Role of Genetic and Epigenetic Alterations in Pathogenesis of Neuroblastoma

Inomistova, M.; Khranovska, N.; Skachkova, O.

doi:10.1016/b978-0-12-812005-7.00002-3

Cited by 3 publications

(9 citation statements)

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“…let-7a miRNA also acts as a tumor suppressor in NB by inhibiting oncogene transcription and stemness features of tumor cells [ 164 ]. It has been found to be downregulated in N- and I-type NB cell lines [ 243 , 244 , 245 ], likely due to its negative regulation by the neural crest-directed expression of LIN28 [ 251 ]. Therefore, difluoromethylornithine (DFMO) treatment on SMS-KCNR and BE(2)-C stem-like cells, characterized by V-Myc avian myelocytomatosis viral oncogene neuroblastoma ( MYCN ) amplification, reduces LIN28 and MYCN protein levels; thus, restoring let-7 miRNA expression and decreasing neurosphere formation [ 163 , 164 ].…”

Section: Mirnas Involved In the Regulation Of Apoptosis In Human Nmentioning

confidence: 99%

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

Diana

Gaido²,

Maxia

et al. 2020

IJMS

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Stemness and apoptosis may highlight the dichotomy between regeneration and demise in the complex pathway proceeding from ontogenesis to the end of life. In the last few years, the concept has emerged that the same microRNAs (miRNAs) can be concurrently implicated in both apoptosis-related mechanisms and cell differentiation. Whether the differentiation process gives rise to the architecture of brain areas, any long-lasting perturbation of miRNA expression can be related to the occurrence of neurodevelopmental/neuropathological conditions. Moreover, as a consequence of neural stem cell (NSC) transformation to cancer stem cells (CSCs), the fine modulation of distinct miRNAs becomes necessary. This event implies controlling the expression of pro/anti-apoptotic target genes, which is crucial for the management of neural/neural crest-derived CSCs in brain tumors, neuroblastoma, and melanoma. From a translational point of view, the current progress on the emerging miRNA-based neuropathology therapeutic applications and antitumor strategies will be disclosed and their advantages and shortcomings discussed.

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Section: Mirnas Involved In the Regulation Of Apoptosis In Human Nmentioning

confidence: 99%

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

Diana

Gaido²,

Maxia

et al. 2020

IJMS

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“…[15] A characteristic feature of NB is its clinical heterogeneity from localised tumours to widespread and early haematogenous metastasizing. This clinical heterogeneity reflects the complexity of genomic abnormalities characterised in NB tumours [16] leading to significant differences in outcome across tumour subtypes. In studies of infants the disease has been known to spontaneously regress without therapy, whereas older children with unfavourable histology tend to have poor outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…In studies of infants the disease has been known to spontaneously regress without therapy, whereas older children with unfavourable histology tend to have poor outcomes. Inomistova et al, [16] explain that there are multiple mechanisms by which cells can progress into malignancy that involves the concerted accumulation and functional cooperation between genetic and epigenetic changes, and not their order of occurrence that results in carcinogenesis. [16] The occurrence of many cancers is the result of the accumulation of genetic and epigenetic changes: epigenetics is concerned with heritable changes in the functioning of genes without changes in the DNA sequence.…”

Section: Introductionmentioning

confidence: 99%

“…Inomistova et al, [16] explain that there are multiple mechanisms by which cells can progress into malignancy that involves the concerted accumulation and functional cooperation between genetic and epigenetic changes, and not their order of occurrence that results in carcinogenesis. [16] The occurrence of many cancers is the result of the accumulation of genetic and epigenetic changes: epigenetics is concerned with heritable changes in the functioning of genes without changes in the DNA sequence. These epigenetic modifications consist mainly of DNA methyl-ation, histone modification, chromatin reorganization, and expression of non-coding RNA.…”

Section: Introductionmentioning

confidence: 99%

“…In the case of cancers, it is nearly impossible to reverse genetic alterations, whereas epigenetic changes "can dynamically respond to signals from the physical, biological and social environment". [16] Inomistova, et al in 2019, reported that the role of MYCN gene amplification in NB pathogenesis was established in the 1980s, due to its association with high-risk tumour and low patient survival. Since then, several other genetic abnormalities have been associated with NB, including gains of whole chromosomes and large-scale chromosomal imbalances, such as loss of heterozygosity (LOH) at chromosomal arm 1p, 3p, 14q, and 11q, unbalanced gain at 1q, 11p, and 17q and numerous mutations in key genes such as ALK, PHOX2B, and PTPRD.…”

