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Neuroblastoma

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https://www.readbyqxmd.com/read/28723622/dual-targeting-of-mdm2-and-bcl2-as-a-therapeutic-strategy-in-neuroblastoma
#1
Alan Van Goethem, Nurten Yigit, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Eveline Barbieri, Frank Speleman, Jason Shohet, Jo Vandesompele, Tom Van Maerken
Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722675/using-droplet-digital-pcr-to-analyze-mycn-and-alk-copy-number-in-plasma-from-patients-with-neuroblastoma
#2
Marco Lodrini, Annika Sprüssel, Kathy Astrahantseff, Daniela Tiburtius, Robert Konschak, Holger N Lode, Matthias Fischer, Ulrich Keilholz, Angelika Eggert, Hedwig E Deubzer
The invasive nature of surgical biopsies deters sequential application, and single biopsies often fail to reflect tumor dynamics, intratumor heterogeneity and drug sensitivities likely to change during tumor evolution and treatment. Implementing molecular characterization of cell-free neuroblastoma-derived DNA isolated from blood plasma could improve disease assessment for treatment selection and monitoring of patients with high-risk neuroblastoma. We established droplet digital PCR (ddPCR) protocols for MYCN and ALK copy number status in plasma from neuroblastoma patients...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#3
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28722341/proteomic-analysis-of-neuroblastoma-derived-exosomes-new-insights-into-a-metastatic-signature
#4
Marta Colletti, Andrea Petretto, Angela Galardi, Virginia Di Paolo, Luigi Tomao, Chiara Lavarello, Elvira Inglese, Maurizio Bruschi, Ana Amor Lopez, Luisa Pascucci, Birgit Geoerger, Hector Peinado, Locatelli Franco, Di Giannatale Angela
Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Around 70% of patients with metastatic disease at diagnosis present bone-marrow infiltration, which is considered a marker of poor outcome; however, the mechanism underlying this specific tropism has to be elucidated. Tumor-derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study was to identify an exosomal signature associated with NB metastatic bone-marrow dissemination...
July 19, 2017: Proteomics
https://www.readbyqxmd.com/read/28721631/1-trichloromethyl-1-2-3-4-tetrahydro-beta-carboline-taclo-alters-cell-cycle-progression-in-human-neuroblastoma-cell-lines
#5
Rakesh Kumar Sharma, Eduardo Candelario-Jalil, Doris Feineis, Gerhard Bringmann, Bernd L Fiebich, Ravi Shankar Akundi
1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline, abbreviated as TaClo, is an endogenous neurotoxin capable of formation in the brain through the condensation of neuronal tryptamine with ingested exogenous toxins such as trichloroethylene or chloral hydrate. Due to its structural resemblance to 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and similar ability to inhibit mitochondrial complex I, TaClo has been implicated in the etiology of Parkinson's disease. Previous studies have shown the cytotoxicity of TaClo in various cell culture models...
July 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28720798/neuroprotective-effect-of-5-aminolevulinic-acid-against-low-inorganic-phosphate-in-neuroblastoma-sh-sy5y-cells
#6
Naoko Takase, Masatoshi Inden, Shin-Ichiro Sekine, Yumi Ishii, Hiroko Yonemitsu, Wakana Iwashita, Hisaka Kurita, Yutaka Taketani, Isao Hozumi
PiT-1 (encoded by SLC20A1) and PiT-2 (encoded by SLC20A2) are type-III sodium-dependent phosphate cotransporters (NaPiTs). Recently, SLC20A2 mutations have been found in patients with idiopathic basal ganglia calcification (IBGC), and were predicted to bring about an inability to transport Pi from the extracellular environment. Here we investigated the effect of low Pi loading on the human neuroblastoma SH-SY5Y and the human glioblastoma A172 cell lines. The results show a different sensitivity to low Pi loading and differential regulation of type-III NaPiTs in these cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718035/elevated-preoperative-neutrophil-lymphocyte-ratio-is-predictive-of-a-poorer-prognosis-for-pediatric-patients-with-solid-tumors
#7
Agnish Nayak, Dermot T McDowell, Stewart J Kellie, Jonathan Karpelowsky
BACKGROUND: An elevated neutrophil-lymphocyte ratio (NLR) has been shown to indicate poorer prognosis for adults with solid tumors and potentially represents an independent, universal adjunct prognostic factor. The value of NLR in a pediatric setting has not been evaluated. This study sought to determine the prognostic value of NLR for pediatric patients with solid tumors. METHODS: Pediatric patients with solid tumors undergoing neoadjuvant chemotherapy followed by surgery with curative intent between 2000 and 2014 were eligible for this study...
