The CpG Island Methylator Phenotype In Colorectal Cancer - Pathways And Precursors
Funder
National Health and Medical Research Council
Funding Amount
$517,272.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four differen ....Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four different subgroups of bowel tumours, and that each of these may have different physical properties and responses to therapy. We aim to better characterise these subgroups to increase our understanding of how normal bowel can change into a small polyp, that may grow into a cancer. Understanding the gene changes leading to each subtype of bowel cancer will in the future allow the development gene markers for early detection as well as the possibility of individualised patient therapy. We are also studying tiny biopsies of normal bowel tissue from patients either with or without polyps, to try to understand the very earliest changes which may underly the development of a bowel polyp.Read moreRead less
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
Peptides Derived From ProGRP As Growth Factors For Gastrointestinal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Our objective is to determine the roles of a growth factor termed bombesin. This peptide, known as GRP in the human, is a growth factor in certain lung cancers but little is known about its role in tumours of the colon. This project is based on our novel observation that the precursor of GRP (proGRP) previously thought to be inactive is in fact active in stimulating the growth of colon cancer cells. A successful outcome will result in novel treatments such as proGRP antagonists.
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
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
Understanding The Role Of PI 3-kinase Mutations In Gastrointestinal Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$283,880.00
Summary
Mutations in the PIK3CA gene are frequently found in bowel cancers but it remains unclear exactly how these mutations are involved in cancer development. We will exploit a unique mouse model to explore the role of PIK3CA mutations in the initiation, progression and-or metastasis of gastrointestinal cancers. This work will provide critical new insights into the biology of PIK3CA mutations and lead to the development of better models for the testing of new anti-cancer therapies.
Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce their own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to deterrmine the potential roles of a growth factor termed bombesin. This peptide, now known as GRP ....Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce their own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to deterrmine the potential roles of a growth factor termed bombesin. This peptide, now known as GRP in mammalian systems, is an established growth factor in certain lung cancers but little is known about its role in tumours of the large bowel. This project is based on our novel observation that the precursor of GRP (proGRP) previously thought to be inactive is in fact biologically active in stimulating the growth of colorectal carcinoma cells. We will determine which parts of the GRP precursor (proGRP) are bioactive, and test the effects of the bioactive regions on growth and cancer spread using a variety of colorectal cancer cell lines. We will also investigate the effects of the bioactive regions of proGRP on the development of colorectal cancer in three animal models, which represent different stages of the progression to invasive cancer. We will then compare the intracellular pathways by which proGRP and GRP communicate with the cell nucleus, and investigate the structure of the cell-surface receptor that binds the proGRP. Finally we will determine the types and amounts of proGRP derived peptides produced by CRC cell lines and by tumours obtained from patients with colorectal cancer. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as proGRP receptor antagonists and radioactive proGRP analogues for radiotherapy.Read moreRead less