This project aims to develop a new therapy for colorectal cancer (CRC). We have already demonstrated that a molecule called PAK1 is the master regulator of several intracellular signalling pathways, and is essential for CRC growth and invasion. We now plan to study whether inhibitors that block PAK1 activity can prevent the growth of human CRC cells in the laboratory or their development into tumours in animals.
Regulation Of Gastric Tumour Invasion And Growth By Gp130 Activating Cytokines.
Funder
National Health and Medical Research Council
Funding Amount
$625,642.00
Summary
Gastric cancer is a major cause of morbidity and death worldwide. We have previously established a very informative animal model of this disease which has facilitated a new understanding of the diverse role of the IL-6 family of cytokines in regulating gastric tumour growth and dissemination to distant organs. This proposal will focus on how the main members of this cytokine family, namely IL-6 and IL-11, inhibit gastric tumour invasion to other organs, and promote tumour growth respectively . A ....Gastric cancer is a major cause of morbidity and death worldwide. We have previously established a very informative animal model of this disease which has facilitated a new understanding of the diverse role of the IL-6 family of cytokines in regulating gastric tumour growth and dissemination to distant organs. This proposal will focus on how the main members of this cytokine family, namely IL-6 and IL-11, inhibit gastric tumour invasion to other organs, and promote tumour growth respectively . An understanding of these processes will aid in designing therapeutic interventions specific for each cytokine and which may lead to drugs aimed at limiting or reversing this disease.Read moreRead less
Epithelial - Stromal Interactions In Pancreatic Cancer: Role Of Pancreatic Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$425,750.00
Summary
The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for ....The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for novel approaches to this lethal disease. The proposed project involves an examination of the local tissue reaction around pancreatic cancer. This tissue reaction is usually prominent and the cells involved may determine the extent of local and distant spread of the cancer. Modulation of this tissue reaction may limit pancreatic cancer growth and thus improve outcome.Read moreRead less
CpG Island Methylation In Microsatellite Stable Colorectal Cancers: Epigenetics Or Epiphenomenon?
Funder
National Health and Medical Research Council
Funding Amount
$245,402.00
Summary
For years researchers have known that changes in the sequence of DNA in genes within a cell can lead to cancer, particularly when those changes are passed on to daughter cells. This has lead to massive research interest in the field of cancer genetics. In the last few years, it has become clear that as well as changes in DNA, other more subtle changes can be passed on. These changes, which do not directly involve changes in DNA sequence, are referred to as epigenetic changes. One of the most com ....For years researchers have known that changes in the sequence of DNA in genes within a cell can lead to cancer, particularly when those changes are passed on to daughter cells. This has lead to massive research interest in the field of cancer genetics. In the last few years, it has become clear that as well as changes in DNA, other more subtle changes can be passed on. These changes, which do not directly involve changes in DNA sequence, are referred to as epigenetic changes. One of the most commonly recognised epigenetic changes is known as methylation. Methylation of genes can switch that gene off, meaning that the protein normally made is no longer present in the cell. This can have profound effects on the way cells behave, and importantly may be involved in the development of cancer. In this study, we will look at a group of colorectal cancers that show abnormally high amounts of DNA methylation , to test our hypothesis that these cancers share a common origin that is distinct from the usual type of bowel cancer. The findings will be important, as they may allow us to show that all bowel cancers are not the same, and that simple gene testing may be able to identify the different subtypes. If bowel cancers can be classified according to the way in which they have developed, then this will help us to understand what causes them why some are more aggressive than others, and why some may respond differently to existing or future cancer treatments.Read moreRead less
Studies Of Genetic Predisposition To Develop Serrated Neoplasia In The Colorectum.
Funder
National Health and Medical Research Council
Funding Amount
$308,291.00
Summary
Colorectal Cancer was once believed to develop only from a certain kind of polyp in the colon called the adenoma. However, recently another type of polyp called the hyperplastic polyp was found to also be capable of producing a cancer. In this proposal, we will look at the possibility that the predisposition to form hyperplastic polyps may be inherited in families.
Role Of Gastrin Prohormones In The Development Of Gastrointestinal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
Gastrin is a stomach hormone which increases acid secretion and the growth of the stomach and bowel. This growth promoting effect may be involved in a number of cancers particularly colon cancer. The different types of gastrin have different effects but we do not know which forms are important and whether all are active. The types and activity of different gastrins will be investigated using cell lines, animal models and colon cancer patients with the view of establishing new treatments.
Defining Iron And Haem-induced Pro-carcinogenic Pathways Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$566,277.00
Summary
Colorectal cancer is very common in Western society. Population studies have reported that high consumption iron-containing foods and red meat, the latter being a source of both haem and iron, are risk factors for colorectal cancer. This study will identify the levels of dietary haem and iron that promote colorectal cancer development. Also, it will determine the mechanisms and relative contribution of iron and haem to pro-carcinogenic pathways that result in colorectal cancer.
Characterization Of ARL6IP5 In Hepatitis C-related Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,283.00
Summary
The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hep ....The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hepatitis C leads to cancer.Read moreRead less
Molecular Markers Of The Progression Of Intestinal Metaplasia To Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$556,618.00
Summary
Gastric cancer (GC) is the second most common cause of cancer-related death globally. It is a surgically treatable disease that has good prognosis if detected at an early stage. The majority of patients in our community are detected at a late stage, where less than 20% of patients survive 5 years. The majority of GC is preceded by distinct histological stages that follow a progression from gastric mucosal inflammation, intestinal metaplasia (IM) and eventually cancer. These stages are characteri ....Gastric cancer (GC) is the second most common cause of cancer-related death globally. It is a surgically treatable disease that has good prognosis if detected at an early stage. The majority of patients in our community are detected at a late stage, where less than 20% of patients survive 5 years. The majority of GC is preceded by distinct histological stages that follow a progression from gastric mucosal inflammation, intestinal metaplasia (IM) and eventually cancer. These stages are characterised by genetic events that are largely unknown and occur over a period that can take years. It is also evident, especially in countries where GC is not as prevalent, that only a proportion of individuals will eventually develop GC. The long latency from the develpoment of IM and diagnosis of GC offers an opportunity to intervene and study the changes that lead to GC as well as find genes that may predict which individuals will progress. IM is the stage in which intervention is obvious. It is very easily diagnosed, is present for a long time and, for certain individuals, will eventually accumulate enough genetic events that will mandate progression to GC. Targeted screening of these individuals will enable a feasible strategy to find early GC, and avoid costly non-targeted screening. This proposal seeks to find key genetic events responsible for the transition of IM to GC. The first step utilises Affymetrix arrays to detect genes expressed in IM and specifically linked to GC. These candidates will be validated and used to study their role in the progression to GC using a mouse model of GC. This study is designed to find genes responsible for GC that can be used as: 1) a marker of progression in humans that will be used as a tool to stratify individuals into a screening protocol; 2) candidates to be tested in animal studies to study the pathogenesis of GC and potentially used as preventative or therapeutic targets.Read moreRead less
Endoscopic Diagnosis And Therapy: The Frontier Of Minimally Invasive Patient Care.
Funder
National Health and Medical Research Council
Funding Amount
$344,644.00
Summary
Minimally invasive diagnosis and treatment is a rapidly developing field, and has potential to significantly improve patient management and health care utilization. This research will apply endoscopic innovations to diagnose and treat early oesophageal and pancreatic cancer, with the aim to improve survival and quality of life. The research will also develop capacity to treat oesophageal motility disorders with minimally invasive endoscopic resection techniques.