumor (pPNET) of the cavernous sinus are extremely uncommon. We present clinical, radiological, pathological findings of Ewing's / pPNET involving the cavernous sinus in an eleven-month-old infant presenting with proptosis and 6th nerve palsy. MRI Contrast scans showed a well-defined, homogenously enhancing mass involving the right cavernous sinus location. Histopathology and immunohistochemical features were consistent with Ewing's/pPNET. The patient succumbed to disease in spite of starting chemotherapy. The clinical, radiological and pathological findings of previously reported cases of Ewing's sarcoma / pPNET involving the cavernous sinus are summarized. The histological differential diagnosis of primary intracranial Ewing's sarcoma / pPNET are discussed. PMID:23344875

Patibandla, Mohana Rao; Uppin, Shantveer G; Thotakura, Amit Kumar; Panigrahi, Manas K; Challa, Sundaram

2013-01-01

62

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

PubMed Central

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

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

2013-01-01

63

A monoclonal antibody specifically reactive with Ewing's sarcoma.  

PubMed Central

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

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

1989-01-01

64

Evidence for heterogeneous groups of neuronal differentiation of Ewing's sarcoma.  

PubMed Central

We have investigated the capability of differentiation of Ewing's sarcoma (ES) towards a neuronal direction through the establishment of four extraosseous ES cell lines and by in vitro stimulation with dibutyryladenosine cyclic monophosphate (db-cAMP) of eight ES lines. All except one of the lines expressed the molecule defined by 5C11, the antibody specifically reactive with ES. Two ES lines expressed a 200 kilodalton (kD) neurofilament protein (NFP) although their original tumours were negative for NFP. Elongation of cytoplasmic processes and increased NFP expression were observed after db-cAMP treatment of these lines and microtubules in the cytoplasmic processes were ultrastructurally demonstrated. Six lines were NFP negative, but three lines changed their morphology after induction of 200 kD NFP expression by db-cAMP treatment. The other three showed no definitive differentiation after db-cAMP treatment. Chromosomal analysis of the new ES lines showed the typical t(11;22) in one line and a +der(22) in two lines. No correlation was observed between the chromosomal abnormality and the differentiation capability. We conclude that ES is a heterogeneous group of tumours with respect to capability of differentiation into the neuronal lineage, but it is clearly distinguished from peripheral primitive neuroectodermal tumours by its 5C11 reactivity. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1764362

Hara, S.; Adachi, Y.; Kaneko, Y.; Fujimoto, J.; Hata, J.

1991-01-01

65

Macrophage Infiltration Predicts a Poor Prognosis for Human Ewing Sarcoma  

PubMed Central

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

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

2011-01-01

66

Nonmetastatic Ewing's Sarcoma of the Lumbar Spine in an Adult Patient  

PubMed Central

Although the spine is frequently involved in metastatic Ewing's sarcoma, primary involvement of the spine, beside sacrum, is much less frequent, especially in adult patients. Because of the low incidence of these tumors, there are currently no clinical guidelines outlining their management and a multitude of therapeutic strategies have been employed with varying success. The definitive management of Ewing's sarcoma of the spine, as in other locations, could include the combination of three main modalities: aggressive surgery, radiotherapy, and combined chemotherapy. Whenever possible, en bloc spondylectomy or extralesional resection is preferable, providing a better oncological result with a longer survival and a better preservation of the spine biomechanics. This is the lesson we learned about the case, we present here, of nonmetastatic lumbar localization by Ewing's sarcoma in as adult patient. PMID:23133768

Iacoangeli, Maurizio; Dobran, Mauro; Di Rienzo, Alessandro; di Somma, Lucia Giovanna Maria; Alvaro, Lorenzo; Moriconi, Elisa; Nocchi, Niccolò; Gladi, Maurizio; Scerrati, Massimo

2012-01-01

67

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

PubMed

Although the spine is frequently involved in metastatic Ewing's sarcoma, primary involvement of the spine, beside sacrum, is much less frequent, especially in adult patients. Because of the low incidence of these tumors, there are currently no clinical guidelines outlining their management and a multitude of therapeutic strategies have been employed with varying success. The definitive management of Ewing's sarcoma of the spine, as in other locations, could include the combination of three main modalities: aggressive surgery, radiotherapy, and combined chemotherapy. Whenever possible, en bloc spondylectomy or extralesional resection is preferable, providing a better oncological result with a longer survival and a better preservation of the spine biomechanics. This is the lesson we learned about the case, we present here, of nonmetastatic lumbar localization by Ewing's sarcoma in as adult patient. PMID:23133768

Iacoangeli, Maurizio; Dobran, Mauro; Di Rienzo, Alessandro; di Somma, Lucia Giovanna Maria; Alvaro, Lorenzo; Moriconi, Elisa; Nocchi, Niccolò; Gladi, Maurizio; Scerrati, Massimo

2012-01-01

68

Huntsman Cancer Institute researchers discover possible new treatment for Ewing sarcoma  

Cancer.gov

Discovery of a new drug with high potential to treat Ewing sarcoma, an often deadly cancer of children and young adults, and the previously unknown mechanism behind it, come hand-in-hand in a new study by researchers from Huntsman Cancer Institute (HCI) at the University of Utah. In the lab, researchers found that an enzyme, called lysine specific demethylase (LSD-1), interacts with EWS/FLI to turn off gene expression in Ewing sarcoma. By turning off specific genes, the EWS/FLI-LSD1 complex causes Ewing sarcoma development. The team is now working to further test LSD inhibitors in animal models as they work toward approval of a first-in-man clinical trial.

69

The EWS/FLI Oncogene Drives Changes in Cellular Morphology, Adhesion, and Migration in Ewing Sarcoma.  

PubMed

Ewing sarcoma is a tumor of the bone and soft tissue caused by the expression of a translocation-derived oncogenic transcription factor, EWS/FLI. Overt metastases are associated with a poor prognosis in Ewing sarcoma, but patients without overt metastases frequently harbor micrometastatic disease at presentation. This suggests that the metastatic potential of Ewing sarcoma exists at an early stage during tumor development. We have therefore explored whether the inciting oncogenic event in Ewing sarcoma, EWS/FLI, directly modulates tumor cell features that support metastasis, such as cell adhesion, cell migration, and cytoarchitecture. We used an RNAi-based approach in patient-derived Ewing sarcoma cell lines. Although we hypothesized that EWS/FLI might induce classic metastatic features, such as increased cell adhesion, migration, and invasion (similar to the phenotypes observed when epithelial malignancies undergo an epithelial-to-mesenchymal transition during the process of metastasis), surprisingly, we found the opposite. Thus, EWS/FLI expression inhibited the adhesion of isolated cells in culture and prevented adhesion in an in vivo mouse lung assay. Cell migration was similarly inhibited by EWS/FLI expression. Furthermore, EWS/FLI expression caused a striking loss of organized actin stress fibers and focal adhesions and a concomitant loss of cell spreading, suggesting that EWS/FLI disrupts the mesenchymal phenotype of a putative tumor cell-of-origin. These data suggest a new paradigm for the dissemination and metastasis of mesenchymally derived tumors: these tumors may disseminate via a "passive/stochastic" model rather than via an "active" epithelial-to-mesenchymal type transition. In the case of Ewing sarcoma, it appears that the loss of cell adhesion needed to promote tumor cell dissemination might be induced by the EWS/FLI oncogene itself rather than via an accumulation of stepwise mutations. PMID:23050043

Chaturvedi, Aashi; Hoffman, Laura M; Welm, Alana L; Lessnick, Stephen L; Beckerle, Mary C

2012-02-01

70

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

PubMed

Alterations in DNA methylation patterns are a hallmark of malignancy. However, the majority of epigenetic studies of Ewing's sarcoma have focused on the analysis of only a few candidate genes. Comprehensive studies are thus lacking and are required. The aim of the present study was to identify novel methylation markers in Ewing's sarcoma using microarray analysis. The current study reports the microarray-based DNA methylation study of 1,505 CpG sites of 807 cancer-related genes from 69 Ewing's sarcoma samples. The Illumina GoldenGate Methylation Cancer Panel I microarray was used, and with the appropriate controls (n=14), a total of 92 hypermethylated genes were identified in the Ewing's sarcoma samples. The majority of the hypermethylated genes were associated with cell adhesion, cell regulation, development and signal transduction. The overall methylation mean values were compared between patients who survived and those that did not. The overall methylation mean was significantly higher in the patients who did not survive (0.25±0.03) than in those who did (0.22±0.05) (P=0.0322). However, the overall methylation mean was not found to significantly correlate with age, gender or tumor location. GDF10, OSM, APC and HOXA11 were the most significant differentially-methylated genes, however, their methylation levels were not found to significantly correlate with the survival rate. The DNA methylation profile of Ewing's sarcoma was characterized and 92 genes that were significantly hypermethylated were detected. A trend towards a more aggressive behavior was identified in the methylated group. The results of this study indicated that methylation may be significant in the development of Ewing's sarcoma. PMID:25202378

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

2014-10-01

71

Development of Ewing's Sarcoma from Primary Bone Marrow Derived Mesenchymal Progenitor Cells  

Microsoft Academic Search

Ewing's sarcoma is a member of Ewing's family tumors (EFTs) and the second most common solid bone and soft tissue malignancy of children and young adults. It is associated in 85% of cases with the t(11;22)(q24:q12) chromosomal trans- location that generates fusion of the 5V segment of the EWS gene with the 3V segment of the ETS family gene FLI-1.

Luisa Cironi; Paolo Provero; Konstantinos Kaloulis; Carlos Garcia-Echeverria; Francesco Hoffmann; Andreas Trumpp; Ivan Stamenkovic

2005-01-01

72

A rare case of primary Ewings sarcoma of the nasal bone.  

PubMed

Primary Ewing's sarcoma of the nasal bone has not been previously described. This case presented as a mass in the left ala of the nose in a five year old female child. The clinical, radiological, microscopic features are described and a review of literature is presented. The case was treated with neoadjuvant chemotherapy and local electron beam radiation therapy. The child was free of disease when she reported for follow up in July 1997. Although wide excision is part of the treatment approach in Ewing's sarcoma, in sites where surgery is not suitable local radiotherapy and chemotherapy adequately controls primary disease. PMID:23119384

Vidyasagar, M S; Rao, S; Fernandes, D J; Ramanujam, A S

1998-01-01

73

Peripheral neuroectodermal tumour of the kidney (Ewing’s sarcoma): Restaging with 18F-fluorodeoxyglucose (FDG)-PET/CT  

PubMed Central

Primitive peripheral neuroectodermal tumour and Ewing’s sarcoma (PNET/EWS) were originally described as two distinct pathologic entities, although both share common stem-cell precursor and unique chromosomal abnormality. Although its incidence has increased recently, its share in all sarcomas is 1%. It is usually seen in men and women in their twenties. We present a case of a 38-year-old woman with a left renal mass detected incidentally. Magnetic resonance imaging revealed a centrally located hypervascular renal mass with diameter of 6 cm with non-homogenous contrast enhancement containing necrotic and calcific areas. The patient was diagnosed as having PNET/EWS by histopathological examination following radical nephrectomy. Para-aortic lymph node metastasis was found on imaging by 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT). PMID:25624967

Ozturk, Hakan

2015-01-01

74

Ewing sarcoma dissemination and response to T-cell therapy in mice assessed by whole-body magnetic resonance imaging  

PubMed Central

Background: Novel treatment strategies in Ewing sarcoma include targeted cellular therapies. Preclinical in vivo models are needed that reflect their activity against systemic (micro)metastatic disease. Methods: Whole-body magnetic resonance imaging (WB-MRI) was used to monitor the engraftment and dissemination of human Ewing sarcoma xenografts in mice. In this model, we evaluated the therapeutic efficacy of T cells redirected against the Ewing sarcoma-associated antigen GD2 by chimeric receptor engineering. Results: Of 18 mice receiving intravenous injections of VH-64 Ewing sarcoma cells, all developed disseminated tumour growth detectable by WB-MRI. All mice had lung tumours, and the majority had additional manifestations in the bone, soft tissues, and/or kidney. Sequential scans revealed in vivo growth of tumours. Diffusion-weighted whole-body imaging with background signal suppression effectively visualised Ewing sarcoma growth in extrapulmonary sites. Animals receiving GD2-targeted T-cell therapy had lower numbers of pulmonary tumours than controls, and the median volume of soft tissue tumours at first detection was lower, with a tumour growth delay over time. Conclusion: Magnetic resonance imaging reliably visualises disseminated Ewing sarcoma growth in mice. GD2-retargeted T cells can noticeably delay tumour growth and reduce pulmonary Ewing sarcoma manifestations in this aggressive disease model. PMID:23839490

Liebsch, L; Kailayangiri, S; Beck, L; Altvater, B; Koch, R; Dierkes, C; Hotfilder, M; Nagelmann, N; Faber, C; Kooijman, H; Ring, J; Vieth, V; Rossig, C

2013-01-01

75

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

PubMed

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

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

2015-01-01

76

Metastatic Ewing's sarcoma/PNET of kidney in 40 year old patient  

PubMed Central

Introduction Primary renal Ewing sarcoma/PNET is an uncommon and very aggressive tumor. Presentation of case : We report the case of a young woman who underwent nephrectomy for a renal mass from unknown etiology. Histologic analysis found small tumoral cells in rosette formation, and immunohistochemical staining was positive for CD99, and focally positive for vimentin and Protein S-100. A post operative abdominal computed tomography (CT) scan revealed a residual renal processus with hepatic wounds and abdominal metastatic nodes. After 6 cycles of chemotherapy including Vincristine, Doxorubicin, Cyclophosphamide, the response was considered as good. Discussion Ewing's sarcoma/PNET of kidney is a member of the family of small round cell tumors and it should be differentiated from Wilms tumor, neuroblastoma, rhabdomyosarcoma and lymphoblastic lymphoma. The principle management of its treatment have been extrapolated from the treatment of osseous Ewing sarcoma of bone. Conclusion Despite aggressive treatment, primary renal Ewing sarcoma/PNET has a poor prognosis. It requires a multidisciplinary approach including oncologists, urologists and radiation oncologists. PMID:22466114

Kairouani, Mouna; Mokrim, Maha; Mellas, Nawfel; Khennoussi, Basma; M’rabti, Hind El; Boutayeb, Saber; Errihani, Hassan

2012-01-01

77

BMI1 Promotes Ewing Sarcoma Tumorigenicity Independent of CDKN2A Repression  

Microsoft Academic Search

Deregulation of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we have investigated if the Ewing sarcoma family of tumors (ESFT) expresses BMI-1 and whether it functions as an oncogene in this highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by ESFT

Dorothea Douglas; Jessie Hao-Ru Hsu; Aaron Cooper; Diana Abdueva; John van Doorninck; Hiro Shimada; Timothy J. Triche; Elizabeth R. Lawlor

2008-01-01

78

Primary spinal intradural extraskeletal Ewing sarcoma mimicking a giant nerve sheath tumor: case report and review of the literature  

PubMed Central

Primary intradural extraskeletal Ewing sarcoma is a very rare form of malignant neoplasm. Only few cases have been reported on the literature. Here, we report a case of a 14-year-old boy who had a chief complaint of pain and tingling in the right lower limb. The patient initially seemed to have a giant nerve sheath tumor but was eventually diagnosed with intradural extraskeletal Ewing sarcoma arising from the nerve roots of the cauda equine. The literature with regard to primary spinal intradural extraskeletal Ewing sarcoma is reviewed.

Zhao, Mingfei; Zhang, Buyi; Liang, Feng; Zhang, Jianmin

2014-01-01

79

Ewing's Sarcoma of the Head and Neck: A Retrospective Analysis of 24 Cases  

PubMed Central

Introduction and purpose. Primary Ewing's sarcoma arising from the bones of the head and neck region is extremely rare representing only 1– 4% of all Ewing's sarcoma cases. Previous reports suggest a better prognosis for that particular anatomic site. The purpose of this study was to analyze the clinico-epidemiologic characteristics of that rare clinical presentation, as well as its patterns of failure and prognosis following treatment. Materials and methods. This study included a retrospective review of the medical records of patients with the diagnosis of Ewing's sarcoma of the head and neck region treated at King Faisal Specialist Hospital and Research Center between 1975 and 1996. Results. Out of a total number of 24 cases analyzed, there were 17 males and 7 females with a ratio of 2.4:1. The median age at diagnosis was 16.5 years. A painful swelling was the most common clinical presentation.The maxilla was the most common site of presentation (9/24 cases). There were 3/24 cases who presented with metastatic disease at diagnosis.The majority of patients (16/24 cases) had a tumor size >10 cm. Most patients were treated with systemic chemotherapy plus localized irradiation following an initial biopsy.With a mean follow up of 3.4 years, the 5-year actual overall survival (OS) for the whole group was 53%, while the 5-year actuarial disease-free survival (DFS) was 30%. These figures were higher than those repor ted from our institution for young patients (? 14 years treated for Ewing' s sarcoma in other anatomic locations (30% v 15%). The response to chemotherapy was the only prognostic factor that affected both the OS and DFS. Conclusion. The prognosis of Ewing's sarcoma of the head and neck region is slightly better than that of other anatomic sites.The response to systemic chemotherapy is one of the most important prognostic factors affecting both DFS and OS of Ewing's sarcoma of the head and neck. Multimodality therapy consisting of an initial biopsy, aggressive combination chemotherapy and localized radiotherapy is the treatment of choice for Ewing's sarcoma of the head and neck region and may result in long-term survival. PMID:18521259

Allam, Ayman; El-Husseiny, Gamal; Khafaga, Yasser; Kandil, Alaa; Gray, Alan; Ezzat, Adnan

1999-01-01

80

Ewing's Sarcoma of the Head and Neck: A Retrospective Analysis of 24 Cases.  

PubMed

Introduction and purpose. Primary Ewing's sarcoma arising from the bones of the head and neck region is extremely rare representing only 1- 4% of all Ewing's sarcoma cases. Previous reports suggest a better prognosis for that particular anatomic site. The purpose of this study was to analyze the clinico-epidemiologic characteristics of that rare clinical presentation, as well as its patterns of failure and prognosis following treatment.Materials and methods. This study included a retrospective review of the medical records of patients with the diagnosis of Ewing's sarcoma of the head and neck region treated at King Faisal Specialist Hospital and Research Center between 1975 and 1996.Results. Out of a total number of 24 cases analyzed, there were 17 males and 7 females with a ratio of 2.4:1. The median age at diagnosis was 16.5 years. A painful swelling was the most common clinical presentation.The maxilla was the most common site of presentation (9/24 cases). There were 3/24 cases who presented with metastatic disease at diagnosis.The majority of patients (16/24 cases) had a tumor size >10 cm. Most patients were treated with systemic chemotherapy plus localized irradiation following an initial biopsy.With a mean follow up of 3.4 years, the 5-year actual overall survival (OS) for the whole group was 53%, while the 5-year actuarial disease-free survival (DFS) was 30%. These figures were higher than those repor ted from our institution for young patients (Ewing' s sarcoma in other anatomic locations (30% v 15%). The response to chemotherapy was the only prognostic factor that affected both the OS and DFS.Conclusion. The prognosis of Ewing's sarcoma of the head and neck region is slightly better than that of other anatomic sites.The response to systemic chemotherapy is one of the most important prognostic factors affecting both DFS and OS of Ewing's sarcoma of the head and neck. Multimodality therapy consisting of an initial biopsy, aggressive combination chemotherapy and localized radiotherapy is the treatment of choice for Ewing's sarcoma of the head and neck region and may result in long-term survival. PMID:18521259

Allam, A; El-Husseiny, G; Khafaga, Y; Kandil, A; Gray, A; Ezzat, A; Schultz, H

1999-01-01

81

BCL11B Is Up-Regulated by EWS/FLI and Contributes to the Transformed Phenotype in Ewing Sarcoma  

PubMed Central

The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines. BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing’s sarcoma and contributes to the EWS/FLI repressed gene signature. BCL11B repressive activity is mediated by the NuRD co-repressor complex. We further demonstrate that re-expression of SPRY1, a repressed target of BCL11B, limits the transformation capacity of Ewing sarcoma cells. These data define a new pathway downstream of EWS/FLI required for oncogenic maintenance in Ewing sarcoma. PMID:23527175

Wiles, Elizabeth T.; Lui-Sargent, Bianca; Bell, Russell; Lessnick, Stephen L.

2013-01-01

82

Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS  

Microsoft Academic Search

Ewing family tumors result from the effects of chromosomal translocations that fuse the Ewing sarcoma (EWS) gene to various genes encoding transcription factors [1]. The resulting chimeric EWS fusion proteins are transcriptional activators with transforming potential that have received much study [2]. By contrast, the cellular function of somatic EWS remains obscure. EWS belongs to a family of RNA-binding proteins

Jason S. Felsch; Ernest G. Peralta

1999-01-01

83

A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma.  

PubMed

Differential diagnosis of small round cell sarcomas (SRCSs) grouped under the Ewing sarcoma family of tumors (ESFT) can be a challenging situation for pathologists. Recent studies have revealed that some groups of Ewing-like sarcoma show typical ESFT morphology but lack any EWSR1-ETS gene fusions. Here we identified a novel gene fusion, CIC-FOXO4, in a case of Ewing-like sarcoma with a t(X;19)(q13;q13.3) translocation. The patient was a 63-year-old man who had an asymptomatic, 30-mm, well-demarcated, intramuscular mass in his right posterior neck, and imaging findings suggested a diagnosis of high-grade sarcoma. He was treated with complete resection and subsequent radiotherapy and chemotherapy. He was alive without local recurrence or distant metastasis 6 months after the operation. Histologic examination revealed SRCS with abundant desmoplastic fibrous stroma suggesting a desmoplastic small round cell tumor. Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively. High-throughput transcriptome sequencing revealed a gene fusion, and the genomic rearrangement between the CIC and FOXO4 genes was identified by fluorescence in situ hybridization. Aside from the desmoplastic stroma, the CIC-FOXO4 fusion sarcoma showed morphologic and immunohistochemical similarity to ESFT and Ewing-like sarcomas, including the recently described CIC-DUX4 fusion sarcoma. Although clinicopathologic analysis with additional cases is necessary, we conclude that CIC-FOXO4 fusion sarcoma is a new type of Ewing-like sarcoma that has a specific genetic signature. These findings have important implications for the differential diagnosis of SRCS. PMID:25007147

Sugita, Shintaro; Arai, Yasuhito; Tonooka, Akiko; Hama, Natsuko; Totoki, Yasushi; Fujii, Tomoki; Aoyama, Tomoyuki; Asanuma, Hiroko; Tsukahara, Tomohide; Kaya, Mitsunori; Shibata, Tatsuhiro; Hasegawa, Tadashi

2014-11-01

84

Microarray analysis of Ewing’s sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy  

Microsoft Academic Search

In Ewing’s sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy.To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH,

Karl-Ludwig Schaefer; Martin Eisenacher; Yvonne Braun; Kristin Brachwitz; Daniel H. Wai; Uta Dirksen; Claudia Lanvers-Kaminsky; Heribert Juergens; David Herrero; Sabine Stegmaier; Ewa Koscielniak; Angelika Eggert; Michaela Nathrath; Georg Gosheger; Dominik T. Schneider; Carsten Bury; Raihanatou Diallo-Danebrock; Laura Ottaviano; Helmut E. Gabbert; Christopher Poremba

2008-01-01

85

RASSF2 methylation is a strong prognostic marker in younger age patients with Ewing sarcoma  

PubMed Central

Ras-association domain family of genes consist of 10 members (RASSF1-RASSF10), all containing a Ras-association (RA) domain in either the C- or the N-terminus. Several members of this gene family are frequently methylated in common sporadic cancers; however, the role of the RASSF gene family in rare types of cancers, such as bone cancer, has remained largely uninvestigated. In this report, we investigated the methylation status of RASSF1A and RASSF2 in Ewing sarcoma (ES). Quantitative real-time methylation analysis (MethyLight) demonstrated that both genes were frequently methylated in Ewing sarcoma tumors (52.5% and 42.5%, respectively) as well as in ES cell lines and gene expression was upregulated in methylated cell lines after treatment with 5-aza-2?-deoxcytidine. Overexpression of either RASSF1A or RASSF2 reduced colony formation ability of ES cells. RASSF2 methylation correlated with poor overall survival (p = 0.028) and this association was more pronounced in patients under the age of 18 y (p = 0.002). These results suggest that both RASSF1A and RASSF2 are novel epigenetically inactivated tumor suppressor genes in Ewing sarcoma and RASSF2 methylation may have prognostic implications for ES patients. PMID:23887284

Gharanei, Seley; Brini, Anna T; Vaiyapuri, Sumathi; Alholle, Abdullah; Dallol, Ashraf; Arrigoni, Elena; Kishida, Takeshi; Hiruma, Toru; Avigad, Smadar; Grimer, Robert; Maher, Eamonn R; Latif, Farida

2013-01-01

86

Cutaneous Ewing's sarcoma secondary to chemotherapy given for testis tumor: Case report  

PubMed Central

INTRODUCTION Testicular cancer has high cure rates, especially after the adjuvant use of chemotherapy. Secondary tumors may develop months and years after the primary tumor. We aimed to report a case of cutaneous Ewing's sarcoma at the site of surgery 3 years after BEP chemotherapy. PRESENTATION OF CASE 21 year old male underwent radical orchiectomy in 2008. After one year surgical site complaints brought him to same hospital. A limited surgical resection was made. As his complaints continued he applied to our clinic. We resected the lesion with a 5 cm safety margin with the light of previous medical history. Pathology revealed cutaneous Ewing's sarcoma, and patient received VACD-IE chemotherapy. He is free of recurrence till now. DISCUSSION Chemotherapy may cause secondary cancer especially in long term. In this case secondary tumor is diagnosed three years after surgery. Patient underwent therapeutic surgery and received chemotherapy (VACD-IE) for secondary Ewing's sarcoma. Early diagnosis and definitive treatment provide recurrence free survival in the patient. CONCLUSION Secondary tumors can emerge months or years after primary tumor therapies, and are not related with the primary tumors. Any lesion or sign should be investigated carefully. Early diagnosis and correct treatment could prevent dramatic results. PMID:25460450

Tan?k, Serhat; Zengin, Kür?ad; Albayrak, Sebahattin; Ery?lmaz, Recep; Y?lmaz, Deniz; Pirinçci, Necip

2014-01-01

87

Primary Ewing's sarcoma family of tumors arising from the broad ligament.  

PubMed

We report a case of a primary Ewing's sarcoma family of tumors (ESFT) that was an incidental finding in the broad ligament of a 53-year-old woman. ESFT now includes tumors previously described as Askin tumor, neuroepithelioma, extraskeletal Ewing's sarcoma, and peripheral primitive neuroectodermal tumor. This is because of the discovery that all of the above tumors contain a specific gene rearrangement involving chromosome 22q12. On microscopic examination, the tumor was composed of small, round cells with mild nuclear pleomorphism and scant eosinophilic cytoplasm. There were large areas of tumor necrosis and numerous mitoses. Immunohistochemically, there was strong membrane staining for CD99 and weak focal staining for CD56 and neuron specific enolase. Fluorescence in situ hybridization revealed a separation of the breakapart probe on chromosome 22q12 consistent with the presence of a gene rearrangement, supporting the diagnosis of ESFT. We believe the importance of recognizing the existence of a primary ESFT in the broad ligament as some primary tumors of the gynecological tract and of other systems may resemble it histologically. To the best of our knowledge, our case is the second case of extraskeletal Ewings sarcoma arising from the broad ligament but the first case that is confirmed by strong CD99 positivity and supported by fluorescence in situ hybridization. PMID:16175085

Lee, Kenneth Maan Liong; Wah, Hock Kua

2005-10-01

88

Antagonizing Bcl-2 Family Members Sensitizes Neuroblastoma and Ewing’s Sarcoma to an Inhibitor of Glutamine Metabolism  

PubMed Central

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

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

2015-01-01

89

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

PubMed Central

Only few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present here two cases of renal ES/PNET with an uncanny presentation. The first case was discovered after the patient presented clinically with irradiating flank pain, mimicking the pain related with kidney stones. The second case had clinical presentation of pulmonary thromboembolism after the patient was involved in an automobilist accident. The tumors were mainly composed of small blue cells which by immunohistochemical were positive for neural markers, and FISH revealed the translocation 22q12 for the EWSR1 gene. The diagnosis of renal primitive neuroectodermal tumor/EWING tumor is very rare and usually involves several different diagnostic techniques. The differential diagnosis is usually broad with frequent overlapping features between the entities. The cases presented in this paper illustrated the difficulties with which routine anatomical pathologist is faced when dealing with rare renal poorly differentiated neoplasm in adults. PMID:22312368

Castro, E. C.; Parwani, A. V.

2012-01-01

90

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

PubMed

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

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

2014-10-01

91

Primary Ewing sarcoma/primitive neuroectodermal tumor of the renal pelvis: a case report.  

PubMed

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a childhood malignancy, typically occurring in the bone and rarely in any other part of the body. We herein present a case of ES/PNET of the renal pelvis. A 37-year-old male patient presented with a chief complaint of pain in the left flank and gross hematuria. The tumor had caused moderate hydronephrosis, and ureteroscopic biopsy findings were highly suspicious of sarcoma. Subsequently, radical nephroureterectomy was performed. On the basis of the pathological and cytogenetic findings, a final diagnosis of primary ES/PNET of left renal pelvis was made. Adjuvant chemotherapy with adriamycin and ifosfamide was initiated as ES/PNET often exhibits aggressive biological behavior. The patient was disease-free at his last regular follow-up visit 18 months after the surgery. To our knowledge, this is the first reported case of primary ES/PNET of the renal pelvis. PMID:25242447

Liu, Zhihong; Wang, Xianding; Lu, You; Chen, Libo; Lu, Yiping

2014-01-01

92

[Detection of EWS-/FLI-1 gene fusion transcripts by RT-PCR as a tool in the diagnosis of tumors of the Ewing sarcoma group].  

PubMed

Recent cloning of the chromosome breakpoint regions of the reciprocal chromosomal t(11;22) (q24;q12) has revealed that the breakpoints were localized within the EWS gene (Ewings sarcoma gene) on chromosome 22 and the FLI-1 gene on chromosome 11. Thus, molecular genetic techniques were applicable for the detection of this genetic aberration, which occurs as a consistent feature of the Ewings tumor family. By reverse transcription and polymerase chain reaction technique (RT-PCR) in 78% of Ewings sarcoma derived cell lines, and in 91% of primary Ewings tumor tissue t(11;22) specific EWS/FLI-1 fusion transcripts were detected. Furthermore, in bone marrow samples from an Ewings sarcoma patient contaminating tumor cells could be shown by RT-PCR. Our results indicate that molecular genetic detection of the t(11;22) translocation opens a new modality for the differential diagnosis and the staging of Ewings tumor patients. PMID:7533989

Dockhorn-Dworniczak, B; Schäfer, K L; Dantcheva, R; Blasius, S; van Valen, F; Burdach, S; Winkelmann, W; Jürgens, J; Böcker, W

1994-01-01

93

Stereotactic Body Radiotherapy for Metastatic and Recurrent Ewing Sarcoma and Osteosarcoma  

PubMed Central

Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma. Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012. Results. We identified 14 patients with a total of 27 lesions from osteosarcoma (n = 19) or ES (n = 8). The median total curative/definitive SBRT dose delivered was 40?Gy in 5 fractions (range, 30–60?Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40?Gy in 5 fractions (range, 16–50?Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation. Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity. PMID:25548538

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

2014-01-01

94

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

SciTech Connect

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.

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

95

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

PubMed

Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma. Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012. Results. We identified 14 patients with a total of 27 lesions from osteosarcoma (n = 19) or ES (n = 8). The median total curative/definitive SBRT dose delivered was 40?Gy in 5 fractions (range, 30-60?Gy in 3-10 fractions). The median total palliative SBRT dose delivered was 40?Gy in 5 fractions (range, 16-50?Gy in 1-10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation. Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity. PMID:25548538

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

2014-01-01

96

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

PubMed Central

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

2014-01-01

97

Extra-osseous Ewing's sarcoma of sciatic nerve masquerading as an infected hemangioma: A rare case report  

PubMed Central

Extra-osseous Ewing's Sarcoma (EES) arising from the peripheral nerve is rarely reported in children. Here, we report an instance of EES arising from the left sciatic nerve mimicking an infected hemangioma. This case highlights the need for a high index of suspicion and early histological diagnosis to avoid diagnostic delay. PMID:25336807

Dhua, Anjan K; Bharathi, Ravindhra; Kiran, Chokka Mahesh; Lingam, Pappu Paramartha; Joshi, Manoj

2014-01-01

98

Pregnancy after limb-sparing hemipelvectomy for Ewing's sarcoma. A case report and review of the literature.  

PubMed

Ewing's sarcoma of the bone is a malignant bone tumor occurring mostly in adolescence and was considered to have poor prognosis. With recent advances in multi-agent combined chemotherapy, prognosis has improved, and more patients with primary lesions in the pelvis opt for limb-saving surgeries. In the present case, Ewing's sarcoma in the left pelvis was diagnosed at the age of 11 and the patient underwent multi-agent chemotherapy combined with limb-sparing hemipelvectomy. She became pregnant at the age of 22. After an uneventful pregnancy, she delivered a healthy child at 37 weeks of gestation by cesarean section because of pelvic distortion. This is the first reported case of pregnancy and delivery after limb-sparing hemipelvectomy due to Ewing's sarcoma. Since the multi-modality treatment improves survival, the number of women with Ewing's sarcoma who desire pregnancy is expected to increase in the future. This is a valuable case that will provide useful information for such patients. PMID:14614252

Chihara, Izumi Goto; Osada, Hisao; Iitsuka, Yoshinori; Masuda, Kentaro; Sekiya, Souei

2003-01-01

99

Intra-neural Ewing's sarcoma of the upper limb mimicking a peripheral nerve tumour. A report of 2 cases.  