July 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28717698/neuroblastoma-in-africa-a-survey-by-the-franco-african-pediatric-oncology-group
#8
Fousseyni Traoré, Francis Eshun, Boubacar Togo, Jean Jacques Atteby Yao, Mbuli Robert Lukamba
PURPOSE: Neuroblastoma is a sympathoadrenal lineage neural crest-derived tumor. It is the third most common childhood malignancy in the Western world. Studies from the United States show that black patients with neuroblastoma have a greater proportion of high-risk neuroblastoma with poorer prognosis compared with white patients. In Africa, there are few published data on the epidemiology and management of neuroblastoma. The primary aim of this study was to assess the diagnostic and therapeutic resources available for the management of neuroblastoma within the Franco-African Pediatric Oncology Group (GFAOP)...
August 2016: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#9
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717400/treatment-of-nras-mutated-advanced-or-metastatic-melanoma-rationale-current-trials-and-evidence-to-date
#10
REVIEW
Amélie Boespflug, Julie Caramel, Stephane Dalle, Luc Thomas
The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15-25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28716816/sphingosine-1-phosphate-receptor-1-promotes-environment-induced-and-acquired-chemoresistance
#11
Veronica Lifshitz, Saul J Priceman, Wenzhao Li, Gregory Cherryholmes, Heehyoung Lee, Adar Makovski-Silverstein, Lucia Borriello, Yves A DeClerck, Hua Yu
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28715613/isolation-and-characterization-of-canine-placenta-derived-mesenchymal-stromal-cells-for-the-treatment-of-neurological-disorders-in-dogs
#12
Connor Long, Lee Lankford, Priyadarsini Kumar, Robert Grahn, Dori L Borjesson, Diana Farmer, Aijun Wang
Spinal cord injury (SCI) is a devastating disorder that affects humans and dogs. The prognosis of SCI depends on the severity of the injury and can include varying levels of motor and sensory deficits including devastating paraplegia and quadriplegia. Placental mesenchymal stromal cells (PMSCs) have been shown to improve wound healing and possess neuroprotective and immunomodulatory capabilities, but have not yet been clinically tested for the treatment of SCI. This study established a protocol to isolate fetal PMSCs from canine placentas and characterized their paracrine secretion profile and ability to stimulate neurons in vitro to assess their potential as a treatment option for neurological disorders in dogs...
July 17, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28714389/a-peptide-based-pro-drug-ameliorates-amyloid-%C3%AE-induced-neuronal-apoptosis-in-in-vitro-sh-sy5y-cells
#13
Sourav Kumar, Ashim Paul, Sourav Kalita, Awanish Kumar, Saurabh Srivastav, Somoday Hazra, Anup Kumar Ghosh, Bhubaneswar Mandal, Amal Chandra Mondal
BACKGROUND: Alzheimer's disease (AD), a common protein misfolding neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) proteins accumulated into interneuronal spaces and plays a crucial role in the disease progression and its pathology. The aggregated Aβ exerts its neurotoxic effects by inducing apoptosis and oxidative damage in neuronal cells. OBJECTIVES: We have investigated the effects of a synthesized Pro-Drug peptide (PDp) on Aβ1-40 induced cytotoxicity in human neuroblastoma SH-SY5Y cells, represents one of the most effective strategies in combating human AD...
