Engineered human mesenchymal stem cells for neuroblastoma therapeutics.

Engineered human mesenchymal stem cells for neuroblastoma therapeutics. Oncol Rep. 2019 May 08;: Authors: Nieddu V, Piredda R, Bexell D, Barton J, Anderson J, Sebire N, Kolluri K, Janes SM, Karteris E, Sala A Abstract Drug-resistant neuroblastoma remains a major challenge in paediatric oncology and novel and less toxic therapeutic approaches are urgently needed to improve survival and reduce the side effects of traditional therapeutic interventions. Mesenchymal stem cells (MSCs) are an attractive candidate for cell and gene therapy since they are recruited by and able to infiltrate tumours. This feature has been exploited by creating genetically modified MSCs that are able to combat cancer by delivering therapeutic molecules. Whether neuroblastomas attract systemically delivered MSCs is still controversial. We investigated whether MSCs engineered to express tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) could: i) cause death of classic and primary neuroblastoma cell lines in vitro; ii) migrate to tumour sites in vivo; and iii) reduce neuroblastoma growth in xenotransplantation experiments. We observed that classic and primary neuroblastoma cell lines expressing death receptors could be killed by TRAIL-loaded MSCs in vitro. When injected in the peritoneum of neuroblastoma-bearing mice, TRAIL-MSCs migrated to tumour sites, but were unable to change the course of cancer development. These results indicated that MSCs have the potential to be...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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ConclusionA new risk score system for patients with first recurrence of stage 4 neuroblastoma aged ≥18 months at diagnosis is proposed.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Publication date: Available online 17 October 2019Source: Cancer CellAuthor(s): Zulekha A. Qadeer, David Valle-Garcia, Dan Hasson, Zhen Sun, April Cook, Christie Nguyen, Aroa Soriano, Anqi Ma, Lyra M. Griffiths, Maged Zeineldin, Dan Filipescu, Luz Jubierre, Asif Chowdhury, Orla Deevy, Xiang Chen, David B. Finkelstein, Armita Bahrami, Elizabeth Stewart, Sara Federico, Soledad GallegoSummaryATRX alterations occur at high frequency in neuroblastoma of adolescents and young adults. Particularly intriguing are the large N-terminal deletions of ATRX (Alpha Thalassemia/Mental Retardation, X-linked) that generate in-frame fusion (...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
Pediatric cancers represent a wide variety of different tumors, though they have unique features that distinguish them from adult cancers. Receptor tyrosine kinases KIT and TrkA functions in AML and NB, respectively, are well-characterized. Though expression of these receptors is found in both tumors, little is known about KIT function in NB and TrkA in AML. By combining gene enrichment analysis with multidimensional scaling we showed that pediatric AMLs with t(8;21) or inv16 and high KIT expression levels stand out from other AML subtypes as they share prominent transcriptomic features exclusively with KIT-overexpressing ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Kim KW, Kim JY, Qiao J, Clark RA, Powers CM, Correa H, Chung DH Abstract Neuroblastoma remains one of the most difficult pediatric solid tumors to treat. In particular, the refractory and relapsing neuroblastomas are highly heterogeneous with diverse molecular profiles. We previously demonstrated that AKT2 plays critical roles in the regulation of neuroblastoma tumorigenesis. Here we hypothesize that targeting AKT2 could block the signal transduction pathways enhanced in chemo- and/or radiation-resistant neuroblastoma cancer stem-like cells. We found cell proliferation and survival signaling pathways AKT2/...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Publication date: 14 October 2019Source: Cancer Cell, Volume 36, Issue 4Author(s): Esther R. Berko, Yael P. MosséMechanisms of acquired resistance to ALK inhibition therapy in neuroblastoma have not yet been elucidated. In a recent issue of Nature, Debruyne et al. demonstrate that resistant MYCN-amplified ALK-mutated neuroblastoma cells overexpress BORIS, resulting in wide-ranging changes in chromatin interaction and transcriptional reprogramming.
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
Abstract PURPOSE: Immunotherapy promises unprecedented benefits to cancer patients. However, the majority of cancer types, including high-risk neuroblastoma remain immunologically unresponsive. High intensity focused ultrasound (HIFU) is a non-invasive technique that can mechanically fractionate tumors, transforming immunologically 'cold' tumors into responsive 'hot' tumors. EXPERIMENTAL DESIGN: We treated
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Ye Xu Successful cancer therapy requires drugs being precisely delivered to tumors. Nanosized drugs have attracted considerable recent attention, but their toxicity and high immunogenicity are important obstacles hampering their clinical translation. Here we report a novel “cocktail therapy” strategy based on excess natural killer cell-derived exosomes (NKEXOs) in combination with their biomimetic core–shell nanoparticles (NNs) for tumor-targeted therapy. The NNs were self- assembled with a dendrimer core loading therapeutic miRNA and a hydrophilic NKEXOs shell. Their successful fab...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
British Journal of Cancer, Published online: 11 October 2019; doi:10.1038/s41416-019-0594-3Monozygotic twins with neuroblastoma MS have a similar molecular profile: a case of twin-to-twin metastasis
Source: British Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
THURSDAY, Oct. 10, 2019 -- Early treatment with an immune-boosting therapy might improve the outlook of young children with an advanced form of cancer, a new small study suggests. The trial involved 43 children with high-risk neuroblastoma, a...
Source: Drugs.com - Daily MedNews - Category: General Medicine Source Type: news
CONCLUSIONS: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma. PMID: 31601569 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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