Anti-EGFR therapy radiosensitizes human lung adenocarcinoma xenograft in nude mouse

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Wang Hui; Li Tianran; Tian Jiahe; Qu Baolin; Zhu Hui

2008-01-01

Objective: To investigate the effect of Gefitinib on radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. Methods: Human lung adenocarcinoma cell line A549 was used to establish nude mouse xenograft tumor model. The mice were derided into 4 groups: control, irradiation alone, Gefinitib alone and radiation combined with Genifitib. Radiation schedule was 3 fractions of 5 Gy, once daily. Gefitinib was daily administered by gavage at 100 mg/(kg·day -1 ) for 14 days. In the combination group, radiotherapy was performed 2 hours after Gefitinib administration. Tumor diameter was measured every other day. Percentage of tumor growth inhibition, growth delay time and regrowth delay time were evaluated. Results: For A549 xenografts in radiation alone, gefitinib alone and combination therapy groups, the percentage of tumor growth inhibition was 22.7%, 12.4% and 38.2%, respectively (F=25.75, P=0.000). Tumor growth delay time was 6.0, 7.8 and 21.6 days, respectively (F=70.49, P=0.000). Tumor regrowth delay time in combination therapy and irradiation alone groups was 23.4 and 10.2 days. (F=174.24, P= 0.000). Sensitizing enhancement ratio of combination group was 1.5 in growth and 1.7 in regrowth. Conclusions: Anti-EGFR therapy enhances the radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. (authors)

Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

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Peterson, Sarah M; Concino, Michael F; Liaw, Lucy; Martini, Paolo GV; Iskenderian, Andrea; Cook, Lynette; Romashko, Alla; Tobin, Kristen; Jones, Michael; Norton, Angela; Gómez-Yafal, Alicia; Heartlein, Michael W

2010-01-01

Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular

Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing's family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression.

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Kang, Min H; Wang, Jing; Makena, Monish R; Lee, Joo-Sang; Paz, Nancy; Hall, Connor P; Song, Michael M; Calderon, Ruben I; Cruz, Riza E; Hindle, Ashly; Ko, Winford; Fitzgerald, Jonathan B; Drummond, Daryl C; Triche, Timothy J; Reynolds, C Patrick

2015-03-01

To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI). Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing's sarcoma family of tumors (EFT), neuroblastoma (NB), and rhabdomyosarcoma (RMS). SLFN11 expression was assessed by Affymetrix HuEx arrays, Taqman RT-PCR, and immunoblotting. Plasma and tumor concentrations of irinotecan and SN-38 (active metabolite) were approximately 10-fold higher for nal-IRI than for irinotecan. Two doses of NAL-IRI (10 mg/kg/dose) achieved complete responses maintained for >100 days in 24 of 27 EFT-xenografted mice. Event-free survival for mice with RMS and NB was significantly shorter than for EFT. High SLFN11 expression has been reported to correlate with sensitivity to DNA damaging agents; median SLFN11 mRNA expression was >100-fold greater in both EFT cell lines and primary tumors compared with NB or RMS cell lines or primary tumors. Cytotoxicity of SN-38 inversely correlated with SLFN11 mRNA expression in 20 EFT cell lines. In pediatric solid tumor xenografts, nal-IRI demonstrated higher systemic and tumor exposures to SN-38 and improved antitumor activity compared with the current clinical formulation of irinotecan. Clinical studies of nal-IRI in pediatric solid tumors (especially EFT) and correlative studies to determine if SLFN11 expression can serve as a biomarker to predict nal-IRI clinical activity are warranted. ©2015 American Association for Cancer Research.

Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

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Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L.

1990-01-01

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively

An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing's sarcoma

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Mosakhani Neda

2012-03-01

Full Text Available Abstract Background Xenografts have been shown to provide a suitable source of tumor tissue for molecular analysis in the absence of primary tumor material. We utilized ES xenograft series for integrated microarray analyses to identify novel biomarkers. Method Microarray technology (array comparative genomic hybridization (aCGH and micro RNA arrays was used to screen and identify copy number changes and differentially expressed miRNAs of 34 and 14 passages, respectively. Incubated cells used for xenografting (Passage 0 were considered to represent the primary tumor. Four important differentially expressed miRNAs (miR-31, miR-31*, miR-145, miR-106 were selected for further validation by real time polymerase chain reaction (RT-PCR. Integrated analysis of aCGH and miRNA data was performed on 14 xenograft passages by bioinformatic methods. Results The most frequent losses and gains of DNA copy number were detected at 9p21.3, 16q and at 8, 15, 17q21.32-qter, 1q21.1-qter, respectively. The presence of these alterations was consistent in all tumor passages. aCGH profiles of xenograft passages of each series resembled their corresponding primary tumors (passage 0. MiR-21, miR-31, miR-31*, miR-106b, miR-145, miR-150*, miR-371-5p, miR-557 and miR-598 showed recurrently altered expression. These miRNAS were predicted to regulate many ES-associated genes, such as genes of the IGF1 pathway, EWSR1, FLI1 and their fusion gene (EWS-FLI1. Twenty differentially expressed miRNAs were pinpointed in regions carrying altered copy numbers. Conclusion In the present study, ES xenografts were successfully applied for integrated microarray analyses. Our findings showed expression changes of miRNAs that were predicted to regulate many ES associated genes, such as IGF1 pathway genes, FLI1, EWSR1, and the EWS-FLI1 fusion genes.

Localization of indium-111 in human malignant tumor xenografts and control by chelators

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Watanabe, Naoyuki; Oriuchi, Noboru; Endo, Keigo; Inoue, Tomio; Tanada, Shuji; Murata, Hajime; Kim, E. Edmund; Sasaki, Yasuhito

1999-01-01

The kinetics of soluble indium-111 ( 111 In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of 111 In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. 111 In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of 111 In-chloride. Secondly, the effect of edetate calcium disodium (CaNa 2 EDTA) on radioactivity in 111 In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa 2 EDTA significantly reduced 111 In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa 2 EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with 111 In-chloride was investigated. In one group of mice CaNa 2 EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of 111 In-chloride (postadministration), the localization of 111 In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa 2 EDTA administered intraperitoneally at 12 and 1 h before injection of 111 In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa 3 DTPA had a more powerful effect than CaNa 2 EDTA. In conclusion, 111 In-activity in tumors consists of intracellular and extracellular components, and the extracellular 111 In may be cleared by

Human airway xenograft models of epithelial cell regeneration

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Puchelle Edith

2000-10-01

Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

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Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

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Francis Richard W

2010-04-01

Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

Neurotensin receptors in human neoplasms: high incidence in Ewing's sarcomas.

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Reubi, J C; Waser, B; Schaer, J C; Laissue, J A

1999-07-19

Receptors for regulatory peptides, such as somatostatin or vasoactive intestinal peptide (VIP), expressed at high density by neoplastic cells, can be instrumental for tumor diagnosis and therapy. Little is known about the expression of neurotensin receptors in human tumors. In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand. Neurotensin receptors were identified and localized in tumor cells of 11/17 Ewing's sarcomas, 21/40 meningiomas, 10/23 astrocytomas, 5/13 medulloblastomas, 7/24 medullary thyroid cancers and 2/8 small cell lung cancers. They were rarely found in non-small cell lung cancers and breast carcinomas; they were absent in prostate, ovarian, renal cell and hepatocellular carcinomas, neuroendocrine gut tumors, pituitary adenomas, schwannomas, neuroblastomas and lymphomas. When present, the receptors bound with nanomolar affinity neurotensin and acetyl-neurotensin-(8-13), with lower affinity neuromedin N, diethylenetriamine penta-acetic acidneurotensin-(8-13) and SR 48692, but not neurotensin-(1-11). They were all of the NT1 type, without high affinity for levocabastine. Further, in 2 receptor-positive Ewing's sarcomas, neurotensin mRNA was detected by in situ hybridization techniques. Since neurotensin is known to stimulate cell proliferation, the presence of neurotensin receptors in human neoplasia may be of biological relevance, possibly as an integrative part of an autocrine feedback mechanism of tumor growth stimulation.

Ewing`s Sarcoma

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Agnieszka Budny

2017-06-01

Full Text Available Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Clinical presentation is usually dominated by local bone pain and a mass. Magnetic resonance best defines the extent of the lesion. Patients diagnosed with Ewing's sarcoma within  last years show a improving  survival rate . Rehabilitation seems to be a crucial part of multimodal therapy.

Matrigel alters the pathophysiology of orthotopic human breast adenocarcinoma xenografts with implications for nanomedicine evaluation.

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Shuhendler, Adam J; Prasad, Preethy; Cai, Ping; Hui, Kelvin K W; Henderson, Jeffrey T; Rauth, Andrew M; Wu, Xiao Yu

2013-08-01

Matrigel, a mouse sarcoma-derived basement membrane protein mixture, is frequently used to facilitate human tumor xenograft growth in rodents. Despite its known effects on tumor growth and metastasis, its impact on tumor pathophysiology and preclinical evaluation of nanomedicines in tumor xenografts has not been reported previously. Herein bilateral MDA435 tumors were established orthotopically with (Mat+) or without (Mat-) co-injection of Matrigel. Tumor perfusion, morphology and nanoparticle retention were evaluated. As compared to Mat- tumors, Mat+tumors exhibited enhanced vascular perfusion and lymphatic flow, greater blood vessel and lymphatic growth within the tumor core, and more deformation and collapse of lymphatics in tumor-associated lymph nodes. These changes were accompanied by reduced nanoparticle retention in Mat+tumors. The results suggest that Matrigel is not a passive medium for tumor growth, but rather significantly alters long-term tumor architecture. These findings have significant implications for the evaluation of therapeutic nanomedicine in xenograft mouse models. Matrigel is utilized in facilitating human tumor xenograft growth in rodents. The authors demonstrate that Matrigel is not a passive medium for tumor growth; instead it significantly alters long-term tumor architecture, with major implications in the evaluation of therapeutic nanomedicine in xenograft mouse models. Copyright © 2013 Elsevier Inc. All rights reserved.

Ewing sarcoma

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Bone cancer - Ewing sarcoma; Ewing family of tumors; Primitive neuroectodermal tumors (PNET); Bone neoplasm - Ewing sarcoma ... to the lungs and other bones. At the time of diagnosis, spread is seen in about one- ...

Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing.

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Shanmugam, Victoria K; Tassi, Elena; Schmidt, Marcel O; McNish, Sean; Baker, Stephen; Attinger, Christopher; Wang, Hong; Shara, Nawar; Wellstein, Anton

2015-12-01

To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Evaluation of 99mTc-Labeled Bevacizumab-N-HYNIC Conjugate in Human Ovarian Tumor Xenografts.

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Shah, Syed Qaiser; Mahmood, Samia

2018-03-20

The aim of the present investigation was to examine the suitability of 99m Tc-N-HYNIC-BZMB as a specific vascular endothelial growth factor (VEGF)-targeting agent. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF. N-hydroxysuccinimide-2-hydrazinonicotinic acid (N-HYNIC) was conjugated to BZMB, followed by labeling with 99m Tc using N-[Tris(hydroxymethyl)methyl] glycine (tricine), ethylenediamine-N,N'-diacetic acid (EDDA), and nicotinic acid as coligands. 99m Tc-labeled BZMB was characterized in terms of 99m TcO 4 , radiocolloids, and labeled N-HYNIC-BZMB using thin-layer chromatography and HPLC. Poor metastatic SKOV-3 and high metastatic SKOV-3.ip1 human ovarian cancer cell lines were used for in vitro binding uptake of 99m Tc-N-HYNIC-BZMB. Biodistribution and scintigraphy accuracy were examined in human ovarian tumor xenografts in rats and rabbits. 99m Tc-N-HYNIC-BZMB prepared by using a mixture of tricine and EDDA demonstrated relatively high radiochemical purity (more than 98%). In L-cysteine and serum, it exhibited a stable behavior up to 16 hours. In vitro binding uptake indicated that it targets high metastatic SKOV-3.ip1 tumors. Biodistribution in human ovarian tumor xenografts in rats confirmed a significant uptake in SKOV-3.ip1 tumors (5.69% ± 1.86%, 4 hours). Scintigraphic accuracy in human ovarian tumor xenografts in rabbits validated its suitability as a high metastatic SKOV-3.ip1 radiotracer. High radiochemical purity, stability in saline and serum, biodistribution, and scintigraphy of 99m Tc-N-HYNIC-BZMB in human ovarian tumor xenografts in rats and rabbits confirmed its suitability as a potential radiotracer for imaging high metastatic SKOV-3.ip1 sites.

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

International Nuclear Information System (INIS)

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

1984-01-01

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

Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

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Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

2017-01-03

Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

A human lung xenograft mouse model of Nipah virus infection.

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Gustavo Valbuena

2014-04-01

Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

Proof of radiation-induced tumour TNF-α expression in Ewing sarcoma cell line RM-82 following clinically relevant in vitro fractionated irradiation and in vivo one-time irradiation

International Nuclear Information System (INIS)

Litzenberger, K.; Ruebe, C.E.; Erren, M.; Liu, L.; Valen, F. van; Palm, J.; Yang, K.; Ruebe, C.

2004-01-01

The purpose of the present study was to investigate the influence of fractionated irradiation on TNF-α expression in Ewing sarcoma cell line RM-82 in vitro and following its establishment as a xenograft tumour in the nude mouse in vivo [de

Fertility Rates of Ewes Treated with Medroxyprogesterone and Injected with Equine Chorionic Gonadotropin plus Human Chorionic Gonadotropin in Anoestrous Season

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I. W. Santos

2010-01-01

Full Text Available The aim of the present paper was to investigate the efficiency of the equine chorionic gonadotropin (eCG plus human chorionic gonadotropin (hCG associated with medroxyprogesterone acetate (MAP to estrous ewes synchronization. Ninety Texel ewes were investigated during seasonal anoestrous. The ewes received intravaginal sponges containing MAP (60 mg for nine days. At the time of sponges' withdrawal, the ewes were divided into three groups (G: (1 receiving 2 mL of saline i.m. (n=30, (2 receiving eCG 400 IU i.m. (n=30, and (3 receiving eCG 400 IU plus hCG 200 IU i.m. (n=30. Twelve h after sponges' removal, teaser rams were used to estrus check and remained with the ewes for 96 h. The artificial insemination was made with fresh semen 10 h after estrus detection. The effect of the treatment was not significant for the estrous rates among the groups: 73%, 90%, and 86%, respectively. The main effect was observed in the pregnancy and lambing rates among the groups: 70%, 86%, 56%, and 80%, 120%, 56%, respectively. Based on these results from our study, the use of the MAP—eCG is the best choice to improve the fertility rate on ewes.

sarcome d'ewing

African Journals Online (AJOL)

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

Impact of the ovarian cycle and pregnancy on plasma chemistry values in ewes.

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Zywicki, Micaela E; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2018-03-01

Normative data for plasma chemistry values in pregnant and non-pregnant reproductive age ewes are scant. Availability of data would aid monitoring of ewe health for both research and veterinary medicine. We determined specific plasma chemistry 95% confidence reference intervals (RIs) in non-pregnant and pregnant ewes. Mixed Western-breed ewes were grouped based on phase of ovarian cycle: luteal ( n = 15), follicular ( n = 17), or late-gestation pregnant ( n = 102). Plasma samples were collected for analysis on a commercial biochemical analyzer. For RIs, chemistry panels for the 3 groups of ewes included nutrients and metabolites (glucose, triglycerides, cholesterol, urea, creatinine, total protein, albumin, and bilirubin), enzymes (lactate dehydrogenase, aspartate transaminase, gamma-glutamyl transferase, alanine aminotransferase, and alkaline phosphatase [ALP]), and micronutrients (calcium, phosphorus, iron, sodium, potassium, and chloride). Sample chemistry values for glucose and total protein in pregnant ewes were lower than in follicular ewes; cholesterol was lower in pregnant and luteal ewes than in follicular ewes. In addition, total bilirubin in pregnant ewes differed from that in luteal ewes, and that in follicular ewes also differed from luteal ewes. ALP in pregnant ewes was higher than other groups; phosphorus in pregnant ewes was lower than in luteal ewes. Iron was higher in pregnant ewes than in luteal ewes, with iron in luteal ewes lower than in follicular ewes. These data provide clinical RIs comparing pregnant and non-pregnant ewes for use in monitoring ewe health in both human research and veterinary medicine.

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

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

2017-11-28

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

Small-molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma.

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Boro, Aleksandar; Prêtre, Kathya; Rechfeld, Florian; Thalhammer, Verena; Oesch, Susanne; Wachtel, Marco; Schäfer, Beat W; Niggli, Felix K

2012-11-01

Ewing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well-characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read-out system, we screened a small-molecule compound library enriched for FDA-approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit-list of nine well-known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes. Copyright © 2012 UICC.

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

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Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

2018-01-01

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Activity of a new nitrosourea (TCNU) in human lung cancer xenografts.

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Fergusson, R. J.; Anderson, L. E.; Macpherson, J. S.; Robins, P.; Smyth, J. F.

1988-01-01

The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts growing in immunodeficient mice. Moderate activity (specific growth delays of 0.63 and 1.13 compared with controls) was seen in two non-small cell tumours after a single oral administration of 20 mg-1kg. This dose was curative in a small cell xenograft. By using high performance liquid chromatography it was possible to detect parent drug in the tumours as well as the plasma and tissues after oral administration of TCNU. Drug sensitivity was correlated inversely with the amount of the DNA repair enzyme 0(6)-methylguanine-DNA methyltransferase assayed from extracts of the tumour cells but not with the levels of parent drug within the tumour. This compound appears to have unique pharmacokinetic properties compared with other chloroethylnitrosoureas. PMID:3390369

Effect of supplementary feeding to ewes and suckling lambs on ewe ...

African Journals Online (AJOL)

A trial was conducted to determine the effects on the performance of creep feeding suckling lambs and supplementing ewes that were grazing wheat stubble. Eight experimental units of South African Mutton Merino (SAMM) ewes and lambs were used in a 2 (supplementing ewes or not) x 2 (creep feeding lambs or not) ...

Stages of Ewing Sarcoma

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... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

Radiation responses of human bladder cancer assessed in vitro or as xenografts in immune-deprived mice

International Nuclear Information System (INIS)

Tannock, I.; Choo, B.; Buick, R.

1984-01-01

The response to radiation of cells derived from transitional cell carcinoma (TCC) of the human bladder has been studied. In vitro radiation survival curves for two established cell lines, RT-4 and MGH-U1, and for a cell line HB-10 derived recently from biopsy of a metastatic lymph node were characterized by values of D 0 and anti n in the range of 1.1-1.5 Gy and 2-7 respectively. The oxygen enhancement ratio of HB-10 cells was 2.8. Xenografts derived from the line HB-10 were irradiated in vivo under both aerobic and hypoxic conditions and cell survival was assessed in agar. Both aerobic and hypoxic survival curves were similar to that obtained for irradiation of hypoxic HB-10 cells in culture. Another tumor line, HB-15, derived from a cystoscopic biopsy of primary TCC, was maintained by transplantation of xenografts. Regrowth curves for HB-15 xenografts after radiation doses of 10 or 20 Gy were parallel to the growth curve for untreated controls but with volume reduced by factors of about 5 and 20 respectively. Cells derived from TCC of the human bladder exhibit parameters of radiation survival similar to those of other mammalian cells, and that xenografts derived from such cells contain a high proportion of hypoxic cells

An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

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Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

2011-10-01

Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

Imaging Ewing's sarcoma

International Nuclear Information System (INIS)

Henk, C.B.; Grampp, S.; Kainberger, F.; Breitenseher, M.; Imhof, H.; Mostbeck, G.H.

1998-01-01

Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and 201 thallium scanning has been shown to be sensitive in the monitoring of treatment response. Today, computed tomography is not longer used to image the tumor site; however, spiral CT of the lungs plays a central role as a staging and follow-up tool. (orig.) [de

Cryopreservation of human colorectal carcinomas prior to xenografting

International Nuclear Information System (INIS)

Linnebacher, Michael; Maletzki, Claudia; Ostwald, Christiane; Klier, Ulrike; Krohn, Mathias; Klar, Ernst; Prall, Friedrich

2010-01-01

Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research

FOXM1 is an oncogenic mediator in Ewing Sarcoma.

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Laura Christensen

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

Vaginal wall weakness in parous ewes: a potential preclinical model of pelvic organ prolapse.

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Young, Natharnia; Rosamilia, Anna; Arkwright, John; Lee, Joseph; Davies-Tuck, Miranda; Melendez, Joan; Werkmeister, Jerome; Gargett, Caroline E

2017-07-01

Ewes develop pelvic organ prolapse (POP) and may be a suitable model for preclinical studies evaluating cell-based therapies for POP. The aim of this study was to establish a clinical score of vaginal weakness and to compare POP Quantification System (POP-Q) values in conscious nulliparous and parous ewes and determine whether ewes are a suitable POP model. Ewes (n = 114) were examined while conscious, without sedation, and standing in a V conveyer by adapting the human POP-Q measurement. Ovine POP was defined as descent to the introitus from POP-Q points Aa 3 cm above the introitus on the anterior wall, Ap 3 cm above the introitus on the posterior wall, or increased Ba anterior wall descent above the urethra (≥0). A test-retest showed good inter- and intrarater reliability. There was no evidence of tissue mobility at Aa, Ap, Ba (all -3 cm) in nulliparous ewes (n = 14). In contrast, multiparous ewes had a median of -1 and interquartile range (IQR) (-2 to 0) for Aa, [0 (-1 to 0)] for Ap and [0 (-2.75 to 0)] for Ba (n = 33; P ewes. Ovine vaginal displacement was seen in 50.9 % of parous ewes and was strongly associated with parity (P = 0.003). A modified POP-Q in conscious ewes was established showing that the vaginal wall of parous animals has similar regions of weakness as do women and may be similarly related to parity. Ewes appear to be a representative preclinical model of human vaginal prolapse.

31P-NMR spectroscopy in measurements of physiological parameters and response to therapy of human melanoma xenografts

International Nuclear Information System (INIS)

Olsen, Dag Rune

1999-01-01

The aim of the study was to investigate whether ''31P-NMR spectroscopy can be utilized in prediction and monitoring of response to therapy or tumours. The specific aims were: 1) To investigate possible correlations between on the one hand bio energetics status, phospholipids resonance ratios, intracellular pH and phosphorus T 1 s and on the other hand tumour blood supply and oxygenation, tumour proliferation and necrotic fraction across tumour lines. 2) Reveal possible correlations between changes in tumour bio energetics status and phosphorus T 1 s and the changes in tumour blood flow, tumour oxygenation and necrotic fraction. 3) To investigate whether irradiation and hyperthermia treatment of tumours affect bio energetics status and phosphorus T 1 s. 4) To identify the tumour physiological factors that is effected by the treatment and influence the bio energetics status and phosphorus T 1 s. The results are presented in 8 papers with titles: 1)''31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma zeno graft lines: Tumour bio energetic status and blood supply. 2) ''31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation. 3) ''31P-nuclear magnetic resonance spectroscopy in vivo of four human melanoma xenograft lines: Spin-lattice relaxation times. 4) Effect of melanin on phosphorus T 1 s in human melanoma xenografts studied by ''31P MRS 5) Spin-lattice relaxation time of inorganic phosphate in human tumour xenografts measured in vivo by ''31P-magnetic resonance spectroscopy influence of oxygen tension. 6) Effects of hyperthermia on bio energetic status and phosphorus T 1 s in human melanoma xenografts monitored by ''31P-MRS. 7) Monitoring of tumour reoxygenation following irradiation by ''31P magnetic resonance spectroscopy an experimental study of human melanoma xenografts. 8) Radiation-induced changes in phosphorus T 1 values in human melanoma xenografts studied

Human tumour xenografts established and serially transplanted in mice immunologically deprived by thymectomy, cytosine arabinoside and whole-body irradiation

International Nuclear Information System (INIS)

Selby, P.J.; Thomas, J.M.; Peckham, M.J.

1980-01-01

Mice immunologically deprived by thymectomy, cytosine arabinoside treatment and whole-body irradiation were used to study the growth of human tumours as xenografts. 10/16 melanoma biopsies, 4/13 ovarian carcinoma biopsies and 3/6 uterine cancer biopsies grew as serially transplantable xenograft lines. The tumour lines were studied through serial passages by histology, histo-chemistry, electron microscopy, chromosome analysis, immune fluorescence, growth rate measurement and mitotic counts. They retained the characteristics of the tumours of origin, with the exception of loss of pigmentation in two melanomas, histological dedifferentiation in the uterine carcinomas, and increased mitotic frequency and growth rate in some melanomas. It was concluded that this type of animal preparation is as useful as alternative methods of immunological deprivation, or as athymic nude mice, for the growth of human tumour xenografts, at least for some experimental purposes. (author)

Multiparous Ewe as a Model for Teaching Vaginal Hysterectomy Techniques.

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Kerbage, Yohan; Cosson, Michel; Hubert, Thomas; Giraudet, Géraldine

2017-12-01

Despite being linked to improving patient outcomes and limiting costs, the use of vaginal hysterectomy is on the wane. Although a combination of reasons might explain this trend, one cause is a lack of practical training. An appropriate teaching model must therefore be devised. Currently, only low-fidelity simulators exist. Ewes provide an appropriate model for pelvic anatomy and are well-suited for testing vaginal mesh properties. This article sets out a vaginal hysterectomy procedure for use as an education and training model. A multiparous ewe was the model. Surgery was performed under general anesthesia. The ewe was in a lithotomy position resembling that assumed by women on the operating table. Two vaginal hysterectomies were performed on two ewes, following every step precisely as if the model were human. Each surgical step of vaginal hysterectomy performed on the ewe and on a woman were compared side by side. We identified that all surgical steps were particularly similar. The main limitations of this model are costs ($500/procedure), logistic problems (housing large animals), and public opposition to animal training models. The ewe appears to be an appropriate model for teaching and training of vaginal hysterectomy.

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

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Jakobsen Maria

2011-02-01

Full Text Available Abstract Background Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα, interleukin-12 (IL-12, and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs. Methods Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels. Results Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by

Ewe Pronunciation.

Science.gov (United States)

Schneeberg, Nan; Kpotufe, Prosper

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

General Information about Ewing Sarcoma

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... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

Treatment Option Overview (Ewing Sarcoma)

Science.gov (United States)

... Ewing Sarcoma Treatment Osteosarcoma Treatment Research Ewing Sarcoma Treatment (PDQ®)–Patient Version General Information About Ewing Sarcoma ... started or in another part of the body. Treatment Option Overview Key Points There are different types ...

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

Directory of Open Access Journals (Sweden)

Patrick P. Lin

2011-01-01

Full Text Available The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC. Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further.

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

Science.gov (United States)

Lin, Patrick P.; Wang, Yongxing; Lozano, Guillermina

2011-01-01

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further. PMID:20953407

Calm Merino ewes have a higher ovulation rate and more multiple pregnancies than nervous ewes.

Science.gov (United States)

van Lier, E; Hart, K W; Viñoles, C; Paganoni, B; Blache, D

2017-07-01

In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; Pewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; Pewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect

Comparison of energy rationing systems for late gestation ewes: Impacts on ewe and lamb performance.

Science.gov (United States)

Campion, F P; McGovern, F M; Lott, S; Fahey, A G; Creighton, P; Boland, T M

2016-08-01

The objectives of this study were 1) to compare the effects of a ME () or a NE () system for rationing ewes during late gestation on ewe and progeny performance and 2) to investigate incremental increases in NE allocation above 100% of recommendation during late gestation on ewe and progeny performance. Fifty-two twin-bearing ewes ( = 13 per treatment) were rationed to either 100% of recommended ME requirements (100% ME) or 100, 110, or 120% of recommended NE requirements (100% NE, 110% NE, and 120% NE) from d 112 of gestation to parturition. Mean energy intake, measured as ME and NE, from Day 112 of gestation to parturition was higher in all NE treatments compared with 100% ME ewes ( = 0.01). Ewes offered the 3 NE treatments had a higher live weight at parturition compared with 100% ME ewes ( = 0.02), with 100% NE and 120% NE ewes still being heavier than 100% ME ewes at 35 d postpartum ( = 0.02). Increasing NE allowance resulted in a linear decrease in the level of BCS loss prepartum ( = 0.01) and a linear increase in the level of BCS loss postpartum ( = 0.01). There was no difference observed between any of the treatments in total colostrum produced to 18 h postpartum ( = 0.29) or in total colostrum intake to 18 h postpartum ( = 0.27). Increasing maternal NE allowance led to a linear increase in lamb serum IgG concentration at 24 h postpartum ( = 0.03). The estimated milk production of 120% NE ewes tended to be higher than all other treatments at wk 6 of lactation ( = 0.08). Colostral SFA levels from 100% ME ewes was lower than that of all 3 NE treatments ( = 0.01), and unsaturated fatty acid (UFA) levels in colostrum of the 100% ME ewes were lower than those of the 100% NE ewes ( = 0.01). Cumulative levels of milk SFA, UFA, and MUFA did not differ between treatments ( = 0.19). Lamb growth rates during the first 5 wk postpartum were unaffected by treatment ( = 0.18) as were days to slaughter ( = 0.34). It can be concluded that both ME and NE systems used in this

A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

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Barbara Klink

Full Text Available Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting.

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Henker, Robert; Scholz, Michael; Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

2013-01-01

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations.

Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting.

Directory of Open Access Journals (Sweden)

Robert Henker

Full Text Available In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations.

Enhanced replication of attenuated HSV-1 in irradiated human glioma xenografts

International Nuclear Information System (INIS)

Advani, Sunil J.; Kataoka, Yasushi; Sibley, Greg S.; Song, Paul Y.; Hallahan, Dennis E.; Roizman, Bernard; Weichselbaum, Ralph R.

1997-01-01

Purpose: Previously we had shown that combining ionizing radiation (IR) with attenuated replication competent HSV-1 (R3616) significantly increased glioma xenograft eradication compared to IR or virus alone. One hypothesis is that IR induces cell factors that contribute to augment viral replication thereby increasing the efficacy of attenuated HSV-1. The purpose of this study was to examine if IR altered viral replication of attenuated HSV-1 in glioma xenografts Material and Methods: Human U-87MG glioma cells were grown in the hindlimb of athymic mice and grown to >200 mm 3 . Tumors were infected with 2x10 7 plaque forming units (pfu) of R3616 ( γ1 34.5 - ) or R7020 (multimutated, γ1 34.5 + ) on day 0 and irradiated with 20 Gy on day 1 and 25 Gy on day 2. Tumors were harvested 3, 5, 7, and 14 days after viral injection. Tumors were homogenized and sonnicated. Serial dilutions of tumor extract were overlaid on Vero cells to determine the number of pfu. In addition, in-situ hybridization to HSV-1 DNA was performed on tumors harvested at day 7. Results: In-situ hybridization revealed larger numbers of glial cells infected with HSV along with a greater distribution in the irradiated tumors compared to non-irradiated tumors. We next quantified viral particles in infected tumors +/- IR: Conclusion: Herein we demonstrate radiation enhanced viral replication as one of the interactive effects of combining IR and attenuated HSV in treating glioma xenografts and a potential therapeutic motif in the treatment of gliomas. To reduce normal tissue toxicity of HSV in glioma therapy, viruses must be attenuated. However, attenuating the virus compromises its replication and thus its potential efficacy. Our results indicate that IR augments the amount of virus recovered from human glioma xenografts for up to 3 days post IR. The results do not appear to be related to a specific mutation in the herpes genome but rather to herpes viruses in general. Yields of R7020 were greater than R

Primary Intradural Extraosseous Ewing's Sarcoma

OpenAIRE

Kim, Seok Won; Shin, Ho

2009-01-01

Ewing's sarcoma usually arises from skeletal bone, but rarely may have an extraskeletal origin. However, Ewing's sarcoma that originates around the spinal column, especially, the intradural extramedullary type is extremely rare. We report a rare case of primary intraspinal extraskeletal Ewing's sarcoma.

Effects of antineoplastic agents and ionizing irradiation on a human testicular cancer xenograft

International Nuclear Information System (INIS)

Osieka, R.; Pfeiffer, R.; Glatte, P.; Schmidt, C.G.; Bamberg, M.; Scherer, E.

1985-01-01

Chemotherapy has afforded a high percentage of definitive cures in advanced testicular cancer. Nevertheless some patients with large tumor burden still succumb to chemorefractory disease. Therefore preclinical and clinical evaluation of new drugs and agents not primarily used against this type of disease are still mandatory. For preclinical drug screening purposes heterotransplantation of specific human tumors yields a model with high validity for tumor markers and drug response. Heterotransplantation of a human embryonal testicular cancer was used for simultaneous testing of established agents such as cisplatin, melphalan, bleomycin, vinblastine, etoposide and adriamycin and some newer derivatives such as PHM or mafosfamide. Furthermore agents such as procarbazine, dacarbazine and methyl-CCNU that cross the blood-brain-barrier displayed some interesting activity. The results hint at a unique chemosensitivity pattern of the xenograft line, with some accordance between clinical response to vinblastine and bleomycin and good response of the xenografts to bleomycin but not to vinblastine. Radiotherapy was also effective against this tumor line, but there was not much difference in response when the schedule of fractionation was changed. It is concluded that a combined modality approach might salvage patients with residual, chemorefractory disease. (orig.) [de

Radiosensitivity and repair capacity of two xenografted human soft tissue sarcomas to photons and fast neutrons

International Nuclear Information System (INIS)

Budach, V.; Stuschke, M.; Budach, W.; Krause, U.; Streffer, C.; Sack, H.

1989-01-01

The radiation response, the relative biological effectiveness (RBE) and sublethal damage repair of two xenografted human soft tissue sarcomas after single doses and fractionated irradiation with 60 Co and 5.8 MeV fast neutrons are presented. (author)

Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors.

Science.gov (United States)

Barkla, D H; Tutton, P J

1981-12-01

Four lines of human colorectal cancer were established and serially propagated as subcutaneous xenographs in immunosuppressed inbred CBA/Lac mice. Established xenografts were then used to investigate the influence of a serotonin antagonist (BW 501c) and a histamine H2 receptor antagonists (Cimetidine) on xenograft growth. The growth of each of the four tumor lines was significantly inhibited by BW 501c throughout the treatment, whereas the growth of only two tumor lines was significantly inhibited by Cimetidine treatment. The response of individual tumor lines was not predictable on the basis of either tumor histopathology or the natural growth rate of the untreated xenograft. A number of alternative, but not mutually exclusive, hypotheses are suggested to explain the results. One hypothesis proposes that colorectal tumors are composed of subpopulations of tumor cells that are variously dependent on or independent of amine hormones. Another hypothesis is that tumor cells exhibit temporal changes in hormone sensitivity to amine hormones during treatment. Finally, it is suggested that serotonin and/or histamine H2 antagonists may be useful in preventing the repopulation of colorectal carcinomas following antineoplastic therapy with the use of conventional drugs.

Dietary -carbamylglutamate and rumen-protected -arginine supplementation ameliorate fetal growth restriction in undernourished ewes.

Science.gov (United States)

Zhang, H; Sun, L W; Wang, Z Y; Deng, M T; Zhang, G M; Guo, R H; Ma, T W; Wang, F

2016-05-01

This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary -carbamylglutamate (NCG) and rumen-protected -Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower ( ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter ( = 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased ( ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced ( ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved ( ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production.

Microsatellites with Macro-Influence in Ewing Sarcoma

Directory of Open Access Journals (Sweden)

Stephen L. Lessnick

2012-07-01

Full Text Available Numerous molecular abnormalities contribute to the genetic derangements involved in tumorigenesis. Chromosomal translocations are a frequent source of these derangements, producing unique fusion proteins with novel oncogenic properties. EWS/ETS fusions in Ewing sarcoma are a prime example of this, resulting in potent chimeric oncoproteins with novel biological properties and a unique transcriptional signature essential for oncogenesis. Recent evidence demonstrates that EWS/FLI, the most common EWS/ETS fusion in Ewing sarcoma, upregulates gene expression using a GGAA microsatellite response element dispersed throughout the human genome. These GGAA microsatellites function as enhancer elements, are sites of epigenetic regulation and are necessary for EWS/FLI DNA binding and upregulation of principal oncogenic targets. An increasing number of GGAA motifs appear to substantially enhance EWS/FLI-mediated gene expression, which has compelling biological implications as these GGAA microsatellites are highly polymorphic within and between ethnically distinct populations. Historically regarded as junk DNA, this emerging evidence clearly demonstrates that microsatellite DNA plays an instrumental role in EWS/FLI-mediated transcriptional regulation and oncogenesis in Ewing sarcoma. This unprecedented role of GGAA microsatellite DNA in Ewing sarcoma provides a unique opportunity to expand our mechanistic understanding of how EWS/ETS fusions influence cancer susceptibility, prognosis and transcriptional regulation.

Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

International Nuclear Information System (INIS)

Loevey, J.; Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J.; Dobos, J.; Vago, A.; Kasler, M.; Doeme, B.; Tovari, J.

2008-01-01

Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOα on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOα at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOα on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1α expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOα and irradiation were also tested in vitro. Results: in vitro, rHuEPOα treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOα administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1α expression but had no effect on tumor growth. At the same time rHuEPOα treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 ± 4.7 mg and 34.9 ± 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPOα treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1α expression, but also by destroying tumoral vessels. (orig.)

Promiscuous partnerships in Ewing's sarcoma.

Science.gov (United States)

Sankar, Savita; Lessnick, Stephen L

2011-07-01

Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing's sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing's sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing's sarcoma. However, in recent years there have been reports of rare fusions in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing's sarcoma and Ewing's-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

Rapid capillary electrophoresis approach for the quantification of ewe milk adulteration with cow milk.

Science.gov (United States)

Trimboli, Francesca; Morittu, Valeria Maria; Cicino, Caterina; Palmieri, Camillo; Britti, Domenico

2017-10-13

The substitution of ewe milk with more economic cow milk is a common fraud. Here we present a capillary electrophoresis method for the quantification of ewe milk in ovine/bovine milk mixtures, which allows for the rapid and inexpensive recognition of ewe milk adulteration with cow milk. We utilized a routine CE method for human blood and urine proteins analysis, which fulfilled the separation of skimmed milk proteins in alkaline buffer. Under this condition, ovine and bovine milk exhibited a recognizable and distinct CE protein profiles, with a specific ewe peak showing a reproducible migration zone in ovine/bovine mixtures. Based on ewe specific CE peak, we developed a method for ewe milk quantification in ovine/bovine skimmed milk mixtures, which showed good linearity, precision and accuracy, and a minimum amount of detectable fraudulent cow milk equal to 5%. Copyright © 2017 Elsevier B.V. All rights reserved.

