A Methylation-Based Assay For The Detection Of Prostate Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$303,712.00
Summary
Prostate Cancer is a major cause of death and morbidity among men in the western world. Little is understood of the early events that lead to the development of prostate cancer though recent evidence suggests that a modification of the DNA called methylation may be an early indictor of disease. Our current work has shown that a gene involved in the detoxification of the cell (called GST) is switched off in over 90% of prostate cancers by this DNA modification. We have studied the methylation pat ....Prostate Cancer is a major cause of death and morbidity among men in the western world. Little is understood of the early events that lead to the development of prostate cancer though recent evidence suggests that a modification of the DNA called methylation may be an early indictor of disease. Our current work has shown that a gene involved in the detoxification of the cell (called GST) is switched off in over 90% of prostate cancers by this DNA modification. We have studied the methylation pattern of the GST gene in prostate cancer and normal prostate tissue and found that the GST gene is modified exclusively in the cancer tissue . This important information has allowed us to design a test to specifically identify prostate cancer cells by assaying for GST modification . In this grant we plan to further optimise this test to ensure its sensitivity and reliability. In particular we plan to compare the effectiveness of our methylation-based test to the PSA and other tests currently used for the detection of prostate cancer. In addition we plan to identify other genes that also may be switched off specifically in prostate cancer by DNA methylation. This data will allow the development of new markers and approaches to stage the progression of prostate and possibly other cancers.Read moreRead less
Glutathione Transferase-derived Compounds As Therapeutic Agents
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
Inhibition of cardiac calcium ion channels may be an effective new way of improving heart performance in patients with heart failure. This project will investigate how a glutathione transferase enzyme inhibits calcium ion channels in the heart and if small fragments of a muscle specific glutathione transferase can be used to specifically modify cardiac ryanodine receptor function. These fragments will provide the basis for the development of a new therapeutic approach.
Pharmacogenetic Investigations Of Glutathione Transferases
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. This study will investigate (1)the genetic mechanisms that alter the production of glutathione transferases, (2) the character ....Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. This study will investigate (1)the genetic mechanisms that alter the production of glutathione transferases, (2) the characteristics of a new class of glutathione transferases and (3) the role of glutathione transferase A4 in protecting against disorders such as atherosclerosis and Parkinson's disease.Read moreRead less
Glutathione Transferase Deficient Mice To Probe For Adverse Drug Reactions
Funder
National Health and Medical Research Council
Funding Amount
$562,933.00
Summary
A family of enzymes called glutathione transferases (GST) that metabolize foreign chemicals and therapeutic drugs have been shown to be a significant cause of drug resistance in cancer chemotherapy. It has been suggested that inhibitors of GSTs could be used in cancer treatment to counter drug resistance or to slow the metabolism and enhance the activity of some drugs. Some GSTs carryout important enzymatic reactions with endogenous substrates and others have important non-enzymatic functions su ....A family of enzymes called glutathione transferases (GST) that metabolize foreign chemicals and therapeutic drugs have been shown to be a significant cause of drug resistance in cancer chemotherapy. It has been suggested that inhibitors of GSTs could be used in cancer treatment to counter drug resistance or to slow the metabolism and enhance the activity of some drugs. Some GSTs carryout important enzymatic reactions with endogenous substrates and others have important non-enzymatic functions such as the regulation of signaling pathways within cells and the modulation of calcium ion channels that are involved in muscle contractions. The generic inhibition of all GSTs could therefore have significant adverse physiological effects. We propose to make mice deficient in specific GSTs and to study their physiological responses. The results of these studies will indicate which GSTs can be safely inhibited without the risk of deleterious side effects. These studies are important because adverse reactions to therapeutic drugs are a significant cause of hospital admissions and death.Read moreRead less