PubMed

Ewing's sarcoma is a malignant round cell tumour of bone commonly affecting children and young adults. Intra-neural Ewings is very rare form of extraosseous Ewing's sarcoma (EES), posing diagnostic and therapeutic challenges. We report two cases of intra-neural EES presenting with elbow pain and swelling, mimicking an upper limb peripheral nerve sheath tumour. Following a CT guided biopsy to confirm diagnosis, the patients were treated with a combination of surgical resection, chemotherapy and radiotherapy. These cases highlight the potential diagnostic challenges as their presentation can be misleading due to the non-specificity of symptoms. These are highly aggressive tumours with the propensity to metastasize. We review importance of collective radiological and immunohistochemical analysis followed by early, aggressive multimodal treatment within a multidisciplinary setting. This provides the best prognosis in the context of upper limb peripheral nerve tumours. PMID:21330228

Mohan, Anita T; Park, Derek H; Jalgaonkar, Azal; Alorjani, Mohammed; Aston, William; Briggs, Tim

2011-06-01

100

The clinical use of biomarkers as prognostic factors in Ewing sarcoma  

PubMed Central

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

2012-01-01

101

EWS/FLI1 regulates EYA3 in Ewing's sarcoma via modulation of microRNA-708, resulting in increased cell survival and chemoresistance  

PubMed Central

Ewing's sarcoma is an aggressive pediatric cancer of the bone and soft tissue, in which patients whose tumors have a poor histological response to initial chemotherapy have a poor overall prognosis. Therefore, it is important to identify molecules involved in resistance to chemotherapy. Herein, we demonstrate that the DNA-repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing's sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell of origin of Ewing's sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor. We further demonstrate that EWS/FLI1 mediates upregulation of EYA3 via repression of miR-708, a microRNA that targets the EYA3 3?UTR, rather than by binding the EYA3 promoter directly. Importantly, we demonstrate that high levels of EYA3 significantly correlate with low levels of miR-708 in Ewing's sarcoma samples, suggesting that this miR-mediated mechanism of EYA3 regulation holds true in human cancers. Because EYA proteins are important for cell survival during development, we examine, and demonstrate, that loss of EYA3 decreases survival of Ewing's sarcoma cells. Most importantly, knockdown of EYA3 in Ewing's sarcoma cells leads to sensitization to DNA-damaging chemotherapeutics used in the treatment of Ewing's sarcoma, and as expected, after chemotherapeutic treatment, EYA3 knockdown cells repair DNA damage less effectively than their control counterparts. These studies identify EYA3 as a novel mediator of chemoresistance in Ewing's sarcoma and define the molecular mechanisms of both EYA3 overexpression and of EYA3-mediated chemoresistance. PMID:22723308

Robin, Tyler P; Smith, Anna; McKinsey, Erin; Reaves, Lisa; Jedlicka, Paul; Ford, Heide L.

2012-01-01

102

A case of primary mediastinal Ewing's sarcoma / primitive neuroectodermal tumor presenting with initial compression of superior vena cava  

PubMed Central

Ewing's sarcomas and peripheral primitive neuroectodermal tumors (ES/PNETs) are high grade malignant neoplasms. These malignancies are characterized by a chromosome 22 rearrangement, arise from bone or soft tissue, predominantly affect children and young adults, and are grouped in the Ewing family of tumors. Multimodality treatment programs are the treatment of choice. Primary localization of ES/PNET in the mediastinum is extremely rare. We describe a case of ES/PNET presenting as a mediastinal mass with tracheal compression and initial signs of superior vena cava in a 66-year-old woman. PMID:23741276

Reali, Alessia; Mortellaro, Gianluca; Allis, Simona; Trevisiol, Edoardo; Anglesio, Silvia Maria; Bartoncini, Sara; Redda, Maria Grazia Ruo

2013-01-01

103

Oncogenic Serine-Threonine Kinase Receptor-Associated Protein Modulates the Function of Ewing Sarcoma Protein through a Novel Mechanism  

Microsoft Academic Search

Although much is known about the oncogenic functions of chimeric Ewing sarcoma (EWS) fusion proteins that result from chromosomal translocations, the cellular role of the normal EWS protein is not well characterized. We have previously identified a WDdomain-containing protein, serine-threonine kinase receptor-associated protein (STRAP), which inhibits transforming growth factor B (TGF-B) signaling through interaction with receptors and Smad7 and promotes

Govindaraj Anumanthan; Sunil K. Halder; David B. Friedman; Pran K. Datta

2006-01-01

104

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

PubMed Central

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

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

2013-01-01

105

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

SciTech Connect

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.

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

106

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

PubMed Central

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

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

2009-01-01

107

MicroRNA expression and its clinical implications in Ewing's sarcoma.  

PubMed

Ewing's sarcoma (EWS) is the second most common primary bone cancer, and is a predominant childhood malignant disease. Due to limited understanding of its pathogenesis and frequent occurrence of resistance to conventional types of treatment, its management remains difficult, and mortality is frequent. Development of EWS is a multistep process involving genetic and epigenetic alterations of protein-coding proto-oncogenes and tumour-suppressor genes. MicroRNAs (miRNAs) have recently been discovered as a new category of non-protein coding; small RNA molecules that regulate gene expression at the post-transcriptional level. Substantial numbers of deregulated miRNAs have been documented in EWS and their biological significance has been confirmed in multiple functional experiments. Several studies have confirmed involvement of miRNAs in various steps of EWS pathogenesis, from occurrence to metastasis. Functionally, miRNA dysregulation may promote cell-cycle progression, confer resistance to apoptosis, and enhance invasiveness and metastasis. These miRNAs have opened a novel field in cancer research with potential clinical utilization for screening, diagnosis, prognostics and prediction of response to treatment. Elucidating biological aspects of miRNA dysregulation may help better understand pathogenesis of EWS and promote development of miRNA directed-therapeutics against it. PMID:25530497

Li, Zheng; Yu, Xin; Shen, Jianxiong; Wu, William Ka Kei; Chan, Matthew T V

2015-02-01

108

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

SciTech Connect

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

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

2009-12-25

109

Antagonizing Bcl-2 Family Members Sensitizes Neuroblastoma and Ewing's Sarcoma to an Inhibitor of Glutamine Metabolism.  

PubMed

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

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

2015-01-01

110

Arsenic trioxide concentration determines the fate of Ewing's sarcoma family tumors and neuroblastoma cells in vitro.  

PubMed

Arsenic trioxide (As(2)O(3)) induces both the differentiation and apoptosis of acute promyelocytic leukemia cells in a concentration dependent manner. We assessed the effects of As(2)O(3) in CADO-ES Ewing's sarcoma (ES), JK-GMS peripheral primitive neuroectodermal tumor (PNET), and SH-SY5Y neuroblastoma cells, as they share common histogenetic backgrounds. As(2)O(3) at low concentrations (0.1-1 microM) induced SH-SY5Y differentiation, and whereas PNET cells acquired a slightly differentiated phenotype, change was minimal in ES cells. Extracellular signal-regulated kinase 2 (ERK2) was activated at low As(2)O(3) concentrations, and PD98059, an inhibitor of MEK-1, blocked SH-SY5Y cell differentiation by As(2)O(3). High concentrations (2-10 microM) of As(2)O(3) induced the apoptosis in all three cell lines, and this was accompanied by the activation of c-jun N-terminal kinase. The generation of H(2)O(2) and activation of caspase 3 were identified as critical components of As(2)O(3)-induced apoptosis in all of the above cell lines. Fibroblast growth factor 2 enhanced As(2)O(3)-induced apoptosis in JK-GMS cells. The overall effects of As(2)O(3) strongly suggest that it has therapeutic potential for the treatment of ES/PNET. PMID:16930595

Jung, Hyun Sook; Kim, Han-Seong; Lee, Min-Jae; Shin, Hee Young; Ahn, Hyo Seop; Ryu, Kyung-Ha; Seoh, Ju-Young; Kim, Chong Jai; Jang, Ja June

2006-09-01

111

Morphoproteomic Profiling of the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Desmoplastic Small Round Cell Tumor (EWS/WT1), Ewing’s Sarcoma (EWS/FLI1) and Wilms’ Tumor(WT1)  

PubMed Central

Background Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing’s sarcoma (EWS) gene with the Wilms’ tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing’s sarcoma (EWS-FLI1) and Wilms’ tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies. Methodology This pilot study assessed patients with DSRCT, Wilms’ tumor and Ewing’s sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls. Principal Findings In DSRCT the PI3K/Akt/mTOR pathway is constitutively activated by p-Akt (Ser 473) expression in the nuclear compartment of the tumor cells and p-mTOR phosphorylated on Ser 2448, suggesting mTORC2 (rictor+mTOR) as the dominant form. Ewing’s sarcoma had upregulated p-Akt and p-mTOR, predominantly mTORC2. In Wilm’s tumor, the mTOR pathway is also activated with most tumor cells moderately expressing p-mTOR (Ser 2448) in plasmalemmal and cytoplasmic compartments. This coincides with the constitutive activation of one of the downstream effectors of the mTORC1 signaling pathway, namely p-p70S6K (Thr 389). There was constitutive activation of the Ras/Raf/ERK pathway p-ERK 1/2 (Thr202/Tyr204) expression in the Wilms tumor and metastatic Ewing’s sarcoma, but not in the DSRCT. Conclusion Morphoproteomic tumor analyses revealed constitutive activation of the mTOR pathway as evidenced by: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic assessments of these tumors are warranted. PMID:23922674

Jiang, Yunyun; Buryanek, Jamie; Hayes-Jordan, Andrea

2013-01-01

112

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

PubMed Central

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

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

2013-01-01

113

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

PubMed Central

Background High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years. Results We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures. Conclusion Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into disease focused phase I/II clinical trials. Examples of new models for early translational and early phase trial collaboration include the European based EuroBoNeT network, the Sarcoma Alliance for Research through Collaboration network (SARC) and the new European collaborative translational trial network, EuroSarc. PMID:22587841

2012-01-01

114

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

PubMed Central

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

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

2015-01-01

115

Peripheral neuroectodermal tumour of the kidney (Ewing's sarcoma): Restaging with (18)F-fluorodeoxyglucose (FDG)-PET/CT.  

PubMed

Primitive peripheral neuroectodermal tumour and Ewing's sarcoma (PNET/EWS) were originally described as two distinct pathologic entities, although both share common stem-cell precursor and unique chromosomal abnormality. Although its incidence has increased recently, its share in all sarcomas is 1%. It is usually seen in men and women in their twenties. We present a case of a 38-year-old woman with a left renal mass detected incidentally. Magnetic resonance imaging revealed a centrally located hypervascular renal mass with diameter of 6 cm with non-homogenous contrast enhancement containing necrotic and calcific areas. The patient was diagnosed as having PNET/EWS by histopathological examination following radical nephrectomy. Para-aortic lymph node metastasis was found on imaging by (18)F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT). PMID:25624967

Ozturk, Hakan

2015-01-01

116

Pharmacokinetic modeling optimizes inhibition of the ‘undruggable’ EWS-FLI1 transcription factor in Ewing Sarcoma  

PubMed Central

Transcription factors have long been deemed ‘undruggable’ targets for therapeutics. Enhanced recognition of protein biochemistry as well as the need to have more targeted approaches to treat cancer has rendered transcription factors approachable for therapeutic development. Since transcription factors lack enzymatic domains, the specific targeting of these proteins has unique challenges. One challenge is the hydrophobic microenvironment that affects small molecules gaining access to block protein interactions. The most attractive transcription factors to target are those formed from tumor specific chromosomal translocations that are validated oncogenic driver proteins. EWS-FLI1 is a fusion protein that results from the pathognomonic translocation of Ewing sarcoma (ES). Our past work created the small molecule YK-4-279 that blocks EWS-FLI1 from interacting with RNA Helicase A (RHA). To fulfill long-standing promise in the field by creating a clinically useful drug, steps are required to allow for in vivo administration. These investigations identify the need for continuous presence of the small molecule protein-protein inhibitor for a period of days. We describe the pharmacokinetics of YK-4-279 and its individual enantiomers. In vivo studies confirm prior in vitro experiments showing (S)-YK-4-279 as the EWS-FLI1 specific enantiomer demonstrating both induction of apoptosis and reduction of EWS-FLI1 regulated caveolin-1 protein. We have created the first rat xenograft model of ES, treated with (S)-YK-4-279 dosing based upon PK modeling leading to a sustained complete response in 2 of 6 ES tumors. Combining laboratory studies, pharmacokinetic measurements, and modeling has allowed us to create a paradigm that can be optimized for in vivo systems using both in vitro data and pharmacokinetic simulations. Thus, (S)-YK-4-279 as a small molecule drug is ready for continued development towards a first-in-human, first-in-class, clinical trial. PMID:24481407

Hong, S. Peter; Kallakury, Bhaskar; Monroe, Phillip; Erkizan, Hayriye V; Barber-Rotenberg, Julie S.; Houghton, Peter; Üren, Aykut; Toretsky, Jeffrey A.

2014-01-01

117

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

PubMed Central

Despite intensive treatment with chemotherapy, radiotherapy and surgery, over 70% of patients with metastatic Ewing's Sarcoma Family of Tumors (EFT) will die of their disease. We hypothesize that properly characterized laboratory models reflecting the drug resistance of clinical tumors will facilitate the application of new therapeutic agents to EFT. To determine resistance patterns, we studied newly established EFT cell lines derived from different points in therapy: two established at diagnosis (CHLA-9, CHLA-32), two after chemotherapy and progressive disease (CHLA-10, CHLA-25), and two at relapse after myeloablative therapy and autologous bone marrow transplantation (post-ABMT) (CHLA-258, COG-E-352). The new lines were compared to widely studied EFT lines TC-71, TC-32, SK-N-MC, and A-673. These lines were extensively characterized with regard to identity (short tandem repeat (STR) analysis), p53, p16/14 status, and EWS/ETS breakpoint and target gene expression profile. The DIMSCAN cytotoxicity assay was used to assess in vitro drug sensitivity to standard chemotherapy agents. No association was found between drug resistance and the expression of EWS/ETS regulated genes in the EFT cell lines. No consistent association was observed between drug sensitivity and p53 functionality or between drug sensitivity and p16/14 functionality across the cell lines. Exposure to chemotherapy prior to cell line initiation correlated with drug resistance of EFT cell lines in 5/8 tested agents at clinically achievable concentrations (CAC) or the lower tested concentration (LTC): (cyclophosphamide (as 4-HC) and doxorubicin at CAC, etoposide, irinotecan (as SN-38) and melphalan at LTC; P<0.1 for one agent, and P<0.05 for four agents. This panel of well-characterized drug-sensitive and drug-resistant cell lines will facilitate in vitro preclinical testing of new agents for EFT. PMID:24312454

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

2013-01-01

118

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

PubMed Central

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

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

2014-01-01

119

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

SciTech Connect

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

La, Trang H. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Meyers, Paul A. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Wexler, Leonard H. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Healey, John H. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Laquaglia, Michael P. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Boland, Patrick J. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Wolden, Suzanne L. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)]. E-mail: woldens@mskcc.org

2006-02-01

120

Trial of Dasatinib in Advanced Sarcomas  

ClinicalTrials.gov

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)

2014-12-17

121

Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed ewing sarcoma at a single institution.  

PubMed

The combination of cyclophosphamide and topotecan (cyclo/topo) has shown objective responses in relapsed Ewing sarcoma, but the response duration is not well documented. We reviewed characteristics and outcome of 14 patients with Ewing sarcoma, treated uniformly at a single institution and offered cyclo/topo at first relapse. Six patients (43%) had relapse at distant sites. All patients received first-line salvage therapy with cyclophosphamide 250 mg/m and topotecan 0.75 mg/m, daily for 5 days repeated every 21 days. The median number of cycles was 4 (range 1 to 10). All toxicities were manageable, the most common being transient cytopenias. There were also 4 episodes of febrile neutropenia, and 3 episodes of gross hematuria. Response was assessable in 13 patients and showed progressive disease in 6 (46%), stable disease in 4 (31%), and partial response in 3 (23%). Nine patients had local control, consisting of radical surgery in 2, radiation in 3, and a combination in 4 patients. Response, when it occurred, was maintained for a median of 8 months (range, 4 to 28 mo). Four patients (29%) are alive at 3, 7, 9, and 110 months after relapse; 1 is receiving cyclo/topo, 1 is on third-line therapy, and 2 are in second and fourth remission. The low toxicity of this combination, and the lack of sustained responses, warrant its investigation in combination with targeted or novel therapeutic agents in relapsed disease. PMID:23042020

Farhat, Rawad; Raad, Roy; Khoury, Nabil J; Feghaly, Julien; Eid, Toufic; Muwakkit, Samar; Abboud, Miguel; El-Solh, Hassan; Saab, Raya

2013-07-01

122

Successful complete resection of Ewing sarcoma arising from the bladder in a 10-year-old boy after chemotherapy.  

PubMed

Ewing sarcoma (ES) of the bladder is extremely rare. Here we report the successful treatment of the youngest case of ES arising from bladder encountered to date and a literature review. A 10-year-old boy who presented with polyuria and lower abdominal swelling was found to have a 13 cm mass arising from the bladder localized to the center of the lower abdomen. Biopsy confirmed ES. Following chemotherapy, the mass shrank to 5 cm and was found to be localized to the right side of the bladder with invasion of the right vas deferens. One-third of the right side of the bladder and part of the right vas deferens were resected. No viable cancer cells were detected in the resected specimen, and the surgical margins were reported to be negative. The patient is currently well with no recurrence or metastases after 11 months. There are 12 cases of Ewings sarcoma arising from the bladder reported in the English literature; two cases in children. Our case will be the third pediatric case and the youngest. PMID:25080033

Sueyoshi, Ryo; Okawada, Manabu; Fujimura, Junya; Saito, Masahiro; Koga, Hiroyuki; Lane, Geoffrey J; Yamataka, Atsuyuki

2014-09-01

123

Soft Tissue Sarcoma in Children  

MedlinePLUS

... for all those affected by children ' s cancer. Search Soft Tissue Sarcoma in Children Soft tissue sarcomas in children are ... tissue sarcomas, the most common of which are rhabdomyosarcoma , osteosarcoma and Ewing sarcoma . Each year, approximately 900 ...

124

Two Cases of Spinal, Extraosseous, Intradural Ewing's sarcoma/Peripheral Neuroectodermal Tumor: Radiologic, Pathologic, and Molecular Analysis.  

PubMed

Extraosseous Ewing's sarcoma/peripheral neuroectodermal tumors (ES/PNETs) are rare neoplasms that account for approximately 10%-15% of soft tissue sarcomas in children and 5% of soft tissue sarcomas in adults. Primary spinal, extraosseous, intradural ES/PNETs are even less common. The diagnosis of ES/PNET is extremely challenging, because the tumor can have a nonspecific radiologic appearance, and the histologic features are shared by many other "small round cell tumors." Thus, ES/PNET should be included in the radiologic and pathologic differential diagnosis, even in older patients and in unusual tumor sites. We report two cases of spinal, extraosseous, intradural ES/PNETs in adults who presented with back pain. Magnetic resonance imaging revealed contrast enhancing, intradural lesions in the area of the conus medullaris. The tumor in Case 1 was partially intramedullary, while the tumor in Case 2 was exclusively extramedullary. In both cases, the radiologic and intraoperative surgical impression favored ependymoma. The diagnosis of ES/PNET was established in both cases by histopathologic, immunohistochemical, and molecular analysis. PMID:24678438

Mardekian, Stacey K; Gandhe, Ashish; Miettinen, Markku; Pack, Svetlana; Curtis, Mark T; Abdullaev, Ziedulla

2014-01-01

125

Two Cases of Spinal, Extraosseous, Intradural Ewing's sarcoma/Peripheral Neuroectodermal Tumor: Radiologic, Pathologic, and Molecular Analysis  

PubMed Central

Extraosseous Ewing's sarcoma/peripheral neuroectodermal tumors (ES/PNETs) are rare neoplasms that account for approximately 10%-15% of soft tissue sarcomas in children and 5% of soft tissue sarcomas in adults. Primary spinal, extraosseous, intradural ES/PNETs are even less common. The diagnosis of ES/PNET is extremely challenging, because the tumor can have a nonspecific radiologic appearance, and the histologic features are shared by many other “small round cell tumors.” Thus, ES/PNET should be included in the radiologic and pathologic differential diagnosis, even in older patients and in unusual tumor sites. We report two cases of spinal, extraosseous, intradural ES/PNETs in adults who presented with back pain. Magnetic resonance imaging revealed contrast enhancing, intradural lesions in the area of the conus medullaris. The tumor in Case 1 was partially intramedullary, while the tumor in Case 2 was exclusively extramedullary. In both cases, the radiologic and intraoperative surgical impression favored ependymoma. The diagnosis of ES/PNET was established in both cases by histopathologic, immunohistochemical, and molecular analysis. PMID:24678438

Mardekian, Stacey K; Gandhe, Ashish; Miettinen, Markku; Pack, Svetlana; Curtis, Mark T; Abdullaev, Ziedulla

2014-01-01

126

Candida tropicalis arthritis of the elbow in a patient with Ewing's sarcoma that successfully responded to itraconazole  

PubMed Central

Fungal infections are rarely responsible for arthritis. Few cases of fungal arthritis have been reported, even in immunocompromised hosts susceptible to low-virulence organisms. Herein, the authors report the first case of Candida tropicalis arthritis in a child with a solid tumor. A 13-year-old boy with Ewing's sarcoma developed arthritis in his elbow during the neutropenic period after chemotherapy. Despite treatment with broad-spectrum antibiotics, his condition did not improve and serial blood cultures failed to reveal any causative organisms. After surgical drainage, culture of the joint fluid revealed the presence of C. tropicalis. Itraconazole treatment was started and after 3 months of therapy, the patient completely recovered full elbow function. PMID:22232632

Kim, Seung Youn; Lim, Jung Sub; Kim, Dong Hwan; Lee, Hyeon Jeong; Cho, Joong Bum; Lee, Jun Ah

2011-01-01

127

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

PubMed Central

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

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

2014-01-01

128

A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma.  

PubMed

Many sarcomas and leukemias carry nonrandom chromosomal translocations encoding tumor-specific mutant fusion transcription factors that are essential to their molecular pathogenesis. Ewing's sarcoma family tumors (ESFTs) contain a characteristic t(11;22) translocation leading to expression of the oncogenic fusion protein EWS-FLI1. EWS-FLI1 is a disordered protein that precludes standard structure-based small-molecule inhibitor design. EWS-FLI1 binding to RNA helicase A (RHA) is important for its oncogenic function. We therefore used surface plasmon resonance screening to identify compounds that bind EWS-FLI1 and might block its interaction with RHA. YK-4-279, a derivative of the lead compound from the screen, blocks RHA binding to EWS-FLI1, induces apoptosis in ESFT cells and reduces the growth of ESFT orthotopic xenografts. These findings provide proof of principle that inhibiting the interaction of mutant cancer-specific transcription factors with the normal cellular binding partners required for their oncogenic activity provides a promising strategy for the development of uniquely effective, tumor-specific anticancer agents. PMID:19584866

Erkizan, Hayriye V; Kong, Yali; Merchant, Melinda; Schlottmann, Silke; Barber-Rotenberg, Julie S; Yuan, Linshan; Abaan, Ogan D; Chou, Tsu-Hang; Dakshanamurthy, Sivanesan; Brown, Milton L; Uren, Aykut; Toretsky, Jeffrey A

2009-07-01

129

Small molecule selected to disrupt oncogenic protein EWS-FLI1 interaction with RNA Helicase A inhibits Ewing's Sarcoma  

PubMed Central

Many sarcomas and leukemias carry non-random chromosomal translocations encoding mutant fusion transcription factors that are essential to their molecular pathogenesis. These novel, tumor-specific proteins provides a unique opportunity for the development of highly selective anticancer drugs that has yet to be exploited. A particularly clear example is provided by Ewing's Sarcoma Family Tumors (ESFT) which contain a characteristic t(11;22) translocation leading to expression of the oncogenic fusion protein EWS-FLI1. EWS-FLI1 is a disordered protein that precluded standard structure-based small molecule inhibitor design. Using surface plasmon resonance screening, we discovered a lead compound, NSC635437. A derivative compound, YK-4-279, blocks RHA binding to EWS-FLI1, induces apoptosis in ESFT cells, and reduces the growth of ESFT orthotopic xenografts. These findings provide proof of principle that inhibiting the interaction of mutant cancer-specific transcription factors with the normal cellular binding partners required for their oncogenic activity provides a promising strategy for the development of uniquely effective, tumor-specific anticancer agents. PMID:19584866

Erkizan, Hayriye V.; Kong, Yali; Merchant, Melinda; Schlottmann, Silke; Barber-Rotenberg, Julie S.; Abaan, Ogan D.; Chou, Tsu-hang; Dakshanamurthy, Sivanesan; Brown, Milton L.; Üren, Aykut; Toretsky, Jeffrey A.

2009-01-01

130

A case with extraosseous Ewing's sarcoma: a late effect related to bone marrow transplantation for thalassemia or a component of a familial cancer syndrome?  

PubMed

Allogeneic bone marrow transplantation has proved to be a radical form of cure in patients with beta-thalassemia major who have a human leukocyte antigen identical donor. Although malignant neoplasms are serious late complications of bone marrow transplantation, very few reports describing the development of malignant tumors after allografting for thalassemia appeared in the literature. A case is presented here of extraosseous Ewing's sarcoma that developed 8 years after allogeneic bone marrow transplantation performed for beta-thalassemia major. The phenotypic features of the patient's family fulfill the criteria for Li-Fraumeni syndrome. The patient was treated with chemotherapy and radiotherapy and died with recurrent disease. To the authors' knowledge, this is the first case of extraosseous Ewing's sarcoma after bone marrow transplantation for thalassemia. The possible contribution of transplantation procedure and the genetic factors as well as the primary genetic hemoglobinopathy to the development of this malignant tumor are discussed. PMID:10914053

Mutafo?lu Uysal, K; Olgun, N; Sarialio?lu, F; Kargi, A; Cevik, N

2000-01-01

131

Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect tumour progression.  

PubMed

Ewing sarcoma is an aggressive round cell sarcoma with poor patient prognosis, particularly in cases of advanced-stage disease. Dynamic tumor-host immune interations within the tumor microenvironment may polarize in situ immune responses and shape tumor development and/or progression. To gain insight into the nature of tumour-host immune interactions within the Ewing sarcoma microenvironment, the presence and spatial distribution of infiltrating CD8(+) /CD4(+) T-lymphocytes were evaluated in therapy-naive Ewing sarcoma. Expression profiling of 40 different chemokines and several chemokine receptors was performed in therapy-naive tumours and cell lines by qPCR, immunohistochemistry, and flow cytometry. Considerable inter-tumour variation was observed regarding density, type, and distribution of infiltrating T-lymphocytes. Tumour-infiltrating T-cells contained significantly higher percentages of CD8(+) T-lymphocytes as compared to stroma-infiltrating cells, suggesting preferential migration of this T-cell type into tumour areas. Gene expression levels of several type 1-associated, pro-inflammatory chemokines (CXCR3- and CCR5-ligands CXCL9, CXCL10, and CCL5) correlated positively with infiltrating (CD8(+) ) T-lymphocyte numbers expressing corresponding chemokine receptors. Survival analyses demonstrated an impact of tumour-infiltrating, and not stroma-infiltrating, CD8(+) T-lymphocytes on tumour progression. At protein level, both tumour and stromal cells expressed the IFN?-inducible chemokines CXCL9 and CXCL10. CCR5-ligand CCL5 was exclusively expressed by non-tumoural stromal/infiltrating cells. Together, our results indicate that an inflammatory immune microenvironment with high expression of type 1-associated chemokines may be critical for the recruitment of (CD8(+) ) T-lymphocytes expressing corresponding chemokine receptors. The observed impact of tumour-infiltrating (CD8(+) ) T-lymphocytes is consistent with a role for adaptive anti-tumour immunity in the prevention of Ewing sarcoma progression. Recognition of the merits and exploitation/induction of an inflammatory microenvironment may improve the efficacy of natural immune responses against, and (adoptive) immunotherapeutic approaches for, Ewing sarcoma. PMID:21171080

Berghuis, Dagmar; Santos, Susy J; Baelde, Hans J; Taminiau, Antonie Hm; Egeler, R Maarten; Schilham, Marco W; Hogendoorn, Pancras Cw; Lankester, Arjan C

2011-02-01

132

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

PubMed Central

Background The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite. Objectives Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target) in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes. Results A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed across a wide range of GGAA motifs, with maximal expression observed in constructs containing 20–26 GGAA motifs. Relative to white European and African controls, the NR0B1 GGAA-microsatellite in tumor cells demonstrated a strong bias for haplotypes containing 21–25 GGAA motifs suggesting a relationship between microsatellite function and disease susceptibility. This selection bias was not a product of microsatellite instability in tumor samples, nor was there a correlation between NR0B1 GGAA-microsatellite polymorphisms and survival outcomes. Conclusions These data suggest that GGAA-microsatellite polymorphisms observed in human populations modulate EWS/FLI-mediated gene expression and may influence disease susceptibility in Ewing sarcoma. PMID:25093581

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

2014-01-01

133

Intra-patient dose escalation in Ewing’s sarcoma treated with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide: a retrospective review  

PubMed Central

Background Data suggests that males experience less toxicity and poorer survival than females treated for Ewing’s sarcoma. We instituted an intra-patient dose escalation (DE) policy with Vincristine/Doxorubicin/Cyclophosphamide (VDC) alternating with Ifosfamide/Etoposide (IE) based on hematological nadirs and report its feasibility and safety. Methods A retrospective review of adherence to DE guidelines and toxicities was conducted for patients who received DE with VDC/IE over 3 years at a single cancer center. Absolute neutrophil counts (ANC) was collected on days 8, 12 and 15 for cycles 1–6. DE of 10%/cycle was applied if ANC?>?1.5×109/L and platelet?>?100×109/L on all blood results. The primary endpoint was the proportion of patients who received appropriate DE. The secondary endpoint was to assess morbidity, changes in hematologic nadirs between gender and age and a comparison with a prior cohort of ESFT patients who did not receive DE. Gender comparisons were assessed via independent 2-sample t-tests assuming unequal variances. Within cycle changes in hematologic nadirs were assessed using repeated measures ANOVA. Relapse free survival and overall survival (OS) curves were estimated using the Kaplan-Meier method. Results 23 patients were identified (mean age: 27; range 17–54). 91 decisions for DE were made (1 decision excluded because of progressive disease) with 90% concordance with guidelines. No adverse outcomes occurred as a result of the inappropriate escalation. Grade 3/4 febrile neutropenia (FN) during VDC and IE was 26.1% (6/23 patients) and 17.4% respectively with no difference for those who were DE. Males were less neutropenic after C1 and C3 of VDC compared to females (P-value C1?=?0.003; C3?=?0.005). VDC was associated with greater neutropenia on day 8 whereas IE had greater neutropenia on day 12 (P-value <0.001). During VDC, a non statistical difference in neutropenia was seen for individuals aged 15–25 (n?=?13) compared with older individuals (P-value?=?0.09). OS comparison for those with localized disease with a prior cohort who were not DE showed similar outcomes (P-value?=?0.37). Conclusions DE is deliverable without increased adverse outcomes. Males have less myelosuppression during VDC, and should be especially considered for DE. PMID:24321600

2013-01-01

134

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

ClinicalTrials.gov

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

2014-04-01

135

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

PubMed Central

Background Insulin-like growth factor 1 receptor (IGF1R) targeted therapies have resulted in responses in a small number of patients with advanced metastatic Ewing's sarcoma. We performed morphoproteomic profiling to better understand response/resistance mechanisms of Ewing's sarcoma to IGF1R inhibitor-based therapy. Methodology/Principal Findings This pilot study assessed two patients with advanced Ewing's sarcoma treated with IGF1R antibody alone followed by combined IGF1R inhibitor plus mammalian target of rapamycin (mTOR) inhibitor treatment once resistance to single-agent IGF1R inhibitor developed. Immunohistochemical probes were applied to detect p-mTOR (Ser2448), p-Akt (Ser473), p-ERK1/2 (Thr202/Tyr204), nestin, and p-STAT3 (Tyr 705) in the original and recurrent tumor. The initial remarkable radiographic responses to IGF1R-antibody therapy was followed by resistance and then response to combined IGF1R plus mTOR inhibitor therapy in both patients, and then resistance to the combination regimen in one patient. In patient 1, upregulation of p-Akt and p-mTOR in the tumor that relapsed after initial response to IGF1R antibody might explain the resistance that developed, and the subsequent response to combined IGF1R plus mTOR inhibitor therapy. In patient 2, upregulation of mTOR was seen in the primary tumor, perhaps explaining the initial response to the IGF1R and mTOR inhibitor combination, while the resistant tumor that emerged showed activation of the ERK pathway as well. Conclusion/Significance Morphoproteomic analysis revealed that the mTOR pathway was activated in these two patients with advanced Ewing's sarcoma who showed response to combined IGF1R and mTOR inhibition, and the ERK pathway in the patient in whom resistance to this combination emerged. Our pilot results suggests that morphoproteomic assessment of signaling pathway activation in Ewing's sarcoma merits further investigation as a guide to understanding response and resistance signatures. PMID:21494688

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

2011-01-01

136

Superficial small round-cell tumors with special reference to the Ewing's sarcoma family of tumors and the spectrum of differential diagnosis.  

PubMed

Superficial/cutaneous small round-cell tumors comprise a heterogeneous group of neoplasms including sarcoma, carcinoma, melanoma, and lymphomas. Among superficial sarcomas, the Ewing's sarcoma family of tumors (ESFT) represents a poorly understood rare variant, having a behavioral difference characterized by a relative favorable prognosis. Several problems are still to be resolved in superficial ESFT, including the differential diagnosis between ESFT of bone (intraosseous or periosteal) with superficial infiltration and superficial ESFT with bone infiltration, especially in the fingers. Our aim is to review the most common types of small round-cell tumors included in the differential diagnosis of superficial ESFT, analyzing the histopathology, phenotype, and molecular alterations of each entity. PMID:23327732

Machado, Isidro; Traves, Victor; Cruz, Julia; Llombart, Beatriz; Navarro, Samuel; Llombart-Bosch, Antonio

2013-02-01

137

PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis.  