Ewing sarcoma

International Nuclear Information System (INIS)

Hamanoue, Satoshi; Makimoto, Atsushi

2007-01-01

Ewing sarcoma is the second most frequent primary bone cancer affecting children or young adults. Advances in molecular biology have revealed common chromosomal translocations such as EWS-FLI1 among Ewing sarcoma and related diseases such as primitive neuroectodermal tumor (PNET), so these are considered as Ewing sarcoma family tumor (ESFT). Although fewer than 10% of patients with ESFT survived before establishment of modern multiagent chemotherapy, the multimodal therapeutic regimens including combination chemotherapy, radiotherapy, and surgery can cure 60% of patients with localized disease, due to the collaborative research in European-American or the international trials. The standard chemotherapy for localized ESFT now comprises vincristine, actinomycin D, cyclophosphamide and doxorubicin (VACD) in Europe or vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC-IE) in North America. Meanwhile, those with metastatic disease have a much worse outcome with an approximately 10-30% 5-year event-free survival rate. New American-European collaborative trials such as EURO-E.W.I.N.G. 99 are in progress for further improvement of the cure rate in localized and metastatic ESFT. In Japan, Japan Ewing Sarcoma Study Group (JESS) phase II clinical trial for localized ESFT, and some clinical trials including new drugs are ongoing and waiting for results. (author)

Volumetrical and morphological responses of human laryngeal squamous cell carcinoma xenografts treated with fractionated irradiation

International Nuclear Information System (INIS)

Hoogenhout, J.; Gasteren, H. van; Jerusalem, C.R.; Kal, H.B.

1988-01-01

Xenografts of both primary human laryngeal squamous cell carcinoma and its metastases were irradiated with five daily fractions of 5.0 Gy. Tumor volume changes, morphology, mitotic index and mitotic figures were studied. Primary xenografts disappeared within 17±3 days. Grafts of metastases showed complete regression within 26±5 days, or regrowth after a delay period. Mitotic activity was higher in the grafts of metastases. The number of mitotic figures decreased and ceased within 14 days in the primary tumor, while some were still occasionally noted in the grafts of metastases. Telophase stages were practically absent after the first fraction. This study suggests that the response of metastases to radiation therapy is lower than the response of the primary tumor. (orig.) [de

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

International Nuclear Information System (INIS)

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

1985-01-01

Review of current data from the Intergroup Ewing Sarcoma Study (IESS) shows that Ewing sarcoma is rare in bones of the hands and feet. The 12 patients from the IESS protocols with hand or foot Ewing sarcoma are comparable to those already reported in the literature. With the exception of lesions in the calcaneus, the prognosis for disease-free survival is excellent. The radiographic features of hand and foot Ewing sarcoma are generally those of classic Ewing sarcoma: permeation, soft-tissue mass, and often, associated sclerotic reaction. However, with the exception of sclerosis, features suggesting bone reaction and slow tumor growth in these patients were distinctly uncommon compared with Ewing sarcoma in general. Apparently location of the lesion is important, since in the reported cases in the literature and in this series, lesions of the calcaneus fared poorly. The importance of this set of patients therefore relates to awareness and early recognition of an unusual appearance and location of Ewing sarcoma

Ewe Basic Course. Revised Version.

Science.gov (United States)

Warburton, Irene; And Others

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

Effects of curcumin on growth of human cervical cancer xenograft in nude mice and underlying mechanism

Directory of Open Access Journals (Sweden)

Aixue LIU

Full Text Available Abstract The present study investigated the effects of curcumin (Cur on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control, 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05. The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05, and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05. Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.

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

Directory of Open Access Journals (Sweden)

Robert M. Whitfield

2011-01-01

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

Prions in milk from ewes incubating natural scrapie.

Directory of Open Access Journals (Sweden)

Caroline Lacroux

2008-12-01

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

Enhanced tumor control of human Glioblastoma Multiforme xenografts with the concomitant use of radiotherapy and an attenuated herpes simplex-1 virus (ASTRO research fellowship)

International Nuclear Information System (INIS)

Song, Paul Y.; Sibley, Gregory S.; Advani, Sunil; Hallahan, Dennis; Hyland, John; Kufe, Donald W.; Chou, Joany; Roizman, Bernard; Weichselbaum, Ralph R.

1996-01-01

Purpose: Glioblastoma Multiforme remains one of the most incurable of human tumors. The current treatment outcomes are dismal. There are several recent reports which suggest that some human glioblastoma xenografts implanted in the brains of athymic mice may be potentially cured with the use of an attenuated herpes simplex-1 virus alone. We have chosen a replication competent, non-neurovirulent HSV-1 mutant, designated R3616 to determine whether there is an interactive cell killing and enhanced tumor control with radiotherapy in the treatment of a human glioblastoma xenograft. Materials and Methods: In vivo, 1 mm 3 pieces of U-87 human glioblastoma cell line xenografts were implanted into the right hind limb of athymic mice and grown to > 200 mm 3 . A total of 112 mice were then equally distributed within four treatment arms (see chart below) based upon tumor volume. Xenografts selected to receive virus as part of the therapy were inoculated with three injections of 2 x 10 7 plaque forming units (PFU) of R3616 virus given on day 1, 2, and 3 for a total dose of 6 x 10 7 PFU. R3616 is a non-neurovirulent HSV-1 mutant created by the deletion of the γ 34.5 gene. Local field irradiation was delivered on day 2 (20 Gy) and day 3 (25 Gy). The mice were then followed for 60 days during which time the xenografts were measured twice weekly. A clinically non-palpable tumor (< 10% original volume) was scored as a cure. In addition percent-fractional tumor volume (FTV) and mean tumor volume (MTV) were calculated for each group. Results: Conclusion: While our tumor control with R3616 alone is similar to that reported in the literature, we have seen significantly enhanced tumor control and cell killing with the addition of RT suggesting a synergistic interaction between an oncolytic virus and radiation in the treatment of human glioblastoma multiforme xenografts

Experimental radioimmunotherapy of a xenografted human glioma using [sup 131]I-labeled monoclonal antibody to epidermal growth factor receptor

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Hiroshi; Nakazawa, Shozo [Nippon Medical School, Tokyo (Japan); Herlyn, D

1993-09-01

[sup 131]I-labeled F (ab')[sub 2] fragments of murine monoclonal antibodies (MAb) 425 specific to the epidermal growth factor receptor expressed on human gliomas were used in experimental human malignant glioma immunotherapy. Two injections of 150 [mu]Ci [sup 131]I-labeled 425 F(ab')[sub 2] achieved growth inhibition of U-87MG human malignant glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')[sub 2] was significantly superior to radiolabeled fragments of an anti-hepatitis virus control MAb A5C3 in influencing tumor growth. However, similar treatment of established human malignant glioma xenografts did not inhibit progressive tumor growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425F(ab')[sub 2]. These studies suggest that [sup 131]I-labeled MAbs have a significant antitumor effect where unmodified antibody is ineffective. Multiple doses of antibody may achieve an increase in labeled MAb concentration in tumors. (author).

Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

Energy Technology Data Exchange (ETDEWEB)

Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Uesato, Shin-ichi [Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680 (Japan); Watanabe, Kazushi [Proubase Technology Inc., Kanagawa 211-0063 (Japan); Tanimura, Susumu [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Koji, Takehiko [Department of Histology and Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kohno, Michiaki, E-mail: kohnom@nagasaki-u.ac.jp [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Proubase Technology Inc., Kanagawa 211-0063 (Japan); Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501 (Japan)

2013-04-19

Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.

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

NARCIS (Netherlands)

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

2010-01-01

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

Global Conservation of Protein Status between Cell Lines and Xenografts

Directory of Open Access Journals (Sweden)

Julian Biau

2016-08-01

Full Text Available Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery.

Characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice by DNA fingerprinting

DEFF Research Database (Denmark)

Türeci, O; Fischer, H; Lagoda, P

1990-01-01

Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. DNA fingerprint patterns from two human gliomas were established using two different hypervariable multilocus probes [( GTG]5 and 33.15). In general the cell lines investigated showed an overall stability in the DNA...... fingerprint pattern. However, differences in the DNA fingerprint patterns were shown to occur depending upon the above mentioned parameters....

Ewing tumors in infants

NARCIS (Netherlands)

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

2008-01-01

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

Next-generation sequence analysis of cancer xenograft models.

Directory of Open Access Journals (Sweden)

Fernando J Rossello

Full Text Available Next-generation sequencing (NGS studies in cancer are limited by the amount, quality and purity of tissue samples. In this situation, primary xenografts have proven useful preclinical models. However, the presence of mouse-derived stromal cells represents a technical challenge to their use in NGS studies. We examined this problem in an established primary xenograft model of small cell lung cancer (SCLC, a malignancy often diagnosed from small biopsy or needle aspirate samples. Using an in silico strategy that assign reads according to species-of-origin, we prospectively compared NGS data from primary xenograft models with matched cell lines and with published datasets. We show here that low-coverage whole-genome analysis demonstrated remarkable concordance between published genome data and internal controls, despite the presence of mouse genomic DNA. Exome capture sequencing revealed that this enrichment procedure was highly species-specific, with less than 4% of reads aligning to the mouse genome. Human-specific expression profiling with RNA-Seq replicated array-based gene expression experiments, whereas mouse-specific transcript profiles correlated with published datasets from human cancer stroma. We conclude that primary xenografts represent a useful platform for complex NGS analysis in cancer research for tumours with limited sample resources, or those with prominent stromal cell populations.

Distribution and pharmacokinetics of the prodrug daunorubicin-GA3 in nude mice bearing human ovarian cancer xenografts

NARCIS (Netherlands)

Houba, PHJ; Boven, E; van der Meulen-Muileman, IH; Leenders, RGG; Scheeren, JW; Pinedo, HM; Haisma, HJ

1999-01-01

N-[4-daunorubicin-N-carbonyl (oxymethyl)phenyl] O-beta-glucuronyl carbamate (DNR-GA3) is a glucuronide prodrug of daunorubicin (DNR) which induced a better tumor growth delay than DNR when studied at equitoxic doses in three human ovarian cancer xenografts. These results suggested that the prodrug

EXTRA-OSSEOUS EWING SARCOMA

NARCIS (Netherlands)

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

2009-01-01

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

Low pasture allowance until late gestation in ewes: behavioural and physiological changes in ewes and lambs from lambing to weaning.

Science.gov (United States)

Freitas-de-Melo, A; Ungerfeld, R; Hötzel, M J; Orihuela, A; Pérez-Clariget, R

2017-02-01

Low pasture allowance during gestation affects ewes' BW at parturition, the bond with their lamb, lamb development, and thus also may affect their responses to weaning. The objectives were to determine if native pasture allowance from before conception until late pregnancy affects ewe-lamb behaviours at lambing, ewes' milk yield, lambs' BW, and the behavioural and physiological changes of ewes and lambs at weaning. From 23 days before conception until 122 days of pregnancy, 24 ewes grazed on two different native pasture allowances: high (10 to 12 kg of dry matter (DM)/100 kg of BW per day; HPA treatment; n=12) or low (5 to 8 kg of DM/100 kg of BW per day; LPA treatment; n=12). Thereafter, all ewes grazed on Festuca arundinacea and received rice bran and crude glycerine. Ewes' body condition score (BCS) and BW were recorded during pregnancy and postpartum periods. Milk yield was determined on days 32, 41 and 54 after lambing. Lambs' BW was recorded from birth until 72 days after lambing. Latency from parturition until the ewe licked her lamb, maternal behaviour score (a test that evaluates maternal attachment to the lamb) and latency for lamb to stand up and suckle were determined. The behaviour of the lambs and ewes was recorded before and after weaning (at 65 days). The ewes' serum total protein, albumin and globulin concentrations were measured before and after weaning. The HPA ewes presented greater BW (Pewes during pregnancy and postpartum (Pewes (Pewes' behavioural and physiological changes at weaning. HPA lambs paced and vocalized more than LPA lambs (Pewes' BW, BCS and milk production were affected by pasture allowance until late pregnancy, this did not affect the behaviours that lead to the establishment of the mother-young bond, nor the ewes' behavioural responses at weaning. Lambs reared by ewes that grazed on low pasture allowance during pregnancy presented fewer behavioural changes and a lower decrease of albumin concentration after weaning. Lambs' BW

Targeting the p53 Pathway in Ewing Sarcoma

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

2011-01-01

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

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

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Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

Ewing's sarcoma, a rare but dangerous tumor

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Theophilus Maksha Dabkana

2015-01-01

Full Text Available Ewing's sarcoma or Ewing tumor is a rare primary bone tumor that affects mainly children and adolescents. It belongs to a group of cancers known collectively as Ewing sarcoma family tumors or Ewing family tumors. By the time, the patients present and diagnosis is made, the disease is usually advanced. We reviewed the case files of two patients managed in our hospital within one (2013. Fine-needle aspirations for cytology (FNAC and tissue biopsy were used for diagnosis in the two patients we had. The two patients, both males aged 20 years and 38 years presented late and FNAC and tissue biopsy revealed Ewing's sarcoma. They were referred for radio- and chemotherapy. However, due to poor socioeconomic status, they died of their primary disease. Unless diagnosed early, and in the absence of a multidisciplinary approach, Ewing's sarcoma is a fatal disease.

A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.

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Leacock, Stefanie W; Basse, Audrey N; Chandler, Garvin L; Kirk, Anne M; Rakheja, Dinesh; Amatruda, James F

2012-01-01

Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

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Berthou Christian

2010-12-01

Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

Kupffer cell blockade prevents rejection of human insulinoma cell xenograft in rats

International Nuclear Information System (INIS)

Lazar, G. Jr.; Farkas, G.; Lazar, G.

1998-01-01

Alloantigens are recognized by T-cells in the context of both class I and class II antigen, but class II antigens predominate in the recognition of xenoantigens. Since class II molecules bind peptides derived from exogenous proteins that have been phagocytized and digested into small fragments by antigen presenting cells, in the present studies the effect of gadolinium chloride (GdCl 3 )-induced Kupffer cell blockade on the survival of discordant insulinoma cell xenografts was investigated. Insulinoma cells isolated by means of collagenase from human insulinoma and cultured were transplanted through the v. portae into the liver of streptozotocin-induced diabetic, male, CFY inbred rats. In the control, streptozotocin-treated rats, the decrease in blood glucose level was only transitory, in contrast with the GdCl 3 -pretreated diabetic rats, which remained normoglycaemic during the 2-week observation period. Histologically, in the liver and lung of rats pre-treated with GdCl 3 , large areas of extensively proliferating insulinoma cells were seen, whereas no insulinoma cells were seen in either the liver or the lung of diabetic-control rats, not-treated with GdCl 3 . These studies suggest that the Kupffer cells play significant roles in the recognition of xenoantigens and the induction of xenograft rejection. (orig.)

Inhibitory effect of Dendrobium officinale polysaccharide on human gastric cancer cell xenografts in nude mice

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Liying ZHANG

2017-10-01

Full Text Available Abstract This study investigated the inhibitory effect of Dendrobium officinale polysaccharide (DOPA on human gastric cancer cell SGC-7901 xenografts in nude mice. The nude mice with SGC-7901 xenografts were randomly divided into model, 5-fluorouracil (5-Fu, low-dose DOPA, middle-dose DOPA and high-dose DOPA group. The later four groups were intragastrically administrated with 100, 200 and 400 mg·kg–1·day–1 DOPA, 400 mg·kg–1·day–1 5-Fu and normal saline, respectively. After treatment for 20 days, the tumor inhibition rate of in high-dose DOPA group was basically equivalent to 5-Fu group. Compared with 5-Fu, DOPA had no obvious toxic side effect on spleen or thymus indexes, routine blood indexes or liver and kidney functions of nude mice. Compared with model group, the serum tumor necrosis factor-α and interleukin-2 levels in middle- and high-dose DOPA group were significantly increased (P < 0.05, Bax protein expression was significantly increased (P < 0.05, and Bcl-2 protein expression was significantly decreased (P < 0.05. DOPA can inhibit the growth of SGC-7901 cell xenografts in nude mice. The mechanism may be related to its increase of serum TNF-α and IL-2 levels, up-regulation of Bax protein expression and down-regulation of Bcl-2 protein expression.

Radiological Findings of Primary Retroperitoneal Ewing Sarcoma

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Ulusan, S.; Koc, Z.; Tuba Canpolat, E.; Colakoglu, T. [Depts. of Radiology, Pathology, and General Surgery, Baskent Univ. Faculty of Medicine, Adana (Turkey)

2007-09-15

Ewing sarcomas are most commonly located in bone, while extra skeletal involvement of the retroperitoneum is extremely rare. We describe the radiologic and pathological findings in an adult patient with retroperitoneal extra skeletal Ewing sarcoma. Keywords: Color Doppler ultrasound; computed tomography; extra skeletal Ewing sarcoma; magnetic resonance imaging; ultrasound.

Radiological Findings of Primary Retroperitoneal Ewing Sarcoma

International Nuclear Information System (INIS)

Ulusan, S.; Koc, Z.; Tuba Canpolat, E.; Colakoglu, T.

2007-01-01

Ewing sarcomas are most commonly located in bone, while extra skeletal involvement of the retroperitoneum is extremely rare. We describe the radiologic and pathological findings in an adult patient with retroperitoneal extra skeletal Ewing sarcoma. Keywords: Color Doppler ultrasound; computed tomography; extra skeletal Ewing sarcoma; magnetic resonance imaging; ultrasound

Pharmacokinetics of lidocaine in nonpregnant and pregnant ewes.

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Santos, A C; Pedersen, H; Morishima, H O; Finster, M; Arthur, G R; Covino, B G

1988-12-01

The pharmacokinetics of lidocaine were studied in nonpregnant and pregnant ewes. The maternal femoral vessels were cannulated and, on the day of study, the urinary bladder was catheterized. Lidocaine HCl, 4-5 mg/kg, was administered by IV injection over 60 seconds. Serial samples of arterial blood and urine were collected over 4 hours, and drug concentrations were determined using a gas chromatographic technique. The volume of the central compartment was greater in pregnant than in nonpregnant ewes (1.51 +/- 0.20 vs. 0.96 +/- 0.16 L/kg) as was the volume of distribution at steady state (Vdss): 3.24 +/- 0.40 vs. 1.88 +/- 0.32 L/kg. The volume of distribution during the terminal exponential phase of drug elimination (Vd beta) and total clearance of lidocaine (Cl) were also higher in pregnant animals: 4.17 +/- 0.50 L/kg and 99.6 +/- 8.5 ml.min-1.kg-1, respectively; compared to 2.46 +/- 0.48 L/kg and 44.1 +/- 6.5 ml.min-1.kg-1, in nonpregnant ewes. However, the balance between these changes in Vd beta and Cl did not result in a significant difference in the elimination half-life of lidocaine (38.1 +/- 2.1 minutes in nonpregnant and 31.9 +/- 3.0 minutes in pregnant ewes). If these data are applicable to humans, the risk of drug accumulation after repeated administration of lidocaine is no greater in pregnant than in nonpregnant patients.

Adrenal Ewing's Sarcoma in an Elderly Man.

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Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

2018-02-15

Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

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Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

2010-03-01

Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

The TCD50 and regrowth delay assay in human tumor xenografts: Differences and implications

International Nuclear Information System (INIS)

Budach, W.; Budach, V.; Stuschke, M.; Dinges, S.; Sack, H.

1993-01-01

The response to irradiation of five human xenograft cell lines - a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma - were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120 mm 3 under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD 50 ) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD 50 was used in order to compare the data to previously published data from spheroids. The lowest TCD 50 was found in the lymphoma with 24.9 Gy, whereas the TCD 50 of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD 50 was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD 50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD 50 and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size

Control of oestrus and ovulation rates in Yankasa ewes

International Nuclear Information System (INIS)

Oyedipe, E.O.; Pathiraja, N.; Gyang, E.O.; Bawa, E.K.; Eduvie, L.O.

1991-01-01

Experiments were carried out in Yankasa sheep to study the efficacy of progesterone for oestrous synchronization and the effect of various gonadotrophin treatments (pregnant mare serum gonadotrophin (PMSG), human chorionic gonadotrophin (HCG) and gonadotrophin releasing hormone (GnRH)) on ovulation rates and litter size, and to elucidate responses by monitoring progesterone concentration. Preliminary studies showed normal progesterone profiles during the cycle, and a mean ovulation rate and litter size of 1.36 ± 0.34 and 1.23 respectively. Following synchronization with progesterone pessaries, PMSG dosage influenced ovulation rates. When 500 IU PMSG was given to ewes, HCG injection had an additive effect of increasing ovulation rate. Plasma progesterone concentrations showed significant treatment effects, being increased in relation to an increase in ovulation rates. Ovulation in Yankasa ewes occurred between 30-32 hours from onset of oestrus. In a fertility trial, mean ovulation rates and corresponding litter size were 2.1 versus 1.8 and 1.5 versus 1.2 for PMSG treated and untreated ewes respectively. 24 refs, 8 figs, 5 tabs

Ewing's sarcoma of the patella.

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Gorelik, Natalia; Dickson, Brendan C; Wunder, Jay S; Bleakney, Robert

2013-05-01

Ewing's sarcoma is a relatively rare malignancy, occurring mainly between 4 and 25 years of age. It usually arises from the pelvis, followed by the femur, tibia, and remainder of both the long bones of the extremities and flat bones of the axial skeleton. To the best of our knowledge, Ewing's sarcoma of the patella has never been reported previously. Patellar tumors occur infrequently and represent an uncommon etiology of anterior knee pain. We describe the rare case of a 41-year-old man who presented with a 3-4 month history of escalating right anterior knee pain and swelling. Imaging demonstrated an aggressive patellar tumor with an adjacent soft tissue mass. The diagnosis of Ewing's sarcoma was confirmed by pathology. Physicians should be aware of atypical locations for Ewing's sarcoma and, conversely, of rare tumors arising in the patella and accounting for anterior knee pain. Early recognition of such malignancies allows prompt initiation of treatment, hence improving prognosis.

Differential expression of CART in ewes with differing ovulation rates.

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Juengel, Jennifer L; French, Michelle C; Quirke, Laurel D; Kauff, Alexia; Smith, George W; Johnstone, Peter D

2017-04-01

We hypothesised that cocaine- and amphetamine-regulated transcript ( CARTPT ) would be differentially expressed in ewes with differing ovulation rates. Expression of mRNA for CARTPT , as well as LHCGR , FSHR , CYP19A1 and CYP17A1 was determined in antral follicles ≥1 mm in diameter collected during the follicular phase in ewes heterozygous for the Booroola and Inverdale genes (I+B+; average ovulation rate 4) and ++ contemporaries (++; average ovulation rate 1.8). In ++ ewes ( n  = 6), CARTPT was expressed in small follicles (1 to ewes. In I+B+ ewes, 5/6 ewes did not have any follicles that expressed CARTPT , and no CART peptide was detected in any follicle examined. Expression pattern of CYP19A1 differed between I+B+ and ++ ewes with an increased percentage of small and medium follicles (3 to ewes. Many of the large follicles from the I+B+ ewes appeared non-functional and expression of LHCGR , FSHR , CYP17A1 and CYP19A1 was less than that observed in ++ ewes. Expression of FSHR and CYP17A1 was not different between groups in small and medium follicles, but LHCGR expression was approximately double in I+B+ ewes compared to that in ++ ewes. Thus, ewes with high ovulation rates had a distinct pattern of expression of CARTPT mRNA and protein compared to ewes with normal ovulation rates, providing evidence for CART being important in the regulation of ovulation rate. © 2017 Society for Reproduction and Fertility.

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

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Margulies, B S; DeBoyace, S D; Damron, T A; Allen, M J

2015-10-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Ewing's Sarcoma of Bone Tumor Cells Produce MCSF that Stimulates Monocyte Proliferation in a Novel Mouse Model of Ewing's Sarcoma of Bone

Science.gov (United States)

Margulies, BS; DeBoyace, SD; Damron, TA; Allen, MJ

2015-01-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy. PMID:26051470

Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

OpenAIRE

Henker, Robert; Scholz, Michael; Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

2013-01-01

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain ...

Is There a Predisposition Gene for Ewing's Sarcoma?

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R. L. Randall

2010-01-01

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

Is There a Predisposition Gene for Ewing's Sarcoma?

Science.gov (United States)

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

2010-01-01

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

Ewing Sarcoma: An Eponym Window to History

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Timothy P. Cripe

2011-01-01

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

Imaging characteristics of primary cranial Ewing sarcoma

International Nuclear Information System (INIS)

Li, Wai-Yung; Saunders, Dawn E.; Brock, Penelope

2005-01-01

Ewing sarcoma accounts for 10-15% of all childhood malignant bone tumours and is second in prevalence to osteosarcoma. The skull bones are an unusual site of origin of primary Ewing sarcoma in children. Previous reports concentrate on the neurosurgical aspects and relatively good outcome compared to other bone tumours of the calvarium. Reported cases mainly describe the imaging characteristics on CT. To describe the MRI and CT features of primary cranial Ewing sarcoma. The neuroimaging of three cases of primary cranial Ewing sarcoma are reviewed. Our three cases show an extra-axial mass that is high attenuation on CT and low signal on T2-weighted MRI. Haemorrhagic components, dural extension and contrast enhancement are also characteristic features. CT attenuation and magnetic resonance signal characteristics reflect sheets of densely packed cells seen in Ewing sarcoma. (orig.)

Ewing's Sarcoma Localized in the Mandible: A Case Report

OpenAIRE

Akbayram, S; Başaranoglu, M; Kaya, A; Açıkgöz, M; Üstyol, L; Taşkın, GA; Dogan, M

2015-01-01

Ewing's sarcoma is one of the most aggressive primary bone tumours. Ewing's sarcoma arising from the bones of the head and neck region is extremely rare; only 4–9% of all Ewing's sarcoma originate in this region. We report a case of Ewing's sarcoma localized in the mandible because of its unusual presentation.

Ewing's Sarcoma of the Adrenal Gland.

Science.gov (United States)

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Vitamin E supplementation of undernourished ewes pre- and post-lambing reduces weight loss of ewes and increases weight of lambs.

Science.gov (United States)

Rosales Nieto, César Augusto; Meza-Herrera, César Alberto; Moron Cedillo, Felipe de Jesús; Flores Najera, Manuel de Jesús; Gámez Vázquez, Hector Guillermo; Ventura Pérez, Felipe de Jesús; Liu, Shimin

2016-03-01

The aim of this study was to test if vitamin E supplementation during late gestation and early lactation would affect the weight of ewes under nutritional restriction and the performance of their lambs. Mature Rambouillet ewes (n = 37) were fed a diet that supplied 70 % of the energy and 80 % of recommended protein requirements and randomly assigned to either vitamin E (vit E, n = 20, 4 IU of α-tocopherol kg(-1) of live weight) or control (n = 17, without vitamin E supplementation). During the experimental period, the mean weight of ewes decreased from 74.6 ± 2.4 to 58.1 ± 2.2 kg. Weight loss of ewes was slightly less for the vit E than the control (-65 vs -124 g day(-1), SEM = 46; P = 0.07). Lambs born from vit E-supplemented ewes were heavier than lambs from the control and grew significantly faster (239 vs 195 g day(-1), SEM = 29.3, P ewes are not met, supplementation of vitamin E during late gestation and early lactation might be an effective strategy to minimise ewe weight loss as well as to increase lamb growth.

[Primitive cutaneous Ewing's sarcoma: a diagnostic and therapeutic dilemma].

Science.gov (United States)

Delaplace, M; Mélard, P; Perrinaud, A; Goré, C; Vergier, B; Machet, L

2011-05-01

Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman. A 21-year-old woman presented with a scapular lesion that had been slowly developing for one year. The 1-cm lesion was removed and histological examination showed proliferation of small round cells in the dermis. Immunostaining revealed cytoplasmic membrane expression of CD99 and a negative immunoprofile for other small round-cell tumors. Ewing's sarcoma fusion gene transcripts were detected using fluorescence in situ hybridization (FISH). A staging examination revealed no other abnormalities. It was decided to treat the lesion as for osseous Ewing's sarcoma with wide resection followed by systemic adjuvant chemotherapy. Cutaneous Ewing's sarcoma raises concerns about diagnosis and treatment. Owing to the non-specificity of its clinical presentation, histology and immunoprofile, diagnosis of superficial Ewing's sarcoma is difficult and numerous differential diagnoses must be considered. When dealing with a surface tumour, the diagnosis of cutaneous Ewing's sarcoma must be considered. CD99 immunostaining and molecular testing for evidence of EWSR1 rearrangement are useful investigations to confirm the diagnosis. Furthermore, modalities of treatment must be carefully discussed. Cutaneous Ewing's sarcoma is currently treated in the same way as osseous Ewing's sarcoma (wide surgical excision, adjuvant radiotherapy when surgical margins are unsatisfactory, systemic adjuvant chemotherapy, and, in some cases, bone marrow transplant). However, some studies show a more favourable prognosis for cutaneous Ewing's sarcoma than for osseous Ewing's sarcoma. We may thus ask whether such aggressive multimodal treatment is needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Comparison of seasonal effects on some hematological and biochemical parameters between ewes with subclinical mastitis and healthy ewes

OpenAIRE

R.N. Sani; M. Moezifar

2016-01-01

This study was conducted to compare the effects of season on some hematological and biochemical parameters in ewes with subclinical mastitis and healthy ewes. A total of 1192 milk and blood samples were collected from ewes between February and April (791 samples in spring), August and October (401 samples in summer). California Mastitis Test (CMT), milk culture, hematologic and serum biochemical parameters were obtained from the medical records. Samples which were positive by bacterial cultur...

Mechanisms of Ewing sarcoma metastasis : biochemistry and biophysics

NARCIS (Netherlands)

Beletkaia, Elena

2015-01-01

Ewing sarcoma (ES) is a special type of bone cancer, first described by Dr. James Ewing in his paper ‘Diffusive endothelioma of bone’. Today Ewing sarcoma represents the second most common bone cancer among adolescents and young adults. Contrary to the positive achievement in treatment of localized

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

OpenAIRE

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

2013-01-01

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

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

Science.gov (United States)

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

2013-06-21

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

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

Science.gov (United States)

García-Santos, G; Martin, V; Rodríguez-Blanco, J; Herrera, F; Casado-Zapico, S; Sánchez-Sánchez, A M; Antolín, I; Rodríguez, C

2012-01-01

Background: Despite recent advances in cancer therapy, the 5-year survival rate for Ewing's sarcoma is still very low, and new therapeutic approaches are necessary. It was found previously that melatonin induces cell death in the Ewing's sarcoma cell line, SK-N-MC, by activating the extrinsic apoptotic pathway. Methods: Melatonin actions were analysed by metabolic viability/survival cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein activation/expression and electrophoretic mobility shift assay for transcription factor activation. Results: Melatonin increases the expression of Fas and its ligand Fas L, this increase being responsible for cell death induced by the indolamine. Melatonin also produces a transient increase in intracellular oxidants and activation of the redox-regulated transcription factor Nuclear factor-kappaB. Inhibition of such activation prevents cell death and Fas/Fas L upregulation. Cytotoxic effect and Fas/Fas L regulation occur in all Ewing's cell lines studied, and do not occur in the other tumour cell lines studied where melatonin does not induce cell death. Conclusion: Our data offers new insights in the study of alternative therapeutic strategies in the treatment of Ewing's sarcoma. Further attention deserves to be given to the differences in the cellular biology of sensitive tumours that could explain the cytotoxic effect of melatonin and the increase in the level of free radicals caused by this molecule, in particular cancer types. PMID:22382690

Dural metastasis of Ewing's sarcoma.

Science.gov (United States)

Ben Nsir, Atef; Boughamoura, Mohamed; Maatouk, Mezri; Kilani, Mohamed; Hattab, Nejib

2013-01-01

Metastatic Ewing's sarcoma to the central nervous system is an uncommon condition and debate concerning the true origin of its metastases is still up to date. To the best of our knowledge, only two cases of dural metastatic Ewing's sarcoma have been published in the English medical literature. We present an additional case in a 24-year-old female and discuss the pathogenesis of these unusual tumors with review of the relevant literature concerning their treatment and outcome. A 24-year-old female with previous history of pelvis Ewing's sarcoma and recently discovered lung metastases, presented with moderate headache for the past 2 weeks and weakness in her left leg for the past 2 days. Computed tomography scan and magnetic resonance imaging revealed an extra-axial right frontoparietal mass invading the superior sagittal sinus but with clear delineation with brain parenchyma. Imaging features were suggestive of a meningioma as no abnormalities in the skull abutting to the tumor were noted. The patient underwent surgical removal of her tumor. Near total resection was achieved and histological examination showed evidence of metastatic Ewing's sarcoma. Postoperative adjuvant radiation and chemotherapy were administered. The patient improved well postoperatively with full recovery of her motor weakness. She is symptom free with no signs of progression, at most recent follow-up, 8 months after surgery. Despite its rarity, metastatic Ewing's sarcoma must be considered in the differential diagnosis of extra-axial dural masses particularly meningiomas.

Clinical activity of pazopanib in metastatic extraosseous Ewing sarcoma

Directory of Open Access Journals (Sweden)

Steven Attia

2015-05-01

Full Text Available We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371. This national multi-institutional study is ongoing.

Importance of prolactin for lactation in the ewe

Energy Technology Data Exchange (ETDEWEB)

Hooley, R D; Campbell, J J; Findlay, J K [Reproduction Research Section, Melbourne Univ., C/- Animal Research Inst., Werribee (Australia)

1978-12-01

The effect of 2-bromo-..cap alpha..-ergocryptine (bromocriptine) on the induction and maintenance of milk secretion was studied in post-parturient ewes and in ovariectomized ewes artificially induced to lactate by treatment with oestrogen plus progesterone and then dexamethasone. Treatment with bromocriptine (about 0.4 mk/kg every 3 days) lowered and maintained the plasma concentration of prolactin at < 12 ng/ml. Ewes receiving bromocriptine concurrently with oestrogen plus progesterone during the priming phase had a significantly lower (P < 0.05) mean cumulative milk yield than control ewes, although the milk of the treated ewes contained normal amounts of fat, protein and lactose. Administration of bromocriptine during dexamethasone-induced lactogenesis had no significant effect on the mean cumulative milk yield but significantly (P < 0.05) increased the milk fat and protein content. In establishing lactation, bromocriptine markedly reduced the milk yield in both intact and ovariectomised ewes. The concentration of protein was not significantly affected although the milk fat content was higher in the bromocriptine-treated than in the control ewes. The effects of bromocriptine on milk yield and composition during galactopoiesis could be reversed by concurrent infusion of prolactin and the results suggest that prolactin is an important hormone during mammogenesis and galactopoiesis in sheep.

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

International Nuclear Information System (INIS)

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

1997-01-01

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

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

Science.gov (United States)

2013-06-20

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

Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

Directory of Open Access Journals (Sweden)

Harold D Love

2009-12-01

Full Text Available Benign prostatic hyperplasia (BPH and prostate carcinoma (CaP are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1 highly expressed in prostate, 2 had significant expression changes in response to androgens, and, 3 encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

The effect of nutrition and body condition of triplet-bearing ewes during late pregnancy on the behaviour of ewes and lambs.

Science.gov (United States)

Gronqvist, Gabriella V; Corner-Thomas, Rene A; Kenyon, Paul R; Stafford, Kevin J; Morris, Stephen T; Hickson, Rebecca Edith

2018-04-12

Triplet-born lambs are less likely to survive to weaning than twin-born or single-born lambs. Appropriate ewe-lamb bonding behaviours and lamb vigour behaviours are necessary for survival of lambs. The aim of this experiment was to determine whether maternal nutrition during late pregnancy influenced behaviour of the ewe and her lambs soon after birth, and to determine whether mid-pregnancy body condition score (BCS) influenced any behavioural response. The experiments included ewes that were in BCS 2.0, 2.5 or 3.0 in mid-pregnancy and were fed either ad libitum or to pregnancy-maintenance requirements in late-pregnancy (day 115 until 136 in experiment one, and day 128 until 141 in experiment two). The time taken for lambs to stand, contact dam, suck from dam and follow dam was recorded three to 18 hours after birth. The number of high- and low-pitched bleats emitted by the ewe and lambs was recorded, along with maternal behaviour score (MBS) of the ewe. Lambs in experiment two underwent a maternal-recognition test at 12 or 24 h. There were significant effects of feeding treatment on bleating behaviour of ewes and lambs, but these were inconsistent among BCS groups and between experiments. Lamb vigour behaviours were not affected by feeding treatment. In experiment one, there was no effect of feeding treatment or BCS on MBS, but in experiment two, ewes in BCS3 in mid-pregnancy had greater MBS than ewes in BCS2 in mid-pregnancy (MBS 3.1/5 vs MBS 2.1/5; Pewes and lambs, ad libitum feeding rather than feeding for pregnancy-maintenance requirements can not be used to improve behaviours soon after birth of triplet-bearing ewes in BCS 2 - 3 and their lambs in extensive pastoral conditions.

Effects of experimental Trypanosoma evansi infection on pregnancy in Yankasa ewes.

Science.gov (United States)

Adeyeye, A A; Ate, I U; Lawal, A I; Adamu, S

2016-03-15

Twenty pregnant Yankasa ewes were assigned to three groups to determine the effect of Trypanosoma evansi infection on pregnancy. Groups A and B comprising seven ewes each were infected with approximately 1.0 × 10(6) cells of T evansi per ewe through venepuncture at the second and third trimesters of pregnancy, respectively. Group C comprising six ewes served as uninfected control. There was slight pyrexia in the infected groups (groups A and B) but was absent in group C. The mean body weight, glucose concentration, and packed cell volume of ewes in group A were not significantly different from those in group C throughout the study. There was also no significant difference in mean glucose concentration between groups B and C. However, in group B, mean body weight was significantly (P ewes in group A was significantly (P ewes in group B decreased significantly (P ewes in the infected groups (groups A and B) compared with those in group C. However, there were significant (P ewes in group B compared with ewes in groups A and C. Mice inoculation with blood from infected ewes postpartum was parasitemic 18 to 25 days pi, for ewes in group B, whereas none of the mice in groups A and C were parasitemic. Lambs born from the infected groups (groups A and B) were also aparasitemic for 40 days postpartum. It was therefore concluded that the T evansi isolate used caused mild trypanosomosis when infected at third trimester, whereas ewes infected at second trimester were resistant. Copyright © 2016 Elsevier Inc. All rights reserved.

Lambing behaviour of Merino ewes from lines subjected to divergent ...

African Journals Online (AJOL)

No line difference was observed in the period that ewes spent grooming. Ewes caring for viable multiples groomed their offspring for a longer period than those caring for singles. Mature ewes tended to groom their lambs for a longer period than primi-parous maidens. A higher proportion of High (H) line ewes groomed their ...

The Use of Longitudinal 18F-FET MicroPET Imaging to Evaluate Response to Irinotecan in Orthotopic Human Glioblastoma Multiforme Xenografts

DEFF Research Database (Denmark)

Nedergaard, Mette K; Kristoffersen, Karina; Michaelsen, Signe R

2014-01-01

was compared. METHODS: Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain......OBJECTIVES: Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET Micro......, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts. CONCLUSIONS: 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio...

Ewing's sarcoma mimicking a meningioma in radiological findings: a case report

International Nuclear Information System (INIS)

Kwon, Hee Jin; Choi, Sun Seob

2007-01-01

Ewing's sarcoma is an uncommon primary bone tumor. Primary Ewing's sarcoma of the cranium is extremely rare and constitutes only 1% of all Ewing's sarcoma cases. Usually, primary Ewing's sarcoma of the carnium manifests as an expansile osteolytic malignant bone tumor with or without intracranial extension. We report here the radiological findings of a case of Ewing's sarcoma mimicking a meningioma in an 18-year-old man

Vascular abnormalities associated with acute hypoxia in human melanoma xenografts

International Nuclear Information System (INIS)

Simonsen, Trude G.; Gaustad, Jon-Vidar; Leinaas, Marit N.; Rofstad, Einar K.

