ABC Transporters and Neuroblastoma.

ABC Transporters and Neuroblastoma. Adv Cancer Res. 2015;125:139-70 Authors: Yu DM, Huynh T, Truong AM, Haber M, Norris MD Abstract Neuroblastoma is the most common cancer of infancy and accounts for 15% of all pediatric oncology deaths. Survival rates of high-risk neuroblastoma remain less than 50%, with amplification of the MYCN oncogene the most important aberration associated with poor outcome. Direct transcriptional targets of MYCN include a number of ATP-binding cassette (ABC) transporters, of which ABCC1 (MRP1), ABCC3 (MRP3), and ABCC4 (MRP4) are the best characterized. These three transporter genes have been shown to be strongly prognostic of neuroblastoma outcome in primary untreated neuroblastoma. In addition to their ability to efflux a number of chemotherapeutic drugs, evidence suggests that these transporters also contribute to neuroblastoma outcome independent of any role in cytotoxic drug efflux. Endogenous substrates of ABCC1 and ABCC4 that may be potential candidates affecting neuroblastoma biology include molecules such as prostaglandins and leukotrienes. These bioactive lipid mediators have the ability to influence biological processes contributing to cancer initiation and progression, such as angiogenesis, cell signaling, inflammation, proliferation, and migration and invasion. ABCC1 and ABCC4 are thus potential targets for therapeutic suppression in high-risk neuroblastoma, and recently developed small-molecule inhibitors may be an e...
Source: Advances in Cancer Research - Category: Cancer & Oncology Authors: Tags: Adv Cancer Res Source Type: research

Related Links:

AbstractEmerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6 ‐AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6‐AS1 in NB progression are not fully understood. Our data showed that DLX6‐AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6‐AS1 silencing repressed NB cell viability, colony form ation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6‐AS1 operated as ...
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH COMMUNICATION Source Type: research
CONCLUSION: Collectively, we concluded that TDG could serve as an effective treatment capable of targeting the NB CSCs and hence overcoming therapy resistance. Yet, future studies are warranted to further investigate its potential role in NB and decipher the subcellular and molecular mechanisms underlying this role. PMID: 33030673 [PubMed - as supplied by publisher]
Source: Pharmacological Reports - Category: Drugs & Pharmacology Authors: Tags: Pharmacol Rep Source Type: research
In this study, we discovered that PF-477736 increased expression of MDM2 oncogene along with CHK1i-induced replication defects in neuroblastoma NB-39-nu cells. A mass spectrometry analysis of protein binding to MDM2 in the presence of CHK1i identified the centrosome-associated family protein 131 (CEP131), which was correlated with unfavorable prognosis of neuroblastoma patients. We revealed that MDM2 was associated with CEP131 protein degradation, whereas overexpression of CEP131 accelerated neuroblastoma cell growth and exhibited resistance to CHK1i-induced replication defects. Thus, these findings may provide a future th...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 — a component of the transcription elongation complex P-TEFb — bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis follow...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
(Lund University) A drug has shown great promise in the treatment of neuroblastoma, an aggressive form of childhood cancer. The study was led by researchers at Lund University in Sweden, and is published in the journal Science Translational Medicine.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Abstract Accurate intraoperative histopathological analysis is critical to the tumor surgery. However, conventional methods are labor- and time-intensive, which greatly delay the intraoperative decision-making. Herein, a matrix metalloproteinase (MMP)14-activated NIR-II nanoprobe (A&MMP@Ag 2 S-AF7P) is presented for rapid and nondestructive histopathological analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag 2 S-AF7P displays the negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) process between Ag 2 S QDs and A1094 med...
Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research
This is the initial report of an α-based pre-targeted radioimmunotherapy (PRIT) using 225Ac and its theranostic pair, 111In. We call our novel tumor-targeting DOTA-hapten PRIT system “proteus-DOTA” or “Pr.” Herein we report the first results of radiochemistry development, radiopharmacology, and stoichiometry of tumor antigen binding, including the role of specific activity, anti-tumor efficacy, and normal tissue toxicity with the Pr-PRIT approach (as α-DOTA-PRIT). A series of α-DOTA-PRIT therapy studies were performed in three solid human cancer xenograft models of colorectal cance...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Conclusion: Our results suggest that significant L-DOX uptake can occur by increasing tumor vascular permeability with microbubble sonopermeation without otherwise damaging the vasculature, as confirmed by in vivo qCEUS imaging and ex vivo analysis. The use of qCEUS imaging to monitor sonopermeation efficiency and predict drug uptake could potentially provide real-time feedback to clinicians for determining treatment efficacy in tumors, leading to better and more efficient personalized therapies. Finally, we demonstrate how the IGDD strategy outlined in this study could be implemented in human patients using a single case study.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Eslicarbazepine acetate (ESL) is a dibenzazepine anticonvulsant approved as adjunctive treatment for partial-onset epileptic seizures. Following first pass hydrolysis of ESL, S-licarbazepine (S-Lic) represents around 95% of circulating active metabolites. S-Lic is the main enantiomer responsible for anticonvulsant activity and this is proposed to be through the blockade of voltage-gated Na+ channels (VGSCs). ESL and S-Lic both have a voltage-dependent inhibitory effect on the Na+ current in N1E-115 neuroblastoma cells expressing neuronal VGSC subtypes including Nav1.1, Nav1.2, Nav1.3, Nav1.6, and Nav1.7. ESL has not been a...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Serine-threonine kinase receptor associated protein (STRAP) is a scaffolding protein implicated in tumorigenicity but has not been explored in neuroblastoma. Stem cell-like cancer cells are believed to be responsible for tumor cell self-renewal and cancer recurrence. We sought to determine the role of STRAP in neuroblastoma stem cell-like cancer cells maintenance.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Pediatric surgery Source Type: research
More News: Biology | Cancer | Cancer & Oncology | Genetics | Neuroblastoma | Neurology | Pediatrics