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Vascular neuroblastoma

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https://www.readbyqxmd.com/read/27922668/dual-inhibition-using-cabozantinib-overcomes-hgf-met-signaling-mediated-resistance-to-pan-vegfr-inhibition-in-orthotopic-and-metastatic-neuroblastoma-tumors
#1
Estelle Daudigeos-Dubus, Ludivine Le Dret, Olivia Bawa, Paule Opolon, Albane Vievard, Irène Villa, Jacques Bosq, Gilles Vassal, Birgit Geoerger
MET is expressed on neuroblastoma cells and may trigger tumor growth, neoangiogenesis and metastasis. MET upregulation further represents an escape mechanism to various anticancer treatments including VEGF signaling inhibitors. We developed in vitro a resistance model to pan-VEGFR inhibition and explored the simultaneous inhibition of VEGFR and MET in neuroblastoma models in vitro and in vivo using cabozantinib, an inhibitor of the tyrosine kinases including VEGFR2, MET, AXL and RET. Resistance in IGR-N91-Luc neuroblastoma cells under continuous in vitro exposure pressure to VEGFR1-3 inhibition using axitinib was associated with HGF and p-ERK overexpression...
December 6, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27861510/heterogeneous-uptake-of-nanoparticles-in-mouse-models-of-pediatric-high-risk-neuroblastoma
#2
Ketan B Ghaghada, Zbigniew A Starosolski, Anna Lakoma, Caterina Kaffes, Saurabh Agarwal, Khannan K Athreya, Jason Shohet, Eugene Kim, Ananth Annapragada
Liposomal chemotherapeutics are exemplified by DOXIL® are commonly used in adult cancers. While these agents exhibit improved safety profile compared to their free drug counterparts, their treatment response rates have been ~ 20%, often attributed to the heterogeneous intratumoral uptake and distribution of liposomal nanoparticles. Non-invasive and quantitative monitoring of the uptake and distribution of liposomal nanoparticles in solid tumors could allow for patient stratification and personalized cancer nanomedicine...
2016: PloS One
https://www.readbyqxmd.com/read/27828922/idiopathic-unilateral-enlargement-of-the-extraocular-muscles-in-an-infant
#3
Yasha Modi, Benjamin Erickson, Isha Ranadive, Joshua Pasol, Sara Wester, Kara Cavuoto
A 6-month-old boy presented with a unilateral motility deficit of the right eye in all fields of gaze. Neuroimaging revealed unilateral enlargement of the medial, lateral, and inferior rectus muscles with sparing of the tendons. An evaluation for thyroid eye disease, idiopathic orbital inflammation, myositis, inflammatory and neoplastic infiltration of the muscle, vascular anomalies, and metastatic neuroblastoma was unrevealing. Biopsy of the muscle revealed normal architecture with an absence of inflammation, infiltration, or fibrosis...
November 2016: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27769056/nuclear-foxo3-predicts-adverse-clinical-outcome-and-promotes-tumor-angiogenesis-in-neuroblastoma
#4
Judith Hagenbuchner, Martina Rupp, Christina Salvador, Bernhard Meister, Ursula Kiechl-Kohlendorfer, Thomas Müller, Kathrin Geiger, Consolato Sergi, Petra Obexer, Michael J Ausserlechner
Neuroblastoma is the most frequent, extracranial solid tumor in children with still poor prognosis in stage IV disease. In this study, we analyzed FOXO3-phosphorylation and cellular localization in tumor biopsies and determined the function of this homeostasis regulator in vitro and in vivo. FOXO3-phosphorylation at threonine-32 (T32) and nuclear localization in biopsies significantly correlated with stage IV disease. DNA-damaging drugs induced nuclear accumulation of FOXO3, which was associated with elevated T32-phosphorylation in stage IV-derived neuroblastoma cells, thereby reflecting the in situ results...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27692178/the-calcium-sensing-receptor-in-health-and-disease
#5
G Díaz-Soto, A Rocher, C García-Rodríguez, L Núñez, C Villalobos
The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca(2+) and by other physiological cations including Mg(2+), amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca(2+) homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca(2+) absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca(2+) metabolism...
