keyword
MENU ▼
Read by QxMD icon Read
search

Ewing AND IGF1R

keyword
https://www.readbyqxmd.com/read/27573658/assessment-of-imaging-modalities-and-response-metrics-in-ewing-sarcoma-correlation-with-survival
#1
Vadim S Koshkin, Vanessa Bolejack, Lawrence H Schwartz, Richard L Wahl, Rashmi Chugh, Denise K Reinke, Binsheng Zhao, Joo H O, Shreyaskumar R Patel, Scott M Schuetze, Laurence H Baker
PURPOSE: Despite the rapidly increasing use of [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET), the comparison of anatomic and functional imaging in the assessment of clinical outcomes has been lacking. In addition, there has not been a rigorous evaluation of how common radiologic criteria or the location of the radiology reader (local v central) compare in the ability to predict benefit. In this study, we aimed to compare the effectiveness of various radiologic response assessments for the prediction of overall survival (OS) within the same data set of patients with sarcoma...
August 29, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27374103/antitumor-efficacy-of-the-heparan-sulfate-mimic-roneparstat-sst0001-against-sarcoma-models-involves-multi-target-inhibition-of-receptor-tyrosine-kinases
#2
Giuliana Cassinelli, Enrica Favini, Laura Dal Bo, Monica Tortoreto, Marcella De Maglie, Gianpaolo Dagrada, Silvana Pilotti, Franco Zunino, Nadia Zaffaroni, Cinzia Lanzi
The heparan sulfate (HS) mimic/heparanase inhibitor roneparstat (SST0001) shows antitumor activity in preclinical sarcoma models. We hypothesized that this 100% N-acetylated and glycol-split heparin could interfere with the functions of several receptor tyrosine kinases (RTK) coexpressed in sarcomas and activated by heparin-binding growth factors. Using a phospho-proteomic approach, we investigated the drug effects on RTK activation in human cell lines representative of different sarcoma subtypes. Inhibition of FGF, IGF, ERBB and PDGF receptors by the drug was biochemically and functionally validated...
June 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27259270/bet-bromodomain-inhibitors-suppress-ews-fli1-dependent-transcription-and-the-igf1-autocrine-mechanism-in-ewing-sarcoma
#3
Sudan N Loganathan, Nan Tang, Jonathan T Fleming, Yufang Ma, Yan Guo, Scott C Borinstein, Chin Chiang, Jialiang Wang
Ewing sarcoma is driven by characteristic chromosomal translocations between the EWSR1 gene with genes encoding ETS family transcription factors (EWS-ETS), most commonly FLI1. However, direct pharmacological inhibition of transcription factors like EWS-FLI1 remains largely unsuccessful. Active gene transcription requires orchestrated actions of many epigenetic regulators, such as the bromodomain and extra-terminal domain (BET) family proteins. Emerging BET bromodomain inhibitors have exhibited promising antineoplastic activities via suppression of oncogenic transcription factors in various cancers...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/26988130/investigational-therapies-for-ewing-sarcoma-a-search-without-a-clear-finding
#4
Olga Vornicova, Gil Bar-Sela
INTRODUCTION: Ewing sarcoma family tumors (ESFT) are a group of aggressive diseases, characterized histologically by small, round, blue cells and genetically by translocation involving EWS and ETS partner genes. The current treatment of localized Ewing sarcoma (ES) requires a multi-disciplinary approach, including multidrug chemotherapy, administrated before and after local treatment, surgery and radiation therapy. Unfortunately, the cure rate of metastatic or refractory/recurrent disease is still very poor...
June 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26173023/igf1r-and-ror1-specific-car-t-cells-as-a-potential-therapy-for-high-risk-sarcomas
#5
Xin Huang, Haein Park, Joseph Greene, James Pao, Erin Mulvey, Sophia X Zhou, Catherine M Albert, Fred Moy, Deepali Sachdev, Douglas Yee, Christoph Rader, Carl V Hamby, David M Loeb, Mitchell S Cairo, Xianzheng Zhou
Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma...
