Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less
Genetic Polymorphisms In Genes Controlling Innate Immunity As Risk Factors For Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$241,500.00
Summary
For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a pro ....For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a process which is vital during early childhood, when clonal expansion of antibodies and other host defences is inadequate. It is becoming increasingly apparent that this innate immune response is not just the first line of defence but a necessary event for the development of an adaptive immune response. We propose that the innate immune system of children carrying TLR gene variants may be less effective at detecting the presence of microbial pathogens in the environment. We hypothesize that by dampening the stimulation of innate immunity in early childhood, TLR gene variants may indirectly cause a dysfunction in the maturation of a child's immune system and increase the chance of a pre-leukaemic clone emerging, leading to the development of childhood leukaemia.Read moreRead less
A Record Linkage Study Of The Relationship Between Intra-uterine Growth, Birth Weight And Childhood Acute Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$126,000.00
Summary
Little is known about the causes of childhood leukaemia and cancer, and this has been the subject of intense study over many years. Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML) are the most common types of childhood cancers. The early age of onset of diagnosis of cancer-leukaemia in childhood has focused attention on factors related to pregnancy. Many studies have investigated the relationship between birth weight and risk of leukaemia. Some studies have reported finding ....Little is known about the causes of childhood leukaemia and cancer, and this has been the subject of intense study over many years. Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML) are the most common types of childhood cancers. The early age of onset of diagnosis of cancer-leukaemia in childhood has focused attention on factors related to pregnancy. Many studies have investigated the relationship between birth weight and risk of leukaemia. Some studies have reported finding an increasing risk of Acute Lymphoblastic Leukaemia with increasing birth weight, but not all studies have reported this relationship. The relationship between birth weight and Acute Myeloid Leukaemia has been even less well described. Many previous studies have not taken account of important factors when analysing the results. This study will use an existing pool of routinely recorded health information, thus ensuring accurate information on birth weight and factors such as maternal height and age and the length of the pregnancy. We will also have complete and accurate information on childhood cancer in Western Australia. Our results will contribute to knowledge about the causes of childhood leukaemia and the biological pathways involved in its development. If growth-related factors do prove to be integrally involved in the aetiology of childhood leukaemia, then the rapidly increasing prevalence of juvenile diabetes, overweight and obesity in Australia and other developed countries could have even more serious implications for the health of our children. It is important that we investigate this question as soon as possible.Read moreRead less
A National Case-Control Study Of The Causes Of Childhood Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$1,159,259.00
Summary
Childhood brain tumours are the second most common childhood cancer (~20%) after leukaemia (~35%) and are the leading cause of cancer death among children. Children who survive a brain tumour are often left with physical and mental problems as a result of treatment. This can have a significant impact on the child, family and community. Greater understanding of the causes of childhood brain tumours may lead to preventative measures. Most children with brain tumours are very young, suggesting that ....Childhood brain tumours are the second most common childhood cancer (~20%) after leukaemia (~35%) and are the leading cause of cancer death among children. Children who survive a brain tumour are often left with physical and mental problems as a result of treatment. This can have a significant impact on the child, family and community. Greater understanding of the causes of childhood brain tumours may lead to preventative measures. Most children with brain tumours are very young, suggesting that factors to which parents are exposed may affect future children. For this reason, it is important to study the parents as well as the child. This study will investigate environmental exposures known to be harmful, such as parental cigarette smoking and exposure to pesticides and other chemicals. Such exposures are also thought to increase the risk of other childhood cancers like Acute Lymphoblastic Leukaemia. We will also investigate whether dietary factors - including vitamin supplements - in the parents or the child can reduce the risk of a child developing a brain tumour. This study also examines genetic factors which can influence the body's ability to deal with toxins. Some genetic variations, combined with diet and lifestyle factors, may alter the risk of developing some cancers. These interactions need to be examined in greater detail for childhood brain tumours. This national study will examine specific genes and analyse them in conjunction with rigorous assessment of exposures throught to be related to the development of childhood brain tumours. Results obtained from children with brain tumours and their parents will be compared with those from healthy 'control' children and their parents. This is the first study to assess gene-environment interactions in relation to the risk of childhood brain tumours.Read moreRead less
Environmental And Genetic Factors In Childhood Acute Lymphoblastic Leukaemia: A Case-control Study.
Funder
National Health and Medical Research Council
Funding Amount
$1,788,500.00
Summary
In most countries, acute lymphoblastic leukaemia is the commonest cancer in children. One in 2000 children will develop this disease before their 15th birthday. New methods of treatment introduced over the last 30 years have resulted in cure for many children. However, one third of children diagnosed with this type of leukaemia still die and, even in those whose lives are saved, cure is achieved at a significant cost to the child, the family and the community. Greater understanding of the develo ....In most countries, acute lymphoblastic leukaemia is the commonest cancer in children. One in 2000 children will develop this disease before their 15th birthday. New methods of treatment introduced over the last 30 years have resulted in cure for many children. However, one third of children diagnosed with this type of leukaemia still die and, even in those whose lives are saved, cure is achieved at a significant cost to the child, the family and the community. Greater understanding of the development of childhood leukaemia may lead to preventive measures. Most children with this type of leukaemia are very young, suggesting that factors to which parents are exposed may affect future children. For this reason, as well as investigating the health and lifestyle of the child, it is essential to study the parents. Recent research suggests an association between the mother's intake of folate during pregnancy and her child's risk of developing the most common type of childhood leukaemia. It is also apparent that genetic differences result in varying abilities to deal with toxins, which may alter the risk of developing some cancers. Diet and lifestyle probably also affect this risk. These observations and interactions need to be examined in greater detail. In this large Australia-wide study specific genes will, for the first time, be examined and analysed in conjunction with rigorous assessment of exposures thought to be related to the development of childhood leukaemia. Results obtained from children with leukaemia and their parents will be compared with those from healthy children and their parents. This study is unique in its attempt to assess gene-environment interactions in Australian children and their parents. It will clarify the role of folate and other potential environmental agents in the development of childhood leukaemia and examine gene variations that may affect cancer risk.Read moreRead less
Investigation Of Molecular And Cellular Determinants Of Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Novel immune-based treatments for advanced, incurable, cancer have significantly improved patient survival. Although these treatments have proven highly effective, they are associated with the unpredictable development of severe and sometimes life-threatening autoimmune disease. We aim to discover ways to predict and potentially prevent these complications by identifying genetic risk factors and markers in blood samples. If successful, this will be a ground breaking advance in cancer care.
Patient Tailored Anti-tumour T Cells To Prevent Relapse In Patients With Acute Myeloid Leukaemia Undergoing Allogeneic Haemopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$190,445.00
Summary
Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults. Patients with high-risk AML have a 2-year survival of less than 20%. Blood or bone marrow transplant from a healthy donor is often the only chance of cure but the leukaemia frequently returns. Dr Blyth will perform a clinical trial giving leukaemia fighting immune cells from the transplant donor to patients with high risk AML to prevent relapse after transplant.
A Phase I Study Of Autologous CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Relapsed And Refractory B-cell Leukaemia And Lymphoma (The Auto-CAR19 Trial).
Funder
National Health and Medical Research Council
Funding Amount
$584,666.00
Summary
Most people with leukaemia and lymphoma who relapse early after chemotherapy die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but the cost of the viral vectors used to make these cells is prohibitively expensive. We will make leukaemia and lymphoma specific immune cells from patients using an inexpensive non-viral system, then administer the immune cells to patients to assess their safety and efficacy.