July 13, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28714346/neuroprotective-effects-of-cassia-tora-against-paraquat-induced-neurodegeneration-relevance-for-parkinson-s-disease
#14
Sunil K Ravi, Ramesh B Narasingappa, Chandrashekar G Joshi, Talakatta K Girish, Bruno Vincent
The aim of the present study was to determine whether Cassia tora extracts could reverse the oxidative stress-induced neurodegeneration in a Parkinson's disease in vitro model. The leaves were treated with ethyl acetate (CtEA) or methanol (CtME). The extracts were first analysed by HPLC for their phenolic content and then tested for their neuroprotective effects in human SK-N-SH neuroblastoma cells. Cells were pre-treated with various concentrations of extracts followed by incubation with paraquat (14 μM)...
July 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28713944/truncated-apolipoprotein-c-i-induces-apoptosis-in-neuroblastoma-by-activating-caspases-in-the-extrinsic-and-intrinsic-pathways
#15
Fei Guo, Wei Zhao, Lin Yang, Yang Yang, Saiqi Wang, Yingjun Wang, Zhaoming Li, Jiaxiang Wang
Truncated apolipoprotein C-I is a post-translationally modified protein characterized by the loss of threonine and proline residues from the N-terminus of the mature peptide. The truncated peptide is involved in many physiological and pathological processes in vivo and is related to malignant diseases. The aim of the present study was to assess the effects of the truncated peptide on tumorigenesis in neuroblastoma. The truncated peptide was chemically synthesized, and a signal peptide was used as the negative control...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28711493/anti-cancer-effect-of-oncolytic-adenovirus-armed-shrna-targeting-mycn-gene-on-doxorubicin-resistant-neuroblastoma-cells
#16
Yuan Li, Baobiao Zhuo, Yiyu Yin, Tao Han, Shixian Li, Zhengwei Li, Jian Wang
Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28711167/perioperative-management-of-hypertensive-neuroblastoma-a-study-from-the-italian-group-of-pediatric-surgical-oncologists-gicop
#17
Luca Pio, Stefano Avanzini, Girolamo Mattioli, Giuseppe Martucciello, Angela Rita Sementa, Massimo Conte, Annarita Gigliotti, Claudio Granata, Ernesto Leva, Anna Maria Fagnani, Umberto Caccioppoli, Nino Tedesco, Jurgen Schleef, Elisa Tirtei, Fortunato Siracusa, Paolo D'Angelo, Pierluigi Lelli Chiesa, Lucia Miglionico, Bruno Noccioli, Elisa Severi, Claudio Carlini, Francesco Vaccarella, Francesco Camoglio, Simone Cesaro, Alessandra Narciso, Giovanna Riccipetitoni, Giovanni Cecchetto, Alessandro Inserra
BACKGROUND: Hypertension (HT) is rarely reported in patients affected by Neuroblastoma (NB), and management guidelines are lacking. Clinical features and perioperative medical treatment in such patients were reviewed to 1) ascertain whether a shared treatment strategy exists among centers and 2) if possible, propose some recommendations for the perioperative management of HT in NB patients. METHODS: A retrospective multicenter survey was conducted on patients affected by NB who presented HT symptoms...
July 3, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28710319/correction-polyphenon-e-enhances-the-antitumor-immune-response-in-neuroblastoma-by-inactivating-myeloid-suppressor-cells
#18
(no author information available yet)
No abstract text is available yet for this article.
July 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28710315/shallow-whole-genome-sequencing-on-circulating-cell-free-dna-allows-reliable-non-invasive-copy-number-profiling-in-neuroblastoma-patients
#19
Nadine Van Roy, Malaika Van der Linden, Björn Menten, Annelies Dheedene, Charlotte Vandeputte, Jo Van Dorpe, Geneviève Laureys, Marleen Renard, Tom Sante, Tim Lammens, Bram De Wilde, Frank Speleman, Katleen De Preter
<p>Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of NB patients could offer a valuable alternative to primary tumor DNA for CNA profiling.</p> <br /><br />Experimental Design: <p>In 37 NB patients cfDNA analysis using shallow whole genome sequencing (sWGS) was compared to arrayCGH analysis of primary tumor tissue...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28710101/superenhancers-drive-neuroblastoma-differentiation-states
#20
(no author information available yet)
Superenhancer-associated transcriptional networks promote neuroblastoma heterogeneity.
July 14, 2017: Cancer Discovery
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