PubMed

Ewing's Sarcoma family tumors (ESFT) are characterized by a translocation t(11:22) forming an aberrant transcription factor EWS-FLI1. Protein tyrosine phosphatase L1 (PTPL1) was identified as a gene upregulated by EWS-FLI1 in transfected cells by microarray. Our results show that PTPL1 is a transcriptional target of EWS-FLI1 both by chromatin immunoprecipitation and promoter activation studies. We demonstrate that PTPL1 is highly expressed in ESFT cells and patient tumors compared with normal tissues, with a trend towards higher expression in metastatic versus primary tumors. Reduction of PTPL1 protein in ESFT cells correlated with a significant reduction in both monolayer and soft-agar cell growth. In addition, these PTPL1-reduced cells were more sensitive to etoposide-induced apoptosis than the controls. We therefore report a novel transcriptional activation of a phosphatase involved in the oncogenesis of ESFT. Increasing interest in specific phosphatase inhibitors would allow PTPL1 to be evaluated as a therapeutic target in ESFT. PMID:15782144

Abaan, Ogan D; Levenson, Amy; Khan, Osman; Furth, Priscilla A; Uren, Aykut; Toretsky, Jeffrey A

2005-04-14

138

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

PubMed Central

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

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

2013-01-01

139

miR-375 Mediated Acquired Chemo-Resistance in Cervical Cancer by Facilitating EMT  

PubMed Central

Acquired chemo-resistance is one of the key causal factors in cancer death. Emerging evidences suggest that miRNA and epithelial–mesenchymal transition play critical roles in the chemo-resistance in cancers. Here, we showed the association of paclitaxel-resistance with miR-375 over-expression and epithelial–mesenchymal transition inducement in cervical cancer. Using different cervical cancer cell models, we found that paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial–mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial–mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells. A reversion of miR-375 or Ecadherin expression may be a novel therapeutic approach for overcoming chemo-resistance in cervical cancer. PMID:25330011

Shen, Yuanming; Zhou, Jiansong; Li, Yang; Ye, Feng; Wan, Xiaoyun; Lu, Weiguo; Xie, Xing; Cheng, Xiaodong

2014-01-01

140

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

PubMed

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

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

2013-06-01

141

Potential of Herpesvirus Saimiri-Based Vectors To Reprogram a Somatic Ewing's Sarcoma Family Tumor Cell Line  

PubMed Central

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

Brown, Hannah F.; Unger, Christian

2013-01-01

142

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

PubMed

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

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

143

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

PubMed Central

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

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

144

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

PubMed

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

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

145

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

PubMed

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

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

2014-12-01

146

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

PubMed Central

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

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

2013-01-01

147

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

PubMed Central

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

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

2012-01-01

148

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

PubMed

The expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, particularly in urine, which is impossible for 35 nm particles. Here, we report that hydrogenated cationic nanodiamonds of primary size 7 nm (ND-H) have also a high affinity for siRNA and are capable of delivering them in cells. With siRNA/ND-H complexes, we measured a high inhibition efficacy of EWS/FLI-1 gene expression in Ewing sarcoma cell line. Electron microscopy investigations showed ND-H in endocytosis compartments, and especially in macropinosomes from which they can escape before siRNA degradation occurred. In addition, the association of EWS/FLI-1 silencing by the siRNA/ND-H complex with a vincristine treatment yielded a potentiation of the toxic effect of this chemotherapeutic drug. Therefore ND-H appears as a promising delivery agent in anti-tumoral gene therapy. PMID:25662499

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

2015-03-01

149

Combined use of expression and CGH arrays pinpoints novel candidate genes in Ewing sarcoma family of tumors  

PubMed Central

Background Ewing sarcoma family of tumors (ESFT), characterized by t(11;22)(q24;q12), is one of the most common tumors of bone in children and young adults. In addition to EWS/FLI1 gene fusion, copy number changes are known to be significant for the underlying neoplastic development of ESFT and for patient outcome. Our genome-wide high-resolution analysis aspired to pinpoint genomic regions of highest interest and possible target genes in these areas. Methods Array comparative genomic hybridization (CGH) and expression arrays were used to screen for copy number alterations and expression changes in ESFT patient samples. A total of 31 ESFT samples were analyzed by aCGH and in 16 patients DNA and RNA level data, created by expression arrays, was integrated. Time of the follow-up of these patients was 5–192 months. Clinical outcome was statistically evaluated by Kaplan-Meier/Logrank methods and RT-PCR was applied on 42 patient samples to study the gene of the highest interest. Results Copy number changes were detected in 87% of the cases. The most recurrent copy number changes were gains at 1q, 2, 8, and 12, and losses at 9p and 16q. Cumulative event free survival (ESFT) and overall survival (OS) were significantly better (P < 0.05) for primary tumors with three or less copy number changes than for tumors with higher number of copy number aberrations. In three samples copy number imbalances were detected in chromosomes 11 and 22 affecting the FLI1 and EWSR1 loci, suggesting that an unbalanced t(11;22) and subsequent duplication of the derivative chromosome harboring fusion gene is a common event in ESFT. Further, amplifications on chromosomes 20 and 22 seen in one patient sample suggest a novel translocation type between EWSR1 and an unidentified fusion partner at 20q. In total 20 novel ESFT associated putative oncogenes and tumor suppressor genes were found in the integration analysis of array CGH and expression data. Quantitative RT-PCR to study the expression levels of the most interesting gene, HDGF, confirmed that its expression was higher than in control samples. However, no association between HDGF expression and patient survival was observed. Conclusion We conclude that array CGH and integration analysis proved to be effective methods to identify chromosome regions and novel target genes involved in the tumorigenesis of ESFT. PMID:19144156

2009-01-01

150

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

PubMed Central

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

Brownhill, Samantha; Cohen, Dena; Burchill, Sue

2014-01-01

151

Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma.  

PubMed

Lysine-specific demethylase 1 (GeneID 23028), a flavin-dependent monoamine oxidoreductase and a histone demethylase, serves as an epigenetic coregulator of transcription. Lysine-specific demethylase 1 is up-regulated in neuroblastoma and in bladder, breast, colorectal, gastric, lung, and neuroendocrine cancers, and its overexpression drives the cell cycle of otherwise nontransformed human cells, suggesting oncogenic properties. Lysine-specific demethylase 1 was recently reported to be also overexpressed in several different mesenchymal tumors. We investigated lysine-specific demethylase 1 expression in over 500 sarcomas by gene expression profiling and tissue microarray-coupled immunohistochemical analyses and confirmed lysine-specific demethylase 1 overexpression in rhabdomyosarcoma and synovial sarcoma. We also show for the first time that lysine-specific demethylase 1 is also overexpressed in chondrosarcoma, Ewing's sarcoma, and osteosarcoma wherein it localizes in cell nuclei. We further show that a US Food and Drug Administration-approved drug that inhibits lysine-specific demethylase 1 also inhibits chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma cell growth in vitro. These data suggest that lysine-specific demethylase 1 plays a role in sarcoma pathology and that lysine-specific demethylase 1 inhibition strategies might represent a novel means to inhibiting growth of lysine-specific demethylase 1-overexpressing sarcomas. PMID:22245111

Bennani-Baiti, Idriss M; Machado, Isidro; Llombart-Bosch, Antonio; Kovar, Heinrich

2012-08-01

152

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

PubMed

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

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

2015-03-01

153

Ewings sarcoma as an etiology for persistent back pain in a 17-year-old girl after trauma to the back.  

PubMed

Back pain--a common complaint familiar to all physicians--can be either a manifestation of musculoskeletal dysfunction or a symptom of a more serious underlying disease. Unfortunately, the diagnosis can be difficult, and back pain that is not resolved by conservative treatment requires aggressive investigation. The author presents the case history of a 17-year-old patient whose back pain had been extensively evaluated by a series of specialists to no avail until further workup revealed the problem to be Ewing's sarcoma. The steps required to diagnose elusive back pain are presented, together with a brief discussion of cauda equina syndrome and conus medullaris syndrome, components of both of which were found in this patient. PMID:7860370

Paul, F A

1995-01-01

154

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

PubMed

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

García Giménez, Dolores; García Prado, Elena; Sáenz Rodríguez, Teresa; Fernández Arche, Angeles; De la Puerta, Rocío

2010-02-01

155

Is fluoride a risk factor for bone cancer? Small area analysis of osteosarcoma and Ewing sarcoma diagnosed among 0–49-year-olds in Great Britain, 1980–2005  

PubMed Central

Background: Artificial fluoridation of drinking water to improve dental health has long been a topic of controversy. Opponents of this public health measure have cited the possibility of bone cancer induction. The study objective was to examine whether increased risk of primary bone cancer was associated with living in areas with higher concentrations of fluoride in drinking water. Methods: Case data on osteosarcoma and Ewing sarcoma, diagnosed at ages 0–49 years in Great Britain (GB) (defined here as England, Scotland and Wales) during the period 1980–2005, were obtained from population-based cancer registries. Data on fluoride levels in drinking water in England and Wales were accessed through regional water companies and the Drinking Water Inspectorate. Scottish Water provided data for Scotland. Negative binomial regression was used to examine the relationship between incidence rates and level of fluoride in drinking water at small area level. Results: The study analysed 2566 osteosarcoma and 1650 Ewing sarcoma cases. There was no evidence of an association between osteosarcoma risk and fluoride in drinking water [relative risk (RR) per one part per million increase in the level of fluoride = 1·001; 90% confidence interval (CI) 0·871, 1·151] and similarly there was no association for Ewing sarcoma (RR = 0·929; 90% CI 0·773, 1·115). Conclusions: The findings from this study provide no evidence that higher levels of fluoride (whether natural or artificial) in drinking water in GB lead to greater risk of either osteosarcoma or Ewing sarcoma. PMID:24425828

Blakey, Karen; Feltbower, Richard G; Parslow, Roger C; James, Peter W; Gómez Pozo, Basilio; Stiller, Charles; Vincent, Tim J; Norman, Paul; McKinney, Patricia A; Murphy, Michael F; Craft, Alan W; McNally, Richard JQ

2014-01-01

156

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

ClinicalTrials.gov

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

2014-08-26

157

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

PubMed

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

Huang, Helen J; Angelo, Laura S; Rodon, Jordi; Sun, Michael; Kuenkele, Klaus-Peter; Parsons, Henrique A; Trent, Jonathan C; Kurzrock, Razelle

2011-01-01

158

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

PubMed

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

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

159

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

PubMed Central

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

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

2014-01-01

160

[ES-IPO-97 treatment protocol for prognostically poor Ewing's sarcoma forms in children: results of implementation].  

PubMed

The paper shows the high efficiency and moderate toxicity of inductive treatment in children with Young sarcoma and primitive neuroectodermal tumors by ES-Ipo-97 protocol that includes alternate chemotherapy by the scheme: vincristine, 1.5 mg/m2/day, on days 1, 8, 15; adriamycin, 37.5 mg/m2/day, on days 1 and 2 as 24-hour infusion; cyclophosphanum, 2.1 g/m2/day, on days 1 and 2 (Block A); iphosphamide, 2.4 g/m2/day on days 1 to 5, etoposide, 100 mg/m2/day, on days 1-5 (Block B). It provides evidence for that this therapy is promising and awaits further developments. PMID:10961143

Ptushkina, E A; Ivanova, N M; Dolgopolov, I S; Izhogin, D G; Petrosian, A S; Glekov, I V; Durnov, L A; Mentkevich, G L

2000-01-01

161

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

PubMed

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

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

2014-07-01

162

Prognostic factors and clinical outcome of patients with Ewing's sarcoma family of tumors in adults: multicentric study of the Anatolian Society of Medical Oncology.  

PubMed

The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with Ewing sarcoma family of tumors (ESFT). Data of patients with ESFTs followed up at different cancer centers in Turkey between 2001 and 2010 were retrospectively analyzed. The median age of 114 patients was 26 years (range 14-66). The median follow-up was 20 months (range 1-118 months). Tumor size was between 1.5 and 14 cm (median 8 cm). Eighty-six percent of patients had localized disease at presentation, and 14 % had metastatic disease. Local therapy was surgery alone in 31 % of patients, surgery combined with radiotherapy in 41 % and radiotherapy alone in 18 %. Approximately 70 % of patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year disease-free survival and overall survival were 60 and 65 %, respectively. At univariate analysis, patients with tumor size ? 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size ? 8 cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. ESFTs are aggressive tumors with a high incidence of local recurrence and distant metastasis. Multimodality treatment consisting of adequate surgical resection, aggressive chemotherapy (VAC alternating with IE) and radiotherapy is recommended for patients with ESFTs. PMID:23345116

Arpaci, Erkan; Yetisyigit, Tarkan; Seker, Metin; Uncu, Dogan; Uyeturk, Ummugul; Oksuzoglu, Berna; Demirci, Umut; Coskun, Ugur; Kucukoner, Mehmet; Is?kdogan, Abdurrahman; Inanc, Mevlude; Alkis, Necati; Ozkan, Metin

2013-03-01

163

DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.  

PubMed Central

The 5' half of the EWS gene has recently been described to be fused to the 3' regions of genes encoding the DNA-binding domain of several transcriptional regulators, including ATF1, FLI-1, and ERG, in several human tumors. The most frequent occurrence of this situation results from the t(11;22)(q24;q12) chromosome translocation specific for Ewing sarcoma (ES) and related tumors which joins EWS sequences to the 3' half of FLI-1, which encodes a member of the Ets family of transcriptional regulators. We show here that this chimeric gene encodes an EWS-FLI-1 nuclear protein which binds DNA with the same sequence specificity as the wild-type parental FLI-1 protein. We further show that EWS-FLI-1 is an efficient sequence-specific transcriptional activator of model promoters containing FLI-1 (Ets)-binding sites, a property which is strictly dependent on the presence of its EWS domain. Comparison of the properties of the N-terminal activation domain of FLI-1 to those of the EWS domain of the fusion protein indicates that EWS-FLI-1 has altered transcriptional activation properties compared with FLI-1. These results suggest that EWS-FLI-1 contributes to the transformed phenotype of ES tumor cells by inducing the deregulated and/or unscheduled activation of genes normally responsive to FLI-1 or to other close members of the Ets family. ES and related tumors are characterized by an elevated level of c-myc expression. We show that EWS-FLI-1 is a transactivator of the c-myc promoter, suggesting that upregulation of c-myc expression is under control of EWS-FLI-1. Images PMID:8164678

Bailly, R A; Bosselut, R; Zucman, J; Cormier, F; Delattre, O; Roussel, M; Thomas, G; Ghysdael, J

1994-01-01

164

Childhood Soft Tissue Sarcoma: Treatment Information  

MedlinePLUS

... Tumors Ewing Sarcoma Eye Cancer Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft ... Leukemia Brain Tumors Ewing Sarcoma Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Lymphoma (non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma ...

165

The combination of CD99 and NKX2.2, a transcriptional target of EWSR1-FLI1, is highly specific for the diagnosis of Ewing sarcoma.  

PubMed

Ewing sarcoma (ES) is a high-grade malignant neoplasm primarily affecting children and young adults. The diagnosis of ES is often difficult because of its broad differential diagnosis comprising a diverse group of small round cell tumors (SRCTs). Although the identification of tumor type-specific fusion genes by molecular testing is the gold standard for the diagnosis of ES, such approaches are not always available in a routine pathology practice. Thus, a reliable immunohistochemical marker is required. A recent study using a limited number of tumor samples has shown that NKX2.2, a putative transcriptional target of EWSR1-FLI1, is a useful marker for the diagnosis of ES. In the present study, the immunohistochemical expression of NKX2.2 was evaluated on 46 genetically confirmed ES and 85 non-ES SRCTs, together with comparative assessment of CD99 and other molecular targets of EWSR1-FLI1, including NR0B1, E2F3, and EZH2. NKX2.2 was expressed in 37 (80 %) of the ES samples with a mostly diffuse and strong staining pattern, and 14 (16 %) of the non-ES SRCTs, including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma, also expressed this marker. The sensitivity and specificity of the NKX2.2 expression in this cohort were 80 and 84 %, respectively. The specificity when combined with CD99 was 98 %, with exceptional expression of both markers in only two non-ES SRCTs, including one case each of mesenchymal chondrosarcoma and small cell carcinoma. NR0B1, E2F3, and EZH2 were less sensitive for specific markers for ES when applied singly or in any combination. In conclusion, the study reinforces that NKX2.2 is a useful immunohistochemical marker for ES, and that the combination of CD99 and NKX2.2 is a powerful diagnostic tool that can differentiate ES from other SRCTs. PMID:25031013

Shibuya, Ryo; Matsuyama, Atsuji; Nakamoto, Mitsuhiro; Shiba, Eisuke; Kasai, Takahiko; Hisaoka, Masanori

2014-11-01

166

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

ClinicalTrials.gov

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

2015-01-30

167

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

ClinicalTrials.gov

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

2014-06-16

168

Genetics Home Reference: Ewing sarcoma  

MedlinePLUS

... of the FLI1 gene, creating the EWSR1/FLI1 fusion gene. This mutation is acquired during a person's ... inherited. The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the ...

169

General Information about Ewing Sarcoma  

MedlinePLUS

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

170

The Epidemiology of Sarcoma  

PubMed Central

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

2012-01-01

171

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

PubMed Central

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

2009-01-01

172

Epstein–Barr virus latent membrane protein 1 increases chemo-resistance of cancer cells via cytoplasmic sequestration of Pim1  

Microsoft Academic Search

Improved treatment of EBV positive lymphoma depends on the identification of molecular mechanism underlying chemo-resistance. LMP1 is an essential transmembrane protein for EBV-induced immortalization of hematopoietic cells. Herein, we show that an oncogenic Pim-1 is translocated to the cytoplasm by LMP1. Three lines of evidence indicate that cytoplasmic sequestration of Pim-1 may be required for LMP1-induced cancer cell survival. First,

Joo Hyun Kim; Won Seog Kim; Yungdae Yun

2010-01-01

173

Combination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX2 signaling pathways  

Microsoft Academic Search

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

Jin-Taek Hwang; Joohun Ha; Ock Jin. Park

2005-01-01

174

The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer.  

PubMed

Docetaxel-based therapy is one of the first-line options for castration-resistant prostate cancer (CRPC). However, a large proportion of CRPC patients show different extents of docetaxel resistance. The current study aims to investigate the role of testicular nuclear receptor 4 (TR4) in docetaxel resistance in CRPC. TR4 expression level in prostate biopsy samples from CRPC patients treated with docetaxel was measured by immunohistochemistry (IHC). Alternation of TR4 expression in prostate cancer (PCa) cell line PC3 was applied to find out the influence of TR4 on half-maximal inhibitory concentration (IC50), cell viability and cell apoptosis. Patients who failed to achieve prostate-specific antigen (PSA) response (<50% PSA reduction from baseline) after docetaxel-based chemotherapy had a comparatively higher TR4 expression than those who achieved PSA response (?50% PSA reduction from baseline). Knocking down TR4 in PC3 cells led to a lower IC50 dose, poorer cell viability and more cell apoptosis when treated with docetaxel, whereas overexpression of TR4 in PC3 led to a higher IC50 dose, better cell viability and less cell apoptosis. TR4 enhances the chemo-resistance of docetaxel in CRPC. It may serve as a biomarker to determine the prognosis of docetaxel-based therapy and as a potential therapy target to combine with docetaxel to better suppress CRPC. PMID:25104727

Chen, B; Yu, S; Ding, X; Jing, C; Xia, L; Wang, M; Matro, E; Rehman, F; Niu, Y; Li, G; Chang, C

2014-10-01

175

A new nanostructured carrier design including oil to enhance the pharmaceutical properties of retinoid therapy and its therapeutic effects on chemo-resistant ovarian cancer.  

PubMed

All-trans retinoic acid (ATRA) is an appealing alternative drug for the cancers that have failed the conventional chemotherapy and become chemo-resistant and more tumorigenic. In this study, we specifically addressed two issues commonly associated with ATRA nanotherapeutics: (1) insufficient, unstable entrapment and uncontrolled release of the highly lipophilic ATRA and (2) lack of studies in therapeutically relevant chemo-resistant cancer cell models. A polymer-oil nanostructured carrier (PONC) composed of oil and PLGA was designed and studied in an ovarian cancer cell subline SKOV-3PR that could withstand up to 300 nM paclitaxel and expressed high levels of multidrug resistance transporter ABCB1 and tumorigenic marker CD133. Differential scanning calorimetry of PONC revealed superior polymer amorphosity and dispersion of the entrapped ATRA in a manner comparable to nanostructured lipid carriers. With this design, the ATRA encapsulation efficiency was increased up to 8.5-fold and a 5-day controlled release profile was obtained. ATRA-PONC was able to induce extensive apoptotic cell death and exert substantially higher long-term anti-tumorigenic effects (IC?? of ATRA-PONC: 2 ?g/ml versus free ATRA: 17.5 ?g/ml; p<0.05) in SKOV-3PR cells. Mechanistic studies indicated that these enhanced anticancer effects were likely attributable to higher cell permeation by the well-dispersed drug/oil steadily released from PONC. To conclude, a nanostructured, oil-in-polymer hybrid carrier design has been developed for efficient ATRA delivery and treatment of the chemo-exposed, chemo-resistant sub-population of ovarian cancer, exemplifying a convenient strategy to vastly improve the pharmaceutical and therapeutic properties of tough-to-deliver lipophilic, poorly water-soluble anticancer compounds. PMID:24816129

Narvekar, Mayuri; Xue, Hui Yi; Tran, Ngoc T; Mikhael, Mariam; Wong, Ho Lun

2014-09-01

176

Rare Cause of Stricture Esophagus-Sarcoma: A Case Report and Review of the literature.  

PubMed

Adenocarcinoma and squamous cell carcinoma account for the vast majority of oesophageal malignancies. Other malignancies known to occur in the oesophagus include melanoma, sarcoma, and lymphoma. Among the sarcomas, carcinosarcoma is the commonest with both carcinomatous and sarcomatous elements followed by leiomyosarcoma of mesenchymal origin. Other sarcomas reported in the literature are liposarcoma, synovial sarcoma, myxofibrosarcoma, Ewing's sarcoma, granulocytic sarcoma, histiocytic sarcoma, schwannoma rhabdomyosarcoma, and epithelioid sarcoma. We report a case of malignant spindle cell tumour of oesophagus. Sarcomas of esophagus present as a polypoid exophytic soft tissue mass. Our patient presented with a stricture which is a rare presentation. Locally aggressive treatment with surgery is beneficial, and local palliative treatment including radiotherapy is worthwhile. PMID:22606414

Patricia, S; Saikat, Das; Rajesh, B; Rajesh, I; Selvamani, B; Subhashini, John

2011-01-01

177

Bone Sarcomas: From Biology to Targeted Therapies  

PubMed Central

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

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

178

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

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

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

2013-01-01

179

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

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.

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

180

ERG EXPRESSION IN EPITHELIOID SARCOMA – A DIAGNOSTIC PITFALL  

PubMed Central

ERG transcription factor is constitutively expressed in endothelial cells. Because benign and malignant vascular endothelia retain the ERG-expression, ERG is considered a useful marker for angiosarcomas and related tumors. ERG is also expressed in a subset of prostate carcinomas and Ewing sarcomas due to ERG-involving translocations, so that this marker is also of high interest for the study of these malignancies. In this study, we evaluated 109 epithelioid sarcomas for ERG expression, based on an initial observation of an ERG-positive case. We also studied expression of other endothelial antigens in epithelioid sarcoma. ERG was expressed in 38% of epithelioid sarcomas (41/109), usually with a uniform nuclear staining, similar to that seen in angiosarcomas. However, all epithelioid sarcomas were negative for ERG gene rearrangement indicating that that ERG expression is not likely related to ERG involving translocations in epithelioid sarcoma. Other endothelial markers, CD31, claudin 5, and Prox1 were absent in epithelioid sarcomas. The only exception was a pulmonary metastasis of epithelioid sarcoma showing focal CD31 expression, which was probably resulting from antigen adsorption onto tumor cell surfaces. However, podoplanin was commonly (7/9) expressed in epithelioid sarcoma, so that this marker is not useful in the distinction of epithelioid sarcoma and angiosarcoma. INI1/SMARCB1 gene product was absent in all epithelioid sarcomas (considered here a definitional feature) but was absent from only one epithelioid angiosarcoma, indicating its relative specificity for epithelioid sarcoma in this differential diagnostic setting. ERG expression is fairly common in epithelioid sarcoma, and should be recognized as a diagnostic pitfall in the differential diagnosis of epithelioid sarcoma and epithelioid angiosarcoma. General lack of endothelial cell specific markers in epithelioid sarcoma helps in this distinction. PMID:23774169

Miettinen, Markku; Wang, Zengfeng; Sarlomo-Rikala, Maarit; Abdullaev, Ziedulla; Pack, Svetlana D.; Fetsch, John F.

2013-01-01

181

Chest wall sarcoma of childhood with a good prognosis.  

PubMed Central

Four cases of a locally invasive sarcoma of the chest wall are described in children aged between 8 and 14 years. Although its morphology resembles a Ewing's sarcoma of bone there are light and electron microscopical features that are distinctive. The sarcoma is thought to represent an entity which has not previously been defined. Its clinical importance lies in the fact that the prognosis with appropriate treatment appears to be good. One child died after 2 1/2 years, but the others are alive 6, 8, and 16 years after presentation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:727812

Barson, A J; Ahmed, A; Gibson, A A; MacDonald, A M

1978-01-01

182

Round cell sarcomas - biologically important refinements in subclassification.  

PubMed

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

Mariño-Enríquez, Adrián; Fletcher, Christopher D M

2014-08-01

183

Chemotherapy for Soft Tissue Sarcomas  

MedlinePLUS

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

184

State-of-the-art approach for bone sarcomas.  

PubMed

Bone sarcomas are a variety of non-epithelial, malignant neoplasms of bone. The most common bone sarcomas are osteosarcoma, Ewing's sarcoma, and chondrosarcoma. The approach to a patient with a suspected bone sarcoma from initial examination to the histological diagnosis and classification is staging. Staging is of critical importance, in order to classify different treatment options and point out which combination of them is more suitable depending on the severity of the tumor in every individual patient. Staging should include medical history, physical and imaging examination, and biopsy. This article presents the current approach for staging, principles of biopsy, tumor classification, treatment, and follow-up of patients with bone sarcomas. PMID:24791747

Mavrogenis, Andreas F; Angelini, Andrea; Vottis, Christos; Palmerini, Emanuela; Rimondi, Eugenio; Rossi, Giuseppe; Papagelopoulos, Panayiotis J; Ruggieri, Pietro

2015-01-01

185

Whole-lung irradiation in the treatment of metastatic synovial sarcoma.  

PubMed

Whole-lung irradiation (WLI) is standard of care in the treatment of patients with rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor and pulmonary metastases. However, it is not routinely utilized in the treatment of pulmonary metastases arising from other soft tissue sarcoma histologies. A patient presented with synovial sarcoma of his groin and punctate pulmonary metastases. After completion of multimodality treatment to his primary lesion, he received WLI. The patient is without evidence of disease at 3.8 years. This case demonstrates the need for further study of WLI in synovial sarcoma as it may improve outcomes in patients with this disease. PMID:24939451

Gerber, Naamit K; Meyers, Paul A; LaQuaglia, Michael P; Wolden, Suzanne L

2014-11-01

186

Epithelioid Sarcoma  

PubMed Central

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

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

2009-01-01

187

Mesenchymal Stromal Cell Dependent Regression of Pulmonary Metastasis from Ewing’s  

PubMed Central

Introduction: Ewing’s sarcoma (ES) is the second most common bone tumor in children. Survival has not improved over the last decade and once pulmonary metastatic disease is present, survival is dismal. Mesenchymal stromal cell (MSC) therapy has shown potential benefit for Kaposi’s sarcoma; however, the role of progenitor cell therapies for cancer remains controversial. MSC treatment of ES or pulmonary metastatic disease has not been demonstrated. We have developed an orthotopic xenograft model of ES in which animals develop spontaneous pulmonary metastases. Within this model, we demonstrate the use of MSCs to target ES lung metastasis. Materials and Methods: Human ES cells were transfected with luciferase and injected into the rib of nude mice. Development of pulmonary metastases was confirmed by imaging. After flow cytometry based characterization, MSCs were injected into the tail vein of nude mice with established local ES tumor or pulmonary metastasis. Mice were treated with intravenous MSCs weekly followed by bioluminescent imaging. Results: The intravenous injection of MSCs in an ES model decreases the volume of pulmonary metastatic lesions; however, no effect on primary chest wall tumor size is observed. Thus verifying the MSC preferential homing to the lung. MSCs are found to “home to” the pulmonary parenchyma and remain engrafted up to 5?days after delivery. Discussion: MSC treatment of ES slows growth of pulmonary metastasis. MSCs have more affinity for pulmonary metastasis and can effect a greater decrease in tumor growth in the lungs compared to the primary tumor site. PMID:24910847

Hayes-Jordan, Andrea; Wang, Yong Xin; Walker, Peter; Cox, Charles S.

2014-01-01

188

Kaposi's sarcoma  

Microsoft Academic Search

Review of histopathological material in nine autopsies and 35 skin biopsy specimens of Kaposi's sarcoma in male homosexuals suggested that aberrant lymphaticovenous connections occur in the earliest stage of the Kaposi lesion. Venular glomeruloid structures in the dermis and their analogous radial venolymphatic channels in medium-sized and larger veins signified coupling of the lymphatic and venous systems, a characteristic previously

Michael Dictor

1986-01-01

189

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.

190

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

PubMed Central

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

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

2011-01-01

191

Mesenchymal Progenitors Expressing TRAIL Induce Apoptosis in Sarcomas.  

PubMed

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 co-cultured 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 co-culture 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 anti-angiogenic functions. Our results suggest that MSC as TRAIL vehicles could open novel therapeutic opportunities for sarcoma by multiple mechanisms. This article is protected by copyright. All rights reserved. PMID:25420617

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

2014-11-25

192

[Prognostic factors of bone and soft tissue sarcoma].  

PubMed

The prognosis of bone and soft tissue sarcoma is influenced by factors such as pulmonary metastasis, local curability and sensitivity to chemotherapy. In cases with pulmonary lesion, the prognosis has not been favorable, but recently long-term survivors are increasing in number by effective chemotherapy, and the removal of primary and metastatic lesions. As in cases without metastatic lesions, the prognosis of high-grade sarcoma were influenced by local curability and sensitivity to chemotherapy. On the other hand, the prognosis in low grade sarcoma is mainly decided by local curability. To assure local curability the following should be considered. 1) safety surgical margin, 2) preoperative radiation therapy if the safety margin is not predicted, and 3) risk factors in local curability, which are lymph node metastasis, skip metastasis and tumor thrombus. If these risk factors are detected before operation, a more radical procedure should be planned. Moreover, cutaneous angiosarcoma and epithelioid sarcoma, which are occasionally associated with these risk factors, should be operated by ablative procedure even if the risk factors are not detected. 4) In cases with pathological fracture or inadequately operated, surgical intervention to prevent transplantation should be undertaken as soon as possible. Effective chemotherapy could improve the prognosis of high grade sarcoma. Thus, chemotherapy should be used for osteosarcoma, Ewings sarcoma, round cell sarcoma etc. However, non-effective chemotherapy might make the prognosis worse. Therefore, alternative administration of effective chemotherapeutic agents proved by clinical evaluation would be more reasonable than remaining with a certain protocol. PMID:8687230

Kawaguchi, N; Matsumoto, S

1996-07-01

193

Histologic Variability and Diverse Oncologic Outcomes of Prostate Sarcomas  

PubMed Central

Purpose Primary prostate sarcomas are a rare type of prostate cancer that account for less than 0.1% of primary prostate malignancies. We analyzed the experience of a single institution with prostate sarcoma over 20 years. Materials and Methods In this case series, the medical records of 20 patients with prostate sarcoma were reviewed from June 1990 to December 2013 to identify symptoms at presentation, diagnostic procedures, metastasis presence and development, histologic subtype, French Fédération Nationale des Centres de Lutte Contre le Cancer grade, primary tumor grade and size, and treatment sequence, including surgery and preoperative and postoperative therapies. The average follow-up period was 23.6 months (range, 1.4-83.3 months). Results The average patient age was 46.3±16.7 years. Most patients presented with lower urinary tract symptoms (55%). The histologic subtype was spindle cell sarcoma in five patients (25%), rhabdomyosarcoma in three patients (15%), synovial sarcoma in three patients (15%), liposarcoma in three patients (15%), stromal sarcoma in three patients (15%), and Ewing sarcoma, nerve sheath tumor, and adenocarcinoma with sarcomatoid component (5% each). For liposarcoma, two patients were alive after complete surgical resection and had a good prognosis. At last follow-up, 15 patients had died of sarcoma. The 2- and 5-year actuarial survival rates for all 20 patients were 53% and 12%, respectively (medial survival, 20 months). Conclusions The disease-specific survival rate of prostate sarcoma is poor. However, sarcoma that is detected early shows a better result with proper management including surgical intervention with radio-chemotherapy than with no treatment. Early diagnosis and complete surgical resection offer patients the best curative chance. PMID:25512813

Sohn, Mooyoung; Kwon, Taekmin; Jeong, In Gab; Hong, Sungwoo; You, Dalsan; Hong, Jun Hyuk; Ahn, Hanjong

2014-01-01

194

Expression of MDR1/P glycoprotein in human sarcomas.  

PubMed

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

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

1993-12-01

195

Kaposi’s sarcoma  

MedlinePLUS

Kaposi's sarcoma is a cancerous tumor of the connective tissue, and is often associated with AIDS . ... Before the AIDS epidemic, Kaposi's sarcoma was seen mainly in ... elderly women. Among this group, the tumors developed slowly. ...

196

Retraction: Primary extraosseous Ewing sarcoma of the lung in children  

PubMed Central

ecancer 7 312 (2013) The report in this article of the treatment the patient received is incorrect. Three of the authors (Jean Luc Michel, Clara Fernandez and Audrey Derouet) were unaware that their names had been added to the author list. The three remaining authors (Nidal Alsit, Linda Sakhri and Augustin Pirvu) were not involved with the treatment of the patient. PMID:23858324

Alsit, Nidal; Fernandez, Clara; Michel, Jean Luc; Sakhri, Linda; Derouet, Audrey; Pirvu, Augustin

2013-01-01

197

Intracranial ewings sarcoma/peripheral primitive neuroectodermal tumor.  

