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You searched for +publisher:"University of New South Wales" +contributor:("Trahair, Toby, Sydney Children\'s Hospital"). One record found.

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University of New South Wales

1. Byrne, Frances Louise. Investigation of stathmin's role in neuroblastoma drug resistance, differentiation and metastasis.

Degree: Children's Cancer Institute Australia for Medical Research, 2012, University of New South Wales

Neuroblastoma is a highly metastatic childhood cancer that originates from primitive cells of the neural crest and contributes to 15% of all paediatric cancer deaths. New drug targets are urgently required to improve treatment and survival outcomes for this disease. Stathmin is a microtubule destabilising protein highly expressed in neuroblastoma. Until now, stathmin’s functional role in this malignancy was unknown. Using an RNAi approach to suppress stathmin expression, stathmin’s function was determined in 2 independent neuroblastoma cell lines. Stathmin suppression did not influence neuroblastoma cell proliferation, drug resistance or anchorage-independent growth. However, stathmin suppression significantly inhibited retinoic-acid induced neurite formation and the migration and invasion of neuroblastoma cells. The cell cytoskeleton was also altered following stathmin suppression and resulted in increased tubulin polymer levels and the phosphorylation of the actin-regulatory proteins cofilin and myosin light chain (MLC). In addition, increases in cofilin and MLC phosphorylation, and reductions in cell invasion following stathmin suppression were reversed by treatment with the Rho associated coiled-coil forming protein kinase (ROCK) inhibitor, Y-27632, in neuroblastoma cells. This data indicated that stathmin regulated neuroblastoma cell migration and invasion via the cell cytoskeleton and that stathmin may influence neuroblastoma metastasis. To examine this phenotype in vivo, stable stathmin-suppressed/luciferase-expressing neuroblastoma cells were orthotopically injected into the left adrenal fat pad of SCID-Beige mice and tumour growth was monitored weekly by bioluminescent imaging (BLI). Stathmin did not influence neuroblastoma tumour growth. In contrast, stathmin suppression significantly reduced metastatic neuroblastoma tumour burden in the lungs of mice by 71% (p<0.01) compared to controls, as determined by BLI. In conclusion, this study has highlighted novel roles for stathmin in neuroblastoma neurite outgrowth, cell migration and invasion. Furthermore, this research has provided the first direct evidence that stathmin regulates neuroblastoma metastasis in vivo and that suppressing stathmin in neuroblastoma may reduce metastatic spread. Therapeutics designed to target stathmin in neuroblastoma may therefore improve treatment and ultimately survival rates for this deadly childhood cancer. Advisors/Committee Members: Kavallaris, Maria, Children's Cancer Institute Australia for Medical Research, Faculty of Medicine, UNSW, McCarroll, Joshua, Children's Cancer Institute Australia for Medical Research, Faculty of Medicine, UNSW, Trahair, Toby, Sydney Children's Hospital.

Subjects/Keywords: Stathmin; Neuroblastoma; Metastasis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Byrne, F. L. (2012). Investigation of stathmin's role in neuroblastoma drug resistance, differentiation and metastasis. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/51779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10446/SOURCE02?view=true

Chicago Manual of Style (16th Edition):

Byrne, Frances Louise. “Investigation of stathmin's role in neuroblastoma drug resistance, differentiation and metastasis.” 2012. Doctoral Dissertation, University of New South Wales. Accessed July 16, 2019. http://handle.unsw.edu.au/1959.4/51779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10446/SOURCE02?view=true.

MLA Handbook (7th Edition):

Byrne, Frances Louise. “Investigation of stathmin's role in neuroblastoma drug resistance, differentiation and metastasis.” 2012. Web. 16 Jul 2019.

Vancouver:

Byrne FL. Investigation of stathmin's role in neuroblastoma drug resistance, differentiation and metastasis. [Internet] [Doctoral dissertation]. University of New South Wales; 2012. [cited 2019 Jul 16]. Available from: http://handle.unsw.edu.au/1959.4/51779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10446/SOURCE02?view=true.

Council of Science Editors:

Byrne FL. Investigation of stathmin's role in neuroblastoma drug resistance, differentiation and metastasis. [Doctoral Dissertation]. University of New South Wales; 2012. Available from: http://handle.unsw.edu.au/1959.4/51779 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10446/SOURCE02?view=true

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