2012-01-01

Background and purpose: The fraction of hypoxic cells has been shown to differ substantially among human tumors of the same histological type. In this study, a window chamber model was used to identify possible mechanisms leading to the development of highly different hypoxic fractions in A-07 and R-18 human melanoma xenografts. Materials and methods: Chronic and acute hypoxia was assessed in intradermal tumors using an immunohistochemical and a radiobiological assay. Functional and morphological parameters of the vascular networks of tumors growing in dorsal window chambers were assessed with intravital microscopy. Results: R-18 tumors showed significantly higher hypoxic fractions than A-07 tumors, and the difference was mostly due to acute hypoxia. Compared to A-07 tumors, R-18 tumors showed low vascular densities, low vessel diameters, long vessel segments, low blood flow velocities, frequent fluctuations in blood flow, and a high fraction of narrow vessels with absent or very low and varying flux of red blood cells. Conclusion: The high fraction of acute hypoxia in R-18 tumors was a consequence of frequent fluctuations in blood flow and red blood cell flux combined with low vascular density. The fluctuations were most likely caused by high geometric resistance to blood flow in the tumor microvasculature.

In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

Science.gov (United States)

Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

2017-03-01

Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

Conception rate and fecundity of Dohne Merino ewes in a ...

African Journals Online (AJOL)

Ninety-two 3-year-old Dohne Merino ewes were used in the trial and allocated to irrigated-lucerne equal-sized paddocks of 0.85 ha. Rotational grazing was applied at a stocking rate of 15 ewes per hectare, with rams left with the ewes continuously. A self-formulated creep feed and lick was provided to the lambs and ewes, ...

Diagnosis and treatment of Ewing's sarcoma

International Nuclear Information System (INIS)

Iwamoto, Yukihide

2007-01-01

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

PNET Ewing's sarcoma: a case report of a 8-year-old child presenting with PNET Ewing sarcoma

International Nuclear Information System (INIS)

Bauskar, Pratibha; Bhalavat, Rajendra; Chandra, Manish; Bauskar, Dipak

2016-01-01

PNET (Primitive Neuro-Ectodermal) mostly present in younger children. PNET Ewing sarcoma Ewing's sarcomas are rare, aggressive tumors, growth from undeveloped brain cells, with a tendency towards recurrence. We report the case of a 8-year-old girl who presented with a one year history of pain in her lower neck region with single episode of un-consciousness associate with left side upper and lower limb weakness. Magnetic resonance imaging demonstrated an abnormal marrow changes involving C5 vertebra and involvement of posterior elements showing expansive changes. Biopsy showed malignant small round cell tumor identifying as PNET Ewing sarcoma. Laminectomy and Decompression of cervical tumor. (author)

Effect of Using Melatonin Implants on Reproductive Performances in Turcana Ewes

Directory of Open Access Journals (Sweden)

Ioan Pădeanu

2011-10-01

Full Text Available It is estimated by some authors that the administration of subcutaneous melatonin implants during a period of 30 days, in lactating or dry ewes, would improve the reproductive performance in some sheep breeds. This study was conducted in Giarmata Mare, Timis County, on 78 lactating ewes and 75 dry ewes, which were individually inserted with implants containing 18 mg melatonin on 31 August 2009. Control group consisted of 100 lactating and dry ewes in equal proportions. The results shown that the main reproduction indices as prolificacy, birth rate and the lamb number productivity index are significantly (p < 0.05 higher in ewes from the experimental group, compared with ewes from the control group, and that treated ewes shortened the period of mating and lambing to half-time comparing to the control group. There is a suggestion that the use of melatonin implants Melovin ® type near the normal breeding season increases the reproductive performance of ewes from Turcana breed.

Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

International Nuclear Information System (INIS)

Schuuring, Janneke; Bussink, Johan; Bernsen, Hans; Peeters, Wenny; Kogel, Albert J. van der

2005-01-01

Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, when combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone

Copy Number Alterations and Methylation in Ewing's Sarcoma

Science.gov (United States)

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

2011-01-01

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

Copy Number Alterations and Methylation in Ewing's Sarcoma

Directory of Open Access Journals (Sweden)

Mona S. Jahromi

2011-01-01

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

The importance of prolactin for lactation in the ewe

International Nuclear Information System (INIS)

Hooley, R.D.; Campbell, J.J.; Findlay, J.K.

1978-01-01

The effect of 2-bromo-α-ergocryptine (bromocriptine) on the induction and maintenance of milk secretion was studied in post-parturient ewes and in ovariectomized ewes artificially induced to lactate by treatment with oestrogen plus progesterone and then dexamethasone. Treatment with bromocriptine (about 0.4 mk/kg every 3 days) lowered and maintained the plasma concentration of prolactin at < 12 ng/ml. Ewes receiving bromocriptine concurrently with oestrogen plus progesterone during the priming phase had a significantly lower (P < 0.05) mean cumulative milk yield than control ewes, although the milk of the treated ewes contained normal amounts of fat, protein and lactose. Administration of bromocriptine during dexamethasone-induced lactogenesis had no significant effect on the mean cumulative milk yield but significantly (P < 0.05) increased the milk fat and protein content. In establishing lactation, bromocriptine markedly reduced the milk yield in both intact and ovariectomised ewes. The concentration of protein was not significantly affected although the milk fat content was higher in the bromocriptine-treated than in the control ewes. The effects of bromocriptine on milk yield and composition during galactopoiesis could be reversed by concurrent infusion of prolactin and the results suggest that prolactin is an important hormone during mammogenesis and galactopoiesis in sheep. (author)

The potential interaction between ewe body condition score and nutrition during very late pregnancy and lactation on the performance of twin-bearing ewes and their lambs.

Science.gov (United States)

Cranston, L M; Kenyon, P R; Corner-Thomas, R A; Morris, S T

2017-09-01

The present study aimed to determine the impact of ewe body condition score (BCS) (over a range of 2.0 to 3.0) and nutritional treatments (consisting of differing herbage masses) during very late pregnancy and lactation and their potential interaction on the performance of twin-bearing ewes and their lambs to weaning. On day 142 of pregnancy, twin-bearing ewes with a BCS of 2.0, 2.5, or 3.0 were allocated to a "Moderate' or 'Unrestricted' nutritional treatment until day 95 of lactation (weaning). The nutritional treatments aimed to achieve average herbage masses of 1,200 to 1,300 kg dry matter (DM)/ha (Moderate) and 1,500 to 1,800 kg DM/ha (Unrestricted). There were no three-way interactions between ewe BCS group, nutritional treatment and time for any ewe or lamb parameter. The nutritional treatments had no effect (p>0.05) on lamb birth or weaning weight. Lambs born to Moderate ewes had greater survival and total litter weight at weaning (pewes had greater body condition and back-fat depth at weaning than Moderate treatment ewes (pEwes of BCS 2.0 group reared lighter lambs to weaning (pewes. This study suggests farmers should aim to have all ewes with a BCS of 2.5 or 3 in late pregnancy for optimal lamb weaning performance. Furthermore, there is no benefit to lamb production of offering ewes pasture masses >1,200 kg DM/ha during very late pregnancy and lactation.

Effect of estrogen withdrawal on energy-rich phosphates and prediction of estrogen dependence monitored by in vivo 31P magnetic resonance spectroscopy of four human breast cancer xenografts

DEFF Research Database (Denmark)

Kristensen, C A; Kristjansen, P E; Brünner, N

1995-01-01

The effect of estrogen withdrawal on energy metabolism was studied in four human breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in ovariectomized nude mice with a s.c. implanted estrogen pellet. After......-clamped tumors prepared 14 days after estrogen removal were analyzed for ATP and phosphocreatine content. Our findings suggest a correlation between estrogen withdrawal and the steady-state concentrations of ATP, phosphocreatine, and Pi in human breast cancer xenografts. Discrimination analysis...

Genetic and environmental parameters for ewe productivity in Merinos

African Journals Online (AJOL)

Data of 3272 lambing records collected on 818 ewes born from 689 dams and sired by 371 rams were used in the evaluation of ewe lifetime productivity (total number born, number weaned and total weight weaned). These records were collected from ewes born from 1969 to 1994 and which gave birth during the period ...

Primary Adult Renal Ewing's Sarcoma: A Rare Entity

OpenAIRE

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

2009-01-01

Background. Ewing's sarcoma of extraskeletal origin is uncommon and that is of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods. A retrospective review of the clinical features, treatment, and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993–December 2007 is reported. Results. Seven adult patien...

pO2 Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

International Nuclear Information System (INIS)

Ellingsen, Christine; Øvrebø, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit; Rofstad, Einar K.

2012-01-01

Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO 2 ) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO 2 fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO 2 was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO 2 fluctuations, the pO 2 fluctuation frequency in these regions, and the relative amplitude of the pO 2 fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO 2 in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO 2 and, thus, protect tumor tissue from cycling hypoxia.

Radiosensitivity of four human tumor xenografts. Influence of hypoxia and cell-cell contact

International Nuclear Information System (INIS)

Guichard, M.; Dertinger, H.; Malaise, E.P.

1983-01-01

Contact effect (CE) and hypoxia have been studied in human tumor cell lines transplanted in athymic nude mice. Four cell lines - one melanoma (Bell) and three colorectal adenocarcinomas (HT29, HRT18, and HCT8) - were studied. Cell survival was determined with an in vivo in vitro colony-forming assay. Survival curves were obtained under three different conditions: (1) tumor cells irradiated in air-breathing mice, (2) tumor cells irradiated in animals asphyxiated for 10 min, and (3) tumor cells plated and irradiated either immediately or 5 hr later. For all cell lines, radiosensitivity appeared to be lower when cells were irradiated in vivo than when they were irradiated in vitro. Only in the case of the HCT8 tumor did the relative in vivo radioresistance seem to be linked to hypoxia; in the other cell lines, hypoxia alone could not account for the lower in vivo radiosensitivity. Our results suggest that a CE plays an important role in the response of human xenografts to irradiation

Effect of space allowance and flooring on the behavior of pregnant ewes.

Science.gov (United States)

Vik, S G; Øyrehagen, O; Bøe, K E

2017-05-01

Space allowance recommendations for pregnant ewes vary considerably. The aim of this experiment was to investigate the effect of space allowance and floor type on activity, lying position, displacements, and aggressive interactions in pregnant ewes. A 3 × 2 factorial experiment was conducted with space allowance (0.75, 1.50, and 2.25 m/ewe) and type of flooring (straw bedding and expanded metal flooring) as the main factors. A total of 48 pregnant ewes were randomly assigned to 6 groups with 8 ewes in each group. All groups were exposed to each treatment for 7 d. The ewes were video recorded for 24 h at the end of each treatment period and general activity, lying position in the pen, and social lying position were scored every 15 min. Displacements and aggressive interactions were scored continuously from 1030 to 1430 h. Mean lying time ( flooring had no significant effect on general activity. Ewes in the straw bedding treatment spent more time lying in the middle of the pen than ewes on expanded metal ( flooring. Hence, recommended space allowance for pregnant ewes should not be lower than 1.50 m/ewe.

Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

Directory of Open Access Journals (Sweden)

Kristina A. Butler

2017-08-01

Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

Experimental study on 211At labelled monoclonal antibody 3H11 and its Fab fragment radioimmunotherapy for human gastric cancer xenografts in nude mice

International Nuclear Information System (INIS)

Jin Jiannan; Liu Ning; Zhang Shuyuan; Zhang Shiyuan; Luo Deyuan; Zhou Maolun

1996-01-01

Experimental radioimmunotherapy investigation of α-emitting radionuclide 211 At labelled anti-gastric cancer monoclonal antibody 3H11 and its Fab fragment for nude mice carrying human gastric cancer xenografts was conducted. Three i.p. injections of 14.8 or 22.2 kBq/g mouse were given, once every 5 days. The results showed that the growth of tumor xenografts was inhibited efficiently. The most evident therapy effect was observed at 15 days after treatment, and the tumor inhibition rates were 65% and 72%, respectively. No radiation injury of important organs was found

Ewing sarcoma versus osteomyelitis: differential diagnosis with magnetic resonance imaging

International Nuclear Information System (INIS)

Henninger, B.; Glodny, B.; Rudisch, A.; Trieb, T.; Loizides, A.; Judmaier, W.; Schocke, M.F.; Putzer, D.

2013-01-01

To find and evaluate characteristic magnetic resonance imaging (MRI) patterns for the differentiation between Ewing sarcoma and osteomyelitis. We identified 28 consecutive patients referred to our department for MRI (1.5 T) of an unclear bone lesion with clinical symptoms suggestive of Ewing sarcoma or osteomyelitis. MRI scans were re-evaluated by two experienced radiologists, typical MR imaging features were documented and a diagnostic decision between Ewing sarcoma and osteomyelitis was made. Statistical significance of the association between MRI features and the biopsy-based diagnosis was assessed using Fisher's exact test. The most clear-cut pattern for determining the correct diagnosis was the presence of a sharp and defined margin of the bone lesion, which was found in all patients with Ewing sarcoma, but in none of the patients with osteomyelitis (P < 0.0001). Contrast enhancing soft tissue was present in all cases with Ewing sarcoma and absent in 4 patients with osteomyelitis (P = 0.0103). Cortical destruction was found in all patients with Ewing sarcoma, 4 patients with osteomyelitis did not present any cortical reaction (P = 0.0103). Cystic or necrotic areas were identified in 13 patients with Ewing sarcoma and in 1 patient with osteomyelitis (P = 0.004). Interobserver reliability was very good (kappa = 1) in Ewing sarcoma and moderate (kappa = 0.6) in patients with osteomyelitis. A sharp and defined margin, optimally visualized on T1-weighted images in comparison to short tau inversion recovery (STIR) images, is the most significant feature of Ewing sarcoma in differentiating from osteomyelitis. (orig.)

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

Science.gov (United States)

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

2015-11-01

High intake of lucerne pastures or feeding of other high quality diets during early pregnancy may increase embryo mortality, negating any benefit of improved nutrition on ovulation rate in ewes. This study was conducted to determine whether grazing ewes on lucerne (Medicago sativa) pastures for 7 days prior to and throughout joining would result in greater foetal numbers than if ewes were removed 7 days after the commencement of joining, or if ewes grazed senescent pasture throughout the joining period. Merino ewes (300) were allocated to two replicates of three treatments, grazing pastures between Days -7 and 36 of an unsynchronised, natural autumn joining. Grazing lucerne to Day 7 of joining resulted in 30% more (Pewe than grazing senescent pasture (1.60±0.07 and 1.31±0.07, respectively), and 19% more lambs marked per ewe joined. Extending grazing of lucerne past Day 7 of joining did not result in additional foetuses per ewe (1.61±0.06) in comparison with only grazing lucerne to Day 7 of joining. Greater than 80% of ewes mated during the first 14 days of joining, and the proportions of ewes returning to oestrus and re-mating (0.18±0.022) and of non-pregnant (0.09±0.017) ewes were similar (P>0.05) among all treatment groups, suggesting no differences between treatments in embryo mortality. Grazing naturally cycling ewes on lucerne prior to and during joinings in autumn is recommended as a means to increase the number of lambs born, although additional gains may not be obtained by grazing past day seven of joining. Copyright © 2015 Elsevier B.V. All rights reserved.

High hRFI expression correlates with resistance to Fluoro pyrimidines in human colon cancer cell lines and in xenografts

International Nuclear Information System (INIS)

Sasaki, S.; Tokyo Univ., Tokyo; Watanabe, T.; Konishi, T.; Kitayama, J.; Nagawa, H.; Kobunai, T.

2005-01-01

We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-α induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoro pyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue micro array consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

Science.gov (United States)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

Hypocalcemia in ewes after a drought

Energy Technology Data Exchange (ETDEWEB)

Larsen, J.W.A.; Constable, P.D.; Napthine, D.V.

1986-01-01

A marked increase in the incidence of hypocalcemia of ewes 2 to 6 weeks before lambing was observed in the Western District of Victoria, following the break of the severe 1982/3 drought. A similar observation was made after the 1968 drought. In western Victoria, hypocalcemia is usually seen annually as sporadic cases or in sporadic outbreaks associated with some predisposing stress. After the drought broke in 1983, many farms reported cases of hypocalcemia in ewes. The incidence of hypocalcemia on the 9 farms the authors studied varied from 1 to 8% of all ewes, with some mobs having an incidence of over 10%. Detailed investigation of 9 farms that affected sheep were grazing pasture of unusually low calcium (Ca) content. Near record rains fell after the drought broke in late March 1983 resulting in luxuriant pasture growth with subterranean clover Trifolium subterraneum and capeweed Arctotheca calendula the dominant species. Cases of hypocalcemia commenced in May 1983 reaching a peak in June-July corresponding with flocks' lambing times, and continued into August. Most occurred spontaneously in mature ewes. A few farms experienced many cases during prelambing crutching.

Congenital Toxoplasmosis in Chronically Infected and Subsequently Challenged Ewes.

Science.gov (United States)

Dos Santos, Thaís Rabelo; Faria, Gabriela da Silva Magalhães; Guerreiro, Bruna Martins; Dal Pietro, Nathalia Helena Pereira da Silva; Lopes, Welber Daniel Zanetti; da Silva, Helenara Machado; Garcia, João Luis; Luvizotto, Maria Cecília Rui; Bresciani, Katia Denise Saraiva; da Costa, Alvimar José

2016-01-01

This experiment studied congenital transmission in sheep experimentally infected with oocysts of Toxoplasma gondii and reinfected at one of three stages of pregnancy. Twenty ewes were experimentally infected with T. gondii strain ME49 (day 0). After the T. gondii infection became chronic (IFAT≤512), the ewes were allocated with rams for coverage. After the diagnosis of pregnancy, these ewes were allocated into four experimental groups (n = 5): I-reinfected with T. gondii on the 40th day of gestation (DG); II-reinfected on DG 80; III-reinfected on DG 120; and IV-saline solution on DG 120 (not reinfected). Five ewes (IFATewes produced lambs serologically positive for T. gondii. The results of the mouse bioassay, immunohistochemistry and PCR assays revealed the presence of T. gondii in all 20 sheep and their lambs. The congenital transmission of T. gondii was associated with fetal loss and abnormalities in persistently infected sheep and in ewes infected and subsequently reinfected by this protozoan. Therefore, congenital T. gondii infection was common when ewes were chronically infected prior to pregnancy, with or without reinfection during at various stages of gestation.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins

NARCIS (Netherlands)

F.H. Jansen (Flip); J. Krijgsveld (Jeroen); A.L. Rijswijk (Angelique); G.J.C.M. van den Bemd (Gert-Jan); M.S. van den Berg (Mirella); W.M. van Weerden (Wytske); R. Willemsen (Rob); L.J.M. Dekker (Lennard); T.M. Luider (Theo); G.W. Jenster (Guido)

2009-01-01

textabstractNovel markers for prostate cancer (PCa) are needed because current established markers such as prostate-specific antigen lack diagnostic specificity and prognostic value. Proteomics analysis of serum from mice grafted with human PCa xenografts resulted in the identification of 44

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Science.gov (United States)

Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

2011-01-01

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Directory of Open Access Journals (Sweden)

Ashley A. Kowalewski

2011-01-01

Full Text Available Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22(q24;q12. This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

Science.gov (United States)

Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

2016-09-01

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Extra osseous primary Ewing's sarcoma.

Science.gov (United States)

Ali, Syed Asad; Muhammad, Agha Taj; Soomro, Abdul Ghani; Siddiqui, Akmal Jamal

2010-01-01

The case of 20 years old boy with an extra osseous Ewing's sarcoma is described. He was initially diagnosed as a case of infiltrative malignant tumour of left suprarenal gland on the basis of preoperative workup but postoperative biopsy of surgically excised specimen confirmed Extra-osseous Ewing's Sarcoma (EES) suprarenal gland with no evidence of malignancy on skeletal scintiscan, bone marrow aspirate and histopathology Suprarenal location of primary EES is unknown and probably has not been reported in literature. We report a unique case of EES.

Radiation induced expression of survivin in Ewing sarcoma cell-lines

International Nuclear Information System (INIS)

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

2009-01-01

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

Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

International Nuclear Information System (INIS)

Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik

2008-01-01

Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses

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

International Nuclear Information System (INIS)

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

1999-01-01

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

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.

Science.gov (United States)

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

2013-05-01

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 (Psheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. Copyright © 2013 Elsevier B.V. All rights reserved.

Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice

OpenAIRE

Yu-Qin Chen; Gang Chen

2015-01-01

Objective: This work was aimed at studying the inhibitory activity of metformin combined with the commonly used chemotherapy drug cisplatin in human lung cancer xenografts in nude mice. We also examined the combined effects of these drugs on the molecular expression of survivin, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor-C (VEGF-C), and vascular endothelial growth factorreceptor-3 (VEGFR-3) to determine the mechanism of action and to explore the potential applicati...

Vaginoscopy in Ewes Utilizing a Laparoscopic Surgical Port Device

Directory of Open Access Journals (Sweden)

Jeremiah Easley

2017-01-01

Full Text Available Vaginoscopy allows for diagnostic evaluation and treatment of the vaginal vault. A laparoscopic surgical port device and rigid telescope were utilized for serial vaginoscopy in 8 healthy anesthetized ewes. Vaginoscopy examinations were performed in each ewe at days 1, 14, and 28. This technique was well-tolerated and facilitated carbon dioxide vaginal inflation, complete vaginal examination, identification of the cervix, and targeted biopsy collection. No complications were encountered during or following the vaginoscopy procedures. The laparoscopic port device was well-suited to the ewe vulvar size. This technique could be applied to clinical evaluation in ewes for the purposes of examination, biopsy, culture, foreign body removal, and minor surgical procedures.

Ewing's Sarcoma of Bone Tumor Cells Produce MCSF that Stimulates Monocyte Proliferation in a Novel Mouse Model of Ewing's Sarcoma of Bone

OpenAIRE

Margulies, BS; DeBoyace, SD; Damron, TA; Allen, MJ

2015-01-01

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, cr...

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

International Nuclear Information System (INIS)

Kodama, Atsushi; Yanai, Tokuma; Sakai, Hiroki; Matsuura, Satoko; Murakami, Mami; Murai, Atsuko; Mori, Takashi; Maruo, Kouji; Kimura, Tohru; Masegi, Toshiaki

2009-01-01

Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. We established 6 xenograft canine HSA

Study the ovarian function in Awassi ewes

International Nuclear Information System (INIS)

Zarkawi, M.

1996-03-01

An experiment was carried out on local Awassi ewes to study the reproductive performance, progesteron concentrations, accuracy of pregnacy diagnosis and other reproduction related criteria of Awassi ewes using radioimunoassay (RIA). A total of 18 nulliparous Awassi ewes, aged about 1 year and weighing on average 36.9 Kg was used. Live-weight changes were recorded weekly. Blood samples (5 ml) were collected from the jugular vein for about 1 year at 10.00h. Sera were prepared and stored at - 20 deg until assyed. The FAO/IAEA progesterone RIA kits were used. Two ewes aborted after about three-and-a-half months of pregnancy due to mechanical reasons. The remaining ewes (16) lambed between 30th November 1994 and 22nd February 1995. Sex ratio was 1:1 (8 males: 8 females). Average birth weights for both sexes was 5210 ± 525 g. Average birth-weight was higher in males than females. Average male birth-weights was 5338 ± 515 g, (4600 - 6000 g) whereas was 5083 ± 538 g, (4180 - 5700 g) for female lambs. Average basal pre-mating progesterone concentration was 0.60 ± 0.42 n mol/l (0-1.7 n mol/l). Average maximum progesterone concentration during the luteal phase in non-pregnant ewes was 11.1 ± 3.1 n mol/l (5.8 -18.00 n mol/l). Average maximum progesterone concentration during gestation was 58.4 ± 20.9 n mol/l (29.25 - 100.00 n mol/l). The accuracy of pregnancy diagnosis at around 21 days post mating using RIA was 100%. It is concluded that RIA could be used for progesterone determination in Awassi sheep successfully, and that more research work on other aspects of reproduction in Awassi sheep should be carried out. (Author). 29 refs., 47 tabs., 5 figs

Clinical and biological significance of hepatoma-derived growth factor in Ewing's sarcoma.

Science.gov (United States)

Yang, Yang; Li, Hui; Zhang, Fenfen; Shi, Huijuan; Zhen, Tiantian; Dai, Sujuan; Kang, Lili; Liang, Yingjie; Wang, Jin; Han, Anjia

2013-11-01

We sought to investigate the clinicopathological significance and biological function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and enhanced sensitization to serum starvation-induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Factors affecting fecal egg counts in periparturient Katahdin ewes and their lambs.

Science.gov (United States)

Notter, D R; Burke, J M; Miller, J E; Morgan, J L M

2017-01-01

Selection for low fecal egg counts (FEC) can be used to genetically enhance resistance to gastrointestinal nematode parasites in growing lambs, thereby reducing the frequency of use of anthelmintics, facilitating marketing of organic lamb, and reducing the risk of development of anthelmintic resistance by the parasite. Recording of FEC in lambs has, therefore, been incorporated into several national sheep genetic evaluation programs. Ewes in late gestation and early lactation are also vulnerable to parasite infection and commonly experience a periparturient rise in FEC. This study was designed to assess factors associated with the periparturient rise in FEC in Katahdin ewes and associated changes in FEC in their lambs. Data came from 1,487 lambings by 931 Katahdin ewes from 11 farms in the Eastern United States. Fecal egg counts were measured in ewes at approximately 0, 30, and 60 d postpartum and in their lambs at approximately 60, 90, and 120 d of age. Approximately 1,400 lambs were evaluated at each measurement age. Data were analyzed separately for ewes and lambs and also initially analyzed separately for each measurement time. Repeated-measures analyses were then used to evaluate responses across measurement times. In ewes, FEC peaked at approximately 28 d postpartum, and we concluded that informative periparturient FEC could be obtained from 1 wk before until approximately 5 wk after lambing. Yearling ewes had higher FEC than adult ewes ( ewes that nursed twin or triplet lambs had higher FEC than ewes that nursed single lambs ( ewes and lambs nursed in larger litters were, like their dams, at greater risk of parasitism ( Ewes and lambs in these groups would benefit from enhanced monitoring of parasite loads at lambing and in early lactation. Correlations () between FEC in lambs at 90 d of age and FEC in ewes at 0, 30, and 60 d postpartum of 0.05 to 0.09 ( ≤ 0.05) support the presence of a genetic relationship between these 2 indicators of parasite

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

Science.gov (United States)

Kozelka, Paul R.

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…

Taste preferences of west African dwarf ewes at different trimester ...

African Journals Online (AJOL)

Taste preferences of pregnant West African dwarf (WAD) ewes were studied at different trimester periods using the multiple choice preference test method. A total of twelve WAD ewes of average body weight of 15.96 ± 4.17 kg, divided into two groups (A and B) were used for the study. Six pregnant ewes (in group A) served ...

Gastrointestinal trichostrongylosis can predispose ewes to clinical mastitis after experimental mammary infection.

Science.gov (United States)

Mavrogianni, V S; Papadopoulos, E; Gougoulis, D A; Gallidis, E; Ptochos, S; Fragkou, I A; Orfanou, D C; Fthenakis, G C

2017-10-15

Objective was to study, in an experimental model, the possible role of gastrointestinal nematode infection in predisposing ewes to mastitis during the lactation period. Twenty-four ewes (A or B [n=12]), free from nematode and trematode helminths, were used. Group A animals received 5000 third-stage larvae of a trichostrongylid helminth cocktail and group B ewes were unparasitised controls. Animals in group A developed gastrointestinal trichostrongylosis confirmed by >500epg in faecal samples; mean epg of group B ewes were Ewes were challenged by deposition of Mannheimia haemolytica into the teat duct. In group A, 7 ewes developed clinical and 5 subclinical mastitis; no ewe in group B developed clinical mastitis, but only subclinical (12 ewes) (P=0.002). M. haemolytica was isolated from 132/132 and 121/132 udder samples from group A or B, respectively (Pewes that developed clinical mastitis than in others which did not (0.709 and 0.162 versus 0.662 and 0.136, respectively; Pewes with subclinical mastitis (in group A or B), inducible-lymphoid-follicles were observed in the teat, which were not observed in ewes with clinical disease. Total pathology scores summed over all days were 127 and 73 for group A or B ewes, respectively (maximum possible 192; Pewes that developed clinical mastitis. It is concluded that, in view of bacterial challenge, gastrointestinal trichostrongylosis and particularly Teladorsagia infection, might lead to clinical mastitis, through various pathogenetic pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Protein metabolism of prolific ewes during late gestation and early lactation

NARCIS (Netherlands)

Sebek, L.B.J.

2001-01-01

Subject headings: protein / metabolism / ewes

Introduction of prolific crossbred ewes and a new protein evaluation system for ruminants, the DVE/OEB system, necessitate a reconsideration of ewe feeding strategies. The objective of this thesis is to investigate the amount

Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

Science.gov (United States)

Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

2011-01-01

Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

Hormonal levels after ovarian X-irradiation of ewes

International Nuclear Information System (INIS)

Driancourt, M.A.; Blanc, M.R.; Mariana, J.C.

1983-01-01

The effects of X-irradiation on ovulation rate, cyclicity and progesterone and FSH levels in Ile-de-France ewes (4 control and 16 irradiated) after they were treated during the breeding season were reported. The doses used (800 and 2400 R) destroyed 50% of all size classes of the follicular population. Ovulation occurred in 87% of the treated ewes (ovulation rate = 1) when they were irradiated 24 h after luteolysis; 78% of the corpora lutea resulting from these ovulations were normal as to length and progesterone production. FSH in treated ewes started to increase 20 h after treatment and remained higher than in the controls until ovulation time. Later, while these levels were similar between groups on the day of ovulation, high ovulatory levels persisted in irradiated ewes. In the next cycles, the length of the follicular phases, ovulation rate and progesterone and FSH levels were similar between groups

Use of tritiated water for estimating body composition in grazing ewes

International Nuclear Information System (INIS)

Russel, A.J.F.; Foot, J.Z.; McFarlane, D.M.

1982-01-01

Tritiated water was used to estimate total body water, body composition and water turnover of non-pregnant, pregnant, non-lactating and lactating grazing sheep. Body composition was estimated from equilibrated and extrapolated values of tritiated water space. These methods both overestimated the total body water measured directly. Body fat could be predicted satisfactorily from tritiated water space within the physiological states of ewes, i.e. lactating, pregnant, etc., although for lactating ewes the error of prediction is greater. It appears inadvisable at this stage to use equations derived from all classes of ewes to estimate body fat in ewes of any one physiological state. Water turnover varied, with the physiological state being highest for lactating ewes. (author)

Transfer of radiocesium from different environmental sources to ewes and suckling lambs

International Nuclear Information System (INIS)

Howard, B.J.; Mayes, R.W.; Beresford, N.A.; Lamb, C.S.

1989-01-01

Indoor experiments are described that compare the transfer of radiocesium to ewe and lamb tissues from different sources. Lactating ewes were fed either perennial ryegrass contaminated by Chernobyl fallout, or saltmarsh vegetation contaminated by marine discharges from the Sellafield reprocessing plant. The transfer to ewe tissues and milk was greater from the Chernobyl contaminated herbage than from saltmarsh vegetation. Lambs receiving a mixture of vegetation and milk were given radiocesium from one of the two vegetation sources or from milk obtained from the experimental ewes. Transfer to lamb tissues declined in the order milk greater than Chernobyl fallout greater than Sellafield discharge. The radiocesium transfer to lamb tissues exceeded that to ewe tissues. Transfer coefficients for 137Cs in the Chernobyl fallout were higher than most previously published figures at 0.12 d kg-1 for ewe muscle and 0.50 d kg-1 for lamb muscle. The transfer coefficient for 137Cs from ewe milk to lamb muscle was 1.20 d kg-1

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

Science.gov (United States)

Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

2015-07-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Primary Occipital Ewing's Sarcoma with Subsequent Spinal Seeding.

Science.gov (United States)

Alqahtani, Ali; Amer, Roaa; Bakhsh, Eman

2017-01-01

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Comparative analysis between endometrial proteomes of pregnant and non-pregnant ewes during the peri-implantation period.

Science.gov (United States)

Zhao, Haichao; Sui, Linlin; Miao, Kai; An, Lei; Wang, Dong; Hou, Zhuocheng; Wang, Rui; Guo, Min; Wang, Zhilong; Xu, Jiqiang; Wu, Zhonghong; Tian, Jianhui

2015-01-01

Early pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy. Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss. In this study, using well-managed recipient ewes that received embryo transfer as model, we compared the endometrial proteome between pregnant and non-pregnant ewes during implantation period. After embryo transfer, recipients were assigned as pregnant or non-pregnant ewes according to the presence or absence of an elongated conceptus at Day 17 of pregnancy. By comparing the endometrial proteomic profiles between pregnant and non-pregnant ewes, we identified 94 and 257 differentially expressed proteins (DEPs) in the endometrial caruncular and intercaruncular areas, respectively. Functional analysis showed that the DEPs were mainly associated with immune response, nutrient transport and utilization, as well as proteasome-mediated proteolysis. These analysis imply that dysfunction of these biological processes or pathways of DEP in the endometrium is highly associated with early pregnancy loss. In addition, many proteins that are essential for the establishment of pregnancy showed dysregulation in the endometrium of non-pregnant ewes. These proteins, as potential candidates, may contribute to early pregnancy loss.

pO{sub 2} Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

Energy Technology Data Exchange (ETDEWEB)

Ellingsen, Christine; Ovrebo, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit [Radiation Biology and Tumor Physiology Group, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway); Rofstad, Einar K., E-mail: einar.k.rofstad@rr-research.no [Radiation Biology and Tumor Physiology Group, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway)

2012-07-15

Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO{sub 2}) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO{sub 2} fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO{sub 2} was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO{sub 2} fluctuations, the pO{sub 2} fluctuation frequency in these regions, and the relative amplitude of the pO{sub 2} fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO{sub 2} in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO{sub 2} and, thus, protect tumor tissue from cycling hypoxia.

Ewing's sarcoma of the head and neck

Directory of Open Access Journals (Sweden)

Adriano Santana Fonseca

2000-11-01

Full Text Available CONTEXT: Ewing's sarcoma is a rare neoplasm, which usually arises in long bones of the limbs and in flat bones of the pelvis, with the involvement of head and neck bones being very unusual. CASE REPORT: a case of Ewing's sarcoma occurring in the mandible of a 35-year-old female. Pain and swelling of the tumor were the main complaints. The early hypothesis was an undifferentiated malignant neoplasm, possibly a sarcoma. The CT scan depicted an expansive lesion, encapsulated, with septa and characteristics of soft tissue, involving the left side of the mandible and extending to the surrounding tissues. The patient underwent surgical excision of the lesion, the definitive diagnosis of Ewing's sarcoma was established, and the patient commenced on radiotherapy.

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

Science.gov (United States)

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

Progesterone Blood Level For Pregnancy Diagnosis And Prediction Of Twinning In Egyptian Ewes

International Nuclear Information System (INIS)

NESSIM, M.Z.; KOTTB, M.K.I.; MUSTAFA, M.M.

2009-01-01

Twenty adult ewes were exposed to natural mating by fertile ram labelled on the chest, and marked ewes were separated from the crew. Blood samples were withdrawn from the jugular vein at the intervals 1, 10, 20,112,119,126,133,140 and 147 days after mating. Pregnancy test had been made through determination of progesterone (P4) level by radioimmunoassay. Plasma glucose, cholesterol and total lipids were determined during the last five weeks of pregnancy. Ewes were weighed on mating day and monthly until parturition and the lambs were weighed at birth. Significant difference (P<0.01) in P4 concentration was observed between day of mating and each of 10 and 20 days post-mating. Plasma P4 levels were increased with significant differences between pregnant ewes with single lamb and those with twin lambs at days 10 (P<0.05) and 20 (P<0.01) of pregnancy. The higher P4 level was detected in ewes carrying twins. Plasma P4 levels were increased during late pregnancy followed by a significant decrease (P<0.01) during the last two weeks of pregnancy, in both single and twin bearing ewes. Plasma glucose levels were found to be higher in twin pregnant ewes than single pregnant ewes at week 4 (P<0.05) and week 2 (P<0.01) before parturition. Non-significant differences were observed in plasma cholesterol and total lipids levels between pregnant ewes carrying single and twin lambs during late pregnancy. Monthly body weights were higher in twin than single pregnant ewes. Correlation between ewe and lamb body weights was observed in twin ewes only.

Association of lameness with milk yield and lactation curves in Chios dairy ewes.

Science.gov (United States)

Gelasakis, Athanasios I; Arsenos, Georgios; Valergakis, Georgios E; Banos, Georgios

2015-05-01

The objective of the study was twofold: (i) to quantify the differences in daily milk yield (DMY) and total milk yield (TMY) between lame and non-lame dairy ewes and (ii) to determine the shape of lactation curves around the lameness incident. The overall study was a prospective study of lameness for the surveyed sheep population, with a nested study including the selection of matching controls for each lame ewe separately. Two intensively reared flocks of purebred Chios ewes and a total of 283 ewes were used. Data, including gait assessment and DMY records, were collected on a weekly basis during on-farm visits across the milking period. A general linear model was developed for the calculation of lactation curves of lame and non-lame ewes, whereas one-way ANOVA was used for the comparisons between lame ewes and their controls. Lameness incidence was 12.4 and 16.8% on Farms A and B, respectively. Average DMY in lame ewes was significantly lower (213.8 g, P ewes was observed during the week 16 of the milking period (P ewes, remained significant at P ewes (about 32.5%), which was maximised 1 week later (35.8%, P ≤ 0.001) and continued for several weeks after recovery, resulting in 19.3% lower TMY for lame ewes for the first 210 d of the milking period (P ewes, as calculated by the general linear model, was 318.9 and 268.0 kg, respectively. The results of this study demonstrate evidence of significant financial losses in dairy sheep due to lameness which, however, need to be accurately estimated in further, more detailed, analyses.

The role of imaging in the evaluation of extraskeletal Ewing's sarcoma

African Journals Online (AJOL)

Primary bone tumours account for 5% of all adolescent and child cancers. When Ewing's sarcoma arises in soft tissue rather than bone, it is referred to as extraskeletal Ewing's sarcoma (ESS). Computed tomography (CT) scanning and magnetic resonance imaging (MRI) features of Ewing's sarcoma are non-specific, and a ...

