Targeting The AGE-RAGE Axis In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$542,859.00
Summary
Based on extensive preliminary data we porpose that the AGE intercation with RAGE plays an important role in diabetes associated atherosclerosis. We will perform studies using a soluble form of the receptor RAGE which will trap AGEs in the blood and tissues and thus prevent diabetes related blood vessel damage. Furthermore, we will investigate if RAGE receptor on inflammatory cells such as macrophages plays a pivotal role in blood vessel injury in diabetes.
Role Of Circulating Advanced Glycation End Products (AGEs) In Diabetic Nephropathy: Effect Of Benfotiamine Intervention
Funder
National Health and Medical Research Council
Funding Amount
$465,000.00
Summary
Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that all ....Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that allow the comprehensive quantification of individual AGE levels in blood. Our study involves the comparison of AGE blood levels, as a group or as specific AGEs with markers of diabetic kidney disease such as albumin (protein) excretion in the urine and the rate that the kidney filters the blood to form urine (glomerular filtration rate). Benfotiamine is a thiamine (vitamin B1) derivative that has been shown to decrease the formation of AGEs and to prevent kidney disease in diabetic animals. The present clinical study will assess whether benfotiamine has similar effects on AGEs and kidney disease in patients with type 2 diabetes. If successful, this study has the potential to provide a new treatment strategy for diabetic kidney disease in humans.Read moreRead less
Proteolytic And Non-proteolytic Roles For PSA And Related Kallikrein Serine Proteases In Prostate Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$480,128.00
Summary
Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the pri ....Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the primary tumour and out of the prostate, it is possible that high production of these kallikrein enzymes by prosttae cancer cells may increase the ability of these cells to metastasise. In previous work, we have studied prostate cancer cells that we have engineered to make the kallikreins, PSA and kallikrein 4. Those cells that make PSA or kallikrein 4 are more elongated in shape and are better able to move across a porous barrier. Another important change is that these cells stop producing a protein that is usually found on the surface of these cells and is important for helping cells to stay attached to each other. When this protein is lost, these tumour cells no longer stay attached to each other and are more likely to move out of the prostate and spread into other parts of the body. The changes we observed in the cells that produce PSA and kallikrein 4 are typical of these more aggressive cancer cells. In this project, we will look at how PSA and kallikrein 4 cause the cells to undergo these changes. The majority of prostate cancer deaths arise from cancer that has spread from the primary tumour and out of the prostate capsule. This project aims to further understand the causes of prostate cancer spread and metastasis. This is a vital research priority if we are to address the mortality associated with prostate cancer metastasis and may lead to new treatment approaches for advanced metastic prostate cancer.Read moreRead less