Parathyroid Tumorigenesis - A Role For The Newly Identified Putative Tumour Suppressor HRPT2
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Primary hyperparathyroidism is one of the most common tumour associated diseases of hormone secreting glands affecting 0.1-0.5% of adults and up to 3.4% of post-menopausal women. It can occur in family members, either alone or with other tumours, and can also occur with no family history (sporadic). Hyperparathyroidism is caused by secretion of excessive levels of parathyroid hormone. Amongst other problems, this causes significant bone disease that can lead to fracture. What is going wrong at t ....Primary hyperparathyroidism is one of the most common tumour associated diseases of hormone secreting glands affecting 0.1-0.5% of adults and up to 3.4% of post-menopausal women. It can occur in family members, either alone or with other tumours, and can also occur with no family history (sporadic). Hyperparathyroidism is caused by secretion of excessive levels of parathyroid hormone. Amongst other problems, this causes significant bone disease that can lead to fracture. What is going wrong at the genetic level to cause this disease is, in most cases, poorly understood. In Hyperparathyroidism Jaw Tumour Syndrome (HPT-JT), one form of familial hyperparathyroidism, we and our international collaborators have recently identified mutations in the gene HRPT2 predicted to lead to loss of function of this gene. HRPT2 has no known similarities to other genes that may give hints as to its function. The overall aim of this project is to test our theory that HRPT2 has an important role in abnormal growth of parathyroid tissue that, in some cases, will lead to cancer. Further, we hypothesise that this gene will have a role in both familial and sporadic presentations of parathyroid disease. We will investigate this gene in parathyroid tumour specimens from patients with familial and sporadic disease for gene mutations and also different levels of gene expression. We will also explore a mechanism for how these mutations may function to cause disease and look at the effect of reduced HRPT2 expression on expression of thousands of other genes using a technique known as microarray analysis. The expected outcomes of this study include the identification of individuals at risk of developing cancer whose treatment will be tailored to their genetic profile. Characterisation of HRPT2, and the genes its expression influence, may lead to the identification of suitable targets for future treatment of hyperparathyroidism and its effects on bone disease.Read moreRead less
A Solution To The Parathyroid Gland Secretion Problem
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
Parathyroid hormone is the master hormone regulator of whole body calcium metabolism and a powerful new treatment for osteoporosis but the mechanism by which its natural secretion is controlled has never been solved. In this project we will apply new insights and advanced technical approaches to resolve this most fundamental question of calcium homeostasis, namely how parathyroid hormone secretion is controlled.
Does Teriparatide Reverse Osteonecrosis Of The Jaw In Patients With Cancer? A Randomised, Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$357,412.00
Summary
Osteonecrosis of the jaw (ONJ) is debilitating and associated with drugs that increase bone strength and reduce the bone remodeling rate (bisphosphonates or denosumab). Up to 15% of patients with bone marrow cancer and 1 out of 952 patients with osteoporosis treated with bisphosphonates may get ONJ. This 8-week trial of subcutaneous teriparatide (a hormone that forms new bone) or placebo injections aims to promote resolution of ONJ, measured clinically and by x-ray, and improve quality of life.