Biological characterization of two xenografts derived from human CUPs (carcinomas of unknown primary

Directory of Open Access Journals (Sweden)

Bernheim Alain

2007-12-01

Full Text Available Abstract Background Carcinomas of unknown primary site (CUP are epithelial malignancies revealed by metastatic lesions in the absence of any detectable primary tumor. Although they often adopt an aggressive clinical pattern, their basic biology remains poorly understood. Laboratory research on their biology have been hampered so far by the absence of cell lines representative of CUPs. Methods We attempted xenografts of CUP clinical specimens in immunodeficient mice and subsequent in vitro culture of transplanted malignant cells. Whenever possible, malignant xenografted or cultured cells were characterized by microsatellite genotyping, immunohistology, electron microscopy, multifish chromosome analysis and search of TP 53 gene mutations. Results Successful xenografts were achieved in 2 cases out of 4. One of them (Capi1 was lost after 3 passages whereas the other one (Capi3 has been adapted to in vitro culture and is currently available to the scientific community with reliable identification based on microsatellite genotyping. Both Capi1 and Capi3 have histological characteristics of adenocarcinomas and display intense expression of EMA, CEA and cytokeratin 7. Multifish chromosome analysis demonstrated a translocation involving chromosomes 4 and 21 in both specimens. Distinct rare missense mutations of the TP53 gene were detected in Capi1 (codon 312 and Capi3 (codon 181; the codon 181 mutation is consistent with a previously reported similar finding in a small series of CUP specimens. Finally, intense membrane expression of c-kit was recorded in Capi3. Conclusion Our data suggest that xenografted tumors can be obtained from a substantial fraction of CUP clinical specimens. The hypothesis of a preferential association of CUPs with TP 53 mutations of codon 181 deserves further investigations. The Capi3 cell line will be a useful tool for assessment of novel c-kit inhibitors.

Changes in ovaries of X-irradiated ewes

International Nuclear Information System (INIS)

Tokos, M.; Arendarcik, J.; Maracek, I.; Stanikova, A.; Balun, J.; Praslicka, M.

1980-01-01

The qualitative histological alterations of ovaries and caryometric changes in the corpora lutea (CL) were studied in the ewes of the Slovak Merino breed after irradiation with X-rays. The experiments were conducted on 12 ewes divided into three groups of four animals. The first group included the control ewes, the second, experimental group was exposed to X-rays applied directly to the ovaries after laparotomy at a rate of 64.4 mC per kg (250 R), and the ewes in the third group were locally irradiated in the hypothalamo-hypophysial region at a rate of 516.5 mC per kg (2000 R). On the 10th day following the irradiation, the animals were killed, ovarian excisions were taken from the carcasses and processed. Changes in the blood vessels of the ovaries of the ewes in the second group were revealed by qualitative microscopic analysis. Pronounced subintimal changes, reminding of foamy cells described in available literature as a consequence of radiation damage to the blood vessels, were observed in the arteries and veins of the marrow and porta of the ovaries. A pronounced alteration of follicular structures was induced by single local irradiation of the ovaries which, at the same time, stimulated CL production. The irradiation of the hypothalamo-hypophysial region resulted in a multiplication of normal tertiary follicles and in an increase of the total number of follicles. No other histological changes were observed in the tissues of ovaries after irradiation of the hypothalamo-hypophysial region

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

Science.gov (United States)

Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

2010-08-18

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

Progesterone pretreatment increases the stress response to social isolation in ewes.

Science.gov (United States)

Freitas-de-Melo, Aline; Damián, Juan Pablo; Hötzel, Maria José; Banchero, Georgget; Ungerfeld, Rodolfo

2016-01-01

In rodents, progesterone (P4) pretreatment increases anxiety and response to stressors. Social isolation is a stressor that generates physiological and behavioural stress responses in sheep. The aim of the study was to compare the stress response of anoestrous ewes previously treated or not with P4 to the social isolation test. Ten ewes received P4 treatment during 13 d (group P4-W) and another 10 remained untreated as controls (group Con). The ewes were individually isolated in a novel place during 10 min, 24 h after the end of P4 pretreatment and their behaviours were recorded. Cortisol and P4 concentrations as well as body surface temperature were recorded before and after the test. Ewes of the P4-W group presented higher cortisol levels 0, 10, 20 and 30 min after the social isolation and had greater area under the curve of cortisol compared to Con ewes (41,785%±4,156% vs. 25,682%±4,565% during 75 min). Progesterone and body surface temperature increased after social isolation, with no differences between P4-W and Con ewes. There were no differences in behavioural responses to social isolation. P4 pretreatment appears to augment the stress response to social isolation in anoestrous ewes.

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

Science.gov (United States)

Fagone, Paolo; Nicoletti, Ferdinando; Salvatorelli, Lucia; Musumeci, Giuseppe; Magro, Gaetano

2015-10-01

Recent immunohistochemical analyses have showed that cyclin D1 is expressed in soft tissue Ewing's sarcoma/peripheral neuroectodermal tumor (PNET) of childhood and adolescents, while it is undetectable in both embryonal and alveolar rhabdomyosarcoma. In the present paper, microarray analysis provided evidence of a significant upregulation of cyclin D1 in Ewing's sarcoma as compared to normal tissues. In addition, we confirmed our previous findings of a significant over-expression of cyclin D1 in Ewing sarcoma as compared to rhabdomyosarcoma. Bioinformatic analysis also allowed to identify some other genes, strongly correlated to cyclin D1, which, although not previously studied in pediatric tumors, could represent novel markers for the diagnosis and prognosis of Ewing's sarcoma/PNET. The data herein provided support not only the use of cyclin D1 as a diagnostic marker of Ewing sarcoma/PNET but also the possibility of using drugs targeting cyclin D1 as potential therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

Effects of Some Environmental Factors on Reproductive Characters of Awassi and Redkaraman Ewes

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ESENBUĞA, Nurinisa

2014-01-01

In this research, the effects of some environmental factors on the reproductive characters of Awassi and Redkaraman ewes reared at the Research and Application Farm of Agricultural College at Atatürk University were investigated. Year, age of ewes, breed and the linear effect of body weight of ewes at the beginning of mating were studied. The year had no significant effect on any of the reproductive characters. Age of ewes, breed and body weight of ewes at the start of mating caused highly...

Primary Adult Renal Ewing's Sarcoma: A Rare Entity

Science.gov (United States)

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

2009-01-01

Background. Ewing's sarcoma of extraskeletal origin is uncommon and that is of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods. A retrospective review of the clinical features, treatment, and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993–December 2007 is reported. Results. Seven adult patients with primary renal Ewing's sarcoma were identified. All four patients with nonmetastatic disease had radical nephrectomy and received adjuvant chemotherapy +/− radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease-free survival in patients with nonmetastatic disease after combined modality treatment was 30.3 months. Conclusion. Primary adult renal Ewing's sarcoma is an aggressive tumor with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival. PMID:19478963

Primary Adult Renal Ewing's Sarcoma: A Rare Entity

Directory of Open Access Journals (Sweden)

Ravindra Mukkunda

2009-01-01

Full Text Available Background. Ewing's sarcoma of extraskeletal origin is uncommon and that is of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods. A retrospective review of the clinical features, treatment, and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993–December 2007 is reported. Results. Seven adult patients with primary renal Ewing's sarcoma were identified. All four patients with nonmetastatic disease had radical nephrectomy and received adjuvant chemotherapy +/− radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease-free survival in patients with nonmetastatic disease after combined modality treatment was 30.3 months. Conclusion. Primary adult renal Ewing's sarcoma is an aggressive tumor with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival.

Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

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Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

2013-01-15

Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

International Nuclear Information System (INIS)

Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.; Ballestas, Mary E.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

2013-01-01

Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

Aggressive Ewing's sarcoma appearing as a cold lesion on bone scan

International Nuclear Information System (INIS)

Chatti, K.; Guezguez, M.; Maha Ben Fredj, M.; Sfar, R.; Essabbah, H.; Mtaoumi, M.; Chatti, K.

2009-01-01

Ewing's sarcoma classically presents as a hot spot on bone scan as a result of increased vascularity of the tumor and new bone formation. Purpose We report and analyze an uncommon pattern of a 'cold' lesion in Ewing's sarcoma on bone scan and its pathophysiologic significance. Case report A 15-year-old boy complaining of thigh pain. CT scan evoked Ewing's sarcoma or osteitis. MRI evoked chronic osteitis. Scintigraphy showed a fairly intense and heterogeneous uptake on the femoral lesion and no abnormal uptake elsewhere. Biopsy showed none pathologic pattern. Three months later, a second biopsy concluded to Ewing's sarcoma. Bone scan showed a larger lesion with peripheral intense uptake centered by enlarged 'cold' area in the left femoral diaphysis and no evident bone metastasis. The patient underwent chemotherapy and surgery. Three months later, bone scan showed extensive skeletal metastasis. Conclusion Ewing's sarcoma appears usually as an intense lesion on bone scan. Nevertheless, decreased radiopharmaceutical uptake or 'cold' lesion may be seen in aggressive Ewing's sarcoma with lytic tumor, growth of which is very rapid and bony reaction is minimal. (authors)

Experimental radioimmunoimaging of human lung small cell carcinoma xenograft H-69 by NCC-ST-433 monoclonal antibody

International Nuclear Information System (INIS)

Kubota, Tetsuro; Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Watanabe, Masahiko; Ishibiki, Kyuya; Abe, Osahiko

1989-01-01

NCC-ST-433 monoclonal antibody raised against human gastric carcinoma xenograft (St-4) was labeled with l25 I using enzymatic and Iodogen methods. While labeling efficiency of the antibody was more excellent by enzymatic method, specific radioactivity of the antibody labeled by Iodogen method was higher than that by enzymatic method. The labeled antibody was stable in vitro and in vivo, and the labeled NCC-ST-433 was specifically accumulated in NCC-ST-433 antigen positive human tumor cell lines in vitro. The specificity of 125 I-NCC-ST-433 in vivo was found to be more excellent when this antibody was labeled by Iodogen method and acutually excellent images of H-69, a human small cell lung carcioma, were obtained 5 days after injection of 7 μg of 125 I-NCC-ST-433 per mouse. This method seemed to be promising for imaging human lung small cell carcinoma. (author)

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

Science.gov (United States)

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

1999-04-01

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 (P0.10) 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

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

Science.gov (United States)

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

2014-10-01

The first ovulation induced by male effect in sheep during seasonal anoestrus usually results in the development of a short cycle that can be avoided by progesterone priming before ram introduction. In elucidating the involvement of the hypothalamic-pituitary-gonadal axis in the occurrence of short cycles, the effects of progesterone and the time of anoestrus on the development of male-induced preovulatory follicles were investigated in anoestrous ewes using morphological, endocrine and molecular approaches. Ewes were primed with progesterone for 2 (CIDR2) or 12 days (CIDR12) and untreated ewes used as controls during early (April) and late (June) anoestrus. The duration of follicular growth and the lifespan of the male-induced preovulatory follicles were prolonged by ∼1.6 days in CIDR12 ewes compared with the controls. These changes were accompanied by a delay in the preovulatory LH and FSH surges and ovulation. Intra-follicular oestradiol concentration and mRNA levels of LHCGR and STAR in the granulosa and theca cells of the preovulatory follicles were higher in CIDR12 ewes than the control ewes. The expression of mRNA levels of CYP11A1 and CYP17A1 also increased in theca cells of CIDR12 ewes. CIDR2 ewes gave intermediate results. Moreover, ewes ovulated earlier in June than in April, without changes in the duration of follicular growth, but these effects were unrelated to the lifespan of corpus luteum. Our results give the first evidence supporting the positive effect of progesterone priming on the completion of growth and maturation of preovulatory follicles induced by male effect in seasonal anoestrous ewes, thereby preventing short cycles. © 2014 Society for Reproduction and Fertility.

The potential interaction between ewe body condition score and nutrition during very late pregnancy and lactation on the performance of twin-bearing ewes and their lambs

Directory of Open Access Journals (Sweden)

L. M. Cranston

2017-09-01

Full Text Available Objective The present study aimed to determine the impact of ewe body condition score (BCS (over a range of 2.0 to 3.0 and nutritional treatments (consisting of differing herbage masses during very late pregnancy and lactation and their potential interaction on the performance of twin-bearing ewes and their lambs to weaning. Methods On day 142 of pregnancy, twin-bearing ewes with a BCS of 2.0, 2.5, or 3.0 were allocated to a “Moderate’ or ‘Unrestricted’ nutritional treatment until day 95 of lactation (weaning. The nutritional treatments aimed to achieve average herbage masses of 1,200 to 1,300 kg dry matter (DM/ha (Moderate and 1,500 to 1,800 kg DM/ha (Unrestricted. Results There were no three-way interactions between ewe BCS group, nutritional treatment and time for any ewe or lamb parameter. The nutritional treatments had no effect (p>0.05 on lamb birth or weaning weight. Lambs born to Moderate ewes had greater survival and total litter weight at weaning (p1,200 kg DM/ha during very late pregnancy and lactation.

Effect of dietary inclusion of lampante olive oil on milk and cheese fatty acid profiles of ewes

DEFF Research Database (Denmark)

Vargas-Bello-Pérez, E.; Vera, R. R.; Aguilar, C.

2013-01-01

The objective of this experiment was to evaluate the effect of a dietary supplementation of lampant olive oil on the fatty aid profiles of the milk and cheese of ewes. Nine lactating ewes were used in a 3 × 3 Latin square design. Dietary treatments were supplemented with 0 (control; T0), 36 (T1......) and 88 (T2) g of lampante olive oil/kg of dry matter intake (DM). DM, milk yield and milk composition (fat and protein) were not affected by dietary treatments. Oleic and vaccenic acids gradually increased (P ... as the concentration of lampante olive oil was increased in dietary rations. Overall, the supplementation of lampante olive oil in the diets of lactating ewes increased monounsaturated FA and decreased saturated FA concentrations in milk and cheese, thus improving their quality from the human health standpoint....

Cytogenetically confirmed primary Ewing's sarcoma of the pancreas.

Science.gov (United States)

Golhar, Ankush; Ray, Samrat; Haugk, Beate; Singhvi, Suresh Kumar

2017-05-04

Ewing's sarcoma is a highly aggressive malignant tumour most commonly affecting long bones in children and adolescents. It is part of the Ewing's sarcoma family of tumours (ESFTs) that also include peripheral primitive neuroectodermal tumour and Askin's tumours. ESFTs share common cytogenetic aberrations, antigenic profiles and proto-oncogene expression with an overall similar clinical course. In 99% of ESFTs, genetic translocation with molecular fusion involves the EWSR1 gene on 22q12. Approximately 30% of ESFTs are extraosseous, most commonly occurring in the soft tissues of extremities, pelvis, retroperitoneum and chest wall. Primary presentation in solid organs is very rare but has been described in multiple sites including the pancreas. Accurate diagnosis of a Ewing's sarcoma in a solid organ is critical in facilitating correct treatment. We report the case of a 17-year-old girl with cytogenetically confirmed primary pancreatic Ewing's sarcoma and provide a brief review of the published literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Estrus resynchronization in ewes with unknown pregnancy status.

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Miranda, Vladinis O; Oliveira, Fernando C; Dias, Jenniffer H; Vargas Júnior, Sergio F; Goularte, Karina L; Sá Filho, Manoel F; Sá Filho, Ocilon G de; Baldassarre, Hernan; Vieira, Arnaldo D; Lucia, Thomaz; Gasperin, Bernardo G

2018-01-15

Although fixed-time artificial insemination (FTAI) protocols are available for sheep, estrus resynchronization has not been previously reported. The objectives of this study were to evaluate the effect of estrus resynchronization with exogenous progestogen on endogenous progesterone levels and to compare pregnancy rates after two consecutive estrus synchronizations in ewes. In Experiment 1, ewes (n = 20) received an intravaginal device (IVD) containing 60 mg medroxyprogesterone acetate (MPA) for 10 days. At the IVD withdrawal (D0), ewes received 250 IU eCG and were allocated into two treatments: either no further treatment (Control; n = 10) or estrus resynchronization (Resynch; n = 10) from D12 to D19. Serum progesterone (P4) levels did not differ at D12 and D19 (P > 0.05), but were greater at D15 for the Control compared with the Resynch group (P ewes (n = 250) were submitted to a first synchronization protocol followed by estrus detection and either artificial insemination (AI) or natural mating (NM). Subsequently, ewes were divided into two groups: Control (n = 104): which received no further treatment and were bred by NM; and Resynch (n = 146): which were submitted to a second synchronization starting on D14 (first IVD withdrawal = D0) and to NM after second IVD withdrawal (D20). Cumulative pregnancy rates did not differ between the Control (67.3%, 70/104) and Resynch (62.3%, 91/146) groups. In a third experiment, ewes (n = 83) were bred by two consecutive FTAI within a 20-day interval. Pregnancy rates after the first (30.1%, 25/83) and the second FTAI (36.2%, 21/58) did not differ (P > 0.05). In conclusion, although exogenous progestogen supplementation reduced circulating levels of P4, pregnancy maintenance was unaffected. Estrus resynchronization in ewes is feasible, resulting in similar fertility after the first and the second services. The use of resynchronization coupled with artificial insemination using semen from genetically

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

Science.gov (United States)

2013-01-01

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

Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.

Science.gov (United States)

Manes, Jorgelina; Ríos, Glenda; Fiorentino, María Andrea; Ungerfeld, Rodolfo

2016-03-15

The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P ewes treated with IS than in the other three treatments (P ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P ewes treated with IS than in the other three groups (P = 0.0005). The functionality and the viability of ram sperm is negatively affected by the cervical mucus of ewes pretreated with progestagen-impregnated IS used in estrous synchronization treatments. This may partially explain the decrease in conception rate obtained with treatments with IS. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of breed type and lactation status on reproductive performance in Awassi ewes

OpenAIRE

Kridli, R.T.; Abdullah, A.Y.; Husein, M.Q.

2009-01-01

This study was conducted to evaluate the effect of breed types and lactation status on reproductive performance of hormonally-treated Awassi ewes. A total of 282 ewes were treated with intravaginal progestagen sponges and equine chorionic gonadotropin. Ewes were mated with fertile rams following sponge removal. Lambing rate was similar between brown-and black-faced ewes, while the percentage of multiple births, fecundity and prolificacy were greater in black-faced ewes. Lambing rate and the p...

U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

Directory of Open Access Journals (Sweden)

Rafal Goraczniak

2013-01-01

Full Text Available U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2 and metabotropic glutamate receptor 1 (GRM1, in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6 indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.

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

Science.gov (United States)

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

2015-11-01

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

Pregnant ewes exposed to multiple endocrine disrupting pollutants through sewage sludge-fertilized pasture show an anti-estrogenic effect in their trabecular bone

International Nuclear Information System (INIS)

Lind, P. Monica; Oberg, Denise; Larsson, Sune; Kyle, Carol E.; Orberg, Jan; Rhind, Stewart M.

2010-01-01

Pregnant ewes were maintained on pastures fertilized, twice yearly, with either sewage sludge (2.25 tonnes dry matter/ha; Treated; T) or inorganic fertilizer containing equivalent amounts of nitrogen (Control; C), to determine effects on maternal and fetal bone structures, density and mechanical properties of exposure to environmental concentrations of multiple endocrine disrupting compounds (EDCs) and heavy metal pollutants. The ewes were maintained on the respective pastures from the age of about 8 months until they were 4-6 years of age and they were slaughtered at 110 d gestation. Metaphyseal parts of adult ewe femurs exhibited a significantly reduced mean, total cross sectional area (CSA, - 4%; p 3 , - 8.0%; p 2 , - 11.1%; p < 0.05) in T compared with C animals. Femurs of T ewes were stronger than those of C ewes but this may reflect greater body weights. At the mid-diaphyseal part of the fetal bones, there was a reduction in endosteal circumference (- 6.7%, p < 0.05) and marrow cavity area (- 13.8%, p < 0.05) in the female T fetuses compared with female C fetuses. In the male fetuses the mid-diaphyseal part total bone mineral content was higher (+ 3.0%, p < 0.05) in T than in C animals. No treatment difference in biomechanical bending was detected in the fetuses. It is concluded that ewes grazing pasture fertilized with sewage sludge exhibited an anti-estrogenic effect on their trabecular bone in the form of reduced mineral content and density, despite increased body weight. It is suggested that human exposure to low levels of multiple EDCs may have implications for bone structure and human health.

Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma

International Nuclear Information System (INIS)

Greve, B.; Sheikh-Mounessi, F.; Ernst, I.; Eich, H.T.; Kemper, B.; Goette, M.

2012-01-01

Background and purpose: Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro. Material and methods: An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation. Results: Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation. Conclusion: Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma. (orig.)

Non-genetic factors of udder morphology traits in Istrian ewes

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Valentino Držaić

2013-05-01

Full Text Available Considering the facts that Istrian sheep is Croatian indigenous breed with the highest milk production, and increasing interest of local farmers for machine milking implementation, the aim of this study was to determine the factors affecting udder morphology traits of Istrian ewes. Ninetythree purebred Istrian ewes with symmetrical udders and no signs of clinical mastitis, from second to fourth lactation, were used for this study. Average udder depth of Istrian ewes was 15.85 cm, udder width 13.05 cm, udder circumference 39.66 cm, cistern height 1.44 cm, teat position 2.85 (scored from 1 to 5, teat angle 47.32°, teat length 3.43 cm and teat width 2.03 cm. The traits related to udder size (depth, width, and circumference were significantly (P<0.01 affected by lactation milk yield. These traits were also in high and positive correlations (P<0.01 with daily milk yield. With the increase of parity, the morphological aptitude of udder to mechanical milking become worse, with an increase (P<0.01 of cistern height, teat angle and position. As lactation of Istrian ewes continued morphological traits defining udder aptitude for machine milking improved (decrease of cistern height, teat angle and position. Ewes with two and more lambs had larger udder (P<0.05 than ewes with a single lamb.

Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma.

Science.gov (United States)

Greve, B; Sheikh-Mounessi, F; Kemper, B; Ernst, I; Götte, M; Eich, H T

2012-11-01

Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro. An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation. Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation. Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma.

Extraskeletal Ewing's Sarcoma: insight into a ten years follow-up.

Science.gov (United States)

Zitelli, A; Manfredelli, S; Brunotti, G; Marcantonio, M; Pontone, S; Angelici, A

2013-01-01

Extraskeletal Ewing's sarcoma is a rare malignant soft tissue tumor, classified within the Ewing's Sarcoma Family Tumors. While the classical Ewing's Sarcoma affects mainly the bone during youth, the Extraskeletal histotype differs for age incidence, primary location and prognosis. Peak incidence and typical location are during adolescence and in the extremities respectively. We report a 30 year old woman case with a positive outcome after ten years from first diagnosis of Extraskeletal Ewing's sarcoma. Treatment was achieved through surgical resection plus adjuvant chemoradiotherapy derived from EW93 and IRS III trials. Conclusion. Our report represents an unusual case due to age of presentation, neoplasm location and long survival reached. In last decades several trials results demonstrated that long survival could be achieved by combined surgery and adjuvant multi-drug treatment.

beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

International Nuclear Information System (INIS)

Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

2008-01-01

β1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of β1 integrin signaling. We showed previously that β1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and β1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo

beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

Energy Technology Data Exchange (ETDEWEB)

Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

2008-06-02

{beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

Metastatic Ewing's sarcoma to the right ventricle

OpenAIRE

Datrice, Nicole; Milliken, Jeffrey; Kirsh, M.; Abolhoda, Amir; Saremi, Farhood; Sender, Leonard

2011-01-01

Ewing's sarcoma is a round cell neoplasm derived from neural crest cells that is part of the primitive neuroectodermal tumor (PNET) family. It is a rare, aggressive malignancy that affects young people, most commonly in the second decade of life. The treatment of localized disease has improved greatly over the past four decades, but the prognosis for metastatic disease remains poor. Cardiac metastases of Ewing's sarcoma are exceedingly rare, with only a few reported cases. This...

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

Czech Academy of Sciences Publication Activity Database

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

2003-01-01

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

Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

Directory of Open Access Journals (Sweden)

Cui Y

2016-11-01

Full Text Available Yanfen Cui,1,* Caiyuan Zhang,1,* Ran Luo,1 Huanhuan Liu,1 Zhongyang Zhang,1 Tianyong Xu,2 Yong Zhang,2 Dengbin Wang11Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 2MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: Arginine-glycine-aspartic acid (RGD-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA-coated ultrasmall superparamagnetic iron oxide (USPIO (referred to as RGD-PAA-USPIO in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC xenograft model by magnetic resonance imaging (MRI.Materials and methods: The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group.Results: The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05.Conclusion: This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

International Nuclear Information System (INIS)

Saland, E; Boutzen, H; Castellano, R; Pouyet, L; Griessinger, E; Larrue, C; Toni, F de; Scotland, S; David, M; Danet-Desnoyers, G; Vergez, F; Barreira, Y; Collette, Y; Récher, C; Sarry, J-E

2015-01-01

Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγ c null mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies

Dystocia due to schistosomus reflexus (cojoined twins in a Yankassa ewe

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Ambali Hauwa Motunrayo

2015-04-01

Full Text Available A two years' old, white and brown Yankassa ewe, weighing 20 kg was presented with dystocia of about 48 h duration at Mabs Veterinary Centre Ltd, Lagos. On thorough physical and vaginal examination, there were evidences of feotal parts and foul smelling discharges per vagina. A systematic and calculated traction and retropulsion revealed schistosomus reflexus cojoined twins. There was a complete recovery of the ewe 3 days post operative management. Finally, this case reported a true schistosomus reflexus cojoined twins in Yankassa ewe which was successfully relieved through traction and retropulsion despite the supposedly small birth canal which precluded the procedure in ewes except for caesarian section or fetotomy

Evaluation of a microbiological indicator test for antibiotic detection in ewe and goat milk.

Science.gov (United States)

Comunian, R; Paba, A; Dupré, I; Daga, E S; Scintu, M F

2010-12-01

Antibiotics are widely used for therapeutic and prophylactic purposes in dairy animals. The presence of residual antibiotics in milk could cause potentially serious problems in human health and have technological implication in the manufacturing of dairy products. The aim of this study was to evaluate Delvotest Accelerator (DSM Food Specialties, Delft, the Netherlands), a new system for a fully automated microbial test to detect antibiotic residues in ewe and goat milk. Forty-three samples of raw, whole, refrigerated bulk-tank milk samples (22 of ewe milk and 21 of goat milk) were analyzed during the whole lactation period. Four concentrations of 4 antibiotics were diluted in milk: penicillin G at 1, 2, 3, and 4 μg/L; sulfadiazine at 25, 50, 100, and 200 μg/L; tetracycline at 50, 100, 200, and 400 μg/L; and gentamicin at 25, 50, 100, and 200 μg/L. The detection limit of the Delvotest Accelerator was calculated as the range of antibiotic concentrations within which 95% of positive result lie. The range of detection limit of penicillin G and sulfadiazine was easily detected by Delvotest Accelerator at or below the European Union maximum residue limits, both for ewe and goat milk samples. In contrast, the system showed a lower ability to detect tetracycline and gentamicin both for ewe and goat milk samples. Very low percentages of false-positive outcomes were obtained. Lactation phase did not seem to be a crucial factor affecting the ability of the Delvotest Accelerator to detect spiked milk samples. A higher detection ability was observed for goat milk samples compared with ewe milk samples. A negative correlation between the percentage of positive milk samples detected and milk fat, protein, and lactose contents was observed for gentamicin only. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Plasma levels of progesterone in cycling and pregnant ewes

International Nuclear Information System (INIS)

Reddy, K.P.; Rao, P.N.; Reddy, B.B.; Murthy, A.S.N.

1989-01-01

The plasma progesterone profile of six cycling and three pregnant Nellore ewes was estimated by radioimmunoassay. The progesterone level of cycling ewes started rising from undetectable level on the day of oestrus to a mean peak value of 0.41 ± 0.09ng/ml during post oestrus day 10 to 14 and then declined to undetectable levels 1 to 2 days before subsequent oestrus. But the progesterone levels of pregnant ewes exhibited further raise from the post oestrus day 14 to the day 40. However, no correlation between oestrous cycle length and the total progesterone produced during the oestrous cycle was observed. (author). 9 refs., 2 figs

Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.

Science.gov (United States)

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

2014-07-01

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

Supplementation of lactating Dorper and Merino ewes on Themeda ...

African Journals Online (AJOL)

1988-04-14

Apr 14, 1988 ... The effects of energy and crude protein (CP) supplementation to lactating ewes on the performance of the ewes and their lambs ... contrast, provision of energy and CP supplements (1983), or incremental levels of energy (1984) during the ...... of starvation on bovine alimentary tract and its contents. Anim.

EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing's Sarcoma.

Science.gov (United States)

Hossain, Mohammad Motarab; Ray, Swapan Kumar

2014-10-01

Ewing's sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing's sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing's sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing's sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing's sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing's sarcoma in cell culture and animal models.

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

African Journals Online (AJOL)

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

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

Science.gov (United States)

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

2015-07-01

Elevated intakes of protein and energy may increase embryo mortality, but it is not clear whether fresh lucerne (Medicago sativa) pasture poses a risk. A two-year pen study using oestrous synchronised and artificially inseminated Merino ewes (n=175 in 2013 and 215 in 2014) evaluated whether feeding freshly cut lucerne pasture (mean crude protein 19.7%, metabolisable energy 9.4MJ/kg DM) at maintenance or ad libitum during different periods around insemination altered reproductive performance in comparison with ewes fed a Control diet (mean crude protein 7.8%, metabolisable energy 9.0MJ/kg DM) of pelleted faba bean hulls and oat grain hulls at maintenance. The proportion of pregnant ewes carrying multiple fetuses was reduced (P=0.026) when ewes were fed lucerne ad libitum between days 0 and 17 after insemination compared with the Control diet (0.18 and 0.34, respectively), but not when ewes were fed lucerne ad libitum between days 0 and 7 after insemination (0.22). Reproductive performance, including the proportion of ewes pregnant and the proportion with multiple fetuses, was not different (P>0.05) when ewes were fed lucerne at maintenance between days 0 and 7 compared with the Control diet. While reproductive performance was similar when ewes were fed lucerne at maintenance between 0 and 17 days after artificial insemination compared with pellets at maintenance, fetal numbers per pregnant ewe were reduced by feeding lucerne ad libitum after insemination. Copyright © 2015 Elsevier B.V. All rights reserved.

Appropriateness of using patient-derived xenograft models for pharmacologic evaluation of novel therapies for esophageal/gastro-esophageal junction cancers.

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Lorin Dodbiba

Full Text Available The high morbidity and mortality of patients with esophageal (E and gastro-esophageal junction (GEJ cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR, and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55 in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32. Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04 and older patients (p=0.01. Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.

Pregnant ewes exposed to multiple endocrine disrupting pollutants through sewage sludge-fertilized pasture show an anti-estrogenic effect in their trabecular bone

Energy Technology Data Exchange (ETDEWEB)

Lind, P. Monica, E-mail: Monica.Lind@medsci.uu.se [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Ullerakersvaegen 40, 751 85 Uppsala (Sweden); Oberg, Denise [Department of Environmental Toxicology, Uppsala University, Uppsala (Sweden); Larsson, Sune [Department of Orthopaedics, Uppsala University, Uppsala (Sweden); Kyle, Carol E. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Orberg, Jan [Department of Environmental Toxicology, Uppsala University, Uppsala (Sweden); Rhind, Stewart M. [Macaulay Land Use Research Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom)

2010-05-01

Pregnant ewes were maintained on pastures fertilized, twice yearly, with either sewage sludge (2.25 tonnes dry matter/ha; Treated; T) or inorganic fertilizer containing equivalent amounts of nitrogen (Control; C), to determine effects on maternal and fetal bone structures, density and mechanical properties of exposure to environmental concentrations of multiple endocrine disrupting compounds (EDCs) and heavy metal pollutants. The ewes were maintained on the respective pastures from the age of about 8 months until they were 4-6 years of age and they were slaughtered at 110 d gestation. Metaphyseal parts of adult ewe femurs exhibited a significantly reduced mean, total cross sectional area (CSA, - 4%; p < 0.05), lower trabecular bone mineral content (BMC, mg/mm; - 18%; p < 0.05), trabecular bone mineral density (BMD, mg/cm{sup 3}, - 8.0%; p < 0.05) and trabecular CSA, mm{sup 2}, - 11.1%; p < 0.05) in T compared with C animals. Femurs of T ewes were stronger than those of C ewes but this may reflect greater body weights. At the mid-diaphyseal part of the fetal bones, there was a reduction in endosteal circumference (- 6.7%, p < 0.05) and marrow cavity area (- 13.8%, p < 0.05) in the female T fetuses compared with female C fetuses. In the male fetuses the mid-diaphyseal part total bone mineral content was higher (+ 3.0%, p < 0.05) in T than in C animals. No treatment difference in biomechanical bending was detected in the fetuses. It is concluded that ewes grazing pasture fertilized with sewage sludge exhibited an anti-estrogenic effect on their trabecular bone in the form of reduced mineral content and density, despite increased body weight. It is suggested that human exposure to low levels of multiple EDCs may have implications for bone structure and human health.

Transarticular spread of Ewing sarcoma mimicking septic arthritis

Energy Technology Data Exchange (ETDEWEB)

Jordanov, Martin I.; Block, John J. [Vanderbilt University Medical Center, Department of Radiology and Radiological Sciences, Nashville, TN (United States); Gonzalez, Adriana L. [Vanderbilt University Medical Center, Department of Pathology, Nashville, TN (United States); Green, Neil E. [Vanderbilt Children' s Hospital, Department of Pediatric Orthopaedics, Nashville, TN (United States)

2009-04-15

Transarticular spread of tumor is rare; it has only been reported in the sacroiliac joint, intervertebral disk spaces, and facet joints. The anatomic and kinetic characteristics of the sacroiliac joint, as well as the changes the joint undergoes during a lifetime, make it particularly vulnerable to transarticular tumor invasion. Although extremely rare, Ewing sarcoma can extend through the sacroiliac joint and be virtually indistinguishable radiologically from septic arthritis. Furthermore, the clinical presentation of a child with Ewing sarcoma can be similar to that of a child with osteomyelitis. Laboratory values are quite nonspecific and are not always helpful in differentiating between the entities. Therefore, the possibility of sacroiliac joint transarticular Ewing sarcoma should be considered in a child presenting with hip pain, despite clinical, radiological and laboratory findings suggesting an infectious process. (orig.)

Transarticular spread of Ewing sarcoma mimicking septic arthritis

International Nuclear Information System (INIS)

Jordanov, Martin I.; Block, John J.; Gonzalez, Adriana L.; Green, Neil E.

2009-01-01

Transarticular spread of tumor is rare; it has only been reported in the sacroiliac joint, intervertebral disk spaces, and facet joints. The anatomic and kinetic characteristics of the sacroiliac joint, as well as the changes the joint undergoes during a lifetime, make it particularly vulnerable to transarticular tumor invasion. Although extremely rare, Ewing sarcoma can extend through the sacroiliac joint and be virtually indistinguishable radiologically from septic arthritis. Furthermore, the clinical presentation of a child with Ewing sarcoma can be similar to that of a child with osteomyelitis. Laboratory values are quite nonspecific and are not always helpful in differentiating between the entities. Therefore, the possibility of sacroiliac joint transarticular Ewing sarcoma should be considered in a child presenting with hip pain, despite clinical, radiological and laboratory findings suggesting an infectious process. (orig.)

Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A.

Science.gov (United States)

Fu, Jiaxin; Jiang, Han; Wu, Chenxuan; Jiang, Yi; Xiao, Lianping; Tian, Yonggang

2016-07-01

Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti‑cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase‑A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab‑resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA‑induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re‑sensitized cetuximab‑resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer‑cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.

Response of SA Mutton Merino ewes and their lambs to ...

African Journals Online (AJOL)

Oat, barley or triticale grain, enriched by addition of nitrogen, minerals, and an ... g per head per day to SA Mutton Merino ewes during late pregnancy and lactation. ... Ewes receiving enriched barley tended to have smaller losses of live mass ...

Antitumor Effects of Flavopiridol on Human Uterine Leiomyoma In Vitro and in a Xenograft Model

Science.gov (United States)

Lee, Hyun-Gyo; Baek, Jong-Woo; Shin, So-Jin; Kwon, Sang-Hoon; Cha, Soon-Do; Park, Won-Jin; Chung, Rosa; Choi, Eun-Som; Lee, Gun-Ho

2014-01-01

Dysregulated cyclin-dependent kinases (CDKs) are considered a potential target for cancer therapy. Flavopiridol is a potent CDK inhibitor. In this study, the antiproliferative effect of the flavonoid compound flavopiridol and its mechanism in human uterine leiomyoma cells were investigated. The present study focused on the effect of flavopiridol in cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Cell viability and cell proliferation assays were conducted. Flow cytometry was performed to determine the effect of flavopiridol on cell cycle. The expression of cell cycle regulatory-related proteins was evaluated by Western blotting. Cell viability and proliferation of uterine leiomyoma cells were significantly reduced by flavopiridol treatment in a dose-dependent manner. Flow cytometry results showed that flavopiridol induced G1 phase arrest. Flavopiridol-induced growth inhibition in uterine leiomyoma cells was associated with increased expression of p21cip/wafl and p27kip1 in a dose-dependent manner. Downregulation of CDK2/4 and Cyclin A with a concomitant increase in dephosphorylation of retinoblastoma was observed. This study demonstrates that flavopiridol inhibits cell proliferation by initiating G1 cell cycle arrest in human uterine leiomyoma. We also found that flavopiridol is effective in inhibiting xenografted human uterine leiomyoma growth. These results indicate that flavopiridol could prove to be a promising chemopreventive and therapeutic agent for human uterine leiomyoma. PMID:24572052

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

Science.gov (United States)

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

2012-01-01

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

Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

Science.gov (United States)

Prasad, Sahdeo; Tyagi, Amit K.; Siddik, Zahid H.; Aggarwal, Bharat B.

2017-01-01

Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa), exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT) relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC). When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin), proliferation (Ki-67 and cyclin D1) and metastasis (ICAM-1 and VEGF), all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3) in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity. PMID:29311914

Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

Directory of Open Access Journals (Sweden)

Sahdeo Prasad

2017-12-01

Full Text Available Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa, exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC. When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin, proliferation (Ki-67 and cyclin D1 and metastasis (ICAM-1 and VEGF, all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3 in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity.

Impact of anemia prevention by recombinant human erythropoietin on the sensitivity of xenografted glioblastomas to fractionated irradiation

International Nuclear Information System (INIS)

Stueben, G.; Poettgen, C.; Knuehmann, K.; Sack, H.; Stuschke, M.; Thews, O.; Vaupel, P.

2003-01-01

Background: Pronounced oxygen deficiency in tumors which might be caused by a diminished oxygen transport capacity of the blood (e.g., in anemia) reduces the efficacy of ionizing radiation. The aim of this study was to analyze whether anemia prevention by recombinant human erythropoietin (rHuEPO) affects the radiosensitivity of human glioblastoma xenografts during fractionated irradiation. Material and Methods: Anemia was induced by total body irradiation (TBI, 2 x 4 Gy) of mice prior to tumor implantation into the subcutis of the hind leg. In one experimental group, the development of anemia was prevented by rHuEPO (750 U/kg s.c.) given three times weekly starting 10 days prior to TBI. 13 days after tumor implantation (tumor volume approx. 40 mm 3 ), fractionated irradiation (4 x 7 Gy, one daily fraction) of the glioblastomas was performed resulting in a growth delay with subsequent regrowth of the tumors. Results: Compared to nonanemic control animals (hemoglobin concentration cHb = 14.7 g/dl), the growth delay in anemic mice (cHb = 9.9 g/dl) was significantly shorter (49 ± 5 days vs. 79 ± 4 days to reach four times the initial tumor volume) upon fractionated radiation. The prevention of anemia by rHuEPO treatment (cHb = 13.3 g/dl) resulted in a significantly prolonged growth delay (61 ± 5 days) compared to the anemia group, even though the growth inhibition found in control animals was not completely achieved. Conclusions: These data indicate that moderate anemia significantly reduces the efficacy of radiotherapy. Prevention of anemia with rHuEPO partially restores the radiosensitivity of xenografted glioblastomas to fractionated irradiation. (orig.)