PubMed

Central nervous system primitive neuroectodermal tumours (CNS PNET) are aggressive embryonal tumours composed of undifferentiated or poorly differentiated neuroepithelial cells seen in the pediatric age group. This is rare and only a handful of cases of ES/pPNET in CNS are reported. We report such a case in a 3 year old child. Reporting of more such cases is needed to better define these rare tumours of the dura. PMID:25237951

Amita, R; Sandhyamani, S; Nair, Suresh; Kapilamoorthy, T R

2014-01-01

198

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.

199

Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas  

SciTech Connect

Purpose: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. Methods and Materials: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologic grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm{sup 3} and 1,194 cm{sup 3} (median 525 cm{sup 3}). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. Results: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. Conclusions: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.

Serizawa, Itsuko, E-mail: s_itsuko@nirs.go.j [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Kagei, Kenji; Kamada, Tadashi; Imai, Reiko; Sugahara, Shinji; Okada, Tohru; Tsuji, Hiroshi [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Ito, Hisao [Department of Radiology, Chiba University, Chiba (Japan); Tsujii, Hirohiko [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

2009-11-15

200

ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone.  

PubMed

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

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

2014-03-31

201

ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone  

PubMed Central

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

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

2014-01-01

202

The soft tissue sarcomas  

SciTech Connect

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

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

1987-01-01

203

Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases.  

PubMed

More than 85% of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), or "Ewing family of tumors" (EFTs), have the translocation, t (11;22) (q24;q12), with others having variant translocations. Identification of these by cytogenetic and/or molecular genetic techniques is specific for EFT and is increasingly recognized as the "gold standard" for diagnosis. However, these techniques are not universally available. We therefore studied a large group of genetically confirmed EFTs to more completely understand the morphologic and immunophenotypic spectrum of this rare sarcoma. Sixty-six cytogenetically, FISH or RT-PCR proven-EFTs were retrieved. In 56 cases, immunohistochemistry (IHC) was performed for pan-cytokeratins (PanCK), high molecular weight cytokeratins (HMWCK), desmin (DES), CD99, CD117, and FLI1 protein using heat-induced epitope retrieval and the Dako Envision system. The cases arose chiefly in children and young adults (median 18 years; range, 3-65 years) of both sexes (male, 32; female, 31; unknown, 3) in a variety of bone (N = 39) and soft tissue (N = 27) sites. Histologically, 46 cases (73%) showed only typical features of ES, 9 cases (16%) showed features of PNET, 3 cases (5%) showed "adamantinoma-like" features, 3 cases (5%) corresponded to "atypical Ewing sarcoma," 3 cases (5%) showed principally intersecting fascicles of spindled cells, and 2 cases had abundant hyalinized matrix. IHC results were as follows: PanCK (18 of 56, 32%), HMWCK (3 of 55, 5%), DES (1 of 56, 2%), CD99 (52 of 52, 100%), CD117 (13 of 54, 24%), and FLI1 (44 of 47, 94%). HMWCK was expressed only in "adamantinoma-like" EFTs, none of which expressed DES. In conclusion, most, but not all, EFTs can be accurately diagnosed using time-honored morphologic criteria and ancillary immunohistochemistry. However, genetic confirmation remains essential for the diagnosis of unusual morphologic variants of EFT, including "adamantinoma-like," spindled, sclerosing, and clear cell/anaplastic variants. Therefore, to exclude or confirm the diagnosis of Ewing's sarcoma in round cell sarcomas having a variety of patterns but not specifically conforming to a tumor of known lineage (eg, rhabdomyosarcoma), cytogenetics, and/or molecular analysis is required. PMID:16006796

Folpe, Andrew L; Goldblum, John R; Rubin, Brian P; Shehata, Bahig M; Liu, Wendy; Dei Tos, Angelo P; Weiss, Sharon W

2005-08-01

204

[Primary pulmonary sarcomas].  

PubMed

Primary pulmonary sarcomas are rare diseases unlike lung carcinomas. The occurence of these sarcomas is between 0.013-0.40% of all malignant lung tumours. There are malignant mesenchymal tumours. They are flowing from the soft tissue of lung. The pulmonary sarcomas are heterogenic group with various biological behaviour. Their morfologic structure does not digger from the sarcomas of soft tissue. The primary pulmonary sarcomas occur more often in childhood and in young people unlike lung carcinomas. Radiation and some toxic substances are noted risk factors. Some gene mutations, infectious pathoghens and contraception have a possible impact on the origin of some types of the sarcomas. The current hypothesis is, that most of the sarcomas, if not all sarcomas, stem from primitive multipotent mesenchymal cell by malignant transformation in one or more lines. The diagnostic standard is biopsy from tumour with histologic and immunohistochemistry examination of a sample. The basic diagnostic problem is exclusion of a secondary origin of sarcomatic cells in the lung, because pulmonary metastasis of extrapulmonary sarcomas are more often than the primary pulmonary involvement.The optimal treatment is a resection of the tumour.The other therapeutic modalities are radiotherapy and chemotherapy, but results of these modalities are unsatisfactory. There are various chemotherapeutic regimes, monotherapy or combination regimes. The basic cytostatics are doxorubicine, iphosphamide, dacarbazine. Problems of the chemotherapy are high toxicity and relatively low curative effect about 20%.The first studies with biological treatment of the sarcomas of soft tissue have been published recently.This types of drugs could be a part of the complex management of these primary pulmonary tumours in the future. The primary pulmonary sarcomas have mostly aggresive course and often recur. Their prognosis is usually not very good. The survival median is 48 months and 5-years survival ranges between 38 and 48%. Prognostic factors are the size of tumour, histological type, grading, clinical stage and measure of a surgery major. PMID:19731876

Jakubcová, T; Jakubec, P

2009-01-01

205

Pediatric Bone Sarcoma: Diagnostic Performance of (18)F-FDG PET/CT Versus Conventional Imaging for Initial Staging and Follow-Up.  

PubMed

OBJECTIVE. The purpose of this study was to compare the diagnostic performance of (18)F-FDG PET/CT and conventional imaging for staging and follow-up of pediatric osteosarcoma and skeletal Ewing sarcoma. MATERIALS AND METHODS. We calculated sensitivity, specificity, and accuracy of PET/CT and conventional imaging (CT, MRI, bone scanning) for sites of disease and number of lesions. Diagnostic benefit, defined as better characterization of lesions, was evaluated on a per-scan basis, comparing PET/CT and conventional imaging. RESULTS. A total of 412 lesions were characterized by imaging in 64 patients (20, osteosarcoma; 44, Ewing sarcoma). For osteosarcoma patients PET/CT was available only at follow-up, where it proved more accurate than conventional imaging for the detection of bone lesions (accuracy, 95% vs 67% for CT and 86% for MRI) and complementary to CT in evaluating lung nodules (sensitivity, 84% vs 94%; specificity, 79% vs 71%) with diagnostic benefit in 18% of examinations. In patients with Ewing sarcoma, PET/CT tended to perform better during follow-up than at initial staging (accuracy, 85% vs 69%). For lung findings, PET/CT was more specific than CT but was less sensitive. The diagnostic benefit of PET/CT was greater at staging (28%) than during followup (9%). On a per-patient basis, PET/CT provided diagnostic benefit in 21 of 44 patients with Ewing sarcoma and nine of 20 patients with osteosarcoma at least once during clinical management. CONCLUSION. FDG PET/CT provides diagnostic benefit in Ewing sarcoma and osteosarcoma, with the exception of small lung nodules. Prospective studies are needed to define the best imaging algorithm and combination of tests in the staging and follow-up of patients with pediatric bone sarcoma. PMID:25539251

Quartuccio, Natale; Fox, Josef; Kuk, Deborah; Wexler, Leonard H; Baldari, Sergio; Cistaro, Angelina; Schöder, Heiko

2015-01-01

206

[Soft tissue sarcoma].  

PubMed

Soft tissue sarcomas are rare tumours of the connective tissue. The knowledge of this rare entity is necessary for an accurate diagnosis. The incidence in Europe is about 3,6/100?000 per year. The first line treatment consists of a wide resection of the tumour, possibly combined with an adjuvant radiation therapy. A chemotherapy can be indicated and has to be evaluated for each case individually. A biopsy should be done before any treatment and in accordance with the oncological resection approach. The management of the soft tissue sarcoma has to be carried out by a specialist sarcoma multidisciplinary team. PMID:24960098

Panotopoulos, J; Funovics, P; Windhager, R

2014-06-01

207

Radiation Therapy for Soft Tissue Sarcomas  

MedlinePLUS

... Chemotherapy for soft tissue sarcomas Targeted therapy for soft tissue sarcoma Clinical trials for soft tissue sarcomas Complementary and ... been proven to be a better treatment for soft tissue sarcoma. Proton beam therapy is not widely available. Another ...

208

Can Soft Tissue Sarcomas Be Found Early?  

MedlinePLUS

... soft tissue sarcomas staged? Survival by stage of soft tissue sarcoma Previous Topic Can soft tissue sarcomas be prevented? ... other symptoms that may be caused by a soft tissue sarcoma. Last Medical Review: 10/21/2013 Last Revised: ...

209

What Is a Soft Tissue Sarcoma?  

MedlinePLUS

... statistics about soft tissue sarcomas? What is a soft tissue sarcoma? A sarcoma is a type of cancer that ... discussed in detail in our document, Uterine Sarcoma . Rhabdomyosarcomas are malignant tumors of skeletal muscle. These tumors ...

210

Influence of supplemental monensin on gestating and lactating ewes  

E-print Network

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...

Peel, Richard Kraig

1997-01-01

211

What Is Uterine Sarcoma?  

MedlinePLUS

... out during childbirth. Cancers of the uterus and endometrium Sarcomas are cancers that start from tissues such ... called a cervical carcinoma . Carcinomas starting in the endometrium, the lining of the uterus, are called endometrial ...

212

Soft tissue sarcomas.  

PubMed

This synthesis of the literature on radiotherapy for sarcomas originating in the body's soft, supportive tissues, ie, muscle, connective tissue, and fatty tissue is based on 71 scientific articles, including 4 randomized studies, 5 prospective studies, and 26 retrospective studies. These studies involve 3,444 patients. Over 90% of patients with soft tissue sarcomas in the arms and legs can be treated in a way that preserves the extremities. Subcutaneous and intramuscular sarcomas can be treated surgically with little functional loss or risk for local recurrence without adjuvant radiotherapy. To avoid amputation, surgery is often combined with radiotherapy for treatment of local relapse. Adequate surgical margins are usually difficult to achieve for head/neck tumors and retroperitoneal tumors, and therefore surgery is often combined with radiotherapy to reduce the risk for local relapse. Pre- and postoperative radiotherapy are similar. A disadvantage of preoperative radiotherapy is that it reduces the opportunity for exact diagnosis and determining morphobiologic sarcoma parameters. To further improve treatment results for advanced sarcomas, it is necessary to introduce other fractionation schedules, mainly hyperfractionation. This places greater demands on radiotherapy, mainly for staff resources. Combining radiotherapy and local intraarterial chemotherapy involves greater risks for complications and has not shown better treatment results than pre- or postoperative radiotherapy alone, and it is not recommended as standard treatment for soft tissue sarcomas. Intraoperative treatment methods should be targeted for further study and development. PMID:9154103

Alvegård, T

1996-01-01

213

CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression.  

PubMed

Recent molecular advances have identified a novel, clinically aggressive subgroup of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high-grade nuclear features, including vesicular chromatin and nucleoli, patchy clear cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases, including 6 newly identified cases, 2 with paired metastases. Given our prior observation of trisomy 8 in these tumors, we assayed for amplification and expression of MYC (c-Myc) and representative downstream targets. Trisomy 8 was detected in 5/7 testable cases, with further amplification of MYC locus in 6/7 testable cases and immunohistochemical expression of MYC in 10/10. The canonical MYC transcriptional target, p21, but not MTDH, was differentially expressed compared with Ewing sarcomas. Given prior observation of induction of ETS-family transcription factors by the fusion oncoprotein, we assayed and identified highly prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary regarding use of these immunostains in prospective case workup, whereas the prevalent MYC amplification may represent a therapeutically targetable oncogenic pathway in CIC-DUX sarcomas. PMID:24947144

Smith, Steven Christopher; Buehler, Darya; Choi, Eun-Young Karen; McHugh, Jonathan B; Rubin, Brian P; Billings, Steven D; Balzer, Bonnie; Thomas, Dafydd G; Lucas, David R; Goldblum, John R; Patel, Rajiv M

2015-01-01

214

Pediatric Soft Tissue Sarcomas  

PubMed Central

Soft tissue sarcomas in children are relatively rare. Approximately 850 to 900 children and adolescents are diagnosed each year with rhabdomyosarcoma (RMS) or one of the non-RMS soft tissue sarcomas (NRSTS). Of these, 350 are cases of RMS. RMS is the most common soft tissue sarcoma in children 14 years old and younger, and NRSTS is more common in adolescents and young adults. Infants also get NRSTS, but their tumors constitute a distinctive set of histologies, including infantile fibrosarcoma and malignant hemangiopericytoma, not seen in adolescents. Surgery is a major therapeutic modality for all pediatric soft tissue sarcomas, and radiation can play a role in the local therapy for these tumors. RMS is always treated with adjuvant chemotherapy, whereas chemotherapy is reserved for the subset of NRSTS that are high grade or unresectable. This review discusses the etiology, biology, and treatment of pediatric soft tissue sarcomas, including new approaches to therapy aimed at improving the dismal prognosis of patients who have recurrent and metastatic disease. PMID:18514702

Loeb, David M.; Thornton, Katherine; Shokek, Ori

2014-01-01

215

Proton therapy for sarcomas.  

PubMed

Sarcomas are a heterogeneous group of tumors that can occur in a wide array of anatomic sites and age ranges with varying histologies. Proton beam therapy, as compared with advanced x-ray radiation therapy techniques, can substantially lower dose to nontarget tissues. This dosimetric advantage can potentially allow for improvement of the therapeutic ratio in the treatment of many of the sarcomas by either increasing the local control, via increased dose to the target, or by decreasing the normal tissue complications, via lowered dose to the avoidance structures. This article reviews the key dosimetric studies and clinical outcomes published to date documenting the potential role proton beam therapy may play in the treatment of sarcomas. PMID:25415687

Keole, Sameer; Ashman, Jonathan B; Daniels, Thomas B

2014-01-01

216

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

ClinicalTrials.gov

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

2013-02-06

217

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

ClinicalTrials.gov

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

2014-08-11

218

Recombinant Interferon Gamma in Treating Patients With Soft Tissue Sarcoma  

ClinicalTrials.gov

Adult Liposarcoma; Adult Synovial Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage IA Adult Soft Tissue Sarcoma; Stage IB Adult Soft Tissue Sarcoma; Stage IIA Adult Soft Tissue Sarcoma; Stage IIB Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

2014-11-17

219

Sorafenib for Kaposi's Sarcoma  

Cancer.gov

In this trial, patients with either AIDS-related or non-AIDS-related Kaposi's sarcoma (KS) will be treated with varying doses of the drug sorafenib (Nexavar®) for up to 54 weeks to examine the safety of the drug and determine how it is processed in patients with KS who are receiving antiretroviral therapy.

220

Health management of ewes during pregnancy.  

PubMed

The objectives of health management of ewes during pregnancy are as follows: (i) successful completion of pregnancy at term, (ii) birth of healthy and viable lambs, with optimal birth and potential weaning bodyweight, (iii) optimum milk production during the subsequent lactation and (iv) improved management in relation to drug residues in animal products. Knowledge of the physiological background of pregnancy in ewes: changes, mechanisms and interactions, during pregnancy is important for the overall health management of ewes during pregnancy. Health management of pregnant ewes includes diagnosis of pregnancy and evaluation of the number of foetuses borne, which will support strategies for subsequent management of the flock. Nutritional management of ewes depends upon the stage of lactation and specifically aims to (i) prevention of pregnancy toxaemia and other metabolic diseases during the peri-partum period, (ii) formation of colostrum in appropriate quantity and quality, (iii) production of lambs with normal future birth bodyweight and (iv) support of increased milk yield during the subsequent lactation. At the end of lactation, udder management of pregnant ewes includes its clinical examination, culling of ewes considered unsuitable for lactation and, possibly, the intramammary administration of antibiotics; objectives of that procedure are (i) to cure infections which have occurred during the previous lactation and (ii) to prevent development of new mammary infection during the dry period. Management of abortions includes the correct and timely diagnosis of the causative agent of the disorder, as well as the strategic administrations of chemotherapeutic agents, aiming to prevent abortions in flocks with confirmed infection with an abortifacient agent, especially if no appropriate vaccinations had been carried out before the mating season. During the final stage of pregnancy, health management of ewes includes administration of appropriate anthelmintic drugs, aiming to eliminate gastrointestinal helminthes (thus, increasing production output of ewes) and preventing the built-up of parasitic burdens in the environment (thus, reducing infection of lambs during their neonatal period). Vaccinations of pregnant ewes aim to protect these animals, as well as their offspring, especially against diseases which are a frequent cause of neonatal mortality (e.g., clostridial infections). Health management also aims to prevent the main metabolic disorders of pregnant ewes (i.e., pregnancy toxaemia and hypocalcaemia), as well as to monitor flocks for development of these disorders. Health management of pregnant ewes is completed with application of husbandry practices before the start of the lambing season. Finally, in some cases, health management may include induction and synchronisation of lambings, which is a management or therapeutic procedure. PMID:22356932

Fthenakis, G C; Arsenos, G; Brozos, C; Fragkou, I A; Giadinis, N D; Giannenas, I; Mavrogianni, V S; Papadopoulos, E; Valasi, I

2012-02-01

221

How Are Soft Tissue Sarcomas Diagnosed?  

MedlinePLUS

... soft tissue sarcomas staged? Survival by stage of soft tissue sarcoma Previous Topic Signs and symptoms of soft tissue ... is often done if the doctor suspects a soft tissue sarcoma in the chest, abdomen, or the retroperitoneum. This ...

222

Survival by Stage of Soft Tissue Sarcoma  

MedlinePLUS

... soft tissue sarcomas treated? Survival by stage of soft tissue sarcoma Survival rates are often used by doctors as ... improved since then, people now being diagnosed with soft tissue sarcoma may have a more favorable outlook. Survival rates ...

223

Thyroid synovial sarcoma: a case report.  

PubMed

Sarcomas are rare tumors account for about 1% of cancers in adult. Soft tissue sarcomas are the most common one. Synovial sarcoma's incident is about 10% of all sarcomas and most commonly rise from para-articular regions in young adults. Based on our knowledge there have been only two reports of thyroid synovial sarcoma in medical literature. We report a 44-year old woman presented with a rapid growing neck mass. The pathology report revealed sarcoma and the immunohistochemistry (IHC) was compatible with synovial sarcoma. It could be understood that synovial sarcoma can be found in various tissues even if there is no synovial cells. PMID:23456589

Ghafouri, Ali; Anbara, Taha; Mir, Ali; Lashkari, Marzieh; Nazari, Mohammad

2013-01-01

224

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

PubMed

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

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

2015-02-01

225

Understanding the Biology of Bone Sarcoma from Early Initiating Events through Late Events in Metastasis and Disease Progression  

PubMed Central

The two most common primary bone malignancies, osteosarcoma (OS), and Ewing sarcoma (ES), are both aggressive, highly metastatic cancers that most often strike teens, though both can be found in younger children and adults. Despite distinct origins and pathogenesis, both diseases share several mechanisms of progression and metastasis, including neovascularization, invasion, anoikis resistance, chemoresistance, and evasion of the immune response. Some of these processes are well-studies in more common carcinoma models, and the observation from adult diseases may be readily applied to pediatric bone sarcomas. Neovascularization, which includes angiogenesis and vasculogenesis, is a clear example of a process that is likely to be similar between carcinomas and sarcomas, since the responding cells are the same in each case. Chemoresistance mechanisms also may be similar between other cancers and the bone sarcomas. Since OS and ES are mesenchymal in origin, the process of epithelial-to-mesenchymal transition is largely absent in bone sarcomas, necessitating different approaches to study progression and metastasis in these diseases. One process that is less well-studied in bone sarcomas is dormancy, which allows micrometastatic disease to remain viable but not growing in distant sites – typically the lungs – for months or years before renewing growth to become overt metastatic disease. By understanding the basic biology of these processes, novel therapeutic strategies may be developed that could improve survival in children with OS or ES. PMID:24062983

Zhu, Limin; McManus, Madonna M.; Hughes, Dennis P. M.

2013-01-01

226

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

PubMed Central

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

2014-01-01

227

Relationships among ewe milk production and ewe and lamb forage intake in Suffolk and Targhee ewes nursing single or twin lambs.  

PubMed

Suffolk and Targhee ewes (30 each) with single or twin lambs were used in four periods beginning in late gestation and continuing through weaning to evaluate breed differences in milk production, lamb BW, and DMI by ewes and lambs. In Periods 1 (late gestation) and 2 (early lactation), ewes (Period 1) and ewes with lambs (Period 2) were individually penned, fed .45 kg of barley x ewe(-1) x d(-1) and allowed ad libitum access to chopped alfalfa. Ewes and lambs grazed native range in Periods 3 and 4. Grazed forage DMI was estimated using chromic oxide. Estimates of milk production were obtained by handmilking. Average lamb age was 4, 45, and 73 d at the beginning of Periods 2, 3, and 4, respectively. Milk production tended (P = .20) to be greater for Suffolk than for Targhee ewes. Targhee ewes produced 85% more (P = .001) wool than Suffolk ewes. From 33 d prepartum to 89 d postpartum, Suffolk ewes consistently weighed more (P = .001) than Targhee ewes. Suffolk ewe BW loss (-.15 kg/d) was greater (P = .01) than Targhee ewe BW loss (-.02 kg/d) from 33 d prepartum to 6 d postpartum. From 6 to 89 d postpartum BW gain did not differ (P = .69; .05 kg/d) between breeds. From birth to 89 d postpartum, Suffolk lambs consistently weighed more than Targhee lambs (P = .003). From birth to 89 d postpartum, ADG was greater for Suffolk than for Targhee lambs (P = .006). Targhee ewes consumed 25% more (P = .01) feed over the course of the study than did Suffolk ewes. Grazed forage DMI by Targhee lambs was 26% greater (P = .01) than DMI by Suffolk lambs. When meat production is the primary income from sheep, one potential advantage of Suffolks compared with Targhees is more rapid gain with less feed intake. PMID:9621929

Ramsey, W S; Hatfield, P G; Wallace, J D

1998-05-01

228

Gene Expression Profiling of Human Sarcomas: Insights into Sarcoma Biology  

Microsoft Academic Search

Sarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differenti- ation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We exam- ined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature

Kristin Baird; Sean Davis; Cristina R. Antonescu; Ursula L. Harper; Robert L. Walker; Yidong Chen; Arthur A. Glatfelter; Paul H. Duray; Paul S. Meltzer

2005-01-01

229

Sarcomas of the skin in the elderly  

Microsoft Academic Search

Malignant mesenchymal neoplasms of skin and soft tissues are characterized by an extreme clinicopathologic heterogeneity. Although all sarcomas of deep soft tissues may also arise in superficial locations, there are important clinicopathologic differences. Lipogenic sarcomas represent the most frequent type of sarcomas in deep soft tissues, but purely dermal liposarcomas are exceedingly rare. Vascular and fibroblastic or myofibroblastic sarcomas, however,

Thomas Mentzel

2011-01-01

230

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma.  

PubMed

Pegylated-liposomal doxorubicin (Doxil) is a unique form of liposomal doxorubicin in which the liposomes are coated with methoxypoly (ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, leading to a longer half-life in blood and a different toxicity profile than nonpegylated liposomes. We performed a phase II study of Doxil in sarcoma. The patient population was primarily previously treated or had diagnoses considered unresponsive to chemotherapy. The initial dose per course was 55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 214 evaluable treatment courses in 47 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. There were: 6 osteosarcomas, 3 Ewings, 1 extraosseous osteosarcoma, 1 chondrosarcoma, 2 alveolar soft part sarcomas, 15 gastrointestinal stromal cell tumors (GIST), and 19 other soft tissue sarcomas. Three of the 47 patients received a CR or PR, although 15 of the 47 patients were felt to have derived clinical benefit from the treatment. Some responses were delayed. These data suggest that pegylated-liposomal doxorubicin has activity in this population of poor prognosis sarcoma and that this treatment is associated with modest toxicity. PMID:12743981

Skubitz, Keith M

2003-04-01

231

Targeted polytherapy in small cell sarcoma and its association with doxorubicin.  

PubMed

A paradigm shift has occurred in the last decade from chemotherapy to targeted therapy for the management of many patients with advanced sarcoma. This work identifies a combination of targeted agents and doxorubicin that are effective against small cell sarcoma cell lines. Three small cell sarcoma cell lines were studied: RD18 (rhabdomyosarcoma), A204 (undifferentiated sarcoma) and TC 71 (Ewing's sarcoma). Each cell line was exposed to increasing concentrations of vorinostat (HDAC inhibitor), 17-DMAG (HSP90 inhibitor), abacavir (anti-telomerase) or sorafenib (tyrosine kinase inhibitor) alone, combined with one another, or combined with doxorubicin. Cell viability, cell cycle analysis and apoptosis were assessed by MTS assay, propidium iodide-Annexin V staining, and caspase 3/7 activity, respectively. The Chou and Talalay combination index (CI) was used to determine whether the effects were additive (CI = 1), synergistic (CI < 1) or antagonistic (CI > 1). In monotherapy, targeted agents achieved 30-90% reductions in viability, with the exception of abacavir. Dual-targeted combination therapies with vorinostat, sorafenib and 17-DMAG demonstrated synergy. Abacavir was antagonistic with every other drug and was not further studied. Both vorinostat and 17-DMAG synergized with doxorubicin, achieving 60% cell killing compared to 12% with doxorubicin alone. No synergy was observed for sorafenib with doxorubicin. The triple therapy vorinostat, 17-DMAG and doxorubicin did not show synergy, but increased the subG1 population at 24H, from 30% to 70% compared to monotherapies with an increase in apoptosis. This work provides evidence of synergy of combinations of vorinostat, 17-DMAG and sorafenib in small cell sarcoma. In addition to doxorubicin, these combinations enhance doxorubicin cytotoxicity at therapeutically relevant concentrations. PMID:24998445

Dumont, S N; Yang, D; Dumont, A G; Reynoso, D; Blay, J-Y; Trent, J C

2014-12-01

232

Lipid requirements in the nutrition of dairy ewes  

Microsoft Academic Search

The aim of this review was to contribute to the knowledge of lipid requirements in dairy ewes, by reviewing experi- mental papers about lipid supplementation in dairy ewe feeding. The number of trials in ewe feeding is lower than that in dairy cow feeding and, leaving calcium soap of palm oil out of consideration, there is a lack of knowledge

Marcello Mele; Arianna Buccioni; Andrea Serra

2005-01-01

233

COMPARATIVE BIOAVAILABILITY OF LEVAMISOLE IN NON LACTATING EWES AND GOATS  

E-print Network

COMPARATIVE BIOAVAILABILITY OF LEVAMISOLE IN NON LACTATING EWES AND GOATS P. GALTIER, L. ESCOULA, R in non lactating adult goats and ewes. In each case, the recommended veterinary therapeutic forms pregnant females (four Romanov ewes and four Alpine goats) were used during a three week-period. Body

Boyer, Edmond

234

Ewe (for Togo): Grammar Handbook. Peace Corps Language Handbook Series.  

ERIC Educational Resources Information Center

This handbook is composed of: (1) 20 grammar lessons; (2) an introduction to the handbook and to the Ewe language; (3) an appendix presenting the most important differences between Ewe and Mina, the lingua franca in the capital and in markets, offices, and work-sites throughout Togo; (4) answers to written summary exercises; (5) an Ewe-English…

Kozelka, Paul R.

235

Peripheral nerve fibromyxoid sarcoma.  

PubMed

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue neoplasm with metastatic potential and needs to be recognized as such, because it can be mistaken for other types of sarcoma due to its unremarkable appearance. This 49-year-old man presented with an approximately 5-cm mass on the anteromedial aspect of his left thigh that slowly increased over 10 years. Clinical symptoms were limited to local discomfort and intermittent distal numbness. Due to the location, imaging findings, and lack of serious symptoms, the initial differential diagnosis favored a schwannoma. An initial biopsy revealed histopathological findings consistent with a perineurioma, although with atypical features. The patient elected to have the mass excised, and the tumor, which arose from a branch of the saphenous nerve, could be separated well from the surrounding soft tissue. Histopathological investigation of the mass displayed characteristic features of a fibromyxoid sarcoma, which was confirmed by subsequent fluorescence in situ hybridization analysis. Due to concerns about infiltration beyond the margins, radical reexcision was advocated and performed, resulting in definite clear surgical margins. At follow-up, the patient had regained full strength with no residual neurological symptoms or any new deficits. He has since been healthy and disease free for a total of 4 years in follow-up. This case documents, to the authors' knowledge, the first observation of an LGFMS associated with a peripheral nerve. It also supports the use of fluorescence in situ hybridization analysis as an essential diagnostic method in establishing the diagnosis of LGFMS. PMID:24766104

Alter, Raanan Y; Wamsley, Christina C; Mullen, John T; Haile, Winta Z; Goldsmith, Jeffrey D; Kasper, Ekkehard M

2014-09-01

236

Strategies for rapid rebreeding of lactating ewes in the spring.  

PubMed

Rapid rebreeding of winter- and spring-lambing ewes is essential if ewes are to lamb more than once per year, but fertility of lactating ewes is often low and early weaning of lambs may be undesirable in forage-based production systems. Selection to improve fertility in spring matings has been successful and led to development of ewes with a reduced seasonal anestrus. Potential for rapid rebreeding of lactating out-of-season breeding (OOS) ewes was tested in three studies. In Experiment 1, effects of short-term lamb removal on rebreeding was evaluated over 2 years using 71 January-lambing OOS ewes. At an average of 63 days postpartum, 36 ewes had lambs removed for 72 h, and all ewes were joined with rams. Circulating progesterone levels indicated that 74% of ewes ovulated before lamb separation; 91% of ewes mated within 5 weeks of ram exposure, 85% were diagnosed as pregnant and 75% lambed. The average interval between lambings was 225 days. In contrast to results observed in cattle, none of the measured variables was affected by lamb separation (P>0.20). Experiment 2 compared rebreeding performance of 24 OOS and 23 St. Croix ewes that lambed in January and averaged 60 days postpartum at ram introduction. More OOS ewes ovulated, mated and became pregnant during the first 21 days of ram exposure (83.3%, 58.3%, and 41.7%, respectively; P<0.001) compared with St. Croix ewes (26.1%, 0%, and 0%, respectively). After 39 days of ram exposure, pregnancy rates still favored OOS ewes (66.7% v. 39.1%; P=0.06), but the percentage of ewes that lambed did not differ (P>0.20) between OOS (47.8%) and St. Croix ewes (34.8%). In the third study, 34 March-lambing OOS ewes were exposed to rams on May 3 at an average of 40 days postpartum to characterize their reproductive performance. After 39 days of ram exposure, 52.9±8.7% of the ewes had mated, and 38.2±8.5% were diagnosed as pregnant. However, only 20.6±7.0% of the ewes produced viable lambs, suggesting a high level of uterine insufficiency. Spring fertility of lactating OOS ewes in these studies was one of the highest reported in the literature and indicated that selection for fertility in spring mating would improve reproductive performance in accelerated lambing programs. However, exposure of lactating OOS ewes to rams at 30 to 50 days postpartum was associated with high prenatal lamb mortality. PMID:24622342

Goff, K J; Notter, D R; Vanimisetti, H-B; Knight, J W

2014-06-01

237

Alisertib in Treating Patients With Advanced or Metastatic Sarcoma  

ClinicalTrials.gov

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

2015-02-11

238

Instantánea del sarcoma de Kaposi  

Cancer.gov

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

239

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.

240

Ewing’s Family of Tumors of the Sinonasal Tract and Maxillary Bone  

Microsoft Academic Search

The Ewing’s family of tumors (EFT) are malignant neoplasms affecting children and young adults. Most cases arise in the long\\u000a bones or the pelvis. Primary EFT of head and neck is uncommon and primary sinonasal EFT is even rarer. Previous studies have\\u000a not focused on the sinonasal region specifically, and the published literature on sinonasal EFT consists of sporadic case

Sara Hafezi; Raja R. Seethala; Edward B. Stelow; Stacey E. Mills; Iona T. Leong; Elaine MacDuff; Jennifer L. Hunt; Bayardo Perez-Ordoñez; Ilan Weinreb

2011-01-01

241

[Orbital granulocytic sarcoma: case report].  

PubMed

Orbital granulocytic sarcoma is a localized tumor consisting of malignant cells of myeloid origin. This tumor may present in association with acute myelogenous leukemia. Granulocytic sarcoma may be found in a variety of locations throughout the body including the orbit and typically affects children and young adults. There is a slight male predominance in these cases. This is an uncommon case report of a 33-year-old Latin-American woman who was admitted to the Hospital for rapidly progressive orbital proptosis. There was no systemic manifestation of leukemia. The occurrence of orbital granulocytic sarcoma before the development of systemic leukemia in children and young adults is not uncommon and these cases frequently develop hematological evidence within 2 months after initial orbital disease. In this case report, there was no systemic manifestation of leukemia in the last 30 months, even in the presence of orbital tumors. Granulocytic sarcoma is most frequently confused with malignant lymphoma, rhabdomyosarcoma and neuroblastoma. The differential diagnosis of these cases can be challenging, particularly when there is no evidence of systemic leukemia, when imaging features are not sufficiently specific to distinguish granulocytic neoplasms from other tumors. To establish the diagnosis often a biopsy is required. The treatment in such cases (orbital granulocytic sarcoma) is not standardized. Orbital granulocytic sarcoma may be suspected in cases of orbital tumors even in the absence of systemic manifestations of leukemia at any age. PMID:16322847

Fonseca Junior, Nilson Lopes da; Paves, Luis; Nakanami, Deise Mitsuko; Seixas, Maria Teresa; Manso, Paulo Góis

2005-01-01

242

Rhodotorula minuta fungemia in a ewe lamb  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

243

Original article Conjunctival vaccination of pregnant ewes  

E-print Network

Original article Conjunctival vaccination of pregnant ewes and goats with Brucella melitensis Rev 1 vaccine: safety and serological responses E Zundel JM Verger M Grayon R Michel 1 Institut National de la Brucella melitensis strain Rev 1 vaccine (Rev 1) is administered by the standard method (1-2 x 109 viable

Paris-Sud XI, Université de

244

Shackleton receives 2002 Maurice Ewing medal  

Microsoft Academic Search

Nicholas Shackleton was awarded the Ewing Medal at the AGU Fall Meeting Honors Ceremony which was held on 8 December 2002, in San Francisco, California. The medal is given for significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering, technology, and instrumentation; and for outstanding service to marine sciences.

