Transcriptional Regulation Of The Tumour Suppressor Gene, Retinoic Acid Receptor Beta
Funder
National Health and Medical Research Council
Funding Amount
$336,540.00
Summary
Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identif ....Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identified that a particular gene retinoic acid receptor beta, known to be involved in the vitamin A anticancer effect may be deficient in some neuroblastoma tumours, and is vital to the anticancer effect of vitamin A in neuroblastoma cells. In this application we hope to define those cellular factors which are necessary for turning on the expression of this gene.Read moreRead less
Improving The Efficacy Of Retinoid Therapy In Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$295,336.00
Summary
Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficie ....Cancer is still the commonest disease causing death in chilhood. Childhood neuroblastoma is a cancer of the nerve tissue which presents usually as a widely spread malignancy, which responds poorly to conventional therapy, indicating the need for novel treatment approaches. Vitamin A derivatives, or retinoids, given in addition to conventional therapy improves the cure rate for children with advanced neuroblastoma to 50%. We have shown that one likely mechanism of retinoid resistance is a deficiency of retinoic acid receptor beta, which is a necessary factor in the neuroblastoma cell for converting the retinoid anti-cancer signal into an irreversible cellular change. In this project we will define why some neuroblastoma cells express low levels of this protein and test new retinoid therapies.Read moreRead less
Randomised Controlled Trial Of Therapeutic Pulmonary Lavage In Meconium Aspiration Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$182,550.00
Summary
Meconium aspiration syndrome (MAS) is a serious respiratory disease of full term infants, which can lead to very severe respiratory failure. It is caused by the inhalation of meconium, the secretion of the fetal intestine, into the lung at or prior to delivery. As a result, the airways and air sacs within the lung are damaged, leading to difficulty with breathing and poor oxygen levels. About one-third of all infants with MAS require mechanical ventilation in the first days of life, and are ofte ....Meconium aspiration syndrome (MAS) is a serious respiratory disease of full term infants, which can lead to very severe respiratory failure. It is caused by the inhalation of meconium, the secretion of the fetal intestine, into the lung at or prior to delivery. As a result, the airways and air sacs within the lung are damaged, leading to difficulty with breathing and poor oxygen levels. About one-third of all infants with MAS require mechanical ventilation in the first days of life, and are often extremely difficult to manage. At present, the main treatments given to a ventilated infant with severe MAS are supportive, rather than curative. Lung cleansing procedures are not part of routine care in this condition, even though removal of meconium from the lung may reduce the amount of damage that occurs. This project is a randomised controlled trial of a lung cleansing procedure called lung lavage in ventilated infants with severe MAS. During the lung lavage, a quantity of cleansing fluid containing a natural substance called surfactant is introduced into the lung, and then removed by suctioning. This procedure cleanses the lung of some of the meconium, and in preliminary testing, appears to be safe and well-tolerated even in the sickest infants. In the proposed trial, we will randomly allocate ventilated infants with severe MAS to receive either a lung lavage procedure, or routine care. This will take place within 24 hours of birth. We are looking to see whether the lavage procedure shortens the duration of ventilation, oxygen therapy or hospitalisation. Because there are only a small number of ventilated infants with MAS at any one centre per year, we will involve as many Australian neonatal intensive care units as we can in the study. We aim to enrol 66 infants in the trial, of whom half will receive lavage therapy.Read moreRead less