Colorectal Cancer - Molecular Basis To Targeted Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$19,818,386.00
Summary
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
EGF Receptor Transactivation In GPCR-mediated Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$710,625.00
Summary
Soon after birth, the muscle cells of the human heart stop dividing and subsequent growth of the heart occurs through enlargement of pre-existing muscle cells in a process referred to as hypertrophy. This normal growth accounts for the difference in size between juvenile and adult human hearts. In certain people, heart cell growth is accelerated as a consequence of complex genetic, hormonal and environmental factors. In others, it occurs as an adaptive response to high blood pressure or damage-d ....Soon after birth, the muscle cells of the human heart stop dividing and subsequent growth of the heart occurs through enlargement of pre-existing muscle cells in a process referred to as hypertrophy. This normal growth accounts for the difference in size between juvenile and adult human hearts. In certain people, heart cell growth is accelerated as a consequence of complex genetic, hormonal and environmental factors. In others, it occurs as an adaptive response to high blood pressure or damage-disease of the heart muscle, such as occurs following a heart attack. As hearts grow inappropriately, they function less efficiently and eventually fail. Cardiac hypertrophy is therefore a major risk factor for heart failure and death. Hormones like adrenalin, angiotensin, and endothelin affect cells of the heart and blood vessels to regulate blood pressure and volume. In addition, these hormones also act directly on heart cells to cause growth, particularly during the accelerated phase associated with cardiac hypertrophy. One attribute shared by these hormones is that they act through G-protein coupled receptors (GPCRs), a superfamily of cell surface proteins. How binding of hormone to its specific GPCR triggers cell growth has been the focus of extensive research. Based on studies of angiotensin receptors in cultured muscle cells, we have observed that the growth action of angiotensin receptors requires them to first hijack another receptor - the epidermal growth factor receptor. By commandeering the EGF receptor, the angiotensin hormone in effect usurps growth-signalling pathways. This application proposes experiments that will investigate the mechanism and consequence of GPCRs stimulation of EGF receptors in heart cells and whole animals. By understanding the mechanism by which angiotensin promotes growth, better therapeutic regimens against abnormal growth of the heart during human cardiovascular disease will evolve.Read moreRead less
Radioimmunotherapy is an experimental method of cancer treatment, involving the use of radioactive isotopes, which are targeted to tumour cells using specific molecules as carriers. These carriers are known as anti-tumour antibodies, and they bind specifically to tumour cells. Recent advances in molecular biology and in the understanding of the nature of tumour cells has resulted in the development of improved anti-tumour antibodies, and such improvements can be expected to continue. However, th ....Radioimmunotherapy is an experimental method of cancer treatment, involving the use of radioactive isotopes, which are targeted to tumour cells using specific molecules as carriers. These carriers are known as anti-tumour antibodies, and they bind specifically to tumour cells. Recent advances in molecular biology and in the understanding of the nature of tumour cells has resulted in the development of improved anti-tumour antibodies, and such improvements can be expected to continue. However, this project is concerned not with the tumour targeting aspect of radioimmunotherapy, but rather with the payload or cytotoxic mechanism, in which the radiation damage is focused on the DNA of the cell. In summary, the project explores a new approach in cancer radioimmunotherapy. This approach will be evaluated firstly in cultures of tumour cells and then in mice bearing transplanted tumours. If successful this project will result in the development of a new cell kill technology that can be combined with different anti-tumour antibodies.Read moreRead less
Muscle cells that constitute the bulk of the human heart do not divide but enlarge as we grow. Accelerated heart cell growth, as a consequence of heart damage or other factors, is a predictor of heart failure and early death. This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. By understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease will evolve.