Updates in Diagnosis, Management, and Treatment of Neuroblastoma

Swift, Caroline C.; Eklund, Meryle J.; Kraveka, Jacqueline M.; Alazraki, Adina

doi:10.1148/rg.2018170132

Cited by 199 publications

(189 citation statements)

References 67 publications

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“…Neuroblastoma is an ambiguous disease with spontaneous remissions in infants with stage 4s while children over 1 year of age with metastatic disease have a persistently poor outcome. 3 Amplification of the MycN gene is found predominantly in advanced stage diseases and is associated with rapid tumor progression and poor prognosis [2,[4][5][6]. Despite intensive therapy the prognosis of patients with high-risk relapsed or refractory neuroblastoma (rNB) comprising up about 60% of cases remains dismal [2,7].…”

Section: Introductionmentioning

confidence: 99%

Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells

Waetzig¹,

Matthes²,

Leister³

et al. 2021

Int. J. Med. Sci.

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The prognosis for patients with relapsed or refractory high-risk neuroblastoma remains dismal and novel therapeutic options are urgently needed. The RIST treatment protocol has a multimodal metronomic therapy design combining molecular-targeted drugs (Rapamycin and Dasatinib) with chemotherapy backbone (Irinotecan and Temozolomide), which is currently verified in a phase II clinical trial (NCT01467986). With the availability of novel and more potent ATP competitive mTOR inhibitors, we expect to improve the RIST combination therapy. By comparing the IC50 values of Torin-1, Torin-2, AZD3147 and PP242 we established that only Torin-2 inhibited cell viability of all three MycN-amplified neuroblastoma cell lines tested at nanomolar concentration. Single treatment of both mTOR inhibitors induced a significant G1 cell cycle arrest and combination treatment with Dasatinib reduced the expression of cell cycle regulator cyclin D1 or increased the expression of cell cycle inhibitor p21. The combinatorial index depicted for both mTOR inhibitors a synergistic effect with Dasatinib. Interestingly, compared to Rapamycin, the combination treatment with Torin-2 resulted in a broader mTOR pathway inhibition as indicated by reduced phosphorylation of AKT (Thr308, Ser473), 4E-BP (Ser65), and S6K (Thr389). Furthermore, substituting Rapamycin in the modified multimodal RIST protocol with Torin-2 reduced cell viability and induced apoptosis despite a significant lower Torin-2 drug concentration applied. The efficacy of nanomolar concentrations may significantly reduce unwanted immunosuppression associated with Rapamycin. However, at this point we cannot rule out that Torin-2 has increased toxicity due to its potency in more complex systems. Nonetheless, our results suggest that including Torin-2 as a substitute for Rapamycin in the RIST protocol may represent a valid option to be evaluated in prospective clinical trials for relapsed or treatment-refractory high-risk neuroblastoma.

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Section: Introductionmentioning

confidence: 99%

Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells

Waetzig¹,

Matthes²,

Leister³

et al. 2021

Int. J. Med. Sci.

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“…Neuroblastoma is the most common type of extracranial solid tumor in children and is responsible for up to 15% of all pediatric oncologic deaths (Whittle et al 2017;Swift et al 2018). Neuroblastoma is a heterogeneous tumor with a wide range of clinical behaviors; some tumors exhibit aggressive growth and are more likely to metastasize (Maris 2010).…”

Section: Discussionmentioning

confidence: 99%

SIRT1 and AROS suppress doxorubicin-induced apoptosis via inhibition of GSK3β activity in neuroblastoma cells

Kim

Yang

Kim

2020

Animal Cells and Systems

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SIRT1, the best-characterized member of the sirtuin family of deacetylases, is involved in cancer, apoptosis, inflammation, and metabolism. Active regulator of SIRT1 (AROS) was the first identified direct regulator of SIRT1. An increasing number of reports have indicated that SIRT1 plays an important role in controlling brain tumors. Here, we demonstrated that depletion of SIRT1 and AROS increases doxorubicin-mediated apoptosis in human neuroblastoma SH-SY5Y cells. Glycogen synthase kinase 3β (GSK3β) promoted doxorubicin-mediated apoptosis, but this effect was abolished by overexpression of SIRT1 and AROS. Interestingly, SIRT1 and AROS interacted with GSK3β and increased inhibitory phosphorylation of GSK3β on Ser9. Finally, we determined that AROS cooperates with SIRT1 to suppress GSK3β acetylation. Taken together, our results suggest that SIRT1 and AROS inhibit GSK3β activity and provide additional insight into drug resistance in the treatment of neuroblastoma.

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“…3 Moreover, different ages, histological and biological characteristics of tumors give rise to different NB progression. 4 High-risk NB with high-risk gene modification and histological defects is a metastatic disease. 5 Despite intensive treatment, patients with advanced or metastatic NB often have a poor prognosis, with less than 40% long-term survival.…”

Section: Introductionmentioning

confidence: 99%

<p>Long Non Coding RNA SNHG16 Facilitates Proliferation, Migration, Invasion and Autophagy of Neuroblastoma Cells via Sponging miR-542-3p and Upregulating ATG5 Expression</p>

Wen¹,

Gong²,

Dong³

et al. 2020

OTT

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Background: Neuroblastoma (NB) is a heterogeneous pediatric malignant tumor with many biological and clinical characteristics. Long non-coding RNA small nucleolar RNA host gene 16 (SNHG16) plays vital role in the development of NB. However, the potential mechanism of SNHG16 in the progression of NB is rarely reported. Methods: The expression levels of SNHG16, miR-542-3p and autophagy-related gene 5 (ATG5) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration and invasion of NB cells were determined using 3-(4, 5-dimethylthiazol-2-YI)-2, 5-diphenyltetrazolium bromide (MTT) or transwell assay. Protein levels of ATG5, microtubule-associated protein A1/1B-light chain3 (LC3-I/II) and p62 were detected by Western blot analysis. The interaction between miR-542-3p and SNHG16 or ATG5 was predicted by starBase and confirmed by dual luciferase reporter assay. Xenograft mice models were constructed to confirm the role of SNHG16 in vivo. Results: SNHG16 was upregulated in NB tissues and cells and associated with clinical stage and poor prognosis of NB. Knockdown of SNHG16 impeded proliferation, migration, invasion and autophagy of NB cells in vitro, and suppressed tumor growth in vivo. Interestingly, SNHG16 mediated ATG5 expression through sponging miR-542-3p in NB cells. Moreover, miR-542-3p downregulation reversed the inhibitory effects of SNHG16 silencing on proliferation, migration, invasion and autophagy of NB cells. Besides, ATG5 overturned the regulatory effects on proliferation, migration, invasion and autophagy of NB cells induced by SNHG16 or miR-542-3p knockdown. Conclusion: SNHG16 facilitated proliferation, migration, invasion and autophagy of NB cells via sponging miR-542-3p and upregulating ATG5 expression in NB.

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Updates in Diagnosis, Management, and Treatment of Neuroblastoma

Cited by 199 publications

References 67 publications

Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells

Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells

SIRT1 and AROS suppress doxorubicin-induced apoptosis via inhibition of GSK3β activity in neuroblastoma cells

<p>Long Non Coding RNA SNHG16 Facilitates Proliferation, Migration, Invasion and Autophagy of Neuroblastoma Cells via Sponging miR-542-3p and Upregulating ATG5 Expression</p>

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