The Roles Of EZH2 And FOXO1A In CNS-PNET Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$467,517.00
Summary
Although CNS-PNETs are the most common embryonal CNS tumours of childhood and cause significant mortality and morbidity, there is a very limited understanding of the pathogenesis of this aggressive disease. This situation is a major handicap to the development of more specific and effective therapies. While a better understanding of the fundamental pathology of CNS-PNETs will have immediate diagnostic implications, the elucidation of the biochemical pathways that are disrupted in these tumours w ....Although CNS-PNETs are the most common embryonal CNS tumours of childhood and cause significant mortality and morbidity, there is a very limited understanding of the pathogenesis of this aggressive disease. This situation is a major handicap to the development of more specific and effective therapies. While a better understanding of the fundamental pathology of CNS-PNETs will have immediate diagnostic implications, the elucidation of the biochemical pathways that are disrupted in these tumours will facilitate the design of new drugs that are specifically directed towards the critical proteins in these pathways. The identification of specific genes and-or pathways that are deregulated in CNS-PNET cells is essential for the development of safer, more directed, and more effective therapies that are urgently required for the treatment of those with this devastating disease.Read moreRead less
Sellar Masses, Pituitary Adenomas And Pathways Of Pituitary Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$90,917.00
Summary
Pituitary tumours encompass a number of pathologies. Their cause is not clearly established. Pituitary adenomas are one of the most frequent intracranial tumours. The genetics of sporadic tumours is unknown. Craniopharyngiomas are rare brain tumours arising in the pituitary stalk area that can have profound effects, presenting in childhood or later. To date there is limited knowledge on the cell signaling pathways causing these tumors, which can help to understand cancer in general.
Role Of Betaglycan In Gonadal And Adrenal Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
TGF-beta and inhibin are related multifunctional growth factors which regulate a number of important cellular functions, including proliferation, differentiation, and survival. Betaglycan is a cell-surface protein that binds both inhibin and TGF-beta. Betaglycan appears to regulate the binding and availability of the TGF-betas and inhibins to their signaling receptors, and its presence on the cell surface increases the efficiency of TGF-beta and inhibin function. Deletion of the inhibin gene in ....TGF-beta and inhibin are related multifunctional growth factors which regulate a number of important cellular functions, including proliferation, differentiation, and survival. Betaglycan is a cell-surface protein that binds both inhibin and TGF-beta. Betaglycan appears to regulate the binding and availability of the TGF-betas and inhibins to their signaling receptors, and its presence on the cell surface increases the efficiency of TGF-beta and inhibin function. Deletion of the inhibin gene in mice produces tumours in the ovary, testis, and adrenal gland in 100% of the mice. In this current proposal, we will delete the betaglycan gene in the primary target tissues for inhibin (the anterior pituitary and gonads). The hypothesis we are testing is that the loss of a co-receptor for inhibin (i.e. betaglycan) results in a loss of cellular sensitivity to inhibin, thus resulting in altered growth characteristics which predispose the gonads and adrenals to cancer. We will examine these cells in culture and in living animals to determine whether our hypotheses are correct. We will also conduct a series of histological, biochemical, and biological experiments in order determine the underlying causes of any observed growth dysregulation. This work is expected to yield information relevant to the role of betaglycan in inhibin-TGFb-regulated processes in normal and cancerous growth, which may allow future design of therapies for cancer.Read moreRead less
Inherited determinants of cancer aetiology. Family history of cancer is a strong risk factor for many cancers. This project will aim to identify inherited factors influencing risk of developing cancer and those factors influencing the course of the disease and outcomes.
A Systematic Evaluation Of The Neurosurgical Application Of Peri-operative And Intra-operative MR Tractography In Different Paediatric Disease States
Funder
National Health and Medical Research Council
Funding Amount
$130,910.00
Summary
My research investigates changes in brain nerve fibre tracts/white matter in paediatric disease states and changes related to surgery by using nerve fibre tract imaging before, during and after surgery. It will also generate an imaging atlas to help understand white matter pathway development. It then serves as normative comparison to better understand aberrations in diseased neural pathways. The outcome will aid understanding in brain development, recovery and plasticity, and helps improve whit ....My research investigates changes in brain nerve fibre tracts/white matter in paediatric disease states and changes related to surgery by using nerve fibre tract imaging before, during and after surgery. It will also generate an imaging atlas to help understand white matter pathway development. It then serves as normative comparison to better understand aberrations in diseased neural pathways. The outcome will aid understanding in brain development, recovery and plasticity, and helps improve white matter lesion localisation.Read moreRead less
Diagnosing Chromosomal Translocations In Solid Tumours
Funder
National Health and Medical Research Council
Funding Amount
$410,997.00
Summary
Mis-repair of broken chromosomes can fuse together genes that then cause cancer. Current clinical tests are only capable of detecting single well-known gene fusions and are incapable of identifying new fusion events or fusion variations. We have developed a diagnostic technology, termed CaptureSeq, that is capable of finding all fusion genes in a patient sample. In this grant, we will demonstrate the use and advantages of CaptureSeq for diagnosing fusion genes in cancer patients.
A 2:1 Randomised Phase II Study Of NivolUmab And Temozolomide Vs Temozolomide In Methylated Newly Diagnosed Elderly Glioblastoma (NUTMEG)
Funder
National Health and Medical Research Council
Funding Amount
$1,608,845.00
Summary
Radiotherapy and Temozolomide (TMZ) chemotherapy treatment for the brain tumour glioblastoma (GBM) is not as effective in elderly patients. If their tumour has a genetic marker called "methylated MGMT", TMZ does work relatively better and is often given alone. Elderly GBM patients with this marker will be randomly selected in this trial to have TMZ alone or TMZ + Nivolumab - a drug that assists the immune system to attack cancer.