Section: Introductionmentioning

confidence: 99%

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Neuroblastoma and its Target Therapies: A Medicinal Chemistry Review

Gerges,

Canning

2024

ChemMedChem

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Neuroblastoma (NB) is a childhood malignant tumour belonging to a group of embryonic tumours originating from progenitor cells of the sympathoadrenal lineage. The heterogeneity of NB is reflected in the survival rates of those with low and intermediate risk diseases who have survival rates ranging from 85 to 90 %. However, for those identified with high‐risk Stage 4 NB, the treatment options are much more limited. For this group, current treatment consists of immunotherapy (monoclonal antibodies) in combination with anti‐cancer drugs and has a 40 to 50 % survival rate. The purpose of this review is to summarise NB research from a medicinal chemistry perspective and to highlight advances in targeted drug therapy in the field. The review examines the medicinal chemistry of a number of drugs tested in research, some of which are currently under clinical trial. It concludes by proposing that future medicinal chemistry research into NB should consider other possible target therapies and adopt a multi‐target drug approach rather than a one‐drug‐one‐target approach for improved efficacy and less drug‐drug interaction for the treatment of NB Stage 4 (NBS4) patients.

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Imidazo-Pyrazole-Loaded Palmitic Acid and Polystyrene-Based Nanoparticles: Synthesis, Characterization and Antiproliferative Activity on Chemo-Resistant Human Neuroblastoma Cells

Valenti,

Marengo,

Milanese

et al. 2023

IJMS

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Neuroblastoma (NB) is a childhood cancer, commonly treated with drugs, such as etoposide (ETO), whose efficacy is limited by the onset of resistance. Here, aiming at identifying new treatments for chemo-resistant NB, the effects of two synthesized imidazo-pyrazoles (IMPs) (4G and 4I) were investigated on ETO-sensitive (HTLA-230) and ETO-resistant (HTLA-ER) NB cells, detecting 4I as the more promising compound, that demonstrated IC50 values lower than those of ETO on HTLA ER. Therefore, to further improve the activity of 4I, we developed 4I-loaded palmitic acid (PA) and polystyrene-based (P5) cationic nanoparticles (P5PA-4I NPs) with high drug loading (21%) and encapsulation efficiency (97%), by a single oil-in-water emulsification technique. Biocompatible PA was adopted as an emulsion stabilizer, while synthesized P5 acted as an encapsulating agent, solubilizer and hydrophilic–lipophilic balance (HLB) improver. Optic microscopy and cytofluorimetric analyses were performed to investigate the micromorphology, size and complexity distributions of P5PA-4I NPs, which were also structurally characterized by chemometric-assisted Fourier transform infrared spectroscopy (FTIR). Potentiometric titrations allowed us to estimate the milliequivalents of PA and basic nitrogen atoms present in NPs. P5PA-4I NPs afforded dispersions in water with excellent buffer capacity, essential to escape lysosomal degradation and promote long residence time inside cells. They were chemically stable in an aqueous medium for at least 40 days, while in dynamic light scattering (DLS) analyses, P5PA-4I showed a mean hydrodynamic diameter of 541 nm, small polydispersity (0.194), and low positive zeta potentials (+8.39 mV), assuring low haemolytic toxicity. Biological experiments on NB cells, demonstrated that P5PA-4I NPs induced ROS-dependent cytotoxic effects significantly higher than those of pristine 4I, showing a major efficacy compared to ETO in reducing cell viability in HTLA-ER cells. Collectively, this 4I-based nano-formulation could represent a new promising macromolecular platform to develop a new delivery system able to increase the cytotoxicity of the anticancer drugs.

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Role of Genetic and Epigenetic Alterations in Pathogenesis of Neuroblastoma

Cited by 3 publications

References 145 publications

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies

Neuroblastoma and its Target Therapies: A Medicinal Chemistry Review

Imidazo-Pyrazole-Loaded Palmitic Acid and Polystyrene-Based Nanoparticles: Synthesis, Characterization and Antiproliferative Activity on Chemo-Resistant Human Neuroblastoma Cells

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