Corpora lutea in superovulated ewes fed different planes of nutrition.

Science.gov (United States)

Kraisoon, A; Redmer, D A; Bass, C S; Navanukraw, C; Dorsam, S T; Valkov, V; Reyaz, A; Grazul-Bilska, A T

2018-01-01

The corpus luteum (CL) is an ovarian structure which is critical for the maintenance of reproductive cyclicity and pregnancy support. Diet and/or diet components may affect some luteal functions. FSH is widely used to induce multiple follicle development and superovulation. We hypothesized that FSH would affect luteal function in ewes fed different nutritional planes. Therefore, the aim of this study was to determine if FSH-treatment affects (1) ovulation rate; (2) CL weight; (3) cell proliferation; (4) vascularity; (5) expression of endothelial nitric oxide (eNOS) and soluble guanylate cyclase (sGC) proteins; and (6) luteal and serum progesterone (P4) concentration in control (C), overfed (O), and underfed (U) ewes at the early- and mid-luteal phases. In addition, data generated from this study were compared to data obtained from nonsuperovulated sheep and described by Bass et al. Ewes were categorized by weight and randomly assigned into nutrition groups: C (2.14 Mcal/kg; n = 11), O (2xC; n = 12), and U (0.6xC; n = 11). Nutritional treatment was initiated 60 d prior to day 0 of the estrous cycle. Ewes were injected with FSH on day 13-15 of the first estrous cycle, and blood samples and ovaries were collected at early- and mid-luteal phases of the second estrous cycle. The number of CL/ewe was determined, and CL was dissected and weighed. CL was fixed for evaluation of expression of Ki67 (a proliferating cell marker), CD31 (an endothelial cell marker), and eNOS and sGC proteins using immunohistochemistry and image analysis. From day 0 until tissue collection, C maintained, O gained, and U lost body weight. The CL number was greater (P ewes; however, concentration of P4 in luteal tissues was similar in both groups. Thus, in superovulated ewes, luteal cell proliferation and vascularity, expression of eNOS, and serum P4 concentration depend on the stage of luteal development, but not diet. Comparison to control ewes demonstrated several differences and some

Ewing's sarcoma: a neuroectodermal tumor of the chest wall

International Nuclear Information System (INIS)

Alcaraz, M. J.; Lorente, M. L.; Martin, A. M.; Gonzalez, I.

2000-01-01

Ewing's sarcoma is the second most common malignant bone tumor in children and young adults. It is most prevalent between the ages of 10 and 15 years. There are present two cases of Ewing's sarcoma of the chest wall. The clinical, radiological and pathological features are described and the therapeutic options are discussed. (Author)

Anterior cruciate ligament reconstruction with a novel porcine xenograft: the initial Italian experience

Science.gov (United States)

ZAFFAGNINI, STEFANO; GRASSI, ALBERTO; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; DI SARSINA, TOMMASO ROBERTI; RAGGI, FEDERICO; BENZI, ANDREA; MARCACCI, MAURILIO

2015-01-01

At the current state of the art in anterior cruciate ligament (ACL) reconstruction, multiple techniques have been presented but none has given clearly defined and improved results. One of the main issues concerns the choice of graft. The concept of using xenograft tissue, defined as a graft tissue from one species and destined for implantation in an unlike species, was introduced in order to try to overcome the mechanical and biological concerns associated with synthetic materials and the safety and quality concerns and availability problems of allograft tissue. Xenograft tissue carries the risk of producing an immunological reaction. In order to try to overcome or attenuate the immune response against porcine xenograft tissue, the Z-Process® (Aperion Biologics Inc, San Antonio, Texas, USA) has been developed and used to produce the Z-Lig® family of devices for ACL reconstruction procedures. Z-Lig® is a tendon graft with or without bone blocks, sourced from animal tissue in a manner consistent with what has normally been sourced from human tissue, and processed to overcome anti-Gal-mediated rejection and to attenuate other immunological recognition in humans. All this while ensuring sterility, viral inactivation and preservation of mechanical proprieties appropriate for an ACL reconstruction device. The Z-Lig® device has been tested in skeletally mature monkeys and given interesting and promising results from the preclinical performance and safety profile point of view. On this basis, it was possible to proceed with the first clinical trial involving humans, which gave similar encouraging results. The Z-Lig® device has also been implanted in Italy at the Rizzoli Orthopaedic Institute in Bologna, as a part of international multicenter prospective randomized blinded controlled study aimed at comparing xenograft with allograft tissue. PMID:26605257

Extraskeletal ewing sarcoma of cervical epidural region: cases report

Energy Technology Data Exchange (ETDEWEB)

Kim, Ki Jun; Jung, Hyun Seouk; Lee, Jae Hee; Sohn, Kyung Myung; Lee, Sung Yong [Our Lady of Mercy Hospital, Inchon (Korea, Republic of)

2003-01-01

Extraskeletal ewing sarcoma is a rare malignant tumor found in children and young adults. It commonly occurs in deep soft tissue of the trunk, especially in the paravertebral region and extremities. We report two cases of extraskeletal ewing sarcoma occurring as a cervical epidural tumor in elderly patients. The MRI and CT findings showed that paravertebral epidural tumors had invaded the spinal canal through the intervertebral foramen. At T1-weighted MR imaging, the masses were isointense to muscle, and at T2* and T2-weighted images were hyperintense, and heterogeneous contrast enhancement was observed. Extraskeletal ewing sarcoma, though quite rare, should be borne in mind in the differential diagnosis of paraspinal epidural tumors.

Extraskeletal ewing sarcoma of cervical epidural region: cases report

International Nuclear Information System (INIS)

Kim, Ki Jun; Jung, Hyun Seouk; Lee, Jae Hee; Sohn, Kyung Myung; Lee, Sung Yong

2003-01-01

Extraskeletal ewing sarcoma is a rare malignant tumor found in children and young adults. It commonly occurs in deep soft tissue of the trunk, especially in the paravertebral region and extremities. We report two cases of extraskeletal ewing sarcoma occurring as a cervical epidural tumor in elderly patients. The MRI and CT findings showed that paravertebral epidural tumors had invaded the spinal canal through the intervertebral foramen. At T1-weighted MR imaging, the masses were isointense to muscle, and at T2* and T2-weighted images were hyperintense, and heterogeneous contrast enhancement was observed. Extraskeletal ewing sarcoma, though quite rare, should be borne in mind in the differential diagnosis of paraspinal epidural tumors

Detection limits of antimicrobials in ewe milk by delvotest photometric measurements.

Science.gov (United States)

Althaus, R L; Torres, A; Montero, A; Balasch, S; Molina, M P

2003-02-01

The Delvotest method detection limits per manufacturer's instructions at a fixed reading time of 3 h for 24 antimicrobial agents were determined in ewe milk by photometric measurement. For each drug, eight concentrations were tested on 20 ewe milk samples from individual ewes. Detection limits, determined by means of logistic regression models, were (microg/kg): 3, amoxycillin; 2, ampicillin; 18, cloxacillin; 1, penicillin "G"; 34, cefadroxil; 430, cephalosporin "C"; 40, cephalexin; 20, cefoperazone; 33, Ceftiofur; 18, cefuroxime; 6100, streptomycin; 1200, gentamycin; 2600, neomycin; 830, erythromycin; 100, tylosin; 180, doxycycline; 320, oxytetracycline; 590, tetracycline; 88, sulfadiazine; 44, sulfamethoxazole; 140, sulfametoxypyridazine; 48, sulfaquinoxaline; 12,000, chloramphenicol; and 290, trimethoprim. Whereas the beta-lactam antibiotics, sulphonamides, and tylosin were detected by Delvotest method at levels equal to those of maximum residue limits, its sensitivity needs to be enhanced to detect aminoglycosides, tetracyclines, streptomycin, chloramphenicol, and trimethoprim residues in ewe milk or to develop an integrated residue detection system for ewe milk with different sensitive microorganisms for each group of antiinfectious agents.

Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

Energy Technology Data Exchange (ETDEWEB)

Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2008-02-15

Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses.

Primary pericranial Ewing's sarcoma on the temporal bone: A case report.

Science.gov (United States)

Kawano, Hiroto; Nitta, Naoki; Ishida, Mitsuaki; Fukami, Tadateru; Nozaki, Kazuhiko

2016-01-01

Primary Ewing's sarcoma originating in the pericranium is an extremely rare disease entity. A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under the left temporal muscle and attached to the surface of the temporal bone. Head computed tomography revealed a mass with bony spicule formation on the temporal bone, however, it did not show bone destruction or intracranial invasion. F-18 fluorodeoxyglucose positron emission tomography showed no lesions other than the mass on the temporal bone. Magnetic resonance imaging showed that the mass was located between the temporal bone and the pericranium. The mass was completely resected with the underlying temporal bone and the overlying deep layer of temporal muscle, and was diagnosed as primary Ewing's sarcoma. Because the tumor was located in the subpericranium, we created a new classification, "pericranial Ewing's sarcoma," and diagnosed the present tumor as pericranial Ewing's sarcoma. We herein present an extremely rare case of primary pericranial Ewing's sarcoma that developed on the temporal bone.

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma

International Nuclear Information System (INIS)

Marinova, L.; Hristozova, I.; Mihaylova, I.; Perenovska, P.

2015-01-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy ± surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. (authors)

Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma.

Science.gov (United States)

Haga, Ayako; Ogawara, Yoko; Kubota, Daisuke; Kitabayashi, Issay; Murakami, Yasufumi; Kondo, Tadashi

2013-06-01

Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In search of better spermatogonial preservation by supplementation of cryopreserved human immature testicular tissue xenografts with N-acetylcysteine and testosterone

Directory of Open Access Journals (Sweden)

Jonathan ePoels

2014-12-01

Full Text Available Controlled slow-freezing is the procedure currently applied for immature testicular tissue cryobanking in clinical practice. Vitrification has been proposed as a promising alternative, with a view to better preserving spermatogonial stem cells for future fertility restoration by autografting in young boys suffering from cancer. It appears that besides the potential influence of the cryopreservation technique used, the transplantation procedure itself has a significant impact on spermatogonial loss observed in ITT xenografts. Eighteen immature testicular tissue pieces issuing from 6 patients aged 2-15 years were used. Fragments of fresh tissue (serving as ungrafted controls, frozen-thawed tissue, frozen-thawed tissue supplemented with N-acetylcysteine and frozen-thawed tissue supplemented with testosterone xenografted to nude mice for 5 days were compared. Upon graft removal, histological and immunohistochemical analyses were performed to evaluate spermatogonia, intratubular proliferation and intrinsic and extrinsic apoptosis. A significant decrease in the integrity of intact seminiferous tubules was found in all three grafted groups. Spermatogonia were observed by immunohistochemistry in all grafted groups, with recovery rates of 67%, 63% and 53% respectively for slow-frozen tissue, slow-frozen tissue supplemented with N-acetylcysteine and slow-frozen tissue supplemented with testosterone. Apoptosis evidenced by active caspase-3 and TUNEL was similar in all grafts. The study is limited by the low availability of immature testicular tissue samples of human origin, and no clear impact of graft supplementation was found. The mouse xenotransplantation model needs to be refined to investigate human spermatogenesis in human immature testicular tissue grafts.

Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

Directory of Open Access Journals (Sweden)

Yingjen Jeffrey Wu

2009-02-01

Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

Directory of Open Access Journals (Sweden)

Hossein Jadvar

2005-04-01

Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

Tumor - host immune interactions in Ewing sarcoma : implications for therapy

NARCIS (Netherlands)

Berghuis, Dagmar

2012-01-01

In this thesis, we report on various aspects of tumor - host (immune) interactions in Ewing sarcoma patients with the aim to obtain leads for immunotherapeutic or targeted treatment strategies. We demonstrate a key role for interferon gamma (IFNg) in enhancing both Ewing sarcoma immunogenicity and

Like or Dislike? Impact of Facebook on Ewing Sarcoma Treatment.

Science.gov (United States)

Ruckenstuhl, Paul; Schippinger, Michael; Liebmann, Paul; Leithner, Andreas; Bernhardt, Gerwin

2016-08-25

An increasing number of patients are raising their voices in online forums to exchange health-related information. Facebook is the leading social media platform with more than 1 billion international daily users recorded in the summer of 2015. Facebook has a dynamic audience and is utilized in a number of ways, discussing medical issues being one of them. Ewing sarcoma mainly affects teenagers and young adults. Additionally, many individuals within this age group are regular users of Facebook. However, little is known about the impact of this modern way of communication via Web-based platforms on patients with Ewing sarcoma and their social environment. The aim of this study was to analyze and compare Ewing sarcoma patients' and relatives' behavior on Facebook to draw conclusions regarding the impact of Facebook on Ewing sarcoma treatment. We examined a Facebook group named "Ewing Sarcoma Awareness" that is used to exchange information for both patients and relatives regarding Ewing sarcoma. A self-designed questionnaire was used to compare patients' and relatives' answers. Additionally, we analyzed all processes (posts, likes, threads, links) in the group for 6 consecutive months. A total of 65 members of the Facebook group (26 patients, 39 relatives) out of 2227 international group members participated in our study. More than 70% (46/65) of all participants reported that they use the group Ewing Sarcoma Awareness as a source of information about Ewing sarcoma. Of the participants, 89% (58/65) agreed on our scale from a little to a lot that being in contact with other affected people through the group makes it easier to handle the diagnosis. In this study, 20% (13/65) of all participants reported that the group affected their choice of treatment and 15% (10/65) of participants were influenced in the selection of their specialist. Regarding the recommendation of the Facebook group toward other people, significant differences (P=.003) were found comparing patients

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Chemokines in Ewing sarcoma

NARCIS (Netherlands)

Sand, L.G.L.

2016-01-01

Ewing sarcoma is an aggressive primary malignant bone tumor with high degree of tumor vascularization and is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. To identify novel therapies and

Successful induction of oestrus, ovulation and pregnancy in adult ewes and ewe lambs out of the breeding season using a GnRH+progesterone oestrus synchronisation protocol.

Science.gov (United States)

Martinez, M F; McLeod, B; Tattersfield, G; Smaill, B; Quirke, L D; Juengel, J L

2015-04-01

A series of experiments was designed to assess the effect of a treatment protocol (U-synch) for inducing oestrus and ovulation out of the breeding season in adult ewes and ewe lambs. The protocol consisted of a 7-day treatment with an intravaginal progesterone-releasing device (IPRD), administration of GnRH at IPRD insertion on Day 0, and equine chorionic gonadotropin (eCG) and prostaglandin F2α at IPRD removal on Day 7. In Experiment 1, 50 or 100 μg GnRH were sufficient to induce ovulation at the beginning of the protocol in 3/9 and 4/9 ewes, respectively; while the resulting proportion of sheep ovulating after the treatment protocol was 88.9% and 77.8% in ewes initially treated with 50 or 100 μg GnRH, respectively. In Experiment 2, the proportion of Romney-cross ewe lambs ovulating was greater (P<0.0001) in the U-synch group (95.4%) than in the untreated Control group (3.2%). In Experiment 3, pregnancy rates of Dorset-cross sheep in the U-synch (60.7%) and Standard (12-day IPRD and eCG treatment; 56.5%) groups were greater (P=0.01) than in the untreated Control group (43.4%). The incidence of twin pregnancies was greater (P=0.005) in the U-synch group than in the Control group. A 7-day IPRD treatment including GnRH treatment at device insertion and eCG treatment at device removal induced oestrus and ovulation during the non-breeding season in a high proportion of mature ewes and ewe lambs. High pregnancy rates to natural mating, with a low rate of triplet pregnancies, were also observed. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of lipopolysaccharide (LPS) induced inflammatory response on early embryo survival in ewes

Science.gov (United States)

Early pregnant ewes were used to determine the effects of endogenous (through LPS activation) and exogenous TNF-alpha tumor necrosis factor-alpha (TNF-alpha) on embryonic loss. Thirty-eight Dorset x Texel ewes were synchronized for estrus and bred to fertile rams (d0). On d5/6, ewes were assigned t...

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

Science.gov (United States)

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

EXTRAOSSEOUS EWINGS/PNET-A CASE REPORT BY FNAC

OpenAIRE

Bharath; Rakesh

2013-01-01

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

Feeding olive cake to ewes improves fatty acid profile of milk and cheese

DEFF Research Database (Denmark)

Vargas-Bello-Pérez, E.; Vera, R. R.; Aguilar, C.

2013-01-01

Olive oil extraction yields a residual cake rich in oil that can be used in animal diets as a source of monounsaturated fat. Milk and cheese from sheep are high in saturated fatty acids (FA) thus, it was hypothesized that supplementing olive cake to lactating ewes would result in naturally enhanced...... milk and cheese with healthier FA profiles for human consumption. Nine lactating ewes were randomly assigned to a replicated (n= s3) 3. ×. 3 Latin square design. Diets were supplemented with 0, 10 or 25% of dry olive cake. Except for total solids, dry matter intake, milk yield and milk composition were...... not affected by dietary treatments. Oleic acid, n-6/. n-3 ratio and monounsaturated FA gradually increased (P. olive cake was increased in dietary treatments. Overall, FA profile of milk and cheese...

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

Science.gov (United States)

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

2015-04-01

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

Expression of the chondroitin sulphate proteoglycan molecular complex in six human melanoma xenograft lines studied by flow cytometry and immunohistochemistry.

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Nagelhus, T A; Rofstad, E K

1993-06-01

The expression of the chondroitin sulphate proteoglycan (CSP) molecular complex in six human melanoma xenograft lines (BEX-t, COX-t, HUX-t, ROX-t, SAX-t, WIX-t) was studied by flow cytometry and immunohistochemistry using the monoclonal antibodies 9.2.27, ME31.3, G7A5, and NKI.M6. The two methods and the four antibodies gave consistent results. The six melanoma lines could be divided into three distinct groups of two lines each; expression was high in the HUX-t and ROX-t lines and intermediate in the BEX-t and SAX-t lines, whereas the COX-t and WIX-t lines were negative. The mean number of epitopes per cell for 9.2.27 was approximately twice as high as for ME31.3, G7A5, and NKI.M6 and was estimated to range from 0.8 +/- 0.1 x 10(5) to 1.9 +/- 0.2 x 10(5) in the positive xenograft lines. The expression of the CSP complex was heterogeneous. The immunofluorescence histograms measured by flow cytometry were therefore broad for all tumour lines. A significant fraction of the HUX-t cells was negative or weakly stained. These cells appeared as clear negative patches in the immunohistochemical preparations. Moreover, most morphologically intact tumour cells adjacent to necrotic areas did not show significant expression of the CSP complex, irrespective of tumour line. These cells were probably hypoxic and thus resistant to radiation therapy. The expression of the CSP complex in the xenograft lines was similar to that reported for melanoma in man.

Induction of cervical dilation for transcervical embryo transfer in ewes

Science.gov (United States)

2014-01-01

Background A major limitation in the application of assisted reproductive technologies in sheep arises from the inability to easily traverse the uterine cervix. The cervix of the non-pregnant ewe is a narrow and rigid structure, with 5–7 spiral folds and crypts that block its lumen. The first two folds closest to the vagina appear to be the greatest obstacle for the instrument insertion into the sheep cervix. Therefore, the dilation of the distal part of the cervix could provide the conformational change necessary to perform non-invasive transcervical procedures. The present study set out to assess the efficacy of Cervidil®, a patented dinoprostone (PgE2)-containing vaginal insert with a controlled-release mechanism, to safely induce sufficient cervical dilation for the purpose of transcervical embryo transfer (TCET) in cyclic ewes. Methods The transfer of frozen-thawed ovine embryos was attempted in 22 cross-bred Rideau Arcott x Polled Dorset ewes, with or without the pre-treatment with Cervidil® for 12 or 24 h prior to TCET. Results Cervical penetration rate was significantly improved after Cervidil® pre-treatment, with 55% (6/11) of treated versus 9% (1/11) of control animals successfully penetrated (χ2-test, p 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

Optical determination of the hemoglobin oxygenation state of breast biopsies and human breast cancer xenografts in nude mice

Science.gov (United States)

Marks, Fay A.

1992-05-01

Differences in the oxygenation state of benign and malignant breast biopsies, and human breast cancer xenografts in immune-deficient mice were monitored using a spectrophotometer with integrating sphere. The breast biopsies were maintained below -50 degree(s)C and the mouse model tumors maintained in growth medium at 0 degree(s)C. Tissue sections 500 (mu) thick were allowed to come up to room temperature for mounting between quartz slides and were evaluated over the wavelength region 240 - 2500 nm. Data collection was done within 10 minutes of the removal of the biopsies from storage and, within 5 minutes for the xenografts. That this preparation protocol allowed us to study the samples very close to the in- vivo state was evident from the lack of deoxyhemoglobin in the benign samples. Component analysis performed in the 300 - 800 nm region showed that the malignant samples contained predominantly deoxygenated blood while the benign samples exhibited oxyhemoglobin signature. Absorption peaks due to fat and traces of bilirubin were also resolved in some of the samples. Assuming that the samples are very nearly representative of the in-vivo condition, these hemoglobin differences may well serve as a basis for imaging tumors or, for tissue characterization in a minimally invasive environment.

depicting the effects of gender, birth type, ewe line and ram breed on ...

African Journals Online (AJOL)

Schalk Cloete

The initial pH of meat from progeny of FW+ Merino ewes was lower than that from progeny of dual-purpose ewes, and Rep+ Merino ewes. .... Maximum shear force values (N) required to shear a cylindrical core of 1.27 cm ... Back pedigrees were not included for sires and dams, since all sires and dams were derived from ...

Diurnal thermoregulatory responses in pregnant Yankasa ewes to the dry season in a tropical Savannah.

Science.gov (United States)

Yaqub, Lukuman Surakat; Ayo, Joseph Olusegun; Kawu, Muhammad Umar; Rekwot, Peter Ibrahim

2017-08-01

The study investigated concomitant effect of gestation and high ambient temperature under a tropical environment on rectal temperature (RT), respiratory rate (RR) and heart rate (HR) responses in Yankasa ewes. Twenty Yankasa ewes, consisting of ten pregnant and ten non-pregnant ewes, were used for the study. Ewes were synchronised and bred, such that each gestation phase coincided with different periods of the dry-seasons, early-gestation (cold/harmattan), mid-gestation (peak hot-dry) and late-gestation (late hot-dry). The RT, RR and HR were recorded thrice, 2 days apart at middle of each gestation period at 06:00, 14:00 and 18:00 h, concurrently with dry- (DBT) and wet-bulb temperatures of the experimental pen. The DBT was positively correlated with RT, RR during the different gestation stages. The RT significantly (P ewes, with peak at 14:00 h. Values of RT and RR were higher (P ewes at mid- and late-gestation, respectively. Mean RT was lower (P ewes at early-gestation (cold-dry). The HR was (P ewes during the different gestation phases. In conclusion, ambient temperature and gestation concomitantly modulate diurnal thermoregulatory responses of the ewes to hot-dry season. Adequate measures should be adopted to mitigate adverse impact of prolonged high RR on the dam and the foetus during the peak of ambient temperature prevailing in the tropical Savannah environment.

Heart rate patterns during courtship and mating in rams and in estrous and nonestrous ewes ().

Science.gov (United States)

Orihuela, A; Omaña, J C; Ungerfeld, R

2016-02-01

The aim of this study was to compare the heart rate (HR) patterns in rams mated with estrous or nonestrous ewes and in mated estrous and nonestrous ewes () during courtship and mating. For this purpose, HR and behavior were recorded using a radio telemetry recording system and a closed-circuit television system with video recording, respectively. Rams were joined with either an estrous ( = 10) or a nonestrous ( = 10) ewe that was restrained in a stanchion by the neck. Data were continuously recorded until each ram performed 3 ejaculations. Eight days later, the HR of the 10 estrous and 10 nonestrous ewes was recorded during mating. Although the time between entrance into the yard and the first ejaculation was similar across rams, rams that mounted estrous ewes were faster at attaining their second (3min5s ± 17 s vs. 5min28s ± 18 s) and third (7min58s ± 45 s vs. 12 min ± 1min14s) ejaculations (all ewes. In all cases, HR reached maximum values immediately after each ejaculation and the HR pattern was similar across ejaculations (first, second, and third). Although HR was similar between estrous and nonestrous ewes before mating, nonestrous ewes had higher HR ( ewes displayed shorter interejaculation periods but HR did not differ between groups of rams during any ejaculation (first, second, or third), 2) HR for both groups of rams peaked shortly after each ejaculation, and 3) HR increased more in nonestrous than in estrous ewes while mating.

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

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Albert D'Souza

2009-01-01

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

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

Science.gov (United States)

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

2014-08-01

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

The use of matrigel has no influence on tumor development or PET imaging in FaDu human head and neck cancer xenografts

DEFF Research Database (Denmark)

Fliedner, Frederikke P.; Hansen, Anders Elias; Jorgensen, Jesper T.

2016-01-01

is currently available. This study evaluates the potential effect of matrigel use in a human head and neck cancer xenograft model (FaDu; hypopharyngeal carcinoma) in NMRI nude mice. The FaDu cell line was chosen based on its frequent use in studies of cancer imaging and tumor microenvironment. Methods: NMRI...... nude mice (n = 34) were divided into two groups and subcutaneously injected with FaDu cells in medium either including (+MG) or excluding matrigel (-MG). In sub study I seven mice from each group (+MG, n = 7; -MG, n = 7) were 18F-fluorodeoxyglucose (18F-FDG) PET/CT scanned on Day 5, 8, 12, 15, and 19...... for the FaDu xenograft model evaluated. Tumors in the -MG group displayed increased angiogenesis compared to the +MG tumors. No difference in 18F-FDG PET uptake for tumors of different groups was found. Based on these observations the influence of matrigel on tumor imaging and tumor microenvironment seems...

The Impact of Group Size on Welfare Indicators of Ewes during Pregnancy

Science.gov (United States)

Averós, Xavier; Beltrán de Heredia, Ignacia; Ruiz, Roberto; Estevez, Inma

2016-01-01

Group size (GS) and space allowance have major implications for the welfare of production species, however their effects are often confounded. In a previous study we investigated the impact of varying space allowance at constant GS. In the present work we report the consequences of varying GS on pregnant ewes while controlling space allowance. We housed ewes at 6 (GS6) or 12 ewes/enclosure (GS12), while controlling space allowance to 1.5 m2/ewe (3 enclosures/treatment), and necessarily varying enclosure size. Therefore, when indicating GS effects we implicitly reflect a confounding effect with that of enclosure size. Movement, use of space, behaviour, serum cortisol concentration and body condition score (BCS) were collected during the last 12 gestation weeks. Movement, use of space, and behaviour were collected every other week, during 2 days/week, using 10 minute continuous scan samplings. Blood was collected during weeks 10, 13, 17, and 21 of gestation, and BCS during weeks 15 and 21. Data were analysed using repeated measures, generalized linear mixed models, with GS, week, and their interaction as fixed effects, and enclosure as random effect. GS mainly affected movement and use of space. GS12 ewes walked longer distances using longer steps (Pewe is given during gestation, larger GS will result in larger effective space, and no major implications for the welfare of ewes should be expected as GS increases. Ewes will adapt their movement patterns and use of space to enclosure size, and no further behavioural, physiological and physical consequences should be expected. PMID:27893817

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

Science.gov (United States)

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

2017-03-01

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

Effect of available space and previous contact in the social integration of Saint Croix and Suffolk ewes.

Science.gov (United States)

Orihuela, A; Averós, X; Solano, J; Clemente, N; Estevez, I

2016-03-01

Reproduction in tropical sheep is not affected by season, whereas the reproductive cycle of temperate-climate breeds such as Suffolk depends on the photoperiod. Close contact with tropical ewes during the anestrous period might induce Suffolk ewes to cycle, making the use of artificial light or hormonal treatments unnecessary. However, the integration of both breeds within the social group would be necessary to trigger this effect, and so the aim of the experiment was to determine the speed of integration of 2 groups of Saint Croix and Suffolk ewes into a single flock, according to space allowance and previous experience. For this, 6 groups of 10 ewes (half from each breed) from both breeds, housed at 2 or 4 m/ewe (3 groups/treatment) and with or without previous contact with the other breed, were monitored for 3 d. Each observation day, the behavior, movement, and use of space of ewes were collected during 10 min at 1-h intervals between 0900 and 1400 h. Generalized linear mixed models were used to test the effects of breed, space allowance, and previous experience on behavior, movement, and use of space. Net distances, interbreed farthest neighbor distance, mean interbreed distance, and walking frequencies were greater at 4 m/ewe ( ewe were greatest for Saint Croix ewes, whereas the opposite was found for lying down ( ewes showed larger intrabreed nearest neighbor distances, minimum convex polygons, and home range overlapping ( ewes at 4 m/ewe showed longest total distances and step lengths and greatest movement activity ( ewes walked longer total distances during Day 1 and 2 ( ewes kept longer interindividual distances during Day 1 ( ewes did not fully integrate into a cohesive flock, with each breed displaying specific behavioral patterns. Decreasing space allowance and previous experience resulted in limited benefits for the successful group cohesion. Longer cohabitation periods might result in complete integration, although practical implementation might be

64Cu-ATSM Reflects pO2 Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with 64CuCl2.

Science.gov (United States)

Li, Fan; Jørgensen, Jesper T; Forman, Julie; Hansen, Anders E; Kjaer, Andreas

2016-03-01

The hypoxia PET tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazonate) ((64)Cu-ATSM) has shown promising results in clinical studies. However, concerns have been raised with regard to the possible effect of copper metabolism and free copper on tumor uptake and thereby the robustness of (64)Cu-ATSM as a hypoxia marker. In this study, accumulation and distribution of (64)Cu-ATSM and (64)CuCl2 in tumor tissue were compared with partial pressure of oxygen (pO2) probe measurements. One-hour dynamic PET scans were performed on nude mice bearing subcutaneous human head and neck tumors (FaDu) and human colorectal tumors (HT29) after administration of either (64)Cu-ATSM or (64)CuCl2. Subsequently, tracks were generated and track markers were positioned in tumors to allow for registration of their exact location on the high-resolution CT scan. After completion of the CT scan, pO2 probe measurements were performed along each track. PET and CT images were coregistered and ROIs drawn on the basis of the location of track markers and pO2 probe measurement depth. A linear mixed model for repeated measures was applied for the comparison of PET tracer uptake to corresponding pO2 values. Comparable uptake of (64)Cu-ATSM and (64)CuCl2 was found in the kidney, muscle, and liver of all animals, but (64)CuCl2 showed a higher uptake 10-60 min after injection in both tumor models. Significant differences were also found for both tumor-to-muscle and tumor-to-liver ratios. The intratumoral distribution of (64)Cu-ATSM, but not (64)CuCl2, showed a significant negative relationship with pO2 measurements in FaDu tumors. However, this relationship was not found in HT29 tumors. (64)Cu-ATSM and (64)CuCl2 displayed different uptake in tumors. In human head and neck xenografts, (64)Cu-ATSM but not (64)CuCl2 reflected pO2 measurements, indicating that (64)Cu-ATSM is a hypoxia-specific marker in this tumor type. However, data from colorectal cancer xenografts indicated that (64)Cu-ATSM may not be

Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

International Nuclear Information System (INIS)

Ahn, Sung Jun; An, Chan Sik; Koom, Woong Sub; Song, Ho Taek; Suh, Jin Suck

2011-01-01

To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 X 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

Energy Technology Data Exchange (ETDEWEB)

Ahn, Sung Jun; An, Chan Sik; Koom, Woong Sub; Song, Ho Taek; Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2011-11-15

To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 X 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

Primary extra-skeletal Ewing's sarcoma mimicking a disc protrusion.

Science.gov (United States)

Ruelle, A; Boccardo, M

1987-07-01

One of the rarest cases of primary epidural neoplasm is a soft tissue sarcoma histologically similar to Ewing's sarcoma of the bone. In the literature only eleven cases of such an extra-skeletal Ewing's sarcoma have been described. The authors report an additional case presenting as a disc protrusion in a young male. The authors include some diagnostic, prognostic and nosologic remarks about this condition.

Clinical mastitis in ewes; bacteriology, epidemiology and clinical features

Directory of Open Access Journals (Sweden)

Kvitle Bjørg

2007-09-01

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

Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

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Lu Dai

Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model.

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Kurundkar, Deepali; Srivastava, Ritesh K; Chaudhary, Sandeep C; Ballestas, Mary E; Kopelovich, Levy; Elmets, Craig A; Athar, Mohammad

2013-01-15

Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling initiation of Ewing sarcoma in human neural crest cells.

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Cornelia von Levetzow

2011-04-01

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

Histologic evaluation of human benign prostatic hyperplasia treated by dutasteride: a study by xenograft model with improved severe combined immunodeficient mice.

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Tsujimura, Akira; Fukuhara, Shinichiro; Soda, Tetsuji; Takezawa, Kentaro; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio; Adachi, Shigeki; Tokita, Yoriko; Nomura, Taisei

2015-01-01

To evaluate histologic change in human prostate samples treated with dutasteride and to elucidate direct effects of dutasteride on human prostate tissue, the present study was conducted by using a xenograft model with improved severe combined immunodeficient (super-SCID) mice, although it is well known that dutasteride reduces prostate volume. After establishment of a xenograft model of human benign prostatic hyperplasia in morphology and function, samples implanted into super-SCID mice with and without dutasteride were evaluated pathohistologically at 2 and 6 months after initiation of dutasteride administration. The proliferative index evaluated by Ki-67 staining was significantly lower in the dutasteride group than the control at 2 and 6 months after administration. Apoptotic index evaluated by the terminal transferase TdT-mediated dUTP-biotin nick end labeling staining was higher in the dutasteride group than the control at 2 and 6 months after administration. Quick scores in the dutasteride group for staining of both cyclooxygenase-2 (Cox-2) and Ras homolog gene family, member A (RhoA) were significantly lower than those in the control group at 2 and 6 months after administration. Dutasteride inhibits cell proliferation and induces apoptosis of prostatic cells, causing a reduced prostate volume. Furthermore, decreased expression of Cox-2 and RhoA within benign prostatic hyperplasia tissue by dutasteride may induce an early effect on improvement of lower urinary tract symptoms, probably by attenuating inflammation reaction of the prostate and decreasing intraurethral pressure, other than the mechanism of reduced prostate volume. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

2015-06-01

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

Identification of factors affecting colostrum quality of dairy Lacaune ewes assessed with the Brix refractometer.

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Torres-Rovira, Laura; Pesantez-Pacheco, Jose-Luis; Hernandez, Fernando; Elvira-Partida, Laura; Perez-Solana, Maria-Luz; Gonzalez-Martin, Juan-Vicente; Gonzalez-Bulnes, Antonio; Astiz, Susana

2017-11-01

In this Research Communication we assessed factors affecting colostrum quality of dairy Lacaune ewes using the Brix-refractometer. Colostrum from 536 lambings from one commercial intensive dairy Lacaune farm were analysed for the following factors with potential influence in colostrum quality: (1) ewe parity (n = 84-132), (2) length of previous dry period (PDP) (n = 23-214), (3) age at first lambing (AFL) of primiparous ewes (n = 9-88), (4) lambing season (n = 192 or 344), and (5) year (2011-2013, n = 142-203). Parity significantly affected colostrum quality, with primiparous ewes showing the highest Brix refractometer values (22·6 ± 5·6%, P ewes. PDP length also significantly affected colostrum quality: ewes with the shortest PDP showed the worst quality (16·8 ± 4·2%, P ewes under intensive management conditions and they further show the usefulness of the Brix refractometer for providing a rough estimation of colostrum quality on-farm. However, further studies are needed to determine a validated cut-off Brix value for identifying good-quality colostra in ovine species.

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

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Julian Catalan

2005-09-01

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

Ewe maternal behavior score to estimate lamb survival and performance during lactation

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Andreia Barros de Moraes

2016-08-01

Full Text Available Mortality of perinatal lambs and low weight at weaning cause huge liabilities to farmers. Current study describes maternal-filial behavior and evaluates the use of maternal behavior score (MBS to estimate the behavior of ewes and lambs soon after birth, and correlate it with lamb mortality and performance during lactation. Thirty-seven Corriedale ewes were used in a completely randomized design. MBS was assessed up to 24 hours after birth, taking into consideration the distance of the ewe from the lamb at the approach of a person. Maternal behavior, placental weight, weight gain of the lambs until weaning and their survival rate were also evaluated until two hours after lambing. More than 90% of the ewes had adequate maternal behavior, with parental care, even though ewes were very sensitive to the presence of people. There was no significant correlation between MBS and maternal behavior, lamb mortality rate and live weight gain. Under these conditions, MBS was not a useful tool to estimate maternal behavior and performance of lambs.

Reproductive characteristics of Awassi ewes under Cornell alternate month accelerated lambing system

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Sabri Gül

2010-04-01

Full Text Available We investigated the reproductive responses of Awassi ewes under Cornell alternate month accelerated lambing (CAMAL system. Ewes were randomly allocated to two experimental groups. The first group (control group consists of 20 ewes exposed to rams in September under conventional management system while the second group (CAMAL were divided into four sub-flocks contain 20 head of ewes each one were exposed to rams to obtain three lambing in two years with different breeding and lambing months. In CAMAL ewes, oestrus was synchronized using intra-vaginal sponges with progesterone and PMSG administration. Results revealed that within CAMAL group, the percentage of animals in heat, onset of oestrus, litter size, birth weight and weaning weight were affected by mating months. September and November were the most appropriate months for oestrus ratio (97.5 % and litter size (1.18 and 0.98, respectively. Lambs of control group were heavier at birth and weaning than those of CAMAL group. On the other hand lamb yield was not affected statistically by the CAMAL administration.

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

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Ahmad F. Kamal

2009-06-01

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

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

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

2014-08-01

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

Fate of ivermectin residues in ewes' milk and derived products.

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Cerkvenik, Vesna; Perko, Bogdan; Rogelj, Irena; Doganoc, Darinka Z; Skubic, Valentin; Beek, Wim M J; Keukens, Henk J

2004-02-01

The fate of ivermectin (IVM) residues was studied throughout the processing of daily bulk milk from 30 ewes (taken up to 33 d following subcutaneous administration of 0.2 mg IVM/kg b.w.) in the following milk products: yoghurt made from raw and pasteurized milk; cheese after pressing; 30- and 60-day ripened cheese; and whey, secondary whey and whey proteins obtained after cheese-making (albumin cheese). The concentration of the H2B1a component of IVM was analysed in these dairy products using an HPLC method with fluorescence detection. The mean recovery of the method was, depending on the matrix, between 87 and 100%. Limits of detection in the order of only 0.1 microg H2B1a/kg of product were achieved. Maximum concentrations of IVM were detected mostly at 2 d after drug administration to the ewes. The highest concentration of IVM was found on day 2 in 60-day ripened cheese (96 microg H2B1a/kg cheese). Secondary whey was the matrix with the lowest concentration of IVM (milk fat and solid content were evident. During yoghurt production, fermentation and thermal stability of IVM was observed. During cheese production, approximately 35% of the IVM, present in the raw (bulk) milk samples, was lost. From the results it was concluded that the processing of ewes' milk did not eliminate the drug residues under investigation. The consequences of IVM in the human diet were discussed. Milk from treated animals should be excluded from production of fat products like cheese for longer after treatment with IVM than for lower fat products.