2015: PloS One
https://www.readbyqxmd.com/read/25917833/undernutrition-and-stage-of-gestation-influence-fetal-adipose-tissue-gene-expression
#6
Jacqueline M Wallace, John S Milne, Raymond P Aitken, Dale A Redmer, Lawrence P Reynolds, Justin S Luther, Graham W Horgan, Clare L Adam
Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both of which are associated with inadequate prenatal adipose tissue development. In the present study, we investigated the impact of maternal undernutrition on the expression of genes that regulate fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145 days). Singleton fetuses were taken from adolescent ewes that were either fed control (C) intake to maintain adiposity throughout pregnancy or were undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group)...
June 2015: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/25609059/trabectedin-efficacy-in-ewing-sarcoma-is-greatly-increased-by-combination-with-anti-igf-signaling-agents
#7
Ana Teresa Amaral, Cecilia Garofalo, Roberta Frapolli, Maria Cristina Manara, Caterina Mancarella, Sarah Uboldi, Silvana Di Giandomenico, Jose Luis Ordóñez, Victoria Sevillano, Roberta Malaguarnera, Piero Picci, A Bass Hassan, Enrique De Alava, Maurizio D'Incalci, Katia Scotlandi
PURPOSE: Goal of this study was to identify mechanisms that limit efficacy of trabectedin (ET-743, Yondelis) in Ewing sarcoma (EWS), so as to develop a clinical applicable combination therapy. EXPERIMENTAL DESIGN: By chromatin immunoprecipitation, we analyzed EWS-FLI1 binding to the promoters of several target genes, such as TGFβR2, CD99, insulin-like growth factor receptor 1 (IGF1R), and IGF1, both in vitro and in xenografts treated with trabectedin or doxorubicin...
March 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/25119929/novel-secondary-somatic-mutations-in-ewing-s-sarcoma-and-desmoplastic-small-round-cell-tumors
#8
Yunyun Jiang, Vivek Subbiah, Filip Janku, Joseph A Ludwig, Aung Naing, Robert S Benjamin, Robert E Brown, Pete Anderson, Razelle Kurzrock
BACKGROUND: Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. METHODOLOGY: Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics...
2014: PloS One
https://www.readbyqxmd.com/read/24994750/pten-deficiency-mediates-a-reciprocal-response-to-igfi-and-mtor-inhibition
#9
Mukund Patel, Nicholas C Gomez, Andrew W McFadden, Billie M Moats-Staats, Sam Wu, Andres Rojas, Travis Sapp, Jeremy M Simon, Scott V Smith, Kathleen Kaiser-Rogers, Ian J Davis
UNLABELLED: Recent evidence implicates the insulin-like growth factor (IGF) pathway in development of Ewing sarcoma, a highly malignant bone and soft-tissue tumor that primarily affects children and young adults. Despite promising results from preclinical studies of therapies that target this pathway, early-phase clinical trials have shown that a significant fraction of patients do not benefit, suggesting that cellular factors determine tumor sensitivity. Using FAIRE-seq, a chromosomal deletion of the PTEN locus in a Ewing sarcoma cell line was identified...
November 2014: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/24388362/pre-clinical-efficacy-of-pu-h71-a-novel-hsp90-inhibitor-alone-and-in-combination-with-bortezomib-in-ewing-sarcoma
#10
Srikanth R Ambati, Eloisi Caldas Lopes, Kohji Kosugi, Ullas Mony, Ahmet Zehir, Smit K Shah, Tony Taldone, Andre L Moreira, Paul A Meyers, Gabriela Chiosis, Malcolm A S Moore
Ewing sarcoma is characterized by multiple deregulated pathways that mediate cell survival and proliferation. Heat shock protein 90 (HSP90) is a critical component of the multi-chaperone complexes that regulate the disposition and activity of a large number of proteins involved in cell-signaling systems. We tested the efficacy of PU-H71, a novel HSP90 inhibitor in Ewing sarcoma cell lines, primary samples, benign mesenchymal stromal cells and hematopoietic stem cells. We performed cell cycle analysis, clonogenic assay, immunoblot analysis and reverse phase protein array in Ewing cell lines and in vivo experiments in NSG and nude mice using the A673 cell line...
