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
Pathophysiology Of Functional Dyspepsia: Integration Of Upper Gut Function, Inflammation And A Systems Biology Approach.
Funder
National Health and Medical Research Council
Funding Amount
$748,593.00
Summary
Functional dyspepsia (FD) is an extremely common and costly problem with no cure. We and others have found that inflammation and immune activation play a role in FD but to date no studies have linked these findings with well known diseases markers including disordered sensory and motor function or psychiatric comorbidity. This study will explore the interrelationships between inflammatory and immune mechanisms, disease markers as well as the microbiome. This study could unravel the cause of FD.
Bacterial pathogens are a major cause of illness and death, producing diseases ranging from acute infections to cancer. However, not all infected individuals will succumb to these pathologies. What factors dictate which individuals develop these diseases is an important complex question. The core focus of my research is the identification and characterisation of novel host factors that are involved in resistance or susceptibility to bacterial-associated diseases of the gastrointestinal tract.
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
Potassium Channel Regulation Of Bacterial-driven Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$576,000.00
Summary
Helicobacter pylori infections cause a chronic inflammation which in some people results in stomach cancer or ulcers. We have used a mouse with natural resistance to H. pylori gastritis to identify a completely novel regulator of the pathology induced by this infection. In this project, we will examine the mechanism by which this regulator protects against disease in mice, and examine its significance in the susceptibility of people to gastric cancer.
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.
Colon cancer causes about 4,000 deaths per year in Australia. A better understanding of the biology of colon cancer will lead to new therapeutics that will aim to overcome the treatment resistance. This project is focused on understanding how a novel protein SLIRP regulates colon cancer growth, and will investigate the mechanisms for its protective effects on the disease. If successful, these studies could provide the foundation for targeting SLIRP for therapeutics.