Theodore C. Moore Jr.; Nicholas Shackleton

2003-01-01

245

Bond Receives 2003 Maurice Ewing Medal  

NASA Astrophysics Data System (ADS)

Gerard C. Bond was awarded the Ewing Medal at the AGU Fall Meeting Honors Ceremony, which was held on 10 December 2003, in San Francisco, California. The medal honors ``significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering, technology, and instrumentation; and for outstanding service to marine sciences.''

Broecker, Wallace S.

2004-02-01

246

Bond Receives 2003 Maurice Ewing Medal  

Microsoft Academic Search

Gerard C. Bond was awarded the Ewing Medal at the AGU Fall Meeting Honors Ceremony, which was held on 10 December 2003, in San Francisco, California. The medal honors ``significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering, technology, and instrumentation; and for outstanding service to marine sciences.''

Wallace S. Broecker

2004-01-01

247

Extraosseous Ewing's tumor of lateral abdominal wall  

PubMed Central

Extraosseous Ewings tumor (EES) is a rare entity. Few cases have been reported in literature. There are no specific guidelines for management of this disease. We are reporting a case of EES arising from left lateral abdominal wall. We did wide excision of tumor followed by chemoradiation. Patient is asymptomatic after 8 months of follow up. PMID:24765376

Gupta, Nikhil; Chand, Tirlok; Yadav, Nidhi; Kumar, Rajeev; Chauhan, Devender S.; Chaudhary, Poras; Arora, Mohinder P.

2011-01-01

248

Sarcomas of the skin in the elderly.  

PubMed

Malignant mesenchymal neoplasms of skin and soft tissues are characterized by an extreme clinicopathologic heterogeneity. Although all sarcomas of deep soft tissues may also arise in superficial locations, there are important clinicopathologic differences. Lipogenic sarcomas represent the most frequent type of sarcomas in deep soft tissues, but purely dermal liposarcomas are exceedingly rare. Vascular and fibroblastic or myofibroblastic sarcomas, however, are much more frequent in dermal location. In contrast with most deep-seated sarcomas, morphologic grading of dermal sarcomas has only a limited importance because most types of dermal sarcoma have a rather favorable clinical prognosis. Important exceptions to this rule are epithelioid sarcoma and cutaneous angiosarcoma, which are aggressive sarcomas with an increased rate of distant metastases and tumor-associated death. Dermal sarcomas arising in elderly patients show some important differences in their incidence and prognosis. Whereas cutaneous angiosarcoma, myxofibrosarcoma, undifferentiated pleomorphic sarcoma of the skin showing morphologic similarities to atypical fibroxanthoma, and cutaneous leiomyosarcoma arise predominantly in elderly patients, dermatofibrosarcoma protuberans, epithelioid sarcoma, and superficially located clear cell sarcoma are seen more often in younger patients. PMID:21146736

Mentzel, Thomas

2011-01-01

249

p53 expression and its relationship to DNA alterations in bone and soft tissue sarcomas.  

PubMed Central

The p53 gene is one of the best studied tumour suppressor genes. Recently we performed mutation analysis on the p53 gene in a large number of bone and soft tissue sarcomas, and found that approximately one-third of the sarcomas have some type of DNA alteration at the p53 locus (Toguchida et al., 1992). However, the expression of the p53 protein resulting from these alterations still remains to be clarified. In this study, p53 expression in the sarcoma tissues was analysed immunohistochemically using antibody PAb421 (Oncogene Science) and its relationship to DNA alterations was examined. Of 113 tumours, 29 (25.7%) showed positive staining for the p53 protein. These included 19 of 67 osteosarcomas, five of 20 chondrosarcomas, four of 11 malignant fibrous histiocytomas (MFHs) and one Ewing's sarcoma. In chondrosarcomas, most of the p53-positive tumours belonged to highly malignant and atypical tumour types (dedifferentiated or mesenchymal type), suggesting a role for p53 mutation in the progression of cartilaginous tumours. All the cases with a missense mutation showed strongly positive staining, while no immunoreactivity was observed in the remaining three-quarters with DNA alterations including gross rearrangement, frame-shift mutation, nonsense mutation or mutation at splicing site except in one case. These results demonstrated the dominance of the p53 mutations with null protein expression in bone and soft tissue sarcomas, showing a unique characteristic of these types of tumours compared with other malignancies such as colon carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:8260365

Wadayama, B.; Toguchida, J.; Yamaguchi, T.; Sasaki, M. S.; Yamamuro, T.

1993-01-01

250

Synovial sarcoma of the sellar region  

PubMed Central

Primary sarcomas of the sellar region are uncommon, although a wide variety have been reported. To date, no cases of primary synovial sarcoma have been described as occurring at this site. We report an immunohistochemically and molecular genetically confirmed primary synovial sarcoma involving the sellar/parasellar region and cavernous sinus in an adult male. Subtotal resection and radiosurgery proved to be efficacious. The spectrum of primary sellar region sarcomas is summarized. PMID:17704363

Scheithauer, Bernd W.; Silva, Ana Isabel; Kattner, Keith; Seibly, Jason; Oliveira, Andre M.; Kovacs, Kalman

2007-01-01

251

Artificial lighting during winter increases milk yield in dairy ewes.  

PubMed

In Australia, the supply of sheep milk is reduced during the winter. Housing dairy animals under lights during winter is a simple technique to increase milk yield; however, it is difficult to predict the magnitude of this increase in dairy ewes, because there are few corroborating data. We studied 220 East Friesian crossbred ewes (50 primiparous and 170 multiparous ewes, respectively) that lambed in April to May 2007 (late autumn, southern hemisphere) and were weaned from their lambs within 24 h of parturition and milked exclusively by machine. These ewes were ranked according to their milk production, and ewes producing > or =1,000 mL/d of milk were allocated to 1 of 2 groups. One group of ewes was kept indoors under a long-day photoperiod (16 h of light), whereas the other group was kept indoors under a naturally declining day length. Ewes were maintained under these conditions for 8 wk. Milk yield was measured twice weekly, and ewe weight and condition were measured at weekly intervals. From a subset of ewes (n = 20 per group), milk samples were collected twice weekly at the morning milking to measure milk lipid, protein, and lactose, and blood samples were collected once a week to measure plasma prolactin concentrations. Mean daily milk yield was analyzed as a percentage of preexperimental milk yield because the milk yield of ewes housed under the long photoperiod was lower than that of ewes under a declining day length when the treatments began. Thus, the ewes under a long photoperiod yielded 91.7% of their starting yield by wk 8 of treatment, whereas ewes under a declining day length yielded 76.25% of their initial value (LSD = 5.1), and this divergence in milk yield was apparent by wk 2 of treatment. Mean plasma prolactin levels were greater in ewes housed under the long-day photoperiod (n = 20) compared with control ewes (n = 20) at wk 6 (168 +/- 27 vs. 72 +/- 19 ng/mL, respectively), wk 7 (125 +/- 28 vs. 37 +/- 7 ng/mL, respectively), and wk 8 of the experiment (132 +/- 35 vs. 31 +/- 7 ng/mL, respectively). The composition of the milk was similar between the groups at each time point, and milk from these ewes (n = 20 per group) contained, on average, 6.1 +/- 0.05% lipid, 4.8 +/- 0.02% protein, and 5.4 +/- 0.01% lactose (n = 309 samples). We concluded that ewes increase milk production in response to being housed under a long-day photoperiod during winter. PMID:18946128

Morrissey, A D; Cameron, A W N; Tilbrook, A J

2008-11-01

252

Primary Sarcomas of the Central Nervous System  

Microsoft Academic Search

The medical files of 14 patients with primary brain and spine sarcomas were retrospectively reviewed. Ten patients had primary brain sarcomas and 4 primary spinal sarcomas. The tumors probably originated in the brain substance or blood vessels, in the meninges or in the inner aspect of the skull. The spinal tumors originated in the nerve roots of the cauda equina

O. Merimsky; C. Lepechoux; P. Terrier; D. Vanel; J. P. Delord; A. LeCesne

2000-01-01

253

Sarcoma risk after radiation exposure  

PubMed Central

Sarcomas were one of the first solid cancers to be linked to ionizing radiation exposure. We reviewed the current evidence on this relationship, focusing particularly on the studies that had individual estimates of radiation doses. There is clear evidence of an increased risk of both bone and soft tissue sarcomas after high-dose fractionated radiation exposure (10?+?Gy) in childhood, and the risk increases approximately linearly in dose, at least up to 40?Gy. There are few studies available of sarcoma after radiotherapy in adulthood for cancer, but data from cancer registries and studies of treatment for benign conditions confirm that the risk of sarcoma is also increased in this age-group after fractionated high-dose exposure. New findings from the long-term follow-up of the Japanese atomic bomb survivors suggest, for the first time, that sarcomas can be induced by acute lower-doses of radiation (<5?Gy) at any age, and the magnitude of the risk is similar to that observed for other solid cancers. While there is evidence that individuals with certain rare familial genetic syndromes predisposing to sarcoma, particularly Nijmegen Breakage Syndrome, are particularly sensitive to the effects of high dose radiation, it is unclear whether this is also true in very low-dose settings (<0.1?Gy). The effects of common low-penetrance alleles on radiosensitivity in the general population have not been well-characterized. Some evidence suggests that it may be possible to identify radiation-induced sarcomas by a distinct molecular signature, but this work needs to be replicated in several dose settings, and the potential role of chemotherapy and tumor heterogeneity needs to be examined in more detail. In summary, radiation exposure remains one of the few established risk factors for both bone and soft tissue sarcomas. Similar to many other cancers children have the highest risks of developing a radiation-related sarcoma. Efforts to limit unnecessary high-dose radiation exposure, particularly in children, therefore remain important given the high fatality rates associated with this disease. PMID:23036235

2012-01-01

254

Conditioning ewes and lambs to increase consumption of spotted knapweed  

Microsoft Academic Search

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

Travis Raymond Whitney; Bret Eugene Olson

2006-01-01

255

Hypofractionated radiotherapy for sarcomas.  

PubMed

In an effort to improve local control in the radiation treatment of sarcomas, up to 7 weekly fractions of 6.6 Gy each were administered to 64 patients. They were divided into two groups: Group A consisted of 37 patients with measurable disease who achieved a partial response rate of 22%, with no complete responses. Group B consisted of 27 postoperative patients with varying degrees of completeness of surgical excision, two have relapsed locally to date. Early radiation damage was documented in 26%, but was not a dose-limiting or incapacitating event in any case. Late normal tissue damage occurred in 23 out of 32 evaluable patients (72% of those at risk), and was a cause of serious morbidity in 6 patients. Response rates were low in Group A compared with other series, but in Group B the local recurrence rate is comparable with other centers using "conventional" fractionation. No apparent improvement in therapeutic gain was demonstrated for large weekly fractions. PMID:3080387

Ashby, M A; Ago, C T; Harmer, C L

1986-01-01

256

Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma.  

PubMed

Trabectedin is a marine-derived cytoxic alkaloid which has shown promising antitumour activity in a variety of human malignancies including sarcoma. Fifty-four patients with advanced sarcoma (age 43 yrs, range 18-70), all pretreated with prior chemotherapy, were enrolled on a named individual basis for treatment with trabectedin. Diagnosis was adult soft tissue sarcoma (STS) in 46 patients, Ewing's family tumour (EFT) in 4, and osteosarcoma (OS) in 4. The initial 23 patients (total number of courses administered: 68) did not receive premedication prior to trabectedin, while the other 31 patients (total number of courses administered: 134) received premedication with dexamethasone 4 mg po bid 24 hours before therapy. Incidence of toxicity (grade 3-4), expressed as percentage of courses, was as follows: in patients without dexamethasone, elevation of transaminases 34%, neutropenia 24% and thrombocytopenia 25%; in patients with prior dexamethasone, elevation of transaminases 2%, neutropenia 2% and no thrombocytopenia. The median received dose intensity of trabectedin was superimposable in the two groups (404 microg and 400 microg per week, respectively), as well as progression-free survival (19% at 6 months). Among STS patients, 9% had objective responses. In this unselected patient series, premedication with dexamethasone strongly reduced drug-induced hepatotoxicity and myelosuppression. PMID:16737808

Grosso, F; Dileo, P; Sanfilippo, R; Stacchiotti, S; Bertulli, R; Piovesan, C; Jimeno, J; D'Incalci, M; Gescher, A; Casali, P G

2006-07-01

257

The role of the CXCL12-CXCR4/CXCR7 axis in the progression and metastasis of bone sarcomas (Review).  

PubMed

Bone sarcomas, which comprise less than 1% of all human malignancies, are a group of relatively rare mesenchymal-derived tumors. They are mainly composed of osteosarcoma, chondrosarcoma and Ewing's sarcoma. In spite of advances in adjuvant chemotherapy and wide surgical resection, prognosis remains poor due to the high propensity for lung metastasis, which is the leading cause of mortality in patients with bone sarcomas. Chemokines are a superfamily of small pro-inflammatory chemoattractant cytokines which can bind to specific G protein-coupled seven-span transmembrane receptors. Chemokine 12 (CXCL12), also designated as stromal cell-derived factor-1 (SDF-1), is able to bind to its cognate receptors, chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7), with high affinity. The binding of CXCL12 to CXCR4/CXCR7 stimulates the activation of several downstream signaling pathways that regulate tumor progression and metastasis. In this review, the structure and function of CXCL12 and its receptors, CXCR4 and CXCR7, as well as many factors affecting their expression are discussed. Phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are the two most important downstream pathways regulated by the CXCL12-CXCR4/CXCR7 interaction. CXCR4 expression in bone sarcomas, including tumor cells and samples and the correlation between CXCR4/CXCR7 expression and the survival of patients with bone sarcomas are also discussed. In addition, we review the involvement of the CXCL12?CXCR4/CXCR7 axis in the growth and metastasis of bone sarcomas and the targeting of this axis in preclinical studies. PMID:24127013

Liao, Yu-Xin; Zhou, Cheng-Hao; Zeng, Hui; Zuo, Dong-Qing; Wang, Zhuo-Ying; Yin, Fei; Hua, Ying-Qing; Cai, Zheng-Dong

2013-12-01

258

Mast cell sarcoma: clinical management.  

PubMed

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

Weiler, Catherine R; Butterfield, Joseph

2014-05-01

259

Suckling behavior of ewes in early lactation.  

PubMed

Previous studies have described the basic suckling behavior of ewe/lamb pairs during daylight hours, but no information is available for the hours of darkness. In this study, the natural pattern of suckling was recorded over a 24-h period once a week for the first 7 weeks of lactation in 7 free-ranging Merino ewes with single lambs. Both the mean suckling frequency per 24 hours and the mean duration of individual suckling bouts declined with increasing age of the lamb. Suckling frequencies fell from 36 +/- 5.5 sucks/24 h at 1-2 weeks of age to 14.3 +/- 2.78 sucks/24 h at 6-7 weeks of age. Individual suckling bout duration fell from 41.1 +/- 9.9 s at 1-2 weeks of age to 11.9 +/- 1.2 s by 6-7 weeks. Suckling frequencies per hour were significantly greater during daylight as compared to darkness (p less than 0.05). We suggest that the declining frequency and duration of suckling bouts with age probably accounts for the waning influence of lactation on the reproductive state of the ewe, and that the maintenance of a critical interbout interval may first break down at night. PMID:1805274

Gordon, K; Siegmann, M

1991-11-01

260

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

ClinicalTrials.gov

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

2015-01-16

261

Prognostic features of renal sarcomas (Review)  

PubMed Central

The aim of the present review was to evaluate the prognostic features of primary sarcomas of the kidney. A literature review was conducted using a number of databases, including Medline (PubMed) and Scopus, for studies published between January 1992 and December 2013. Of the studies published in English, those describing the prognostic features of primary sarcomas of the kidney were recorded. The electronic search was limited to the following keywords: Sarcoma, renal sarcoma, prognosis, diagnosis, immunohistochemistry, genetic and survey. Subsequent to the search, no review articles and/or meta-analyses associated with the prognosis of primary sarcomas of the kidney were identified. In total, 31 studies, which consisted of case studies, case series and studies concerned with the overall prognosis of urological soft-tissue sarcomas, were reviewed. Primary sarcoma of the kidney has a poor prognosis compared with other sarcomas of the urogenital system. In addition to the surgical excision of renal sarcomas, pathological, molecular and genetic prognostic factors are also considered. Due to the small number of cases, previous studies have not randomized the prognostic features of primary sarcomas of the kidney. The elucidation of the so-called ‘chaotic’ genetic and molecular basis of renal sarcomas will help to predict patient prognoses. Surgical excision is the most significant parameter for determining the prognosis of sarcomas of the kidney. However, sarcomas also exhibit prognostic features that are based upon pathological, genetic and molecular factors. The present review suggests that additional factors may be important in predicting the prognosis of patients with renal sarcomas, and that clinicians should plan treatment and follow-up regimens according to these factors. PMID:25663853

ÖZTÜRK, HAKAN

2015-01-01

262

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

Microsoft Academic Search

BACKGROUND: A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. RESULTS: We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted

Tatiana Baumuratova; Didier Surdez; Bernard Delyon; Gautier Stoll; Olivier Delattre; Ovidiu Radulescu; Anne Siegel

2010-01-01

263

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

E-print Network

, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish....pone.0000979.g004 Ewsr1 in Mitosis PLoS ONE | www.plosone.org 4 October 2007 | Issue 10 | e979 Loss of mitotic integrity accompanied by mislocalization of Aurora B proteins in EWSR1 deficient Hela cells The Ewsr1 knockdown in zebrafish embryos induced mitotic...

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

2007-10-03

264

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

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

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

2014-06-01

265

FREE AMINO ACID CONTENT OF EWE UTERINE FLUID  

E-print Network

FREE AMINO ACID CONTENT OF EWE UTERINE FLUID UNDER VARIOUS HORMONAL TREATMENTS DURING EARLY Recherches zootechniques, I. N. R. A., i'8350 Jouy en Josas SUMMARY Free amino acids are dosed in ewe uterine secretions are very rich in free amino acids, especially glutamic acid + glutamine and glycine. However

Paris-Sud XI, Université de

266

and Christina C. Leslie Bonventre, Heather Ewing, Michael H. Gelb  

E-print Network

and Christina C. Leslie Bonventre, Heather Ewing, Michael H. Gelb V.Benjamin F. Cravatt, Ku. Bonventre3 , Heather Ewing4 , Michael H. Gelb4,5 , and Christina C. Leslie1,6,7 From the 1 Department Jackson St, Denver, CO 80206, USA. Tel: (303) 398-1214; E-mail: lesliec@njhealth.org Key words: calcium

Gelb, Michael

267

Adaptation of pregnant ewes to an exclusive onion diet.  

PubMed

A diet consisting entirely of cull onions fed to pregnant ewes produced Heinz body hemolytic anemia in all sheep after 21 d. After 28 d of daily consumption of 20 kg of onions/ewe, the anemia stabilized, and for the remaining 74 d the packed cell volume increased in the majority of sheep, although it did not return to normal. Compared to control ewes fed an alfalfa and grain diet, the onion-fed ewes had comparable body condition scores and fleece weights. There was no significant difference (alpha = 0.05) in pregnancy or lambing rate, number of lambs born/ewe exposed, or number of lambs born/ewe lambing. Greater numbers of sulfate-reducing bacteria (Desulfovibrio spp) and more ruminal hydrogen sulfide were present in onion-fed sheep compared to controls. Although an average 27% reduction in packed cell volume and Heinz body anemia developed in the onion-fed ewes, on the basis of this study it appears that pregnant ewes may be fed a pure onion diet with minimal detrimental effects. This adaptation to a pure onion diet is in part likely due to the apparent ability of the sheep's rumen to quickly develop a population of sulfate-reducing bacteria that decrease the toxicity of onion disulfides. PMID:10670075

Knight, A P; Lassen, D; McBride, T; Marsh, D; Kimberling, C; Delgado, M G; Gould, D

2000-02-01

268

PHASE II STUDY OF HIGH DOSE PHOTON/PROTON RADIOTHERAPY IN THE MANAGEMENT OF SPINE SARCOMAS  

PubMed Central

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. Materials/Methods Eligible patients had non-metastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or post-op photon/proton XRT +/- radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (GyRBE) to subclinical disease, 70.2 GyRBE to microscopic disease in the tumor bed, and 77.4 GyRBE to gross disease at 1.8 GyRBE q.d. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 GyRBE to surface/center. Intra-operative boost doses of 7.5-10 Gy could be given by dural plaque. Results 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, five-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 following 77.12-77.4 GyRBE. 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 GyRBE are at risk for late toxicity. PMID:19095372

DeLaney, Thomas F.; Liebsch, Norbert J.; Pedlow, Francis X.; Adams, Judith; Dean, Susan; Yeap, Beow Y.; McManus, Patricia; Rosenberg, Andrew E.; Nielsen, G. Petur; Harmon, David C.; Spiro, Ira J.; Raskin, Kevin A.; Suit, Herman D.; Yoon, Sam S.; Hornicek, Francis J.

2009-01-01

269

Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children  

PubMed Central

Purpose Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. Materials and Methods We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. Results A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. Conclusion Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children. PMID:25143049

Lim, Sun Min; Yoo, Cheol Joo; Han, Jung Woo; Cho, Yong Jin; Kim, Soo Hee; Ahn, Joong Bae; Rha, Sun Young; Shin, Sang Joon; Chung, Hyun Cheol; Yang, Woo Ick; Shin, Kyoo-Ho; Rho, Jae Kyung; Kim, Hyo Song

2015-01-01

270

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...

271

What Are the Key Statistics about Soft Tissue Sarcoma?  

MedlinePLUS

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

272

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

MedlinePLUS

... resources for soft tissue sarcoma What`s new in soft tissue sarcoma research and treatment? Research is ongoing in the ... MFH) are actually high-grade forms of liposarcoma, rhabdomyosarcoma , leiomyosarcoma, other sarcomas, and even carcinomas or lymphomas. ...

273

CASE REPORT Open Access Isolated granulocytic sarcoma of the pancreas  

E-print Network

CASE REPORT Open Access Isolated granulocytic sarcoma of the pancreas: A tricky diagnostic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological and therapeutic strategies. Keywords: Granulocytic sarcoma, Chloroma, Myeloid tumor, Pancreas. Background

Boyer, Edmond

274

Soft tissue sarcomas with complex genomic profiles  

Microsoft Academic Search

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell\\/pleomorphic\\u000a sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral\\u000a nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell\\/pleomorphic unclassified sarcoma (previously\\u000a called spindle cell\\/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses\\u000a of numerous chromosomes or chromosome regions, as

Louis Guillou; Alain Aurias

2010-01-01

275

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

ClinicalTrials.gov

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

2015-01-20

276

Proton Radiotherapy for Pediatric Sarcoma  

PubMed Central

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

Ladra, Matthew M.; Yock, Torunn I.

2014-01-01

277

Evaluating Dactinomycin and Vincristine in Young Patients With Cancer  

ClinicalTrials.gov

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

2014-08-06

278

Adult human sarcomas. I. Basic science.  

PubMed

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

Sinkovics, Joseph G

2007-01-01

279

Current soft-tissue sarcoma classifications.  

PubMed

In order to analyse the impact of modern sarcoma classification criteria, pathological material from 281 extremity soft-tissue sarcomas (STS) was reviewed. The cases were originally diagnosed between 1972 and 1994, and the most frequent diagnoses then were malignant fibrous histiocytoma (MFH) (26%), liposarcoma (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the proportions had changed significantly, with the largest group now being leiomyosarcomas (20%), liposarcomas (17%), synovial sarcomas (14%), and sarcomas "not otherwise specified" (NOS) (11%). The original diagnosis was changed in 57% of the cases; in particular, the number of fibrosarcomas was reduced from 32 to 6, and MFHs from 72 to 2, with 22 renamed as myxofibrosarcomas; 20 (7%) were found not to be sarcomas. The main reasons for these results are the recent advances in immunohistochemistry (IHC) together with changes in nomenclature. The findings have obvious implications, in particular for retrospective research. PMID:14962721

Daugaard, S

2004-03-01

280

Paratesticular sarcomas: two cases with different evolutions.  

PubMed

Paratesticular sarcomas are rare and account for less than 1% of all adult sarcomas. Intrascrotal tumours can be testicular or paratesticular, paratesticular tumours being rarer (7-10%). Only 30% of paratesticular tumours are malignant and 90% of these are sarcomas. Histological subtypes include leiomyosarcoma, rhabdomyosarcoma, liposarcoma and undifferentiated high-grade pleomorphic sarcoma. Recurrence is frequent in this type of tumour and can occur years from initial diagnosis. These reports show two cases of paratesticular sarcoma with very distinct evolutions. The first case concerns a patient who presented with low-grade leiomyosarcoma with two local recurrences treated with surgery, and distance recurrence with cutaneous, subcutaneous, pulmonary and hepatic metastasis 30?years after surgery of the primary tumour. The second case reports of a patient who presented with high-grade myxoid liposarcoma with local and distance recurrence 3?years after surgery of the primary tumour, which progressed after chemotherapy; the patient died 7?months after diagnosis of recurrence. PMID:25145896

Matias, Margarida; Carvalho, Miguel; Xavier, Luisa; Teixeira, José Alberto

2014-01-01

281

The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma.  

PubMed

Clear cell sarcoma (CCS) is associated with the EWS/ATF1 oncogene that is created by chromosomal fusion of the Ewings Sarcoma oncogene (EWS) and the cellular transcription factor ATF1. The melanocytic character of CCS suggests that the microphthalmia-associated transcription factor (Mitf), a major inducer of melanocytic differentiation, may be miss-expressed in CCS. Accordingly, we show that the mRNA and protein of the melanocyte-specific isoform of Mitf (Mitf-M) are present in several cultured CCS cell lines (Su-ccs-1, DTC1, Kao, MST-1, MST-2 and MST-3). The above cell lines thus provide a valuable experimental resource for examining the role of Mitf-M in both CCS and melanocyte differentiation. Melanocyte-specific expression of Mitf-M is achieved via an ATF-dependent melanocyte-specific cAMP-response element in the Mitf-M promoter, and expression of Mitf-M in CCS cells suggests that EWS/ATF1 (a potent and promiscuous activator of cAMP-inducible promoters) may activate the Mitf-M promoter. Surprisingly, however, the Mitf-M promoter is not activated by EWS/ATF1 in transient assays employing CCS cells, melanocytes or nonmelanocytic cells. Thus, our results indicate that Mitf-M promoter activation may require an appropriate chromosomal context in CCS cells or alternatively that the Mitf-M promoter is not directly activated by EWS/ATF1. PMID:12966428

Li, K K C; Goodall, J; Goding, C R; Liao, S-K; Wang, C-H; Lin, Y-C; Hiraga, H; Nojima, T; Nagashima, K; Schaefer, K-L; Lee, K A W

2003-09-15

282

ESF-EMBO Symposium “Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence” Sept 29–Oct 4, Polonia Castle Pultusk, Poland  

PubMed Central

Rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are among the most common pediatric sarcomas (Arndt et al., 2012). Despite sarcomas representing a highly heterogeneous group of tumors, ES and alveolar RMS (ARMS) typically share one common genetic characteristic, namely a specific chromosomal translocation (Helman and Meltzer, 2003; Lessnick and Ladanyi, 2012). These translocations generate fusion proteins, which are composed of two transcription factors (TF). Typically, one TF is a developmentally regulated factor that is essential for proper specification of a given lineage and provides the DNA-binding domain, while the partner TF contributes a transactivation domain that drives aberrant expression of target genes. Based on these common genetic characteristics, the first ESF-EMBO research conference entitled “Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence” with special focus on RMS and ES was held at the Polonia Castle in Pultusk, Poland. The conference gathered 70 participants from more than 15 countries and several continents representing most research groups that are active in this field. PMID:23761860

Schäfer, Beat W.; Koscielniak, Ewa; Kovar, Heinrich; Fulda, Simone

2013-01-01

283

Durable remissions are rare following high dose therapy with autologous stem cell transplantation for adults with "paediatric" bone and soft tissue sarcomas.  

PubMed

BACKGROUND: The role of high dose therapy (HDT) with autologous stem cell transplantation (AuSCT) for the treatment of bone and soft tissue sarcomas remains investigational. There are few reports examining this strategy focusing on the adult population. METHODS: We retrospectively reviewed our experience of adult patients undergoing HDT and AuSCT for 'paediatric' sarcomas. RESULTS: A total of 17 patients (14 male, 3 female) with median age at transplant of 24 years (range 20 - 41) were identified. The diagnosis was Ewings sarcoma/PNET (10), osteosarcoma (5) and rhabdomyosarcoma (2). Status prior to HDT, following conventional-dose chemotherapy +/- surgery +/- radiotherapy, was complete remission (CR) (6), partial remission (PR) (6), stable disease (1) and progressive disease (4). There was no transplant-related mortality. Two patients remain disease free beyond four years and both received HDT as part of their primary therapy (CR1 and PR1) however, the median progression free survival and overall survival following AuSCT for the entire cohort was only 7 months (range: 2-92 months) and 13 months (range: 2 - 92 months), respectively. CONCLUSION: HDT and AuSCT infrequently achieves prolonged remissions in adult patients and should only be considered in patients who are in a PR or CR following conventional-dose therapy. Further studies are required to define the role of HDT with AuSCT for adult patients with sarcoma. PMID:15927067

Nath, Shriram V; Prince, H Miles; Choong, Peter Fm; Toner, Guy C

2005-05-31

284

Neuronal Differentiation of Synovial Sarcoma and Its Therapeutic Application  

Microsoft Academic Search

Synovial sarcoma is a rare sarcoma of unknown histologic origin. We previously reported the gene expression profile of synovial\\u000a sarcoma was closely related to that of malignant peripheral nerve sheath tumors, and the fibroblast growth factor (FGF) signal\\u000a was one of the main growth signals in synovial sarcoma. Here we further demonstrate the neural origin of synovial sarcoma\\u000a using primary

Tatsuya Ishibe; Tomitaka Nakayama; Tomoki Aoyama; Takashi Nakamura; Junya Toguchida

2008-01-01

285

Kaposi sarcoma in unusual locations  

PubMed Central

Kaposi sarcoma (KS) is a multifocal, vascular lesion of low-grade malignant potential that presents most frequently in mucocutaneous sites. KS also commonly involves lymph nodes and visceral organs. This article deals with the manifestation of KS in unusual anatomic regions. Unusual locations of KS involvement include the musculoskeletal system, central and peripheral nervous system, larynx, eye, major salivary glands, endocrine organs, heart, thoracic duct, urinary system and breast. The development of KS within wounds and blood clots is also presented. KS in these atypical sites may prove difficult to diagnose, resulting in patient mismanagement. Theories to explain the rarity and development of KS in these unusual sites are discussed. PMID:18605999

Pantanowitz, Liron; Dezube, Bruce J

2008-01-01

286

Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery  

ClinicalTrials.gov

Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

2013-12-10

287

Tyrosine kinase inhibitors in treating soft tissue sarcomas: sunitinib in non-GIST sarcomas  

Microsoft Academic Search

Sarcomas are uncommon malignancies that represent more than 50 different tumor types. Surgery remains the mainstay of treating\\u000a localised disease. Anthracycline and ifosfamide-based chemotherapy is an option for advanced disease; however, effective treatment\\u000a of advanced soft tissue sarcoma remains a challenge. Advances in understanding the genetic nature of cancer have led to the\\u000a development of new treatment options for sarcoma.

Blanca Homet Moreno; Elena Garralda Cabanas; Ricardo Hitt

2010-01-01

288

Synovial Sarcoma of the Abdominal Wall  

PubMed Central

A case report is presented of a synovial sarcoma arising in the abdominal wall. This is the seventh such case to be reported. A brief review of the clinical and pathological features of synovial sarcoma is made. Pre-operative diagnosis of an abdominal wall synovial sarcoma is virtually impossible, but should be considered when a soft tissue swelling is found to show amorphous stippled calcification on X-ray. ImagesFig. 1Figs. 2-3Figs. 4-5 PMID:4319939

Hale, J. E.; Calder, I. M.

1970-01-01

289

Primary Undifferentiated Penile Sarcoma in Adolescence  

PubMed Central

We report a case of primary penile undifferentiated sarcoma. A 16-year-old adolescent man visited Pusan National University Hospital complaining of a painless mass on his penis that was increasing in size. Magnetic resonance images revealed a 5×5-cm mass and pathological examinations revealed small round cell sarcomas with neuroendocrine differentiation. The tumor, which had metastatic pulmonary nodules, was treated by tumorectomy and systemic chemotherapy. Thirty-four months after the initial diagnosis, the patient was still alive without evidence of local recurrence or metastatic disease. This is our second case of an undifferentiated penile sarcoma. PMID:23136636

Choi, Young Hoon; Kim, Hyeon Woo; Ahn, Jae Hyun; Hwang, Dae Sung; Lee, Jung Woo; Lee, Byung Ki; Jun, So Eun; Lim, Young Tak; Lee, Sang Don

2012-01-01

290

Alveolar soft part sarcoma causing perianal abscess.  

PubMed

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

Sullivan, Niall; McCulloch, Tom; Leverton, David

2011-07-01

291

Airspace effects on the yield and quality of ewe milk.  