March 2014: Molecular Oncology
https://www.readbyqxmd.com/read/24108072/maternal-dietary-restriction-during-the-periconceptional-period-in-normal-weight-or-obese-ewes-results-in-adrenocortical-hypertrophy-an-up-regulation-of-the-jak-stat-and-down-regulation-of-the-igf1r-signaling-pathways-in-the-adrenal-of-the-postnatal-lamb
#11
RANDOMIZED CONTROLLED TRIAL
Song Zhang, Janna L Morrison, Amreet Gill, Leewen Rattanatray, Severence M MacLaughlin, David Kleemann, Simon K Walker, I Caroline McMillen
Maternal dietary restriction during the periconceptional period results in an increase in adrenal growth and in the cortisol stress response in the offspring. The intraadrenal mechanisms that result in the programming of these changes are not clear. Activation of the IGF and the signal transducer and activator of transcription (STAT)/suppressors of cytokine signaling (SOCS) pathways regulate adrenal growth. We have used an embryo transfer model in sheep to investigate the impact of exposure to either dietary restriction in normal or obese mothers or to maternal obesity during the periconceptional period on adrenal growth and function in the offspring...
December 2013: Endocrinology
https://www.readbyqxmd.com/read/23922674/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
#12
Vivek Subbiah, Robert E Brown, Yunyun Jiang, Jamie Buryanek, Andrea Hayes-Jordan, Razelle Kurzrock, Pete M Anderson
BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies. METHODOLOGY: This pilot study assessed patients with DSRCT, Wilms' tumor and Ewing's sarcoma...
2013: PloS One
https://www.readbyqxmd.com/read/23457541/the-pancreas-is-altered-by-in-utero-androgen-exposure-implications-for-clinical-conditions-such-as-polycystic-ovary-syndrome-pcos
#13
Mick Rae, Cathal Grace, Kirsten Hogg, Lisa Marie Wilson, Sophie L McHaffie, Seshadri Ramaswamy, Janis MacCallum, Fiona Connolly, Alan S McNeilly, Colin Duncan
Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection - MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation...
2013: PloS One
https://www.readbyqxmd.com/read/23431249/insulin-like-growth-factor-1-receptor-as-a-therapeutic-target-in-ewing-sarcoma-lack-of-consistent-upregulation-or-recurrent-mutation-and-a-review-of-the-clinical-trial-literature
#14
Alison O'Neill, Nilay Shah, Naamah Zitomersky, Marc Ladanyi, Neerav Shukla, Aykut Uren, David Loeb, Jeffrey Toretsky
The insulin-like growth factor 1 receptor (IGF-1R) has been considered an important therapeutic target in Ewing sarcoma (ES), generating a need to identify the subset of patients most likely to respond to IGF-1R inhibitors. We assessed IGF-1R expression in ES cell lines and patient tumors to understand the variable clinical responses to anti-IGF-1R therapy. Using ligand-binding displacement, we measured between 13,000 and 40,000 receptors per cell in ES cell lines. We used ELISA to quantify IGF-1R in patient tumors, which expressed 4...
2013: Sarcoma
https://www.readbyqxmd.com/read/23091403/a-novel-role-of-igf1-in-apo2l-trail-mediated-apoptosis-of-ewing-tumor-cells
#15
Frans van Valen, Henning Harrer, Marc Hotfilder, Uta Dirksen, Thomas Pap, George Gosheger, Hans-Ulrich Humpf, Heribert Jürgens
Insulin-like growth factor 1 (IGF1) reputedly opposes chemotoxicity in Ewing sarcoma family of tumor (ESFT) cells. However, the effect of IGF1 on apoptosis induced by apoptosis ligand 2 (Apo2L)/tumor necrosis factor (TNF-) related apoptosis-inducing ligand (TRAIL) remains to be established. We find that opposite to the partial survival effect of short-term IGF1 treatment, long-term IGF1 treatment amplified Apo2L/TRAIL-induced apoptosis in Apo2L/TRAIL-sensitive but not resistant ESFT cell lines. Remarkably, the specific IGF1 receptor (IGF1R) antibody α-IR3 was functionally equivalent to IGF1...
