Interplay Between Mutant P53 And PML; Implications For Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
The most important agent of the body for fighting cancer is the cellular protein p53. In more than 50% of all human cancers, it looses its anticancer properties through mutation. In an insidious manner this new mutant form then acts to promote cancer. To better treat cancer we need to understand how mutant p53 functions. We will study how it interacts with its molecular partners in cancer cells.
Bombesin Like Peptides As Autocrine Growth Factors In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
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 its 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 determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now kn ....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 its 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 determine the potential roles of a growth factor termed Bombesin Like Peptide. 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. We will study the expression and production of GRP and its receptors at the gene and protein level, the ability of GRP to stimulate growth, the chemical structures of GRP, and the potential of antagonists of GRP to modulate growth. Studies will be performed in patients with bowel cancer, in animal models of bowel cancer, and with bowel tumours removed from patients and bowel cancer cell lines. 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 GRP receptor antagonists and radiolabelled GRP analogues for radiotherapy.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.
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
Physiology And Pathology Of Novel Forms Of Progastrin
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
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 especially colon cancer. The different types of gastrins have different effects but we do not know which forms are important and whether all are active. The types and activity of the different gastrins will be investigated using cell lines, animal models and colon cancer patients with the view of establishing new treatments.
Defining The Role Of Microphthalmia-associated Transcription Factor (MITF) In Melanoma Heterogeneity By Real-time Cell Cycle Imaging
Funder
National Health and Medical Research Council
Funding Amount
$613,705.00
Summary
Metastatic melanoma is highly therapy-resistant. Modern targeted therapy is promising but suffers from rapid onset of drug resistance. Tumours consist of zones of fast growing cells next to zones of dormant cells. This tumour heterogeneity is one of the reasons for cancer drug resistance, as cells in different growth states respond differently to drugs. By understanding the causes of tumour heterogeneity we will set the basis for innovative clinical approaches against this devastating disease.