ANALYSIS OF KNEE KINEMATICS- An MRI Study Of The Normal, Anterior Cruciate Injured, And Reconstructed Knee.
Funder
National Health and Medical Research Council
Funding Amount
$161,320.00
Summary
People with anterior cruciate ligament damage to the knee tend to develop osteoarthritis in this knee, perhaps because the instability produced by the ligament tear changes the patterns of wear on the joint surfaces. There are several studies using cadaver knees which examine the impact on the joint surfaces of cutting the anterior cruciate ligament, but very little of people moving voluntarily. This study plans to use MRI images of people with a torn cruciate ligament in one knee, and one norma ....People with anterior cruciate ligament damage to the knee tend to develop osteoarthritis in this knee, perhaps because the instability produced by the ligament tear changes the patterns of wear on the joint surfaces. There are several studies using cadaver knees which examine the impact on the joint surfaces of cutting the anterior cruciate ligament, but very little of people moving voluntarily. This study plans to use MRI images of people with a torn cruciate ligament in one knee, and one normal knee. The subjects will simulate a squat inside the MRI magnet against a weighted footplate. The images will be taken at fifteen degree intervals of knee movement. The contact points between the joint surfaces will be measured and compared to the normal knee. This imaging will be repeated after surgical repair, and then again two years later, to assess whether the normal movement pattern has been restored.Read moreRead less
Targeting The Vicious Cycle Of Cancer-induced Bone Disease With TRAIL And Bisphosphonates
Funder
National Health and Medical Research Council
Funding Amount
$443,696.00
Summary
The most serious clinical problem with patients with many forms of solid tumours is metastasis to bone, which leads to potentially debilitating complications that can cause erosion of the patient's quality of life, and eventually death. Unfortunately, bony metastases usually occur before pre-emptive treatments can be applied to prevent it. We have recently shown that recombinant soluble TRAIL is a potent anticancer agent that prevents cancer-induced bone destruction in a mouse model by directly ....The most serious clinical problem with patients with many forms of solid tumours is metastasis to bone, which leads to potentially debilitating complications that can cause erosion of the patient's quality of life, and eventually death. Unfortunately, bony metastases usually occur before pre-emptive treatments can be applied to prevent it. We have recently shown that recombinant soluble TRAIL is a potent anticancer agent that prevents cancer-induced bone destruction in a mouse model by directly targeting cancer cells within bone, and with no evidence of toxic side effects to normal tissues. Death receptor targeting by TRAIL, and bisphosphonates induce cancer cell apoptosis through different but overlapping signaling pathways. Therefore, combination of the two approaches may facilitate killing of tumour cells that resist death induction through either one of the pathways. Combination therapy may also reduce the probability of acquired resistance to either therapy. We propose that a combinatorial approach, using bisphosphonates to selectively target osteoclasts and TRAIL to selectively target cancer cells, would be an ideal therapeutic and safe approach to delay, slow or completely eliminate growth of cancer within bone.Read moreRead less
Antitumour Efficacy Of TRAIL: An Immunotherapeutic Approach For The Treatment Of Skeletal Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$459,034.00
Summary
The most serious clinical problem with patients with solid tumours is metastasis to bone, which leads to complications that can cause erosion of the patient's quality of life, and eventually death. TRAIL is a new cancer therapeutic that selectively kills cancer cells while sparing normal cells. The use of TRAIL agonistic antibodies that do not bind OPG and have increased serum half life offers an exciting approach for the treatment of skeletal malignancies that is non toxic and safe.
Histone Deacetylase Inhibitors (HDIs) With Antineoplastic And Antiosteolytic Properties
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Metastatic bone disease is very common in patients with many forms of solid tumours. Our approach to use Histone Deacetylase Inhibitors (HDIs), to target bone metastases offers an exciting therapeutic potential. Treatment with HDIs will have the potential to suppress cancer-induced bone destruction by integrating the cytotoxic and osteotropic properties that reside within the same compound. Our preclinical data will facilitate the translation of HDIs to clinical trials for bone cancer.