Conditionally Replicative Adenoviruses For Mesothelioma Therapy
Funder
National Health and Medical Research Council
Funding Amount
$260,600.00
Summary
Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy ....Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy relies on selective viral replication in (and therefore death of) tumour cells but not normal cells. In principle, mesothelioma is an attractive target for this therapeutic approach owing to its propensity to remain localised to the pleural space until late in the disease. However, for any CRAd strategy to succeed, viral replication must be limited to the tumour cells so as not to cause unnecessary toxicity to normal tissues. This level of specificity can potentially be achieved by using cell-specific promoters to control the expression of viral genes essential for replication. To date however, there have been no reports evaluating candidate mesothelioma-specific promoters in adenoviral vectors. Furthermore, other issues such as tumour a lack of viral receptors or tumour-associated fibrosis could limit viral spread through a mesothelioma mass and reduce the efficacy of the approach. In this proposal we will contruct and test CRAds which are controlled by promoters which we believe will be highly active in mesothelioma, but very poorly active in other tissues. We will test the ability of these new agents to kill mesothelioma cells in tissue culture, in pieces of mesothelioma tumours removed from patients, and in animal models. If successful, this approach could offer new hope for mesothelioma patients.Read moreRead less
Regulation Of Sympathetic Vasomotor Function By Brain Angiotensin: Cell-specific Modulation Of Function In Vivo.
Funder
National Health and Medical Research Council
Funding Amount
$354,975.00
Summary
Adequate blood pressure is necessary for normal function. High blood pressure occurs in a proportion of the human population and causes many diseases such as stroke and heart failure. The factors producing high blood pressure are not known for most people who have this condition. We are investigating the role of the brain in the regulation of blood pressure and in this application we are testing whether increased activity in certain brain regions can cause high blood pressure.
Combined Novel Tumour-targeted Molecular And Traditional Chemotherapy For Treating Androgen Refractory Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$551,398.00
Summary
Consistent with Cancer Australia and PCFA priorities, in preclinical studies we will evaluate triple therapy for advanced prostate cancer.The three treatments to be tested together are adenoviruses, gene therapy and docetaxel, each of which has therapeutic potential individually. The combination should increase therapeutic effiacy and decrease the doses required, thus reducing side effects and increasing quality of life. Results obtained should enable translation to a clinical trial.