Animal-Based Measures to Assess the Welfare of Extensively Managed Ewes

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Hemsworth, Paul; Doyle, Rebecca

2017-01-01

Simple Summary The aim of this study was to assess the reliability and practicality of 10 animal-based welfare measures for extensively managed ewes, which were derived from the scientific literature, previous welfare protocols and through consultation with veterinarians and animal welfare scientists. Measures were examined on 100 Merino ewes, which were individually identified and repeatedly examined at mid-pregnancy, mid-lactation and weaning. Body condition score, fleece condition, skin lesions, tail length, dag score and lameness are proposed for on-farm use in welfare assessments of extensive sheep production systems. These six welfare measures, which address the main welfare concerns for extensively managed ewes, can be reliably and feasibly measured in the field. Abstract The reliability and feasibility of 10 animal-based measures of ewe welfare were examined for use in extensive sheep production systems. Measures were: Body condition score (BCS), rumen fill, fleece cleanliness, fleece condition, skin lesions, tail length, dag score, foot-wall integrity, hoof overgrowth and lameness, and all were examined on 100 Merino ewes (aged 2–4 years) during mid-pregnancy, mid-lactation and weaning by a pool of nine trained observers. The measures of BCS, fleece condition, skin lesions, tail length, dag score and lameness were deemed to be reliable and feasible. All had good observer agreement, as determined by the percentage of agreement, Kendall’s coefficient of concordance (W) and Kappa (k) values. When combined, these nutritional and health measures provide a snapshot of the current welfare status of ewes, as well as evidencing previous or potential welfare issues. PMID:29295551

The effect of ewes relocation on milk composition and milk flow kinetics

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Lucia Jackuliaková

2014-02-01

Full Text Available The investigation of an influence of ewes relocation and milking in other parlour (treatment on milk flow kinetics, milkability and milk composition was the aim of this study. In total 34 ewes of two breeds and crosbreeds Tsigai (14 heads and Improved Valachian (20 heads with Lacaune were tested. Two weeks after lamb weaning the ewes were milked in parallel milking parlour (1x16 stalls under shelter. On the last evening milking (first experimental milking, EB before relocation of flock to another parlour, and during next three continuous evening milkings (E0 - second, E1 - third and E2 - fourth milking of exp. after relocation the milk flow kinetics were measured using electronic collection jar. On day E0 after morning milking the flock was moved on a pasture and milked in other parlour (1x24-stalls. During E0 we recorded a significant decrease of total milk yield in comparison with EB (0.527 ±0.04 and 0.647 ±0.04 L. Significant differences were also recorded in machine milk yield, machine stripping, milking time and in maximum milk flow rate. During E0 there was a higher number of nonbimodal and lower numbers of bimodal flow types. The response of ewe to E0 depended on its response to EB. Ewes with bimodal flow at EB responded more negatively to E0 than ewes with nonbimodal or plateau flow. During E2 there were significantly increased protein content and solids not fat in milk. Thus the treatment significantly influenced the milkability of ewes in a negative way, but more clear response was found out in ewes with bimodal flow response to machine milking before treatment. We could assume that relocation to other milking conditions caused only short-term changes in milk flow kinetic and milk yield. Normal 0 21 false false false SK X-NONE X-NONE

Ovarian and cervical cancer patient derived xenografts: The past, present, and future.

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Boone, Jonathan D; Dobbin, Zachary C; Straughn, J Michael; Buchsbaum, Donald J

2015-08-01

Preclinical research in gynecologic malignancies has largely relied upon cloned cancer-derived cell lines and tumor xenografts derived from these cell lines. Unfortunately, the use of cell lines for translational research has disadvantages because genetic and phenotypic alterations from serial passaging have resulted in expression profiles that are different from the original patient tumors. The patient-derived xenograft (PDX) model derived from human tumor not previously cultured has shown better representation of the heterogeneity of gynecologic malignancies and the human tumor microenvironment with preservation of cytogenetics, cellular complexity, and vascular and stromal tumor architecture. Studies have shown promise with these models to analyze tumor development and adaptation, test drug efficacy, and predict clinical outcomes. Their ultimate value may be seen with preclinical drug screening including novel targeted therapies, biomarker identification, and the development of individualized treatment plans. This article reviews PDX model development, current studies testing chemotherapeutics and targeted therapies, and limitations of the PDX model in gynecologic malignancies. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

2010-12-01

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

Reproductive performance of Santa Inês ewes fed protected fat diet

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Ricardo Lopes Dias da Costa

2011-06-01

Full Text Available The objective of this work was to evaluate the reproductive performance of Santa Inês ewes fed a diet supplemented with protected fat. Intervals from lambing to first clinical estrus and to conception, conception rate, prolificacy, live weight and body condition were determined. After lambing, 60 ewes and their offsprings were weighted and randomly assigned to three treatments, based on age, body weight and number of born lambs. Treatments consisted of: control diet, or control diet plus 30 g of protected fat, from lambing to day 25 of post-lambing (Sup25, or to day 60 of post-lambing (Sup60. Out of 60 evaluated ewes, 93.3% returned to estrus, and 74.5% got pregnant, with 73.53% lambing rate and 196.5 days lambing interval. The average periods from lambing to first estrus were 32.4, 27.2 and 35.5 days for ewes fed the control diet, Sup25, and Sup60, respectively. The intervals from lambing to conception were 45.2, 46.5 and 45.2 days, and the supplemented diets did not show differences in comparison to the control diet. Supplementation with protected fat to well-nourished Santa Inês ewes does not improve their reproductive performance.

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

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

2012-11-10

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

Physiological Changes in Ewes Conceived Single or Twins Fetuses Related with Survivability of Lambs

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El-Tarabany, A.A.

2012-01-01

The number of 239 (137 in year 2009 and 102 in 2010) pregnant ewes with the same age and average live body weight were used in the present study. The experimental does reared under same conditions during May to September in 2009 and August to December in 2010, respectively. The available data for each animal were obtained from the recodes. The classified of breeds and total numbers used in this study were (Ossimi =49, Barki =47, Rahmani =60 and crossbred =83). Season of lambing started in October to November in 2009 and January and February in 2010. After parturition, the does were classified according to litter size into two groups. The ewes in the 1st and 2nd groups were labor single or twins lamb, respectively. The results showed that progressed pregnancy stages related with decreases in concentrations of immunity function (total proteins, albumin and globulin), cholesterol, glucose and calcium in serum of pregnant ewes. On the other hand, enzymes activities of liver functions (GOT, GPT and γGT), creatinine, triglycerides and phosphorus increased in serum of pregnant ewes with progressed pregnancy stages. Progesterone and parathormone concentrations showed opposite trends to those obtained levels with progressed pregnancy stages. Comparison between ewes conceived single or twins fetuses showed that most blood components values are related with survivability of lambs. In ewes conceived single fetus recorded higher values of total proteins, albumin, globulin, glucose and calcium than ewes conceived twins fetuses. On the other hand, GOT, GPT and γGT, cholesterol, triglycerides, creatinine, urea and phosphorus concentrations were lower in ewes conceived single fetus than in ewes conceived twins fetuses. On the opposite, progesterone and parathormone concentrations were lower in single than in twins fetuses

The effect of superovulation prior to mating on fetal growth in Iambs from Javanese thin-tail ewes

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W Manalu

1999-12-01

Full Text Available Twenty-nine fetuses (11 fetuses from 9 non-superovulated ewes and 18 fetuses from 8 superovulated ewes were used to study the effect of superovulation of ewes prior to mating on fetal weight, fetal length, the length of the body and limbs, chest circumference, weights of the body, head, neck, limb, and viscera. Superovulated ewes, though with a higher litter size, had a greater fetal growth as was indicated by the greater fetal weight and length, the length and weight of the body and limb on day 49 of pregnancy. On day 105 of pregnancy, superovulated ewes with multiple fetuses (≥3 had similar fetal growth than nonsuperovulated ewes with single and twin fetuses. However, superovulated ewes with a single fetus had greater fetal growth as was shown by the greater fetal weight and length, the length of the body and limbs, chest circumference, and weight of the body, limb, and viscera when compared to those non-superovulated ewes with a single or twin fetuses. The results of the experiment suggested that superovulation of ewes prior to mating could be used to improve fetal prenatal growth during pregnancy

INFLUENCE OF DIETARY SELENIUM SUPPLEMENTATION OF EWES ON PRODUCTION TRAITS, ANTIOXIDANT STATUS AND METABOLIC PROFILE OF LAMBS

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Josip Novoselec

2013-12-01

Full Text Available The aim of this study was to determine the effect of dietary selenium supplementation (organic, inorganic of high pregnant ewes on the production traits of lambs, the concentration of selenium in the blood of ewes and their lambs, indicators of antioxidant status in the blood of ewes and their lambs, the metabolic profile of ewes and their lambs and concentrations of thyroid hormones. Ewes were in the last third of pregnancy, the average age of four years, healthy and in good condition, divided into three groups of 10 animals. The research lasted 4 months respectively, 2 months with ewes during high pregnancy, 2 months with ewes during lactation and on their lambs during suckling period. Ewes ration from control group one was composed from 300 g/day/animal feed mixture without addition of selenium and 150 g/day/animal barley and alfalfa hay that they had ad libitum. Feed mixture from second group of ewes was supplemented with 0.3 mg/kg organic form of selenium (Sel-Plex®, and feed mixture from third group with the same amount inorganic form of selenium (sodium selenite. Selenium supplementation of ewes feed mixture did not significantly influence on the production traits of their lambs postpartum. Selenium supplementation of ewes and their lambs had influence on a significant (P<0.01; P<0.05 increase in the concentration of selenium, GSH-Px and SOD in whole blood compared to control group of ewes. Organic selenium supplement had a more significant impact on the increase in concentration of selenium and GSH-Px in the blood. In the ewes and lambs blood was determined decrease of MDA with increasing concentrations of selenium in the blood. Generally, the selenium supplementation led to an increase (P<0.05 in the number of WBC and lymphocytes in the blood of ewes and lambs. Also, the increase in the number of RBC, HGB content and MCV in lambs and MCH as well as MCHC in ewes that had a selenium supplement in feed mixture were determined

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

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Huang, Peigen; Allam, Ayman; Perez, Luis A; Taghian, Alphonse; Freeman, Jill; Suit, Herman D

1995-04-30

Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-{alpha}) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-{alpha} with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm{sup 3}, mice were randomly assigned to treatment: rHuTNF-{alpha} alone compared with normal saline control; or local radiation plus rHuTNF-{alpha} vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-{alpha} on this tumor. The TCD{sub 50} (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-{alpha} with local radiation. Results: Tumor growth in mice treated with a dose of 150 {mu}g/kg body weight rHuTNF-{alpha}, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-{alpha} also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-{alpha} starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD{sub 50} from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-{alpha} exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD{sub 50} value in the treatment vs. the

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

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

2015-12-01

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

Second malignancies after treatment for Ewing's sarcoma

International Nuclear Information System (INIS)

Ahrens, Susanne; Dunst, Juergen; Ruebe, Christian; Paulussen, Michael; Hoffmann, Christine; Juergens, Herbert

1997-01-01

Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated

Second malignancies after treatment for Ewing's sarcoma

Energy Technology Data Exchange (ETDEWEB)

Ahrens, Susanne; Dunst, Juergen; Ruebe, Christian; Paulussen, Michael; Hoffmann, Christine; Juergens, Herbert

1997-07-01

Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated

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

Science.gov (United States)

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

2015-11-09

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

Comparison of two new angiogenesis PET tracers 68Ga-NODAGA-E[c(RGDyK)]2 and 64Cu-NODAGA-E[c(RGDyK)]2; in vivo imaging studies in human xenograft tumors

DEFF Research Database (Denmark)

Oxbøl, Jytte; Brandt-Larsen, Malene; Schjøth-Eskesen, Christina

2014-01-01

INTRODUCTION: The aim of this study was to synthesize and perform a side-by-side comparison of two new tumor-angiogenesis PET tracers (68)Ga-NODAGA-E[c(RGDyK)](2) and (64)Cu-NODAGA-E[c(RGDyK)](2) in vivo using human xenograft tumors in mice. Human radiation burden was estimated to evaluate...... potential for future use as clinical PET tracers for imaging of neo-angiogenesis. METHODS: A (68)Ge/(68)Ga generator was used for the synthesis of (68)Ga-NODAGA-E[c(RGDyK)](2). (68)Ga and (64)Cu labeled NODAGA-E[c(RGDyK)](2) tracers were administrated in nude mice bearing either human glioblastoma (U87MG......) or human neuroendocrine (H727) xenograft tumors. PET/CT scans at 3 time points were used for calculating the tracer uptake in tumors (%ID/g), integrin αVβ3 target specificity was shown by blocking with cold NODAGA-E[c(RGDyK)](2), and biodistribution in normal organs were also examined. From biodistribution...

Effects of the level of early productivity on the lifespan of ewes in contrasting flock environments.

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Douhard, F; Jopson, N B; Friggens, N C; Amer, P R

2016-12-01

Selection for high levels of prolificacy has allowed substantial improvements in the production efficiency of New Zealand (NZ) sheep farms, but the consequences on ewe lifetime performance are mostly unknown. In this study, the relationship between the level of prolificacy early in ewes' productive lives and their probability to survive later (i.e. stayability) was evaluated in two contrasting NZ flock environments. Records were obtained from 6605 ewes from four ram breeder flocks representing either a moderate (n=2) or a highly variable (n=2) nutritional environment. All ewes lambed for the first time at 2 years of age and were mated the following year. The number of lambs born during the first 2 years of productive life (NLB2-3) was used as a measure of early prolificacy. Effects of NLB2-3 on stayability to 4, 5, 6, 7 and 8 years old were analysed using logistic regression. Curvilinear effects (logit-transformed) were detected (Pewe stayability was reduced when the proportion of the litter that survived from birth to weaning (i.e. ewe rearing ability) was submaximal during the early productive life. High prolific ewes had a low rearing ability whatever the environment whereas the rearing ability of lowly prolific ewes was apparently more sensitive to the nutritional environment. The poor maternal performance of ewes with low levels of NLB2-3 led to a premature culling by breeders whereas the high early reproductive effort associated with high levels of NLB2-3 seemed to be at the cost of ewes' survival, even in the moderate flock environment. In conclusion, the flock environment influenced the level of early prolificacy beyond which ewe longevity was reduced. It is suggested that further selection for high and early prolificacy in NZ flocks is likely to impair ewes' lifetime productivity.

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

Science.gov (United States)

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...

Ewing's sarcoma of the tarsal bone

International Nuclear Information System (INIS)

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

1985-01-01

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

Ewing's sarcoma of the tarsal bone

Energy Technology Data Exchange (ETDEWEB)

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

1985-06-15

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

Effects of diet and arginine treatment during the luteal phase on ovarian NO/PGC-1α signaling in ewes.

Science.gov (United States)

Guo, Yi-Xuan; Nie, Hai-Tao; Sun, Ling-Wei; Zhang, Guo-Min; Deng, Kai-Ping; Fan, Yi-Xuan; Wang, Feng

2017-07-01

The aim of this study was to determine whether arginine (Arg) supplementation of malnourished ewes affects the expression of key NO/PGC-1α signaling pathway genes in the ovary. On Day 6-15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.53 kg) were randomly assigned to three groups: control group (CG; n = 6), restriction group (RG; n = 9) and l-arginine group (AG; n = 9), and administered Arg treatment (or vehicle) three times per day. The ewes were slaughtered at the end of treatment, and blood samples and ovaries were collected for analysis. The results of our analyses showed that both short-term feed-restriction and/or supplementation with L-Arg-HCl affected the number of different size follicles observed in the ovary, and the relative day of estrus behavior initiation of ewes. Specifically, the relative day of estrus behavior initiation was significantly advanced in AG compared with that in RG ewes (P ewes. RG ewes exhibited a higher proportion of ≤2 mm (P 5 mm follicles than did CG ewes (P ewes. Furthermore, the expression of eNOS, nNOS, iNOS, PDE5A, PDE9A, PRKG2, and PPARGC1A varied significantly among the treatment groups (P ewes (P ewes (P ewes (P ewes (P ewes (P ewes. In conclusion, the results of the present study indicate that feed-restriction negatively affects follicular development, and that Arg-supplementation may modulate the expression of key NO/PGC-1α signaling pathway genes in the ovary and thereby accelerate ovulatory processes and the estrous rate. Elucidation of mechanisms underlying these effects of Arg on gene expression in the ewe ovary requires further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality

Energy Technology Data Exchange (ETDEWEB)

Jiang, Yanyan; Verbiest, Tom; Devery, Aoife M.; Bokobza, Sivan M.; Weber, Anika M.; Leszczynska, Katarzyna B.; Hammond, Ester M.; Ryan, Anderson J., E-mail: anderson.ryan@oncology.ox.ac.uk

2016-06-01

Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors potentiate radiation therapy in preclinical models of human non-small cell lung cancer (NSCLC) and other types of cancer. However, the mechanisms underlying radiosensitization in vivo are incompletely understood. Herein, we investigated the impact of hypoxia on radiosensitization by the PARP inhibitor olaparib in human NSCLC xenograft models. Methods and Materials: NSCLC Calu-6 and Calu-3 cells were irradiated in the presence of olaparib or vehicle under normoxic (21% O{sub 2}) or hypoxic (1% O{sub 2}) conditions. In vitro radiosensitivity was assessed by clonogenic survival assay and γH2AX foci assay. Established Calu-6 and Calu-3 subcutaneous xenografts were treated with olaparib (50 mg/kg, daily for 3 days), radiation (10 Gy), or both. Tumors (n=3/group) were collected 24 or 72 hours after the first treatment. Immunohistochemistry was performed to assess hypoxia (carbonic anhydrase IX [CA9]), vessels (CD31), DNA double strand breaks (DSB) (γH2AX), and apoptosis (cleaved caspase 3 [CC3]). The remaining xenografts (n=6/group) were monitored for tumor growth. Results: In vitro, olaparib showed a greater radiation-sensitizing effect in Calu-3 and Calu-6 cells in hypoxic conditions (1% O{sub 2}). In vivo, Calu-3 tumors were well-oxygenated, whereas Calu-6 tumors had extensive regions of hypoxia associated with down-regulation of the homologous recombination protein RAD51. Olaparib treatment increased unrepaired DNA DSB (P<.001) and apoptosis (P<.001) in hypoxic cells of Calu-6 tumors following radiation, whereas it had no significant effect on radiation-induced DNA damage response in nonhypoxic cells of Calu-6 tumors or in the tumor cells of well-oxygenated Calu-3 tumors. Consequently, olaparib significantly increased radiation-induced growth inhibition in Calu-6 tumors (P<.001) but not in Calu-3 tumors. Conclusions: Our data suggest that hypoxia potentiates the radiation-sensitizing effects of

Response of the Syrian awassi ewes to the synthetic prostaglandin, prosolvin

International Nuclear Information System (INIS)

Zarkawi, M.

1999-11-01

Thirty Awassi ewes were divided equally into 3 groups. Ewes in the first (T10) and second groups (T15) were injected intramuscularly twice with either 10 mg (T10) or 15 mg (T15) of prosolvin, with an interval of 11 days. Whereas, the third group (C) was used as a control group. Progesterone levels were measured in the sera of the ewes using radioimmunoassay (RIA). Oestrus behaviour appeared in the ewes in group T10 on average after 83.3 hours, while oestrus appeared in the ewes in group T15 on average after 136.5 hours, after the second injection of prosolvin. In the control group (C), oestrus behaviour appeared on average after 251.2 hours, post ram introduction. The differences between the treated and the control animals in the time of oestrus behaviour was significant (p < 0.05). Average concentration of progesterone at mating was 0.64, 0.48 and 0.32 nmol/l for T10, T15 and C groups, respectively. The treatment had a luteolytic effect on the active corpora lutea. Progesterone concentration dropped sharply within 24 hours after the second prosolvin injection. The concentration dropped from 8.48 n mol/l to 0.52 n mol/l in the sera of group T10, and from 7.95 n mol/l to 0.45 n mol/l for the group T15. The treatment had no effect on the duration of pregnancy or birth weight. It could be concluded that it is possible to use the synthetic prostaglandin, prosolvin, for oestrous synchronization in the local Awassi ewes inside the breeding season at the doses of 10 and 15 mg. (author)

Response of the Syrian awassi ewes to the synthetic prostaglandin, prosolvin

International Nuclear Information System (INIS)

Zarkawi, M.

2000-01-01

Thirty Awassi ewes were divided equally into 3 groups. Ewes in the first (T10) and second groups (T15) were injected intramuscularly twice with either 10 mg (T10) or 15 mg (T15) of prosolvin, with an interval of 11 days. Whereas, the third group (C) was used as a control group. Progesterone levels were measured in the sera of the ewes using radioimmunoassay (RIA). Oestrus behaviour appeared in the ewes in group T10 on average after 83.3 hours, while oestrus appeared in the ewes in group T15 on average after 136.5 hours, after the second injection of prosolvin. In the control group (C), oestrus behaviour appeared on average after 251.2 hours, post ram introduction. The differences between the treated and the control animals in the time of oestrus behaviour was significant (p < 0.05). Average concentration of progesterone at mating was 0.64, 0.48 and 0.32 nmol/l for T10, T15 and C groups, respectively. The treatment had a luteolytic effect on the active corpora lutea. Progesterone concentration dropped sharply within 24 hours after the second prosolvin injection. The concentration dropped from 8.48 n mol/l to 0.52 n mol/l in the sera of group T10, and from 7.95 n mol/l to 0.45 n mol/l for the group T15. The treatment had no effect on the duration of pregnancy or birth weight. It could be concluded that it is possible to use the synthetic prostaglandin, prosolvin, for oestrous synchronization in the local Awassi ewes inside the breeding season at the doses of 10 and 15 mg. (author)

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

Science.gov (United States)

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

2014-10-01

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

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

Science.gov (United States)

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

2012-01-01

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

Puberty and Fertility of Ewe Lambs Fed on By-products of Palm and Olive Oil

International Nuclear Information System (INIS)

EL-T arabany, A.A.; Mostafa, M.M.M.; Mohamed, A.K.

2017-01-01

The present study aims to elucidate the effect of palm and olive oil by-products adding to rations on production and reproductive performance of Rahmani and Osimi female sheep. After weaning, Rahmani and Osimi ewe lambs (24 for each) of similar birth type were identified to compare between two rations containing hard fatty acids (HFA) or olive cake (OC) on sexual puberty and fertility of two breeds. The lambs of both breed were randomly divided into three groups: the first group is considered control and received ration which contained concentrate feed mixture (CFM). The second group nourished (OC) consisted of CFM +HFA and the third group nourished (HFA) composed of CFM +OC. The CFM was offered as basal ration to all experimental lambs. Body weight, functions of the liver, kidney, thyroid and progesterone hormones at puberty, and the fertility traits were assayed in the two breeds of ewes. The average body weight of female lambs was higher (P<0.05) with OC than HFA. Female lambs supplied OC reached puberty faster and their thyroid and sexual hormones (progesterone) have been developed earlier than ewe lambs given HFA and those in the control group. Age at puberty and progesterone level in both Rahmani and Osimi ewe lambs were better in ewes fed on OC , than other two groups. The fertility (%) from total ewe lambs and birth weight in ewe lambs fed on OC were higher than ewes fed on HFA and the control. It may be concluded that feeding ewe lambs on diet containing HFA from weaning had positive effects on age at puberty, reproductive fertility and prolificacy

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

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Chi-Man Yip

2009-06-01

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

A novel measure of ewe efficiency for breeding and benchmarking purposes.

Science.gov (United States)

McHugh, N; Pabiou, T; McDermott, K; Wall, E; Berry, D P

2018-04-19

Ewe efficiency has traditionally been defined as the ratio of litter weight to ewe weight; given the statistical properties of ratio traits, an alternative strategy is proposed in the present study. The concept of using the deviation in performance of an animal from the population norm has grown in popularity as a measure of animal-level efficiency. The objective of the present study was to define novel measures of efficiency for sheep which considers the combined weight of a litter of lambs relative to the weight of their dam, and vice versa. Two novel traits, representing the deviation in total litter weight at 40 d (DEV40L) or weaning (DEVweanL), was calculated from the residuals of a statistical model, with litter weight as the dependent variable and with the fixed effects of litter rearing size, contemporary group and ewe weight. The deviation in ewe weight at 40 d post lambing (DEV40E) or weaning (DEVweanE) was derived using a similar approach but with ewe weight and litter weight interchanged as the dependent variable. Variance components for each trait were estimated by first deriving the litter or ewe weight deviation phenotype and subsequently estimating the variance components. The phenotypic SD in DEV40L and DEVweanL was 8.46 kg and 15.37 kg, respectively; the mean litter weight at 40 d and weaning was 30.97 kg and 47.68 kg, respectively. The genetic SD and heritability for DEV40L was 2.65 kg and 0.12, respectively. For DEVweanL, the genetic SD and heritability was 4.94 kg and 0.13, respectively. The average ewe weight at 40 d post lambing and at weaning was 66.43 kg and 66.87 kg, respectively. The genetic SD and heritability for DEV40E was 4.33 kg and 0.24. The heritability estimated for DEVweanE was 0.31. The traits derived in the present study may be useful for phenotypic benchmarking of ewes within flock on performance but also for benchmarking flocks against each other; furthermore the extent of genetic variability in all traits, coupled with the

Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

International Nuclear Information System (INIS)

Moestue, Siver A; Borgan, Eldrid; Huuse, Else M; Lindholm, Evita M; Sitter, Beathe; Børresen-Dale, Anne-Lise; Engebraaten, Olav; Mælandsmo, Gunhild M; Gribbestad, Ingrid S

2010-01-01

Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood. The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses. The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer. In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (CHKA, CHKB) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (PLA2G4A) and phospholipase B1 (PLB1) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer. The differences in choline metabolite

Evaluation of Rambouillet, Polypay, and Romanov-White Dorper × Rambouillet ewes mated to terminal sires in an extensive rangeland production system: Lamb production.

Science.gov (United States)

Notter, D R; Mousel, M R; Lewis, G S; Leymaster, K A; Taylor, J B

2017-09-01

Ewe productivity (i.e., total number or weight of lambs weaned per breeding ewe) is a key indicator of lamb production efficiency. This study compared various measures of ewe productivity and ewe and lamb performance among ewes of 3 breed types mated to rams of 4 terminal-sire breed types in an extensive rangeland production system. Purebred Rambouillet ( = 212), purebred Polypay ( = 236), and crossbred Romanov-White Dorper × Rambouillet (RW-RA; = 231) ewes were produced from locally adapted Polypay and Rambouillet ewes and then annually mated to Columbia, Suffolk, Columbia × Suffolk, or Suffolk × Columbia sires for up to 4 yr, beginning at 1 yr of age. The cumulative number and weight of lambs weaned through 4 yr were greater for RW-RA (5.9 lambs and 153 kg, respectively) and Polypay ewes (4.9 lambs and 123 kg, respectively) than for Rambouillet ewes (2.9 lambs and 99 kg, respectively) and also were greater for RW-RA ewes than for Polypay ewes (all ewes, compared with Rambouillet ewes, was driven by greater lambing rates (ewes lambing per ewe exposed) as ewe lambs (87 and 77 vs. 31%, respectively; ewe lambs (1.3, 1.3, and 1.0, respectively) and adult ewes (2.1, 2.0, and 1.6, respectively). The RW-RA ewes also had greater longevity ( ewes. Lamb BW at birth and weaning in adult ewes favored less-prolific Rambouillet ewes ( ewe breed types were small and not significant ( = 0.08). Effects of sire breed type on measures of cumulative ewe productivity were not significant ( > 0.74), but Suffolk-sired lambs had the heaviest adjusted birth weights ( = 0.01) and Columbia-sired lambs tended to have the lightest adjusted weaning weights ( = 0.12). Combined effects of heterosis and additive breed effects were associated with greater lambing rates in ewe lambs, larger litters at all ages, and substantially greater number and weight of lambs weaned for Polypay and RW-RA ewes than for Rambouillet ewes.

Effect of supplementing a diet with monensin sodium and Saccharomyces Cerevisiae on reproductive performance of Ghezel ewes.

Science.gov (United States)

Ahmadzadeh, Leila; Hosseinkhani, Ali; Daghigh Kia, Hossein

2018-01-01

Effect of supplementing a diet, in an attempt to enhance reproduction, with monensin sodium and Saccharomyces cerevisiae yeast on reproductive performance was investigated during the breeding season using 44 Ghezel ewes (body weight 56.97±7.47kg, age 2-5 years and body condition score (BCS) 2.5) which were allocated randomly in equal numbers to the four dietary treatments as follows: 1) Basal diet plus supplemental feed (450g/ewe/d) plus monensin sodium (30mg/ewe/d) (MS); 2) Basal diet plus supplemental feed (450 g/ewe/d) plus Saccharomyces cerevisiae yeast (4×10 9 CFU/ewe/d) (SC); 3) Basal diet plus supplemental feed (450g/ewe/d) (FG); 4) Basal diet (only grazing on pasture, Control; G). Estrous synchronization of all ewes was done using controlled internal drug release (CIDR) and all ewes were mated with purebred Ghezel rams after CIDR removal. The results indicated that MS and SC treatments with 15 lambs had greater number of lambs than ewes of the other two treatment groups. Ewes in MS group with 50% twining rate had the greatest value followed by the FG, SC and G treatment groups (Pewes in MS and SC groups were heavier in weight than those in FG and G treatments (Pewes in MS and SC groups had greater concentrations of 17β-estradiol (E2), progesterone (P4), blood urea nitrogen (Pewes of the other groups. These results indicated that using a diet for enhancing reproduction, including monensin sodium and Saccharomyces cerevisiae yeast in the breeding season could have beneficial effects on reproductive performance of Ghezel ewes. Copyright © 2017 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

OpenAIRE

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

1999-01-01

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

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

DEFF Research Database (Denmark)

Rygaard, K; Møller, C; Bock, E

1992-01-01

characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

Identification of Genetic on Blood Serum Protein of Prolific Ewes

Science.gov (United States)

Sutiyono; Ondho, Y. S.; Setiatin, E. T.; Sutopo; Laily, A. N.; Prasetyowati, D. E.; Noviani, F.

2018-02-01

The aim of the research was to identify the genetic specification of blood plasma protein in ewes that are prolific. The material of study of local sheep in Bawen and Jambu Sub-district of Semarang Regency is 132 which is determined by purposive sampling that have been give lambing three times. Ewes were divided into three groups that always has a single child (L1), ever had twins (L2) and twins more than two (LM2). Blood sampling was performed using dispossible syringe in jugular vein as much as 5 ml per ewe. Blood plasma was analyzed by Polyacrylamide Gel Electrophoresis-Thin Layer (PAGETLE) method in Biochemistry Laboratory of Veterinary Faculty of Gadjah Mada University. Data analysis is using descriptive statistics and the laws of equilibrium Hardy-Weberg. The research parameters were comparison type of ewes and frequency genetic of protein of blood serum. The results showed that the parent comparisons of L1, L2 and LM2 were 66 (50.00%), 49 (37.12%) and 17 (12.88%), respectively. The frequency genes haven a high propensity to relationship of prolificacy nature parent are Pal2, AlbB, CPF, TFB, PTFS and AmlB on pointes, 67.65, 55.88, 91.17, 70.59, 79.41 and 91.18%. Conclusion the mostly LM2 ewes have genotypes Pal1Pal2, AlbBAlbC, CpFCpF, TfATfB, PtfSPtfS and AmlBAmlB whit frequency are 52.94%, 52.94%, 88.24, 47.06, 64.71 and 88.24% respectively.

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

African Journals Online (AJOL)

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

Genetic evaluation of the probability of lambing in yearling Targhee ewes

Science.gov (United States)

The objective of this study was to determine the additive genetic control of lambing percentage in yearling Targhee ewes. The records of 3,103 ewe lambs born from 1989 to 2011 and mated at approximately 7.5 mo of age were analyzed. Records included sire, dam, weaning weight, breeding pen, age of dam...

Epidemiology and effects of gastrointestinal nematode infection on milk productions of dairy ewes

Directory of Open Access Journals (Sweden)

Suarez V.H.

2009-06-01

Full Text Available 66 Pampinta breed ewes were studied during milking to evaluate the infection and the effect of gastrointestinal nematode on milk production sheep system. Naturally infected ewes on pasture were randomly allocated to two groups: TG, suppressively treated group every four weeks with levamisole and UG, untreated group. Faecal nematode egg counts and larval differentiation were conducted monthly. Successive groups of worm free tracer lambs were grazed with ewes and then slaughtered for worm counts. Test-day milk yield of individual ewes was recorded and ewe machine-milking period length (MPL were estimated. Faecal egg counts and tracer nematode numbers increased towards midsummer and declined sharply toward the end of the study. TG (188.0 ± 60 liters produced more (p < 0.066 milk liters than UG (171.9 ± 52.2 and TG had significantly more extended (p < 0.041 MPL than those of UG. The present study showed that dairy sheep were negatively affected by worms, even when exposed to short periods of high acute nematode (mainly Haemonchus contortus infection.

Do ewes born with a male co-twin have greater longevity with lambing over time?

Science.gov (United States)

Based on a recent analysis of historical records, ewes born co-twin to a ram had greater lifetime reproductive performance than ewes born co-twin to a ewe. We are interested in determining what component(s) of lifetime reproductive performance may be associated with a ewe’s co-twin sex. As an initi...

Assessing the usefulness of prostaglandin E2 (Cervidil) for transcervical artificial insemination in ewes.

Science.gov (United States)

Bartlewski, Pawel M; Candappa, Ivanka B R

2015-12-01

The underlying theme of this study involved the evaluation of the dilatory effects of prostaglandin E2 on the ovine cervix and thus the assessment of its potential applicability to transcervical artificial insemination (TCAI) in ewes. A novel method of prostaglandin E2 administration (controlled slow-release vaginal inserts) was examined, and the practical implications of this approach including cervical penetrability and posttreatment pregnancy rates were evaluated. The Guelph method of TCAI was performed during the seasonal anestrus (n = 40) and the breeding season (n = 40) on multiparous Rideau Arcott × Polled Dorset ewes, with or without the pretreatment with Cervidil (for a duration of 12 hours or 24 hours before TCAI). Cervical penetration rates averaged 82.5% (66 of 80), and they varied neither (P > 0.05) between the two seasons nor between Cervidil-treated ewes and their respective controls. Cervidil priming significantly reduced the total time required for TCAI during the breeding season in comparison with controls (54 vs. 98 seconds), especially after the 24-hour exposure (38 vs. 108 seconds). The time taken to traverse the uterine cervix was negatively correlated (P ewes. Four out of 36 (11%) successfully penetrated ewes in the breeding season (three ewes allocated to the 12-hour control group and one ewe that had received Cervidil for 12 hours) became pregnant and carried the lambs to term. Vaginal mucus impedance at TCAI was significantly and positively correlated with the total time required to complete the procedure in cyclic ewes, and the negative correlation between vaginal mucus impedance and total time values at the time of controlled intravaginal drug release device removal approached to significance in anestrous ewes. The present results indicate a moderate benefit of using Cervidil for inducing cervical dilation before TCAI in ewes, mainly in the breeding season. The specific reason(s) for impaired fertility after the TCAI using

Radiobiological hypoxic fraction does not correlate with pO2 measurements in eight human tumor xenografts into nude mice

International Nuclear Information System (INIS)

Taghian, A.; Huang, P.; Griffon, G.; Hartford, A.; Allam, A.; Costa, A. da; Kozin, S.; Suit, H.D.

1997-01-01

Purpose/Objective: Clinical and laboratory reports suggest that hypoxia limits local control probability in tumors treated by radiation. Significant increase in the TCD 50 (the dose of radiation needed to control 50% of the tumors) was obtained in a number of tumor models when the tumors were rendered hypoxic by clamping. Furthermore, recent data have shown the value of measuring the pO2 using electrodes in predicting the tumor response to radiation in cervical cancer. The aim of this study is to investigate the correlation between the radiobiological hypoxic fraction (HF) and the pO2 measurements of human tumor xenografts. Materials and Methods: Eight human tumor xenografts (five glioblastoma, one squamous cell carcinoma, one colon cancer, and one soft tissue sarcoma) were used in these experiments. Tumor chunks 2 mm in diameter were implanted into the hindleg of 5 Gy whole-body irradiated nude mice. When the tumor size reached 110 mm 3 , radiation was administered in a single dose ranging from 17.5 Gy to 90 Gy in hypoxic conditions. Acute hypoxia was induced by clamping the tumor bearing leg three minutes before and during the treatment. When aerobic conditions were required, the tumor bearing leg was immobilized by a hook which fitted around the ankle. Seven to 10 tumors were assigned to each dose level in each assay; there were 6 to 8 dose levels per assay. Starting at 2-3 weeks after irradiation, the animals were examined once per week and scored for presence of local tumor; if present, tumor diameters were measured. Tumor response is described in terms of radiation dose (in Gy) required to control 50% of the xenografts (TCD 50 ). The (HF) was determined using the formula of Howes (HF=e - ((TCD 50 hypoxic-TCD 50 air)(Do hypoxic)) and assuming an oxygen enhancement ratio of 3.0: (D o hyp=D o air x 3.0) (the D o air was separately determined in vitro for the corresponding cell lines). The pO2 measurements used electrodes as published (Boucher et al

Radioimmunoimaging of human breast carcinoma xenografts in nude mouse model with 111In-labeled new monoclonal antibody EBA-1 and F(ab')2 fragments

International Nuclear Information System (INIS)

Yemul, Shrishailam; Leon, J.A.; Pozniakoff, Ted; Esser, P.D.; Estabrook, Alison; Met-Path Inc., Teterboro, NJ

1993-01-01

Radioimmunoimaging characteristics of a new monoclonal antibody EBA-1 and its F(ab') 2 fragments utilizing nu/nu mice bearing human breast carcinoma xenografts are described. 111 In-DPTA conjugates of EBA-1 localized with tumor/blood ratios of 0.99 ± 0.10 (P 2 radioconjugates at 48 h. These results suggest that EBA-1 and its F(ab') 2 might be useful reagents in radioimmunoimaging and radioimmunotherapy. (author)

Circalunar Rhythms Induced Changes in the Body Functions and Reproductive Performance in Pregnant Ewes

International Nuclear Information System (INIS)

El-Darawany, A.A.; El-Tarabany, A.A.; Teama, F.E.I.

