Targeted Therapy of Ewing's Sarcoma

Refractory and/or recurrent Ewing's sarcoma (EWS) remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R) antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22) translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS

G96-1276 Creep Feeding Growing Horses

This NebGuide discusses the benefits and implications of creep feeding horses during the growing period of development. Creep feeding, providing a place where foals can eat without interference from the mare and other horses, should be used if foals are to grow at optimum rates. Creep feeders are used to provide a nutritionally balanced, digestible concentrate to young nursing foals before weaning. The practice of creep feeding serves to supply nutrients beyond what a foal receives from mare\u27s milk. And, creep feeding minimizes foals\u27 intake of broodmare feed which often lacks the concentrated amounts of protein and minerals relative to the energy needed by foals. Creep feeders also decrease the chances for injury to a foal when competing for feed from the mare\u27s feeder. Finally, creep feeders allow foals to become accustomed to eating concentrates before weaning time, thus reducing weaning stress

G96-1276 Creep Feeding Growing Horses

This NebGuide discusses the benefits and implications of creep feeding horses during the growing period of development. Creep feeding, providing a place where foals can eat without interference from the mare and other horses, should be used if foals are to grow at optimum rates. Creep feeders are used to provide a nutritionally balanced, digestible concentrate to young nursing foals before weaning. The practice of creep feeding serves to supply nutrients beyond what a foal receives from mare\u27s milk. And, creep feeding minimizes foals\u27 intake of broodmare feed which often lacks the concentrated amounts of protein and minerals relative to the energy needed by foals. Creep feeders also decrease the chances for injury to a foal when competing for feed from the mare\u27s feeder. Finally, creep feeders allow foals to become accustomed to eating concentrates before weaning time, thus reducing weaning stress

Prospectus, December 6, 1978

WHICH IS BETTER-- TICCIT OR PLATO?; Internship applications accepted; PC business instructor receives service award; Education in the 80\u27s to be topic of talk; Brown resigns as Day Senator; Faculty invited to student forum; Canteen requests to raise food prices at Parkland; PC band to perform at Market Place; PC singers to give concerts this Sunday; Teachers essential for PLATO; PC students--on PLATO; Parkland to offer class; PC Women\u27s Program to host workshop; PC club to show attire; Heart\u27s melody rocks fans; Springsteen and the E Street Band electrify audience; Patton Woods gets clean-up; LRC detection system saves PC library $16,000 a year; Basketball season opens; WPCD\u27s Top 10 for the week of Dec. 4; Classifieds; Women win opener; New league ready to start; Women\u27s Box Score; Cobras start great; Dubinski and Goodwin finish with 1-1 records; Bouncing Bob; Reed wins Bouncing Bob; Fast Freddy contestants have hard time picking this week\u27s winnershttps://spark.parkland.edu/prospectus_1978/1001/thumbnail.jp

Prospectus, February 28, 1979

COBRAS GO TO STATE; Friends: top of the list; Letters to the editor: Vick Rogers apologizes for past letter to editor, Former griper changes mind about Canteen; PC presents aging sessions; Parkland Players present production; Trustees approve the letting of bids; Apply for PC award; WIU rep. here today; Register to vote; A day to remember...; Blood drive today; Seminar at PC Mar. 7; Political discussion; Tournaments coming to PC; Sleep seminar; WPCD\u27s Best Music List; Classifieds; Goin\u27 for it all; Sectional champion Cobras go to state; Track places second in Parkland Invitationalhttps://spark.parkland.edu/prospectus_1979/1024/thumbnail.jp

The feasibility of a community-university based physiotherapy programme for stroke patients for student learning and patient care

Introduction: There is a need for long term community physiotherapy based stroke care. An innovative pilot scheme involving students contribute to achieve this - benefiting both students and patients. Methods: This report considers the use and value of an innovative pilot programme which provided community stroke rehabilitation utilising student volunteers. Eight students, 4 stroke patients and 1 carer completed a post pilot project scheme. Results: Three themes; (1) The Value of the Programme (2) The Outcomes from the Programme (3) Development of the Programme. Key benefits for students included the long-term interaction with patients in a friendly and secure environment that focussed upon patient care and practice of clinical skills with formative, rather than summative assessment. The key benefit for the patients was the supported long term nature of the programme. Conclusion: There is an urgent need to consider an extended version of this project that is able to adapt to the needs of the patient and student and consider the value (educational, economical and clinical) of such a programme long-term

Morphoproteomic profiling of the mammalian target of rapamycin (mTOR) signaling pathway in desmoplastic small round cell tumor (EWS/WT1), Ewing's sarcoma (EWS/FLI1) and Wilms' tumor(WT1).

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

Novel secondary somatic mutations in Ewing's sarcoma and desmoplastic small round cell tumors.

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

Beef Cattle Management Update: Feedbunk Management for Maximum Consistent Intake, Issue 12

This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu