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FANCD2 is a Potential Therapeutic Target and Biomarker in Alveolar Rhabdomyosarcoma Harboring the PAX3/FOXO1 Fusion Gene
Mamata Singh, Justin M Leasure, Christopher Chronowski, Brian Geier, Kathryn Bondra, Wenrui Duan, Lauren A Hensley, Miguel Villalona-Calero, Ning Li, Anthony M Vergis, Raushan T. Kurmasheva, Changxian Shen, Gary Woods, Nikhil Sebastian, Denise Fabian, Rita Kaplon, Sue Hammond, Peter Houghton, Kamalakannan Palanichamy, and Arnab Chakravarti - Clinical Cancer Research, Online First, 30 April 2014
Purpose: Alveolar rhabdomyosarcoma that harbors the PAX3/FOXO1 fusion gene (t-ARMS) is a common and lethal subtype of this childhood malignancy. Improvement in clinical outcomes in this disease is predicated upon the identification of novel therapeutic targets. Experimental Design: Robust mouse models were used for in vivo analysis, and molecular studies were performed on xenografts treated in parallel. Two independent patient sets (n=101 and 124) of clinically-annotated tumor specimens were used for analysis of FANCD2 levels and its association with clinical and molecular characteristics and outcomes. Results: Our xenograft studies reveal a selective suppression of FANCD2 by m-TOR kinase inhibition and radiosensitization of the t-ARMS line only. In the initial patient set, we showFANCD2 transcript levels are prognostic in univariate analysis, and are significantly associated with metastatic disease and that the co-presence of the translocation and high expression of FANCD2 is independently prognostic. We also demonstrate a significant and non-random enrichment of mTOR-associated genes that correlate with FANCD2 gene expression within the t-ARMS samples, but not within other cases. In the second patient set, we show that, on a protein level, FANCD2 expression correlates with PAX3/FOXO1 fusion gene and is strongly associated with phospho-p70S6K expression in cases with the fusion gene. Conclusions: Our data demonstrate that FANCD2 may have a significant role in the radiation resistance and virulence of t-ARMS. Indirectly targeting this DNA repair protein, through mTOR inhibition, may represent a novel and selective treatment strategy.

A systematic review of the clinical effectiveness of advanced functional imaging assessment in children and young people with rhabdomyosarcoma
D Fayter, G Norman, B Phillips, K Lewis-Light - 2014
Background Rhabdomyosarcoma (RMS) is a very rare cancer of childhood and
adolescence. The disease frequently presents as a soft-tissue mass with the commonest
sites of origin being the head and neck, the genitourinary tract, and the limbs. In the UK ...

Congenital rhabdomyosarcoma of tongue
S Soomro, SA Mughal - Rawal Medical Journal, 2014
ABSTRACT and managed successfully.(Rawal Med J Congenital Rhabdomyosarcoma
arising from 2014; 39: 222-223). tongue is an extremely uncommon entity. We Key words:
Rhabdomyosarcoma, tongue tumors, present the case of a newborn baby presented oral ...

AIEOPyin Lab Pavia, Italy 8–9 October 2013 Working Group AIEOP Cellular and Molecular Biology
I Napoli - J Pediatr Hematol Oncol, 2014
... Central Nervous System Involvement in Children With Rhabdomyosarcoma: Molecular
Characterization of Cere- brospinal Fluid Angelica Zin1, Elena Poli2, Gianni Bisogno2, Antonella
Brunello3, Alberto Garaventa4, Roberta Burnelli5, Patrizia Bertolini6, Lucia Miglionico7 ...

Ewing Sarcoma of the Scrotum
GM Grimsby, CB Harrison - Urology, 2014
... Soft-tissue malignancies must be kept in the differential diagnosis of any solid
paratesticular mass in a child. Although rhabdomyosarcoma is the most common,
as this case demonstrates, other rare sarcomas are also possible. ...

Orthodontic and orthognathic treatment including transplanted teeth after radiotherapy for rhabdomyosacroma
S Ohba - 2014 Annual Meeting, 2014
... We herein report a case of a 14-year-old male who underwent the multidisciplinary treatment
for rhabdomyosarcoma of his right cheek when he was 3-year-old. ... Pediatric
rhabdomyosarcoma of the head and neck. Curr Treat Opt Oncol 7: 13-22, 2006. ...

Immunotherapy in Sarcoma: A New Frontier
BA Wilky, JM Goldberg - Discovery Medicine, 2014
... NCT00923351 harvests tumors from pediatric patients with recurrent Ewing's sarcoma or
rhabdomyosarcoma and loads tumor lysates from the KLH tumor cell line into autologous dendritic
cells, which are then administered after recombinant human interleukin-7 following ...

