Search results for "neuroblastoma."
showing 10 items of 238 documents
Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma
2019
Background Vitronectin is a multifunctional glycoprotein known in several human tumors for its adhesive role in processes such as cell growth, angiogenesis and metastasis. In this study, we examined vitronectin expression in neuroblastoma to investigate whether this molecule takes part in cell-cell or cell-extracellular matrix interactions that may confer mechanical properties to promote tumor aggressiveness. Methods We used immunohistochemistry and image analysis tools to characterize vitronectin expression and to test its prognostic value in 91 neuroblastoma patients. To better understand the effect of vitronectin, we studied its in vitro expression using commercial neuroblastoma cell lin…
Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
2017
AbstractPurpose: Despite advances in multimodal therapy, neuroblastomas with hemizygous deletion in chromosome 11q (20%–30%) undergo consecutive recurrences with poor outcome. We hypothesized that patients with 11q-loss may share a druggable molecular target(s) that can be exploited for a precision medicine strategy to improve treatment outcome.Experimental Design: SNP arrays were combined with next-generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma etiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in v…
The genetic tumor background is an important determinant for heterogeneous MYCN ‐amplified neuroblastoma
2016
Amplification of MYCN is the signature genetic aberration of 20–25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN‐FISH. Tumors of patients ≤18m were mostly an…
Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
2021
Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gainslength+%losseslength), (2) copy number load (CNL) (%gainslength-%losseslength) and (3) net genomic load (NGL) (%gainsamount-%lossesamount). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with…
Small Bowel Carcinomas in Coeliac or Crohn’s Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer I…
2017
Background and aims An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. Methods A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. Results CD-SBC showed a significantly better sex-, age-, and st…
NeuPAT: an intranet database supporting translational research in neuroblastic tumors.
2013
Translational research in oncology is directed mainly towards establishing a better risk stratification and searching for appropriate therapeutic targets. This research generates a tremendous amount of complex clinical and biological data needing speedy and effective management. The authors describe the design, implementation and early experiences of a computer-aided system for the integration and management of data for neuroblastoma patients. NeuPAT facilitates clinical and translational research, minimizes the workload in consolidating the information, reduces errors and increases correlation of data through extensive coding. This design can also be applied to other tumor types.
Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration
2014
AbstractNeuroblastoma (NB) is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX) protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years) formed part of the c…
Acitretin, an Enhancer of Alpha-Secretase Expression, Crosses the Blood-Brain Barrier and Is Not Eliminated by P-Glycoprotein
2011
<i>Background:</i> ADAM10 (a disintegrin and metalloproteinase 10) has been demonstrated to act as the main physiological α-secretase. Enzymatic activity of the α-secretase on the one hand prevents the formation of toxic Aβ peptides and on the other hand promotes the secretion of a neurotrophic and neuroprotective amyloid precursor protein fragment (APPs-α) by cleaving the amyloid precursor protein within its Aβ sequence. Enhancement of ADAM10’s gene expression may therefore present a valuable therapeutic approach for the treatment of Alzheimer’s disease (AD), where Aβ peptides are severely involved in the pathogenesis. <i>Objective:</i> In cell culture and in a tran…
Study of Proliferation and Apoptosis in Neuroblastoma. Their Relation with Other Prognostic Factors
2002
Abstract Background Our objective was to study the proliferation and apoptotic process in 111 cases of neuroblastoma (NB) and to seek their relationship with other prognostic factors and survival. Methods Immunohistochemistry following ABC peroxidase was carried out for PCNA, Ki-67, bcl-2, and p53 proteins. Apoptosis analysis was performed with in situ detection of chromosomal breakdown. Molecular detection of DNA ladders by electrophoresis and amplification of MYCN was studied with PCR and Southern blot. Statistical study was performed with Pearson χ 2 and Kruskal-Wallis tests and Cox regression. Results Our results indicate that proliferative factors PCNA and Ki-67 were correlated to each…
Esthesioneuroblastoma: Ultrastructural, immunohistological and biochemical investigation of one case
1984
A case of esthesioneuroblastoma, the pathological diagnosis of which almost always causes great difficulties, was investigated ultrastructurally, biochemically, and immunohistologically, using antibodies against the five known types of intermediate filaments [keratin, vimentin, desmin, glial fibrillary acidic protein (GFAP) and neurofilaments]. The tumour cells did not react with antibodies against any of the five intermediate filament proteins. Ultrastructural investigations showed dense cored secretory granules in the cytoplasm and cell processes. Thus, immunohistology offers by "exclusion" a differential diagnosis to avoid often misdiagnosed tumours (undifferentiated carcinomas, embryona…