2016: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/27669225/plgf-and-vegf-a-regulate-growth-of-high-risk-mycn-single-copy-neuroblastoma-xenografts-via-different-mechanisms
#6
Karin Zins, Daniel Kovatchki, Trevor Lucas, Dietmar Abraham
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood and is a rapidly growing, highly-vascularized cancer. NBs frequently express angiogenic factors and high tumor angiogenesis has been associated with poor outcomes. Placental growth factor (PlGF) is an angiogenic protein belonging to the vascular endothelial growth factor (VEGF) family and is up-regulated mainly in pathologic conditions. Recently, PlGF was identified as a member of a gene expression signature characterizing highly malignant NB stem cells drawing attention as a potential therapeutic target in NB...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27610342/history-of-the-infantile-hepatic-hemangioma-from-imaging-to-generating-a-differential-diagnosis
#7
REVIEW
Maria Gnarra, Gerald Behr, Alison Kitajewski, June K Wu, Sudha A Anupindi, Carrie J Shawber, Nick Zavras, Dimitrios Schizas, Chris Salakos, Konstantinos P Economopoulos
We aim to provide an up-to-date summary of infantile hepatic hemangioma (IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver. Eligible peer-reviewed articles on hepatic infantile hemangiomas, published between 2000 and 2015, were reviewed for this study. IHH is the most common hepatic vascular tumor in children. Once a liver mass is identified in an infant, the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma, hepatoblastoma, metastatic neuroblastoma, so careful physical examination, imaging studies, and, if indicated, tumor markers and biopsy, are of pivotal importance to ascertain the correct diagnosis...
August 8, 2016: World Journal of Clinical Pediatrics
https://www.readbyqxmd.com/read/27586230/the-novel-kinase-inhibitor-ponatinib-is-an-effective-anti-angiogenic-agent-against-neuroblastoma
#8
Sarah B Whittle, Kalyani Patel, Linna Zhang, Sarah E Woodfield, Michael Du, Valeria Smith, Peter E Zage
Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib would be effective against neuroblastoma in preclinical models. Methods We evaluated the effects of ponatinib on survival and migration of human neuroblastoma cells in vitro. Using orthotopic xenograft mouse models of human neuroblastoma, we analyzed tumors treated with ponatinib for growth, gross and histologic appearance, and vascularity...
September 1, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27323822/frizzled2-signaling-regulates-growth-of-high-risk-neuroblastomas-by-interfering-with-%C3%AE-catenin-dependent-and-%C3%AE-catenin-independent-signaling-pathways
#9
Karin Zins, Romana Schäfer, Patrick Paulus, Silvia Dobler, Nazak Fakhari, Mouldy Sioud, Seyedhossein Aharinejad, Dietmar Abraham
Frizzled2 (FZD2) is a receptor for Wnts and may activate both canonical and non-canonical Wnt signaling pathways in cancer. However, no studies have reported an association between FZD2 signaling and high-risk NB so far. Here we report that FZD2 signaling pathways are critical to NB growth in MYCN-single copy SK-N-AS and MYCN-amplified SK-N-DZ high-risk NB cells. We demonstrate that stimulation of FZD2 by Wnt3a and Wnt5a regulates β-catenin-dependent and -independent Wnt signaling factors. FZD2 blockade suppressed β-catenin-dependent signaling activity and increased phosphorylation of PKC, AKT and ERK in vitro, consistent with upregulation of β-catenin-independent signaling activity...
June 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27072241/tumour-suppressive-effects-of-wee1-gene-silencing-in-neuroblastomas
#10
Ahmad Hosseini Tashnizi, Mansooreh Jaberipour, Mahboobeh Razmkhah, Susan Rahnama, Mojtaba Habibagahi
AIM OF STUDY: WEE1, a member of serine/threonine protein kinase family is the master inhibitor of cyclin-dependent kinase 1 in cell cycle. Over-expression of WEE1 in glioblastomas (GBMs) and some other cancers has been shown. Here, we investigated the expression of WEE1 in 13 brain samples from GBM patients and two GBM cell lines. Further to that, we asked whether if knocking down WEE1 expression in the cell lines change tumor cells' reaction. MATERIALS AND METHODS: All brain tumor samples were collected after confirmed pathological diagnosis...