Metastasis of an undifferentiated fetal soft tissue sarcoma to the maternal compartment of the placenta. Maternal aspects, pathology findings and review of the literature on fetal malignancies with placenta metastases
P Reif, N Hofer, V Kolovetsiou‐Kreiner, C Benedicic… - Histopathology, 2014
... [26]. Crist WM, Anderson JR, Meza JL et al. Intergroup rhabdomyosarcoma study-IV: results for
patients with nonmetastatic disease. ... Foetal rhabdomyosarcoma with massive cardiac and placental
infiltration associated with intrauterine foetal death. Z Geburtshilfe Neonatol. ...

Sphingosine arrests the cell cycle and induces apoptosis by targeting sphingosine-dependent protein kinase and protein kinase Cδ in vitro
T Kanno, A Gotoh, T Nishizaki - Personalized Medicine Universe, 2014
... is produced from sphingosine by sphingosine kinases (SphKs) such as SphK1 and SphK2, plays
an important role in neuronal cell apoptosis, tumorigenesis, and neovascularization as a lipid
mediator [5] and [6]. Sphingosine induces apoptosis in rhabdomyosarcoma cells by ...

Lessons learned from adult clinical experience to inform evaluations of VEGF pathway inhibitors in children with cancer
MA Smith - Pediatric Blood & Cancer, 2014
... need in this setting is great, given the 30–40% treatment-failure rate for children with various
types of cancer who have localized disease for which effective local therapy is available and
for which adjuvant therapy is needed for cure (eg, rhabdomyosarcoma, Ewing sarcoma ...

The expression of the tumour suppressor HBP1 is down-regulated by growth factors via the PI3K/PKB/FOXO pathway
CB Alexandra, B Emeline, E Astrid, RS Audrey… - Biochemical Journal, 2014
... FOXO factors are considered as tumour suppressors [7] and are dysregulated in breast cancer
and in other types of tumours including rhabdomyosarcoma, leukaemia, glioblastoma and prostate
cancer [8]. In more than 70% of breast cancers, mutations and/or amplifications are ...

Computed tomography and magnetic resonance imaging observations of rhabdomyosarcoma in the head and neck
J Zhu, J Zhang, G Tang, S Hu, G Zhou, Y Liu, L Dai… - Oncology Letters
Abstract Head and neck (HN) rhabdomyosarcoma (RMS) is an aggressive malignancy,
which is rarely encountered and is commonly misdiagnosed as another type of tumor. The
aim of the present study was to investigate the computed tomography (CT) and magnetic ...

Cervical Rhabdomyosarcoma and Exit procedure; Case report
G Miyano, Y Nakazawa, M Mitsunaga, M Kaneshiro… - Journal of Pediatric Surgery …, 2014
Abstract A 37 year-old primipara women was referred for management of a large solid tumor
found in the neck of her fetus, showing the trachea to be compressed by the mass, and
intubation through the ex utero intrapartum treatment (EXIT) was planned. After the mother ...

Acute and late side effects to salivary glands and oral mucosa following head/neck radiotherapy in children and adolescents
T Bölling, J Weege, HT Eich, B Timmermann, FM Meyer… - Head & neck, 2014
... (14) published an analysis regarding the long-term effects in 17 children receiving radiotherapy
for head and neck rhabdomyosarcoma. ... function was not presented. Meazza et al (15) published
a series of 90 pediatric patients diagnosed with head-and-neck rhabdomyosarcoma. ...

Gene Selection
B Nabet, JD Licht - http://AtlasGeneticsOncology. org, 2014
... Embryonal rhabdomyosarcoma subtype (ERMS) Note cDNA microarray and Affymetrix
microarray experiments revealed that SPRY1 mRNA expression is elevated in ERMS tumors
compared to alveolar rhabdomyosarcoma subtype (RMS) tumors. ...

DICER1-Related Disorders.
RA Pagon, MP Adam, HH Ardinger, TD Bird, CR Dolan…
... Less commonly observed tumors are ciliary body medulloepithelioma (CBME); botryoid-type
embryonal rhabdomyosarcoma (ERMS) of the cervix or other sites; nasal chondromesenchymal
hamartoma (NCMH); renal sarcoma; pituitary blastoma; and pineoblastoma. ...

Calixarenes and related macrocycles as gene delivery vehicles
RV Rodik, AS Klymchenko, Y Mely, VI Kalchenko - Journal of Inclusion Phenomena …, 2014
... Transfection experiments performed using plasmid DNA pEGFP-C1, encoding the green
fluorescent protein showed that complexes of calixarenes 15–17 with DNA did not exhibit
any transfection activity in cell line RD-4 human rhabdomyosarcoma. ...

Adverse Drug Event Detection in Pediatric Oncology and Hematology Patients: Using Medication Triggers to Identify Patient Harm in a Specialized Pediatric Patient Population
RJ Call, JD Burlison, JJ Robertson, JR Scott, DK Baker… - The Journal of Pediatrics, 2014
... The patient was readmitted required increased monitoring. 6. Rhabdomyosarcoma, Lorazepam,
The patient had increased sedation when lorazepam was given around the same time as
hydromorphone. The patient required increased monitoring, 6. Naloxone, ...