2012: Sarcoma
https://www.readbyqxmd.com/read/22742646/ewing-s-sarcoma-overcoming-the-therapeutic-plateau
#16
Vivek Subbiah, Razelle Kurzrock
The hallmark of Ewing's sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene. Because EWS afflicts young patients, it stands out among the diverse sarcoma subtypes. The frontline, standard-of-care cytotoxic chemotherapy regimens produce minimal benefit in patients with metastases at presentation or those with relapsed disease. While the outcomes of chemorefractory EWS patients are generally poor, recent developments have led to the promising use of targeted therapy...
June 2012: Discovery Medicine
https://www.readbyqxmd.com/read/22665677/effects-of-overfeeding-naturally-mated-adolescent-ewes-on-maternal-fetal-and-postnatal-lamb-growth
#17
R K Peel, G J Eckerle, R V Anthony
The objective of this study was to evaluate the effects of overfeeding naturally-mated adolescent ewes (Ovis aries) on maternal, fetal, and postnatal lamb growth, hormone concentrations, and lamb carcass characteristics. Two experiments were conducted in which singleton-bearing adolescent ewes were fed a diet containing 2.72 Mcal/kg ME at a rate which met NRC gestational age requirements (MN; n = 10 in Exp. 1, n = 7 in Exp. 2) or were fed the same diet ad libitum (15% refusal rate) throughout gestation (HN; n = 7 in Exp...
November 2012: Journal of Animal Science
https://www.readbyqxmd.com/read/22508822/phase-ii-study-of-ganitumab-a-fully-human-anti-type-1-insulin-like-growth-factor-receptor-antibody-in-patients-with-metastatic-ewing-family-tumors-or-desmoplastic-small-round-cell-tumors
#18
William D Tap, George Demetri, Phillip Barnette, Jayesh Desai, Petr Kavan, Richard Tozer, Pasquale W Benedetto, Gregory Friberg, Hongjie Deng, Ian McCaffery, Ian Leitch, Sunita Badola, Sung Chang, Min Zhu, Anthony Tolcher
PURPOSE: Ganitumab is a fully human monoclonal antibody against type-1 insulin-like growth factor receptor (IGF1R). An open-label phase II study was conducted to evaluate the efficacy and safety of ganitumab monotherapy in patients with metastatic Ewing family tumors (EFT) or desmoplastic small round cell tumors (DSRCT). PATIENTS AND METHODS: Patients ≥16 years of age with relapsed or refractory EFT or DSRCT received 12 mg/kg of ganitumab every 2 weeks. Objective response rate (ORR) was the primary end point...
May 20, 2012: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/21611203/igf1r-signaling-in-ewing-sarcoma-is-shaped-by-clathrin-caveolin-dependent-endocytosis
#19
Ana Sofia Martins, José Luis Ordóñez, Ana Teresa Amaral, Frans Prins, Giuseppe Floris, Maria Debiec-Rychter, Pancras C W Hogendoorn, Enrique de Alava
Receptor endocytosis is critical for cell signaling. IGF1R mediates an autocrine loop that is de-regulated in Ewing Sarcoma (ES) cells. Here we study the impact of IGF1R internalization, mediated by clathrin and caveolin-1 (CAV1), in ES signaling. We used clathrin and CAV1-siRNA to interfere in clathrin- and caveolin-dependent endocytosis. Chlorpromazine (CPMZ) and methyl-beta-cyclo-dextrin (MCD) were also used in order to inhibit clathrin- and caveolin-dependent endocytosis, respectively. We analyzed IGF1R internalization and co-localization with clathrin and CAV1 upon ligand binding, as well as the status of the IGF1R pathway, cellular proliferation, and the apoptosis of interfered and inhibited ES cells...
2011: PloS One
https://www.readbyqxmd.com/read/21519259/phase-1-clinical-trials-for-sarcomas-the-cutting-edge
#20
REVIEW
Vivek Subbiah, Razelle Kurzrock
PURPOSE OF REVIEW: Few standard second-line treatment options exist for advanced sarcoma patients. Some of these patients are offered early-phase clinical trials involving targeted or nontargeted agents. This review outlines recent phase 1 trials involving sarcoma patients, explores current challenges and highlights future opportunities in sarcoma developmental therapeutics. RECENT FINDINGS: New molecularly targeted phase 1 studies have demonstrated efficacy in sarcomas...
July 2011: Current Opinion in Oncology
keyword
keyword
72708
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"