High dose chemotherapy and autologous stem cell rescue for children with high risk neuroblastoma

Yalçın, Bilgehan; Dalen, Elvira C. van; Caron, Huib N.; Kremer, Leontien

doi:10.1002/14651858.cd006301

Cited by 6 publications

(2 citation statements)

References 25 publications

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“…It is the most common extra-cranial solid tumor of early childhood [ 3 ]. Neuroblastoma is a complex disease that has high genetic, biological, clinical, and morphological heterogeneity, so the treatment in pediatric populations is complex and difficult, and there is a high incidence of death, regardless of the use of intensive multimodality therapies [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival

Paccosi

Costantino

Balzerano

et al. 2021

IJMS

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Neuroblastoma, the most common extra-cranial solid tumor of early childhood, is one of the major therapeutic challenges in child oncology: it is highly heterogenic at a genetic, biological, and clinical level. The high-risk cases have one of the least favorable outcomes amongst pediatric tumors, and the mortality rate is still high, regardless of the use of intensive multimodality therapies. Here, we observed that neuroblastoma cells display an increased expression of Cockayne Syndrome group B (CSB), a pleiotropic protein involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division, and were recently found to confer cell robustness when they are up-regulated. In this study, we demonstrated that RNAi-mediated suppression of CSB drastically impairs tumorigenicity of neuroblastoma cells by hampering their proliferative, clonogenic, and invasive capabilities. In particular, we observed that CSB ablation induces cytokinesis failure, leading to caspases 9 and 3 activation and, subsequently, to massive apoptotic cell death. Worthy of note, a new frontier in cancer treatment, already proved to be successful, is cytokinesis-failure-induced cell death. In this context, CSB ablation seems to be a new and promising anticancer strategy for neuroblastoma therapy.

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Section: Introductionmentioning

confidence: 99%

Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival

Paccosi

Costantino

Balzerano

et al. 2021

IJMS

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“…Neuroblastoma (NB) is one of the most common extracranial solid tumors in children, with an annual incidence of 0.3–5.5 per 100,000, and accounting for 7%–8% of all childhood tumors. The mortality rate from NB is 15% . This tumor is composed of undifferentiated neuroblasts, and it differs from adult solid tumors in its tumorigenesis and development.…”

Section: Introductionmentioning

confidence: 99%

Legumain correlates with neuroblastoma differentiation and can be used in prodrug design

et al. 2017

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Neuroblastoma (NB) is a highly malignant solid tumor in children. The cysteine endopeptidase legumain is expressed in adult solid tumors, but its expression in NB has not been examined. In this study, we assayed legumain expression in two NB cell lines and in microarrays of tumor tissues collected from 46 children with undifferentiated NB, differentiated NB, and ganglioneuroblastoma. Correlation analyses showed that legumain was expressed in all NB cell lines tested and that expression correlated with the degree of tumor differentiation. The efficacy, specificity, and toxicity of EMC-AANL-DOX, a novel doxorubicin-based legumain-activated prodrug, were then evaluated in mouse model of NB. Compared with DOX, EMC-AANL-DOX showed greater inhibition of tumor growth and a lower toxicity at high doses. Neither leukocyte or platelet counts nor renal function or cardiac anatomy differed significantly between the EMC-AANL-DOX and control groups (p > .05), suggesting that the prodrug caused minimal bone marrow depression and did not induce renal or cardiac damage. The good specificity and efficacy of EMC-AANL-DOX and low toxicity recommend its use in the treatment of NB. Correlation analyses of NB differentiation and legumain expression may reveal a novel anti-tumor-related functions of the drug and a new strategy for the treatment of pediatric solid tumors.

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High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma

Yalçın

Kremer

Caron

et al. 2013

Cochrane Database of Systematic Reviews

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Based on the currently available evidence, myeloablative therapy seems to work in terms of event-free survival. For overall survival there is currently no evidence of effect when additional follow-up data are included. No definitive conclusions can be made regarding adverse effects and quality of life, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (e.g. stage of disease and patient age) and have a long-term follow-up. Different risk groups, using the most recent definitions, should be taken into account.It should be kept in mind that recently the age cut-off for high risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease have been included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease.

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High dose chemotherapy and autologous stem cell rescue for children with high risk neuroblastoma

Cited by 6 publications

References 25 publications

Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival

Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival

Legumain correlates with neuroblastoma differentiation and can be used in prodrug design

High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma

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