MICROFABRICATED DEVICES: A SIGNIFICANT ADVANCE FOR THE DETECTION AND MOLECULAR ANALYSES OF CIRCULATING CANCER CELLS?
Funder
National Health and Medical Research Council
Funding Amount
$422,107.00
Summary
Using advanced microfabrication concepts, this project aims to develop a platform technology able to capture tumour cells circulating in the blood of cancer patients. Although present only in extremely small numbers, these cells provide invaluable insights into the pathophysiology of the disease and consequently provide vital diagnostic and prognostic information. Molecular analyses of these cancer cells could ultimately enable the design of improved and personalized cancer treatment.
Improved Formulations Of Anti-cancer Agents 5-Fluorouracil And Oxaliplatin Using Excipient Technology
Funder
National Health and Medical Research Council
Funding Amount
$202,973.00
Summary
Chemotherapy plays a key role in cancer treatment, however, problems persist with severe adverse toxic effects. Combinations of anti-cancer agents give better results, but these agents still have major negative effects, for example, on veins and peripheral nerves and they must be given separately. We have developed a novel, all-in-one formulation of Oxaliplatin with 5-Fluorouracil and Leucovorin, with the potential for fewer toxic effects and improved patient care.
The steroid hormone estrogen plays a critical role in the development of human breast cancer. Anti-estrogen therapy has been believed to be an effective treatment of breast cancer over more than 100 years. However, the anti-estrogen therapy is still restricted mainly because of that estrogen has fundamental physiological actions and a wide range of beneficial effects on bone, brain, cardiovascular and other targeted tissues. Thus, it has become a primary focus of inquiry to understand how estrog ....The steroid hormone estrogen plays a critical role in the development of human breast cancer. Anti-estrogen therapy has been believed to be an effective treatment of breast cancer over more than 100 years. However, the anti-estrogen therapy is still restricted mainly because of that estrogen has fundamental physiological actions and a wide range of beneficial effects on bone, brain, cardiovascular and other targeted tissues. Thus, it has become a primary focus of inquiry to understand how estrogen specifically functions in breast cancer but not in normal tissues. Estrogen serves different functions involving a series of biochemical reactions called signal transduction pathways that can couple estrogen to a specific function, such as cancer formation. We have recently found that a enzyme named sphingosine kinase (SK) activation triggers a novel signal transduction pathway in regulation of cell growth and tumour formation, and that this pathway was activated by estrogen in human breast cancer cells. Thus, we seek to identify how estrogen activate SK and how they contribute to the development of breast cancer. It will ultimately provide a potential target for therapeutic intervention and may yield new compounds that have clinical benefit for anti-breast-cancer.Read moreRead less
In Vivo Models For Understanding The Cellular And Molecular Pathogenesis Of Barrett's Oesophagus
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce th ....The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce the normal layered structure of the human oesophageal lining in the laboratory and we propose to use these models to address key issues in the biology of Barrett's oesophagus. In aim 1, we wish to determine if the cells in patients with Barrett's have been permanently, or only transiently, altered and to understand the role of gastric acid- bile and accessory cells in this transformation. In aim 2 we will look more closely at the molecular changes that drive the cellular transformation characteristic of Barrett's. We will do this by manipulating the expression of selected genes in human oesophageal cells and assessing the effects of these genes on cell growth and differentiation using our cell culture models. The results of these studies will pave the way for the design of appropriate clinical strategies to treat Barrett's oesophagus and prevent the progression of this premalignant condition to oesophageal adenocarcinoma.Read moreRead less
Development Of DNA Phosphate Crosslinking Agents As Potential Anticancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar ....The principal difficulty in the treatment of the common solid tumours that cause the majority of cancer deaths is the problem of drug resistance. For example, many patients with cancer of the lung, breast or colon respond well to drug treatment with their tumours initially regressing, only to return later in an aggressive drug-resistant form. In this event, the inevitable outcome is that the tumour grows through drug treatment and the patient eventually succumbs and dies. This is also a familiar scenario in the treatment of adults with leukaemias and non-Hodgkins lymphomas. The underlying cause of drug resistance is the genetic instability of cancer cells which results in tumours that are heterogeneous, making it almost inevitable that a cancer cell will arise that is resistant to treatment. There are many mechanisms of resistance, some of which are peculiar to particular drug types, some are permeability barriers and some involve genetic deregulation of the biochemistry of cell death. Alkylating agents are one of the most important classes of anticancer drug. They bind irreversibly to the bases in DNA and weld the two strands of the double helix together. This cross-link is a powerful block to DNA replication and leads to the death of cancer cells by the process of programmed cell death. Cancer cells generally become resistant to alkylating agents by invoking repair mechanisms that remove the drug from the DNA bases, a response which breaks the cross-link and returns the DNA to its normal state. In this project, we are developing a new type of alkylating agent that reacts not with the DNA bases but with the phosphate groups of the DNA backbone. By this means the strands of DNA can again be cross-linked but now the linkage is between parts of the DNA that cancer cells cannot separate. In this way, we hope to be able to devise new drugs that are resistant to the normal mechanisms of DNA repair so that they will be active against drug-resistant tumours.Read moreRead less