Dataset Information

Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies.

ABSTRACT: Limited research exists regarding the most aggressive forms of hepatoblastoma. Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not only difficult to attain but also challenging to characterize histologically. A community-driven approach to educating parents and families, regarding the need for donated tissue, is necessary for scientists to have access to resources for murine models and drug discovery. Herein, we describe the currently available resources, existing gaps in research, and the path to move forward for uniform cure of hepatoblastoma.

SUBMITTER: Rikhi RR

PROVIDER: S-EPMC4800278 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies.

Rikhi Rishi Raj RR Spady Kimberlee K KK Hoffman Ruth I RI Bateman Michael S MS Bateman Max M Howard Lisa Easom LE

Frontiers in pediatrics 20160321

Limited research exists regarding the most aggressive forms of hepatoblastoma. Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not only difficult to attain but also challenging to characterize histologically. A community-driven approach to educating parents and families, regarding the need for donated tissue, is necessary for scientists to have access to resources for murine models and drug discovery. Herein, we describe the currently available resources, existing gaps ...[more]

PMID: 27047905

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Project description:Tumours contain heterogeneous cell populations. A population enriched in tumour-initiating potential has been identified in soft-tissue sarcoma (STS) by the isolation of side population (SP) cells. In this study, we compared the gene expression profiles of SP and non-SP cells in STS and identified Hedgehog (Hh) and Notch pathways as potential candidates for the targeting of SP cells. Upon verification of the activation of these pathways in SP cells, using primary tumor xenografts in NOD-SCID mice as our experimental model, we used the Hh blocker Triparanol and the Notch blocker DAPT to demonstrate that the suppression of these pathways effectively depleted the abundance of SP cells, reduced tumour growth, and inhibited the tumour-initiating potential of the treated sarcoma cells upon secondary transplantation. The data provide additional evidence that SP cells act as tumour initiating cells and points to Hh and Notch pathways as enticing targets for developing potential cancer therapies. We used microarrays to detail the difference in gene expressions between the side population cells in soft-tissue sarcoma in comparison to the bulk non-side-population cells. To examine whether certain pathways may be differentially regulated in SP cells versus non-SP cells, which represent the bulk of tumour cells, we compared the gene expression profiles of SP and non-SP cells in four primary STS tumours each from different patient. Upon surgical excision, these tumours were dissociated mechanically and enzymatically into individual cells. Via Hoechst dye staining and flow-cytometry, these primary tumour cells were sorted into distinct side population and non-side population fractions. Total RNA is extracted from an equal number of SP and NSP cell from each primary tumour. cDNA from each sample was generated from the isolated total RNA and hybridized onto Affymetrix Human Genome EukGE-WS2v4 gene chips against the same reference cDNA library. After initial processing of the raw data, using the Genespring® GX software, the expression of SP cells from each tumour was normalized against the expression of the corresponding non-SP cells. A gene list was constructed by selecting genes that were regulated in the same direction (SP vs. NSP) in all sample pairs with a fold change greater than 1.25. This list was examined using Genespring® GX significant pathway function to identify differentially regulated pathways.

Dataset Information

Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies.

Publications

Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies.

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