PubMed

Three groups of 12 midlactating Comisana ewes were housed in separate rooms of the same building and assigned to treatments of low (LV, 4.1 m3), medium (MV, 5.6 m3), or high (HV, 7.3 m3) airspace/animal. The concentrations of airborne microorganisms in the experimental rooms were measured twice weekly at 0930 and 1630. Ewe milk yield was recorded daily. Individual milk samples were analyzed weekly for milk composition, coagulating properties, somatic cell concentration (SCC), and polymorphonuclear neutrophil leukocyte count (PMNLC), and fortnightly for bacteriological characteristics; samples with more than 10(6) somatic cells/ml were cultured for mastitis-related pathogens. The LV and MV treatments resulted in higher relative humidity and air concentrations of staphylococci than the HV treatment. Greater amounts of air mesophilic bacteria were also found in the LV than in the HV room. Ewes in the HV group gave greater yields of milk than those in the LV and MV groups. LV milk also had a lower casein content than HV milk. Significant interactions of treatment x time were found for milk protein and fat content as well as for clotting time and clot firmness, with LV milk having the poorest composition and deteriorated renneting ability during the last 3 wk of the trial. The HV ewes had lower SCC and PMNLC and psychrotroph counts in their milk than LV and MV ewes and smaller amounts of mesophilic bacteria and fecal coliforms than LV animals. Subclinical mastitis occurred in two ewes of the LV and one of the MV groups, while no cases were recorded in the HV group. Results suggest that airspace is a critical factor in dairy sheep housing and indicate that a volume allocation of less than 7 m3/animal may adversely affect the performance and health of the lactating ewe. PMID:11814019

Sevi, A; Taibi, L; Albenzio, M; Annicchiarico, G; Muscio, A

2001-12-01

292

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

Microsoft Academic Search

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

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

2009-01-01

293

Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas.  

PubMed

Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation. PMID:21896345

Baird, Kristin; Fry, Terry J; Steinberg, Seth M; Bishop, Michael R; Fowler, Daniel H; Delbrook, Cynthia P; Humphrey, Jennifer L; Rager, Alison; Richards, Kelly; Wayne, Alan S; Mackall, Crystal L

2012-05-01

294

The Effect of Protein Level On Feedlot Performance And Carcass Characteristics Of Texas Rambouillet Ewes  

Microsoft Academic Search

Aged Rambouillet ewes, 5 to 7 years old, are usually culled in Texas. Some producers have chosen to feed their aged ewes high energy diets, a feedlot practice, before they send them to harvest. This practice may prove to be profitable as the ewes will gain extra weight and bring more money at sale time. Research on the feedlot performance

Norberto Mendoza Jr.; Brian J. May; Michael W. Salisbury; Gil R. Engdahl

2007-01-01

295

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

E-print Network

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

Lazzaro, Brian

296

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

297

DETECTION OF PREGNANCY IN EWES WITH THE U LTRASON IC SCANOPR EG 1,2  

Microsoft Academic Search

Summary The accuracy of the ultrasonic Scanopreg was evaluated in tests with 25 commercials, West Virginia ewe flocks. Two Scanopreg units were used to check for pregnancy in 1,644 ewes that had been exposed to rams during the faU breeding season. Predictions were compared against lambing records. Possible accuracy errors were: type 1 (ewes diagnosed pregnant but failed to lamb)

P. E. Lewis

2010-01-01

298

Effects of essential oils on milk production, milk composition, and rumen microbiota in Chios dairy ewes  

Microsoft Academic Search

The effect of the addition of an essential oil (EO) preparation (containing a mixture of natural and nature-identical EO) on the performance of dairy ewes of the Chios breed was investigated. Eighty lactating ewes were allocated into 4 equal groups in a randomized block design, each with 4 replicates of 5 ewes housed in the same pen. The 4groups were

I. Giannenas; J. Skoufos; C. Giannakopoulos; M. Wiemann; O. Gortzi; S. Lalas; I. Kyriazakis

2011-01-01

299

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.

300

Biphasic synovial sarcoma in mandibular region  

PubMed Central

The term synovioma was coined by Smith in 1927, and later in 1936 Knox suggested the name synovial sarcoma. It occurs primarily in the paraarticular regions, usually in close association with tendon sheaths, bursae, and joint capsules. On rare occasions it may be seen in areas without any apparent relationship to synovial structures as in parapharyngeal region or the abdominal cavity. The first description of synovial sarcoma in the head and neck region was by Pack and Ariel in 1950. The majority of these tumors seem to take origin from paravertebral connective tissue spaces and manifest as solitary retropharyngeal or parapharyngeal masses near the carotid bifurcation. Synovial sarcoma has been reported in soft palate, tongue, maxillofacial region, angle of mandible, sternoclavicular region, scapular region, and the esophagus. We report a case of 28-year-old male patient with synovial sarcoma in mandibular region with biphasic pattern. PMID:22529590

Wadhwan, Vijay; Malik, Sangeeta; Bhola, Nitin; Chaudhary, Minal

2011-01-01

301

Primary clear cell sarcoma of the tongue.  

PubMed

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

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

2013-11-01

302

General Information about Childhood Soft Tissue Sarcoma  

MedlinePLUS

... tissue sarcoma include having the following inherited disorders: Li-Fraumeni syndrome . Neurofibromatosis type 1 (NF1). Familial adenomatous ... clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. If these tests ...

303

Kaposi’s Sarcoma and the Lymphatics  

Microsoft Academic Search

Kaposi’s sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS). KS presents as multifocal, angiogenic\\u000a lesions involving an inflammatory infiltrate and KSHV-infected spindle cells display characteristic markers of lymphatic endothelia.\\u000a The precise origin of the spindle cell component of KS lesions is uncertain and may derive from the reprogramming of the transcriptome\\u000a of endothelial cells or their precursors

Victoria Emuss; Chris Boshoff

304

Technetium scanning in Kaposi's sarcoma and its simulators  

SciTech Connect

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.

Gunnoe, R.; Kalivas, J.

1982-04-01

305

Detection of fusion gene transcripts in fresh-frozen and formalin-fixed paraffin-embedded tissue sections of soft-tissue sarcomas after laser capture microdissection and rt-PCR.  

PubMed

The diagnosis of small round cell sarcomas is often very difficult, especially when only small biopsy specimens are available for examination. Recent studies have shown that some sarcomas have specific recurrent chromosomal translocations producing chimeric gene fusions, which can be detected by reverse transcription-polymerase chain reaction (RT-PCR), fluorescent in situ hybridization (FISH), or cytogenetic analysis. In this study, 12 cases of well-defined sarcomas including Ewings sarcoma/primitive neuroectodermal tumors (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumors (DSRCT) were used to collect specific numbers of cells by laser capture microdissection (LCM), subsequently used for RT-PCR to detect specific chimeric gene transcripts. Tumor cells from fresh-frozen (FS) tissue sections and paraffin-embedded (PS) tissue sections from the same cases were compared directly to evaluate the sensitivity of FS and PS sections as the starting material for analysis. Samples were used for RNA extraction, RT-PCR analysis, and Southern hybridization with fluorescein-labeled internal probes followed by enhance chemiluminescence (ECL) detection. The fusion gene transcripts could be detected using 50 cells from FS materials in all cases and from 1 cell in 9 of 12 cases. For PS, a positive signal could be detected using 200 to 1000 cells in all cases, while weaker signals were detected using 50 cells in most cases. These results indicate that the fusion gene products from small round cell sarcomas can be detected by RT-PCR with 10 to 200 cells from FS and PS tissues. The sensitivity of RT-PCR with FS was 10- to 50-fold greater than with PS. These results also suggest that RT-PCR analysis for sarcoma fusion gene products can be successfully performed when only a few cells are available for analysis, although this is not recommended for routine clinical use. PMID:14639108

Jin, L; Majerus, J; Oliveira, A; Inwards, C Y; Nascimento, A G; Burgart, L J; Lloyd, R V

2003-12-01

306

Yeasts associated with Sardinian ewe's dairy products.  

PubMed

In the present work, the occurrence of yeasts in different types of typical Sardinian ewe's cheeses (32 samples of pecorino, 32 of caciotta, 40 of feta, 56 of ricotta) was determined. For the strains isolated the following properties were studied: proteolytic and lipolytic activities, the ability to grow at different temperatures, different concentrations of salt, and to assimilate and/or ferment compounds like lactate, citrate, lactose, glucose, galactose, lactic acid. Of 160 samples analysed, 76.2% yielded growth of yeasts. Yeast counts showed a certain variability among the samples. The highest levels were observed in caciotta and feta cheeses. A total of 281 strains belonging to 16 genera and 25 species were identified. In general, Debaryomyces hansenii was the dominant species, representing 28.8% of the total isolates. Other frequently appearing species were Geotrichum candidum, Kluyveromyces lactis and K. marxianus. Other genera encountered were Pichia, Candida, Dekkera, Yarrowia and Rhodotorula. With regard to the biochemical and technological properties of the yeasts, only K. lactis, K. marxianus and Dek. anomala assimilated and fermented lactose, whereas the majority of the species assimilated lactic acid. The assimilation of citrate was a characteristic of D. hansenii, R. rubra and Y. lipolytica. On the whole, the yeasts were weakly proteolytic while lipolytic activity was present in several species. A high percentage of strains showed a certain tolerance to low temperatures while only some strains of D. hansenii and K. lactis were able to grow at a 10% NaCl concentration. PMID:11589560

Cosentino, S; Fadda, M E; Deplano, M; Mulargia, A F; Palmas, F

2001-09-19

307

Maurice Ewing Medalist: Xavier Le Pichon  

NASA Astrophysics Data System (ADS)

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.

Ewing, John I.; Le Pichon, Xavier

1984-04-01

308

Rhodotorula minuta fungemia in a ewe lamb.  

PubMed

An 8-month-old crossbred ewe, normal upon physical examination, was humanely euthanized for tissue collection. After approximately 3 weeks in tissue culture, fungi began budding out of cells obtained from the choroid plexus. After an additional 3 weeks, budding was observed in kidney cell cultures and eventually in monocyte cultures as well. Serum from the lamb was submitted to the Veterinary Diagnostic Laboratory at Colorado State University for fungal diagnosis and was found negative for Aspergillus, Blastomyces, Coccidioidomycosis and Histoplasmosis. DNA was isolated from fungi collected from tissue culture supernatants and used in a set of pan-fungal PCR assays with DNA from Candida acting as a positive control. PCR products were sequenced and BLAST analysis performed. The unknown fungal sequence aligned with 100% identity to Rhodotorula minuta an emerging opportunistic pathogen. Samples were submitted to The Fungal Testing Laboratory at The University of Texas Health Science Center at San Antonio for additional validation. We believe this to be the first report of Rhodotorula fungemia in a sheep in the United States. PMID:23347360

Chitko-McKown, C G; Leymaster, K A; Heaton, M P; Griffin, D D; Veatch, J K; Jones, S A; Clawson, M L

2014-12-01

309

Sarcoma botryoides in an infant.  

PubMed

A 17-month-old girl with no medical history presented at our emergency room with abnormal vaginal bleeding and vaginal tissue loss with a "grape bunch" appearance. Physical examination showed no abnormalities, but gynaecological examination showed abnormal vaginal tissue protruding through the vagina introitus. Given the typical clinical presentation, the age of the girl and the location and aspect of the lesion, there was a high suspicion of the botryoid variant of embryonal rhabdomyosarcoma of the vagina. Histology of a biopsy of the lesion was consistent with embryonal rhabdomyosarcoma. As no metastases were detected, the girl received chemotherapy. This case report describes the importance of early recognition of the typical clinical symptoms of sarcoma botryoides, since a rapid diagnosis followed by treatment is necessary to prevent death. PMID:25519859

van Sambeeck, S J; Mavinkurve-Groothuis, Amc; Flucke, U; Dors, N

2014-01-01

310

New Therapeutic Targets in Soft Tissue Sarcoma  

PubMed Central

Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

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

2012-01-01

311

Application of Proteomics to Soft Tissue Sarcomas  

PubMed Central

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

Kondo, Tadashi; Kubota, Daisuke; Kawai, Akira

2012-01-01

312

New therapeutic targets in soft tissue sarcoma.  

PubMed

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

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

2012-05-01

313

Protection of Ewing’s sarcoma family tumor (ESFT) cell line SK-N-MC from betulinic acid induced apoptosis by ?- dl-tocopherol  

Microsoft Academic Search

Betulinic acid (BA) is known to induce apoptosis in melanoma neuroectodermal and malignant brain cancer cell lines. Present report describes the role of antioxidants on the BA-induced toxicity to human cell line SK-N-MC. Hydrophilic antioxidants viz., l-ascorbic acid (VitC) and N-acetyl-l-cysteine (l-NAC) had no protective effect on BA-induced apoptosis at the maximal concentrations tested. The lipophilic antioxidant, ?-dl-tocopherol (VitE) showed

D. V. Raghuvar Gopal; A. A. Narkar; Y. Badrinath; K. P. Mishra; D. S. Joshi

2004-01-01

314

Prognostic factors in localized Ewing's tumours and peripheral neuroectodermal tumours: the third study of the French Society of Paediatric Oncology (EW88 study)  

PubMed Central

Purpose: (1) To improve survival rates in patients with Ewing's sarcoma (ES) or peripheral neuroectodermal tumours (PNET) using semi-continuous chemotherapy and aiming to peform surgery in all; (2) To identify early prognostic factors to tailor therapy for future studies. Patients and methods One hundred and forty-one patients were entered onto the trial between January 1988 and December 1991. Induction therapy consisted of five courses of Cytoxan, 150?mg/m2 × 7 days, followed by Doxorubicin, 35?mg/m2 i.v on day 8 given at short intervals. Surgery was recommended whenever possible. The delivery of radiation therapy was based on the quality of resection and the histological response to CT. Maintenance chemotherapy consisted of vincristine + actinomycin and cytoxan + doxorubicin. The total duration of therapy was 10 months. Results After a median follow-up of 8.5 years, the projected overall survival at 5 years was 66% and disease-free survival (DFS) was 58%. In patients treated by surgery, only the histological response to CT had an influence on survival: 75% DFS for patients with a good histological response (less than 5% of cells), 48% for intermediate responders and only 20% for poor responders (? 30% of cells), P < 0.0001. The initial tumor volume by itself had no influence on DFS in these patients. In contrast, the tumour volume had a strong impact on DFS in patients treated by radiation therapy alone. Age had no impact on outcome. Conclusion Therapeutic trials for localized Ewing's sarcoma should be based on the histological response to chemotherapy or on the tumour volume according to the modality used for local therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11742482

Oberlin, O; Deley, M C Le; Bui, B N'Guyen; Gentet, J C; Philip, T; Terrier, P; Carrie, C; Mechinaud, F; Schmitt, C; Babin-Boillettot, A; Michon, J

2001-01-01

315

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 ... develop. In areas of the world (such as Africa) where KSHV and HIV infection rates are high, ...

316

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 ...

317

Soft tissue sarcomas: pattern diagnosis or entity?  

PubMed

Soft tissue sarcomas (STS) are a diverse and heterogeneous group of tumours. The sub-classification of these tumours is of importance for both prognosis and treatment. Classically, sub-categorization is based purely on histomorphological grounds, but as new techniques evolve, a more conclusive and accurate diagnosis can be made. This study describes the prevalence of soft tissue sarcomas in adults diagnosed at The Aga Khan University Hospital (AKUH) and the impact of immunohistochemistry (IHC) on the precise sub-categorization of these tumours. The study included 364 adults (age 16+) who were diagnosed as soft tissue sarcoma in the past six years (May 1991-July 1997) at the Histopathology lab of the AKUH. Where indicated, tumours were stained with a panel of antibodies using the PAP technique. Of these, 237 (65%) were male and 127 (35%) were female. The median age at which all sarcomas were diagnosed was 39.5 years. The most common site was the lower extremity (29%). The most frequently diagnosed sarcoma was leiomyosarcoma (13%), followed by malignant nerve sheath tumour (12%), rhabdomyosarcoma (10%) and liposarcoma (10%). Cases were further analyzed by dividing them into two groups, each group comprised of all sarcomas diagnosed during the specified period. In the period 1991-1994, only 16% of cases were further analyzed using IHC, while in the period 1995-1997, IHC was performed on 59% of cases. In the 1991-1994 group, a conclusive diagnosis was made in 57% of the cases and in the 1995-1997 group in 78%. A Chi-square test was performed, which proved that these results were statistically significant. Soft tissue sarcoma is one of the key areas in surgical pathology where immunohistochemistry plays an important role in both precise diagnosis and sub-categorization. PMID:10028795

Talati, N; Pervez, S

1998-09-01

318

Behavioral and endocrine responses of hair sheep ewes exposed to different mating stimuli around estrus.  

PubMed

Hair sheep ewes were used to evaluate the influence of various levels of mating stimuli on the duration and timing of estrus and LH concentrations around estrus. Ewes were treated with PGF2alpha (15 mg, im) 10 d apart. At the time of the second PGF2alpha treatment (Day 0) ewes were placed in groups and exposed to different types of mating stimuli. One group of ewes (n = 16) was exposed to an epididymectomized ram (RAM), a second group of ewes (n = 16) was exposed to an epididymectomized ram wearing an apron to prevent intromission (APRON) and a third group of ewes (n = 17) was exposed to an androgenized ovariectomized ewe (T-EWE). Jugular blood samples were collected from ewes at 6-h intervals through Day 5. Plasma was harvested and LH concentration was determined by RIA. The ewes were observed at 6-h intervals to detect estrus. A ewe was considered to be out of estrus when she no longer stood to be mounted by the teaser animal. There was no difference (P > 0.10) in the proportion of ewes expressing estrus (79.6%) or having an LH surge (85.7%) among the treatments. Neither the time to estrus nor the duration of estrus were different (P > 0.10) among APRON, RAM or T-EWE groups (41.6+/-3.8 vs 43.6+/-3.6 vs 46.1+/-3.6 h, respectively, and 26.5+/-2.2 vs 24.8+/-2.3 vs 30.5+/-2.2 h, respectively). The time to LH surge was similar (P > 0.10) among APRON, RAM and T-EWE groups (51.2+/-4.5 vs 51.2+/-4.7 vs 52.7+/-4.5 h, respectively). The magnitude of the LH surge was similar (P > 0.10) in the T-EWE, APRON and RAM ewes (99.7+/-4.9 vs 87.2+/-4.9 vs 85.8+/-5.0 ng/mL, respectively). The time from estrus to the LH surge was not different (P > 0.10) among APRON, RAM or T-EWE ewes (10.1+/-2.2 vs 9.8+/-2.3 vs 11.6+/-2.3 h, respectively). These results show that the expression and duration of estrus are not influenced by different types of mating stimuli in hair sheep ewes. In addition, the timing and the magnitude of LH release does not appear to be influenced by mating stimuli around the time of estrus. PMID:11291911

Godfrey, R W; Collins, J R; Hensley, E L

2001-03-01

319

Immunoglobulin G Locus Events in Soft Tissue Sarcoma Cell Lines  

Microsoft Academic Search

Recently immunoglobulins (Igs) have been found to be expressed by cells other than B lymphocytes, including various human carcinoma cells. Sarcomas are derived from mesenchyme, and the knowledge about the occurrence of Ig production in sarcoma cells is very limited. Here we investigated the phenomenon of immunoglobulin G (IgG) expression and its molecular basis in 3 sarcoma cell lines. The

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

2011-01-01

320

Primary osteogenic sarcoma of the mediastinum  

PubMed Central

Ikeda, T., Ishihara, T., Yoshimatsu, H., Kikuchi, K., Murakami, M., Kobayashi, K., Inoue, H., and Kasahara, M. (1974). Thorax, 582-588. Primary osteogenic sarcoma of the mediastinum. A 22-year-old man with primary osteogenic sarcoma of the superior mediastinum is reported. This case is the second instance of primary osteogenic sarcoma of the mediastinum and the first case of superior mediastinal origin to be reported. The patient had local recurrence one year after the first operation. After resection of the recurrent tumour with left upper lobectomy and partial pericardectomy followed by radiation, he has been well for more than five years without recurrence. Extraosseous osteogenic sarcoma of soft tissue is very rare and has been reported in 103 patients. The five-year survival of patients with extraosseous osteogenic sarcoma is 22·4%. The distribution and prognosis of this tumour are similar to those of rhabdomyosarcoma in soft tissue. Primary amputation or wide excision is the treatment of choice. Images PMID:4530480

Ikeda, Takaaki; Ishihara, Tsuneo; Yoshimatsu, Hiroshi; Kikuchi, Keiichi; Murakami, Masaru; Kobayashi, Koichi; Inoue, Hiroshi; Kasahara, Masao

1974-01-01

321

William J. Jenkins Receives 2010 Maurice Ewing Medal  

NASA Astrophysics Data System (ADS)

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.”

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

2011-02-01

322

Bighorn ewes transfer the costs of reproduction to their lambs.  

PubMed

Several studies of large mammals report no direct reproductive costs for females. Individual heterogeneity may hide fitness costs of reproduction, but mothers could also transfer some costs to their offspring. Using data on 442 lambs weaned by 146 bighorn sheep (Ovis canadensis) ewes at Ram Mountain, Alberta, we studied how reproductive effort varied with environmental and maternal conditions. During summer, lactating ewes should gain enough mass to survive the winter and to support their next gestation, while nursing their current lamb. We measured reproductive effort as summer mass gain by lambs corrected for maternal mass in June and maternal mass gain during summer. Females lowered their reproductive effort when population density increased and if they had weaned a lamb the previous year. A reduction in reproductive effort led to lower winter survival by lambs. Bighorn ewes have a conservative reproductive tactic and always favor their own body condition over that of their lambs. When resources are limited, ewes appear to transfer reproductive costs to their lambs, as expected from the much greater relative fitness consequences of a reduction in maternal than in offspring survival. PMID:20735260

Martin, Julien G A; Festa-Bianchet, Marco

2010-10-01

323

Ellen Thomas Receives 2012 Maurice Ewing Medal: Response  

NASA Astrophysics Data System (ADS)

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.

Thomas, Ellen

2013-01-01

324

Induction of cervical dilation for transcervical embryo transfer in ewes  

PubMed Central

Background A major limitation in the application of assisted reproductive technologies in sheep arises from the inability to easily traverse the uterine cervix. The cervix of the non-pregnant ewe is a narrow and rigid structure, with 5–7 spiral folds and crypts that block its lumen. The first two folds closest to the vagina appear to be the greatest obstacle for the instrument insertion into the sheep cervix. Therefore, the dilation of the distal part of the cervix could provide the conformational change necessary to perform non-invasive transcervical procedures. The present study set out to assess the efficacy of Cervidil®, a patented dinoprostone (PgE2)-containing vaginal insert with a controlled-release mechanism, to safely induce sufficient cervical dilation for the purpose of transcervical embryo transfer (TCET) in cyclic ewes. Methods The transfer of frozen-thawed ovine embryos was attempted in 22 cross-bred Rideau Arcott x Polled Dorset ewes, with or without the pre-treatment with Cervidil® for 12 or 24 h prior to TCET. Results Cervical penetration rate was significantly improved after Cervidil® pre-treatment, with 55% (6/11) of treated versus 9% (1/11) of control animals successfully penetrated (?2-test, p?ewes that were penetrated, 67% (4/6) had been exposed to Cervidil(R) for 24 h and 33% (2/6) had had a 12-h exposure (p?>?0.05). Variations in the age, weight, genotype, parity, lifetime lamb production (LLP) and post-partum interval (PPI) between penetrated and non-penetrated ewes were not significant (p?>?0.05). The time taken to traverse the uterine cervix was negatively correlated (p?ewes, but no fetuses were detected ultrasonographically 55 days post-TCET. Conclusions The present results indicate a significant benefit of using Cervidil® for inducing cervical dilation during the mid-luteal phase in ewes but the reason(s) for impaired fertility after the transfer of frozen-thawed ovine embryos remains to be elucidated. PMID:24467737

2014-01-01

325

Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma  

ClinicalTrials.gov

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

2014-09-08

326

Progesterone administration reduces the behavioural and physiological responses of ewes to abrupt weaning of lambs.  

PubMed

Abrupt weaning, a usual management in sheep productive systems, may provoke behavioural and physiological responses indicative of stress in ewes and lambs. Progesterone (P4) has anxiolytic and sedative effects through the union of its metabolites that contain 3?-hydroxyl group to the ?-aminobutyricacidA receptor. Our first aim was to determine whether P4 administration reduces the behavioural and physiological responses of ewes to abrupt weaning of lambs. A complementary aim was to determine whether P4 treatment affects the milk yield and composition of ewes, and the BW of their lambs. In experiment 1, seven ewes received P4 treatment for 32 days (group E1-P4), and eight ewes remained as an untreated control group (group E1-C). BW of the lambs was recorded during P4 treatment. Lambs were weaned at 59 days (Day 0 = weaning). The main behaviours of the ewes before and after weaning were recorded using 10 min scan sampling. The ewes' serum total protein, albumin and globulin concentrations were measured before and after weaning of the lambs. In experiment 2, milk yield and composition were determined in two different groups of six ewes treated with P4 (group E2-P4) for 16 days and in five untreated controls (group E2-C). The BW of lambs increased with time (P = 0.001) in both groups and did not differ. The percentage of observations in which the ewes were seen pacing on Day 0 was greater in the E1-C group than in the E1-P4 group (P = 0.0007). Similarly, the percentage of observations in which the ewes were recorded vocalizing on Day 0 was greater in the E1-C group than in the E1-P4 group (P = 0.04). The percentage of observations in which E1-C ewes were recorded lying did not change from Days 0 to 1; however, it increased in E1-P4 ewes. Total serum protein concentration did not change in E1-P4 ewes from Days 0 to 3, although a decrease was seen in E1-C ewes (P = 0.04). Serum globulin concentration was greater in E1-P4 ewes on Day 3 than in E1-C ewes (P = 0.0008). In experiment 2, there were no differences between E2-P4 and E2-C ewes in terms of milk yield, protein, fat and lactose content. Progesterone administration reduced the behavioural and physiological responses of ewes to abrupt weaning of lambs, and this effect was not mediated by changes in milk yield and composition, or by lambs' BW. PMID:23597263

Freitas-de-Melo, A; Banchero, G; Hötzel, M J; Damián, J P; Ungerfeld, R

2013-08-01

327

Effect of the addition of calcium soap to ewes' diet on fatty acid composition of ewe milk and subcutaneous fat of suckling lambs reared on ewe milk.  

PubMed

The aim of this work was to study the effect of the inclusion of calcium soap (CS) in ewes' diet on the fatty acid profile of suckling lambs. Sixty suckling lambs of three breeds (Castellana, Churra and Assaf) were divided into two equal groups. One group was fed with a diet composed of beetroot pulp, alfalfa, barley, corn, soy, cotton and 4% of CS, and the other with a control diet without CS. The fatty acid profiles of the ewe's milk samples collected on the day before slaughter and of the lamb subcutaneous fat collected from the back of the carcasses were analysed. The addition of calcium soap to the ewe's diet did not change the milk fatty acid profile but significantly increased SFA and decreased both the PUFA and MUFA levels of suckling lamb fat. PCA analysis revealed a good separation of the lamb samples according to the diet of the mothers, showing that diet is more important than breed in explaining sample variability. PMID:20374842

Lurueña-Martínez, M A; Palacios, C; Vivar-Quintana, A M; Revilla, I

2010-04-01

328

Targeting protein kinase C in sarcoma.  

PubMed

Protein kinase C (PKC) is a family of serine/threonine tyrosine kinases that regulate many cellular processes including division, proliferation, survival, anoikis and polarity. PKC is abundant in many human cancers and aberrant PKC signalling has been demonstrated in cancer models. On this basis, PKC has become an attractive target for small molecule inhibition within oncology drug development programmes. Sarcoma is a heterogeneous group of mesenchymal malignancies. Due to their relative insensitivity to conventional chemotherapies and the increasing recognition of the driving molecular events of sarcomagenesis, sarcoma provides an excellent platform to test novel therapeutics. In this review we provide a structure-function overview of the PKC family, the rationale for targeting these kinases in sarcoma and the state of play with regard to PKC inhibition in the clinic. PMID:25453364

Martin-Liberal, J; Cameron, A J; Claus, J; Judson, I R; Parker, P J; Linch, M

2014-12-01

329

Sarcomas in north west England: II. Incidence.  

PubMed Central

Incidence data on a population-based series of bone, soft tissue and visceral sarcomas from the North West of England are presented. The data are derived mainly from a total of 429 cases registered with the North Western Regional Cancer Registry and diagnosed during the period 1982-84, 76% of which were confirmed as sarcomas by a panel of five pathologists. Overall incidence of confirmed sarcomas per million person years was slightly higher in females (26.81) than in males (24.71) but there was no sex difference when 38 non-reviewed cases were taken into consideration (females 29.07, males (28.83). After exclusion of tumours of female genital tract, incidence of soft tissue tumours was very similar in both sexes (females 18.25, males 18.70). Bone tumours were almost twice as frequent in males (6.01) as in females (3.55). PMID:1662534

Hartley, A. L.; Blair, V.; Harris, M.; Birch, J. M.; Banerjee, S. S.; Freemont, A. J.; McClure, J.; McWilliam, L. J.

1991-01-01

330

Plasma Cell Sarcoma in a Cat  

PubMed Central

Lytic lesions occurring in conjunction with plasma cell sarcoma (multiple myeloma) have rarely been reported in cats. A plasma cell sarcoma was diagnosed in a 13 year old castrated male Siamese cat with hind limb paresis resulting from osteolysis of the second lumbar vertebra. Serum electrophoresis showed a monoclonal gammopathy. A uniform population of plasma cells was found in and around the second lumbar vertebra and in the bone marrow of the femora, humeri, pelvis and the fifth lumbar vertebra. The neoplastic cells were identified as IgA and kappa chain specific by direct immunofluorescence. ImagesFigure 2.Figure 3.Figure 4. PMID:17422518

Mitcham, S. A.; McGillivray, S. R.; Haines, D. M.

1985-01-01

331

Clinical pathological analysis of synovial sarcoma  

Microsoft Academic Search

Objective  To investigate the clinical diagnosis and differential diagnosis of synovial sarcoma (SS).\\u000a \\u000a \\u000a \\u000a Methods  A total of 41 paraffin-embedded synovial sarcoma samples were examined by H&E staining, immunohistochemistry staining and\\u000a the reverse transcriptase polymerase chain reaction (RT-PCR), in order to provide a scientific bases for diagnosis and differential\\u000a diagnosis.\\u000a \\u000a \\u000a \\u000a Results  Twelve cases were a biphasic type, 22 cases were a monophasic fibrous type,

Ling Yang; Bogen Song; zhongjie Lin; Weiming Zhang; Qinhe Fan

2007-01-01

332

Reversion of murine sarcoma virus transformed mouse cells: variants without a rescuable sarcoma virus.  

PubMed

Murine sarcoma virus transformed mouse 3T3 cells, which are negative for murine leukemia virus and which yield sarcoma virus after superinfection with murine leukenmia virus, spotaneously give rise to flat variants front which murine sarcoma virus can no longer be rescued. The revertants support leukemia viruis growth and show an enhanced sensitivity to murine sarcoma superinfection and, like normal cells, do not release RNA-dependent DNA polymerase activity. Because revertants could be obtained with high frequency from progeny of single transformed cells, each cell that containts the sarconma virus genome seems to have the capacity to suppress or eliminate an RNA tumor virus native to its species of origin. PMID:4338196

Fischinger, P J; Nomura, S; Peebles, P T; Haapala, D K; Bassin, R H

1972-06-01

333

Pazopanib Hydrochloride Followed By Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma  

ClinicalTrials.gov

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Stage IIA Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

2014-12-08

334

Normal pregnancies and live births after autograft of frozen-thawed hemi-ovaries into ewes  

Microsoft Academic Search

Objective: To evaluate long-term outcome of autotransplantation of cryopreserved hemi-ovaries into ewes.Design: Animal study.Setting: University fertility center, Hospices Civils de Lyon; and Ecole Nationale Vétérinaire de Lyon.Patients(s): Grivette ewes.Intervention(s): Six hemi-ovaries from 6 ewes aged 6 to 12 months were frozen with a slow cooling protocol using 2 M of dimethyl sulfoxide as cryoprotectant. After dissection of the medulla, the

Bruno Salle; Banu Demirci; Michel Franck; René Charles Rudigoz; Jean François Guerin; Jacqueline Lornage

2002-01-01

335

EFFECTS OF FEEDING AND MANAGEMENT SYSTEMS ON BODY WEIGHT AND REPRODUCTIVE PERFORMANCE OF BALOCHI EWES  

Microsoft Academic Search

This study was conducted to assess the performance of Balochi ewes under three management systems i.e. T1-Extensive (grazing only), T2-Semi-extensive (grazing plus daily feed supplementation for nine months @ 0.625 kg\\/ewe\\/day) and T3-Intensive (experimental ration only @ 1.5625 kg\\/ewe\\/day). Animals under T1 lost as high as 7.9 kg body weight during winter. T2 flock maintained their body weights and T3

M. MUNIR; A. W. JASRA; M. A. MIRZA

336

SECRETION OF PROSTAGLANDIN F2o~ IN CYCLING AND PREGNANT EWES 1 ,2  

Microsoft Academic Search

SUMMARY Indwelling cannulas were placed into a branch of the uterine vein and int.o the utero- ovarian vein of 10 nonpregnant ewes and into the utero-ovarian vein only of eight pregnant ewes. Blood samples were collected into chilled, heparinized tubes at 3-hr intervals from days 11 to 14 (three pregnant and five cycling ewes) or from days 14 to 17

T. M. Nett; R. B. Staigmiller; A. M. Akbar; M. A. Diekman; W. E. Ellinwood; G. D. Niswender; Fort Collins

337

Biological Therapy to Treat Kaposi Sarcoma  

Cancer.gov

Researchers with this study are investigating whether bevacizumab (Avastin®), a type of biological agent that blocks the formation and growth of new blood vessels, is effective in the treatment of Kaposi sarcoma (KS). Blood vessel cells are the main component of KS lesions.

338

Radiation therapy of retroperitoneal soft tissue sarcomas  

Microsoft Academic Search

Between 1971 and 1982, 23 patients have been treated with radiation therpy at the Massachusetts General Hospital(MGH) for retroperitoneal soft tissue sarcomas. Seventeen patients were treated with curative intent and six with palliative intent. Of the patients treated with curative intent, the 5 year actuarial survivial rate was 54% and the 5 year actuarial local control rate was also 54%.

Joel E Tepper; Herman D Suit; William C Wood; Karl H Proppe; David Harmon; Pat McNulty

1984-01-01

339

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.