January 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/26986724/microrna-mir-93-5p-regulates-expression-of-il-8-and-vegf-in-neuroblastoma-sk-n-as-cells
#11
Enrica Fabbri, Giulia Montagner, Nicoletta Bianchi, Alessia Finotti, Monica Borgatti, Ilaria Lampronti, Giulio Cabrini, Roberto Gambari
The role of the microRNA miR-93-5p on the secretome profile and the expression levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) was investigated in the neuroblastoma SK-N-AS cell line by Bio-Plex analysis and RT-qPCR. The results indicate that VEGF and IL-8 are the major miR-93-5p molecular targets. This conclusion was based on in vitro transfection with pre-miR-93-5p and anti-miR-93-5p; these treatments inversely modulated both VEGF and IL-8 gene expression and protein release in the neuroblastoma SK-N-AS cell line...
May 2016: Oncology Reports
https://www.readbyqxmd.com/read/26973724/primary-pancreatic-neuroblastoma-presenting-with-opsoclonus-myoclonus-syndrome
#12
Samuel Galgano, Stuart Royal
Although neuroblastoma is a common solid organ malignancy in children, primary pancreatic neuroblastoma is a rare entity in children, with very few cases reported in the literature. The case discusses the presentation of a 21-month-old female presenting to the neurology clinic with ataxia and erratic eye movements. Our case illustrates the computed tomography, ultrasound, and scintigraphic findings of primary pancreatic neuroblastoma presenting as opsoclonus-myoclonus syndrome. Computed tomography and ultrasound demonstrated a vascular, enhancing mass in the pancreatic body clearly separate from the adrenal gland...
March 2016: Radiology case reports
https://www.readbyqxmd.com/read/26959744/combination-of-metronomic-cyclophosphamide-and-dietary-intervention-inhibits-neuroblastoma-growth-in-a-cd1-nu-mouse-model
#13
Raphael Johannes Morscher, Sepideh Aminzadeh-Gohari, Cornelia Hauser-Kronberger, René Günther Feichtinger, Wolfgang Sperl, Barbara Kofler
BACKGROUND: MYCN-amplification in high-grade Neuroblastoma (NB) tumors correlates with increased vascularization and therapy resistance. This study combines an anti-angiogenic approach with targeting NB metabolism for treatment. METHODS AND RESULTS: Metronomic cyclophosphamide (MCP) monotherapy significantly inhibited NB growth and prolonged host survival. Growth inhibition was more pronounced in MYCN-amplified xenografts. Immunohistochemical evaluation of this subtype showed significant decrease in blood vessel density and intratumoral hemorrhage accompanied by blood vessel maturation and perivascular fibrosis...
March 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/26934471/tumour-angiogenesis-origin-of-blood-vessels
#14
REVIEW
S Krishna Priya, R P Nagare, V S Sneha, C Sidhanth, S Bindhya, P Manasa, T S Ganesan
The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26907918/high-dose-single-fraction-irradiation-rapidly-reduces-tumor-vasculature-and-perfusion-in-a-xenograft-model-of-neuroblastoma
#15
Ashish Jani, Fauzia Shaikh, Sunjay Barton, Callen Willis, Debarshi Banerjee, Jason Mitchell, Sonia L Hernandez, Tom Hei, Angela Kadenhe-Chiweshe, Darrell J Yamashiro, Eileen P Connolly
PURPOSE: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)-pericyte interaction as a potential target for combined treatment with antiangiogenic agents. METHODS AND MATERIALS: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed...
