Glycobiology of Neuroblastoma: Impact on Tumor Behavior, Prognosis, and Therapeutic Strategies

Berois, Nora; Osinaga, Eduardo

doi:10.3389/fonc.2014.00114

Cited by 31 publications

(35 citation statements)

References 173 publications

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“…Additionally, these molecules are also involved in various biological pathways that are implicated in pathogenesis and progression of tumors (Ahmed & Cheung, ). GD2 has a high expression on the surface of tumor cells originating from neuroectoderm, such as NB and melanoma, while has limited expression on normal tissues, principally in the cerebellum and peripheral nerves (Ahmed & Cheung, ; Berois & Osinaga, ; Saito et al, ; Suzuki & Cheung, ). Several reports revealed that GD2 contribute to the attachment of NB cells to the extracellular matrix (Ahmed & Cheung, ; Cheung et al, ; Kushner, Kramer, Modak, & Cheung, ).…”

Section: Introductionmentioning

confidence: 99%

GD2‐targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma

Gholamin

Mirzaei

Razavi

et al. 2017

Journal Cellular Physiology

103

112

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Neuroblastoma (NB) with various clinical presentation is a known childhood malignancy. Despite significant progress in treatment of NB afflicted patients, high risk disease is usually associated with poor outcome, resulting in long-term survival of less that 50%. Known as a disease most commonly originated form the nerve roots, the variants involved in NB imitation and progression remain to be elucidated. The outcome of low to intermediate risk disease is favorable whereas the high risk NB disease with dismal prognosis, positing the necessity of novel approaches for early detection and prognostication of advanced disease. Tailored immunotherapy approaches have shown significant improvement in high-risk NB patients. It has found a link between Gangliosides and progression of NB. The vast majority of neuroblastoma tumors express elevated levels of GD2, opening new insight into using anti-GD2 drugs as potential treatments for NBs. Implication of anti-GD2 monoclonal antibodies for treatment of high risk NBs triggers further investigation to unearth novel biomarkers as prognostic and response biomarker to guide additional multimodal tailored treatment approaches. A growing body of evidence supports the usefulness of miRNAs to evaluate high risk NBs response to anti-GD2 drugs and further prevent drug-related toxicities in refractory or recurrent NBs. miRNAs and circulating proteins in body fluids (plasma and serum) present as potential biomarkers in early detection of NBs. Here, we summarize various biomarkers involved in diagnosis, prognosis and response to treatment in patients with NB. We further attempted to overview prognostic biomarkers in response to treatment with anti-GD2 drugs.

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Section: Introductionmentioning

confidence: 99%

GD2‐targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma

Gholamin

Mirzaei

Razavi

et al. 2017

Journal Cellular Physiology

103

112

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“…Galectin‐1 is involved in the regulation of cell growth, adhesion, signalling, differentiation and development, as well as immune system and host–pathogen interactions . Galectin‐1 plays an important role in sensory neuron development and synaptic connection in the embryonic spinal cord, and is overexpressed in various stages of cancer, with its role in cancer progression and metastasis being intensively reviewed . To date, several different types of synthetic glycoconjugates have been reported against galectin‐1 .…”

Section: Introductionmentioning

confidence: 99%

Lactulose as a novel template for anticancer drug development targeting galectins

2018

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Galectins are carbohydrate binding proteins (lectins), which characteristically bind β-galactosides. Galectins play a role in tumour progression through involvement in proliferation, metastasis, angiogenesis, immune evasion and drug resistance. There is need for inhibitors (antagonists) that are specific for distinct galectins and that can interfere with galectin-carbohydrate interactions during cancer progression. Here, we propose that lactulose, a non-digestible galactose-fructose disaccharide, presents a novel inhibitor scaffold for design of inhibitors against galectins. Thermodynamic evaluation displays binding affinity of lactulose against the galectin-1 and galectin-3 carbohydrate recognition domain (CRD). Crystal structures of galectin-1 and galectin-3 in complex with lactulose reveal for the first time the molecular basis of the galectin-lactulose interactions. Molecular modelling was implemented to propose novel lactulose derivatives as potent anti-cancer agents.

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“…However, within this positive population there remains heterogeneous expression of GD2 (Figure B). Clinically, the majority of neuroblastoma tumor cells exhibit GD2 on the cell membrane making it a prominent therapeutic target . Furthermore, high expression of GD2 is one of the hall marks of high‐risk neuroblastoma .…”

Section: Discussionmentioning

confidence: 99%

Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

et al. 2020

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Immunotherapy targeting GD2 is a primary treatment for patients with high-risk neuroblastoma. Dinutuximab is a monoclonal antibody with great clinical promise but is limited by side effects such as severe pain. Local delivery has emerged as a potential mechanism to deliver higher doses of therapeutics into the tumor bed, while limiting systemic toxicity. We aim to deliver dinutuximab locally in a lyophilized silk fibroin foam for the treatment of an orthotopic neuroblastoma mouse model. Dinutuximabloaded silk fibroin foams were fabricated through lyophilization. In vitro release profile and bioactivity of the release through complement-dependent cytotoxicity were characterized. MYCN-amplified neuroblastoma cells (KELLY) were injected into the left gland of mice to generate an orthotopic neuroblastoma model. Once the tumor volume reached 100 mm 3 , dinutuximab-, human IgG-, or buffer-loaded foams were implanted into the tumor and growth was monitored using high-resolution ultrasound. Post-resection histology was performed on tumors. Dinutuximab-loaded silk fibroin foams exhibited a burst release, with slow release thereafter in vitro with maintenance of bioactivity. The dinutuximab-loaded foam significantly inhibited xenograft tumor growth compared to IgG-and buffer-loaded foams. Histological analysis revealed the presence of dinutuximab within the tumor and neutrophils and macrophages infiltrating into dinutuximab-loaded silk foam. Tumors treated with local dinutuximab had decreased MYCN expression on histology compared to control or IgG-treated tumors. Silk fibroin foams offer a mechanism for local release of dinutuximab within the neuroblastoma tumor. This local delivery achieved a significant decrease in tumor growth rate in a mouse orthotopic tumor model. K E Y W O R D SCh14.18, dinutuximab, immunotherapy, local delivery, neuroblastoma, silk fibroin

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Glycobiology of Neuroblastoma: Impact on Tumor Behavior, Prognosis, and Therapeutic Strategies

Cited by 31 publications

References 173 publications

GD2‐targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma

GD2‐targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma

Lactulose as a novel template for anticancer drug development targeting galectins

Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

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