2014-01-01

A total number of 136 pregnant ewes with the same age and parity were used in the present study. The experimental ewes reared during Arabic months or lunar months, from the 1st Gomady to Zol-hega, 1432 AH. The available data for each animal were obtained from the records of Sheep Farm, Project of Experimental Farms. Lambing season started at months, Shawal to Zol-hega. After lambing, the ewes were divided into three groups according to moon phases. Ewes in the 1st group laboured in new moon phase period. The ewes in the 2nd and the 3rd groups laboured in full and old moon phases, respectively. The study was conducted to determine the changes in the body functions and reproductive of pregnant ewes due to the effect of lunar cycle which causes the increase of births by up to 72% in the full moon phase. The results showed that, a significant increase in feed and water consumption, the activity of liver enzymes, concentration of cholesterol, triglyceride, kidney functions and also the hormone thyroxine and triiodothyronine was recorded during full moon, on the contrary, there was a significant decrease in the concentration of total protein, albumin, glucose, calcium, phosphorus and cortisol in the blood of pregnant ewes was recorded during full moon phases followed by new and old moon. On the other hand, reproductive traits including litter size at birth and weaning and mortality rate were recorded during different moon phases.

Blood profile of ewes during third trimester of pregnancy and lactation

African Journals Online (AJOL)

The packed cell volume, haemoglobin, red blood cell and leukocyte count of ewes in group A were not significantly (p>0.05) different from those in group B. However, there were significant (p<0.05) differences in the potassium, bicarbonate and urea concentrations between ewes in groups A and B. The glucose, sodium and ...

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

Science.gov (United States)

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

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

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

Science.gov (United States)

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-07-16

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Zhou, Yan; Chen, Yue [Department of Medical Imaging, Luzhou Medical College, Luzhou (China); Yang, LingLin, E-mail: yanglinglin2003@tom.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, JingBo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

2013-10-01

Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang; Zhou, Yan; Chen, Yue; Yang, LingLin; Wu, JingBo

2013-01-01

Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I

Protection of ewes against Teladorsagia circumcincta infection in the periparturient period by vaccination with recombinant antigens.

Science.gov (United States)

Nisbet, Alasdair J; McNeilly, Tom N; Greer, Andrew W; Bartley, Yvonne; Oliver, E Margaret; Smith, Stephen; Palarea-Albaladejo, Javier; Matthews, Jacqueline B

2016-09-15

Teladorsagiosis is a major production-limiting disease in ruminants in temperate regions throughout the world and one of the key interventions in the management of the disease is the prevention of pasture contamination with Teladorsagia circumcincta eggs by ewes during the periparturient relaxation in immunity which occurs in the period around lambing. Here, we describe the immunisation of twin-bearing ewes with a T. circumcincta recombinant subunit vaccine and the impact that vaccination has on their immune responses and shedding of parasite eggs during a continuous T. circumcincta challenge period spanning late gestation and lactation. In ewes which displayed a clear periparturient relaxation in immunity, vaccination resulted in a 45% reduction in mean cumulative faecal egg count (cFEC, p=0.027) compared to control (immunised with adjuvant only) ewes. Recombinant antigen-specific IgG and IgA, which bound each of the vaccine antigens, were detected in the serum of vaccinated ewes following each immunisation and in colostrum taken from vaccinated ewes post-partum whereas low levels of antigen-specific IgG were detected in serum and colostrum from control ewes. Antigen-specific IgG and IgA levels in blood collected within 48h of birth from lambs largely reflected those in the colostrum of their ewes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

(LH) secretion in fasted prepubertal ewes

African Journals Online (AJOL)

DR. NJ TONUKARI

2012-01-10

Jan 10, 2012 ... decreased luteinizing hormone (LH) secretion in fasted prepubertal ewes .... kisspeptin-10 injection could restore the baseline levels of. LH changed by ..... Terasawa E (2005). Role of GABA in the mechanism of the onset of.

Re-alimentation strategy to manoeuvre body condition and carcass characteristics in cull ewes.

Science.gov (United States)

Bhatt, R S; Soren, N M; Sahoo, A; Karim, S A

2012-01-01

Improvement in body condition and carcass traits through nutritional intervention was studied in cull ewes. Sixty-eight adult non-productive Malpura ewes (average body weight 26.7 ± 0.33 kg) were randomly divided into four equal groups: G0 maintained on free grazing for 8 h on protected natural rangeland with ad libitum guar (Cyamopsis tetragonoloba) straw (GS) after grazing; G1, G2 and G3 fed with supplemental concentrate at the rate of 250 g, 2.5% of live weight (LW) and ad libitum, respectively. The experiment was continued for 90 days and daily feed intake, weekly LW and body condition score (BCS) were recorded. Intake and digestibility of nutrients were assessed by indicator method. Rumen fermentation attributes and blood biochemical profile were studied to assess the dietary effects and animals were slaughtered at the end of experiment for evaluation of carcass characteristics. Higher dry matter (DM) intake and improvement in plane of nutrition was observed in G2 and G3 with a higher LW gain (LWG) and improvement in BCS than in G0. The digestibility of DM, organic matter, CP, ADF and cellulose was higher (P alimentation of cull ewes with challenged feeding of concentrate at 2.5% of LW on a basal roughage diet for a period of 3 months may have promise for better economic return to the farmers with possibly meeting quality mutton for human consumption.

[Seasonal variations in estrus behavior and ovulatory activity in Chios and Serres ewes in Greece].

Science.gov (United States)

Avdi, M; Driancourt, M A; Chemineau, P

1993-01-01

Sheep are seasonal breeders, but a lower seasonality has been reported for sheep breeds from the Mediterranean countries enabling spring matings. To further substantiate this, the present study compared seasonal variation in oestrus behaviour and ovulation in two Greek breeds (Chios and Serres) maintained in the same environment. In 27 adult ewes of each breed, oestrus behaviour, the occurrence of ovulation and ovulation rate were monitored during 2 successive years by daily inspection by rams, weekly progesterone assay in circulating blood plasma and monthly ovarian laparoscopy. The periods of anoestrus (109 +/- 8 (wk) vs 178 +/- 5 d) and anovulation (63 +/- 8 vs 149 +/- 6 d) were significantly shorter (P duration of oestrus was also longer in Chios ewes (1.8 +/- 0.05 vs 1.5 +/- 0.06 d; P = 0.002). There were significant correlations between the duration of anovulatory periods of the 2 successive years in Chios (r = 0.43) but not Serres ewes. Ovulation rate was positively related to the onset of the sexual season in Serres but not in Chios ewes. The present data suggest that: i) the efficiency of Serres but not in Chios ewes. The present data suggest that: i) the efficiency of spring mating in these breeds is suboptimal since it is a period when the percentage of ewes exhibiting oestrus and ovulation as well as ovulation rate are limited, ii) owing to the large variation in seasonality within Chios ewes and to the good between year correlation in features of seasonality, selection against seasonality in Chios ewes could be worthwhile.

Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts

Directory of Open Access Journals (Sweden)

Rémy Nicolle

2017-11-01

Full Text Available Preclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively. Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.

Tumor Repression of VCaP Xenografts by a Pyrrole-Imidazole Polyamide.

Directory of Open Access Journals (Sweden)

Amanda E Hargrove

Full Text Available Pyrrole-imidazole (Py-Im polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model. In addition to the effects on AR regulated transcription, RNA-seq analysis revealed inhibition of topoisomerase-DNA binding as a potential mechanism that contributes to the antitumor effects of polyamides in cell culture and in xenografts. These studies support the therapeutic potential of Py-Im polyamides to target multiple aspects of transcriptional regulation in prostate cancers without genotoxic stress.

Evaluation of a nutritional strategy to increase ovulation rate in merino ewes mated in late spring-early summer.

Science.gov (United States)

Nottle, M B; Kleemann, D O; Grosser, T I; Seamark, R F

1997-07-01

A nutritional strategy for increasing ovulation rate in Merino ewes mated in late spring-early summer was evaluated on two commercial farms. The strategy used the 'ram effect' to induce oestrus in seasonally anoestrus ewes and supplementary feeding of lupin grain six days prior to oestrus to increase ovulation rate. Ewes that had been isolated from rams for 6 weeks were exposed to vasectomised rams for 2 weeks and then mated to fertile rams for 6 weeks. Feeding 500 g lupins/head/day for 14 days commencing 12 days after the introduction of vasectomised rams, increased the number of ovulations from 126 to 146 per 100 ewes exposed to rams (P < 0.05). This increase was reflected in an improvement in fecundity (lambs born per ewe lambing; P < 0.05) but not fertility (ewes lambing per ewe mated to rams). Net reproductive performance (the product of fertility, fecundity and lamb survival) was increased by 11 lambs weaned per 100 ewes exposed to rams due to lupin supplementation at mating.

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

Indian Academy of Sciences (India)

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

Uterine Torsion in a West African Dwarf Ewe in Ibadan, Nigeria ...

African Journals Online (AJOL)

Keywords: Uterine torsion, West African Dwarf Ewe, Ibadan A case of uterine torsion in a 21/2 year old pluriparous West Africa Dwarf (WAD) ewe raised semi intensively with adequate veterinary care before the death of the dam and the lamb is presented. The dam had been off feed for 3 days and was found straining a night ...

Primary ewing sarcoma of the anterior mandible localized to the midline

NARCIS (Netherlands)

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

2013-01-01

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

Concluding Remarks | Ewing | Rwanda Journal

African Journals Online (AJOL)

Rwanda Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 2, No 2 (2015) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Concluding Remarks. Helen Ewing. Abstract. No Abstract. Full Text:.

Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

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Ingrid R. Cordeiro

2015-09-01

Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.

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Mohamed A Alfaleh

Full Text Available Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN. Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')/sub 2/ fragments

Energy Technology Data Exchange (ETDEWEB)

Herlyn, D.; Munz, D.L.; Herlyn, M.; Koprowski, H.; Powe, J.; Alavi, A.; Meinken, G.E.; Srivastava, S.C.

1986-01-01

Procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice compared to experimentally immunosuppressed mice due to the higher tumor viability. MAb localization in tumor tissue was greatly enhanced when F(ab')/sub 2/ fragments rather than intact antibody molecules were used. Although tumors could be visualized with /sup 131/I-, /sup 123/I-or /sup 111/In-labeled MAb fragments without background subtraction, tumor-to-background ratios of radioactivity were highest for /sup 131/I-labeled fragments. /sup 131/I-labeled F(ab')/sub 2/ fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by ..gamma..-scintigraphy. Some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')/sub 2/ fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-08-15

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

Productive response of hair ewes crossed with Damara and Dorper and growth of their lambs

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T. Salinas-Rios

Full Text Available ABSTRACT Profitability of sheep production depends on the reproductive response of ewes and growth of their lambs, which can be improved through the ram genotype. The aim of this study was to evaluate the reproductive response of Blackbelly (Bb, Pelibuey (Pb, Katahdin (Kat and Dorper (Dor ewes crossed with Damara (Dam and Dor rams and the growth of their offspring. To measure percentage of single and multiple lambings (MLP, 234 Bb, Pb, Kat and Dor ewes were used. To measure lamb growth, the offspring of 86 Bb x Pb (BbPb ewes and 73 Kat x Dor (KatDOR ewes were used. Four Dor x BbPb, six Dam x BbPb and six Dam x KatDor lambs were slaughtered for carcass assessment. MLP was analyzed with the CATMOD procedure considering the factors age and breed. Lamb growth data were analyzed with the MIXED procedure, and those of carcass characteristics with the GLM procedure of SAS, using weight at slaughter as covariable. MLP was higher (P0.05 by effect of ram breed. It is concluded that Bb ewes are more prolific than Dor ewes; male lambs of Dam rams had post-weaning growth response and carcass yield similar to those of Dor rams, although the female lambs of Dor rams were heavier than those of Dam rams.

Histomorphological changes in follicular apparatus of ewe ovaries following irradiation

International Nuclear Information System (INIS)

Halagan, J.; Arendarcik, J.; Molnarova, M.; Stanikova, A.

1985-01-01

Histological changes in primary follicles of ewes after a five-day protracted exposure to gamma rays were studied by qualitative and micrometric methods. The experiment was carried out in the anoestrous period with 21 ewes of the Slovak Merino breed, divided into three groups. The first control group (five ewes) was not irradiated. The second and third groups (each included eight ewes) were irradiated with 60 Co gamma rays for a period of five days to the total dose of 4.8 Gy. All ewes including the control ones were given Ampicillin Spofa 250 mg per head/day during the period of ten days after irradiation. The third group was administered apart from this a mixture of vitamins, Roboran H, at the dose of 10 g per head/day. The animals were slaughtered on the fifth day of irradiation and on the tenth day after the end of irradiation. The ovaries processed by a routine histological method were cut in 7 μm slices in a series of 70 μm and stained with hematoxylin-eosine. By qualitative histomorphological analysis of the oocytes of primary follicles, chromatin aggregation, pycnosis of nuclei, pronounced acidophilia of oocyte cytoplasm, their shrinking and disintegration were determined. In intact primary follicles, mitotic division of follicular cells stopped and the proportion of follicular cells with pycnotic nuclei increased after irradiation. The results show that the five-day protracted exposure to gamma rays to the total dose of 4.8 Gy caused pronounced degenerative changes in the anoestrous period. Administration of antibiotics or vitamins had no significant effect on the stated histomorphological changes. (author)

Monitoring the reproductive performance in awassi ewes using progesterone radioimmunoassay

International Nuclear Information System (INIS)

Zarkawi, M.

1999-01-01

Jugular serum progesterone (P-4) concentrations were assessed using radioimmunoassay (RIA) kits for about 1 year in 16 local Awassi ewes aged about 1 year and weighing on average 37.4 ±4.9 (range 29.5-44.0 kg). Average pre-mating live weight of animals was different (P 0.05) between animals in average basal pre-mating P-4 concentration, maximum P-4 concentration during the luteal phase in non-pregnant ewes and in the length of the gestation period average basal pre-mating P-4 concentration was 0.62±0.44 (range 0-1.7 nmol l -1 ). Average maximum P-4 concentration during the luteal phase in non-pregnant ewes was 11.0±3.3 (range 5.8-18 nmol l -1 ). Length of gestation period varied from 149 to 155 days with an average of 152±2.3 days. Maximum P-4 concentration during gestation was different (P -1 ). The accuracy of pregnancy diagnosis at around 21 days pot-mating using RIA was 100%. It was concluded that Awassi sheep in Syria have a long breeding season that could start as early as April and last through September. Therefore, ewes might be included in oestrous synchronisation programmes to give three lambs in 2 years. It was also concluded that P-4 concentration under 3.18 nmol l -1 is indicative of either anoestrous or follicular and early luteal phase of the oestrous cycle in Awassi ewes kept in Syria and that RIA could be used for P-4 determination and successful early diagnosis of pregnancy in Awassi sheep. (author)

Serum profile of cytokines interferon gamma and interleukin-10 in ewes subjected to artificial insemination by cervical retraction.

Science.gov (United States)

Alvares, C T G; Cruz, J F; Romano, C C; Brandão, F Z

2016-04-15

This study evaluated the influence of artificial insemination (AI) by cervical retraction (CRI) on serum levels of interferon gamma (IFNγ) and interleukin-10 (IL-10) in ewes. Synchronized pluriparous Santa Inês ewes were subjected to natural mating (NM, n = 8) and AI, which was performed for a fixed time (55 ± 1 hour) by CRI (n = 8) or laparoscopy (n = 8). Ewes were classified as pregnant, with return to estrus (RE) or with embryonic loss (EL). Blood samples were collected on Day 0, Day 3, Day 5, Day 12, and Day 17 (Day 0 = AI/NM) for progesterone dosage and cytokines were quantified from Day 0 to Day 12. Progesterone levels were constant, except for a decrease in ewes with RE at Day 17 (P ewes with EL had lower serum levels of IFNγ and IL-10 than pregnant ewes and ewes with RE, regardless of the reproductive method used, with averages of 769.1, 714.9, and 555.7 pg/mL for IFNγ and 713.8, 699.3, and 578.7 pg/mL for IL-10 in pregnant ewes, ewes with RE and EL, respectively (P ewes does not alter the profile of serum cytokines IFNγ and IL-10 and does not induce an inflammatory reaction that can compromise pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Crude glycerin decreases nonesterified fatty acid concentration in ewes during late gestation and early lactation.

Science.gov (United States)

Polizel, D M; Susin, I; Gentil, R S; Ferreira, E M; de Souza, R A; Freire, A P A; Pires, A V; Ferraz, M V C; Rodrigues, P H M; Eastridge, M L

2017-02-01

Crude glycerin is a gluconeogenic substrate in ruminants and may help to decrease the occurrence of pregnancy toxemia. The objective in this trial was to determine the effects of feeding a diet containing crude glycerin on DMI, milk yield, milk composition, and blood metabolites in periparturient ewes and lamb performance. One hundred eighteen 90 (±1.1)-d pregnant Santa Inês ewes were used. After lambing, 32 ewes (62.8 ± 1.3 kg BW) were allotted in a randomized complete block design defined by prelambing diet, BW, BCS, lambing date, type of birth (single or twin), and sex of offspring. Diets were isonitrogenous (13.0 ± 0.3% CP, DM basis), composed of concentrate and raw sugarcane bagasse (70:30 ratio, DM basis), and fed ad libitum daily. Crude glycerin (83.6% glycerol) levels were 0 or 10% (DM basis), corresponding to the experimental diets G0 and G10, respectively. From 8 until 56 d of lactation, DMI was determined. In the same period, once a week at 1000 h, the ewes were separated from the lambs and mechanically milked after intravenous administration of 10 IU of synthetic oxytocin. Three hours after the first milking, ewes were milked again and milk yield and composition were determined. Glucose, NEFA, and β-hydroxybutyrate (BHBA) were determined at -14, -7, 0, 7, 14, 28, and 56 d relative to lambing and insulin was determined at -14, -7, 0, and 7 d. Crude glycerin did not affect DMI (2.2 kg/d for G0 vs. 2.2 kg/d for G10; = 0.93) or milk production (171 g/3 h for G0 vs. 164 g/3 h for G10; = 0.66). However, there was a decrease ( = 0.01) in milk fat percentage (8.1% for G0 vs. 7.0% for G10) for ewes fed glycerin. Ewes fed the G10 diet had decreased ( ewes fed the G10 diet (0.46 mmol/L for G0 vs. 0.61 mmol/L for G10). There was no effect of diets fed to ewes on lamb growth from birth to weaning. Crude glycerin improved energy balance of periparturient ewes, suggesting a reduced risk of developing clinical metabolic-related disorders. Crude glycerin can be

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

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Dirksen Uta

2010-07-01

Full Text Available Abstract Background Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor. Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. Methods HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. Results 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Conclusions Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

The importance of PET/CT in the evaluation of patients with Ewing tumors

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Júlio Brandão Guimarães

2015-06-01

Full Text Available Abstract The effective evaluation for the treatment of patients with Ewing tumors depends on the accuracy in the determination of the primary tumor extent and the presence of metastatic disease. Currently, no universally accepted staging system is available to assess Ewing tumors. The present study aimed at discussing the use of PET/CT as a tool for staging, restaging and assessment of therapeutic response in patients with Ewing tumors. In spite of some limitations of PET/CT as compared with anatomical imaging methods, its relevance in the assessment of these patients is related to the capacity of the method to provide further physiological information, which often generates important clinical implications. Currently, the assessment of patients with Ewing tumor should comprise a study with PET/CT combined with other anatomical imaging modalities, such as radiography, computed tomography and magnetic resonance imaging.

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

Science.gov (United States)

Lingis, Melissa; Richards, Elaine M.

2011-01-01

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

Evaluation of an accelerated lambing system in Syrian Awassi ewes, using hormonal treatments inside and outside the breeding season

International Nuclear Information System (INIS)

Zarkawi, M.

2010-04-01

An experiment was carried out on Syrian Awassi ewes to assess the accelerated lambing system (three lambings in 2 years) by synchronising and induction of oestrus and increasing ovulation rate using hormonal treatments (intravaginal sponges: FGA + equine chorionic gonadotrophin: eCG). Fifty intact cyclic Syrian Awassi ewes aged 2- 4 years with an average live weight of 51.4 kg were used for 4 years (6 lambings). Ewes were divided into 2 groups: 40 ewes in the treated (T) and 10 in the control (C). Ewes in the T group were treated with FGA for 14 days and injected intramuscularly at sponge withdrawal with 500 IU eCG. Results indicated that, throughout the 6 breeding periods, oestrus induction rate was 100%, and all ewes in the T group were mated within 1-5 days post sponge removal as compared to 10-11 days for ewes in the C group. Treated ewes had higher rates of lambing, multiple birth and fecundity. Repeated administration of eCG (6 times at 8 months interval) had no negative effect on fertility of Syrian Awassi ewes. However, anti-eCG antibodies were produced following eCG injections. (author)

Relationship between energy intake and chewing index of diets fed to pregnant ewes

DEFF Research Database (Denmark)

Nielsen, Mette Vestergaard; Nadeau, E.; Markussen, Bo

2015-01-01

The objective was to determine whether a linear relationship exists between the metabolizable energy (ME) intake of pregnant ewes and a dietary chewing index (CI). The relationship was studied using five feeding trials with intake data from 108 pregnant ewes, 4 to 1 weeks before lambing, giving...... includes random variation of week within experiment on the intercept and linear fixed effect of week before lambing on parameter k. The maximum daily chewing time, CTmax, for the pregnant ewes was predicted to be 1/(4 × k). The MEI declined linearly with increasing dietary CI (P

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

Science.gov (United States)

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

2015-10-01

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

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

Science.gov (United States)

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

2014-01-01

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

Evaluation of therapeutic results in Ewing's sarcoma

International Nuclear Information System (INIS)

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

1975-01-01

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

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

Science.gov (United States)

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

2015-03-01

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

Novel Combination Chemotherapy for Localized Ewing Sarcoma

Science.gov (United States)

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

Changes in the metabolic profile of pregnant ewes to an acute feed restriction in late gestation.

Science.gov (United States)

Cal-Pereyra, L; Benech, A; González-Montaña, J R; Acosta-Dibarrat, J; Da Silva, S; Martín, A

2015-05-01

To detect early changes in the metabolic profile of pregnant ewes subject to acute feed restriction at 130 days of gestation, and to establish indicators of risk for ovine pregnancy toxaemia (OPT) for diagnostic purposes. Twenty Corriedale ewes with known mating dates, carrying a single fetus, were used. Ewes were maintained on meadow grasslands and at 130 days of gestation were randomly divided in two groups of 10 ewes. The control group had ad libitum access to pasture. Ewes in the restricted group were subjected to an acute feed restriction for a maximum of 144 hours (6 days), with free access to water. From the start (0 hours) until the end of feed restriction, blood samples were collected from all ewes to monitor concentrations of cortisol, non-esterified fatty acids (NEFA), ß-hydroxybutyrate (BOHB) daily, and glucose in plasma every 6 hours; urinary pH was also measured. Every 6 hours the food restricted ewes were observed to detect clinical signs of OPT e.g. apathy, grinding teeth, empty chewing movements, head leaning against the wall, tachypnea and not drinking water. In food-restricted ewes, concentrations of glucose decreased and differed from control ewes from 54 to 90 hours (pewes after 48 to 144 hours (pewes showed clinical signs of OPT after 102-132 hours. Mean concentrations of glucose, BOHB and cortisol differed between control and restricted ewes prior to the onset of clinical signs of OPT, after 48-96 hours of feed restriction (p<0.01). Mean gestational length, and time from birth to placental expulsion was not affected by the feed restriction. Our results suggest that concentrations of glucose, BOHB and cortisol in plasma may provide a precocious diagnosis of subclinical OPT, using values of 1.59 (SD 0.24) mmol/L, 2.26 (SD 1.03) mmol/L and 15.09 (SD 7.75) nmol/L, respectively. The identification of a potentially harmful metabolic imbalance could lead to the improvement of treatment success.

Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts.

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Ana de la Cueva

Full Text Available Colorectal cancer (CRC is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα, an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy.ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The effects on thymidilate synthase (TS and thymidine kinase (TK1 levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action.Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.

An Unusual Cause of Urinary Incontinence: Ewing's Sarcoma

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Serhan Kupeli

2015-03-01

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

Evaluation of different models to segregate Pelibuey and Katahdin ewes into resistant or susceptible to gastrointestinal nematodes.

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Palomo-Couoh, Jovanny Gaspar; Aguilar-Caballero, Armando Jacinto; Torres-Acosta, Juan Felipe de Jesús; Magaña-Monforte, Juan Gabriel

2016-12-01

This study evaluated four models based on the number of eggs per gram of faeces (EPG) to segregate Pelibuey or Katahdin ewes during the lactation period into resistant or susceptible to gastrointestinal nematodes (GIN) in tropical Mexico. Nine hundred and thirty EPG counts of Pelibuey ewes and 710 of Katahdin ewes were obtained during 10 weeks of lactation. Ewes were segregated into resistant, intermediate and susceptible, using their individual EPG every week. Then, data of every ewe was used to provide a reference classification, which included all the EPG values of each animal. Then, four models were evaluated against such reference. Model 1 was based on the 10-week mean EPG count ± 2 SE. Models 2, 3 and 4 were based on the mean EPG count of 10, 5 and 2 weeks of lactation. The cutoff points for the segregation of ewe in those three models were the quartiles ≤Q1 (low elimination) and ≥Q3 (high elimination). In all the models evaluated, the ewes classified as resistant had lower EPG than intermediates and susceptible (P ewes classified as susceptible had higher EPG than intermediate and resistant (P 70 %). Model 3 tended to show higher sensitivity and specificity with the reference data, but no difference was found with other models. The present study showed that the phenotypic marker EPG might serve to identify and segregate populations of adult ewes during the lactation period. All models used served to segregate Pelibuey and Katahdin ewes into resistant, intermediate and susceptible. The model 3 (mean of 5 weeks) could be used because it required less sampling effort without losing sensitivity or specificity in the segregation of animals. However, model 2 (mean of 2 weeks) was less labour-intensive.

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

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

2011-08-01

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

Elimination of [14C]heptachlor from body stores of lactating ewes treated with ovine growth hormone

International Nuclear Information System (INIS)

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

1988-01-01

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

Hemithorax irradiation for Ewing tumors of the chest wall

International Nuclear Information System (INIS)

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

2002-01-01

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

Comparison of two long acting pre-lambing anthelmintic treatments on the productivity of ewes in low body condition.

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Bingham, C; Hodge, A; Mariadass, B

2017-05-01

To determine if there was a benefit from treating ewes with a low body condition score (BCS) with long acting anthelmintic products pre-lambing and to compare the effects of two commonly used treatment options. The study was conducted on a single commercial hill country sheep and beef property in the central North Island of New Zealand. Mixed age twin-bearing ewes were preselected by the farmer as being in poor condition 4 weeks before the planned start of lambing, and were sequentially drafted into three equal groups identified with coloured ear tags. The negative control group (n=199) received no anthelmintic treatment; the other two groups received either a controlled release capsule (CRC) containing abamectin, albendazole, Se and Co (n=200) or a long-acting injection of moxidectin (n=200). All ewes were body condition scored (1-5 scale) and weighed at pre-lambing, docking (65 days after treatment) and at weaning (127 days after treatment). Faecal nematode egg counts (FEC) were carried out on 10 ewes from each group at these three times. Most lambs were matched to the ewe treatment groups at weaning, and weighed. At weaning the mean body weight of ewes treated with moxidectin was 3.2 (95% CI=2.3-4.3) kg heavier than controls, and of ewes treated with CRC was 3.6 (95% CI=2.5-4.5) kg heavier than control ewes (pewes had a BCS≥3. At weaning, more ewes treated with CRC (140/194; 72%) or moxidectin (122/187; 65%) had a BCS≥3 than control ewes (55/179 (31%); pewes from the treatment groups, the mean weight at weaning of lambs from ewes treated with moxidectin was 2.6 (95% CI=1.9-3.3) kg heavier, and from ewes treated with CRC was 2.6 (95% CI=1.9-3.4) kg heavier than lambs from control ewes (pewes with low BCS pre-lambing with long acting anthelmintic treatments (moxidectin long acting injection or CRC) resulted in an increase in mean body weight of the ewes and lambs at weaning. There were no significant differences between the two pre-lambing treatments used

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

NARCIS (Netherlands)

E.C. Townsend (Elizabeth); M.A. Murakami (Mark); A. Christodoulou (Alexandra); A.L. Christie (Amanda); J. Köster (Johannes); T.A. DeSouza (Tiffany); E.A. Morgan (Elizabeth); S.P. Kallgren (Scott); H. Liu (Huiyun); S.-C. Wu (Shuo-Chieh); O. Plana (Olivia); J. Montero (Joan); K.E. Stevenson (Kristen); P. Rao (Prakash); R. Vadhi (Raga); M. Andreeff (Michael); P. Armand (Philippe); K.K. Ballen (Karen); P. Barzaghi-Rinaudo (Patrizia); S. Cahill (Sarah); R.A. Clark (Rachael); V.G. Cooke (Vesselina); M.S. Davids (Matthew); D.J. DeAngelo (Daniel); D.M. Dorfman; H. Eaton (Hilary); B.L. Ebert (Benjamin); J. Etchin (Julia); B. Firestone (Brant); D.C. Fisher (David); A.S. Freedman (Arnold); I.A. Galinsky, () (Ilene); H. Gao (Hui); J.S. Garcia, () (Jacqueline); F. Gamache-Ottou (Francine); T.A. Graubert (Timothy); A. Gutierrez (Alejandro); E. Halilovic (Ensar); M.H. Harris (Marian); Z.T. Herbert (Zachary); S.M. Horwitz (Steven); G. Inghirami (Giorgio); A.M. Intlekofer (Andrew); M. Ito (Moriko); S. Izraeli (Shai); E.D. Jacobsen (Eric); C.A. Jacobson (Caron); S. Jeay (Sébastien); I. Jeremias (Irmela); M.A. Kelliher (Michelle); R. Koch (Raphael); M. Konopleva (Marina); N. Kopp (Nadja); S.M. Kornblau (Steven); A.L. Kung (Andrew); T.S. Kupper (Thomas); N.R. LeBoeuf (Nicole); A.S. LaCasce (Ann); E. Lees (Emma); L.S. Li (Loretta); A.T. Look (Thomas); M. Murakami (Masato); M. Muschen (Markus); D. Neuberg (Donna); S.Y. Ng (Samuel); O.O. Odejde (Oreofe); S.H. Orkin (Stuart); R.R. Paquette (Rachel); A.A. Place (Andrew); J.E. Roderick (Justine); J.A. Ryan (Jeremy); S.E. Sallan (Stephen); B. Shoji (Brent); L.B. Silverman (Lewis); R.J. Soiffer (Robert); D.P. Steensma (David); K. Stegmaier (Kimberley); R.M. Stone (Richard); J. Tamburini (Jerome); A.R. Thorner (Aaron); P. van Hummelen (Paul); M. Wadleigh (Martha); M. Wiesmann (Marion); A.P. Weng (Andrew); J.U. Wuerthner (Jens); D.A. Williams (David); B.M. Wollison (Bruce); A.A. Lane (Andrew); A. Letai (Anthony); M.M. Bertagnolli (Monica); J. Ritz (Jerome); M. Brown (Myles); H. Long (Henry); J.C. Aster (Jon); M.A. Shipp (Margaret); J.D. Griffin (James); D.M. Weinstock (David)

2016-01-01

textabstractMore than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address

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

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Redini, Françoise; Heymann, Dominique

2015-01-01

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

Negligible colon cancer risk from food-borne acrylamide exposure in male F344 rats and nude (nu/nu mice-bearing human colon tumor xenografts.

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Jayadev Raju

Full Text Available Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a "complete carcinogen", but acts as a "co-carcinogen" by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters.

Oestrus synchronization in local Awassi ewes using a synthetic prostaglandin

International Nuclear Information System (INIS)

Zarkawi, M.

1998-01-01

Twenty-two local Awassi ewes, at different ages, and weighing on average 53.0 ± 9.7 kg were used to evaluate the effect of Prosolvin, a synthetic prostaglandin, on oestrus synchronization. The results indicate that 47.7 % of the treated animals showed oestrus behaviour and mated within 68 hours after the second injection of Prosolvin, with an average of 54.4 ± 12.8 hours. There was significant (P<0.05) difference within the treated animals to the treatment . Among the treated ewes that showed oestrus. 71.4 % conceived and lambed. Progesterone concentrations dropped sharply within 24 hours after the second injection of Prosolvin 60 % of the animals that conceived and lambed. It could be concluded that Prosolvin could be used in oestrus synchronization in the breeding season, and that Awassi ewes could be added to oestrus synchronization programmes to give 3 lambs in 2 years. (Author)

Study of Blood Metabolites Changes of Purebred Ghezel and Crossbred Arkhar Merinos × Ghezel Ewes during Late Pregnancy

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Leila Ahmadzadeh

2016-11-01

Full Text Available Introduction As pregnancy progresses, nutrient requirements of fetus and thereby ewe increases and some changes in the levels of blood metabolites including glucose, cholesterol and total protein may occur. During gestation, maternal tissues contribute to supplying energy that required for fetus resulting in changes of ewe blood metabolites; however other factors such as breed, age, feeding type of ewes during gestation and season may influence them. The study of blood metabolic changes in different phases of reproductive cycle can be helpful in detecting abnormal situations of ewes and preventing of metabolic disorders such as pregnancy toxemia and fatty liver syndrome. There is little information about the effect of different genotypes on blood metabolites and the occurrence of metabolic disorders in late pregnancy. Therefore the aim of the present study was to determine changes in blood metabolites of purebred Ghezel and ArkharMerino× Ghezel crossbred ewes during late pregnancy and effect of crossbreeding of Iranian purebred sheep with Merino sheep on metabolite level changes in these two groups of sheep and study of susceptibility to metabolic disease in late pregnancy. Materials and Methods In the present study, fifty five pregnant Ghezel ewes (36 singles and 15 twins and 34 pregnant crossbred ewes (20 singles and 14 twins were used. Estrus synchronization of all ewes was done using CIDR. CIDR were removed 14 days later and all ewes were injected PMSG intramuscularly and then mated with rams. All of the ewes were grazing in the pasture during pregnancy, but in the last two months of pregnancy, feeding of ewes was manually. Blood samples were collected by vacuum tubes during four hours after feeding from the jugular vein of ewes on 15 days prior to mating period and on days 90, 120 and 140 of the pregnancy. Blood samples were centrifuged with 4000 rpm for 12 minutes to extract blood serum and then sera were frozen in -20oC until further

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

International Nuclear Information System (INIS)

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

2001-01-01

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

Numerical and Weight Productivities of Crossbred D’man by Local Queue Fine de l’Ouest Ewes

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M. Rekik

2005-01-01

Full Text Available Productivity of F1 crossbred ewes between the prolific D’man and the local Queue fine de l’Ouest breeds (D’man x QFO mated with terminal sires of the Brune noire de Suisse (BNS breed was evaluated and compared to that of (i QFO and D’man ewes respectively mated to rams of the same breed in a research station (ESAK and of (ii QFO ewes mated to rams of the same breed in a commercial farm (El-Mabrouka. In ESAK station, data collected between 1995 and 2003, and related to 343, 168 and 323 lambings of QFO, D’man, and F1 crosses D’man x QFO ewes, respectively, were used. At birth, the mean litter size was 1.17 ± 0.37, 1.76 ± 0.71, and 1.40 ± 0.54 for ewes of the QFO, D’man, and crosses D’man x QFO genotypes, respectively, whereas at 90 days after lambing, the corresponding figures were 1.13 ± 0.40, 1.65 ± 0.70, and 1.31 ± 0.54. The year of lambing, genotype of the ewe as well as their interaction were significant sources of variation of all litter sizes. At 10 days after lambing, the weight productivity of QFO ewes was 7.3 ± 2.5 kg, and was thus significantly higher (p < 0.05 than that of D’man (6.6 ± 2.7 kg, and D’man x QFO (7.0 ± 2.3 kg ewes. This trend was reversed 90 days after lambing with weight productivity of D’man x QFO, and D’man ewes reaching 22.9 ± 7.7 and 22.5 ± 12.0 kg, respectively, and that of QFO sheep 19.5 ± 6.7 kg. With the exception of the age of the ewe, all other sources of variation highly influenced (p < 0.001 most weight productivity traits. In El-Mabrouka farm, the data used concerned 1048 and 529 lambings of QFO, and D’man x QFO breeds, respectively, that occurred during years 1999, 2000 and 2001. The year of lambing, genotype of the ewe as well as its age were highly significant sources of variation for the litter size at birth. Crossbred ewes produced on average 0.2 lamb more than QFOs (p < 0.05. Difference in productivity at 70 days after lambing was approximately 3 kg in favor of D�

Performance of Nursing Awassi Ewes Fed Different Levels of Bread By-product

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B. S. Obeidat

2012-08-01

Full Text Available Objective of this experiment was to evaluate the effect of partial substitution of barley grain with bread by-product (BB on performance of Awassi ewes and their lambs. Forty Awassi ewes rearing single lambs were randomly allotted into four experimental diets containing various levels of BB. The experimental diets contained 0 (BB0, 10 (BB10, 15 (BB15, and 20% (BB20 of BB on dietary dry matter (DM. The study lasted for eight weeks, in which the first week was used as an adaptation period and seven weeks of data collection. Ewes and their lambs were penned individually where they were fed their lactating diets ad libitum. Ewes and lambs body weights were measured at the beginning and at the end of the experiment. However, milk production and composition were evaluated biweekly. Feeding BB had no effect (p>0.05 on dry matter (DM, organic matter (OM, and crude protein (CP intakes. However, neutral detergent fiber (NDF intake was the lowest (p0.05 on ewes body weight change and on lamb performance (i.e., weaning body weight and average daily gain. Similarly, no differences (p>0.05 were observed either in milk production or composition by the BB substitution. Inclusion of BB reduced feed cost by 9, 14, and 18% for the BB10, BB15, and BB20 diets, respectively. No differences were observed in milk efficiency (DM intake: milk production; p>0.05 among diets. However, cost of milk production ($US/kg milk was the lowest (p<0.05 in the diet containing BB20. Results of the present study indicate that feeding bread by-product up to 20% of the diet DM had no effect on performance of Awassi ewes and their lambs and reduced feed cost.

Performance of Nursing Awassi Ewes Fed Different Levels of Bread By-product

Science.gov (United States)

Obeidat, B. S.; Haddad, S. G.; Titi, H. H.; Abu Ishmais, M. A.; Telfah, B. T.

2012-01-01

Objective of this experiment was to evaluate the effect of partial substitution of barley grain with bread by-product (BB) on performance of Awassi ewes and their lambs. Forty Awassi ewes rearing single lambs were randomly allotted into four experimental diets containing various levels of BB. The experimental diets contained 0 (BB0), 10 (BB10), 15 (BB15), and 20% (BB20) of BB on dietary dry matter (DM). The study lasted for eight weeks, in which the first week was used as an adaptation period and seven weeks of data collection. Ewes and their lambs were penned individually where they were fed their lactating diets ad libitum. Ewes and lambs body weights were measured at the beginning and at the end of the experiment. However, milk production and composition were evaluated biweekly. Feeding BB had no effect (p>0.05) on dry matter (DM), organic matter (OM), and crude protein (CP) intakes. However, neutral detergent fiber (NDF) intake was the lowest (pby-product had no effect (p>0.05) on ewes body weight change and on lamb performance (i.e., weaning body weight and average daily gain). Similarly, no differences (p>0.05) were observed either in milk production or composition by the BB substitution. Inclusion of BB reduced feed cost by 9, 14, and 18% for the BB10, BB15, and BB20 diets, respectively. No differences were observed in milk efficiency (DM intake: milk production; p>0.05) among diets. However, cost of milk production ($US/kg milk) was the lowest (pby-product up to 20% of the diet DM had no effect on performance of Awassi ewes and their lambs and reduced feed cost. PMID:25049672

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

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Yehuda Kollender

1999-01-01

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

Neutrality of miniSTR D22S1045 marker by Ewing's sarcoma phenotype.