340

Primary Kaposi sarcoma of the subcutaneous tissue  

Microsoft Academic Search

BACKGROUND: Involvement of the subcutis by Kaposi sarcoma (KS) occurs primarily when cutaneous KS lesions evolve into deep penetrating nodular tumors. Primary KS of the subcutaneous tissue is an exceptional manifestation of this low-grade vascular neoplasm. CASE PRESENTATION: We present a unique case of acquired immune deficiency syndrome (AIDS)-associated KS manifesting primarily in the subcutaneous tissue of the anterior thigh

Liron Pantanowitz; John Mullen; Bruce J Dezube

2008-01-01

341

CA125 Expression in Epithelioid Sarcoma  

Microsoft Academic Search

Objective: There has been no report on useful immunohistological markers for epithelioid sarcoma (ES) so far. The purpose of this study is to evaluate the positivity and specificity of CA125 as a marker for the correct diagnosis of ES. Methods: This study was performed in 11 patients with ES (nine men and two women; distal type: 10 cases; proximal type:

Hiroshi Kato; Masahito Hatori; Shoichi Kokubun; Mika Watanabe; Richard A Smith; Tetsuo Hotta; Akira Ogose; Tetsuro Morita; Takashi Murakami; Setsuya Aiba

342

Effect of supplemental yeast culture and physiological factors on colostrum and milk composition of Pelibuey ewes.  

PubMed

The effects of supplemental yeast culture, litter size, stage and number of lactation on milk composition were studied in Pelibuey ewes. Twenty ewes were randomly assigned to one of two dietary treatments. Ten control ewes grazed on guinea grass (Panicum maximum) and were supplemented with concentrate. A further ten ewes received the same diet with 14 g/head/day of yeast culture (Saccharomyces cerevisiae). Colostrum was collected within 24 h after parturition, and subsequently, milk samples were collected at fortnightly intervals (7, 21, 35, and 49 days). Total solids content averaged 32% in colostrum and 12.5% in milk. Colostrum of primiparous ewes had higher total solids content than that of ewes with more than five lactations. However, ewes with more than five lactations produced milk with higher net energy, total solids, protein, and casein than ewes with fewer lactations. Milk at 7 days had a significantly higher content of energy, total solids, and fat than milk at 21, 35, and 49 days. Total solids content was lower for ewes rearing one lamb than larger litter sizes. Supplementation with yeast culture did not affect the composition of colostrum and milk, which was mainly affected by the stage and number of lactation. PMID:22124973

Macedo, Rafael Julio; Arredondo, Victalina; García, Fernando; Aguilar, Miguel; Prado, Omar; Rodríguez, Rosario

2012-02-01

343

Influence of space allowance and housing conditions on the welfare, immune response and production performance of dairy ewes.  

PubMed

The experiment used 45 Comisana ewes, divided into 3 groups of 15. The aim was to determine the effects of two different stocking densities and two different housing conditions on welfare, and on production performance of dairy ewes. The stocking densities tested were: high stocking density (1 x 5 m2/ewe, HD group) and low stocking density (3 m2/ewe, LD group); the two housing conditions tested were: ewes housed indoors (LD group, 3 m2/ewe) and ewes allowed to use an outdoor area (LDP group, 3 m2/ewe divided into 1 x 5 m2/ewe indoors and 1 x 5 m2/ewe outdoors). At the beginning of the experiment, and then every 2 months, the cell-mediated immune status of sheep was evaluated. One month after the beginning of the experiment, and 20 d later, the ewes were injected with chicken egg albumin (OVA) to assess their humoural immune responses. Starting from the beginning of the experiment and then monthly, behavioural activities of ewes were monitored using 15-min scans. After lamb weaning, milk yield from individual ewes was measured and milk composition analysed weekly. Housing conditions (low density reared ewes indoors v. low density reared ewes with free access to an outdoor area) affected cell-mediated response, which was higher in LDP than in LD ewes. Concentrations of anti-OVA IgG were mainly influenced by space allowance, with higher antibody titres in LD than in HD ewes throughout the experiment. Both housing conditions and space allowance affected sheep behavioural activities: a greater proportion of LDP ewes displayed standing and drinking behaviours than LD ewes, and a greater proportion of LD ewes was observed walking than HD ewes. Ewes allowed access to the outdoor area had a higher protein content and lower somatic cell count in their milk, whereas reduced space allowance led to a reduction in milk yield and an increase in somatic cell count of milk. Results indicate that both increased space allowance and availability of outdoor area can improve the welfare and production performance of the lactating ewe. PMID:18922201

Caroprese, Mariangela; Annicchiarico, Giovanni; Schena, Laura; Muscio, Antonio; Migliore, Raffaella; Sevi, Agostino

2009-02-01

344

Cell cycle inhibition and apoptosis induced by curcumin in Ewing sarcoma cell line SK-NEP-1  

Microsoft Academic Search

Curcumin is a naturally occurring polyphenolic compound found in the turmeric, which is used as food additive in Indian cooking\\u000a and as a therapeutic agent in traditional Indian medicine. Curcumin is currently under investigation as a chemotherapeutic\\u000a and chemopreventive agent in adult cancer models at both pre-clinical and clinical levels. In this preliminary study, we show\\u000a that curcumin is effective

Mansher Singh; Ambarish Pandey; Collins A. Karikari; Gayatri Singh; Dinesh Rakheja

2010-01-01

345

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

ClinicalTrials.gov

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

2014-08-12

346

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

ClinicalTrials.gov

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; 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; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Hemangioendothelioma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Hemangiopericytoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

2015-01-05

347

TAG composition of ewe's milk fat. Detection of foreign fats  

Microsoft Academic Search

The TAG composition of 45 samples of ewe's milk, collected throughout the year from five Spanish breeds, was analyzed according\\u000a to their carbon number by using short capillary column GC. The TAG content had a bimodal distribution with maxima at C38 (12.8%) and C52 (8.4%). The TAG composition did not vary significantly with respect to the time of year of

Hanane Goudjil; Javier Fontecha; Ma Jesús Fraga; Manuela Juárez

2003-01-01

348

KINETICS OF EXPERIMENTAL SALMONELLA ABORTUS OVIS INFECTION IN EWES  

E-print Network

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

Paris-Sud XI, Université de

349

Impacts of Maternal Obesity on Metabolic Profiles in Postpartum Ewes  

E-print Network

and 150, glucose tolerance tests were administered to ewes. At both PPD1 and PPD150, obesity resulted in insulin resistance, impairment of whole-body glucose utilization, increased levels of circulating leptin, and altered profiles of amino acids... on testing the significant association of these guidelines to important clinical outcomes (Cedergren 2007). The majority of these studies found that weight gains within the IOM?s ranges were coupled to a better pregnancy outcome than weight gains outside...

McKnight, Jason Ray

2011-10-21

350

Fungal diversity in cow, goat and ewe milk.  

PubMed

Knowledge of fungal diversity in the environment is poor compared with bacterial biodiversity. In this study, we applied the denaturing high-performance liquid chromatography (D-HPLC) technique, combined with the amplification of the ITS1 region from fungal rDNA, for the rapid identification of major fungal species in 9 raw milk samples from cow, ewe and goat, collected at different periods of the year. A total of 27 fungal species were identified. Yeast species belonged to Candida, Cryptococcus, Debaryomyces, Geotrichum, Kluyveromyces, Malassezia, Pichia, Rhodotorula and Trichosporon genera; and mold species belonged to Aspergillus, Chrysosporium, Cladosporium, Engyodontium, Fusarium, Penicillium and Torrubiella genera. Cow milk samples harbored the highest fungal diversity with a maximum of 15 species in a single sample, whereas a maximum of 4 and 6 different species were recovered in goat and ewe milk respectively. Commonly encountered genera in cow and goat milk were Geotrichum candidum, Kluyveromyces marxianus and Candida spp. (C. catenulata and C. inconspicua); whereas Candida parapsilosis was frequently found in ewe milk samples. Most of detected species were previously described in literature data. A few species were uncultured fungi and others (Torrubiella and Malassezia) were described for the first time in milk. PMID:21944758

Delavenne, Emilie; Mounier, Jerome; Asmani, Katia; Jany, Jean-Luc; Barbier, Georges; Le Blay, Gwenaelle

2011-12-01

351

Specificity of TLE1 expression in unclassified high-grade sarcomas for the diagnosis of synovial sarcoma.  

PubMed

Expression of the transducin-like enhancer of split 1 (TLE1) by immunohistochemistry (IHC) has been widely used as a biomarker for the diagnosis of synovial sarcoma. Although TLE1 expression can be identified in more than 90% of synovial sarcomas, positive staining has been reported in up to one third of nonsynovial sarcomas, including peripheral nerve sheath tumors and neoplasms of fibrous and adipose tissues. The low specificity of this test in soft tissue tumors raises concern on its clinical application as a diagnostic biomarker. As synovial sarcoma is frequent among the differential diagnosis of unclassified high-grade sarcomas, and considering that the specificity of TLE1 antibody in this tumor group remains unclear, we evaluated TLE1 expression by IHC in 42 unclassified high-grade sarcomas. SS18 (SYT) gene break-apart analyses by fluorescence in situ hybridization were simultaneously performed as a gold standard biomarker for synovial sarcoma. Five cases that were positive for the SS18 break-apart by fluorescence in situ hybridization were also positive for TLE1 by IHC, whereas the remaining 37 cases negative for SS18 break-apart were all negative for TLE1. The results showed no evidence of nonspecific TLE1 expression in the nonsynovial high-grade sarcomas. We concluded that TLE1 is a highly specific biomarker for synovial sarcoma in the setting of differential diagnosis of unclassified high-grade sarcomas. PMID:23197007

Valente, Alfredo L; Tull, Jamie; Zhang, Shengle

2013-10-01

352

Pathogenesis of reproductive failure induced by Trypanosoma vivax in experimentally infected pregnant ewes  

PubMed Central

The present study was aimed at investigating the effect of experimental infection by Trypanosoma vivax in different stages of pregnancy, determining the pathogenesis of reproductive failure, and confirming transplacental transmission. We used 12 pregnant ewes distributed into four experimental groups: G1, was formed by three ewes infected with T. vivax in the first third of pregnancy (30 days); G2 comprised three infected ewes in the final third of pregnancy (100 days); G3 and G4 were composed of three non-infected ewes with the same gestational period, respectively. Each ewe of G1 and G2 was inoculated with 1.25 × 105 tripomastigotes. Clinical examination, determination of parasitemia, serum biochemistry (albumin, total protein, glucose, cholesterol, and urea), packed cell volume (PCV), serum progesterone, and pathological examination were performed. Placenta, amniotic fluid, blood and tissues from the fetuses and stillbirths were submitted to PCR. Two ewes of G1 (Ewe 1 and 3) presented severe infection and died in the 34th and 35th days post-infection (dpi), respectively; but both fetuses were recovered during necropsy. In G2, Ewe 5 aborted two fetuses on the 130th day (30 dpi) of pregnancy; and Ewe 6 aborted one fetus in the 140th day (40 dpi) of gestation. Ewes 2 and 4 delivered two weak lambs that died five days after birth. Factors possibly involved with the reproductive failure included high parasitemia, fever, low PCV, body score, serum glucose, total protein, cholesterol, and progesterone. Hepatitis, pericarditis, and encephalitis were observed in the aborted fetuses. The presence of T. vivax DNA in the placenta, amniotic fluid, blood, and tissues from the fetuses confirms the transplacental transmission of the parasite. Histological lesion in the fetuses and placenta also suggest the involvement of the parasite in the etiopathogenesis of reproductive failure in ewes. PMID:23289625

2013-01-01

353

Composition and sensory profiling of probiotic Scamorza ewe milk cheese.  

PubMed

The present study aimed to assess the effect of the addition of different usually recognized as probiotic bacterial strains on chemical composition and sensory properties of Scamorza cheese manufactured from ewe milk. To define the sensory profile of Scamorza cheese, a qualitative and quantitative reference frame specific for a pasta filata cheese was constructed. According to the presence of probiotic bacteria, cheeses were denoted S-BB for Scamorza cheese made using a mix of Bifidobacterium longum 46 and Bifidobacterium lactis BB-12, and S-LA for Scamorza cheese made using Lactobacillus acidophilus LA-5. The designation for control Scamorza cheese was S-CO. Analyses were performed at 15d of ripening. The moisture content of Scamorza ewe milk cheese ranged between 44.61 and 47.16% (wt/wt), showing higher values in S-CO and S-BB cheeses than in S-LA cheese; the fat percentage ranged between 25.43 and 28.68% (wt/wt), showing higher value in S-LA cheese. The NaCl percentage in Scamorza cheese from ewe milk was 1.75 ± 0.04% (wt/wt). Protein and casein percentages were the highest in Scamorza cheese containing a mix of bifidobacteria; also, the percentage of the proteose-peptone fraction showed the highest value in S-BB, highlighting the major proteolysis carried out by enzymes associated with B. longum and B. lactis strains. Texture and appearance attributes were able to differentiate probiotic bacteria-added cheeses from the untreated control product. In particular, S-BB and S-LA Scamorza cheeses showed higher color uniformity compared with S-CO cheese. Furthermore, the control cheese showed higher yellowness and lower structure uniformity than S-BB. The control product was less creamy and grainy than S-BB; conversely, the inclusion of probiotics into the cheese determined lower adhesivity and friability in S-BB and S-LA than in S-CO. This study allowed the definition of the principal composition and sensory properties of Scamorza ewe milk cheese. The specific quantitative vocabulary for sensory analysis and reference frame for assessor training also established in this study should be implemented to systematically monitor the quality of this new typology of ewe milk cheese. PMID:23522674

Albenzio, M; Santillo, A; Caroprese, M; Braghieri, A; Sevi, A; Napolitano, F

2013-05-01

354

Breast sarcoma in a pregnant patient A case report.  

PubMed

Sarcoma of the breast is a rare and heterogeneous lesion. We describe a case of a patient surgically treated for a breast lesion during pregnancy. The lesion resulted in a concentric neoplasia with the histological features of high grade sarcoma growing in a phyllodes tumor which was at the time grown in a fibroadenoma. Key words: Breast sarcoma, Non-epithelial breast tumour, Phillode, Pregnancy. PMID:23070281

Pasta, Vittorio; Amabile, Maria Ida; Bizzarri, Mariano; Monti, Massimo

2012-01-01

355

Imaging of the most frequent superficial soft-tissue sarcomas  

Microsoft Academic Search

Superficial soft-tissue sarcomas are malignant mesenchymal tumors located within the cutaneous and\\/or subcutaneous layers.\\u000a Most superficial soft-tissue sarcomas are low-grade tumors; yet, the risk of local recurrence is high, and initial wide surgery\\u000a is the main prognostic factor. Some of these superficial sarcomas may grow, following an infiltrative pattern, and their real\\u000a extent may be underestimated clinically. Imaging techniques are

Mélanie Morel; Sophie Taïeb; Nicolas Penel; Laurent Mortier; Luc Vanseymortier; Y. Marie Robin; Pierre Gosset; Anne Cotten; Luc Ceugnart

2011-01-01

356

Alveolar soft part sarcoma with breast metastases: a case report.  

PubMed

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor, accounting for <1 % of all soft tissue sarcomas. It appears mainly in young adults, has a female predominance and follows an indolent natural history. Like other sarcomas, it can metastasize to the lungs, liver, bones and the brain, but unusual sites have also been described, including the vagina, the orbit, colonic mucosa and the breast. This paper presents a case report of a 31-year-old patient with metastatic ASPS, who developed two highly vascular breast nodules that following an excisional biopsy, were shown to represent metastases from the patient's known sarcoma. PMID:23263847

Orphanos, George; Ioannidis, Georgios; Ioannou, Rena; Zouvani, Ioanna

2013-03-01

357

Primary synovial sarcoma of the uterus.  

PubMed

We report a case of a 52-year-old female with synovial sarcoma of the uterine corpus. Grossly, the partly polypoid tumor involved the endometrium with invasion into the inner half of the myometrium. Histologically, the tumor showed biphasic structure with the predominance of poorly differentiated small to medium sized round to oval cells. These cells showed high nuclear to cytoplasmic ratio and were arranged in diffuse sheets. Other component consisted of larger epitheloid cells with ample eosinophilic cytoplasm arranged in irregular nests. These cells were only present in a small amount. Immunohistochemically, the tumor cells in both components showed the expression of EMA, S-100 protein, CD99, and NSE. RT-PCR analysis showed the presence of SYT-SSX1 fusion transcript. At present, the patient shows no signs of tumor relapse 56 months after the diagnosis. To the best of our knowledge, this is the first report of synovial sarcoma arising in uterus. PMID:21491161

Dundr, Pavel; Fischerová, Daniela; Povýšil, Ctibor; Tvrdík, Daniel; Cibula, David

2012-04-01

358

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma.  

PubMed

Synovial sarcoma and malignant peripheral nerve sheath tumor pose a significant diagnostic challenge given similar histomorphology. The distinction is further complicated by similar immunophenotype and especially by occasional synovial sarcomas that present as intraneural tumors. Although the presence of a t(X;18) rearrangement or expression of TLE1 can help confirm the diagnosis of synovial sarcoma, negative results for these tests are not diagnostic of malignant peripheral nerve sheath tumor. The SOX10 transcription factor, a putative marker of neural crest differentiation, may have diagnostic utility in this differential, but immunohistochemical data are limited. The goal of the present study was to determine the diagnostic utility of SOX10 to discriminate between synovial sarcoma and malignant peripheral nerve sheath tumor. Forty-eight cases of malignant peripheral nerve sheath tumor, all from patients with documented neurofibromatosis, and 97 cases of genetically confirmed synovial sarcoma, including 4 intraneural synovial sarcomas, were immunohistochemically stained for SOX10. The stain was scored for intensity and fraction of cells staining. Thirty-two of 48 malignant peripheral nerve sheath tumors (67%) were SOX10-positive. The majority of malignant peripheral nerve sheath tumors showed ?2+ staining, but staining did not correlate with grade. By contrast, only 7/97 (7%) synovial sarcomas were SOX10-positive. Only three synovial sarcomas showed ?2+ staining but, importantly, two of these were intraneural synovial sarcoma. Therefore, SOX10 is a specific (93%), albeit not very sensitive (67%), diagnostic marker to support a diagnosis of malignant peripheral nerve sheath tumor over synovial sarcoma. Furthermore, the stain needs to be interpreted with caution in intraneural tumors in order to avoid a potential diagnostic pitfall. It remains to be determined whether SOX10-positive cells in intraneural synovial sarcoma represent entrapped Schwann cells, synovial sarcoma cells or both. PMID:23929265

Kang, Yuna; Pekmezci, Melike; Folpe, Andrew L; Ersen, Ayca; Horvai, Andrew E

2014-01-01

359

Timing the breeding season of the ewe : what is the role of daylength ?  

E-print Network

Timing the breeding season of the ewe : what is the role of daylength ? Jane E. ROBINSON F. J. Although sheep are regarded as a short-day breeding species, the reproductive period of the Suffolk ewe between the breeding season and anoestrus are not actively generated by changing ambient photoperiod

Paris-Sud XI, Université de

360

Melatonin and light treatment of ewes for autumn lambing H. WILLIAMS Sandra WARD  

E-print Network

Melatonin and light treatment of ewes for autumn lambing H. WILLIAMS Sandra WARD Kim CAIRNS Jackie II and III were group fed a diet containing melatonin and providing 3 mg/ewe at 16.00 hrs daily lowland systems of UK sheep production demands compact lambing and a high lambing percentage

Paris-Sud XI, Université de

361

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

E-print Network

to determine the effects of AMPT on the rectal temperatures of newborn lambs. Lambs were housed in environmental chambers (20'C) until time of slaughter (12 h of age). Low-Cu fed ewes had lower (P liver Cu concentrations than the high-Cu ewes (173 vs 802...

Eckert, Gregory Evan

2012-06-07

362

Ewe (for Togo). Special Skills Handbook. Peace Corps Language Handbook Series.  

ERIC Educational Resources Information Center

A book of language and cultural material for teachers and students of Ewe presents vocabulary lists and samples of Ewe language in various contexts, including letters, essays, and newspaper articles. Although not presented in lesson format, the material can be adapted by teachers or used by students for independent study. It is divided into two…

Kozelka, Paul R., Comp.; Agbovi, Yao Ete, Comp.

363

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

E-print Network

no effect on the dry matter intake, the size or the weight of the litter and the length of pregnancy. PlasmaOriginal article Iodine nutrition in ewes : effects of low to high iodine intake on iodine content, for pregnancy and lactation. In a second experiment, 3 groups of 10 nullipa- rous ewes received diets which

Boyer, Edmond

364

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

E-print Network

pregnancy 1. - Ewe body weight, uterine contents, and lamb birth weight (1) D. STERN J. H. ADLER H. TAGARI E Summary A study was made of the effects of nutritional levels in pregnant dairy ewes in which three basic (maintenance) levels and three levels of late pregnancy allowance (steaming up) were compared. During the last

Paris-Sud XI, Université de

365

RELATIONSHIP BETWEEN AGING AND NUTRITIONAL CONTROLLED GROWTH RATE ON HEAT PRODUCTION OF EWE LAMBS  

Technology Transfer Automated Retrieval System (TEKTRAN)

The objective of this study was to determine how reducing growth rate nutritionally alters the relationship between heat production per unit body weight and aging. Fasting heat production of 12 Dorset ewe lambs at 114 ± 2 d of age was determined, and ewes were assigned to treatments. Treatments co...

366

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

E-print Network

of LH and the frequency of LH pulses increased (P < 0.01) as ewe lambs matured. In the POA/Periventricular area (PEV), the number of Kiss1-expressing cells was greater (P < 0.04) in 30- and 35-wk-old than in 25-wk-old ewe lambs. In the arcuate nucleus...

Redmond, Jeremy Scott

2012-02-14

367

LOW FERTILITY IN NURSING EWES DURING THE NON-BREEDING SEASON  

E-print Network

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

Paris-Sud XI, Université de

368

Composite trait selection to improve reproduction and ewe productivity: a review  

Microsoft Academic Search

Reproductionandeweproductivityarecomplexcompositetraitsthatareinfluencedbyseveralcomponenttraits. Genetic improvement by selection for an individual component trait may not always be advantageous because adverse or neutral genetic relationships can exist among the component traits. Selection for an overall composite trait of ewe productivity, defined as litter weight weaned per ewe joined, can result in a balanced biological composite trait with favourableresponsesincomponenttraitsincludingfertility,numberoflambsborn,lambsurvival,lactationandlambgrowth. Selection for litter weight weaned may

G. D. SnowderA; N. M. FogartyB

2009-01-01

369

Study of male effect on feeding and estrus behavior of Afshari ewes.  

PubMed

This study was conducted to evaluate the male effect on the manifestation of estrus and feeding behavior of Afshari ewes during their breeding season. The study consists of 48 Afshari ewes, 3 years old, 67?±?2 kg live weight, body condition score 3, along with 10 Afshari rams. The study was for a period of 6 weeks in a complementary randomized design. Ewes were equally divided into three treatments (T1, T2, and T3) along with a control (T4) with six animals in each group. Variable factors of treatments was the distance of the ram box (from the ewes), which was determined to be the T1 (0-5 m), T2 (10-15 m), and T3 (25-30 m). Exposure of the ewes to the rams resulted in an earlier manifestation of estrus signs (p?ewes due to the distance from the rams (p?ewes from the rams significantly affected feed intake of the Afshari ewes. PMID:25315371

Asgari Safdar, Amir Hossein; Sadeghi, Ali Asghar

2015-01-01

370

Treating soft tissue sarcomas with adjuvant chemotherapy  

Microsoft Academic Search

Opinion statement  Surgery remains the cornerstone of treatment and the only curative loco-regional approach of localized resectable soft tissue\\u000a sarcoma (STS) in 2011: the usual first-line treatment is wide margin surgery plus radiotherapy, especially in the case of\\u000a primary tumors arising in the limbs. An optimal initial R0 resection is one of the most reproducible and reliable prognostic\\u000a factors for survival

Anna Patrikidou; Julien Domont; Angela Cioffi; Axel Le Cesne

2011-01-01

371

Multimodality Local Therapy for Retroperitoneal Sarcoma  

SciTech Connect

Purpose: Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival. Methods and Materials: Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era. Results: The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%). Conclusion: For retroperitoneal sarcoma, local control remains a challenge and combined-modality therapy may be associated with significant acute and late morbidity. Our patterns of failure data suggest that improvements in local control may translate into a survival benefit.

Paryani, Nitesh N.; Zlotecki, Robert A.; Swanson, Erika L.; Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Grobmyer, Stephen R.; Hochwald, Steven N. [Department of General Surgery, 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); Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

2012-03-01

372

Response to lactation induction differs by season of year and breed of dairy ewes.  

PubMed

Lactation artificially induced (ART) by steroid hormones and natural lactation (NAT) after lambing were compared in 2 dairy sheep breeds (Manchega and Lacaune) in 2 experiments conducted during winter and spring. In experiment 1, ART ewes (14 Manchega and 9 Lacaune) were induced into lactation in winter by the standard protocol, which consisted of s.c. injections of estradiol and progesterone administered in 2 portions daily from d 1 to 7. Hydrocortisone acetate was injected s.c. daily on d 18 to 20. Milking was initiated on d 21 and continued for 13 wk. A similar group of NAT ewes was selected for the contemporary comparison of NAT vs. ART lactation. All Lacaune ewes, but only 3 of the 14 Manchega ewes (21%), were successfully induced into lactation. Despite the successful induction of lactation in Lacaune ewes, milk yield was much lower than that obtained in NAT lactation (1.23 +/- 0.14 vs. 2.51 +/- 0.15 L/ d). Milk composition from wk 5 to 13 did not differ between groups, except for whey protein, which was greater in ART than in NAT ewes (1.47 vs. 1.25%). In experiment 2, 19 Manchega ewes were divided into 2 groups and induced into lactation in spring by using the standard induction protocol, similar to that used in experiment 1 (control, n = 9), or the standard protocol modified with bovine somatotropin (bST, 250 mg/ewe on d 11; n = 10). Manchega ewes had an improved response to the standard protocol of lactation induction in spring compared with winter. Milk yield in bST-treated Manchega ewes was 98% greater than that in control ewes (402 +/- 85 vs. 203 +/- 86 mL/d). The use of bST during mammogenesis did not affect milk composition. In conclusion, marked differences between Manchega and Lacaune dairy ewes were observed in their response to lactation induction when using the standard protocol during different photoperiod conditions. The Manchega ewes were unable to establish lactation in winter but were able to do so in spring. The response to lactation induction in dairy ewes seems to be related to their endogenous levels of prolactin and growth hormone, the use of which should be explored more deeply in future research. PMID:18487652

Andrade, B Ramírez; Salama, A A K; Caja, G; Castillo, V; Albanell, E; Such, X

2008-06-01

373

[Principles of surgery for retroperitoneal sarcoma].  

PubMed

The successful treatment of retroperitoneal soft tissue sarcomas requires an experienced team consisting of not only surgeons but also pathologists and radiologists with a high case load in these tumours. The decisive step in the preoperative work-up of these, often late detected, tumours is their reliable grading as well as, if necessary, recognition of the sarcoma subtype as a basis for determining the direction of treatment. Imaging methods provide essential information with regard to the detection of infiltration of neighbouring structures and organs. Magnetic resonance imaging (MRI) is the most suitable method for this purpose. Punch needle biopsy is to be preferred over fine-needle biopsy in all cases for histological confirmation. The surgical standard procedure for the majority of the patients comprises multivisceral resection as principle, with additional colon resection, nephrectomy, and resection of abdominal wall musculature or, respectively, the psoas muscle in order to achieve an R0 resection of the retroperitoneal compartment. If only small margins of clearance are to be expected, a preoperative (neoadjuvant) treatment with radiation and/or chemotherapy even in combination with deep wave hyperthermia for high grade sarcomas should be strongly considered. Adjuvant postoperative radiation therapy often cannot be adequately applied due to the occupation of the former tumour bed by abdominal organs that were displaced by the mass effect, especially the radiation-sensitive small bowel. The optimal treatment strategy for these patients must be discussed in a multidisciplinary tumour board prior to any diagnostic or therapeutic procedure. PMID:23115028

Hohenberger, P; Dinter, D; Stroebel, P; Kasper, B; Wenz, F

2014-12-01

374

Sarcoma Immunotherapy: Past Approaches and Future Directions  

PubMed Central

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

D'Angelo, S. P.; Tap, W. D.; Schwartz, G. K.; Carvajal, R. D.

2014-01-01

375

What regulates placental steroidogenesis in 90-day pregnant ewes?  

PubMed

By day-90, the placenta secretes half of the circulating progesterone and 85% of the circulating estradiol-17beta [Weems YS, Vincent D, Tanaka Y, et al. Effects of prostaglandin F(2alpha) 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 F(2alpha) (PGF(2alpha)) on secretion of estradiol-17beta and cortisol in 90-100 day hysterectomized, intact, or ovariectomized pregnant ewes. Prostaglandins 1994;48:139-57]. Ovariectomy (OVX) or prostaglandin (PG) F(2alpha) (PGF(2alpha)) does not abort intact or OVX 90-day pregnant ewes and PGF(2alpha) regresses the corpus luteum, but does not affect placental progesterone secretion in vivo [Weems YS, Vincent D, Tanaka Y, et al. Effects of prostaglandin F(2alpha) on sources of progesterone and pregnancy in intact, ovariectomized, and hysterectomized 90-100 day pregnant ewes. Prostaglandins 1992;43:203-22]. Luteal progesterone secretion in vitro at day-90 of pregnancy in ewes is regulated by PGE(1)and/or PGE(2), not by ovine luteinizing hormone (LH; 3). Concentrations of PGE in uterine or ovarian venous plasma averaged 6 ng/ml at 90-100 days of pregnancy in ewes [Weems YS, Vincent DL, Tanaka Y, Nusser K, Ledgerwood KS, Weems CW. Effect of prostaglandin F(2alpha) on uterine or ovarian secretion of prostaglandins E and F(2alpha) (PGE; PGF(2alpha)) in vivo in 90-100 day hysterectomized, intact or ovariectomized pregnant ewes. Prostaglandins. 1993;46:277-96]. Ovine placental PGE secretion is regulated by LH up to day-50 and by pregnancy specific protein B (PSPB) after day-50 of pregnancy [Weems YS, Kim L, Humphreys V, Tsuda V, Weems CW. Effect of luteinizing hormone (LH), pregnancy specific protein B (PSPB), or arachidonic acid (AA) on ovine endometrium of the estrous cycle or placental secretion of prostaglandins E(2) (PGE(2)) and F(2alpha) (PGF(2alpha)), and progesterone in vitro. Prostaglandins Other Lipid Mediators 2003;71:55-73]. Indomethacin (INDO), a prostaglandin synthesis inhibitor [Lands WEM. The biosynthesis and metabolism of prostaglandins. Annu Rev Physiol 1979;41:633-46], lowers jugular venous progesterone [Bridges PJ, Weems YS, Kim L, et al. Effect of prostaglandin F(2alpha) (PGF(2alpha)), indomethacin, tamoxifen or estradiol-17beta on pregnancy, progesterone and pregnancy specific protein B (PSPB) secretion in 88-90 day pregnant ewes. Prostaglandins Other Lipid Mediators 1999;58:113-24] and inferior vena cava PGE of pregnant ewes with ovaries by half at day-90 [Bridges PJ, Weems YS, Kim L, LeaMaster BR, Vincent DL, Weems CW. Effect of prostaglandin F(2alpha) (PGF(2alpha)), indomethacin, tamoxifen or estradiol-17beta on prostaglandin E (PGE), PGF(2alpha) and estradiol-17beta secretion in 88-90 day pregnant sheep. Prostaglandins Other Lipid Mediators 1999;58:167-78]. In addition, treatment of 90 day ovine diced placental slices with androstenedione in vitro increased placental estradiol-17beta, but treatment with PGF(2alpha)in vitro did not decrease placental progesterone secretion, which indicates that ovine placenta progesterone secretion is resistant to the luteolytic action of PGF(2alpha) [Weems YS, Bridges PJ, LeaMaster BR, Sasser RG, Vincent DL, Weems CW. Secretion of progesterone, estradiol-17beta, prostaglandins (PG) E (PGE), F(2alpha) (PGF(2alpha)), and pregnancy specific protein B (PSPB) by day 90 intact or ovariectomized pregnant ewes. Prostaglandins Other Lipid Mediators 1999;58:139-48]. This also explains why ovine uterine secretion of decreased around day-50 [Weems YS, Kim L, Humphreys V, Tsuda V, Weems CW. Effect of luteinizing hormone (LH), pregnancy specific protein B (PSPB), or arachidonic acid (AA) on ovine endometrium of the estrous cycle or placental secretion of prostaglandins E(2) (PGE(2)) and F(2alpha) (PGF(2alpha)), and progesterone in vitro. Prostaglandins Other Lipid Mediators 2003;71:55-73], when placental estradiol-17beta secretion is increasing [Weems C, Weems Y, Vincent D. Maternal recognitio

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

2007-08-01

376

Relationships between LH and estradiol-17 beta after removal of luteal progesterone in the ewe.  

PubMed

Three experiments were conducted to examine the relationship between systemic concentrations of luteinizing hormone (LH) and estradiol-17 beta (E2) after withdrawal of progesterone in cycling ewes. In Exp. 1, ewes were assigned randomly to one of three treatments: laparotomy (C), removal of the luteal ovary (ULO), or ULO plus anesthesia with sodium pentobarbital for 6 h beginning 4 h after surgery. Anesthesia was used in an attempt to block the expected increase in tonic secretion of LH. Patterns of LH and E2 in these three groups did not differ during the 24-h experimental period. In Exp. 2, a longer period of anesthesia was utilized. Forty-eight ewes were assigned at random to one of four treatments: C, ULO, lutectomy or an intrafollicular injection of prostaglandin F2 alpha (PGF2 alpha). One-half of the ewes in each group were anesthetized with sodium pentobarbital from initiation of treatment (0 h) until 10 h after surgery. Sodium pentobarbital did not suppress the increases in LH and E2 after progesterone withdrawal. The regression of concentrations of E2 on concentration of LH was not significant. In Exp. 3, ewes were infused with either saline or dopamine after receiving an im injection of PGF2 alpha. Tonic secretion of LH increased after 4 h in ewes infused with saline, but not in ewes infused with dopamine. Despite the suppression of LH, concentrations of E2 increased in dopamine-treated ewes as in control ewes. Therefore, the initial increase in E2 after a decline of progesterone in cycling ewes is independent of increases in LH. PMID:6584418

Gust, C M; Deaver, D R; Dailey, R A; Inskeep, E K

1984-02-01

377

Ram-induced oestrus and ovulation in lactating and weaned Corriedale ewes.  

