Development Of Modified IGF-binding Proteins As Novel Anti-cancer Chemotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$77,375.00
Summary
We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof ....We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof of concept in vivo in order to attract commercial funding for clinical trials.Read moreRead less
P14ARF Induces P53-independent Growth Arrest By Modulating The Activities Of The E4F And E2F Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Cutaneous malignant melanoma is an important public health problem, affecting 1 in 30 Australians at some time in their lives, and the incidence of this disaese is increasing rapidly. Approximately 10% of people in Australia are at high risk of developing melanoma because they carry a faulty gene. Many of these melanoma-prone individuals carry a single mutation that can disrupt two genes, p16INK4a and p14ARF, that are involved in regulating the growth of cells via different pathways. The role of ....Cutaneous malignant melanoma is an important public health problem, affecting 1 in 30 Australians at some time in their lives, and the incidence of this disaese is increasing rapidly. Approximately 10% of people in Australia are at high risk of developing melanoma because they carry a faulty gene. Many of these melanoma-prone individuals carry a single mutation that can disrupt two genes, p16INK4a and p14ARF, that are involved in regulating the growth of cells via different pathways. The role of p16INK4a in maintaining cell cycle control is well understood and the many functions of this gene are under intense investigation. In contrast, the functions of p14ARF in normal cell regulation are not well understood. We will be analysing in detail how p14ARF protects the cell from uncontrolled growth and inhibits cancer development. Our research will dissect the functions of p14ARF and determine the protein partners that co-operate with p14ARF in maintaining normal cell growth. This work is essential to our understanding of normal cell proliferation and melanoma development and will provide clinically useful information regarding the biology of human cancer.Read moreRead less
TRF2 Protein And T-loop Replication In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Telomere loss acts as a clock telling cells when to stop proliferating. Cancer cells ignore this clock and grow indefinitely by preventing the normal loss of telomeres. Little is known about one of the methods cancers use to preserve telomeres, called ALT, which is employed by some brain tumours and other cancers. We will determine if the TRF2 protein is involved in controlling ALT. This will lay the basis for future anti-cancer treatments targeted at ALT.
The Importance Of VEGF-D, An Angiogenic Protein, For Lymphangiogenesis, Tumor Growth And Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Tumors attract blood vessels to obtain the nutrients for growth. Furthermore, the presence of blood vessels in a tumor enables tumor cells to enter the bloodstream and spread to distant parts of the body - a process known as metastatis that is the major cause of death in cancer patients. The growth of blood vessels - angiogenesis - is the mechanism by which tumors attract the vasculature. The capacity to block tumor angiogenesis would be of great benefit in the clinic as it would restrict both t ....Tumors attract blood vessels to obtain the nutrients for growth. Furthermore, the presence of blood vessels in a tumor enables tumor cells to enter the bloodstream and spread to distant parts of the body - a process known as metastatis that is the major cause of death in cancer patients. The growth of blood vessels - angiogenesis - is the mechanism by which tumors attract the vasculature. The capacity to block tumor angiogenesis would be of great benefit in the clinic as it would restrict both the growth and spread of tumors. Tumor cells attract blood vessels by secreting angiogenic growth factors that stimulate the proliferation of endothelial cells - the cells that form the inner lining of blood vessels. These Vascular Endothelial Growth Factors (VEGFs) are proteins. One VEGF, namely VEGF-D, was discovered in our laboratory at the Melbourne Branch of the Ludwig Institute for Cancer Research. VEGF-D stimulates the growth of blood vessels and possibly lymphatic vessels and is present in the most common human cancers including malignant melanoma and cancer of the breast and lung. We hypothesize that angiogenesis in some tumors is dependent on VEGF-D. Moreover, VEGF-D secreted by tumor cells may stimulate growth of lymphatic vessels - lymphangiogenesis. As metastatic spread often occurs via the lymphatic vessels, tumor lymphangiogenesis induced by VEGF-D may contribute to metastasis. The purpose of the research project is to determine the role of VEGF-D in tumor angiogenesis and lymphangiogenesis. Firstly we will thoroughly characterize the localization of VEGF-D in human cancer. Secondly, we will test VEGF-D for lymphangiogenic activity. Thirdly, the growth and metastatic spread in mice of tumors overexpressing VEGF-D will be analysed. Finally, aspects of VEGF-D biochemistry and gene regulation will be studied to develop strategies for inhibition of VEGF-D action in cancer.Read moreRead less
The Role Of CD30 Overexpression In CD30-positive Non-Hodgkins Lymphomas
Funder
National Health and Medical Research Council
Funding Amount
$457,242.00
Summary
The CD30 molecule sits on the surface of normal blood cells, but in a type of cancer called Lymphoma, CD30 concentration is high. The level of expression of CD30 may determine if the cancer cell is killed by the normal defense mechanisms or is able to grow uncontrollably. We are studying the control elements of the CD30 gene to understand how control is lost when the cell becomes cancerous. This knowledge may lead to therapeutic strategies to control lymphoma.
An understanding of the way cells control their complex internal circuitry is relevant to diseases like cancer and leukemia. The main focus of this project is a cellular regulator we identified several years ago called BORIS. Normally dormant in all cells outside the male reproductive organs, BORIS is reactivated in many cancers. We will study the network of factors perturbed when BORIS becomes inappropriately active in cancer cells. Ultimately this project may lead to new treatments for cancer.
CHARACTERIZATION OF THE NOVEL LEUKEMIA-INDUCING GENE MLF1
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
All of the circulating blood cells (including red cells and white cells) arise from haemopoietic stem cells found in the adult bone marrow. Stem cells gradually develop into one cell type. Once they have started down a particular pathway, they no longer generate cells of another pathway (e.g. once a stem cell begins to develop into red blood cells, they do not change into white cells). However, there are a few examples of mature cells that have changed pathways. We generated a red blood cell lin ....All of the circulating blood cells (including red cells and white cells) arise from haemopoietic stem cells found in the adult bone marrow. Stem cells gradually develop into one cell type. Once they have started down a particular pathway, they no longer generate cells of another pathway (e.g. once a stem cell begins to develop into red blood cells, they do not change into white cells). However, there are a few examples of mature cells that have changed pathways. We generated a red blood cell line, which has on occasions changed into macrophages (white blood cells) when grown under stressful conditions. Using these cells, we identified a gene, HLS7, which was involved in the change to macrophages. An American group has independently shown this gene can cause leukemia (blood cancer). We have shown HLS7 has dramatic effects on normal blood development and, together with its effect on leukemias, demonstrates its importance to the blood system. Through our studies on how HLS7 works, we have identified another gene, Madm, which may be an important regulator of HLS7. We plan to investigate the normal function of HLS7, how it interacts with Madm and how it causes leukemias. Analysis of these genes will further our knowledge in this field of blood cell development and cancer formation.Read moreRead less