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Targeting calcium signalling pathways to control medulloblastoma

Citation

Azimi, I, Targeting calcium signalling pathways to control medulloblastoma, 16th Meeting of Asian Society for Neuro-Oncology, 26-29 September 2019, Taipai, Taiwan (2019) [Conference Extract]


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Abstract

Background: Medulloblastoma (MB) is the most common malignant childhood brain tumour. MB contains four molecular subgroups of WNT, SHH, Group 3 and Group 4. Groups 3 and 4 (accounting for >60% of all MBs) are associated with high metastasis and poor patient survival rate of around 60%. Due to the harsh nature of current treatments (surgery, radio/chemotherapy), children who survive the cancer often show impaired physical and cognitive function. There is therefore a clear need for new treatment options for these aggressive MBs. Calcium ion is an intracellular messenger involved in a variety of cellular processes from gene expression to cell growth and death. Calcium signalling is also widely implicated in a variety of the cancer hallmarks including proliferation, angiogenesis and metastasis are regulated by calcium signalling.

Methods: Gene expression of calcium transporters were evaluated in in-silico analysis of tumours from four molecular subgroups. Expression of transporters with higher levels in aggressive Groups 3/4 MB were further correlated with metastasis and patient survival rates. In-vitro analysis assessed the effect of pharmacological inhibition of selected transporters on cell proliferation (WST-1 assay), metabolism (ATP assay), cologenicity and sphere formation ability of MB cells.

Results: in-silico analysis revealed overexpression of specific calcium channels in Groups 3 and 4 MB and their correlation with metastasis and patient survival rates. In-vitro analysis of a member of the transient-receptor potential (TRP) channels (as one of the identified transporters from the in-silico analysis), demonstrated its upregulation in MB cell lines corresponding to Groups 3 and 4. Pharmacological inhibition of this channel, concentration- dependently inhibited proliferation of D341 cells and sphere formation of CHLA-01R-MED cells.

Conclusion: These studies identified specific calcium channels as potential critical proteins in MB progression. Further studies are warranted to evaluate the potential of targeting these proteins for the control of MB

Item Details

Item Type:Conference Extract
Keywords:calcium signalling, medulloblastoma
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:151235
Year Published:2019
Deposited By:Pharmacy
Deposited On:2022-07-25
Last Modified:2022-07-28
Downloads:0

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