PubMed

Two experiments were conducted in consecutive years in which recently (Experiment 1) or temporarily (Experiment 2) weaned ewes and matched post-partum non-lactating flockmates (DRY) were exposed to a stimulus group of rams and oestrous ewes (10 and 20 in Experiment 1, 20 and 20 in Experiment 2) for 28 days in spring. Lactating ewes (n = 130) in Experiment 1 were isolated from their lambs 4 (W-4), 2 (W-2), 1 (W-1) or 0 (W-0) days in advance and exposed along with a group of 32 DRY flockmates. Lactating ewes in Experiment 2 (n = 230) were allocated to an unreplicated factorial of two levels of temporary weaning before stimulation (B0: control; B24: lambs removed 24 h before stimulation) by four levels of ewe-lamb contact imposed at the start of the stimulation (A0: control; A12, A24 and A36: lamb-ewe separation during the initial 12, 24 or 36 h of exposure); DRY ewes (n = 54) acted as an augmented factorial control. Oestrus (rump marks) and ovulation (laparoscopy on day 5 and on day 28 (Experiment 1) or day 32 (Experiment 2)) were recorded. Ovulation and oestrous responses in Experiment 1 were similar for DRY (90.6% and 55.2%, respectively) and recently weaned ewes (83.8% and 53.7%, respectively). Amongst recently weaned ewes, the immediate ovulation response to the rams and the proportion of ewes still cycling by day 28 tended to be lower (P = 0.065 and P = 0.011) in ewes weaned on the day of ram exposure (71.9% and 54.8% v. 87.8% and 80.0%, respectively). Ovulation rate was lower (P < 0.003) in W-2 ewes (1.3 ± 0.10) than in the other recently weaned groups. In Experiment 2, ovulation (83.3%) and oestrous (68.9%) responses in DRY ewes were higher (P = 0.022 and P = 0.053, respectively) than in lactating ewes (66.2% and 51.0%, respectively). More ewes ovulated (P = 0.036) in B24 (70.5%) than in B0 (61.8%). Ewes having their lambs returned 12 h after the onset of stimulation (A12) had poorer ovulation responses (54.9%) than control ewes (A0, 72.9%, P < 0.05); this was probably associated to lamb restitution after the sunset. Main conclusions were that (i) the presence of the lambs is a depressing factor of both ovulation and oestrous responses to the ram effect in lactating ewes, (ii) the ovulation response of lactating ewes will probably benefit from removing lambs for a period of 24 h before the onset of stimulation, (iii) until additional information becomes available, temporary weaning protocols should be designed avoiding lamb restitution during the night. PMID:22443952

Pevsner, D A; Rodríguez Iglesias, R M; Ciccioli, N H

2010-03-01

378

18F-FDG PET in sarcoma treatment response imaging  

PubMed Central

Sarcomas are a biologically complex group of diseases that exhibit variable responses to single or combination therapy. 18F-FDG PET imaging contributes to sarcoma treatment response assessment as an objective semiquantitative biomarker of response. In this review, background and experience in 18F-FDG PET as a biomarker that successfully identifies tumor response is assessed. PMID:23133794

Eary, Janet F; Hawkins, Douglas S; Rodler, Eve T; Conrad, Ernest U

2011-01-01

379

Estrus synchronization and artificial insemination of hair sheep ewes in the tropics.  

PubMed

Hair sheep ewes (St. Croix White and Barbados Blackbelly) were used to evaluate 3 methods of estrus synchronization for use with transcervical artificial insemination (TAI). To synchronize estrus, ewes (n = 18) were treated with PGF2alpha (15 mg, im) 10 d apart, with controlled internal drug release (CIDR) devices containing 300 mg progesterone for 12 d (n = 18), or with intravaginal sponges containing 500 mg progesterone for 12 d (n = 18). On the day of the second PGF2alpha injection or at CIDR or sponge removal, sterile rams were placed with the ewes. Jugular blood samples were collected from the ewes at 6-h intervals until the time of ovulation, and daily for 16 d after estrus (Day 0). Plasma was harvested and stored at -20 degrees C until LH, and progesterone concentrations were determined by RIA. There was no difference (P>0.10) in time to estrus among the CIDR-, PGF2alpha- or sponge-treated ewes. All of the ewes in the CIDR group and 94.4% of the sponge treated ewes exhibited estrus by 36 h after ram introduction, while only 72.2% of PGF2alpha-treated ewes showed signs of estrus by this time (P<0.06). The time from ram introduction to ovulation was not different (P>0.10) among the CIDR-, PGF2alpha- or sponge-treated ewes. The time to the preovulatory LH surge was similar (P>0.10) among CIDR, PGF2alpha and sponge treated ewes. Progesterone levels through Day 16 after the synchronized estrus were not different (P>0.10) among treatment groups. Hair sheep ewes (n = 23) were synchronized using PGF2alpha and bred by TAI using frozen-thawed semen 48 h after the second injection. The conception rate to TAI was 2/23 (8.7%) and produced 3 ram lambs. In a subsequent trial, 17 ewes were synchronized with CIDR devices and bred by TAI using frozen-thawed semen 48 h after CIDR removal, resulting in a conception rate of 52.9% (9/17). It is possible to synchronize estrus in hair sheep using either CIDRs, sponges or PGF2alpha. Even though there were no significant differences in the timing of ovulation or the LH surge among the treatment groups, a higher conception rate was achieved in ewes synchronized with CIDR devices during the second trial. This may reflect an increase in the skill level of the TAI technician. PMID:10729020

Godfrey, R W; Collins, J R; Hensley, E L; Wheaton, J E

1999-04-01

380

Effect of prepartum photoperiod on milk production and prolactin concentration of dairy ewes.  

PubMed

Long photoperiods during established lactation increase milk production in dairy cattle and dairy sheep, but recent research in cattle and dairy goats suggests an additional influence of prepartum day length on milk yield in the subsequent lactation. The proposed mechanism of function is the level and role of circulating prolactin in mammary development. The objectives of this study were to evaluate the effect of prepartum photoperiod on milk production, milk composition, and prolactin concentration of 22 multiparous dairy ewes exposed to short day prepartum photoperiod (SDPP; 8 h of light:16 h of dark) or long day prepartum photoperiod (LDPP; 16 h of light:8 h of dark) for at least 6 wk prepartum. During the first 8 wk of lactation, SDPP ewes tended to produce more milk than LDPP ewes (2.43 vs. 2.29 kg/d, respectively), and the milk of SDPP ewes had a greater fat percentage than that of LDPP ewes (6.04 vs. 5.51%, respectively). Due to daily milk yield and greater fat content, SDPP ewes produced more 6.5% fat-corrected milk (+0.30 +/- 0.08 kg/d) and 6.5% fat- and 5.8% protein-corrected milk (+0.28 +/- 0.08 kg/d) than LDPP ewes. For the lactation period of 180 d, SDPP ewes produced more test day milk than LDPP ewes (1.76 vs. 1.60 +/- 0.05 kg/d, respectively), but there were no differences in milk fat or protein percentages. Ewes in both treatments experienced a prolactin surge at lambing, but SDPP ewes had lower circulating prolactin concentration than LDPP ewes from 4 to 0.5 wk before lambing (14.7 vs. 51.3 +/- 4.2 mg/dL, respectively). These data suggest that decreased prepartum photoperiod may be important for increasing milk production in dairy ewes and may provide a management strategy for dairy sheep producers to increase milk yield. PMID:18096928

Mikolayunas, C M; Thomas, D L; Dahl, G E; Gressley, T F; Berger, Y M

2008-01-01

381

Synovial Sarcoma of the Buccal Mucosa: A Rare Case Report  

PubMed Central

Synovial sarcoma (SS) is a rare malignant neoplasm that arises most commonly in joint capsules and articular tendons, but its relationship to the synovium is not always obvious. Synovial sarcoma is a malignant soft tissue tumor representing 5.6% to 10% of all soft tissue sarcomas. They are termed SS because of their histologic resemblance to the synovium, but they rarely involve a synovial structure and are thought to arise from pluripotential mesenchymal cells. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the para-articular regions of the extremities, with approximately 9% occurring in the head and neck region. Synovial sarcoma has been reported rarely in the oral cavity. We report a very rare case of Synovial sarcoma of the buccal mucosa in a 24-year-old male patient. PMID:23762651

Mahesh, Kumar T. S.; Ponnuswamy, Indira Annamalai; David, Maria Priscilla; Shivhare, Peeyush; Puttaranganayak, Mahalakshmi Ikkanur; Sinha, Pooja

2013-01-01

382

Optimal management of primary retroperitoneal sarcoma: an update.  

PubMed

Soft tissue sarcomas are a group of heterogeneous neoplasms with more than 50 histological subtypes exhibiting major differences in terms of pathogenesis, genetic alterations and clinical behavior. Sarcomas represent approximately 1% of malignancies with retroperitoneal sarcomas representing 10-15% of all soft tissue sarcomas. Surgery is currently the only modality which offers the chance of cure. Surgery for retroperitoneal sarcomas presents specific challenges due their location in a complex space surrounded by vital structures and visceral organs often prohibiting resection with wide margins. Furthermore, even after complete resection local recurrence is common and the leading cause of death. In this article the authors describe the initial investigations, prognostic factors and optimal surgical management. The evidence and current research as regards the role of multimodality treatment is reviewed and discussed. PMID:24524274

Miah, Aisha B; Hannay, Jonathan; Benson, Charlotte; Thway, Khin; Messiou, Christina; Hayes, Andrew J; Strauss, Dirk C

2014-05-01

383

Recent advances in the treatment of sarcomas in gynecology.  

PubMed

Uterine sarcomas are a heterologous group of rare malignancies accounting for 8-10% of all uterine malignancies, but are significantly more aggressive and have worse prognoses. Management of uterine sarcomas including leiomyosarcoma and endometrial stromal sarcoma are reviewed here, with additional discussions regarding high-grade undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are currently staged and treated similar to high-grade epithelial endometrial carcinomas, thus will not be discussed in this review. Gemcitabine/docetaxel with adriamycin holds promise for the treatment of leiomyosarcoma, but currently, limited advancements have been made in discovering targeted therapies to these tumors. Continued translational research in both medical oncology and gynecologic oncology is necessary to forward the development of novel and targeted therapeutic agents in the treatment of sarcoma. Enrollment of these patients in clinical trials is encouraged, and will allow for the development of safer and more effective therapies. PMID:25227754

Lange, Sara S; Novetsky, Akiva P; Powell, Matthew A

2014-09-01

384

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

Microsoft Academic Search

Between 1934 and 1983, 23 patients with well-documented diagnosis of radiation-associated sarcoma (RAS) were seen at the University of Michigan Medical Center. The median latent period from irradiation to diagnosis of RAS was 13 years with a minimum latent period of 3 and a maximum of 34 years. All sarcomas originated in previously normal tissues within the irradiated field. Pathology

Beatriz E. Amendola; Marco A. Amendola; Kenneth D. McClatchey; Charles H. Miller

1989-01-01

385

Kaposi's Sarcoma-Associated Herpesvirus Viremia is Associated with the Progression of Classic and Endemic Kaposi's Sarcoma  

Microsoft Academic Search

In order to gain further insight on the role of Kaposi's sarcoma-associated herpesvirus (KSHV) in classic and endemic Kaposi's sarcoma (KS) pathogenesis, we aimed to determine (i) whether KSHV is detectable in peripheral blood mononuclear cells (PBMCs), (ii) which PBMCs subpopulation harbor the virus, (iii) which clinical, histologic, and immunologic parameters are associated with KSHV viremia in a population of

Claire Pellet; Delphine Kerob; Alain Dupuy; Mary V Carmagnat; Samia Mourah; Marie-Pierre Podgorniak; Cecile Toledano; Patrice Morel; Olivier Vérola; Christine Dosquet; Yamina Hamel; Fabien Calvo; Claire Rabian; Céleste Lebbé

2006-01-01

386

Establishment and characterization of a small round cell sarcoma cell line, SCCH-196, with t(11;22)(q24;q12).  

PubMed

A cell line designated SCCH-196 was established from an extraskeletal small round cell sarcoma developed in a 16-year-old Japanese girl. The cells grew as a monolayer, and have been continuously propagated by serial subcultures during the past 26 months. Cells from the primary tumor and those from the SCCH-196 cell line at passage 10 both showed the same karyotype, 51,XX, +8, +20, +21, t(11;22)(q24;q12), +i(1q), +i(1q). Histologically the primary tumor was difficult to classify as either Ewing's sarcoma (ES) or peripheral neuroepithelioma (NE). Neuron-specific enolase-positive cells in the primary tumor and the occurrence in the upper extremity were in favor of NE, while positive reaction of SCCH-196 cells to an ES-specific monoclonal antibody 5C11 suggested a diagnosis of ES. The SCCH-196 cell line may be useful for basic studies on differentiation of neuroectodermal tumors, and for future cloning of still unidentified genes which may be located at the breakpoints of the 11;22 translocation. PMID:2513302

Homma, C; Kaneko, Y; Sekine, K; Hara, S; Hata, J; Sakurai, M

1989-09-01

387

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

ClinicalTrials.gov

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 Unclassified Pleomorphic Sarcoma of Bone; Childhood Anaplastic Rhabdomyosarcoma; 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 Mixed Alveolar Rhabdomyosarcoma; 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

2015-02-18

388

Contrasting epidemiology of childhood osteosarcoma, Ewing's tumor, and rhabdomyosarcoma  

SciTech Connect

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.

Miller, R.W.

1981-04-01

389

Histological variants of cutaneous Kaposi sarcoma  

PubMed Central

This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS) lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage); morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented. PMID:18655700

Grayson, Wayne; Pantanowitz, Liron

2008-01-01

390

Pulmonary metastasectomy for soft tissue sarcoma.  

PubMed

The American Cancer Society predicts 10,520 new cases and 3920 deaths from soft tissue sarcoma (STS) for 2010. STS disseminates primarily via the hematogenous route, although lymphatic spread does occur with certain subtypes. The lung is the most common metastatic site in most large series, accounting for up to 80% of metastases. The median overall survival for pulmonary metastatic disease with current multidisciplinary treatment is approximately 12 to 14 months. Pulmonary metastasectomy (PM) represents the only potentially curative treatment for patients with STS and lung metastases. This article discusses the management of STS using PM. PMID:22365519

Smith, Richard; Demmy, Todd L

2012-04-01

391

Studies of Kaposi's sarcoma with infrared photography  

SciTech Connect

Infrared photography, known to be useful in the study of cutaneous vascular structures but not yet extensively explored in the investigation of skin diseases, was used to study lesions of Kaposi's sarcoma in three patients. In all photographs, the tumors appeared as a stain which was lighter in color than the normal skin. In two patients, the infrared photographs showed a tumor identical with that seen clinically. In the third patient, the tumor showed a larger extension than it seemed to have on physical examination. We believe that this technique can be of value in establishing the presence of such tumors and evaluating their actual size.

Wolf, R.; Sandbank, M.

1982-08-01

392

100 years of Rous sarcoma virus.  

PubMed

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

Weiss, Robin A; Vogt, Peter K

2011-11-21

393

Follicular dendritic cell sarcoma of the tonsil.  

PubMed

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that occurs extranodally and nodally. The following case report describes a 24-year-old male patient who suffered from FDCS of the tonsil. He presented at the ENT Department of the University Hospital Magdeburg with throat pain that had lasted for 3 months. There were neither B symptoms nor abnormal fatigue. An extended tonsillectomy was performed. The morphological and immunohistochemical findings confirmed the diagnosis of FDCS. FDCS should be considered as an important differential diagnosis in spindle cell tumors of the tonsil. PMID:25512260

Vorsprach, Monique; Kalinski, Thomas; Vorwerk, Ulrich

2015-01-01

394

Fifty-one Kaposi sarcoma patients  

Microsoft Academic Search

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

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

395

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

E-print Network

to determine if there was an induction of estrus and an addition twenty-five day sampling period was undertaken. Ewe Preparation Prior to initiation of the study, ewes were sonogrammed to determine reproductive status. Ewes were randomly confined.../ml in cyclic dairy heifers and beef cows, respectively. In heifers where serum progesterone concentrations were measured, Burke et al. (22) found maximal levels of 3 ng/ml around day 14 and basal levels of less than 0.25 ng/ml at the time of estrus...

Satterfield, Michael Carey

2005-02-17

396

A typical case of hydrallantois accompanied by fetal monstrosity in a local ewe of Kashmir  

PubMed Central

A full termed local ewe with the history of continuous straining with labored breathing for last 24 hours was presented. The animal was disinclined to move with tense and round abdomen which developed rapidly during last two weeks. Caesarean section revealed hydrallantois accompanied by multiple fetal congenital abnormalities. The ewe was under observation for four weeks. Metritis developed 12 days post-operation and was treated successfully. The ewe was found active on 25 days post-surgery with gain of extra 3 kg bodyweight.

Bhattacharyya, Hiranya Kumar; Hussain Dar, Shahid; Fazili, Mujeeb-ur-Rehman; Hafiz, Abdul

2012-01-01

397

Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.  

PubMed

Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ? 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ? 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (P<0.01), and OOS ewes were intermediate to, and tended to differ from (P<0.10), the other two breeds. We conclude that OOS ewes developed by selection for fertility in spring matings had an abbreviated seasonal anestrus that is one of the shortest ever reported for temperate breeds, and that tropical St. Croix sheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. PMID:23528712

Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

2013-05-01

398

ChildSeq-RNA: A next-generation sequencing-based diagnostic assay to identify known fusion transcripts in childhood sarcomas.  

PubMed

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

Qadir, Mohammed A; Zhan, Shing H; Kwok, Brian; Bruestle, Jeremy; Drees, Becky; Popescu, Oana-Eugenia; Sorensen, Poul H

2014-05-01

399

Effect of parity on milk yield, composition, somatic cell count, renneting parameters and bacteria counts of Comisana ewes.  

PubMed

Twenty-four Comisana ewes, with no history of mastitis, were included in this study, with eight ewes each in parities 1, 2 and 3. Groups were separately penned on straw litter and ewes were individually checked for yield, composition, renneting properties and bacteriological characteristics of milk from January, when separated from their lambs (50+/-3 days after lambing), to May. Samples with more than 3.5x10(5) somatic cells/ml were cultured for mastitis related pathogens. Milk yield was not significantly affected by parity. The P3 ewes had significantly higher milk protein, casein and fat contents compared to the P1 and P2 ewes. The P3 ewes also had improved renneting ability of milk as compared to the P1 ewes. Quality of milk decreased with lower lactations. The milk of P1 ewes had significantly greater amounts of mesophilic bacteria than the P2 and P3 ewes, as well as higher concentrations of psychrotrophs and total coliforms in their milk with respect to the P3 ewes. Somatic cell counts in milk and the prevalence of subclinical mastitis were not changed by parity, although mastitis infection set in progressively earlier as the number of lactations decreased. These results suggest that ewes in first or second lactation have a less favourable milk secretion status in relation to mastitis than ewes with a higher number of lactations. Milk yield and quality of younger ewes may be improved by offering feed rations that take into account this reduced capacity to mobilise body reserves. Also, most scrupulous control of sanitation of housing, equipment and personnel is necessary. PMID:10818309

Sevi; Taibi; Albenzio; Muscio; Annicchiarico

2000-07-01

400

Simulated effects of culling ewes for age and failure to conceive on biological efficiency of an annual lambing production system.  

PubMed

A deterministic computer simulation model was used to estimate the effects of different culling strategies for nonconception and age on the biological efficiency of an annual lambing system. Interaction among culling strategy and genotype for system efficiency was estimated by also varying ewe genetic potentials for fertility, precocity of fertility, and litter size. Biological efficiency was defined as grams of empty body weight equivalent value of market lamb, cull ewe, and wool output per kilogram input of TDN. Pure breeding with random selection of intraflock replacement ewe lambs was assumed. Sheep were fed to maintain normal weight. Maximum allowable ewe age (i.e., time at culling for age) was varied from 2 to 10 yr. The four strategies of culling for nonconception that were simulated ranged from no removal for nonconception to removal of all nonpregnant ewes 15 wk after exposure. During calculation of lamb empty body weight equivalent, relative values per kilogram of output for market lambs, cull ewes, and clean wool were assumed to be 1 to .33 to 2.04 for most simulation runs. In addition, relative value of cull ewes was varied to .01, .16, .50, or .99 for some simulations. The effect of strategy for removal of nonconceiving ewes on system efficiency depended on maximum ewe age and genotype. In general, if relative value per kilogram of cull ewes to market lambs was < or = .50, ewes should be allowed to produce through 4 or 5 yr of age and then be salvaged. Unless salvage value of culled ewes approaches that of market lambs, ewe lambs should not be culled for failure to conceive. PMID:8440649

Nugent, R A; Jenkins, T G

1993-02-01

401

The epidemiology of soft tissue sarcoma.  

PubMed

Soft tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed annually in the United States. Population-based data from Connecticut covering the years 1935-1989 have shown an increasing incidence of STS in both genders, with a greater increase among men than women. The recent increase in acquired immune deficiency syndrome-related Kaposi's sarcoma does not explain the upward trend in STS, dating back decades. Etiologic heterogeneity is suggested by epidemiologic variations that have been observed by subsite and cell type. Among the environmental factors associated with STS are external radiation therapy, Thorotrast, arsenical pesticides and medications, phenoxyherbicides, dioxin, vinyl chloride, immunosuppressive drugs, alkylating agents, androgen-anabolic steroids, human immunodeficiency virus, and human herpes virus type 8. In addition, STS occurs excessively among persons with certain heritable states including retinoblastoma, Li-Fraumeni syndrome, Gardner's syndrome, Werner's syndrome, nevoid basal cell carcinoma syndrome, neurofibromatosis type 1, and some immunodeficiency syndromes. These risk factors account for a minority of STS cases but provide leads for further epidemiologic and interdisciplinary studies into the genetic and environmental determinants of various forms of STS. PMID:9344316

Zahm, S H; Fraumeni, J F

1997-10-01

402

Follow-up in soft tissue sarcomas.  

PubMed

The strategy for the follow-up of soft tissue sarcomas (STS) after therapy is tailored to the individual risk of recurrence and based on efficient rather than sophisticated methods of observation. Along with advances in the treatment of sarcomas, earlier detection of a less advanced and resectable recurrent disease (local or metastasis-especially to the lungs) can prolong patient survival. Since the majority of STS relapses occur within 5 years after treatment (approximately 80?% of metastases to the lung and close to 70?% of local recurrences within the first 2-3 years), in the period between 2 and 3 years after treatment, it is mandatory to follow-up patients every 3 months and perform careful history and physical examination (especially scars after surgery of the primary site) and a chest X-ray. There is no reason to perform other studies in asymptomatic patients (unless the patient reports symptoms). In case of retroperitoneal or intraperitoneal STS (including gastrointestinal stromal tumor), contrast-enhanced computed tomography of the abdomen and pelvis is recommended as the follow-up modality of choice. In this paper we outline the current recommendations for the follow-up strategy. PMID:25089160

Rutkowski, Piotr; Lugowska, Iwona

2014-01-01

403

Multidisciplinary Management of Soft Tissue Sarcoma  

PubMed Central

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

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

2013-01-01

404

Primary oral myeloid sarcoma: Report of a case  

PubMed Central

Myeloid sarcoma is defined as a tumor mass of immature myeloid cells that may be observed in a variety of locations including bone, skin, lymph nodes and soft tissues. However, oral involvement of myeloid sarcoma is extremely rare. These tumors are considered as specific lesions of acute myeloid leukemia. We present a case of a myeloid sarcoma of the upper vestibular gingiva in a 29-year-old woman who has no hematologic disease history. Multiple metastases were found in floor of the nasal cavity, left breast, and left lacrimal gland 12 months after primary diagnosis. PMID:24574662

Kurdo?lu, Ba?ak; Öztemel, Ak?n; Bar??, Emre; Sengüven, Burcu

2013-01-01

405

Primary oral myeloid sarcoma: Report of a case.  

PubMed

Myeloid sarcoma is defined as a tumor mass of immature myeloid cells that may be observed in a variety of locations including bone, skin, lymph nodes and soft tissues. However, oral involvement of myeloid sarcoma is extremely rare. These tumors are considered as specific lesions of acute myeloid leukemia. We present a case of a myeloid sarcoma of the upper vestibular gingiva in a 29-year-old woman who has no hematologic disease history. Multiple metastases were found in floor of the nasal cavity, left breast, and left lacrimal gland 12 months after primary diagnosis. PMID:24574662

Kurdo?lu, Ba?ak; Oztemel, Ak?n; Bar??, Emre; Sengüven, Burcu

2013-09-01

406

Advances in sarcoma genomics and new therapeutic targets  

PubMed Central

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

Taylor, Barry S.; Barretina, Jordi; Maki, Robert G.; Antonescu, Cristina R.; Singer, Samuel; Ladanyi, Marc

2012-01-01

407

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

E-print Network

enhanced brown adipose tissue (BAT) thermogenesis and increased birth weights and survival rates. The first study was designed to determine the effects of late-gestation shearing on lamb birth weights and survival in West Texas conditions. Ramboillet ewes...

Falck, Stephanie Joy

2001-01-01

408

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

E-print Network

; maternal effects; maternal expenditure; Ovis canadensis; population density; ungulates. Abstract In the Ram Mountain bighorn sheep (Ovis canadensis) population, ewes differing by more than 30% in body mass weaned

Réale, Denis

409

Ewes are more attentive to their offspring experiencing pain but not stress  

Microsoft Academic Search

The goal of this experiment was to detect if maternal care by ewes could be effective in mitigating psychological or physiological stress or pain in their offspring. We hypothesised that ewes are able to recognise when their offspring undergo an adverse experience and will adapt their maternal behaviour to buffer the effect of such events. Thirty-one pairs of 2-day-old lambs

Sophie Hild; Corinna C. A. Clark; Catherine M. Dwyer; Joanna C. Murrell; Mike Mendl; Adroaldo J. Zanella

2011-01-01

410

Effect of estrous synchronization on the histology of the oviduct and uterus of the ewe  

E-print Network

. It seems logical then that a comprehensive study of the effects of this treatment upon the oviductal and uterine environment be attempted to determine if the cellular and glandular structure varies from that of the normal cycling and bred ewe... with a plastic speculum and plunger and allowed to remain there fourteen days. 12 Upon removal of the pessaries, the ewes were observed twice daily and bred each time estrus was exhibited. Surgery was scheduled 48 or 72 hours following the last...

Hoermann, Albert LeRoy

1969-01-01

411

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

Microsoft Academic Search

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

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

412

Screening of antibiotic residues in ewes' milk destined to cheese by a commercial microbiological inhibition assay  

Microsoft Academic Search

Bulk ewes’ milk from Spanish dairy farms in the Castilla-La Mancha region and destined for production of protected denomination of origin (PDO) Manchego cheese were analysed each month for antimicrobial residues during the course of 1 year. A microbiological assay specific for ewes’ milk (Eclipse ‘100ov’®) was used. The number of positive samples by the Eclipse ‘100ov’ test was 2.6%.

M. Yamaki; M. I. Berruga; R. L. Althaus; M. P. Molina; A. Molina

2006-01-01

413

Evaluation of Screening Test for Detection of Antimicrobial Residues in Ewe Milk  

Microsoft Academic Search

The effects of preservatives (potassium dichromate andsodiumazide),heattreatment(untreatedand82°C\\/ 10 min), and lactation stage upon the response of the microbial tests (BRT AiM and Delvotest) utilized for the detection of residues of antimicrobial substances in ewe milk were examined. Milk samples were collected from the morning milking of 50 Manchega ewes every 2 wk, from 15 d postpartum until the end of

M. P. Molina; R. L. Althaus; S. Balasch; A. Torres; C. Peris; N. Fernandez

2003-01-01

414

Intrauterine bacterial inoculation and level of dietary methionine alter amino acid metabolism in nulliparous yearling ewes.  

PubMed

Using an intrauterine bacterial inoculation method, our objective was to determine the effects of acute sepsis and level of dietary metabolizable Met (MM) on splanchnic metabolism of AA in ewes. Twenty-four nulliparous yearling Rambouillet-cross ewes (initial BW = 65.1 +/- 0.6 kg), surgically fitted with chronic-indwelling catheters in hepatic and portal veins, a mesenteric vein and artery, and the uterine lumen, were assigned to a 2 x 2 factorial arrangement of treatments. Factors were intrauterine bacterial inoculation (noninoculated vs. inoculated) and level of MM [low (2.28 g/d) vs. high (3.91 g/d)]. Beginning 12 h before sampling, inoculated and noninoculated ewes received 10-mL intrauterine infusions of Escherichia coli (9.69 x 10(11) cfu) + Arcanobacterium pyogenes (2.76 x 10(12) cfu) and of sterile saline, respectively. Uterine infection was induced in ewes that received intrauterine bacterial inoculations, but not in ewes infused with sterile saline. Bacterial inoculation resulted in increased hepatic release and plasma concentrations of aromatic AA used for acute-phase protein synthesis, increased hepatic removal and decreased plasma concentrations of AA used for glutathione synthesis, and decreased plasma concentrations of some gluconeogenic and acetogenic AA used for glucose recycling and anaerobic energy production, respectively (P < 0.05). In ewes fed high-MM diets, compared with low-MM diets, a consistent net hepatic uptake of Phe occurred throughout the sampling period, more Asp was released from the portal-drained viscera, and hepatic vein glucose concentrations were greater (P < 0.05). We conclude that Met seemed to be limiting in low-MM ewes, and as such, would continue to be limiting during sepsis. However, additional MM, in excess of the dietary requirement, would not necessarily result in a benefit to ewes experiencing acute sepsis. PMID:17785602

Thelen, T M; Löest, C A; Taylor, J B; Wang, S; Lewis, G S

2007-12-01

415

AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants?  

Microsoft Academic Search

Background  Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral\\u000a organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and\\u000a in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study\\u000a aimed to investigate whether the ultrasound pattern

Francesco M Solivetti; Fulvia Elia; Alessandra Latini; Carlo Cota; Paola Cordiali-Fei; Aldo Di Carlo

2011-01-01

416

Serum enzyme status of Chios ewes fed increasing amounts of copper from copper sulfate.  

PubMed

This study aimed to evaluate effects of orally administered copper (Cu) to Chios sheep breed on serum levels of aspartate aminotransferase (AST), l-alanine aminotransferase (ALT), lactate deydrogenase (LDH) and alkaline phosphatase (ALP), in order to establish a practical and effective method in diagnosing the prehemolytic stage of chronic Cu poisoning. Eighteen ewes were allocated to three treatments of six ewes and fed a diet that contained 16.4 mg/day of Cu. Ewes in treatment Cu-0 received no additional Cu (control), while those in treatments Cu-60 and Cu-95 received 60 and 95 mg additional Cu/day, respectively, as an oral solution of copper sulfate. Therefore the ewes in treatment Cu-0, Cu-60 and Cu-95 consumed 16.4, 76.4 and 111.4 mg Cu/day, respectively. Serum enzyme levels were similar among treatments and all ewes remained clinically healthy until the end of the experiment. Results suggest that Chios ewes exhibit tolerance to Cu supplementation for up to 6 weeks. PMID:20045542

Bampidis, V A; Christodoulou, V; Chatzipanagiotou, A; Sossidou, E; Salangoudis, A

2010-06-01

417

What Are the Risk Factors for Uterine Sarcoma?  

MedlinePLUS

... t mean that you won't get the disease. Only a few factors are known to change the risk of developing a uterine sarcoma. Pelvic radiation therapy High-energy (ionizing) radiation used to treat some cancers can damage ...

418

Thalidomide Shows Activity Against AIDS-Related Kaposi's Sarcoma  

Cancer.gov

The drug thalidomide, used in the 1950s and 1960s as a sedative which led to birth defects in newborns of mothers who took the drug, has now been shown to have clinical activity against Kaposi's sarcoma (KS).

419

Aggressive multiple surgical interventions to pulmonary artery sarcoma.  

PubMed

We describe our experience with a patient who had metastasized pulmonary artery sarcoma, but survived 7 years after diagnosis. A 61-year-old man was diagnosed with pulmonary artery intimal sarcoma after resection of metastatic tumours to the bilateral lungs. The primary lesion in the pulmonary artery trunk extending into the bilateral branches was treated by tumour endoarterectomy followed by chemotherapy. He underwent resections of lung metastases two more times before detection of recurrent obstructive pulmonary artery sarcoma 4 years after the tumour endoarterectomy. En bloc resection of the tumour including the pulmonary artery trunk, valve and interventricular septum was performed, and the right ventricular out flow tract was reconstructed with a stentless pulmonary valve and equine pericardium. He died of the disease soon after an operation for metastatic brain tumour 3 years later. Pulmonary artery sarcoma has a dismal prognosis, but aggressively repeated surgical interventions may lengthen survival. PMID:24780741

Tanaka, Akiko; Shirasaka, Tomonori; Okada, Kenji; Okita, Yutaka

2015-02-01

420

NCI Researchers Identify Novel Mechanism for Spread of Sarcoma Tumors  

Cancer.gov

A team of researchers at the National Cancer Institute (NCI), using a mouse model, have uncovered a novel protein interaction that promotes the spread of cancer cells (a process known as metastasis) in a class of tumors collectively called sarcomas.

421

Sarcomas of the heart as a difficult interdisciplinary problem  

PubMed Central

Cardiac tumors are assumed to be a rare entity. Metastases to the heart are more frequent than primary lesions. Sarcomas make up the majority of cardiac malignant neoplasms. Among them angiosarcoma is the most common and associated with the worst prognosis. Malignant fibrous histiocytoma comprises the minority of cardiac sarcomas and has uncertain etiology as well as pathogenesis. Transthoracic echocardiography remains the widely available screening examination for the initial diagnosis of a cardiac tumor. The clinical presentation is non-specific and the diagnosis is established usually at an advanced stage of the disease. Sarcomas spread preferentially through blood due to their immature vessels without endothelial lining. Surgery remains the method of choice for treatment. Radicalness of the excision is still the most valuable prognostic factor. Adjuvant therapy is unlikely to be effective. The management of cardiac sarcomas must be individualized due to their rarity and significant differences in the course of disease. PMID:24701226

Marcinkiewicz, Anna; Ko?mider, Anna; Jaszewski, Ryszard

2014-01-01