The Limb Bud As A Model For Gubernacular Migration During Inguinoscrotal Testicular Descent.
Funder
National Health and Medical Research Council
Funding Amount
$439,073.00
Summary
This project examines the mechanism of descent of the testes from its original position inside the abdomen of the fetus to the scrotum in baby boys. When this process is abnormal, it leads to the common anomaly of undescended testes. Tha ultimate aim is to understand the process well enough to consider nonoperative treatment. The study will look at the tip of the gubernaculum, the ligament that anchors the testis to the groin early in development, and how it develops a growing tip that elongates ....This project examines the mechanism of descent of the testes from its original position inside the abdomen of the fetus to the scrotum in baby boys. When this process is abnormal, it leads to the common anomaly of undescended testes. Tha ultimate aim is to understand the process well enough to consider nonoperative treatment. The study will look at the tip of the gubernaculum, the ligament that anchors the testis to the groin early in development, and how it develops a growing tip that elongates towards the scrotum. The project will examine the factors controlling this process as well as the embryological mechanism involved.Read moreRead less
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
The Genitofemoral Nerve And Gubernaculum In Testicular Descent And Inguinal Hernia
Funder
National Health and Medical Research Council
Funding Amount
$339,750.00
Summary
This project examines the mechanism of descent of the testis, which when abnormal, leads to the common anomaly in infant boys of undescended testes. In addition, the tunnel through the abdominal wall which permits testicular descent very commonly fails to close afterwards, allowing the intestines to protrude through the hole to cause an inguinal hernia, which is a tender lump in the groin,and requires surgery to resolve. Our long-term aim is to understand testicular descent and inguinal closure ....This project examines the mechanism of descent of the testis, which when abnormal, leads to the common anomaly in infant boys of undescended testes. In addition, the tunnel through the abdominal wall which permits testicular descent very commonly fails to close afterwards, allowing the intestines to protrude through the hole to cause an inguinal hernia, which is a tender lump in the groin,and requires surgery to resolve. Our long-term aim is to understand testicular descent and inguinal closure well enough to develop non-surgical treatments for these two conditions, which are the two commonest abnormalities in children requiring surgery. We will examine how male hormones control descent of the testis indirectly by altering the anatomy and function of a specific nerve suplying the groin and scrotum. A simple and safe treatment that avoided surgery would be a major advance for infants in the developing world.Read moreRead less
Skeletal disease is a major problem for children with mucopolysaccharidoses (MPS). Patients suffer from early onset osteoporosis and osteoarthritis, severely affecting their quality of life. We will evaluate a lentiviral gene therapy vector developed in-house for its capacity to transduce bone, cartilage, synovial and ligament cells in a mouse model of MPS VI. Our goal is to generate high level, sustained expression of the deficient MPS enzyme and alter the course of skeletal disease in MPS.
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
This project examines the mechanism of descent of the testis, which when abnormal, leads to the common anomaly in children of undescended testes. Our long-term aims is to find a non-surgical treatment for undescended testes, and these studies will significantly aid in that goal. We will look at a completely new testicular hormone as well as a molecule released from nerves to determine their exact role in the mechanism. This project should allow us to understand finally one of the unresolved puzz ....This project examines the mechanism of descent of the testis, which when abnormal, leads to the common anomaly in children of undescended testes. Our long-term aims is to find a non-surgical treatment for undescended testes, and these studies will significantly aid in that goal. We will look at a completely new testicular hormone as well as a molecule released from nerves to determine their exact role in the mechanism. This project should allow us to understand finally one of the unresolved puzzles of the anatomical differences between males and females.Read moreRead less