Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western soc ....Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western societies (namely acid reflux, obesity and poor diet), there are strong grounds for predicting that incidence will continue to rise, and that oesophageal cancer will constitute an increasingly large burden on society. Unfortunately, treatment options are limited, survival is often short, and there is no way of identifying which tumours will respond to therapy. This proposal will collect treatment and health outcomes data for a population-based cohort of patients with oesophageal cancer. The goal is to identify prognostic and predictive markers to aid patients and clinicians when making treatment decisions, as now exist for breast cancer. Such markers may also serve as novel targets for therapy. The proposed study builds upon the platform of the Australian Cancer Study [ACS], one of the world's largest studies of oesophageal cancer. This represents a unique opportunity to investigate a pressing clinical problem by building upon a study of acknowledged international importance.Read moreRead less
Improving The Surgical Outcomes For Barretts-derived Oesophageal Adenocarcinoma Through Early Detection.
Funder
National Health and Medical Research Council
Funding Amount
$796,144.00
Summary
Some people with severe reflux develop Barrett's oesophagus, which puts them at high risk of developing cancer. Patients with Barrett's can be monitored by regular endoscopy to detect cancer early enough so that they can be treated successfully with surgery. The aim of this work is to identify patients who are at highest risk of cancer using molecular biomarkers. We will then determine the cost effectiveness of using biomarkers for surveillance of patients with Barrett's oesophagus.
Role Of The Tissue Kallikrein-kinin System In Abdominal Aortic Aneurysm Formation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$457,779.00
Summary
Up to 5% of people over 60 years develop weakening of their aorta leading to slow dilation of the vessel, which may burst resulting in sudden death. The only treatment is surgery, which has complications and is unsuitable for some patients. Drugs which slow the disease would be invaluable. We have identified a role for kinins in aneurysms. We will investigate how these molecules contribute to aortic disease and if blocking them can be used as a basis for medical treatment of artery weakening.
Barrett's Oesophagus And Reflux Oesophagitis : Efficacy Of Medical Vs Surgical Management
Funder
National Health and Medical Research Council
Funding Amount
$510,750.00
Summary
Gastro-oesophageal reflux disease is very common. In some people it leads to oesophageal cancer, which is increasing in incidence more rapidly than any other cancer in the developed world. Significant resources are required for its diagnosis, surveillance and treatment. There are two main forms of treatment, acid suppressing drugs which may be required for the rest of the person's life, or surgery. The goal of treatment is the control of the symptoms such as heartburn, and the prevention of canc ....Gastro-oesophageal reflux disease is very common. In some people it leads to oesophageal cancer, which is increasing in incidence more rapidly than any other cancer in the developed world. Significant resources are required for its diagnosis, surveillance and treatment. There are two main forms of treatment, acid suppressing drugs which may be required for the rest of the person's life, or surgery. The goal of treatment is the control of the symptoms such as heartburn, and the prevention of cancer. It is relatively easy to determine if the symptoms are controlled, and both medical and surgical treatments do this. It is not as easy to measure if a treatment will reduce the risk of cancer, because it takes so long to develop. We will compare a group of patients with reflux disease treated with drugs with a group treated by surgery. In each group we will take oesophageal tissue before treatment and compare it with similar tissue taken after treatment. We will look for reductions in abnormal cells and genes that are in diseased tissue and are important in the development of cancer. This study will help us understand the mechanisms by which reflux causes damage to the oesophagus and how it ultimately leads to cancer. We will learn if medical or surgical treatment is better in healing the underlying damage in the oesophagus, and which treatment is more likely to prevent cancer developing. It may result in more effective management of reflux in our community and help reduce the number of cases of oesophageal cancer.Read moreRead less
Prospective Evaluation Of A Model To Predict Outcomes Following Endovascular Aortic Aneurysm Repair
Funder
National Health and Medical Research Council
Funding Amount
$1,098,901.00
Summary
Once present, abdominal aortic aneurysms tend to enlarge over time resulting in an increased risk of death if they rupture. Endovascular aneurysm repair may be used to fix the aneurysm but this procedure can result in complications over time. We developed a model that uses pre-operative information to predict the chance of an individual having poor results.This study aims to assess whether the model is a good predictor of outcomes and whether extra information will improve its accuracy.
Mechanisms Of CD44v2-10-mediated Tumour Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, includi ....Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, including tumour progression and metastasis. CD44 has considerable molecular diversity and its broad range of known biological activities suggests that multiple domains in the molecule may confer different biological functions. The core CD44 molecule, termed CD44s, is the most commonly expressed CD44 molecule. CD44 variants (termed CD44v) are much more restricted in their expression in normal tissues, and hence may make specific targets for anti-metastasis therapy. We have shown that CD44 variants are expressed by colorectal tumours from the earliest stages of tumour development, and that theses variants are found to be expressed by colorectal hepatic metastases. We targeted two key domains in the variants and found that by inhibiting expression in these domains we showed complete abrogation of metastasis, and of primary tumour growth in mice. Hence these domains in the CD44 molecule are directly involved in cancer spread. We propose to investigate the mechanisms by which specificdomains in the CD44 variants actually cause tumour spread. Understanding of the various mechanisms involved in tumour spread, and targeting the functions of the domains has enormous potential as a therapeutic target.Read moreRead less
Improved Ex-vivo Culture Of Keratinocytes For Clinical Applications
Funder
National Health and Medical Research Council
Funding Amount
$275,203.00
Summary
Skin cells grown for clinical applications currently require animal-derived cells and-or non-defined products for their expansion in the laboratory; these reagents can potentially infect patients who receive these therapies. This project will identify the essential components provided by these reagents and develop a fully synthetic and defined culture system. This improvement will provide safer, cost-effective grafts and cell-based therapies that will benefit patients suffering burns and wounds.
Optimizing Implanted Cell Survival Using A Tissue Engineering Model
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
Cell therapy and tissue engineering involve the insertion of specific cells into damaged tissues or into a bioraector in a patient's body to generate new replacement tissues. This project seeks to improve two factors associated with inserting cells : 1. The innate survival characteristics of the cells being inserted, and 2. The blood vessel supply at the site of insertion. These techniques will greatly improve the survival of inserted cells.