April 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/26835320/wilms-tumor-with-intravascular-tumor-thrombus
#16
Suna Emir
Wilms tumor (WT) is one of the most common solid tumors in children. It is the second most common extracranial solid tumor after neuroblastoma. WT has a strong tendency to invade blood vessels in the form of tumor thrombus, into the renal veins, and inferior vena cava and even into the right atrium. Extension of tumor thrombus along to the renal vein into the inferior vena cava occurs in 4-10% of all patients. Tumor thrombus extending to the right atrium is less reported as 0.7-1%. WT with renal vein thrombus has been reported to be more common in the right kidney because of the shorter right renal vein...
January 2014: Translational pediatrics
https://www.readbyqxmd.com/read/26824183/microrna-497-impairs-the-growth-of-chemoresistant-neuroblastoma-cells-by-targeting-cell-cycle-survival-and-vascular-permeability-genes
#17
Aroa Soriano, Laia París-Coderch, Luz Jubierre, Alba Martínez, Xiangyu Zhou, Olga Piskareva, Isabella Bray, Isaac Vidal, Ana Almazán-Moga, Carla Molist, Josep Roma, José R Bayascas, Oriol Casanovas, Raymond L Stallings, José Sánchez de Toledo, Soledad Gallego, Miguel F Segura
Despite multimodal therapies, a high percentage of high-risk neuroblastoma (NB) become refractory to current treatments, most of which interfere with cell cycle and DNA synthesis or function, activating the DNA damage response (DDR). In cancer, this process is frequently altered by deregulated expression or function of several genes which contribute to multidrug resistance (MDR). MicroRNAs are outstanding candidates for therapy since a single microRNA can modulate the expression of multiple genes of the same or different pathways, thus hindering the development of resistance mechanisms by the tumor...
February 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/26788968/coffee-induces-vascular-endothelial-growth-factor-vegf-expression-in-human-neuroblastama-sh-sy5y-cells
#18
Shota Kakio, Megumi Funakoshi-Tago, Kenji Kobata, Hiroomi Tamura
Recent evidence indicates that hypoxia-inducible vascular endothelial growth factor (VEGF) has neurotrophic and neuroprotective effects on neuronal and glial cells. On the other hand, recent epidemiological studies showed that daily coffee consumption has been associated with a lower risk of several neuronal disorders. Therefore, we investigated the effect of coffee on VEGF expression in human neuroblastoma SH-SY5Y cells. We found that even low concentration of coffee (<2%) strongly induced VEGF expression via an activation of HIF-1α...
January 20, 2016: Nutritional Neuroscience
https://www.readbyqxmd.com/read/26617481/hypoxia-affects-neprilysin-expression-through-caspase-activation-and-an-app-intracellular-domain-dependent-mechanism
#19
Caroline Kerridge, Daria I Kozlova, Natalia N Nalivaeva, Anthony J Turner
While gene mutations in the amyloid precursor protein (APP) and the presenilins lead to an accumulation of the amyloid β-peptide (Aβ) in the brain causing neurodegeneration and familial Alzheimer's disease (AD), over 95% of all AD cases are sporadic. Despite the pathologies being indistinguishable, relatively little is known about the mechanisms affecting generation of Aβ in the sporadic cases. Vascular disorders such as ischaemia and stroke are well established risk factors for the development of neurodegenerative diseases and systemic hypoxic episodes have been shown to increase Aβ production and accumulation...
2015: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/26549645/neuropeptide-y-npy-in-tumor-growth-and-progression-lessons-learned-from-pediatric-oncology
#20
REVIEW
Jason Tilan, Joanna Kitlinska
Neuropeptide Y (NPY) is a sympathetic neurotransmitter with pleiotropic actions, many of which are highly relevant to tumor biology. Consequently, the peptide has been implicated as a factor regulating the growth of a variety of tumors. Among them, two pediatric malignancies with high endogenous NPY synthesis and release - neuroblastoma and Ewing sarcoma - became excellent models to investigate the role of NPY in tumor growth and progression. The stimulatory effect on tumor cell proliferation, survival, and migration, as well as angiogenesis in these tumors, is mediated by two NPY receptors, Y2R and Y5R, which are expressed in either a constitutive or inducible manner...
February 2016: Neuropeptides
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