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Silva, Deborah S B S; Raimann, Paulo E; Moro, Tatiane; Picanço, Juliane B; Abujamra, Ana L; de Farias, Caroline B; Roesler, Rafael; Brunetto, Algemir L; Alho, Clarice S

2013-11-01

Neutrality investigations of markers with forensic use are important to see if a phenotypic trait is being expressed in relation to the alleles of the marker. MiniSTR marker D22S1045 (locus 22q12.3) is localized near the breakpoint region of the EWS gene (22q12.2), which leads to the development of Ewing's Sarcoma. Analyzing allele frequencies and linkage disequilibrium in Ewing's sarcoma patients and non-affected populations, we found that the marker mD22S1045 was neutral when related to Ewing's Sarcoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Maternal undernutrition during the pre- and post-conception periods in twin-bearing hairsheep ewes: effects on fetal and placental development at mid-gestation.

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Macías-Cruz, Ulises; Vicente-Pérez, Ricardo; Mellado, Miguel; Correa-Calderón, Abelardo; Meza-Herrera, Cesar A; Avendaño-Reyes, Leonel

2017-10-01

To evaluate the effects of pre- and post-conception undernutrition (UN) on fetal and placental development at mid-gestation, 28 Katahdin × Pelibuey multiparous ewes were blocked by weight and assigned to the following four dietary treatments (n = 7 each): ewes fed 100% (control) or 60% of their nutritional requirements 30 days before mating (UNPre), 50 days after mating (UNPost) or during both periods (UNB). Four twin-bearing ewes were selected per treatment at day 50 post-conception and then slaughtered at day 75 of gestation to analyze their fetuses. Control fetuses were heavier (P ewes than UNB ewes, but not relative to ewes of other treatments. The number of placentomes per ewe and placental efficiency were unaffected by UN treatments. Compared to control, only UNB ewes exhibited variations (P ewes than placentas of control ewes (P ewes carrying twins is mainly altered when nutritional restriction occurs simultaneously before conception and during the first third of pregnancy.

EFFECT OF SHEARING DURING PREGNANCY ON PRODUCTIVE PERFORMANCE IN THE POST-PARTUM PERIOD OF EWES ON EXTENSIVE HUSBANDRY

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Viviane Marques Guyoti

2015-04-01

Full Text Available The use of shearing during pregnancy has been described as a tool for improving productivity in sheep and for minimizing perinatal mortality in lambs through the increase of fetal development. This study assessed the effect of shearing around 74 days of gestation on the productive performance of ewes and lambs during the first month of life. Forty Corriedale ewes were inseminated in autumn in Southern Brazil. All ewes were kept together at the same pasture under extensive husbandry conditions. The ewes were randomly separated into two treatment groups: twenty animals were completely sheared at 74 ± 6 days of pregnancy, and twenty were kept without sheared during pregnancy, composing the control group. Ewes and their lambs were evaluated at three different times during the experiment: at birth, between 15 and 21 days post-partum and between 22 and 45 days post-partum. Ewes had their body condition score, body weight, placental weight, milk production and serum concentrations of beta-hydroxybutyrate measured, while lambs had hematocrit, hemoglobin, and plasma lactate and glucose, as well as body weight at birth and until wean determined. Values of hematocrit and hemoglobin were lower and body weight at birth and at wean was higher in the group of lambs born from sheared ewes. Placenta weight was higher in sheared ewes. Body condition score and beta-hydroxybutyrate showed no differences between groups. Milk production of sheared ewes (1.26 L/day was higher than in control group (0.93 L/day. Shearing ewes at 74 days of pregnancy was efficient for the better development of lambs at post-birth, reducing perinatal mortality rates.

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

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Martin Sebastian Staege

2016-01-01

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

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

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

2016-12-01

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

Quantitative proteomics and transcriptomics reveals metabolic differences in attracting and non-attracting human-in-mouse glioma stem cell xenografts and stromal cells

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Norelle C. Wildburger

2015-09-01

Full Text Available Bone marrow-derived human mesenchymal stem cells (BM-hMSCs show promise as cell-based delivery vehicles for anti-glioma therapeutics, due to innate tropism for gliomas. However, in clinically relevant human-in-mouse glioma stem cell xenograft models, BM-hMSCs tropism is variable. We compared the proteomic profile of cancer and stromal cells in GSCXs that attract BM-hMSCs (“attractors” with those to do not (“non-attractors” to identify pathways that may modulate BM-hMSC homing, followed by targeted transcriptomics. The results provide the first link between fatty acid metabolism, glucose metabolism, ROS, and N-glycosylation patterns in attractors. Reciprocal expression of these pathways in the stromal cells suggests microenvironmental cross-talk.

The effect of superovulation prior to mating on fetal growth in Iambs from Javanese thin-tail ewes

OpenAIRE

W Manalu

1999-01-01

Twenty-nine fetuses (11 fetuses from 9 non-superovulated ewes and 18 fetuses from 8 superovulated ewes) were used to study the effect of superovulation of ewes prior to mating on fetal weight, fetal length, the length of the body and limbs, chest circumference, weights of the body, head, neck, limb, and viscera. Superovulated ewes, though with a higher litter size, had a greater fetal growth as was indicated by the greater fetal weight and length, the length and weight of the body and limb on...

The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot})

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Sarkaria, Jann N; Fowler, John F; Lindstrom, Mary J; Jordan, V Craig; Mulcahy, R Timothy

1995-02-15

Purpose: Repopulation during fractionated radiotherapy has been postulated to result in a significant loss in local control in rapidly proliferating tumors. Clinical data suggest that accelerated fractionation schedules can overcome the influence of repopulation by limiting the overall treatment time. Unfortunately, accelerated therapy frequently leads to increased acute reactions, which may become dose limiting. An alternative to accelerated fractionation would be to decrease the rate of repopulation during therapy. To test the potential efficacy of this alternative, we examined the effect of reducing tumor proliferation rate on the response of MCF-7 human breast carcinoma xenografts treated with a short vs. a long course of fractionated therapy. To reduce the proliferation rate, we deprived nude mice transplanted with MCF-7 xenografts of the growth-stimulating hormone estradiol (E{sub 2}). We have previously reported that E{sub 2} deprivation increases the potential doubling time (T{sub pot}) for MCF-7 xenografts from a mean of 2.6 days to 5.3 days (p < 0.001). Methods and Materials: E{sub 2}-stimulated and E{sub 2}-deprived MCF-7 breast carcinoma xenografts were clamped hypoxically and irradiated with four fractions of 5 Gy each, using either a short (3-day) or long (9-day) treatment course. E{sub 2} stimulation was restored in all animals at the completion of irradiation. Radiation response was determined by regrowth time and regrowth delay of the irradiated tumors as compared to unirradiated controls. Results: Prolongation of therapy in rapidly proliferating, E{sub 2}-stimulated tumors (T{sub pot} {approx} 2.6 days) resulted in a significant decrease in regrowth time in two identical experiments. With results pooled for analysis, the regrowth times for the short and long treatments were 62 and 32 days, respectively (combined p < 0.001). The shorter regrowth times suggest that there was less overall tumor damage with the longer fractionated radiotherapy course

Allografts versus Equine Xenografts in Calcaneal Fracture Repair.

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Sonmez, Mehmet Mesut; Armagan, Raffi; Ugurlar, Meric; Eren, Tugrul

Displaced intra-articular calcaneal fractures are difficult to treat. We determined the functional results and complications of using allografts or equine xenografts in treating these fractures. We reviewed patients seen at our center from May 2011 to December 2014 with Sanders type III or IV unilateral calcaneal fractures treated with locking plates and an additional bone allograft or equine xenograft. A minimum of 1 year after surgery, a history of infection and functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society clinical rating system. Changes in the Gissane angle (GA) and Böhler angle were assessed from radiographs. Of the 91 eligible patients, 15 were lost to follow-up, leaving a sample of 76 patients (42 males): 45 received allografts (19 for type III and 26 for type IV fractures) and 31 received xenografts (20 for type III and 11 for type IV fractures). The mean age was about 40 years in both groups. After ≥1 year of follow-up, the proportion of patients in the American Orthopaedic Foot and Ankle Society scoring categories did not differ significantly between the 2 groups (mean ankle score, 86.5 in the allograft group and 85.1 in the xenograft group), and the American Orthopaedic Foot and Ankle Society functional outcomes were good or excellent in 69% and 68%, respectively (p = .986). The groups did not differ in the incidence of superficial or deep infection (p = 1.000). The Böhler angles were significantly decreased in the xenograft group. Xenografts might be preferred for repairing intra-articular calcaneal fractures because they can perform as well as allografts, avoid donor site morbidities, and are more available and less expensive than allografts. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

[Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice].

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Liu, G Y; Gao, Z H; Li, L; Song, T T; Sheng, X G

2016-06-25

To investigate the expression of Jagged1 in human epithelial ovarian carcinoma tissues and the effect of Jagged1 on growth of xenograft in nude mice. (1) Forty-eight cases of ovarian cancer and 30 cases of patients with benign epithelial ovarian tumor in the Henan Province Xinxiang Central Hospital during Feb. 2011 to Mar. 2014 were enrolled in this study. The mRNA expression of Jagged1, Notch1 and the downstream target genes Hes1, Hey1 were analyzed by using realtime PCR method. (2) The ovarian cancer xenograft models in nude mice were constructed by injecting SKOV3 cells in axillary subcutaneouswere. The nude mice were randomly divided into Jagged1 interference group, blank plasmid group and control group. Each group had 10 mice. They were transfected with pcDNA3.1(+)-siRNA-Jagged1, blank plasmid pDC3.1 and phosphate buffer, respectively. The tumor volumes and tumor masses were measured 14 days after transfection and the inhibition rate was calculated. The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues after transfection in each group was detected by using realtime PCR technique and the relative protein expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues was detected by utilizing western blot method. (1) The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in ovarian cancer tissues were higher than benign ovarian tumor tissues, the differences were statistically significant (Ptissues of nude micein Jagged1 interference group were lower than that in the other two groups, the differences were statistically significant (Ptissues of nude mice among the three groups (P>0.05). Jagged1 is highly expressed in epithelial ovarian carcinoma. Jagged1 gene interference in xenograft tumor can inhibit ovarian cancer cell growth and improve tumor suppressor rate, which probably play roles by inhibiting Notch1 signaling pathway.

Impacts of supplemental arginine on the reproductive performance of fall lambing ewes.

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Crane, A R; Redden, R R; Van Emon, M L; Neville, T L; Reynolds, L P; Caton, J S; Schauer, C S

2016-08-01

In sheep, embryonic and fetal death during pregnancy can account for 25% to 50% of the total number of corpora lutea (and thus potential embryos). The objective of this study was to determine the effects of injectable and oral Arg supplementation provided for 14 d postbreeding on the reproductive performance of naturally stimulated fall lambing ewes. Rambouillet ewes ( = 210) were exposed to rams equipped with marking harnesses to induce cyclicity in April 2012. Upon estrus detection (d 0) ewes were randomly assigned, in a completely random design, to 1 of 6 treatments for a 14-d treatment period: injectable saline (CON; = 25), injectable Ala (IVALA; = 20), injectable Arg (IVARG; = 23), oral rumen-protected Arg (RPARG; = 20), oral fish meal (FM; = 24), or oral soybean meal (SBM; = 23). Daily treatments, except CON, IVALA, and SBM, were formulated to provide supplemental Arg at 30 mg·kg BW·d and were provided at 0800 h daily. Ewes receiving injectable treatments were provided 454 g corn/d postinjection, whereas ewes receiving oral supplements were provided a ground ration of their respective treatments with corn individually at 0800 h daily. Plasma and serum samples were collected on d 0, 2, 4, 6, 8, 10, 12, and 14 from 12 ewes per treatment to evaluate plasma progesterone and serum AA concentrations. At lambing, birth weight, birth type, and sex were recorded. Weaning weights were recorded when the average age of lambs was 85 d. No differences ( ≥ 0.39) were detected for pregnancy, prolificacy, and lambing rates or lamb birth weights among treatments. However, litter weaning weight tended to be greater ( = 0.06) and weaning rates were greater ( = 0.05) in Arg-injected ewes (1.09, 0.95, 1.29, 0.72, 1.00, and 0.86, respectively). Plasma progesterone and serum Arg concentrations showed a treatment and day effect ( < 0.001), but no treatment × day interaction ( ≥ 0.99) was observed. In contrast to previous research, supplemental Arg during the first 14 d of

Seroprevalence and molecular characterization of Chlamydia abortus in frozen fetal and placental tissues of aborting ewes in northeastern Algeria.

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Hireche, Sana; Ababneh, Mustafa Mohammed Kheir; Bouaziz, Omar; Boussena, Sabrina

2016-02-01

Enzootic abortion of ewes is one of the most serious health problems in sheep flocks worldwide. It has a significant economic impact because abortion, decrease in milk production and weak lambs. Besides, the bacteria is zoonotic. A cross-sectional study was conducted to determine the seroprevalence and risk factors associated with Chlamydia abortus infection in 552 ewes in Constantine using a C. abortus-specific indirect ELISA kit. Chlamydial DNA was investigated in ten ovine fetuses and eight placentas using PCR- restriction fragment length polymorphism (RFLP) and DNA sequencing. The study concluded that 7.2 % of ewes were seropositive and 33.3 % of sheep flocks had at least one seropositive ewe. Adjacent farmworker visits (OR = 7.667, 95 % CI (OR) = 2.307; 27.203) was defined as a risk factor. Deliveries of weak lambs (OR = 2.920, 95 % CI (OR) = 1.022; 8.342) and septicemia in lambs (OR = 9.971, 95 % CI (OR) = 2.383; 41.713) were significantly associated with chlamydial infection. PCR-RFLP analysis revealed positive signals to C. abortus in six fetuses and four placentas. Sequencing of the omp2 gene revealed that the Algerian strain is 96 % similar with C. abortus FAS strain. C. abortus plays a major role in abortion in northeastern Algeria. Appropriate control measures must be implemented to reduce economic losses and to avoid human contamination.

Upregulation of growth signaling and nutrient transporters in cotyledons of early to mid-gestational nutrient restricted ewes

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Ma, Yan; Zhu, Mei J.; Uthlaut, Adam B.; Nijland, Mark J.; Nathanielsz, Peter W.; Hess, Bret W.; Ford, Stephen P.

2011-01-01

Multiparous ewes received 100% (control, C, n=13) or 50% (nutrient restricted, NR, n=14) of NRC dietary requirements from d28-d78 of gestation. On d78, 5 C and 6 NR ewes were necropsied. The remaining 8 C and 8 NR ewes were fed to 100% of NRC from d78-d135 and necropsied. Maternal blood was collected at both necropsies and at weekly intervals for assay of glucose, insulin and leptin. Fetal blood was collected at d78 and d135 necropsies for assay of glucose and lipids. Cotyledonary (COT) tissue was evaluated for protein and mRNA expression [fatty acid transporter (FATP)1, FATP4, CD36, glucose transporter (GLUT)1 and GLUT3], mRNA expression only [placenta fatty acid binding protein (FABPpm) and lipoprotein lipase (LPL)], or expression of phosphorylated and total protein forms [AMP kinase (AMPK)α, acetyl-CoA carboxylase (ACC), extracellular signal-regulated kinase (Erk)1/2, mammalian target of rapamycin (mTOR) and protein kinase B (Akt)]. On d78, but not d135, placental and fetal weights were reduced (P ewes. Maternal circulating glucose, insulin and leptin levels were decreased in NR vs. C ewes on d78 (P ewes (P ewes. AMPK, ACC, and Erk1/2 activities were also increased (P ewes on d135. These data demonstrate placental adaptation to maternal NR through increasing nutrient transporter production and growth signaling activity. PMID:21292322

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

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Kelly M. Bailey

2016-08-01

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

Study of the ovarian function in Awassi ewes

International Nuclear Information System (INIS)

Zarkawi, M.

1997-01-01

An experiment was carried out on indigenous Awassi ewes to study some reproductive criteria by measuring the changes of progesterone concentrations in the blood sera for about one year using radioimmunoassay (RIA). Average basal pre-mating progesterone concentration was 0.60 ± 0.42 n mol/1 (0-107 n mol/1). Average maximum progesterone concentration during the luteal phase in non-pregnant ewes was 11.1 ± mol/1 (5.8-18.00 n mol/1). Average maximum progesterone concentration during gestation was 58.4 ± 20.9 n mol/1 (29.25-100.00 n mol/1). The accuracy of pregnancy diagnosis at around 21 days post mating using RIA was 100%. (author)

Using Longitudinal Assessment on Extensively Managed Ewes to Quantify Welfare Compromise and Risks

Science.gov (United States)

Barber, Stuart; Hemsworth, Paul; Doyle, Rebecca

2018-01-01

Simple Summary Sheep managed extensively can be exposed to several welfare challenges during the year, and the risk of some diseases can increase in warmer and wetter seasons. In this study, the welfare of Merino ewes was examined over a calendar year. The welfare of these animals, kept on a single farm with consistent management, varied substantially. Overall, the largest number of ewes experienced compromise and risk to welfare at weaning, indicating that this was the most vulnerable time. The main welfare issues identified were under and over feeding, ewe mortality, lameness, ecto-parasites (flystrike) and mastitis, all of which could be improved by modifying management practices, such as improved nutritional management and monitoring and better tail docking procedures. Future research must consider that significant variation in the on-farm welfare of ewes occurs during a calendar year, which needs to be accounted for when conducting on-farm assessments. Abstract This study examined variation in the welfare of extensively managed ewes and potential welfare risks. A total of 100 Merino ewes (aged 2–4 years) were individually identified and examined at three key stages: pregnancy, lactation and weaning. Eight animal-based welfare measures were used to assess welfare: flight distance, body condition score (BCS), fleece condition, skin lesions, tail length, dag score, lameness and mastitis. Data were analysed by ANOVA and McNemar’s statistics. Overall, the average BCS of the group was in agreement with industry recommendations. However, a number of animals were classified with inadequate condition (either too thin or too fat) across the three observation periods. The presence of heavy dags was greatest at mid-lactation (87%, P welfare issues identified were under and over feeding, ewe mortality, lameness, ecto-parasites (flystrike) and mastitis, all of which have the potential to be reduced with improved management practices. Future welfare assessment programs

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

International Nuclear Information System (INIS)

Huang, Peigen; Allam, Ayman; Perez, Luis A.; Taghian, Alphonse; Freeman, Jill; Suit, Herman D.

1995-01-01

Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm 3 , mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD 50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD 50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

Effectiveness of controlled internal drug release device treatment to alleviate reproductive seasonality in anestrus lactating or dry Barki and Rahmani ewes during non-breeding season.

Science.gov (United States)

El-Mokadem, M Y; Nour El-Din, Anm; Ramadan, T A; Rashad, A M; Taha, T A; Samak, M A; Salem, M H

2018-04-01

This study aimed to evaluate the effectiveness of hormonal treatments on ovarian activity and reproductive performance in Barki and Rahmani ewes during non-breeding season. Forty-eight multiparous ewes, 24 Barki and 24 Rahmani ewes were divided into two groups, 12 lactating and 12 dry ewes for each breed. Controlled internal drug release (CIDR) device was inserted in all ewes for 14 days in conjunction with intramuscular 500 IU equine chronic gonadotrophin (eCG) at day of CIDR removal. Data were analysed using PROC MIXED of SAS for repeated measures. Breed, physiological status and days were used as fixed effects and individual ewes as random effects. Barki ewes recorded higher (p ewes. Lactating ewes recorded higher (p ewes. Number and diameter of large follicles recorded the highest (p ewes recorded longer (p ewes. In conclusion, CIDR-eCG protocol was more potent in improving ovarian activity in Barki compared to Rahmani ewes, but this protocol seems to induce hormonal imbalance in Barki ewes that resulted in increasing conception failure compared to Rahmani ewes. © 2017 Blackwell Verlag GmbH.

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

Science.gov (United States)

Chaturvedi, Aashi; Hoffman, Laura M.; Jensen, Christopher C.; Lin, Yi-Chun; Grossmann, Allie H.; Randall, R. Lor; Lessnick, Stephen L.; Welm, Alana L.; Beckerle, Mary C.

2014-01-01

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised. PMID:25057021

Ewes carrying the Booroola and Vacaria prolificacy alleles respond differently to ovulation induction with equine chorionic gonadotrophin.

Science.gov (United States)

Moraes, J C F; Souza, C J H

2017-09-21

The magnitude of ovulation rate (OR) after hormonal induction in sheep should be considered when prolific genotypes are used. We investigated for the first time the effect of the Vacaria allele and its combined effect with the Booroola prolificacy mutation on OR after hormonal treatment during breeding and anoestrous season. A hundred forty-nine Ile de France crossbred ewes, raised in natural pastures in South Brazil, were used to evaluate the OR after treatment with progestagen (MAP) followed or not by equine chorionic gonadotrophin (eCG) treatment (MAP + eCG). During the breeding season, 96% MAP-treated ewes ovulated in comparison to 97% of MAP + eCG-treated females. The double heterozygous carriers (BNVN) presented the higher OR, followed by the single Vacaria (NNVN) and Booroola (BNNN) heterozygous females and least the wild-type (NNNN) ewes. During anoestrus, 96% eCG-treated ewes ovulated, in contrast to 6% treated with MAP alone. The OR of the gonadotrophin-treated females was higher in BNVN and BNNN than NNVN and NNNN ewes. An additive effect in the OR of the two mutations was observed since OR in double heterozygous ewes was similar to the sum of the effects of the alleles of the single heterozygous carrier ewes.

HEALTH AND HYGIENIC CONDITIONS OF EWE'S MILK PROCESSING FROM THE ASPECT OF FOOD SAFETY

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Jana Pukáčová

2010-07-01

Full Text Available Totally, 47 strains of S. aureus and 578 coagulase negative staphylococci were detected in samples from raw ewe milk. The 35 out 47 isolates of S. aureus from ewe milk were positive for the presence of staphylococcal enterotoxin genes: sea(4 %, sec (48 % a sed (48 %. Staphylococcus epidermis (33.04%, Staphylococcus caprae (21.28% were more prevalent. Staphylococcus chromogenes (7.44 %, Staphylococcus hominis (7.09%, Staphylococcus xylosus (6,92 %, a Staphylococcus warneri (6.40 % were isolated also in ewes milk. Staphylococcus haemolyticus (3.11 %, Staphylococcus capitis (2.94 %, Staphylococcus simulans (2.08 % and Staphylococcus saprophyticus (1.73 % were isolated very rarely from the taken individual milk ewe samples. Sporadically, only in few cases, the others coagulase negative staphylococci were isolated (Staphylococcus cohnii cohnii, Staphylococcus sciuri, Staphylococcus closii, Staphylococcus lugdunensis, Staphylococcus auricularis and Staphylococcus equorum.   doi:10.5219/24

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

Science.gov (United States)

Gupta, Divya; Gulati, Achal; Purnima

2017-09-01

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

Ewing's Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies.

Science.gov (United States)

Wolpert, Fabian; Grotzer, Michael A; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth; Bode-Lesniewska, Beata

2016-01-01

Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing's sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing's sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing's sarcoma is summarized and possible pathogenic mechanisms are critically discussed.

Factors affecting the fertility of ewes after intrauterine insemination with frozen-thawed semen during the non-breeding season.

Science.gov (United States)

Fukui, Yutaka; Kohno, Hirohide; Okabe, Kentaro; Katsuki, Sara; Yoshizawa, Masahiro; Togari, Tetsuro; Watanabe, Hiroyuki

2010-08-01

In this study, two successive field trials were conducted during the non-breeding season to investigate various factors affecting on fertility of Suffolk ewes after intrauterine insemination with frozen-thawed semen. In the first year (Experiment 1), three sperm numbers per insemination dose (0.25, 0.5 and 1 million sperm) and five sheep farms were used, and in the second year (Experiment 2), parity, age, body weight, body condition score (BCS) and postpartum days were investigated to compare pregnancy and lambing rates. High pregnancy and lambing rates (70.6 and 70.6%, respectively) were obtained with 0.25 million sperm per dose. There were no significant differences in the pregnancy and lambing rates among the five farms, but there was a tendency for one farm to have higher pregnancy (75.8%, P=0.065) and lambing (72.7%, P=0.077) rates than those (46.7-53.3% and 45.2-53.3% for the pregnancy and lambing rates, respectively) of the other farms. In Experiment 2, ewe age significantly affected both the pregnancy and lambing rates. Nulliparous ewes had a higher lambing rate (72.0%) than that (44.2%) of multiparous ewes, but a significant difference was not revealed. Regardless of body weight, BCS tended to be an important factor influencing on fertility of ewes. Body weight and the postpartum days did not affect the fertility of ewes. It was concluded from these results that the fertility of Suffolk ewes after intrauterine insemination with frozen semen was significantly influenced by sperm number per dose and ewe age. Nulliparous ewes at less than three years of age and with a BCS of more than 3.0 are expected to have higher fertility than other ewes.

plasma luteinizing horiione leveis in ewes failing

African Journals Online (AJOL)

The mean plasrm LH bvels duing livc consecutive. &yr, in the various .... ewes in continuous contact with rams (least square ana- ... (Nankin & Troen, 1972; Root, De-Cherney, Russ, Duckett, ... Such fluctuations in hormone levels can have an.

The antitumour activity of alkylating agents is not correlated with the levels of glutathione, glutathione transferase and O6-alkylguanine-DNA-alkyltransferase of human tumour xenografts. EORTC SPG and PAMM Groups.

Science.gov (United States)

D'Incalci, M; Bonfanti, M; Pifferi, A; Mascellani, E; Tagliabue, G; Berger, D; Fiebig, H H

1998-10-01

Twenty-three human xenografts, including five colon, five gastric, nine lung (three small cell lung cancer) and four breast carcinomas, were investigated for their sensitivity to nitrosoureas, dacarbazine (DTIC), cyclophosphamide (CTX) and cisplatin (DDP). In 12 cases, at least one of the drugs produced complete or partial remission, in 2, a minor regression was observed and in the other 9, treatment was ineffective. The level of sensitivity to each drug, using a score from 1 to 5, was correlated to three biochemical parameters reported to be involved in resistance to alkylating agents: glutathione (GSH), glutathione transferase (GST) and O6-alkylguanine-DNA-alkyltransferase (AGT). A wide variability was found in these parameters in the xenografts investigated. No correlation was found between any of the three parameters and sensitivity to the drugs used or between sensitivity to one drug and to any of the other drugs tested. These results illustrate the complexity of the question of resistance to alkylating agents and indicate that, at least in xenografts, the biochemical parameters examined are not predictive of response to alkylating agents.

Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts

Energy Technology Data Exchange (ETDEWEB)

Goetze, K.; Meyer, S.S.; Mueller-Klieser, W. [University Medical Center Mainz Univ. (Germany). Inst. of Physiology and Pathophysiology; Yaromina, A. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Zips, D. [University Hospital Tuebingen (Germany). Dept. of Radiation Oncology; Baumann, M. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Dresden Technical Univ. Dresden (Germany). Dept. of Radiation Oncology

2013-09-15

Background and purpose: Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. Materials and methods: Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. Results: Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. Conclusion: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment. (orig.)

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

NARCIS (Netherlands)

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

2005-01-01

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

Evaluation of Rambouillet, Polypay, and Romanov-White Dorper x Rambouillet ewes mated to terminal sires in an extensive rangeland production system: Lamb production

Science.gov (United States)

Ewe productivity (i.e., total numbers or weight of lamb weaned ÷ number of breeding ewes) is a key indicator of lamb production efficiency. This second-generation study compared various measures of ewe productivity and ewe and lamb performance in an extensive rangeland production system of ewes of 3...

EFFECT OF FLUOROGESTONE ACETATE ON THE VAGINAL MICROBIOTA FROM EWES PELIBUEY IN THE PAPALOAPAN REGION

Directory of Open Access Journals (Sweden)

Nohemí Gabriela Cortés-López

2013-09-01

Full Text Available Ewes are polyoestrous seasonal animals, however in order to increase their fertility, progesterone derivatives are used by means of impregnated sponges with 20 mg of fluorogestone acetate (FGA. Nevertheless, the use of sponges with FGA generates vaginitis, erythema and interferes with fertility. This paper studies the effect of FGA and sponge over the microbiota vaginal in ewes anestrous. To obtain experimental samples, fifteen ewes anestrous were used. Five ewes were used as control group. Ten ewes anestrous were used and data were collected before, withdrawal and 56 h after withdrawal of sponges with and without FGA, in order to quantify, identify and evaluate changes in the vaginal bacterial microbiota. In the normal microbiota were found Escherichia and Klebsiella strains; however, after removal of the devices, were found enteropathogenic coliform bacterias and some opportunistic as Shigella, Enterobacter, Citrobacter, E. coli, Pseudomonas and Acinetobacter. Also found that the device without FGA, induces a change in the vaginal microbiota, thus, causes vaginitis. In vitro sensitivity tests were performed on the strains identified using twelve different antibiotics; the results showed a higher sensibility to enoxacin, then to the trimethoprim-sulfamethoxazole, ceftriaxone, chloramphenicol and ampicillin. Antibiotics use is necessary to prevent the vaginitis in ewes with dispositive. In conclusion, the intravaginal sponges promote of the vagina inflammation and produce coliform bacteria in vagina.

Production performance and plasma metabolites of dairy ewes in early lactation as affected by chitosan

Energy Technology Data Exchange (ETDEWEB)

Garcia-Rodriguez, A.; Arranz, J.; Mandaluniz, N.; Beltrán-de-Heredia, I.; Ruiz, R.; Goiri, I.

2015-07-01

The objective of this study was to evaluate the effects of chitosan (CHI) supplementation on production performance and blood parameters in dairy ewes. Twenty-four multiparous Latxa dairy ewes at d 16 of lactation were divided into two groups of 12 ewes each. Ewes were fed one of two experimental concentrates (0.840 kg dry matter/d), control or supplemented with 1.2% CHI, on a dry matter basis. Ewes also had free access to tall fescue hay, water, and mineral salts. The experimental period lasted for 25 d, of which the first 14 d were for treatment adaptation and the last 11 d for measurements and samplings. Supplementation with CHI decreased total (p=0.043) and fescue (p=0.035) dry matter intake (DMI), but did not affect concentrate DMI. Supplementation with CHI, moreover, increased plasma glucose (p=0.013) and BUN concentrations (p=0.035), but did not affect those of non-esterified fatty acids. Dietary supplementation with CHI, however, did not affect milk yield, 6.5% FCM, milk composition, or BW, but it improved dietary apparent efficiency by increasing the milk yield-to-DMI (p=0.055) and 6.5% FCM-to-DMI (p=0.045) ratios. In conclusion, dietary supplementation of chitosan maintained ewe performance while reducing feed intake and improving dietary apparent efficiency. (Author)

Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

International Nuclear Information System (INIS)

Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

2005-01-01

The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

DEFF Research Database (Denmark)

Persson, Morten; Rasmussen, Palle; Madsen, Jacob

2012-01-01

-of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. MethodsA DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29...... for the first time the in vivo efficacy of an uPAR-targeted radionuclide therapeutic intervention on both tumor size and its content of uPAR expressing cells thus setting the stage for future translation into clinical use. © 2012 Elsevier Inc. All rights reserved....

Green leaf allowance and dairy ewe performance grazing on tropical pasture.

Science.gov (United States)

De Souza, J; Batistel, F; Ticiani, E; Sandri, E C; Pedreira, C G S; Oliveira, D E

2014-06-01

The objective of this study was to explain the influence of green leaf allowance levels on the performance of dairy ewes grazing a tropical grass. Seventy-two lactating ewes grazed Aruana guineagrass (Panicum maximum Jacq. cv. Aruana) for 80 d. The treatments were 4 daily levels of green leaf allowance (GLA) on a DM basis corresponding to 4, 7, 10, and 13 kg DM/100 kg BW, which were named low, medium-low, medium-high, and high level, respectively. The experimental design was completely randomized with 3 replications. During the experimental period, 4 grazing cycles were evaluated in a rotational stocking grazing method (4 d of grazing and 16 d of rest). There was a linear effect of GLA on forage mass, and increasing GLA resulted in increased total leaf mass, reaching an asymptotic plateau around the medium-high GLA level. The stem mass increased with increased GLA, and a pronounced increase was observed between medium-high and high GLAs. Increasing GLA increased both forage disappearance rate and postgrazing forage mass. Leaf proportion increased with GLA, peaking at the medium-high level, and the opposite occurred for stem proportions, which reduced until medium-high GLA level, followed by an increase on high GLA. Forage CP decreased linearly with GLA, and increasing GLA from low to high reduced CP content by 31%. On the other hand, NDF increased 14% and ADF increased 26%, both linearly in response to greater GLA levels. Total digestible nutrients decreased linearly by 8% when GLA increased from low to high level. Milk yield increased, peaking at medium-high GLA (1.75 kg ewe(-1) d(-1)) and decreased at high GLA level (1.40 kg ewe(-1) d(-1)). Milk composition was not affected by the GLA levels. There was a reduction in stocking rate from 72 to 43 ewes/ha when GLA increased from low to high level. Productivity (milk yield kg ha(-1) d(-1)) increased as GLA increased, peaking at medium-low level (115 kg ha(-1) d(-1)). Although this tropical grass showed the same

Biodistribution of 99mTc-labeled anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody h-R3 in a xenograft model of human lung adenocarcinoma

International Nuclear Information System (INIS)

Morales-Morales, Alejo; Duconge, Jorge; Caballero-Torres, Idania; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Iznaga-Escobar, Normando

1999-01-01

The anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody (MAb) h-R3 is an (IgG 1 ), which binds to an extracellular domain of EGF-R. It was used to evaluate the biodistribution on nude mice xenografted with H-125 human lung adenocarcinoma cell line. Results were compared with its murine version of the MAb ior-egf/r3. Twenty-one athymic female 4NMRI nu/nu mice were injected intraperitoneally with 10 μg/100 μCi of 99m Tc-labeled MAbs. Immunoreactivity of 99m Tc-labeled MAbs were measured by enzyme-linked immunosorbent assay (ELISA) on H-125 cell line and the immunoreactive fractions was determined by the Lindmo method. Among all organs, significant accumulation was found in serum (27.05 ± 2.08 %ID/g) and tumor (3.903 ± 0.89 %ID/g) at 4 h after injection. These values decreased to 5.03 ± 0.50 %ID/g and 2.19 ± 0.56 %ID/g for serum and tumor, respectively. The immunoreactive fraction was found to be 0.70, with a correlation coefficient r=0.9984. With the good biodistribution and tumor uptake of the 99m Tc-labeled humanized antibody h-R3, a phase I diagnostic clinical trial of tumor with epithelial origin should be pursued

Impact of Brazilian red propolis extract on blood metabolites, milk production, and lamb performance of Santa Inês ewes.

Science.gov (United States)

Morsy, Amr S; Soltan, Yosra A; Sallam, Sobhy M A; Alencar, Severino M; Abdalla, Adibe L

2016-06-01

Twenty Santa Inês ewes used to evaluate effects of oral administration of Brazilian red propolis extract on blood metabolites, milk production, and lamb performance were randomly grouped (n = 10 ewes/group) to control without propolis administration and propolis treated (3 g red propolis extract/ewe/day) 21 days before expected lambing date. Blood samples were collected weekly, and daily milk yield was recorded twice weekly until 7 weeks postpartum. Propolis administration increased (P lamb birth and weaning weights. The prepartum administration of propolis extract supported positively the transition of ewes from pregnancy to lactation with health benefits achieved for both of ewes and lambs performances.

Therapy of Ewing's sarcoma

International Nuclear Information System (INIS)

Dunst, J.; Sauer, R.

1993-01-01

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

Short-term progestagen treatment in ewes during the breeding season

OpenAIRE

Almeida, José Carlos; Simões, João; Valentim, Ramiro; Mascarenhas, R.; Fontes, Paulo; Azevedo, Jorge

2006-01-01

To characterize the efficiency of oestrus synchronization with short-term progestagen treatment (stFGA), 20 Ile de France (IF) and 19 Churra da Terra Quente (CTQ) ewes were used during the mid-breeding season. At day 0 (D0), a 40 mg FGA sponge was inserted in all animals and 120 µg cloprostenol was injected. Five days later (D5), all sponges were removed and ewes were divided into two groups: group A (10 IF and 10 CTQ), treated with eCG (250 UI) at sponge withdrawal and group II (10 IF and 9 ...

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

Science.gov (United States)

Khanna, Nehal; Pandey, Avinash; Bajpai, Jyoti

2017-01-01

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

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

Science.gov (United States)

Castle, Maria; Rivero, Mónica; Marquez, Javier

2013-02-01

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

Herbage intake of dairy cows in mixed sequential grazing with breeding ewes as followers.

Science.gov (United States)

Jiménez-Rosales, Juan Daniel; Améndola-Massiotti, Ricardo Daniel; Burgueño-Ferreira, Juan Andrés; Ramírez-Valverde, Rodolfo; Topete-Pelayo, Pedro; Huerta-Bravo, Maximino

2018-03-01

This study aimed to evaluate the hypothesis that mixed sequential grazing of dairy cows and breeding ewes is beneficial. During the seasons of spring-summer 2013 and autumn-winter 2013-2014, 12 (spring-summer) and 16 (autumn-winter) Holstein Friesian cows and 24 gestating (spring-summer) and lactating (autumn-winter) Pelibuey ewes grazed on six (spring-summer) and nine (autumn-winter) paddocks of alfalfa and orchard grass mixed pastures. The treatments "single species cow grazing" (CowG) and "mixed sequential grazing with ewes as followers of cows" (MixG) were evaluated, under a completely randomized design with two replicates per paddock. Herbage mass on offer (HO) and residual herbage mass (RH) were estimated by cutting samples. The estimate of herbage intake (HI) of cows was based on the use of internal and external markers; the apparent HI of ewes was calculated as the difference between HO (RH of cows) and RH. Even though HO was higher in CowG, the HI of cows was higher in MixG during spring-summer and similar in both treatments during autumn-winter, implying that in MixG the effects on the cows HI of higher alfalfa proportion and herbage accumulation rate evolving from lower residual herbage mass in the previous cycle counteracted that of a higher HO in CowG. The HI of ewes was sufficient to enable satisfactory performance as breeding ewes. Thus, the benefits of mixed sequential grazing arose from higher herbage accumulation, positive changes in botanical composition, and the achievement of sheep production without negative effects on the herbage intake of cows.

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

International Nuclear Information System (INIS)

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-01-01

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas

Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis.

Directory of Open Access Journals (Sweden)

Valentina E Schneeberger

Full Text Available Patient-derived xenograft (PDX mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR amplicon length (ssPAL differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS, an immunomagnetic mouse cell depletion (MCD approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors.

Reproductive performance of Karakul ewes following different ...