Search results for "NEUROBLASTOMA"

A subset of flavaglines inhibits KRAS nanoclustering and activation.

2020

The RAS oncogenes are frequently mutated in human cancers and among the three isoforms (KRAS, HRAS and NRAS), KRAS is the most frequently mutated oncogene. Here, we demonstrate that a subset of flavaglines, a class of natural anti-tumour drugs and chemical ligands of prohibitins, inhibit RAS GTP loading and oncogene activation in cells at nanomolar concentrations. Treatment with rocaglamide, the first discovered flavagline, inhibited the nanoclustering of KRAS, but not HRAS and NRAS, at specific phospholipid-enriched plasma membrane domains. We further demonstrate that plasma membrane-associated prohibitins directly interact with KRAS, phosphatidylserine and phosphatidic acid, and these int…

Análisis digital del infiltrado inmune en neuroblastoma. Impacto pronóstico.

2018

El neuroblastoma es el tumor sólido extracraneal más común en la niñez con un índice de supervivencia a los cinco años del 40% en pacientes de riesgo elevado a pesar de terapias intensivas. Recientemente, aunque la inmunoterapia, incluida la terapia de células T con receptor de antígeno quimérico, representa un tratamiento revolucionario para las neoplasias hematológicas, sigue habiendo grandes desafíos para aplicar esta estrategia terapéutica con los tumores sólidos, incluido el neuroblastoma, como resultado de la naturaleza inmunosupresiva del microambiente tumoral. Se ha descrito que las células cancerosas desarrollan múltiples mecanismos para escapar del reconocimiento inmune o para mod…

Comparative genetic study of intratumoral heterogenous MYCN amplified neuroblastoma versus aggressive genetic profile neuroblastic tumors.

2016

Intratumoral heterogeneous MYCN amplification (hetMNA) is an unusual event in neuroblastoma with unascertained biological and clinical implications. Diagnosis is based on the detection of MYCN amplification surrounded by non-amplified tumor cells by fluorescence in situ hybridization (FISH). To better define the genetic features of hetMNA tumors, we studied the Spanish cohort of neuroblastic tumors by FISH and single nucleotide polymorphism arrays. We compared hetMNA tumors with homogeneous MNA (homMNA) and nonMNA tumors with 11q deletion (nonMNA w11q-). Of 1091 primary tumors, 28 were hetMNA by FISH. Intratumoral heterogeneity of 1p, 2p, 11q and 17q was closely associated with hetMNA tumor…

Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients

2018

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in b…

Alternative lengthening of telomeres--an enhanced chromosomal instability in aggressive non-MYCN amplified and telomere elongated neuroblastomas

2010

Telomere length alterations are known to cause genomic instability and influence clinical course in several tumor types, but have been little investigated in neuroblastoma (NB), one of the most common childhood tumors. In the present study, telomere-dependent chromosomal instability and telomere length were determined in six NB cell lines and fifty tumor biopsies. The alternative lengthening of telomeres (ALT) pathway was assayed by scoring ALT-associated promyelocytic leukemia (PML) bodies (APBs). We found a reduced probability of overall survival for tumors with increased telomere length compared to cases with reduced or unchanged telomere length. In non-MYCN amplified tumors, a reduced o…

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction

2015

Background Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. Results We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being …

RAS mutations and cetuximab in locally advanced rectal cancer: Results of the EXPERT-C trial

2013

Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial. Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-di…

Magnetic resonance imaging in primary cerebral neuroblastoma

1989

Extra-Adrenal Adult Neuroblastoma With Aberrant Germ Cell Marker Expression: Maturation After Chemotherapy as an Important Clue to a Challenging Diag…

2019

Adult neuroblastoma is an extremely infrequent neoplasm, usually occurring in the adrenal medulla or in the paraspinal sympathetic ganglia, as its childhood counterpart. We report a very unusual case of a Schwannian stroma-poor adult neuroblastoma of inguinal location, showing aberrant expression of germ cell markers: SALL4 and OCT4. This aberrant marker expression, the unusual positivity for NKX2.2 and the very scattered (instead of diffuse strong) PHOX2B expression, complicated the initial diagnosis. In this case, the posttreatment histological evaluation revealed the neuroblastic nature of the lesion. Neuroblastoma maturation after treatment is an unusual finding in adults, and in this …

Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany

2001

Neuroblastoma is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 183 children under the age of 8 with neuroblastoma diagnosed in 1988-1994 and 1785 control children sampled from population registration files participated. Information on potential risk factors was obtained from the children's parents by a self-administered questionnaire and subsequent telephone interview. We observed positive associations with the use of oral contraceptives or other sex hormones during pregnancy (particularly with male offspring), a shorter gestational duration, lower birth weight, and maternal alcohol consumption during pregnancy. While …